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Foods to help balance fatty liver

The Truth News — Sun, 23 Jun 2024 18:09:19 +0000

Foods to help balance fatty liver

1. What is fatty liver disease?

Fatty liver disease is a condition in which too many fat cells accumulate in the liver cells. Normally, there is still fat in the liver, but when the number of fat cells increases, accounting for more than 5% – 10% of the weight of the liver, it can be considered as fatty liver. Excess fat accumulation in the liver makes the liver more susceptible to damage, which can lead to hepatitis, cirrhosis, and liver failure.

There are many causes for a person to have fatty liver such as hepatitis C, metabolic diseases such as diabetes, thyroid disease. Fatty liver disease is classified into two groups:

Alcoholic fatty liver disease: With fatty liver disease caused by alcohol, the important treatment is to stop drinking alcohol, otherwise the disease will get worse. , which can lead to cirrhosis, even liver cancer.

Non-alcoholic fatty degeneration: Mainly due to metabolic disorders, and a small part due to viral hepatitis. In the case of fatty liver disease caused by metabolic disorders – excess energy, the important treatment measure is to change lifestyle. For example, an improper vegetarian diet can also lead to fatty liver disease. A vegetarian diet that is completely protein-free or a vegetarian but still drinking alcohol will not provide enough energy for the body, which will weaken the immune system.

Fatty liver is a common disease with an increasing incidence. Fatty liver disease, if not detected and treated early, can lead to hepatitis, cirrhosis, and even liver cancer. Therefore, it is best to prevent disease with foods that help balance fatty liver.

2. Fatty liver eat what?

Fatty liver disease if not detected and treated early can lead to hepatitis, cirrhosis, even liver cancer. So how should the diet and daily activities need to be changed to help improve the problem of fatty liver? The following are foods that help balance fatty liver:

Turmeric: Not only is turmeric a favorite spice often added to dishes, but turmeric also offers many great health benefits. Turmeric helps prevent and treat fatty liver disease through stimulating the digestion of fat in the body, reducing the amount of fat cells that accumulate in the liver. To effectively treat people with fatty liver, you can take half a teaspoon of turmeric powder mixed in a glass of hot water, wait until it cools and drink three glasses a day. You can also mix half a teaspoon of turmeric powder with a glass of warm milk.

Lemon: Lemon is a fruit rich in vitamin C, a very good natural antioxidant that helps the liver produce more glutathione and plays an important role in the detoxification process for the body. Recent studies have shown that lemons contain a compound called naringenin, which reduces liver inflammation associated with fatty liver disease. Drinking fresh lemon juice 2-3 times a day, continuously for a month or thinly sliced lemon in a bottle of water and drinking daily also helps improve fatty liver.

Apple juice: Apple juice and apple cider vinegar are among the best foods in treating fatty liver disease, promoting weight loss and helping to reduce fat accumulation in the liver. Mix a tablespoon of apple cider vinegar with a teaspoon of honey mixed in a glass of warm milk, drink every day before meals, continuously for many months will bring great results.

Green Tea: Green tea is packed with nutrients and is rich in antioxidants that are important for the body. Green tea not only supports brain function, is good for the stomach, kills bacteria, but also boosts fat burning in the body and reduces the risk of cancer. Therefore, drinking green tea water is one of the most effective measures in preventing fatty liver disease, especially for people with non-alcoholic fatty liver disease.

Dandelion: Dandelion is a very liver tonic herb, helps to activate better liver function and is used to treat fatty liver disease not caused by alcohol but related to obesity, because dandelion He has the effect of enhancing the metabolism of fat accumulated in the liver. Use dandelion by mixing a teaspoon of dandelion powder with hot water, let it cool for a few minutes before drinking. You can also add a little honey to enhance the taste. Drink one glass a day, divided into 2-3 times, continuously for several weeks. Note, dandelion should not be used by people with diabetes because it can cause unwanted side effects.

Papaya: Papaya fruit and papaya seeds have great fat burning benefits that accumulate in the liver. So papaya is very good to improve fatty liver.

Protein: Foods that provide protein such as lean meats, poultry, fish, seafood, eggs, soybeans, legumes are good for weight loss and weight maintenance. Milk and dairy products: Nutrient-rich but low-fat milk as well as healthy dairy products including fat-free or low-fat milk, yogurt and cheese should be added to your daily diet. people with fatty liver disease.

Other foods: Licorice can be mixed with warm water or used as a supplement to treat nonalcoholic fatty liver disease. Grapefruit juice contains powerful antioxidants that enhance liver function.

3. Lifestyle changes in fatty liver disease

In addition to paying attention to what fatty liver disease eats, lifestyle changes are also a measure to help balance fatty liver. Lifestyle change measures include:
Control and maintain ideal weight: Regular monitoring of weight as well as weight gain is essential in controlling fatty liver disease, helping to control fatty liver disease. Regulates excess fat accumulation in the liver. When you are overweight or obese, you need to actively lose weight to achieve your ideal weight.

Change your diet and eating habits to ensure liver health:

A healthy diet consists mainly of plants with fruits, vegetables, whole grains, and vegetable oils. Green vegetables and fruits will provide the body with many important vitamins and minerals, in which vitamins A and E work to prevent the accumulation of extra fat in the liver. This will support the liver to work better and prevent the liver from working too hard. Avoid fatty foods, fast foods, processed foods, and junk foods. Exercise regularly and regularly, for at least 30 minutes a day and at least 5 days a week. If you are new to exercise, you should start with gentle exercises, then gradually increase the intensity. Regular exercise helps to increase metabolism and burn excess fat in the body, helping to lose weight and maintain a healthy weight. In a nutshell, fatty liver disease means the accumulation of fat in the liver cells and makes the liver more susceptible to damage, which can lead to hepatitis, liver failure. Currently, there is no specific treatment for fatty liver disease that can only be reversed by changes in diet and daily activities. source

The BEST Drink for a Fatty Liver

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Some research suggests that dandelion may help prevent and treat nonalcoholic fatty liver disease (NAFLD). For example, a 2013 study found that dandelion leaf extract (DLE) improved insulin resistance and reduced lipid accumulation in the livers of mice fed a high-fat diet. DLE also suppressed total cholesterol, triglycerides, fasting glucose, and insulin levels in the serum.

Dandelion root tea is also believed by some to help detoxify the liver and relieve symptoms of liver disease. To make dandelion tea, you can steep one tablespoon of dandelion roots or flowers in five ounces of boiling water for 30 minutes, then strain or drink the mixture.

However, you should avoid dandelion tea if you are pregnant or breastfeeding, taking diuretics, or taking antibiotics like Cipro or Levaquin. Dandelion also has natural diuretic properties, so it may interfere with the action of lithium and similar medications. If you are being treated for liver or kidney issues, you should also avoid dandelion or dandelion tea unless your doctor says it’s okay.

Easy Liver Cleanse Recipe: Detox Naturally with Lemon and Olive Oil

You only need to look at simple liver cleanse recipes that combine the flavorful combination of lemon and olive oil. This cleansing method supports liver function and promotes general well-being by utilizing the natural detoxifying qualities of these herbs in a gentle yet effective way.

Olive oil and lemon are the main ingredients in the main cuisine of European restaurants. Many people say that the combination of lemon juice and olive oil can treat many diseases like gallbladder stones.

Furthermore, research has looked at the possible health benefits of the components in lemon juice and olive oil independently.

This article will talk about the fact that studies support the purported health benefits of combining lemon juice with olive oil.

We’ll also review the olive oil lemon juice liver cleanse recipe.

Discover the Mutual Impact of Olive Oil and Lemon on liver

There we will learn about the combination of lemon juice and olive oil. Lemon and olive oil make an extremely unique combination. It is open to all, committed, and productive for the skin, liver, and even blood flow.

Let’s first explore the two fruits independently: The ability of lemon to act as an acidifying agent is its power.

The human body can become acidified if its pH level is out of balance, which can have major negative effects on health. Hyperacidity is countered and the pH value is adjusted during alkalizing. Therefore, sick cells typically lose their strength as well as their breeding ground.

There are many liver cleansing recipes with lemon juice and olive oil. Because these are the most easily used liver detox. Lemon Liver detox works properly to clean liver stones and many other harmful small agents.

Olive oil and Lemon Juice Liver Cleanse Recipe

Ingredients:

1/2 cup of extra virgin olive oil
1/4 cup of freshly squeezed lemon juice
1-2 cloves of minced garlic

Instructions:

Before beginning the cleanse, fast for a minimum of 12 hours to enable your liver to get ready for detoxification.
In a bowl, thoroughly mix the olive oil, lemon juice, and minced garlic.
During one to two hours, take one tiny serving (about one to two tablespoons) of the olive oil mixture every fifteen minutes.
After you’ve finished the olive oil mixture, lie on your right side with your knees pulled up to your chest for half an hour.
Spend the rest of the evening sleeping so that the cleanse has time to work.

How do you know that this combination is best for you?

Some research shows that eating lemon juice and olive oil together has health benefits. Many claim that they can aid in weight loss, treat and prevent gallstones, and perform cleanses and detoxes.

Let’s look at each of these claims properly.

Cleansing and Detoxification Ideas

A fast internet search will bring up a variety of recipes claiming to use lemon juice, olive oil, or both to detox and cleanse. It is said that waste and toxins that have accumulated in your body over time are taken out by cleanses and detoxes.

On the other hand, research on the potential cleansing and detoxifying effects of lemon juice and olive oil does not seem to be very extensive.

When compared to those who consumed other plant oils, the researchers discovered that those who consumed olive oil during the study period had greater levels of HDL (good) cholesterol and lower levels of LDL (bad) cholesterol in their blood.

In this article, we will give you the natural liver detox recipe for your best hygiene.

However, the polyphenols and antioxidants in lemon juice and olive oil could be referred to as “cleansing” because they “clean up” or neutralize dangerous free radicals. Which otherwise damages cells and may be a factor in sickness and disease.

Lemon and olive oil are recommended as the best quick liver detox. The human body uses a variety of biological processes to get rid of pollutants and keep itself operating at its best.

I suggest eating a diet that is rich in fruits, vegetables, whole grains, legumes, nuts, seeds, and lean protein sources to support your body’s optimal functioning.

Weight Loss

Vitamin C is rich in lemon juice. 38.7 mg, or 43% of the Recommended Dietary Allowance (RDA) for men and 52% of the RDA for women, is present in a 3-ounce (100-gram) serving. Vitamin C plays a crucial role in the body’s synthesis of carnitine.

A substance called carnitine is responsible for moving fat molecules into cells so they may be broken down and used as an energy source. Thus, a low vitamin C consumption could result in less fat being broken down. For

weight loss, many quick liver detox drinks are also available in the market.

Health Benefits of using Liver oil and Lemon Cleanse

What health advantages are associated with gallbladder cleansing?

To prevent gallstones, certain supporters of alternative healthcare advise liver cleansing. They maintain that the liver releases the gallstones as a result of the liver cleaning.

The gallstones should then ideally pass via the stool. This would mean that the patient would have fewer gallstones left to produce uncomfortable symptoms and might be able to avoid surgery.

There are various kinds of liver cleanses. Alternative medicine practitioners provide many ” liver detox recipes” and traditional treatments online.

Olive oil and lemon juice. Using this method, you will fast for 12 hours during the day and then drink 4 tablespoons of olive oil and 1 tablespoon of lemon juice, eight times every 15 minutes, starting at 7 p.m.
Vegetables and apple juice. Using this method, all you consume till five o’clock in the evening is apple and vegetable juice. Every fifteen minutes after 5 p.m., ingest eight ounces of olive oil by consuming 18 milliliters (ml) of olive oil mixed with 9 ml of lemon juice.

In these points, we tell you about the easy liver detox remedy that you can use at home easily.

How might a liver cleanse cause side effects?

Depending on the “recipe” one follows, cleansing may have different adverse effects. For example, a lot of individuals cleanse their livers using olive oil. When consumed in excess, this may have a laxative effect.

The following symptoms are possible for some people to experience after a gallbladder cleanse:

Diarrhea vomiting nausea
Depending on the herbs or other things someone utilizes in their cleanse, there could be additional negative consequences.

Furthermore, a person may perform a gallbladder cleansing yet still not be able to get rid of their gallstones. To prevent their symptoms from getting worse or an infection in their gallbladder. They probably need to have surgery at that point.

How to liver cleanse at home?

To support your liver’s natural detoxification activities and enhance general well-being. Liver cleansing at home might be a quick and easy solution. A possible strategy is to consume fewer processed meals, alcoholic beverages, and added sugars while increasing your intake of foods high in fiber, such as fruits, vegetables, and whole grains.

Furthermore, drinking lots of water throughout the day to stay hydrated promotes liver function and the removal of toxins. Herbal teas that you can drink regularly, like milk thistle or dandelion root, are also well-known for their liver-cleansing qualities. Different liver detox tea recipes are also present on the internet.

How much olive oil for detox?

Depending on things like tolerance levels, individual health status, and particular detox procedures, there are differences in the suggested quantity of olive oil for detoxification. In general, it’s important to balance safety and efficacy while using olive oil in a detox program.

As part of a detox treatment, it is generally recommended to ingest 1-2 tablespoons of extra virgin olive oil daily.

The body’s natural detoxification processes are supported by this moderate amount of beneficial substances, which do not overburden the system. These components include antioxidants and monounsaturated fats.

Conclusion

Cleanse Your Liver

In addition to lifestyle changes, nutrition can have an impact on liver health. Check out these beverages that can aid in improving liver function.

Your liver plays many important roles in your physical health. It aids in digestion and metabolism and acts as a filter for the blood, breaking down harmful substances into waste that is expelled from the body through urine and stool.

According to the Mayo Clinic, symptoms of liver dysfunction include:

Skin and eyes that appear yellowish (jaundice)
Abdominal pain and swelling
Swelling in the legs and ankles
Itchy skin
Dark urine color
Pale stool color
Chronic fatigue
Nausea or vomiting
Loss of appetite
Tendency to bruise easily

Liver disease can be genetic. Other factors like viral infections, age, obesity, or excessive alcohol use may also cause liver damage or dysfunction. If left untreated, this damage can be fatal.

The good news is the liver is the only organ in the body with the ability to regenerate new cells and repair damaged ones. Repairing liver damage can be challenging; however, it is possible through consistent diet and lifestyle changes. These include:

Maintaining a healthy weight
Eating nutritious food and having a balanced diet
Getting regular exercise
Avoiding harmful additives and chemicals
Avoiding excessive or continued alcohol or illegal drug use (damage from alcohol abuse can cause irreversible cirrhosis of the liver)

Also, many beverages, such as water, tea, and grapefruit juice, can be beneficial for your overall health and may aid detoxification of the body and liver.

Water

Staying properly hydrated is an important factor in maintaining a healthy liver. Dehydration can greatly affect liver function, especially the ability to detoxify blood. On average, you should drink eight to ten glasses of water a day; those with health conditions may need to increase their water intake beyond the recommended amount.

Teas

There are a few natural teas that may assist in liver function. Several popular and possibly beneficial teas for liver health include:

Lemon Ginger Tea – reduces the risk of liver disease
Peppermint Tea – improves digestion and detoxifying functions of the liver
Green Tea – reduces the accumulation of lipids in the liver and contains antioxidants

Research the health effects and benefits of specific teas or discuss recommendations with your health care provider to ensure safe recommended use.

Grapefruit Juice

Grapefruit juice contains specific antioxidants that stimulate the liver and help filter and excrete chemicals from the body. Grapefruit also contains flavonoids naringin and naringenin, which have anti-inflammatory and antioxidant properties that may help protect the liver. However, it is recommended to not consume more than six ounces of grapefruit juice per day. Grapefruit juice also interacts with many prescription medications, so please check with your doctor or pharmacist and read your medication warning labels before adding it to your diet.

Turmeric Water

Turmeric is a commonly used supplement that may decrease inflammation and assist with liver repair, due to its ability to help flush out harmful toxins while decreasing fat buildup in the liver. For safe use, medical studies recommend mixing one to three grams of dried turmeric root in hot water each day for up to three months.

Lemon Water

Many citrus fruits, including lemon, can be added to water to help stimulate and flush out the liver. Lemons are high in nutrients like vitamin C and antioxidants. To help prevent liver disease, enjoy four to six tablespoons of lemon juice mixed with water each day.

Ginger Water

Ginger helps protect your liver and reduces inflammation in the body. It may also boost immunity and improve digestive health. The recommended consumption is less than four grams of ginger per day, mixed with warm or cold water.

As with any change in nutritional intake or supplement use, please use caution. Some people may experience unwanted results or side effects, and some herbs and foods may interact with certain medications. Also, the information presented above is based on adult studies and should not be used for children. Research any supplements and consult a health care professional before making abrupt changes to your diet or lifestyle. source

DRINK 1 CUP PER DAY to Remove Fat from Your Liver – Dr. Berg

Many people have a fatty liver and don’t even know it.

Today I want to help you better understand the liver and how to remove fat from the liver. The purpose of the liver is to break down toxins into harmless particles. A fatty liver can become heavy and enlarged. This can lead to fullness under the right rib cage and shoulder pain.

Important functions of the liver:

It makes bile
It helps convert thyroid hormones
It buffers excess sex hormones

Bile is made by the liver, and it helps you break down fat. A lack of bile can lead to a lot of various health problems. Bile is also very important to keep fat out of the liver. Anything you can do to help increase bile reserves will help you remove liver fat. You may even want to take purified bile salts. Keep in mind that the ketogenic diet and intermittent fasting can help remove fat from the liver. I believe this is essential if you have a fatty liver.

A great shake to keep fat off the liver: Ingredients (organic if possible):

2 cups kale (frozen)
1 cup blueberries (frozen)
1 cup water
1 cup plain whole-milk kefir (organic and grass-fed if possible)

Instructions: Blend all of the ingredients in a blender for a couple of minutes. Drink once a day in combination with a Healthy Keto diet and intermittent fasting.

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

Abstract

Chronic excessive alcohol consumption (more than 40-80 g/day for males and more than 20-40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

PubMed Disclaimer

1. Introduction

Alcohol abuse and alcoholism could lead to serious health and socioeconomic problems worldwide. Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females) could lead to several illnesses, such as gastrointestinal damage, pancreatitis, alcoholic liver disease, neurologic disorders, diabetes mellitus, and cancer [1, 2]. Among these diseases, alcoholic liver disease has attracted more attention due to its high morbidity and mortality. Alcoholic liver disease is a major type of chronic liver disease throughout the world and can progress to liver cirrhosis and liver cancer.

Chronic alcohol consumption can generate abundant reactive oxygen species (ROS), including superoxide anion radical (O₂^−•), hydroxyl radical (OH^•), and hydrogen peroxide (H₂O₂). The ROS can react with most cellular macromolecules and subsequently cause cellular damage [3]. Therefore, the excessive ROS induced by alcohol is regarded as an important factor in the development of alcohol-induced liver injury. Various enzymatic and nonenzymatic antioxidants are related to protecting cells against ROS. Antioxidant enzymes include catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and nonenzymatic antioxidants include glutathione (GSH), vitamin E, ascorbate, vitamin A, and ubiquinone [4]. Nonenzymatic antioxidants can be enhanced by antioxidant intake. In recent years, many natural products that have abundant antioxidants were reported to possess the effect of scavenging free radicals and protecting the liver from oxidative damage [4, 5].

Lemon is a popular fruit consumed as juice and contains high contents of vitamins and polyphenols (mainly flavonoids), such as hesperidin, eriocitrin, naringin, neohesperidin, rutin quercetin, chlorogenic acid, luteolin, and kaempferol [6]. The in vivo and in vitro experiments have shown that lemon has various health benefits, such as anticancer effect, antimicrobial effect, lipid-lowering effect, and protective effect against cardiovascular diseases [6]. In addition, lemon is used to treat liver ailments in tribal medicine [7]. However, effects of lemon juice on chronic alcohol-induced liver injury have not been reported in the literature. The objective of this study is to investigate the effects of lemon juice on chronic alcohol-induced liver injury in mice. In addition, the in vitro antioxidant capacities of lemon juice were evaluated. The results of this study could supply valuable information for the general public to reduce harm of alcohol consumption.

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2. Materials and Methods

2.1. Chemicals and Reagents

The compounds 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,4,6-tri(2-pyridyl)- S-triazine (TPTZ), quercetin, gallic acid, and Folin–Ciocalteu’s phenol reagent were purchased from Sigma-Aldrich (St. Louis, MO, USA). Assay kits for the determination of SOD, lipid peroxidation, CAT, and TG contents were purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, China). Other chemicals were of analytical grade.

2.2. Materials

Lemon was obtained from markets in Guangzhou, China. The fruit was cleaned with deionized water. The edible portion was weighed precisely and mixed with deionized water (1 : 1, m/v), and the mixture was ground into a homogenate with a homogenizer. Then, the homogenate was centrifuged at 5,000g for 10 min, and the supernatant was obtained. The supernatant was used for the measurement of antioxidant capacity, total phenolic contents (TPC), and total flavonoid contents (TFC) and for animal experiments. Moreover, in animal experiments, the original supernatant and the diluted supernatant (1 : 5 and 1 : 10, m/v) were used as the high, medium, and low dose, respectively. The lemon juice was freshly prepared before gavage every time.

2.3. Animal Study

Male C57BL/6 mice (20–25 g) were employed in this study. Thirty mice were randomly divided into 5 groups, each group containing 6 mice. They were maintained in a SPF laboratory animal room, which kept a 12 h light/dark cycle at 22 ± 0.5°C with 40%–60% relative humidity. The animal study was performed according to the “Principles of Laboratory Animal Care” and approved by the Institutional Animal Ethics Committee of Sun Yat-sen University. The model group was treated daily with ethanol and distilled water (10 mL/kg) at the same time; the lemon juice treatment groups were treated daily with different concentrations (high dose 1 : 1 (m/v), medium dose 1 : 5, and low dose 1 : 10) of lemon juice (10 mL/kg) and ethanol simultaneously; the control group was treated daily with isometric distilled water. The model group and the lemon juice treatment groups were given ethanol according to the following ways: 35% ethanol (v/v) at a dose of 3 g/kg body weight for 7 days, 40% ethanol (v/v) at a dose of 4 g/kg body weight for the next 7 days, and 52% ethanol (v/v) at a dose of 5 g/kg body weight on the 15th day [8]. All the intervention methods were intragastric administration. The blood and liver were collected from mice 9 h after the last ethanol administration. The blood sample was centrifuged at 4,000g for 10 min and the serum was collected. The obtained serums were stored at −22°C before determination. A piece of tissue was taken from liver and fixed in 4% paraformaldehyde, and then the remaining liver tissue was stored at −22°C until use.

2.4. Measurement of Biochemical Parameters in the Serum

The levels of ALT, AST, and TG in serum were determined by a Hitachi-7180 automated biochemistry analyzer (Hitachi, Japan) with the corresponding reagent kit.

2.5. Measurement of TG and Antioxidant Enzyme Activities in the Liver

The levels of TG, SOD, and CAT in liver tissue were measured using the commercial detection kits according to the manufacturer’s instructions.

2.6. Measurement of Lipid Peroxidation Levels in the Liver

The levels of lipid peroxidation in liver tissue were measured by thiobarbituric acid (TBA) method using the commercial detection kits according to the manufacturer’s instructions. The reference standard was malondialdehyde (MDA), and the results were expressed as nmol MDA equivalent/mg prot.

2.7. Liver Histopathological Assessment

The liver tissue fixed in 4% paraformaldehyde was embedded in paraffin, sectioned into 5 μm thickness, and stained with hematoxylin-eosin (H&E) for evaluation of histopathological changes. The histopathological changes of stained liver slices were observed under a bright-field microscope.

2.8. Ferric-Reducing Antioxidant Power (FRAP) Assay

The FRAP assay was performed based on the method described in the literature [9]. In brief, the FRAP reagent was prepared from 10 mmol/L TPTZ solution, 20 mmol/L iron(III) chloride solution, and 300 mmol/L sodium acetate buffer solution (pH 3.6) in a volume ratio of 1 : 1 : 10, respectively. 100 μL of the diluted sample was added to 3 mL of the FRAP reagent and the mixture was measured after 4 min at 593 nm. The standard curve was established using FeSO₄ solution, and the results were expressed as μmol Fe(II)/g dry weight of lemon.

2.9. Trolox Equivalent Antioxidant Capacity (TEAC) Assay

The TEAC assay was carried out according to the procedure in the literature [10]. Briefly, the ABTS^•+ stock solution was prepared from 2.45 mmol/L potassium persulfate and 7 mmol/L ABTS solution in a volume ratio of 1 : 1 and then placed in the dark for 16 h at room temperature. The ABTS^•+ working solution was prepared by diluting the stock solution, and the absorbance of ABTS^•+ working solution was 0.710 ± 0.05 at 734 nm. 100 μL of the diluted sample was mixed with 3.8 mL ABTS^•+ working solution, and the absorbance of the mixture was measured at 734 nm after 6 min, and the percent of inhibition of absorbance at 734 nm was calculated. The reference standard was Trolox, and the results were expressed as μmol Trolox/g dry weight of lemon.

2.10. Determination of TPC

TPC were measured according to the literature [11]. Briefly, 0.50 mL of the diluted sample was added to 2.5 mL of 0.2 mmol/L Folin–Ciocalteu reagent. After 4 min, 2 mL of saturated sodium carbonate solution was added. After incubation for 2 h at room temperature, the absorbance of the mixture was measured at 760 nm. The reference standard was gallic acid, and the results were expressed as mg gallic acid equivalent (GAE)/g dry weight of lemon.

2.11. Determination of TFC

TFC were measured according to the literature [12]. In brief, 0.50 mL of the sample was mixed with 1.5 mL of 95% ethanol (v/v), 0.1 mL of 10% aluminum chloride (w/v), 0.1 mL of 1 mol/L potassium acetate, and 2.8 mL of water. After incubation for 30 min at room temperature, the absorbance of the mixture was determined at 415 nm. The reference standard was quercetin, and the results were expressed as mg of quercetin equivalent (QE)/g dry weight of lemon.

2.12. Statistical Analysis

Statistical analysis was carried out by one-way analysis of variance (ANOVA) with post hoc LSD test using SPSS 13.0 software. p < 0.05 was regarded as significant.

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3. Results

3.1. Effects of Lemon Juice on the Levels of ALT and AST in Serum

As shown in Figure 1, the administration of alcohol led to a significant (p < 0.05) elevation of alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum of the model group compared with that of the control group. The administration of low and medium concentration of lemon juice slightly prevented the elevation of serum level of AST, while a high dose of lemon juice significantly (p < 0.05) decreased it. At the same time, the prevention of the elevation of serum levels of ALT was observed significantly (p < 0.05) in medium and high concentration of lemon juice group and displayed a dose-effect relationship.

Figure 1

Effects of lemon juice on the levels of AST (a) and ALT (b) in serum of mice. Control: normal group; Model: alcohol group; LL: alcohol and low dose of lemon juice group; LM: alcohol and medium dose of lemon juice group; LH: alcohol and high dose of lemon juice group. ∗ means the levels of parameters in the model group were significantly (p < 0.05) different from those of the control group. # means the levels of parameters in the treatment group were significantly (p < 0.05) different from those of the model group.

3.2. Effects of Lemon Juice on the Levels of TG in Serum and Liver

Triacylglycerol (TG) content in serum was significantly (p < 0.05) increased in the model group compared with that in the control group (Figure 2(a)). Administration of lemon juice reduced the accumulation of TG in a dose-dependent manner, especially in high concentration of lemon juice group (p < 0.05). In addition, hepatic TG content was significantly (p < 0.05) increased in model group compared with that in the control group (Figure 2(b)). Administration of medium and high concentration of lemon juice significantly (p < 0.05) reduced the accumulation of hepatic TG in a dose-dependent manner.

Figure 2

Effects of lemon juice on TG contents in serum (a) and liver (b). Control: normal group; Model: alcohol group; LL: alcohol and low dose of lemon juice group; LM: alcohol and medium dose of lemon juice group; LH: alcohol and high dose of lemon juice group. ∗ means the levels of parameters in the model group were significantly (p < 0.05) different from those of the control group. # means the levels of the parameters in the treatment group were significantly (p < 0.05) different from those of the model group.

3.3. Effects of Lemon Juice on Liver Lipid Peroxidation Levels

The lipid peroxidation levels in liver tissue are shown in Figure 3. Compared with that of the control group, there was a significant (p < 0.05) increase in the lipid peroxidation level of the model group. The administration of lemon juice significantly (p < 0.05) decreased the level of lipid peroxidation in a dose-dependent manner.

Figure 3

Effects of lemon juice on hepatic lipid peroxidation level in mice. Control: normal group; Model: alcohol group; LL: alcohol and low dose of lemon juice group; LM: alcohol and medium dose of lemon juice group; LH: alcohol and high dose of lemon juice group. ∗ means the levels of the parameters in the model group were significantly (p < 0.05) different from those of the control group. # means the levels of the parameters in the treatment group were significantly (p < 0.05) different from those of the model group.

3.4. Effects of Lemon Juice on Liver Antioxidant Enzyme Activities

Figure 4 represents the results of hepatic antioxidant enzyme activities in five groups. The SOD level in the liver increased significantly (p < 0.05) in the model group compared with that in the control group. The CAT level in the liver decreased only slightly (p > 0.05) in the model group compared with the control group in this study. However, treatment with lemon juice significantly (p < 0.05) decreased the levels of SOD and CAT compared with those of the model group. In addition, all the biochemical parameters are summarized in Table 1.

Figure 4

Effects of lemon juice on the activities of SOD (a) and CAT (b) in liver. Control: normal group; Model: alcohol group; LL: alcohol and low dose of lemon juice group; LM: alcohol and medium dose of lemon juice group; LH: alcohol and high dose of lemon juice group. ∗ means the levels of the parameters in the model group were significantly (p < 0.05) different from those of the control group. # means the levels of the parameters in the treatment group were significantly (p < 0.05) different from those of the model group.

Table 1

Effects of lemon juice on the levels of several biochemical parameters.

Parameters	Control	Model	LL	LM	LH
AST (U/L)	103 ± 10.45	136.53 ± 19.94^∗	117.88 ± 15.37	113.5 ± 7.7	98.85 ± 10.94^#
ALT (U/L)	40.5 ± 3.89	54.32 ± 4.76^∗	54.05 ± 7.18	41.32 ± 6.25^#	34.68 ± 2.71^#
Serum TG (nmol/L)	0.4 ± 0.06	1.01 ± 0.12^∗	1.09 ± 0.04	1.03 ± 0.05	0.82 ± 0.08^#
Liver TG (mmol/g prot)	0.07 ± 0.01	0.1 ± 0.02^∗	0.09 ± 0.01	0.07 ± 0.01^#	0.06 ± 0.01^#
Lipid peroxidation (nmol MDA equivalent/mg prot)	0.64 ± 0.14	1.26 ± 0.22^∗	0.88 ± 0.12^#	0.84 ± 0.15^#	0.72 ± 0.13^#
SOD (U/mg prot)	89.6 ± 3.42	97.51 ± 3.96^∗	85.27 ± 5.57^#	83 ± 9.28^#	81.03 ± 6.65^#
CAT (U/mg prot)	6.55 ± 0.41	6.29 ± 0.39	5.55 ± 0.64^#	5.47 ± 0.28^#	5.17 ± 0.51^#

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Note. Control: normal group; Model: alcohol group; LL: alcohol and low dose of lemon juice group; LM: alcohol and medium dose of lemon juice group; LH: alcohol and high dose of lemon juice group. ∗ means the levels of the parameters in the model group were significantly (p < 0.05) different from that of the control group. # means the levels of the parameters in the treatment group were significantly (p < 0.05) different from that of the model group.

3.5. Histopathological Evaluation

Histopathology assessment of the liver was carried out for all groups (Figure 5). There was no pathological abnormality observed in the liver of the control group with preserved cytoplasm and distinct nucleus as shown in Figure 5(a). In Figure 5(b), it was observed in the model group that ethanol induced necrosis changes and substantial small fat droplets changes in liver section. However, livers of mice in all lemon juice treated groups showed noticeable recovery from ethanol induced liver damage with fewer small fat droplets changes and hepatocytes necrosis features.

Figure 5

The photomicrographs of liver sections taken from mice. (a) Normal group; (b) alcohol group; (c) alcohol and low dose of lemon juice group; (d) alcohol and medium dose of lemon juice group; (e) alcohol and high dose of lemon juice group. Arrow indicates a condition of small fat droplets changes, and the circle indicates hepatocytes necrosis, which mainly occurs in alcohol model group.

3.6. The In Vitro Antioxidant Activity, Total Phenolic Contents (TPC), and Total Flavonoid Contents (TFC) of Lemon Juice

The in vitro antioxidant activities of lemon were evaluated using ferric-reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays. The FRAP and TEAC values were 50.82 ± 2.70 μmol Fe(II)/g dry weight (DW) and 19.88 ± 0.66 μmol Trolox/g DW, respectively. The total phenolic contents (TPC) and total flavonoid contents (TFC) of lemon were 6.21 ± 0.28 mg GAE/g DW and 0.30 ± 0.03 mg QE/g DW, respectively.

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4. Discussion

Alcohol use disorder causes substantial diseases, and the liver is the most adversely affected organ. In the present study, the effects of lemon juice on chronic alcohol-induced liver injury in mice were investigated. Ethanol induced impairment of liver in mice was evidenced by increased AST and ALT levels. Treatment with lemon juice lowered the increased levels of AST and ALT in serum. The return of the activities of aminotransferases (AST or ALT) in serum to normal indicates the regeneration of hepatocytes and the healing of hepatic parenchyma; therefore, lemon juice had a protective effect on alcohol-induced liver injury. The results were in agreement with previous reports that showed lemon possessing a hepatoprotective effect on liver injury induced by carbon tetrachloride and acute exercise [7, 13]. In addition, the chronic alcohol-induced liver damage was further confirmed by liver histopathological changes in the present study, and treatment with lemon juice also remarkably improved the liver histopathological changes, which further confirmed the hepatoprotective activity of lemon juice on alcohol-induced liver injury in mice.

Various factors and mechanisms are associated with the pathological progress of alcohol-induced liver injury, and oxidative stress was one of them [3]. ROS is one kind of prooxidants including hydroxyl radical, superoxide radical, and hydrogen peroxide, which are frequently generated spontaneously during metabolism. Normally produced ROS is rapidly eliminated by the antioxidant defense system. The antioxidant defense system is able to scavenge ROS and terminate chain reaction of free radicals in vivo. Alcoholic exposure can result in excessive accumulation of ROS and contribute to cellular damage. Excessive accumulation of ROS could cause lipid peroxidation of hepatocytes, which was regarded as the primary mechanism concerned with chronic alcohol-induced liver damage [8]. MDA, the product of lipid peroxidation induced by ROS, also accumulates in the alcohol-damaged liver and represents a good estimation of the total oxidative stress [3]. In the present study, alcohol significantly augmented lipid peroxidation levels, which was similar to the previous study that showed increased lipid peroxidation in alcoholic patients [14]. Treatment with lemon juice reduced the level of lipid peroxidation to a normal level, which showed a significant protective effect of lemon juice against alcohol-induced oxidative stress.

Liver steatosis is the earliest disease of the liver on account of chronic ethanol consumption, with the characteristic of fat accumulation. It is generally accepted that, in the development of hepatic steatosis, ethanol exposure increases the ratio of reduced nicotinamide adenine dinucleotide/oxidized nicotinamide adenine dinucleotide in hepatocytes, which disturb mitochondrial fatty acid β-oxidation and induce steatosis further [15]. In this study, alcohol-induced occurrence of hepatic steatosis was confirmed by increased hepatic TG contents and histopathological changes. Treatment with lemon juice significantly lowered the hepatic TG contents and improved the damaged histopathological changes. In particular, the mice given high dose of lemon juice had almost completely recovered to normal.

The antioxidant enzymes, such as SOD and CAT, represent the defense response system to excessive ROS. SOD catalyzes the dismutation of two superoxide anions to hydrogen peroxide and oxygen, and then CAT degrades two hydrogen peroxide molecules to water and oxygen [16]. SOD is also considered as front line among antioxidant enzymes in defense against free radicals. In the literature, the effects of alcohol treatment on the levels of SOD/CAT are controversial. SOD showed an increase, no changes, or a decrease, depending on the model, diet, duration, and amount of alcohol consumption [17–19]. In addition, it was reported that CAT activity decreased upon chronic ethanol consumption in a study [20]. However, another study showed that CAT activity was increased in rat liver [18]. In our study, the alcohol treatment significantly increased the activity of SOD and slightly decreased the activity of CAT, while treatment with lemon juice decreased the activities of SOD and CAT. The increased activity of SOD reflects the activation of the compensatory mechanism which might be an attempt to counteract free radicals in the liver [21]. The treatment with lemon juice prevented ROS accumulation, and the compensatory effects were not available in the liver. Therefore, lemon juice decreased the activities of SOD and CAT. The results were similar to the report of Gasparotto et al. [22]. In addition, the in vitro antioxidant experiment of lemon also showed that lemon had medium in vitro antioxidant capacities, which contribute to the explanation of the in vivo free radical scavenging effect of lemon.

Lemon contains numerous beneficial bioactive compositions, including phenolic compounds (mainly flavonoids), vitamins, carotenoids, essential oils, minerals, and dietary fiber [6]. The hepatoprotective effect of lemon may be attributable to the presence of vitamins, flavonoids, essential oils, and pectin. Vitamin C, a water-soluble antioxidant in lemon, is in a unique position to scavenge aqueous peroxyl radicals and react with free radicals, thus preventing oxidative damage including lipid peroxidation [14]. Sometimes, vitamin C could exert prooxidative effects at low concentrations and in the existence of transition metal ions [23], which might aggravate oxidative stress. However, it is difficult for vitamin C to have prooxidative effects in vivo due to the presence of NADPH-dependent recycling systems and glutathione [24]. In addition, there were some literatures reporting that vitamin C supplementation alone could reduce oxidative stress induced by ethanol, and the hepatoprotective effect of vitamin C treatment was more effective than silymarin, quercetin, and thiamine [25, 26]. Flavonoids, a class of secondary plant phenolics, can interact with hydroxyl radicals, chelate metal catalysts, and inhibit oxidases [27]. In previous studies, lemon flavonoid was shown to possess a hepatoprotective effect on liver damage induced by carbon tetrachloride and acute exercise, and the mechanism of the protective effect was related to the antioxidant capacity [7, 13]. Lemon essential oils and pectin were found to have protective effects on stomach and intestine barrier function [28, 29]. Ethanol exposure can injure the defensive intestinal barrier and increase the permeability of the small intestine, which lead to bacterial endotoxins leakage [25]. The bacterial endotoxins leakage is an important factor in the pathogenesis of alcohol-induced liver injury [30]. Therefore, the lemon essential oils and pectin might protect the intestine barrier function, thus indirectly protecting against alcohol-induced liver injury.

In this study, lemon juice revealed a protective effect on chronic alcohol-induced liver injury. Due to the fact that lemon contains a variety of bioactive ingredients, the hepatoprotective effect might be the result of joint action of multiple mechanisms, and it is difficult to clarify the specific mechanism of effect. The medium in vitro antioxidant capacities of lemon and reduced in vivo MDA levels indicated that lemon might reduce the oxidative stress induced by ethanol, thus exerting hepatoprotective effects. This study has found that lemon juice has a strong hepatoprotective effect, which provides valuable information for the general public to reduce harm of alcohol consumption. In the future, active components in lemon juice should be separated and identified, and the mechanism of action of the purified compound should be explored, including the action on the small intestine.

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5. Conclusions

Chronic alcohol consumption could induce liver injury. Lemon juice is readily available as a widely consumed beverage. In this study, we found that treatment with lemon juice exerted hepatoprotective effects on alcohol-induced liver injury in mice through decreasing the levels of serum ALT and AST as well as hepatic TG and lipid peroxidation. In addition, the in vitro antioxidant experiment of lemon showed that lemon had medium in vitro antioxidant capacities. Therefore, we speculate that the hepatoprotective effects might be related to the antioxidant capacities of lemon juice. The results showed that lemon juice might be a potential dietary supplement for the prevention and treatment of liver injury related to chronic alcohol consumption.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81372976), Key Project of Guangdong Provincial Science and Technology Program (no. 2014B020205002), and the Hundred-Talents Scheme of Sun Yat-sen University.

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Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

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Authors’ Contributions

Tong Zhou and Yu-Jie Zhang contributed equally to this work.

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References

1. Zhou Y., Zheng J., Li S., Zhou T., Zhang P., Li H.-B. Alcoholic beverage consumption and chronic diseases. International Journal of Environmental Research and Public Health. 2016;13(6, article 522) doi: 10.3390/ijerph13060522. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

2. Arteel G., Marsano L., Mendez C., Bentley F., McClain C. J. Advances in alcoholic liver disease. Best Practice and Research in Clinical Gastroenterology. 2003;17(4):625–647. [PubMed] [Google Scholar]

3. Cao Y.-W., Jiang Y., Zhang D.-Y., et al. Protective effects of Penthorum Chinense Pursh against chronic ethanol-induced liver injury in mice. Journal of Ethnopharmacology. 2015;161:92–98. doi: 10.1016/j.jep.2014.12.013. [PubMed] [CrossRef] [Google Scholar]

4. Li S., Tan H.-Y., Wang N., et al. The role of oxidative stress and antioxidants in liver diseases. International Journal of Molecular Sciences. 2015;16(11):26087–26124. doi: 10.3390/ijms161125942. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

5. Wang F., Li Y., Zhang Y. J., Zhou Y., Li S., Li H. B. Natural products for the prevention and treatment of hangover and alcohol use disorder. Molecules. 2016;21(1, article 64) doi: 10.3390/molecules21010064. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

6. González-Molina E., Domínguez-Perles R., Moreno D. A., García-Viguera C. Natural bioactive compounds of Citrus limon for food and health. Journal of Pharmaceutical and Biomedical Analysis. 2010;51(2):327–345. doi: 10.1016/j.jpba.2009.07.027. [PubMed] [CrossRef] [Google Scholar]

7. Bhavsar S. K., Joshi P., Shah M. B., Santani D. D. Investigation into hepatoprotective activity of Citrus limon. Pharmaceutical Biology. 2007;45(4):303–311. doi: 10.1080/13880200701214995. [CrossRef] [Google Scholar]

8. Zhang Y., Zhou T., Wang F., et al. The effects of syzygium samarangense, passiflora edulis and solanum muricatum on alcohol-induced liver injury. International Journal of Molecular Sciences. 2016;17(10, article 1616) doi: 10.3390/ijms17101616. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Benzie I. F. F., Strain J. J. The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Analytical Biochemistry. 1996;239(1):70–76. doi: 10.1006/abio.1996.0292. [PubMed] [CrossRef] [Google Scholar]

10. Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine. 1999;26(9-10):1231–1237. doi: 10.1016/S0891-5849(98)00315-3. [PubMed] [CrossRef] [Google Scholar]

11. Li A.-N., Li S., Li H.-B., Xu D.-P., Xu X.-R., Chen F. Total phenolic contents and antioxidant capacities of 51 edible and wild flowers. Journal of Functional Foods. 2014;6(1):319–330. doi: 10.1016/j.jff.2013.10.022. [CrossRef] [Google Scholar]

12. Kosalec I., Bakmaz M., Pepeljnjak S., Vladimir-Knezevic S. Quantitative analysis of the flavonoids in raw propolis from northern Croatia. Acta Pharmaceutica. 2004;54(1):65–72. [PubMed] [Google Scholar]

13. Minato K.-I., Miyake Y., Fukumoto S., et al. Lemon flavonoid, eriocitrin, suppresses exercise-induced oxidative damage in rat liver. Life Sciences. 2003;72(14):1609–1616. doi: 10.1016/S0024-3205(02)02443-8. [PubMed] [CrossRef] [Google Scholar]

14. Masalkar P. D., Abhang S. A. Oxidative stress and antioxidant status in patients with alcoholic liver disease. Clinica Chimica Acta. 2005;355(1-2):61–65. doi: 10.1016/j.cccn.2004.12.012. [PubMed] [CrossRef] [Google Scholar]

15. Gu J., Zhang Y., Xu D., et al. Ethanol-induced hepatic steatosis is modulated by glycogen level in the liver. Journal of Lipid Research. 2015;56(7):1329–1339. doi: 10.1194/jlr.M056978. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

16. Li G., Ye Y., Kang J., et al. L-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes. Food and Chemical Toxicology. 2012;50(2):363–372. doi: 10.1016/j.fct.2011.10.036. [PubMed] [CrossRef] [Google Scholar]

17. Cheng N., Du B., Wang Y., et al. Antioxidant properties of jujube honey and its protective effects against chronic alcohol-induced liver damage in mice. Food and Function. 2014;5(5):900–908. doi: 10.1039/c3fo60623f. [PubMed] [CrossRef] [Google Scholar]

18. Ignatowicz E., Wozniak A., Kulza M., et al. Exposure to alcohol and tobacco smoke causes oxidative stress in rats. Pharmacological Reports. 2013;65(4):906–913. doi: 10.1016/S1734-1140(13)71072-7. [PubMed] [CrossRef] [Google Scholar]

19. Kanbagli O., Balkan J., Aykac-Toker G., Uysal M. Hepatic mitochondrial prooxidant and antioxidant status in ethanol-induced liver injury in rats. Biologicala and Pharmaceutical Bulletin. 2002;25(11):1482–1484. [PubMed] [Google Scholar]

20. Das S. K., Dhanya L., Varadhan S., Mukherjee S., Vasudevan D. M. Effects of chronic ethanol consumption in blood: a time dependent study on rat. Indian Journal of Clinical Biochemistry. 2009;24(3):301–306. doi: 10.1007/s12291-009-0056-4. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

21. De David C., Rodrigues G., Bona S., et al. Role of quercetin in preventing thioacetamide-induced liver injury in rats. Toxicologic Pathology. 2011;39(6):949–957. doi: 10.1177/0192623311418680. [PubMed] [CrossRef] [Google Scholar]

22. Gasparotto J., Somensi N., Bortolin R. C., et al. Preventive supplementation with fresh and preserved peach attenuates CCl₄-induced oxidative stress, inflammation and tissue damage. Journal of Nutritional Biochemistry. 2014;25(12):1282–1295. doi: 10.1016/j.jnutbio.2014.07.004. [PubMed] [CrossRef] [Google Scholar]

23. Jurczuk M., Brzóska M. M., Moniuszko-Jakoniuk J. Hepatic and renal concentrations of vitamins E and C in lead- and ethanol-exposed rats. An assessment of their involvement in the mechanisms of peroxidative damage. Food and Chemical Toxicology. 2007;45(8):1478–1486. doi: 10.1016/j.fct.2007.02.007. [PubMed] [CrossRef] [Google Scholar]

24. Cobley J. N., McHardy H., Morton J. P., Nikolaidis M. G., Close G. L. Influence of vitamin C and vitamin e on redox signaling: implications for exercise adaptations. Free Radical Biology and Medicine. 2015;84:65–76. doi: 10.1016/j.freeradbiomed.2015.03.018. [PubMed] [CrossRef] [Google Scholar]

25. Abhilash P. A., Harikrishnan R., Indira M. Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: a mechanistic approach. Toxicology and Applied Pharmacology. 2014;274(2):215–224. doi: 10.1016/j.taap.2013.11.005. [PubMed] [CrossRef] [Google Scholar]

26. Ambadath V., Venu R. G., Madambath I. Comparative study of the efficacy of ascorbic acid, quercetin, and thiamine for reversing ethanol-induced toxicity. Journal of Medicinal Food. 2010;13(6):1485–1489. [PubMed] [Google Scholar]

27. Heim K. E., Tagliaferro A. R., Bobilya D. J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. Journal of Nutritional Biochemistry. 2002;13(10):572–584. doi: 10.1016/S0955-2863(02)00208-5. [PubMed] [CrossRef] [Google Scholar]

28. Vogt L. M., Sahasrabudhe N. M., Ramasamy U., et al. The impact of lemon pectin characteristics on TLR activation and T84 intestinal epithelial cell barrier function. Journal of Functional Foods. 2016;22:398–407. doi: 10.1016/j.jff.2016.02.002. [CrossRef] [Google Scholar]

29. Rozza A. L., Moraes T. D. M., Kushima H., et al. Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E2. Chemico-Biological Interactions. 2011;189(1-2):82–89. doi: 10.1016/j.cbi.2010.09.031. [PubMed] [CrossRef] [Google Scholar]

30. Wang Y., Kirpich I., Liu Y., et al. Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. American Journal of Pathology. 2011;179(6):2866–2875. doi: 10.1016/j.ajpath.2011.08.039. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

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References

1. Zhou Y., Zheng J., Li S., Zhou T., Zhang P., Li H.-B. Alcoholic beverage consumption and chronic diseases. International Journal of Environmental Research and Public Health. 2016;13(6, article 522) doi: 10.3390/ijerph13060522. – DOI – PMC – PubMed
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Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure

Abstract

Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. Methods: Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200–250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). Results: The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. Conclusions: This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment.

Keywords: acute on chronic liver failure, hepatoprotective, oxidative stress, Taraxacum officinale, 3-nitrotyrosine

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1. Introduction

Liver diseases are one of the major health problems in the world and became a general health care problem due to the high morbidity rate. They are associated with several risk factors such as inadequate nutrition, metabolic diseases, viral infection, ethanol, and drug use. Liver injury may trigger the onset of liver failure, a common medical condition with very high mortality [1]. Liver failure can progress as acute liver failure (ALF), as acute on chronic liver failure (ACLF), or as acute decompensation of end-stage liver disease [2]. ALF is defined as a severe liver injury in the absence of pre-existing liver disease. According to the World Gastroenterology Organization ACLF is defined as “a syndrome in patients with chronic liver disease with or without previously diagnosed cirrhosis, characterized by acute hepatic decompensation resulting in liver failure (jaundice and prolongation of the international normalized ratio) and one or more extrahepatic organ failures, associated with increased mortality up to three months” [2,3]. The prevalence of ACLF ranges from 24% to 40%, and it usually occurs in young or middle-aged patients [4] and it is potentially reversible [2].

The exact mechanism of ACLF is not fully elucidated but based on what was found the pathophysiology was described using a four-stage model: precipitating event, hepatic injury due to precipitating event, response to injury, and failure of other organs [4,5]. The precipitating event can be triggered by one or more factors, identified or unidentified, like infections, alcohol, gastrointestinal bleeding, reactivation of viral hepatitis B (HBV), superinfection with hepatitis A or E virus, acute episodes of autoimmune hepatitis, Wilson’s disease, or vascular liver disease [2,6,7]. During the propagation phase, the number of proinflammatory mediators increases, a systemic inflammatory response syndrome and a vascular endothelial dysfunction will be activated, with progression to organs failure. At the same time, liver macrophages release anti-inflammatory cytokines that will initiate a compensatory anti-inflammatory response syndrome, leading to an acquired immunodeficiency, a “paralysis of the immune response” [4,8]. Measurement of oxidative stress, inflammation, necrosis, and apoptosis biomarkers can define the risk profile of ACLF [4,8]. The presence of multiple organ failure is a requirement for the diagnosis of ACLF, and the number of affected systems has a prognostic value. The kidneys are the most commonly affected organs [2,3].

Thus, the therapy for chronic hepatic diseases needs to develop new prophylactic agents to prevent ACLF. With the extended studies upon the use of medicinal plants, phytotherapy became an important support for the treatment of many diseases. The use of medicinal plants in the treatment of liver diseases has a long history worldwide because many phytochemicals have hepatoprotective activity [1,9,10]. Only a few of the ethnomedicinal effects have been scientifically validated [11]. Considering that in ACLF inflammation and oxidative stress are important pathogenetic mechanisms, the herbal medicines that have anti-inflammatory and antioxidant effects could be a promising source of bioactive compounds [12].

The Taraxacum officinale F. H. Wigg. (TO) (dandelion) species belong to the Asteraceae family, includes 30–57 varieties, and are widely distributed in the warm-temperate zones of the Northern Hemisphere [13,14,15]. It is a plant used in folk medicine from ancient times as anti-inflammatory, antioxidant, diuretic, choleretic, laxative, and hepatoprotective. Because the phytochemical components may define the medicinal value of a plant, their identification and effects mechanism in disease prevention and treatment is a necessity [11]. Furthermore, it has to be considered that the chemical composition of the TO extracts depends on both the extraction protocol and the solvents used (ethanol, acetone, water, or methanol) [16], but also on which part of the plant has been used (whole plant, roots, stem, leaves, flowers).

TO is also frequently used in different food products, and dietary supplements [17]. These plants were found to be rich in polyphenolic compounds, vitamins, inositol, lecithin, and minerals, and to exhibit antioxidant, anti-inflammatory, antiallergic, anti-hyperglycemic, hypolipidemic, and anticoagulant activities [9,18,19], to protect against hepatic injuries, but the mechanisms of action are still incompletely investigated [20].

It was demonstrated that TO root extract may protect against some toxic hepatic injury [11,13,21,22], but there are no studies on the potential hepatoprotective effect of this extract in ACLF. Therefore, our study aimed to extend the characterization of the ethanolic TO root extract (TOERE) and evaluate the potential use as a preventive hepatoprotective agent in a rat d-galactosamine and lipopolysaccharide (D-Gal-LPS)-induced rat ACLF model.

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2. Materials and Methods

2.1. Chemicals

Phenolic compounds Sigma (St. Louis, MO, USA), Roth (Karlsruhe, Germany), Dalton (Toronto, ON, Canada); phytosterols Sigma (St. Louis, MO, USA); Folin–Ciocâlteu reagent, sulfanylamide (SULF), N- (1-Naphthyl) ethylenediamine dihydrochloric acid (NEDD), vanadium chloride (III) (VCl3), methanol, diethyl ether, xylenol orange [o-cresosulfonphthalein-3,3-bis (sodium methyliminodiacetate)], orthodianisidinedihydrochloric acid (3-3′-dimethoxybenzidine), ferrous ammonium sulfate, hydrogen peroxide (H2O2), sulfuric acid, hydrochloric acid, glycerol, trichloroacetic acid (TCA), ethylenediaminetetra-acetic acid, sodium dodecal, sulfate butylated hydroxytoluene, thiobarbituric acid, 1,1,3,3-tetraethoxypropane, 2,4-dinitrophenylhydrazine (DNPH), 5,5’-dithionitrobis 2-nitrobenzoic acid (DTNB), 1,1-diphenyl-2-picrilhydrazyl (DPPH), o-phthalaldehyde Merck (Darmstadt, Germany); Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) Alfa-Aesar (Karlsruhe, Germany); Freund’s adjuvant, d-galactosamine (D-Gal) and lipopolysaccharide (LPS) from Merck and Sigma-Aldrich (Taufkirchen, Germany); Human serum albumin (HSA) (Octapharma GmbH, Austria). All chemicals were of analytical grade. Aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma glutamate transferase, creatinine, and urea kits were purchased from Spinreact (Sant Esteve de Bas, Spain). ELISA kit for 3-nitrotyrosine (KA0445-ABNOVA EMBLEM, Heidelberg, Germany) and primary antibody to 3-Nitrotyrosine for immunohistochemistry (Code ALX-804-505-C050, Enzo Life Sciences) were also used.

2.2. Plant Material

Fresh T. officinale F.H. Wigg. roots from the Alexandru Borza Botanical Garden “Babes-Bolyai” University of Cluj-Napoca, Romania, were purchased in June 2020, deposited in “Alexandru Borza” Botanical Garden Herbarium (Voucher CL:669002), and plant extract was prepared as previously described [23]. The roots were dried in a shaded place, grounded in a coffee grinder (Argis, RC-21, Electroarges SA, Curtea de Arges, Romania) for 5 min, and then the powder was screened through a 200 μm Retsch sieve [24]. Fifty grams were weighed and extracted with 70% ethanol, twice for 30 min using the UltraTurrax extraction apparatus (T 18; IKA Labortechnik, Staufen, Germany) at room temperature. The samples were then centrifuged at 4000 rpm for 30 min, and the supernatant was recovered, and filtered through a 0.45 μm micropore membrane (PTFE, Waters, Milford, MA, USA). The solvent was evaporated at 40 °C using a rotary evaporator (Hei-VAP, Heidolph Instruments GmbH & Co., Schwabach, Germany). Further, the obtained extracts were lyophilized (Advantage 2.0, SP Scientific, Warminster, PA, USA) [24]. The extract powder was stored at room temperature in airtight bottles. The extraction yield was 15.2% (w/w).

2.3. Phytochemical Analysis

Identification and Quantification of Polyphenolic Compounds by HPLC-DAD-ESI MS

The phenolic compounds of the T. officinale extracts were determined as previously described [23,24] with some modifications. Prior to LC analysis, the lyophilized extract was dissolved in MeOH. Chlorogenic acid was used for phenolic acid quantification, and results were expressed as mg chlorogenic acid equiv./g of dry plant material (mg CA/g d.w.) [25].

2.4. Animals and Experimental Design

The experiments were carried out on adult male Albino Wistar rats (strain Crl: WI), weighing 200–250 g, bred in the Animal Facility of Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca as previously described [23]. Animals were randomly divided into 6 groups (n = 5): Control group with no disease and no treatment, acute on chronic liver failure (ACLF) group, ACLF with Silymarin pretreatment (ACLF-SYL) group (200 mg/kg b.w./day) [26], ACLF groups with TOERE pretreatment in three doses, respectively ACLF-TO200 (200 mg dry plant material/kg b.w./day), ACLF–TO100 (100 mg dry plant material/kg b.w./day), and ACLF-TO50 (50mg dry plant material/kg b.w./day). The daily dose of TOERE has been dissolved in corn oil (1ml/day/animal). All the procedures performed on laboratory animals, comply with the Directive 2010/63/EU, and Romanian national law 43/2014 for animal protection used for scientific purposes. The project was approved by the Veterinary Sanitary Direction and Food Safety Cluj-Napoca as previously described (no. 19/ 13.12.2016) [23].

The ACLF rat model was induced by human serum albumin (HSA), d-galactosamine (D-Gal), and lipopolysaccharide (LPS) as previously described [27,28]. Silymarin (SYL) or TO have been administrated per os (p.o.) by gavage for 7 days. The ACLF group was pretreated for 7 days with physiological saline (1 mL/day/animal). After completing the treatments, on day 8 in the ACLF, ACLF-TO200, ACLF-TO100, ACLF–TO50, and ACLF-SYL groups ACLF was induced by the intraperitoneal injection (i.p.) of d-galactosamine (D-Gal) (400 mg/kg b.w.) and lipopolysaccharide (LPS) (100 μg/kg b.w.) [27,29]. Six hours after ACLF induction the rats were anesthetized with ketamine (60 mg/kg b.w.) and xylazine (15 mg/kg b.w.), blood was withdrawn by retro-orbital puncture, serum was separated by centrifugation, and stored at −80 °C until use. At the end of the experiment, under general anesthesia animals were killed by cervical dislocation and liver biopsy was harvested from each animal. The experiments were performed in triplicate.

2.5. Biochemical Serum Analysis

The hepatic injury was evaluated with conventional serum liver markers: serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (BT), alkaline phosphatase (ALP), and gamma glutamate transferase (GGT) as previously described [23]. Oxidative stress associated with liver injury was evaluated by measuring serum total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), malondialdehyde (MDA), total thiols (SH), total nitrites, and nitrates (NOx) and 3-nitrotyrosine (3NT) levels as previously described [23,30,31]. Renal failure induced by ACLF was diagnosed with creatinine and urea.

2.6. Histological Assessment

For the histological analysis two liver fragments were collected from the left lateral and right medial lobes [32], fixed in 10% phosphate-buffered formalin for 24 h, and routinely processed and embedded in paraffin wax. From each tissue fragment, two serial sections of 3 µm were stained with hematoxylin and eosin (H&E). The hepatic parenchyma was histologically assessed for intralobular and periportal degeneration/necrosis, portal inflammation, and fibrosis, and the Histological Activity Index (HAI) was calculated [33,34].

2.7. Immunohistochemical Analysis of 3-Nitrotyrosine

For the immunohistochemical analysis of 3NT, the paraffin sections were dewaxed in xylene, followed by rehydration in decreasing the concentration of alcohol. Sodium citrate buffer (pH = 6) was used for epitope retrieval and endogenous peroxidase was blocked with peroxidase for 5 min. The primary mouse monoclonal [clone 39B6] antibody to 3NT was diluted in 1% PBS-BSA (bovine serum albumin) at 1:200, and maintained overnight at 4 °C in a humid chamber, followed by placing the secondary antibody. The reaction was visualized using 3,3’-diaminobenzidine. Finally, the sections were counterstained with Mayer’s hematoxylin. The positive reaction was given by the brown labeling of the hepatocytes. Immunopositivity for 3NT was evaluated and scored, as follows: grade 0, no staining; grade 1, positive staining in less than 10% of hepatocytes/10 high power fields; grade 2, positive staining in more than 10% but less than 50% of hepatocytes/10 high power fields; grade 3, positive staining of more than 50% of hepatocytes/10 high power fields [35].

The sections were independently examined by two pathologists (MT and CT) using a light Olympus BX-41 microscope, and a multi-head microscope Zeiss Axio Scope A1 (Carl Zeiss Microscopy GmbH, Germany). When there was a divergence of opinion, an agreed diagnosis was reached by a simultaneous evaluation in a multi-head microscope Zeiss Axio Scope A1 (Carl Zeiss Microscopy GmbH, Germany). The photomicrographs were taken using an Olympus SP 350 digital camera and Stream Basic imaging software (Olympus Corporation, Tokyo, Japan).

2.8. Statistical Analysis

All results were expressed as mean ± standard deviation (SD) whenever data were normally distributed. Comparisons between the different experimental groups were performed using the one-way ANOVA test and the post hoc Bonferroni–Holm test. The correlations analysis was performed with the Pearson test. Values of p < 0.05 were considered statistically significant. The analysis was performed using IBM SPSS Statistics, version 20 (SPSS Inc. Chicago, IL, USA).

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3. Results

3.1. Phytochemical Analysis

In our study, HPLC-DAD-ESI MS identified significant concentrations of hydroxybenzoic, caffeic, and chicoric acids (Figure 1, Table 1).

Figure 1

Chromatogram obtained by HPLC-DAD-ESI MS analysis of a Taraxacum officinale root extract at 340 nm. For peak assignments, see Table 1.

Table 1

Identification and quantification of Taraxacum officinale root extract polyphenols from hydroxybenzoic and hydroxycinnamic acids groups.

No	Retention Time R_t (min)	UV λ_max (nm)	[M+H]⁺ (m/z)	Tentative Identification	Concentration * mg CA/ g TOERE
1	2.95	270	138	Hydroxybenzoic acid	3.65 ± 0.15
2	13.62	320	181, 163	Caffeic acid	1.09 ± 0.02
3	14.19	322	475, 312	Chicoric acid	1.95 ± 0.15
4	15.50	322	369	Feruloylquinic acid	0.6 ± 0.08
5	19.93	322	516, 181,163	Dicaffeoylquinic acid	0.53 ± 0.04
6	20.12	322	516, 181,163	Dicaffeoylquinic acid isomer	0.4 ± 0.03

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* mg CA/g TOERE-chlorogenic acid equiv. mg/g Taraxacum officinale ethanolic root extract. Values are the mean ± SD (n = 3).

3.2. Biochemical Serum Analysis

The hepatic injury was evaluated by measuring liver markers (AST, ALT, ALP, GGT, TB) [36] (Table 2). ACLF induction by D-Gal-LPS caused a severe increase of the liver markers than in Control animals (p < 0.001). Administration for a week of three different doses of TOERE or SYL in ACLF animals significantly prevented severe ACLF-induced increase of the AST, ALT, ALP, GGT, and TB (p < 0.001). Furthermore, the TOERE effect was dose-dependent, with the 100 mg TOERE/kg b.w./day concentration having the best inhibitory effect. In ACLF-TO200 and ACLF-TO100 groups TOERE hepatoprotective effects were better than in ACLF-SYL animals (p < 0.01) (Table 2).

Table 2

Liver and renal screening tests of the study groups.

Groups	AST (U/L)	ALT (U/L)	TB (mg/dL)	ALP (mg/dL)	GGT (mg/dL)	Urea (mg/dL)	CR (mg/dL)
ACLF-TO200	81.12 ^a ± 5.27	71.64 ^a,b,c ± 11.32	2.27 ^a,b,c ± 0.37	328.45 ^a,b ± 14.72	60.42 ^a,b,c ± 9.20	67.14 ^a,b,c ± 4.21	1.75 ^a,b ± 0.21
ACLF-TO100	82.14 ^a,b,c ± 4.20	54.08 ^b,c ± 12.37	1.30 ^b,c ± 0.27	310.38 ^a,b,c ± 11.19	49.97 ^b,c ± 8.37	78.93 ^a,b ± 5.18	1.78 ^a,b ± 0.14
ACLF-TO50	84.24 ^a,b,c ± 8.06	144.93 ^a,b,c ± 19.79	2.02 ^a,b ± 0.51	329.61 ^a,b ± 37.89	107.34 ^a,b,c ± 18.33	110.30 ^a,b,c ± 7.89	2.15 ^a,b ± 0.40
ACLF-SYL	126.37 ^a,b ± 6.58	111.67 ^a,b ± 13.04	2.44 ^a,b ± 0.13	332.59 ^a ± 29.20	74.51 ^a,b ± 9.86	81.25 ^a,b ± 12.15	2.02 ^a,b ± 0.29
ACLF	222.65 ^a,c ± 11.08	174.08 ^a,c ± 15.16	3.74 ^a,c ± 0.53	358.94 ^a,c ± 13.55	117.71 ^a,c ± 15.47	255.49 ^a,c ± 19.48	3.53 ^a,c ± 0.28
Control	35.04 ± 6.63	47.55 ± 10.08	1.01 ± 0.11	263.75 ± 15.20	44.31 ± 4.58	39.16 ± 2.71	0.57 ± 0.04

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Results are expressed as mean ± SD. Values are expressed as mean ± SD (n = 5). ^a p ˂ 0.05, versus Control; ^b p ˂ 0.05, versus ACLF; ^c p ˂ 0.05, versus SYL. AST—aspartate aminotransferase; ALT—alanine aminotransferase; TB—total bilirubin; ALP—alkaline phosphatase; GGT—gamma-glutamyltransferase; CR—creatinine; ACLF-TO200- acute on chronic liver failure pretreated with 200 mg TOERE/kg b.w./day; ACLF-TO100—acute on chronic liver failure pretreated with 100mg TOERE/kg b.w./day; ACLF-TO50—acute on chronic liver failure pretreated with 50 mg TOERE/kg b.w./day; ACLF-SYL—acute on chronic liver failure pretreated with 200 mg silymarin/kg b.w./d; ACLF—acute on chronic liver failure; Control—negative control.

Considering that in ACLF kidneys are the most affected organs, in a study of a plant with possible hepatoprotective use in ACLF it is also important to determine the nephroprotective activity. ACLF induction by D-Gal- LPS caused a severe increase of creatinine and urea (p < 0.001). Renal dysfunction tests were positively correlated with the liver markers (r = 0.6–0.9) in ACLF animals. The treatments of ACLF rats with TOERE or SYL caused a smaller increase of serum creatinine and urea after ACLF induction (p < 0.001). SYL effect was comparable to that from ACLF-TO200 and ACLF-TO100 groups, but better than that from ACLF-TO50 animals (Table 2).

In our study systemic oxidative stress was also evaluated. Compared to the control, serum TOS, OSI, and MDA were elevated in ACLF animals (p < 0.001. The treatment with TOERE or SYL reduced TOS, OSI and MDA increase after ACLF induction (p < 0.01). TOERE effect on the oxidative stress was dose-dependent, the higher concentration having the best antioxidant effect (Table 3).

Table 3

Oxidative stress tests of the study groups.

Groups	TOS (µM H₂O₂/L)	TAR (mM TROLOX/L)	OSI	MDA (nM/L)	NOx (µM/L)	3NT (nmol/L)	SH (mM GSH/L)
ACLF-TO200	30.61 ^a,b,c ± 6.85	1.088 ± 0.001	31.57 ^a,b,c ± 6.13	3.05 ^a,b,c ± 0.28	21.92 ^b,c ± 3.74	769.36 ^a,b,c ± 78.46	0.48 ^a,b ± 0.03
ACLF-TO100	35.50 ^a,b,c ± 7.27	1.089 ± 0.001	31.17 ^a,b,c ± 4.84	3.67 ^b ± 0.59	25.76 ^a,b,c ± 4.50	768.66 ^a,b,c ± 69.75	0.48 ^a,b ± 0.08
ACLF-TO50	40.45 ^a,b,c ± 8.46	1.089 ± 0.001	31.82 ^a,b,c ± 9.39	3.95 ^a,b ± 0.47	30.52 ^a,b,c ± 7.60	820.20 ^a,b,c ± 48.43	0.48 ^a,b ± 0.02
ACLF-SYL	36.41 ^a,b ± 7.75	1.092 ± 0.003	37.03 ^a,b ± 8.27	3.83 ^a,b ± 0.34	36.56 ^a,b ± 6.76	971.07 ^a,b ± 68.34	0.52 ^a,b ± 0.02
ACLF	47.98 ^a,c ± 7.95	1.089 ± 0.001	40.40 ^a,c ± 8.60	5.37 ^a,c ± 0.08	51.49 ^a,c ± 7.32	1053.99 ^a,c ± 91.15	0.40 ^a,c ± 0.03
Control	21.18 ± 1.72	1.089 ± 0.001	21.59 ± 4.61	3.57 ± 0.36	19.98 ± 1.99	480.45 ± 56.62	0.59 ± 0.01

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Results are expressed as mean ± SD. ^a p ˂ 0.05, versus Control; ^b p ˂ 0.05, versus ACLF; ^c p ˂ 0.05, versus SYL. TOS—total oxidative status; TAR—total antioxidant reactivity; OSI—oxidative stress index; NOx—nitric oxide; 3NT—3-nitrotyrosine; MDA—malondialdehyde; SH—total thiols; ACLF-TO200—acute on chronic liver failure pretreated with 200 mg TOERE/kg b.w./day; ACLF-TO100—acute on chronic liver failure pretreated with 100 mg TOERE/kg b.w./day; ACLF-TO50—acute on chronic liver failure pretreated with 50 mg TOERE/kg b.w./day; ACLF-SYL—acute on chronic liver failure pretreated with 200 mg silymarin/kg b.w./d; ACLFacute on chronic liver failure; Control—negative control.

In ACLF rats NOx and 3NT were also increased (p < 0.001). TOERE pretreatments prevented NOx and 3NT elevation (p < 0.001) after ACLF induction in a dose-dependent way, with a higher concentration having a better inhibitory activity. SYL was also a good inhibitor of NO production and peroxidation in ACLF animals (p < 0.001), but the effect was smaller than that of TOERE (Table 3).

Additionally, serum antioxidative activity was evaluated by measuring TAR and SH. TAR was not influenced by ACLF induction (p > 0.05). A depletion in the level of SH was observed in ACLF rats (p < 0.01), and the treatment with TO or SYL prevent SH reduction (p < 0.05) after ACLF induction. SYL has a better effect than TO on SH (Table 3).

3.3. Histological Assessment

In the livers of the Control group, no significant structural changes were observed (Figure 2a).

Figure 2

Photomicrographs of the liver tissues from the control and experimental animals. H&E stain: (a). Control; (b). ACLF; (c). ACLF-SYL; (d). ACLF-TO200; (e). ACLF-TO100; (f). ACLF-TO50; Bar = 50 µm (a–c,f) and 20 µm (d,e). ACLF—acute on chronic liver failure; ACLF-SYL—acute on chronic liver failure pretreated with 200 mg silymarin/kg b.w./d; ACLF-TO200—acute on chronic liver failure pretreated with 200 mg TOERE/kg b.w./day; ACLF-TO100—acute on chronic liver failure pretreated with 100 mg TOERE/kg b.w./day; ACLF-TO50—acute on chronic liver failure pretreated with 50 mg TOERE/kg b.w./day.

The highest histological scores were identified in the livers of the ACLF group (p < 0.001) (Table 4). The changes were represented by congestion, hemorrhages, multifocal to coalescing areas of coagulative necrosis, randomly distributed within the hepatic lobules or centered on periportal regions and associated with severe and mixed inflammatory infiltrates. The portal spaces were also affected and expanded by fibrosis, bile duct hyperplasia, and large numbers of inflammatory cells, predominated by small lymphocytes and macrophages (Figure 2b). The microscopical examination of the livers from the group ACLF-SYL group (Figure 2c) revealed the lowest histological scores if compared to ACLF, ACLF-TO200, ACLF-TO100, and ACLF-TO50 (p < 0,001). Compared to the untreated ACLF group, in ACLF-TO200 (Figure 2d), ACLF-TO100 (Figure 2e), and ACLF-TO50 (Figure 2f) animals, the hepatic injuries were significantly reduced by the TOERE pretreatments (p < 0.001), with no important differences between different TOERE doses (p > 0.05). Liver necroinflammatory scores and serum liver tests were positively correlated.

Table 4

Histological and IHC scores of the liver biopsies.

Groups	Portal Inflammation	Periportal Degeneration/ Necrosis	Intralobular Degeneration/ Necrosis	Fibrosis	HAI	3NT
ACLF-TO200	1.60 ^a,b,c ± 0.89	2.20 ^a,b,c ± 0.10	1.00 ^a,b,c ± 0.01	1.20 ^a,c ± 0.10	5.80 ^a,c ± 1.92	1.40 ^a,b,c ± 0.55
ACLF-TO100	2.20 ^a,b,c ± 0.10	2.60 ^a,b,c ± 0.89	1.40 ^a,b,c ± 0.89	1.00 ^a,c ± 0.10	7.20 ^a,b,c ± 1.10	1.40 ^a,b,c ± 0.55
ACLF-TO50	2.60 ^a,b,c ± 0.89	2.20 ^a,b,c ± 1.10	2.20 ^a,b,c ± 1.10	1.00 ^a,c ± 0.10	8.00 ^a,b,c ± 1.41	1.80 ^a,b,c ± 0.45
ACLF-SYL	1.00 ^a,b ± 0.00	0.60 ^a,b ± 0.55	0.80 ^a,b ± 0.45	0.40 ^a,b ± 0.55	2.80 ^a,b ± 0.45	1.20 ^a,b ± 0.45
ACLF	3.60 ^a,c ± 0.55	4.80 ^a,c ± 0.84	3.60 ^a,b ± 0.55	1.00 ^a,b ± 0.10	12.80 ^a,b ± 1.64	2.40 ^a,b ± 0.55
Control	0.40 ± 0.55	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.20 ± 0.45	0.00 ± 0.00

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Results are expressed as mean ± SD. ^a p ˂ 0.05, versus Control; ^b p ˂ 0.05, versus ACLF; ^c p ˂ 0.05, versus SYL; ACLF-TO200—acute on chronic liver failure pretreated with 200 mg TOERE/kg b.w./day; ACLF-TO100—acute on chronic liver failure pretreated with 100mg TOERE/kg b.w./day; ACLF-TO50—acute on chronic liver failure pretreated with 50 mg TOERE/kg b.w./day; ACLF-SYL—acute on chronic liver failure pretreated with 200 mg silymarin/kg b.w./d; ACLF—acute on chronic liver failure; Control—negative control; HAI—histological activity index; 3NT—3-nitrotyrosine.

3.4. 3-Nitrityrosine Evaluation

3-NT immunoexpression was negative in the livers of the control group (Figure 3a). A marked hepatocellular immunoexpression of 3-NT with a diffuse or mediolobular pattern was found in all liver samples from the ACLF group (Figure 3b) (p < 0.01). In the group ACLF-SYL, the 3-NT expression was reduced compared to the ACLF group (p < 0.01), being mainly limited to hepatocytes near the portal spaces (Figure 3c) (Table 4).

Figure 3

Immunohistochemical expression of 3-nitrotyrosine (3-NT) in liver tissues from the control and experimental animals: (a). Control; (b). ACLF; (c). ACLF-SYL; (d). ACLF-TO200; (e). ACLF-TO100; (f). ACLF-TO50; Bar = 50 μm (a) and 20 μm (b–f). ACLF-TO200—acute on chronic liver failure pretreated with 200 mg TOERE/kg b.w./day; ACLF-TO100—acute on chronic liver failure pretreated with 100 mg TOERE/kg b.w./day; ACLF-TO50—acute on chronic liver failure pretreated with 50 mg TOERE/kg b.w./day; ACLF-SYL—acute on chronic liver failure pretreated with 200 mg silymarin/kg b.w./d.

As compared to the ACLF group, the expression of 3NT was lower in liver biopsies from TOERE treated animals, particularly in the ACLF-TO200 (Figure 3d) and ACLF-TO100 (Figure 3e) (p < 0.01) groups. The expression of 3NT in the ACLF-TO50 group (Figure 3f) was higher compared to the other treated groups. SYL effect on 3NT expression was better than that of TOERE (p < 0.05) (Table 4).

The correlation between the histological scores and biochemical tests were also analyzed. In ACLF, ACLF-TO200, ACLF-TO100, ACLF-TO50, and ACLF-SYL groups all histopathological scores were positively correlated with liver, renal, and oxidative stress markers.

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4. Discussion

In the current study, D-Gal-LPS-induced ACLF in rats with HAS-induced chronic liver failure triggered an immune-mediated liver injury with pathological serum liver marker tests and histological liver changes. The liver injuries were also associated with renal failure and systemic oxidative stress. A seven days pretreatment with TOERE reduced ACLF induced liver injury. The protecting effect of TOERE can be attributed, at least in part, to the reduction of the oxidative stress associated with immune liver injury in D-Gal-LPS-induced ACLF. Depending on the dose, the hepatoprotective effect of TOERE was similar or lower than that of SYL, an already used hepatoprotective drug.

By analyzing the TOERE extract, other studies identified sesquiterpenes, various triterpenes, phenolic compounds, and phytosterols. Our previous phytochemical analysis [23] showed that the tested TO root extract had a lower TPC than in Aremu et al.’s analysis of TO root extract (1.14 ± 0.01 mg/100 GAE/mg extract) and TO leaf extract (4.35 ± 0.15 mg GAE/mg extract) [37], but higher than in the TO aerial part extract (15.50 mg GAE/g d.w.) [38].

The HPLC-DAD-ESI MS analysis of our TO root extract identified, caffeic acid, chicoric acid, as previously described [23], plus feruloylquinic acid, dicaffeoylquinic acid, and dicaffeoylquinic acid isomer. All these compounds have anti-inflammatory and antioxidant properties [11,23,39,40,41]. The antioxidant activity of the TOERE measured by DPPH and FRAP tests was proved in our previous study [23].

Because the chemical composition correlates with the pharmacological effects, TO extracts from different plant parts had different activities. Several studies demonstrated that the TO roots extract reduces alcohol-induced oxidative stress, TO leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver, and TO flower extract can scavenge reactive oxygen species [22]. Similar to other studies [16,42,43], and based on the evidence of the phytochemical analysis results, our TO root extract can be considered a good natural antioxidant candidate. These results encouraged us to continue by testing the in vivo hepatoprotective and antioxidant effects of TOERE in an experimental ACLF.

For ACLF experimental model, first HAS administration in rats caused an immune liver injury and fibrosis, and then LPS stimulated liver macrophages leading to hepatic necro-inflammatory change. D-Gal, an amino sugar metabolized selectively by the hepatocytes, in a few hours potentiated the hepatotoxic effect of LPS by inhibiting mRNA and protein synthesis, leading to acute hepatitis [28]. The hepatoprotective effect of the TOERE was evaluated by using serum liver markers and liver histological analysis [2,3]. AST and ALT elevation reflects generalized damage to hepatocytes, TB increase reflects liver metabolism, ALP and GGT elevation reflects cholestasis [20,43,44]. In ACLF rats, liver markers were consistent with hepatocytes injury, cholestasis and, lower liver metabolism, demonstrating that an ACLF model was successfully induced [27]. The preliminary tests evaluating the TOERE effect on negative control animals indicated that the product had no significant activity on the healthy liver and oxidative stress (see supplemental data). In ACLF TO pretreatment reduced liver markers, suggesting that TOERE may prevent severe ACLF and by that to reduce the mortality due to ACLF. ACLF-TO100 group had the best hepatoprotective effect. In a previous study, we also evaluated in the TO root extract some phytosterols with anti-inflammatory and antioxidative properties [23]. It was demonstrated that due to their structural similarity with cholesterol, phytosterols are prone to be oxidized and transformed into oxyphytosterols [45,46,47], and from antioxidants to become pro-oxidants. By lowering the dose of TO from 200 to 100mg dry plant material/kg b.w./day, phytosterol reduction may be involved in the better hepatoprotective effect of ACLF-TO100 than of ACLF-TO200.

Liver injury diagnosed by serum liver tests was further confirmed by histopathological characteristics. In a normal liver, there is a hypoimmune response, and in chronic liver inflammation there is a high cellular recruitment, extended tissue damage, and the repair process leads to tissue remodeling, fibrosis, and liver dysfunction [41,48,49]. Fibrosis represents a key characteristic of progression towards liver cirrhosis and hepatic failure. In the present work liver biopsy of the ACLF animals showed extended necro-inflammatory changes, fibrosis, and bile ducts hyperplasia. In ACLF rats, like previously observed, histopathological scores increased due to the ongoing inflammation activation and the direct cytotoxic effect of cell death products [50]. Pretreatment with our TOERE in ACLF had hepatoprotective activity by reducing liver necro-inflammatory changes, with no important effect on liver fibrosis.

Under physiological conditions, free radicals are scavenged by antioxidant mechanisms. If there is an excess of free radicals or if there is a deficiency of antioxidants, oxidative stress will build up and will cause oxidative damage of lipids, proteins, and DNA [2,43,49]. In D-Gal-LPS-induced ACLF, immune-induced liver injury triggered an important liver inflammatory response and systemic oxidative stress, with high serum TOS and OSI, along with increased production of MDA, NOx, and 3NT.

Many studies correlated the hepatoprotective activity of the medicinal plant extracts with the antioxidant compounds from these plants [51]. Moreover, other experimental studies demonstrated that the polyphenolic compounds isolated from TO extracts had a hepatoprotective effect by reducing oxidative stress through direct free radical scavenging activity, metal ions chelation, and regeneration of the membrane-bound antioxidants [40,49]. In the present work, TOERE decreased serum TOS, OSI, and MDA levels in a dose-dependent way. MDA reduction was relevant because recently lipid peroxidation was considered a vital process in chronic liver diseases [44]. TOERE did not affect TAR, and SH was just slightly increased, indicating that this extract reduced systemic oxidative stress mainly by scavenging the oxidants and less by increasing the antioxidant capacity.

In mammals there are three NO synthase (NOS) isoenzymes that are involved in NO synthesis: neuronal (nNOS/NOS-1), inducible (iNOS/NOS-2), and endothelial (eNOS/NOS-3). Inflammatory stimuli up-regulate iNOS, and excessively generate NO induces nitrosative and oxidative damage. In liver injury, NO can be produced by hepatocytes, Kupffer cells, hepatic stellate cells (HSCs), and hepatic sinusoidal endothelial cells. It was observed that NO may have a dichotomous effect on liver disease, respectively in chronic liver diseases NO can promote HSC apoptosis, but in acute liver diseases, NO may increase liver damage. In LPS-treated rats, the marked hepatocellular immunoexpression of 3NT indicated that the iNOS-ROS cycle augments liver injury [52]. In this study, we found that liver 3NT was down-regulated following treatment with TOERE, suggesting that TOERE may reduce liver inflammatory responses and oxidative stress by reducing NO production through the inhibition of iNOS gene expression. These properties of TOERE may be explained by the high content of antioxidant phytochemicals.

Only iNOS and eNOS were highly expressed in acute liver failure (ALF) liver tissue, causing plasma NO elevation, and in humans increased plasma NO levels were correlated to the clinical severity of ALF [52]. In D-Gal-LPS-induced ACLF elevation of serum NOx and 3NT confirmed excessive NO synthesis due to the severe liver injury and inflammation. The treatment with TOERE reduced the serum NOx and 3NT, indirectly indicating that TOERE had a significant inhibitory effect on systemic NO production.

Because systemic oxidative stress markers reduction was correlated with serum liver markers and liver histopathological scores improvement, we concluded that TOERE lowered liver injury by reducing oxidative stress. Like in other studies [10], it was found that the antioxidant effect of TOERE was dose-dependent, the higher extract concentration had better antioxidant activity due to the high concentration of antioxidant ingredients.

According to the World Gastroenterology Organization ACLF is characterized by acute liver failure and one or more extrahepatic organ failure because in ACLF liver inflammation may trigger systemic inflammation. The kidneys are the most commonly affected organs and renal failure range from acute kidney injury (AKI) to acute-on-chronic kidney failure [2,3]. Therefore, acute kidney injury (AKI) was tested as a major criterion in ACLF severity grading [53]. In ACLF two subgroups of secondary renal dysfunctions with different pathophysiology and prognosis can be associated. One is the hepatorenal syndrome-acute kidney injury (HRS-AKI), a reduction of kidney function without parenchymal damage caused by prerenal insults such as hypovolemia. The other one is the non–HRS-AKI, induced by a renal insult such as inflammatory tubular injury in sepsis, bile acid nephropathy, and drug-induced tubular damage [54]. In ACLF liver protein synthesis lowers and may cause complications like coagulopathy, hemodynamic instability, jaundice, hepatic encephalopathy, hepatorenal syndrome, and sepsis [50]. At the same time, the systemic inflammatory response may also cause an inflammatory kidney injury with anon–HRS-AKI. Moreover, in experimental ACLF proinflammatory cytokines and LPS can cause directly renal tubular injury with cell apoptosis. Intrahepatic cholestasis from ACLF with increased serum bilirubin and bile acids may induce renal injury due to the direct renal toxicity and by tubular obstruction [54]. In our study, in ACLF animals creatinine and urea reached AKI levels, and there was a positive correlation between serum creatinine and urea, liver biopsy scores, and serum liver test. TOERE and SYL pretreatments reduced serum creatinine and urea in a dose-dependent way, indicating that in ACLF animals TOERE hepatoprotective activity is associated with a nephroprotective effect.

Lately, SYL has been used as a hepatoprotective agent due to its antioxidant and anti-inflammatory effects [55]. A finding of the study was that in experimental ACLF TO roots extract effects on serum liver markers were better than those of SYL, and SYL caused a higher reduction of the liver histological scores and 3NT immunoexpression. These differences suggested that TOERE better prevented acute liver injury and SYL reduces more the chronic response to liver injury. Even when SYL can reduce oxidative stress by scavenging ROS, by inhibiting ROS production [56], and by activating antioxidant enzymes [55], in our study it had a lower systemic antioxidant activity than TOERE.

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5. Conclusions

This report highlights the hepatoprotective and nephroprotective effects of an ethanolic TO root extract on D-Gal-LPS-induced ACLF. The mechanism proposed is the antioxidant activity of the bioactive components of the TOERE. These findings suggest for the first time that TOERE may be a potential preventive therapeutic agent for the severe liver and renal inflammatory injury associated with ACLF. These observations are important considering that ACLF has a high mortality rate. Further studies and clinical trials are required to fully elucidate the beneficial effects of TO root extract supplementation to prevent ACLF.

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Author Contributions

Conceptualization, I.O.P. and A.E.P.; methodology, T.A., R.M.P., L.V., and A.U.; software, R.M.P. and A.U.; validation, I.O.P., A.E.P., and R.O.; formal analysis, D.T. and C.T.; investigation, T.A., R.M.P., L.V., A.U, and C.T.; resources, I.O.P. and M.T.; writing—original draft preparation, I.O.P., A.E.P., R.M.P., and M.T. All authors have read and agreed to the published version of the manuscript.

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Funding

This research received no external funding.

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Institutional Review Board Statement

The study was approved by the Institutional Review Board (or Ethics Committee) of “Iuliu Hațieganu University of Medicine and Pharmacy”, Cluj-Napoca (no. 19/ 13.12.2016).

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Informed Consent Statement

Not applicable.

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Data Availability Statement

Not applicable.

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Conflicts of Interest

The authors declare no conflict of interest.

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Footnotes

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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References

1. Ali S.A., Sharief N.H., Mohamed Y.S. Hepatoprotective Activity of Some Medicinal Plants in Sudan. Evid.-Based Complement. Altern. Med. 2019;2019:1–16. doi: 10.1155/2019/2196315. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

2. Sarin S.K., Choudhury A., Sharma M.K., Maiwall R., Al Mahtab M., Rahman S., Saigal S., Saraf N., Soin A.S., Devarbhavi H., et al. Acute-on-Chronic Liver Failure: Consensus Recommendations of the Asian Pacific Association for the Study of the Liver (APASL): An Update. Hepatol. Int. 2019;13:353–390. doi: 10.1007/s12072-019-09946-3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

3. Bajaj J.S., Moreau R., Kamath P.S., Vargas H.E., Arroyo V., Reddy K.R., Szabo G., Tandon P., Olson J., Karvellas C., et al. Acute-on-Chronic Liver Failure: Getting Ready for Prime Time? Hepatology. 2018;68:1621–1632. doi: 10.1002/hep.30056. [PubMed] [CrossRef] [Google Scholar]

4. Asrani S.K., Simonetto D.A., Kamath P.S. Acute-on-Chronic Liver Failure. Clin. Gastroenterol. Hepatol. 2015;13:2128–2139. doi: 10.1016/j.cgh.2015.07.008. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

5. Jalan R., Saliba F., Pavesi M., Amoros A., Moreau R., Ginès P., Levesque E., Durand F., Angeli P., Caraceni P., et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J. Hepatol. 2014;61:1038–1047. doi: 10.1016/j.jhep.2014.06.012. [PubMed] [CrossRef] [Google Scholar]

6. van Leeuwen D.J., Alves V., Balabaud C., Bhathal P.S., Bioulac-Sage P., Colombari R., Crawford J.M., Dhillon A.P., Ferrell L., Gill R.M., et al. Acute-on-chronic liver failure 2018: A need for (urgent) liver biopsy? Expert Rev. Gastroenterol. Hepatol. 2018;12:565–573. doi: 10.1080/17474124.2018.1481388. [PubMed] [CrossRef] [Google Scholar]

7. Amarapurkar D., Dharod M.V., Chandnani M., Baijal R., Kumar P., Jain M., Patel N., Kamani P., Issar S., Shah N., et al. Acute-on-chronic liver failure: A prospective study to determine the clinical profile, outcome, and factors predicting mortality. Indian J. Gastroenterol. 2015;34:216–224. doi: 10.1007/s12664-015-0574-3. [PubMed] [CrossRef] [Google Scholar]

8. Triantafyllou E., Woollard K.J., McPhail M.J.W., Antoniades C.G., Possamai L.A. The Role of Monocytes and Macrophages in Acute and Acute-on-Chronic Liver Failure. Front. Immunol. 2018;9:2948. doi: 10.3389/fimmu.2018.02948. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Domitrović R., Potočnjak I. A comprehensive overview of hepatoprotective natural compounds: Mechanism of action and clinical perspectives. Arch. Toxicol. 2016;90:39–79. doi: 10.1007/s00204-015-1580-z. [PubMed] [CrossRef] [Google Scholar]

10. Aabideen Z.U., Waseem Mumtaz M., Tayyab Akhtar M., Mukhtar H., Raza S.A., Touqeer T., Saari N. Anti-Obesity Attributes; UHPLC-QTOF-MS/MS-Based Metabolite Profiling and Molecular Docking Insights of Taraxacum officinale. Molecules. 2020;25:4935. doi: 10.3390/molecules25214935. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

11. Gerbino A., Russo D., Colella M., Procino G., Svelto M., Milella L., Carmosino M. Dandelion root extract induces intracellular Ca2+ increases in HEK293 cells. Int. J. Mol. Sci. 2018;19:1112. doi: 10.3390/ijms19041112. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12. Lam P., Cheung F., Tan H.Y., Wang N., Yuen M.F., Feng Y. Hepatoprotective effects of chinese medicinal herbs: A focus on anti-inflammatory and anti-oxidative activities. Int. J. Mol. Sci. 2016;17:465. doi: 10.3390/ijms17040465. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

13. Zhu H., Zhao H., Zhang L., Xu J., Zhu C., Zhao H., Lv G. Dandelion root extract suppressed gastric cancer cells proliferation and migration through targeting lncRNA-CCAT1. Biomed. Pharmacother. 2017;93:1010–1017. doi: 10.1016/j.biopha.2017.07.007. [PubMed] [CrossRef] [Google Scholar]

14. Saratale R.G., Benelli G., Kumar G., Kim D.S., Saratale G.D. Bio-fabrication of silver nanoparticles using the leaf extract of an ancient herbal medicine, dandelion (Taraxacum officinale), evaluation of their antioxidant, anticancer potential, and antimicrobial activity against phytopathogens. Environ. Sci. Pollut. Res. 2018;25:10392–10406. doi: 10.1007/s11356-017-9581-5. [PubMed] [CrossRef] [Google Scholar]

15. Huang S., Meng N., Liu Z., Guo L., Dong L., Li B., Ye Q. Neuroprotective effects of Taraxacum officinale wigg. extract on glutamate-induced oxidative stress in HT22 cells via HO-1/Nrf2 pathways. Nutrients. 2018;10:926. doi: 10.3390/nu10070926. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

16. Miłek M., Marcinčáková D., Legáth J. Polyphenols content, antioxidant activity, and cytotoxicity assessment of Taraxacum officinale extracts prepared through the micelle-mediated extraction method. Molecules. 2019;24:1025. doi: 10.3390/molecules24061025. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

17. Martinez M., Poirrier P., Chamy R., Prüfer D., Schulze-Gronover C., Jorquera L., Ruiz G. Taraxacum officinale and related species—An ethnopharmacological review and its potential as a commercial medicinal plant. J. Ethnopharmacol. 2015;169:244–262. doi: 10.1016/j.jep.2015.03.067. [PubMed] [CrossRef] [Google Scholar]

18. Chung H.J., Noh Y., Kim M.S., Jang A., Lee C.E., Myung S.C. Steroidogenic effects of Taraxacum officinale extract on the levels of steroidogenic enzymes in mouse Leydig cells. Anim. Cells Syst. 2018;22:407–414. doi: 10.1080/19768354.2018.1494628. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

19. Jedrejek D., Lis B., Rolnik A., Stochmal A., Olas B. Comparative phytochemical, cytotoxicity, antioxidant and haemostatic studies of Taraxacum officinale root preparations. Food Chem. Toxicol. 2019;126:233–247. doi: 10.1016/j.fct.2019.02.017. [PubMed] [CrossRef] [Google Scholar]

20. Abdel-Magied N., Abdel Fattah S.M., Elkady A.A. Differential effect of Taraxacum officinale L. (dandelion) root extract on hepatic and testicular tissues of rats exposed to ionizing radiation. Mol. Biol. Rep. 2019;46:4893–4907. doi: 10.1007/s11033-019-04939-9. [PubMed] [CrossRef] [Google Scholar]

21. Al-Rasheed N., Faddah L., Sharaf I.A., Mohamed A.M., Al-Rasheed N., Abdel Baky N.A. Assessment of the potential role of silymarin alone or in combination with vitamin E and/or curcumin on the carbon tetrachloride induced liver injury in rat. Braz. Arch. Biol. Technol. 2015;58:833–842. doi: 10.1590/S1516-891320150232. [CrossRef] [Google Scholar]

22. Cai L., Wan D., Yi F., Luan L. Purification, Preliminary characterization and Hepatoprotective effects of polysaccharides from dandelion Root. Molecules. 2017;22:1409. doi: 10.3390/molecules22091409. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

23. Pfingstgraf I.O., Taulescu M., Orasan R., Pop R.M., Laurian V., Toma C. Alina Elena Parvu Effect of Taraxacum officinale L. (dandelion) root extract in experimental chronic liver failure. Rev. Rom. Med. Vet. 2020;30:85–91. [PMC free article] [PubMed] [Google Scholar]

24. Rusu M.E., Gheldiu A.M., Mocan A., Moldovan C., Popa D.S., Tomuta I., Vlase L. Process optimization for improved phenolic compounds recovery from walnut (Juglans regia L.) Septum: Phytochemical profile and biological activities. Molecules. 2018;23:2814. doi: 10.3390/molecules23112814. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

25. Mocan A., Zengin G., Simirgiotis M., Schafberg M., Mollica A., Vodnar D.C., Crişan G., Rohn S. Functional constituents of wild and cultivated Goji (L. barbarum L.) leaves: Phytochemical characterization, biological profile, and computational studies. J. Enzym. Inhib. Med. Chem. 2017;32:153–168. doi: 10.1080/14756366.2016.1243535. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

26. Jalali S.M., Najafzadeh H., Bahmei S. Protective role of silymarin and D-penicillamine against lead-induced liver toxicity and oxidative stress. Toxicol. Ind. Health. 2017;33:512–518. doi: 10.1177/0748233716685660. [PubMed] [CrossRef] [Google Scholar]

27. Wang L.W., Wang L.K., Chen H., Fan C., Li X., He C.M., Gong Z.J. Ethyl pyruvate protects against experimental acute-onchronic liver failure in rats. World J. Gastroenterol. 2012;18:5709–5718. doi: 10.3748/wjg.v18.i40.5709. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

28. Wu Y.-L., Lian L.-H., Jiang Y.-Z., Nan J.-X. Hepatoprotective effects of salidroside on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice. J. Pharm. Pharmacol. 2009;61:1375–1382. doi: 10.1211/jpp.61.10.0015. [PubMed] [CrossRef] [Google Scholar]

29. Li F., Miao L., Sun H., Zhang Y., Bao X., Zhang D. Establishment of a new acute-on-chronic liver failure model. Acta Pharm. Sin. B. 2017;7:326–333. doi: 10.1016/j.apsb.2016.09.003. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

30. Pârvu M., Moţ C.A., Pârvu A.E., Mircea C., Stoeber L., Roşca-Casian O., Ţigu A.B. Allium sativum extract chemical composition, antioxidant activity and antifungal effect against meyerozyma guilliermondii and rhodotorula mucilaginosa causing onychomycosis. Molecules. 2019;24:3958. doi: 10.3390/molecules24213958. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

31. Andreicut A.-D., Pârvu A.E., Mot A.C., Pârvu M., Fischer Fodor E., Cătoi A.F., Feldrihan V., Cecan M., Irimie A. Phytochemical Analysis of Anti-Inflammatory and Antioxidant Effects of Mahonia aquifolium Flower and Fruit Extracts. Oxid. Med. Cell. Longev. 2018;2018:2879793. doi: 10.1155/2018/2879793. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

32. Ruehl-Fehlert C., Kittel B., Morawietz G., Deslex P., Keenan C.M., Mahrt C.R., Nolte T., Robinson M., Stuart B.P., Deschl U., et al. Revised guides for organ sampling and trimming in rats and mice—Part 1. A joint publication of the RITA and NACAD groups. Exp. Toxicol. Pathol. 2003 doi: 10.1078/0940-2993-00311. [PubMed] [CrossRef] [Google Scholar]

33. Knodell R.G., Ishak K.G., Black W.C., Chen T.S., Craig R., Kaplowitz N., Kiernan T.W., Wollman J. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981;1:431–435. doi: 10.1002/hep.1840010511. [PubMed] [CrossRef] [Google Scholar]

34. Mester A., Ciobanu L., Taulescu M., Apostu D., Lucaciu O., Filip G.A., Feldrihan V., Licarete E., Ilea A., Piciu A., et al. Periodontal disease may induce liver fibrosis in an experimental study on Wistar rats. J. Periodontol. 2019;90:911–919. doi: 10.1002/JPER.18-0585. [PubMed] [CrossRef] [Google Scholar]

35. García-Monzón C., Majano P.L., Zubia I., Sanz P., Apolinario A., Moreno-Otero R. Intrahepatic accumulation of nitrotyrosine in chronic viral hepatitis is associated with histological severity of liver disease. J. Hepatol. 2000;32:331–338. doi: 10.1016/S0168-8278(00)80080-X. [PubMed] [CrossRef] [Google Scholar]

36. Lazarova I., Simeonova R., Vitcheva V., Kondeva-Burdina M., Gevrenova R., Zheleva-Dimitrova D., Zengin G., Danchev N.D. Hepatoprotective and antioxidant potential of Asphodeline lutea (L.) Rchb. roots extract in experimental models in vitro/in vivo. Biomed. Pharmacother. 2016;83:70–78. doi: 10.1016/j.biopha.2016.06.023. [PubMed] [CrossRef] [Google Scholar]

37. Aremu O.O., Oyedeji A.O., Oyedeji O.O., Nkeh-Chungag B.N., Rusike C.R.S. In Vitro and In Vivo Antioxidant Properties of Taraxacum officinale in Nω-Nitro-l-Arginine Methyl Ester (L-NAME)-Induced Hypertensive Rats. Antioxidants. 2019;8:309. doi: 10.3390/antiox8080309. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

38. Sengul M., Yildiz H., Gungor N., Cetin B., Eser Z., Ercisli S. Total phenolic content, antioxidant and antimicrobial activities of some medicinal plants. Pak. J. Pharm. Sci. 2009;22:102–106. [PubMed] [Google Scholar]

39. Hu C., Kitts D.D. Antioxidant, prooxidant, and cytotoxic activities of solvent-fractionated dandelion (Taraxacum officinale) flower extracts in vitro. J. Agric. Food Chem. 2003 doi: 10.1021/jf0258858. [PubMed] [CrossRef] [Google Scholar]

40. Sharifi-Rad M., Roberts T.H., Matthews K.R., Bezerra C.F., Morais-Braga M.F.B., Coutinho H.D.M., Sharopov F., Salehi B., Yousaf Z., Sharifi-Rad M., et al. Ethnobotany of the genus Taraxacum—Phytochemicals and antimicrobial activity. Phyther. Res. 2018;32:2131–2145. doi: 10.1002/ptr.6157. [PubMed] [CrossRef] [Google Scholar]

41. Karakuş A., Değer Y., Yıldırım S. Protective effect of Silybum marianum and Taraxacum officinale extracts against oxidative kidney injuries induced by carbon tetrachloride in rats. Ren. Fail. 2017;39:1–6. doi: 10.1080/0886022X.2016.1244070. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

42. Choi J., Yoon K.D., Kim J. Chemical constituents from Taraxacum officinale and their α-glucosidase inhibitory activities. Bioorganic Med. Chem. Lett. 2018;28:476–481. doi: 10.1016/j.bmcl.2017.12.014. [PubMed] [CrossRef] [Google Scholar]

43. Majewski M., Lis B., Juśkiewicz J., Ognik K., Borkowska-Sztachańska M., Jedrejek D., Stochmal A., Olas B. Phenolic Fractions from Dandelion Leaves and Petals as Modulators of the Antioxidant Status and Lipid Profile in an In Vivo Study. Antioxidants. 2020;9:131. doi: 10.3390/antiox9020131. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

44. Ma J., Li M., Kalavagunta P.K., Li J., He Q., Zhang Y., Ahmad O., Yin H., Wang T., Shang J. Protective effects of cichoric acid on H2O2-induced oxidative injury in hepatocytes and larval zebrafish models. Biomed. Pharmacother. 2018;104:679–685. doi: 10.1016/j.biopha.2018.05.081. [PubMed] [CrossRef] [Google Scholar]

45. Massaad C., Iuliano L., Lizard G. Oxysterols and phytosterols in human health. Chem. Phys. Lipids. 2017;207:49–50. doi: 10.1016/j.chemphyslip.2017.08.003. [PubMed] [CrossRef] [Google Scholar]

46. Vilahur G., Ben-Aicha S., Diaz-Riera E., Badimon L., Padró T. Phytosterols and Inflammation. Curr. Med. Chem. 2018;26:6724–6734. doi: 10.2174/0929867325666180622151438. [PubMed] [CrossRef] [Google Scholar]

47. Hovenkamp E., Demonty I., Plat J., Lütjohann D., Mensink R.P., Trautwein E.A. Biological effects of oxidized phytosterols: A review of the current knowledge. Prog. Lipid Res. 2008;47:37–49. doi: 10.1016/j.plipres.2007.10.001. [PubMed] [CrossRef] [Google Scholar]

48. Kubes P., Jenne C., Snyder J. Annual Review of Immunology Immune Responses in the Liver. Annu. Rev. Immunol. 2018;36:1–31. doi: 10.1146/annurev-immunol-051116-052415. [PubMed] [CrossRef] [Google Scholar]

49. Hfaiedh M., Brahmi D., Zourgui L. Hepatoprotective effect of Taraxacum officinale leaf extract on sodium dichromate-induced liver injury in rats. Environ. Toxicol. 2016 doi: 10.1002/tox.22048. [PubMed] [CrossRef] [Google Scholar]

50. Macdonald S., Andreola F., Bachtiger P., Amoros A., Pavesi M., Mookerjee R., Zheng Y.B., Gronbaek H., Gerbes A.L., Sola E., et al. Cell death markers in patients with cirrhosis and acute decompensation. Hepatology. 2018;67:989–1002. doi: 10.1002/hep.29581. [PubMed] [CrossRef] [Google Scholar]

51. Hamza A.A., Mohamed M.G., Lashin F.M., Amin A. Dandelion prevents liver fibrosis, inflammatory response, and oxidative stress in rats. J. Basic Appl. Zool. 2020;9 doi: 10.1186/s41936-020-00177-9. [CrossRef] [Google Scholar]

52. Jin L., Gao H., Wang J.P., Yang S.J., Wang J., Liu J.F., Yang Y., Yan T.T., Chen T., Zhao Y., et al. Role and regulation of autophagy and apoptosis by nitric oxide in hepatic stellate cells during acute liver failure. Liver Int. 2017;37:1651–1659. doi: 10.1111/liv.13476. [PubMed] [CrossRef] [Google Scholar]

53. Chen N., Chen X., Ding X., Teng J. Analysis of the high incidence of acute kidney injury associated with acute-on-chronic liver failure. Hepatol. Int. 2018;12:262–268. doi: 10.1007/s12072-018-9866-x. [PubMed] [CrossRef] [Google Scholar]

54. Davenport A., Sheikh M.F., Lamb E., Agarwal B., Jalan R. Acute kidney injury in acute-on-chronic liver failure: Where does hepatorenal syndrome fit? Kidney Int. 2017;92:1058–1070. doi: 10.1016/j.kint.2017.04.048. [PubMed] [CrossRef] [Google Scholar]

55. Owatari M.S., Alves Jesus G.F., Brum A., Pereira S.A., Lehmann N.B., de Pádua Pereira U., Martins M.L., Pedreira Mouriño J.L. Sylimarin as hepatic protector and immunomodulator in Nile tilapia during Streptococcus agalactiae infection. Fish Shellfish Immunol. 2018;82:565–572. doi: 10.1016/j.fsi.2018.08.061. [PubMed] [CrossRef] [Google Scholar]

56. Dong S., Cai F.F., Chen Q.L., Song Y.N., Sun Y., Wei B., Li X.Y., Hu Y.Y., Liu P., Su S.B. Chinese herbal formula Fuzheng Huayu alleviates CCl 4-induced liver fibrosis in rats: A transcriptomic and proteomic analysis. Acta Pharmacol. Sin. 2018;39:930–941. doi: 10.1038/aps.2017.150. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

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The Benefits of a Lactobacillus to Your Health

The Truth News — Sat, 15 Jun 2024 09:07:52 +0000

The Benefits of a Lactobacillus to Your Health

Lactobacillus is a type of bacteria of which Lactobacillus gasseri is one type. You can find these ‘friendly’ Lactobacillus bacteria naturally in the human gut, urinary tract, and genital system. We can also get these helpful bacteria from certain foods and from dietary supplements called probiotics.

In general, Lactobacillus helps the body to break down food, absorb nutrients, and fight disease-causing organisms. Lactobacillus is also useful for preventing and treating diarrhea. Specifically, it is helpful for fighting diarrhea related to antibiotics use (1).

In this article, we’ll look more closely at probiotics and outline some health benefits of taking a Lactobacillus gasseri probiotic.

What are Probiotics?

Every human being is born with a certain ‘gut flora’. This flora consists of beneficial microorganisms, like bacteria, that you inherit for your mother. After birth, other helpful flora begins to ‘colonize’ your body. Although this may sound like some sort of alien invasion, it isn’t.

These beneficial or ‘friendly’ bacteria perform a number of roles in your body including immune system support, synthesizing certain vitamins, and converting fiber into acids (2).

So, probiotics are live microorganisms that are good for your health. Taking probiotics as a dietary supplement can help you boost your gut flora, the healthy bacteria in your gut (3). When taken in the correct amounts, your gut is healthier, and so are you!

Specific Health Benefits of Lactobacillus Gasseri

Lactobacillus gasseri is a probiotic which is useful for a number of health conditions. In addition to its general contribution to digestive and gut health, Lactobacillus gasseri probiotic is helpful for a number of other health conditions:

Weight Loss

According to some research, Lactobacillus gasseri couple possibly encourage weight loss and reduce abdominal fat. A British Journal of Nutrition study published in 2013 surveyed 210 obese adults.

These people were either given milk enriched with Lactobacillus gasseri or a placebo (milk without Lactobacillus gasseri). In the end, the Lactobacillus group saw an 8.5% reduction in abdominal fat compared to the placebo group after 12 weeks (4).

Vaginal Health

Lactobacillus gasseri probiotic also promotes vaginal health by preventing bacterial vaginosis. However, it is most effective when taken as a suppository. What’s more, studies suggest that Lactobacillus gasseri probiotic may also decrease menstrual pain in women (5).

Cholesterol

In one study, participants received a product containing Lactobacillus gasseri and insulin. This product helped reduced total blood cholesterol, LDL (low-density cholesterol), lipoproteins, and triglycerides in both men and women with high cholesterol (8).

Boosts Immunity

Heat-killed Lactobacillus gasseri has been shown to boost immunity in elderly adults by increasing the number of T cells (9).

Allergies

In one study involved participants with an allergy to Japanese cedar, heat-killed Lactobacillus gasseri improved their nasal symptoms and enhanced their immune response (10).

Fatigue

When university athletes were given Lactobacillus gasseri probiotic after strenuous exercise, they experienced less resting fatigue. On top of that, Lactobacillus gasseri probiotic also elevated their moods (11).

Summary

Lactobacillus bacteria are friendly microorganisms that are native to the human gut. They help with a number of normal processes and help keep us healthy. Generally speaking, Lactobacillus helps you break down food, absorb nutrients, and fight certain unhealthy microorganisms. What’s more, it also supports your immune system support and helps your body synthesize certain vitamins. When our gut flora is out of balance, our health can suffer.

In addition to balancing gut flora, taking Lactobacillus gasseri probiotic is beneficial for a number of other reasons. It is frequently used for treating and preventing diarrhea, especially diarrhea caused by antibiotics. Furthermore, it boosts vaginal health in women and eases menstrual pain in women with endometriosis.

References

9 Ways Lactobacillus Acidophilus Can Benefit Your Health

L. acidophilus is a beneficial bacteria found in your intestines that helps protect against various illnesses. To boost levels, consume fermented goods or take supplements.

Probiotics are becoming popular food supplements.

Interestingly, each probiotic can have different effects on your body.

Lactobacillus acidophilus is one of the most common types of probiotics and can be found in fermented foods, yogurt and supplements.

What Is Lactobacillus Acidophilus?

Lactobacillus acidophilus is a type of bacteria found in your intestines.

It’s a member of the Lactobacillus genus of bacteria, and it plays an important role in human health (1Trusted Source).

Its name gives an indication of what it produces — lactic acid. It does this by producing an enzyme called lactase. Lactase breaks down lactose, a sugar found in milk, into lactic acid.

Lactobacillus acidophilus is also sometimes referred to as L. acidophilus or simply acidophilus.

Lactobacilli, particularly L. acidophilus, are often used as probiotics.

The World Health Organization defines probiotics as “live micro-organisms which, when administered in adequate amounts, confer a health beneﬁt on the host” (2Trusted Source).

Unfortunately, food manufacturers have overused the word “probiotic,” applying it to bacteria that haven’t been scientifically proven to have any specific health benefits.

This has led the European Food Safety Authority to ban the word “probiotic” on all foods in the EU.

L. acidophilus has been extensively studied as a probiotic, and evidence has shown that it may provide a number of health benefits. However, there are many different strains of L. acidophilus, and they can each have different effects on your body (3Trusted Source).

In addition to probiotic supplements, L. acidophilus can be found naturally in a number of fermented foods, including sauerkraut, miso and tempeh.

Also, it’s added to other foods like cheese and yogurt as a probiotic.

Below are 9 ways in which Lactobacillus acidophilus may benefit your health

1. It May Help Reduce Cholesterol

High cholesterol levels may increase the risk of heart disease. This is especially true for “bad” LDL cholesterol.

Fortunately, studies suggest that certain probiotics can help reduce cholesterol levels and that L. acidophilus may be more effective than other types of probiotics (4Trusted Source, 5Trusted Source).

Some of these studies have examined probiotics on their own, while others have used milk drinks fermented by probiotics.

One study found that taking L. acidophilus and another probiotic for six weeks significantly lowered total and LDL cholesterol, but also “good” HDL cholesterol (6Trusted Source).

A similar six-week study found that L. acidophilus on its own had no effect (7Trusted Source).

However, there is evidence that combining L. acidophilus with prebiotics, or indigestible carbs that help good bacteria grow, can help increase HDL cholesterol and lower blood sugar.

This has been demonstrated in studies using probiotics and prebiotics, both as supplements and in fermented milk drinks (8Trusted Source).

Furthermore, a number of other studies have shown that yogurt supplemented with L. acidophilus helped reduce cholesterol levels by up to 7% more than ordinary yogurt (9Trusted Source, 10Trusted Source, 11Trusted Source, 12Trusted Source).

This suggests that L. acidophilus — not another ingredient in the yogurt — was responsible for the beneficial effect.

SUMMARY:L. acidophilus consumed on its own, in milk or yogurt or in combination with prebiotics may help lower cholesterol.

2. It May Prevent and Reduce Diarrhea

Diarrhea affects people for a number of reasons, including bacterial infections.

It can be dangerous if it lasts a long time, as it results in fluid loss and, in some cases, dehydration.

A number of studies have shown that probiotics like L. acidophilus may help prevent and reduce diarrhea that’s associated with various diseases (13Trusted Source).

Evidence on the ability of L. acidophilus to treat acute diarrhea in children is mixed. Some studies have shown a beneficial effect, while others have shown no effect (14Trusted Source, 15Trusted Source).

One meta-analysis involving more than 300 children found that L. acidophilus helped reduce diarrhea, but only in hospitalized children (16Trusted Source).

What’s more, when consumed in combination with another probiotic, L. acidophilus may help reduce diarrhea caused by radiotherapy in adult cancer patients (17Trusted Source).

Similarly, it may help reduce diarrhea associated with antibiotics and a common infection called Clostridium difficile, or C. diff (18Trusted Source).

Diarrhea is also common in people who travel to different countries and are exposed to new foods and environments.

A review of 12 studies found that probiotics are effective at preventing traveler’s diarrhea and that Lactobacillus acidophilus, in combination with another probiotic, was most effective at doing so (19Trusted Source).

SUMMARY:When consumed in combination with other probiotics, L. acidophilus may help prevent and treat diarrhea.

3. It Can Improve Symptoms of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) affects up to one in five people in certain countries. Its symptoms include abdominal pain, bloating and unusual bowel movements (20Trusted Source).

While little is known about the cause of IBS, some research suggests it might be caused by certain types of bacteria in the intestines (21Trusted Source).

Therefore, a number of studies have examined whether probiotics can help improve its symptoms.

In a study in 60 people with functional bowel disorders including IBS, taking a combination of L. acidophilus and another probiotic for one to two months improved bloating (22Trusted Source).

A similar study found that L. acidophilus alone also reduced abdominal pain in IBS patients (23Trusted Source).

On the other hand, a study that examined a mixture of L. acidophilus and other probiotics found that it had no effect IBS symptoms (24Trusted Source).

This might be explained by another study suggesting that taking a low dose of single-strain probiotics for a short duration may improve IBS symptoms the most.

Specifically, the study indicates that the best way to take probiotics for IBS is to use single-strain probiotics, rather than a mix, for less than eight weeks, as well as a dose of less than 10 billion colony-forming units (CFUs) per day (25Trusted Source).

However, it’s important to choose a probiotic supplement that has been scientifically proven to benefit IBS.

SUMMARY:L. acidophilus probiotics may improve symptoms of IBS, such as abdominal pain and bloating.

4. It Can Help Treat and Prevent Vaginal Infections

Vaginosis and vulvovaginal candidiasis are common types of vaginal infections.

There is good evidence that L. acidophilus can help treat and prevent such infections.

Lactobacilli are typically the most common bacteria in the vagina. They produce lactic acid, which prevents the growth of other harmful bacteria (26Trusted Source).

However, in cases of certain vaginal disorders, other species of bacteria begin to outnumber lactobacilli (27Trusted Source, 28Trusted Source).

A number of studies have found taking L. acidophilus as a probiotic supplement can prevent and treat vaginal infections by increasing lactobacilli in the vagina (29Trusted Source, 30Trusted Source).

Nevertheless, other studies have found no effect (31Trusted Source, 32Trusted Source).

Eating yogurt that contains L. acidophilus may also prevent vaginal infections. Yet, both of the studies that examined this were quite small and would need to be replicated on a larger scale before any conclusions could be made (33Trusted Source, 34Trusted Source).

SUMMARY:L. acidophilus as a probiotic supplement may be useful in preventing vaginal disorders, such as vaginosis and vulvovaginal candidiasis.

5. It May Promote Weight Loss

The bacteria in your intestines help control food digestion and a number of other bodily processes.

Therefore, they influence your weight.

There is some evidence that probiotics may help you lose weight, especially when multiple species are consumed together. However, the evidence on L. acidophilus alone is unclear (35Trusted Source).

A recent study that combined the results of 17 human studies and over 60 animal studies found that some lactobacilli species led to weight loss, while others may have contributed to weight gain (36Trusted Source).

It suggested that L. acidophilus was one of the species that led to weight gain. However, most of the studies were conducted in farm animals, not humans.

Furthermore, some of these older studies used probiotics that were originally thought to be L. acidophilus, but have since been identified as different species (37Trusted Source).

Therefore, the evidence on L. acidophilus affecting weight is unclear, and more rigorous studies are needed.

SUMMARY:Probiotics may be effective for weight loss, but more research is needed to determine whether L. acidophilus, in particular, has a significant effect on weight in humans.

6. It May Help Prevent and Reduce Cold and Flu Symptoms

Healthy bacteria like L. acidophilus can boost the immune system and thus help reduce the risk of viral infections.

In fact, some studies have suggested that probiotics may prevent and improve symptoms of the common cold (38Trusted Source, 39Trusted Source).

A few of these studies examined how effectively L. acidophilus treated colds in children.

In one study in 326 children, six months of daily L. acidophilus probiotics reduced fever by 53%, coughing by 41%, antibiotic use by 68% and days absent from school by 32% (40Trusted Source).

The same study found that combining L. acidophilus with another probiotic was even more effective (40Trusted Source).

A similar study on L. acidophilus and another probiotic also found similar positive results for reducing cold symptoms in children (41Trusted Source).

SUMMARY:L. acidophilus on its own and in combination with other probiotics may reduce cold symptoms, especially in children.

7. It May Help Prevent and Reduce Allergy Symptoms

Allergies are common and can cause symptoms such as a runny nose or itchy eyes.

Fortunately, some evidence suggests that certain probiotics can reduce the symptoms of some allergies (42Trusted Source).

One study showed that consuming a fermented milk drink containing L. acidophilus improved symptoms of Japanese cedar pollen allergy (43Trusted Source).

Similarly, taking L. acidophilus for four months reduced nasal swelling and other symptoms in children with perennial allergic rhinitis, a disorder that causes hay fever-like symptoms throughout the year (44Trusted Source).

A larger study in 47 children found similar results. It showed that taking a combination of L. acidophilus and another probiotic reduced runny nose, nasal blocking and other symptoms of pollen allergy (45Trusted Source).

Interestingly, the probiotics reduced the amount of an antibody called immunoglobulin A, which is involved in these allergic reactions, in the intestines.

SUMMARY:L. acidophilus probiotics can reduce the symptoms of certain allergies.

8. It May Help Prevent and Reduce Symptoms of Eczema

Eczema is a condition in which the skin becomes inflamed, resulting in itchiness and pain. The most common form is called atopic dermatitis.

Evidence suggests that probiotics can reduce the symptoms of this inflammatory condition in both adults and children (46Trusted Source).

One study found that giving a mix of L. acidophilus and other probiotics to pregnant women and their infants during the first three months of life reduced the prevalence of eczema by 22% by the time the infants reached one year of age (47Trusted Source).

A similar study found that L. acidophilus, in combination with traditional medical therapy, significantly improved atopic dermatitis symptoms in children (48Trusted Source).

However, not all studies have shown positive effects. A large study in 231 newborn children given L. acidophilus for the first six months of life found no beneficial effect in cases of atopic dermatosis (49Trusted Source). In fact, it increased sensitivity to allergens.

SUMMARY:Some studies have shown that L. acidophilus probiotics can help reduce the prevalence and symptoms of eczema, while other studies show no benefit.

9. It’s Good for Your Gut Health

Your gut is lined with trillions of bacteria that play an important role in your health.

Generally, lactobacilli are very good for gut health.

They produce lactic acid, which may prevent harmful bacteria from colonizing the intestines. They also ensure the lining of the intestines stays intact (50Trusted Source).

L. acidophilus can increase the amounts of other healthy bacteria in the gut, including other lactobacilli and Bifidobacteria.

It can also increase levels of short-chain fatty acids, such as butyrate, which promote gut health (51Trusted Source).

Another study carefully examined the effects of L. acidophilus on the gut. It found that taking it as a probiotic increased the expression of genes in the intestines that are involved in immune response (52Trusted Source).

These results suggest that L. acidophilus may support a healthy immune system.

A separate study examined how the combination of L. acidophilus and a prebiotic affected human gut health.

It found that the combined supplement increased the amounts of lactobacilli and Bifidobacteria in the intestines, as well as branched-chain fatty acids, which are an important part of a healthy gut (53Trusted Source).

SUMMARY:L. acidophilus can support gut health by increasing the amounts of healthy bacteria in the intestines.

How to Reap the Most from L. Acidophilus

L. acidophilus is a normal bacteria in healthy intestines, but you can reap a number of health benefits by taking it as a supplement or consuming foods that contain it.

L. acidophilus can be consumed in probiotic supplements, either on its own or in combination with other probiotics or prebiotics.

However, it’s also found in a number of foods, particularly fermented foods.

The best food sources of L. acidophilus are:

Yogurt: Yogurt is typically made from bacteria such as L. bulgaricus and S. thermophilus. Some yogurts also contain L. acidophilus, but only those that list it in the ingredients and state “live and active cultures.”
Kefir: Kefir is made of “grains” of bacteria and yeast, which can be added to milk or water to produce a healthy fermented drink. The types of bacteria and yeast in kefir can vary, but it commonly contains L. acidophilus, among others.
Miso: Miso is a paste originating from Japan that is made by fermenting soybeans. Although the primary microbe in miso is a fungus called Aspergillus oryzae, miso can also contain many bacteria, including L. acidophilus.
Tempeh: Tempeh is another food made from fermented soybeans. It can contain a number of different microorganisms, including L. acidophilus.
Cheese: Different varieties of cheese are produced by using different bacteria. L. acidophilus is not commonly used as a cheese starter culture, but a number of studies have examined the effects of adding it as a probiotic (54Trusted Source).
Sauerkraut: Sauerkraut is a fermented food made from cabbage. Most of the bacteria in sauerkraut are Lactobacillus species, including L. acidophilus (55Trusted Source).

Other than food, the best way to get L. acidophilus is directly through supplements.

A number of L. acidophilus probiotic supplements are available, either on their own or in combination with other probiotics. Aim for a probiotic with at least one billion CFUs per serving.

If taking a probiotic, it’s usually best to do so with a meal, ideally breakfast.

If you are new to probiotics, try taking them once daily for a week or two and then assess how you feel before continuing.

SUMMARY:L. acidophilus can be taken as a probiotic supplement, but it’s also found in high quantities in a number of fermented foods.

The Bottom Line

L. acidophilus is a probotic bacteria that’s normally found in your intestines and crucial to health.

Due to its ability to produce lactic acid and interact with your immune system, it may help prevent and treat symptoms of various diseases.

In order to increase L. acidophilus in your intestines, eat fermented foods, including those listed above.

Alternatively, L. acidophilus supplements can be beneficial, especially if you suffer from one of the disorders mentioned in this article.

Whether it’s obtained through foods or supplements, L. acidophilus can provide health benefits for everyone.\

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How To: Culture Lactobacillus (LAB) for Horticultural use

Generally when it comes to bacteria and microbes we’d be referring to the aerobic type you’d hope to produce in a Compost Tea (AACT) system, the reason being that the presence of anaerobic bacteria in these systems are nearly always ‘bad news’. However there are useful anaerobes out there and it is very much worth looking in to putting them to use in your horticultural endeavours!!

Enter Lactobacillus….

Lactobacillus is a facultive anaerobe that we are generally interested in for it’s ability to ferment a wide variety of things. It is this process that makes Lactobacillus or LAB the cornerstone of a range of processes the savvy gardener will find extremely useful. I’ll mention more about that later in this piece and in further blogs, but lets show you how to culture your own Lactobacillus first….

Step 1 – Rice wash

Technically you can use any reasonable carbohydrate source (preferably not simple sugars) but in this instance we’ll go with a Rice wash – I will be trying other more exciting things in the future, but until then….. Well the title says it all really, wash some rice and collect the water. This milky wash will now contain some of the starches from the rice and provide a food source for your bacteria.

Step 2 – Collect your initial culture

Place your rice wash in a suitable vessel (a jar…) and protect the neck with some kind of net to stop anything random getting in. Ideally you’ll want to place this outside, in a garden, on a balcony ect away from the elements but open to the air. This will allow the bacteria to go to work on the wash. A day or so should be fine. You will notice a change in the wash as the bacteria start to work, it will start to smell slightly sour and three distinct layers should be visible. You now need to collect the middle of these layers – the best way is with a siphon, but a syringe or whatever you have to hand will work – just try not to disrupt the layers.

Step 3 – Feed the LAB

Now it’s time to culture just the LAB that are present and nothing else. To do this we add milk to the liquid we collected at about 10:1, so for every 10ml of liquid you want to add 100ml of milk – You can use pretty much any milk as it’s the LAB in the wash we are culturing, however the least adulterated milk you can get your hands on the better. It’s probably worth saying you can’t use a lactose free milk for fairly obvious reasons….Finally we want to store this in an anaerobic state, so you have a few options – Ideally you can use a container with an airlock – the same as homebrewers use (or make one), you could use a bottle or jar and release the pressure every so often (not the best plan) or as I have use a heavy lid with a seal so any gas can escape but will then re-seal (not ideal to be honest….go buy some airlocks, you’ll want them for further projects!)

Step 4 – Prep & Store the LAB

After about a week you should notice a distinct change – You’ll have a layer of curds and a liquid layer – whey. It’s this liquid layer we want. Nothing too stressful here, just use a sieve and collect the liquid in a vessel – The curds can be put on the compost or whatever, it will be a great addition. Again your brew should smell sour (actually quite pleasant if you’re in to sour beers at all….) but not rancid, if it is bin it. OK, now you have your liquid you have 2 options, store it in the fridge where it will keep for about a week or mix it with Molasses to stabilise the culture where it will keep for 6 months or more. To stabilise mix the culture 1:1 with molasses, so 1 litre culture to 1 Litre of Molasses gives you 2 Litres…..it’s worth airlocking this too until the mix stabilises.

What’s the point?

Excellent question :o) The more mundane uses for LAB include using it as an odour neutraliser if you happen to keep chickens etc – Mix 30ml per litre of water and spray around the coop to reduce the smell – Unblock drains – 15ml per litre and let it go to work over night and many more! For your growing needs however mix 30ml or so with every litre of your plant’s water. The microbes will help cycle the nutrients in the soil making them more available to the plant! Add your LAB to compost – 30ml per litre and damp down every time you add to the pile or as you’re layering up. The Lactobacillus will speed up decomposition and start to cycle the nutrients! Finally (and more excitingly), I mentioned earlier that LAB is the cornerstone of further processes that are highly beneficial to a gardener. For instance LAB can be used for Bokashi composting, no more need to buy bran for your indoor composting! If you’ve never heard of Bokashi, I’ll cover it at some point. LAB can also be used to ferment plant material, for instance if you already add seaweed meal to your feeding regime, imagine if you could ‘pre-digest’ the nutrients held within the seaweed – making the non soluble elements readily available at application….with LAB you can. If you’re a gardener familiar with the process of rotting comfrey or nettles in a bucket to annoy your plot mates, why not use LAB to break down the vegetable matter without the smell, and more importantly, without the risk of culturing the bad anaerobic bacteria. Using these principles it’s basically possible to make your own organic liquid plant food for free and without losing friends or neighbours….. The last point for this post is probably my favourite – With LAB it’s possible to create your own fish fertiliser (Fish hydrolysate) this in conjunction with your nettle/seaweed/comfrey/grass brews will give you the perfect base for making your own liquid organic fertiliser…. …that’s not bad for a little milk and help from a bacterium.

Foot notes – There should really be a sequence of pictures to go with this post, but frankly they weren’t up to scratch. If anything needs clearing up drop me an email or comment below. – N.D source

LACTIC ACID BACTERIA: GARDEN AND SOIL BENEFITS(click Here)

Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives

Abstract

In recent decades, probiotic bacteria have become increasingly popular as a result of mounting scientific evidence to indicate their beneficial role in modulating human health. Although there is strong evidence associating various Lactobacillus probiotics to various health benefits, further research is needed, in particular to determine the various mechanisms by which probiotics may exert these effects and indeed to gauge inter-individual value one can expect from consuming these products. One must take into consideration the differences in individual and combination strains, and conditions which create difficulty in making direct comparisons. The aim of this paper is to review the current understanding of the means by which Lactobacillus species stand to benefit our gastrointestinal health.

Keywords: lactobacillus, probiotic, microbiota, gastrointestinal barrier, inflammation

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Introduction

Ilya Ilyich Mechnikov (Elie Metchnikoff), a Nobel Laureate for his work on macrophage phagocytosis, is credited as the first to propose that the gut microbiota could be manipulated to benefit the host. Mechnikov believed that putrefactive activity of microbes in the intestine produced toxic substances that were damaging to the nervous and vascular systems and caused humans to age. He had observed that Bulgarian peasants consumed large quantities of yogurt and had a long life expectancy. He also observed that natural fermentation of food by lactic acid-producing bacteria prevented the growth of putrefactive organisms. In his book, titled ‘The Prolongation of Life’, he concludes that: “as lactic fermentation serves so well to arrest putrefaction in general, why should it not be used for the same purpose within the digestive tube?” (1). Although Mechnikov’s concept of aging by “intestinal auto-intoxication” has no scientific basis today, Mechnikov’s theories remain influential and have contributed to the commonly held opinion that Lactobacilli display important functional characteristics that contribute to gut health.

Lactobacillus is a genus of rod-shaped, gram-positive, non-spore-forming, facultative anaerobic bacteria of the phylum ‘Firmicutes’ (2, 3). Lactobacilli metabolise carbohydrates to produce lactic acid making them the largest genus within the lactic acid bacteria (LAB) group. As of March 2020 the 261 species of the Lactobacillacae were reclassified into 25 genera (including 23 novel genera) due to their extremely high genotypic, phenotypic and ecological diversity (4). For the purpose of this review, ‘Lactobacillus’ will refer to those species previously classified as Lactobacillus. Traditionally, Lactobacillus species may be divided into three groups based on their metabolism. The obligate homofermentative group which ferment carbohydrates to produce lactic acid as the main by-product (e.g. L. acidophilus and L. salivarius), the facultatively heterofermentative group which, under certain conditions or with certain substrates, ferment carbohydrates to produce lactic acid, ethanol/acetic acid and carbon dioxide as by-products (e.g. L. casei and L. plantarum) and the obligately heterofermentative group which always ferment carbohydrates to produce lactic acid, ethanol/acetic acid and carbon dioxide as by-products (e.g. L. reuteri and L. fermentum) (5).

Lactobacilli have colonised multiple areas of the human body, most notably the digestive tract including the oral cavity, and the female genital tract (6). The association between Lactobacilli and humans is a mutualistic relationship, with Lactobacillus species offering the host aid in digestion of certain dietary substrates, as well as protection from pathogens, in return for accommodation and nutrients (7). Lactobacillus species possess qualities that are commercially desirable both as health supplements and as tools in the food technology sector. The main uses for Lactobacilli are in the manufacturing process of fermented dairy, meat, or vegetable foods and sourdough breads, and they are also widely used as probiotics i.e., live micro-organisms that, when administered in adequate amounts, confer a health benefit on the host (8, 9). Lactobacilli have been granted a ‘generally recognised as safe’ (GRAS) status from the U.S. Food and Drug Administration (USFDA) and ‘qualified presumption of safety’ (QPS) status from the European Food Safety Authority (EFSA) thus making their use in food manufacture relatively straightforward. Due to their economic importance, Lactobacilli are highly studied and, relative to other bacterial genus’, are well characterised in terms of genomics and also their interactions with humans in terms of both health and disease. These features make Lactobacillus species ideal probiotic candidates.

Considering the widespread media attention that the microbiota have attracted in recent years with many news outlets covering this link between microbes and health it is little wonder that the commercial probiotic market is worth approximately $54 billion USD worldwide (10). For a list including some of the most common Lactobacillus strains found in probiotic products and their sources see George Kerry et al. (11). Although the strain L. rhamnosus GG is one of the most heavily studied, L. acidophilus is the most commonly used in commercial products. For an in-depth review of common commercial Lactobacillus strains see the chapter by Tang and Zhao in the book ‘Lactic Acid Bacteria: Omics and Functional Evaluation’ (12).

In 2002 a joint Food and Agriculture Organisation (FAO) and WHO working group released guidelines for the evaluation of probiotics in food (8). The minimum requirements include: assessment of strain identity (genus, species, strain), in vitro tests to show probiotic effects (e.g. resistance to gastric acidity, digestive enzymes and bile acid, and anti-microbial activity against pathogens), safety assessment to prove that the probiotic product is safe for consumption and without contamination, and finally in vivo studies to authenticate the purported health claims of the product (13). In Europe, the EFSA considers the terms ‘probiotic’, ‘prebiotic’ and the words ‘live’ or ‘active’ when used in relation to bacteria, to be health claims. Legislation on products purporting to carry health claims are strictly controlled although in recent years countries including Spain, Denmark and the Netherlands have released national guidelines allowing use of the word probiotic under certain conditions. This has renewed appeals to the EU Commission to reconsider the strict regulation. Unfortunately, in the US and Canada the FAO/WHO guidelines are not followed and indeed the use of the term probiotic has not been controlled by legislation. This means that any product can use the word ‘probiotic’ on its packaging thereby making it extremely difficult for consumers to determine which products are genuine probiotics that may actually be beneficial for their health (14).

In order to be considered efficacious, a probiotic must have the capacity to survive in the gastrointestinal (GI) tract, must resist the low pH of the stomach, must lack antibiotic resistance genes and must provide a clear benefit to the host (15). Of all probiotics, Lactobacillus species are the most widely used and studied (16). The main probiotic Lactobacillus species include: L. acidophilus, L. brevis, L. casei, L. delbrueckii subsp. bulgaricus, L. delbrueckii subsp. lactis, L. fermentum, L. gasseri, L. helveticus, L. johnsonii, L. paracasei subsp. paracasei, L. plantarum, L. reuteri and L. rhamnosus. There is much research into the potential health benefits of Lactobacillus species, although evidence indicates that many features of these probiotic bacteria are both species and strain -dependent (17). Despite this it has been observed that a single probiotic species may demonstrate improvement in different patient cohorts eg. L. rhamnosus GG (18) and additionally that a range of different probiotics or probiotic combinations may demonstrate efficacy in the same condition eg. C. difficile infection (19) highlighting the existence of conserved beneficial features. As is the case for many translational therapies, efficacy is not always maintained from in vitro observations through preclinical to clinical studies for a myriad of factors. Unfortunately, for many probiotics, one of these factors being that the mechanisms of action by which beneficial clinical outcomes are achieved have yet to be elucidated (20). The consequences for this mean that we are not utilising these tools to their full potential, opportunities for improving existing treatments may not be realised and we are at risk of probiotic treatments resulting in worse outcomes for particular subsets of patients (21). Additionally, mechanistic data may be required in order to gain approval from regulatory bodies for health claims – a mode of action is defined by the World Health Organisation (WHO) and EFSA as ‘a biologically plausible sequence of key events leading to an observed effect supported by robust experimental observations and mechanistic data’ (22). Kleerebezem and colleagues (23) propose the establishment of a translational pipeline connecting mechanistic insights to probiotic efficacy in order to improve the initial selection of probiotic strains by being able to predict their expected outcomes while supporting the design of the most appropriate clinical trials in well-defined subpopulations. They also suggest that this would be used in the inverse allowing us to predict explanations for observed clinical effects by drawing on existing knowledge of the probiotic modes of action. Determining the precise beneficial features of probiotics would certainly allow us to make better predictions for improved health outcomes.

On this note, further research is exploring ways to increase the efficiency, efficacy, safety and quality of probiotics by isolating probiotic-derived biomolecules. These have been described as postbiotics, paraprobiotics, heat-killed probiotics, Tyndallised probiotics among others: generally referring to metabolic products or secreted products of the bacteria, non-viable microbial cells (intact or broken) or crude cell extracts; specifically this includes enzymes, secreted peptides/proteins, bacteriocins, short chain fatty acids (SCFA), organic acids and cell envelope components of bacteria including peptidoglycans, teichoic acids, cell surface proteins and cell wall polysaccharides (24). The International Scientific Association for Probiotics and Prebiotics (ISAPP) has released a consensus statement on the definition of postbiotics establishing it as a “preparation of inanimate micro-organisms and/or their components that confers a health benefit on the host. Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits”. (25). Postbiotics maintain several advantages over probiotics as described by Pique et al. (26): (I) No risk of translocation from the gut lumen to blood among vulnerable subjects, (II) No risk of acquisition and transfer of antibiotic resistance genes, (III) No risk of interference with normal gut colonisation in neonates, (IV) Release of active molecules from the disrupted inactivated cells, pass through the mucus layers and stimulate epithelial cells more directly, (V) Loss of viability by cell lysis can produce further more complex beneficial effects and (VI) Easier to extract, standardize, transport, and store. Accordingly, the use of postbiotics may very well represent a much-improved alternative to live probiotics and would be a likely replacement for them in future. A recent review has nicely summarised the composition and beneficial functions of postbiotics from Lactobacillus species (27). In short, postbiotics derived from Lactobacillus comprise a range of molecules which have various beneficial effects including immunomodulation, epithelial barrier protection, anti-pathogenic effects and anti-tumour effects.

Lactobacilli have demonstrated efficacy in treating various conditions including bacterial vaginosis, atopic dermatitis, and upper respiratory tract infections (28–30). However, as first proposed by Mechnikov over 100 years ago, the majority of Lactobacillus probiotics are consumed with a view to improving GI health. In the century since this hypothesis, interest and knowledge surrounding this subject has grown massively, however the potential for further growth in this area is exponential and much more work will be required before we fully understand and profit from the complexities of the relationships between Lactobacillus and gut health.

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Lactobacillus spp. and Intestinal Barrier Integrity

The GI mucosa is the largest and one of the most critical barrier sites of the body where foreign antigens, microbes and potential pathogens come into close contact with the host’s immune system. It is a semi-permeable barrier which allows for the absorption of nutrients and immune sensing while restricting the influx of potentially harmful antigens or microbes. The GI barrier is composed of four major elements: the commensal microbiota, the mucus layer – which contains secretory IgA molecules (sIgA) and anti-microbial peptides, the intestinal epithelial cell (IEC) monolayer, and the gut associated lymphoid tissue (GALT) – which constitutes various populations of immune cells in compartments along the GI tract. The complexity of regulating this semi-permeable barrier is mitigated by dynamic inter-regulation between these elements which work together to maintain intestinal barrier integrity and homeostasis (31). Loss of intestinal barrier function has been implicated as an early event in the pathogenesis of various GI disorders, such as coeliac disease and inflammatory bowel disease, as well as systemic disorders including type I diabetes, obesity and multiple sclerosis (31).

Intestinal barrier function may be enhanced with the intake of non-pathogenic micro-organisms which augment the physical barrier of the mucus layer, enhance innate defence against pathogens and decrease paracellular permeability of IECs (32). Lactobacillus strains consumed as probiotics are thought to modulate the native intestinal microbiota and improve health via multiple mechanisms of action. As illustrated in Figure 1, probiotics strengthen intestinal barrier function by increasing mucus production, stimulating release of anti-microbial peptides, and production of secretory immunoglobulin A (sIgA) production, increasing tight junction integrity of IECs and providing a competitive resistance against pathogens such as for host colonisation receptors (33, 34).

Figure 1

Probiotic mechanisms of intestinal barrier enhancement.

Mucus Production

Goblet cells (GC) of the GI tract express rod-shaped mucins which either adhere to the epithelium or are released into the GI lumen. These mucins are highly glycosylated and link together via di-sulfide bonds to form a glycoprotein matrix that shields the intestinal epithelium from gut luminal contents (containing digestive enzymes), prevents interaction between pathogenic antigens/bacteria and the epithelial monolayer, and also aids GI motility. The mucus layer is generally between 50-800 µm thick and in healthy individuals the first 30 µm closest to the epithelial surface should be free of microbes. Lactobacillus species are believed to enhance intestinal barrier defence by promoting mucus secretion. In vitro studies have demonstrated that conditioned media from L. casei T21 can up-regulate the mucosal protective MUC2 gene in colonic epithelial cells (Caco2 and HT29) challenged with C. difficile (35). Although it has been proposed that acid may stimulate enteric cells to produce mucins (36) incubating HT29 cells with lactic acid did not replicate these findings indicating that other substances secreted by L. casei T21 are responsible for the increased gene expression. Similar results have also been obtained in the Caco-2 intestinal epithelial cell line using L. casei GG (37). In terms of in vivo studies, L. rhamnosus CNCM I-3690 has recently been shown to protect and/or restore the GC population and protect mucus layer thickness in mice following low-grade colon inflammation (38). Similarly, mice administered one of two strains of L. reuteri (L. reuteri R2LC or 4659) and exposed to DSS colitis displayed reduced colitis severity which the authors attribute at least partly to the increase in mucus thickness seen in mice given the probiotic both in control and inflammatory conditions (39).

The commercially available probiotic VSL#3 contains a combination of eight lactic acid producing bacteria of which four are Lactobacilli (L. plantarum, L. delbrueckii subsp. Bulgaricus, L. casei, L. acidophilus, Bifidobacterium breve, B. longum, B. infantis and Streptococcus salivarius subsp. thermophilus). Although the contribution of each bacterial strain cannot be clarified, both in vitro and in vivo experiments by Caballero-Franco et al. (40) using this probiotic in rats have indicated enhancement of the mucus layer measured by over-expression of mucin genes and increased basal luminal mucin content. Conversely, a similar study in mice failed to show altered mucin expression or mucus layer thickness using this probiotic (41). Further work is required to determine whether the in vitro effects of probiotics on mucus production are maintained in vivo.

Anti-Microbial Peptides/Factors

Host-produced GI anti-microbial peptides are generally categorised into cathelicidins and defensins. Cathelicidins are α-helical cationic peptides constitutively expressed in the GI tract which may also be activated by butyrate. Butyrate is produced by the enteric microbiota however few studies have examined the effect of probiotics on cathelicidin expression. Defensins are small, cationic peptides further classified into β-defensins, produced by epithelial cells throughout the intestine, and α-defensins, expressed in the small intestine. Defensins are constitutively expressed in the GI tract and display anti-microbial activity against many bacteria, fungi and some viruses. L. acidophilus PZ1138 and L. fermentum PZ1162, were shown to induce expression of human β-defensin-2 gene in Caco-2 cells via classic pro-inflammatory mechanisms (42). L. reuteri (FINELACT^®) administered to broiler chicks was associated with anti-microbial peptide modulation in the cecum and ileum in addition to upregulation of pro-inflammatory mediators (43).

In addition to host-derived anti-microbial peptide stimulation, commensal bacteria also produce anti-microbial factors to aid in host barrier defence. These factors include short chain fatty acids (SCFA), hydrogen peroxide and bacteriocins. Lactobacilli alter luminal pH by producing lactic acid. This inhibits the growth of some bacteria and damages the outer cell membrane of Gram-negative bacteria, including E. coli O157:H7, Pseudomonas aeruginosa, and Salmonella enterica serovar Typhimurium making them more vulnerable to other anti-microbial molecules (44). Anti-microbial activity by L. johnsonii NCC533 has been associated with lactic acid and hydrogen peroxide production (45). Bacteriocins are small, ribosomally synthesised, heat-stable peptides produced by many species of bacteria which function to inhibit the growth of (bacteriostatic), or kill (bactericidal), other bacteria (46). Bacteriocins produced by Gram-positive bacteria generally exert their antibiotic effects by destabilisation of membrane function, typically against other Gram-positive bacteria, though some Gram-negative bacteria may also be susceptible (47). Lactobacillus strains produce SCFAs including acetate, propionate and butyrate, which have been shown to shown to increase transepithelial electrical resistance and stimulate the formation of tight junction in Caco-2 intestinal epithelial cells in vitro via inhibition of the NLRP3 inflammasome and autophagy (48). L. plantarum strains produce several bacteriocins which demonstrate anti-microbial activity against food borne pathogens such as Listeria monocytogenes as well as food spoilage bacteria are applied in food production to reduce the use of chemical preservatives (49). Corr et al. (50) demonstrated that Abp118 produced by L. salivarius UCC118 in vivo protects mice against L. monocytogenes infection. Two other bacteriocins analogous to Abp118 have since been identified by comparative genome hybridisation analysis from L. salivarius DPC6488: salivaricin L and T. Both bacteriocins demonstrated inhibitory activity towards L. delbrueckii subsp bulgaricus LMG 6901 with salivaricin L additionally inhibiting L. monocytogenes NCTC 11994 and L. innocua DPC3572 (51).

Secretory IgA

The production of IgA is an important strategy utilised by the GI tract to generate immune protection in a non-inflammatory mode (52). IgA dimers (secreted by intestinal B cells located in Peyer’s patches or lamina propria) interact with the polymeric IG receptor (pIgR) on the basolateral surface of epithelial cells, translocate to the surface of the epithelial cells and are released as sIgA (53). sIgA primarily promotes the maintenance of suitable commensal bacterial communities in the gut by binding dietary antigens and potential pathogens in the mucus and down-regulating the expression of pro-inflammatory bacterial epitopes on commensal bacteria (54). Furthermore, sIgA enhances the intestinal barrier by blocking microbial components involved in epithelial adherence, facilitating intraepithelial defence against pathogens and microbial products and enabling antigen sampling (55). In addition, locally released IgA dimers function to remove micro-organisms that have breached the epithelial barrier by facilitating their removal or promoting their clearance by binding to the CD89 receptor on immune cells such as dendritic cells, neutrophils and other phagocytes (56). Although commensal bacteria are believed to induce sIgA expression in the GI tract the mechanisms are not well understood, although there appear to be differences in the microbes responsible for small intestine and large intestine sIgA induction (57). Various Lactobacillus strains including L. paracasei MCC1849, L. gasseri SBT2055, and L. plantarum AYA are known to increase sIgA levels in the small intestine (58–60). In a clinical trial of children 12 to 24 months old, supplementation with L. plantarum IS-10506 increased sIgA faecal titres and a significant positive correlation was observed between this and TGF-β1/TNF-α ratios (61). The authors propose a probiotic induced immune activation of TGF-β1, which in turn increases the production of sIgA.

Epithelial Cell Barrier

As previously described, IECs form a monolayer of cells which act as a physical barrier between the external environment of the gut lumen and the host’s immune system. The integrity of this barrier is ensured by tight junctions (TJ) which are multi-protein complexes that bind the cells tightly together as well as adherens junctions, gap junctions and desmosomes. TJs are located towards the apical side of the epithelial cells. They consist of transmembrane proteins (claudin, occludin, and junctional adhesion molecules) which interact extra-cellularly with similar proteins of TJs in neighbouring cells and intra-cellularly with the cells own cytoskeleton via zonula occludens (ZO) proteins and filamentous actin (62). Loss of TJ integrity has been observed in chronic inflammatory disease, and mechanisms of disrupting TJ proteins in order to breach the GI barrier have been observed in infection by enteric pathogens such as C. difficile, E. coli, Salmonella Typhimurium, C. rodentium, Vibrio cholera among others (62). It has been demonstrated that L. rhamnosus GG ATCC 53103 up-regulates ZO-1, claudin and occludin expression in Caco-2 cells (63). This probiotic strain has been observed to increase levels of ZO-1 expression and enhance distribution of claudin-1 protein as a protective mechanism against enterohemorrhagic E. coli O157:H7 infection (64). Increased expression of ZO and occludin was also observed using various L. plantarum strains (L. plantarum WCSF1, CGMCC 1258, and MB 452) (65–67). L. plantarum WCSF1 administration into the duodenum of healthy human subjects increased ZO-1 and occludin staining in the vicinity of TJ structures via activation of TLR-2 (65). The addition of a TLR-2 agonist PCSK to Caco2 monolayers in vitro increased staining of occludin in TJ regions and was protective against epithelial barrier disruption. TLR-2 ligand binding leads to PKC activation which has been demonstrated to cause translocation of tight junction components (68) thereby it is likely that barrier integrity is enhanced by alterations to composition of tight junction proteins rather than an increase in these proteins. Lactobacillus species may also stabilise adherens junctions by increasing expression of E-cadherin, as well as by strengthening the E-cadherin/β-catenin complex (which connects adherens junctions to the cytoskeleton) via enhanced phosphorylation of β-catenin (69). In a clinical study of small intestine barrier function, biopsy samples demonstrated that L. plantarum strain TIFN101 and to a lesser extent L. plantarum WCFS1 and CIP104448, modulated an increase in gene expression of TJ and adherens junction proteins (70).

Competitive Resistance

Lactobacilli also aid intestinal barrier resistance to invading pathogens by competing for binding sites on IECs, glycoproteins in the mucus layer or to the plasminogen of extracellular matrix (71). In order to facilitate the necessary interactions with host cells, Lactobacillus species display various different components on their outer surface. These may include cell wall proteins, S-layer proteins, pili proteins, and moonlight proteins (72) (see Figure 2). These surface proteins facilitate adhesion of Lactobacilli to the host, for example LPXTG proteins found in several Lactobacillus strains are cell surface proteins covalently bound to the peptidoglycan layer and can bind to both mucus and epithelial cells (73). Several Lactobacillus strains possess a crystalline, glycoprotein surface layer, also known as the S-layer, non-covalently anchored to the peptidoglycan cell wall (74). The S-layer S-proteins of L. acidophilus ATCC 4356 have demonstrated anti-viral activity against alphavirus and flavivirus infection of 3T3 cells by blocking pathogen adhesion to C-type Leptin receptors (DC-SIGN) an attachment factor which strongly promoted viral infection (75). Further work is required to elucidate the mechanism for this, which may be multi-faceted, though the time-dependant aspect of the anti-viral function may indicate that S-layer proteins are activating downstream anti-viral signalling pathways.

Figure 2

Representation of the Lactobacillus cell surface structure including important effector molecules.

Pili are long protein structures, first observed in a non-pathogenic bacteria in L. rhamnosus GG, which protrude from the bacterial cell playing a major role in adhesion to the epithelium. In L. rhamnosus GG (ATCC 53103) SpaC pili have been demonstrated to out-compete the pathogenic Enterococcus faecium (76).

Moonlighting proteins are multifunctional proteins in which one polypeptide chain performs more than one unrelated biochemical or biophysical function (77). In Lactobacilli, moonlighting proteins may have a primary function as intracellular proteins but are also found on the cell surface where they facilitate adhesion, for example, L. plantarum 299v (78), L. acidophilus (79), L. reuteri ZJ617 (80), display GAPDH on their surface to mediate adhesion and colonisation of the GI tract. So far in the case of L. plantarum 299v it has been demonstrated that this results in competitive exclusion and displacement of pathogenic bacteria (81). The mechanism for the secretion of moonlighting proteins to the cell surface has not yet been elucidated.

L. rhamnosus R0011 and L. acidophilus R0052 adhere to Hep-2 and T84 intestinal cell lines in vitro preventing the binding of enterohemorrhagic E. coli and enteropathogenic E. coli (82). In Caco-2 cells, various strains of L. reuteri (LR5, LR6, LR9, LR11, LR19, LR20, LR26, and LR34) have been shown to adhere and inhibit and displace the binding of E. coli ATCC 25922, S. Typhi NCDC 113, L. monocytogenes ATCC 53135, and E. faecalis NCDC115 (83). It should be noted that competition for binding sites is species and strain -specific; L. rhamnosus ATCC 53103, L. gasseri DSM 20243, L. casei ATCC 393 and L. plantarum ATCC 14917 pre-treatments did not block enterohemorrhagic E. coli binding to human colon epithelial cell line C2BBe1 cells (although the L. rhamnosus strain prevented internalisation of E. coli into the cell line) (84). In a chronic stress model in vivo, pre-treatment with L. helveticus R0052 and L. rhamnosus R0011 reduced commensal adherence and translocation (85). Interestingly, in a hemorrhagic shock model in vivo, L. rhamnosus LMG P-22799 but not L. fermentum NumRes2 reduced bacterial translocation and cytoskeleton rearrangement despite both strains displaying similar pathogen exclusion properties in vitro in Caco2 cells (86). Indeed, L. fermentum NumRes2 increased bacterial translocation, primarily Lactobacillus spp., to the spleen highlighting the need for careful characterisation of the effects of individual.

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Lactobacillus spp. and Gastrointestinal Infection

Understandably, the beneficial impact on gut health is one of the most widely studied topics in probiotic research. As discussed in the previous section, Lactobacilli protect the intestinal barrier from infection by promoting mucus production and barrier-related proteins, secreting anti-microbial substances such as SCFAs, bacteriocins and hydrogen peroxide which inhibit the growth of or kill pathogens, by modulating the host’s immune response to pathogens, and preventing adherence of pathogens and competing for binding sites. Thus, Lactobacilli are capable of preventing intestinal damage caused by certain bacterial infections. Lactobacillus probiotics have been demonstrated to inhibit the development of infection by pathogenic bacteria, such as C. difficile and C. perfringens (87), Campylobacter jejuni (88), S. Enteritidis (89), E. coli (90), Staphylococcus aureus (91), and Yersinia (92), among others. Two major GI disorders resulting from infection, H. pylori infection and antibiotic-associated diarrhoea, have been shown to greatly benefit from Lactobacillus probiotics and are outlined below.

H. pylori Infection and Lactobacilli

H. pylori infection is one of the most common bacterial infections in the world with more than half of the global population infected; though prevalence ranges from 24% in Oceania to 70% in Africa (93). H. pylori infects the epithelial lining of the stomach causing disorders such as peptic ulcer disease, chronic gastritis, and gastric cancer although many infected individuals are asymptomatic (94). Twenty percent of infected patients develop symptomatic gastritis, gastric or duodenal ulcers, gastric adenocarcinoma, or non-Hodgkin’s gastric lymphoma. The current recommended treatment for H. pylori infection involves multiple antibiotic drugs as well as a proton pump inhibitor however the effectiveness of this treatment is decreasing as H. pylori antibiotic resistance rises. The addition of a Lactobacillus probiotic (L. casei DN-114 001 (OAC-LC) and L. casei Shirota separately) and an L. acidophilus LB postbiotic have been shown to improve the efficacy of this therapy in various randomised controlled trials (95–97), however some trials have found no or only slight beneficial effects (98–101). Although the probiotic L. johnsonii NCC533 failed to eradicate H. pylori infection when administered alone, it did decrease inflammatory scores and urea breath test (used for the diagnosis of H. pylori infection) values (102, 103).

Cell-free spent culture supernatants (CFCS) derived from L. casei Shirota exhibited pH-dependant bactericidal activity against H. pylori in vitro (104). The CFCS of L. johnsonii NCC533 and L. acidophilus LB both resulted in the loss of H. pylori viability (105–107). Furthermore, the CFCS from these three Lactobacillus strains resulted in altered morphology of H. pylori bacteria to U-shaped or coccoid forms which are dormant forms of the bacteria with the coccoid form being less capable of colonising and inducing inflammation (108, 109). L. johnsonii NCC 533 and L. casei Shirota are also known to produce bacteriocins which are active against H. pylori (110). H. pylori is a spiral-shaped bacterium with multiple flagella allowing it to swim in the gastric mucus layer and interact with epithelial cells, an ability which is required for colonisation in the stomach (111). L. casei Shirota has been demonstrated to cause H. pylori to lose its flagellar motility due to transformation into dormant forms with no flagella and also by secretion of small anti-microbial compounds which inhibit swimming ability (104). Similarly, L. johnsonii NCC 533 also secretes compounds that inhibit the swimming ability of H. pylori (112). In order to survive in the low pH of the stomach, H. pylori expresses urease as a surface protein to neutralise the surrounding acidic environment. CFCSs from L. acidophilus LB and L. johnsonii La1 have been demonstrated to reduce urease activity of H. pylori (105, 106). In terms of adherence, L. acidophilus CFCS prevented the adhesion of H. pylori onto human HT-29 cells resulting in the death of adhering cells and reducing the urease activity of remaining adherent cells causing their lysis (105).

Antibiotic-Associated Diarrhoea and Lactobacilli

Antibiotic-associated diarrhoea (AAD) results from disruption of the normal microbiota of the gut by antibiotics with symptoms ranging from mild diarrhoea to more serious disease like pseudomembranous colitis (PMC) (113). AAD occurs in 5-30% of patients receiving antibiotics either during antibiotic therapy or up to 2 months after cessation of treatment. One of the major pathogens associated with AAD is C. difficile, responsible for 10-30% of normal AAD cases and 90-100% of severe cases such as PMC (114). Although other microbes including C. perfringens, S. aureus and Klebsiella oxytoca are associated with this disorder, they are not common (113). As the cause for AAD is known to be disruption of the normal intestinal microflora, and also due to the fears surrounding anti-microbial resistance, recent therapeutic research has focused on the use of probiotics or faecal microbiota transplantation to restore microbial equilibrium (115, 116). Though the mechanism of action of probiotics is not explicitly known in this case their efficacy seems to be maintenance of gut flora, out-competing pathogenic bacteria, preservation of intestinal barrier function and potentially immunomodulation. Treatment with several Lactobacillus strains including L. rhamnosus GG (ATCC 53103) and L. gasseri have been shown to be effective as a preventive measure for AAD (117). However, the effects are strain-dependent. A systematic review examined 51 randomised controlled trials and found that L. rhamnosus GG was significantly more effective than other probiotics, however L. casei species were most effective against C. difficile infection (118). Another recent review demonstrated similar results in children concluding that L. rhamnosus GG (ATCC 53103) can be safely given to prevent AAD and additionally to manage symptoms of acute gastroenteritis (119).

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Lactobacillus spp. and Intestinal Inflammation

In humans, the immune system can be divided into the innate immune system and the adaptive immune system. Innate immunity is the first line of immune defence and is a non-specific response which acts as an immediate reaction to pathogens. Phagocytic cells such as natural killer (NK) cells, macrophages, monocytes and neutrophils recognise pathogenic targets and engulf and destroy them. Antigen presenting cells (APC) such as dendritic cells (DC) maybe activated via the innate response and in turn activate the adaptive immune response. The adaptive immune response relies largely on activation and differentiation of B and T cells. B cells recognise antigens via B cell receptors and act by secreting antibodies (humoral immunity). T cells recognise antigens via T cell receptors and differentiate into T helper cells (Th; CD4+) or cytotoxic T cells (CD8+). Th cells recognise antigen via MHC class I complexes and CD8+ cells do this via MHC class II complexes. Th cells differentiate into Th1 or Th2 effector cells which activate and regulate macrophages (Th1) and B cells (Th2) while CD8+ cells convert into cytotoxic T cells. In the GI tract the immune system is made up of the epithelial layer, the lamina propria and the gut associated lymphoid tissue. The GALT is populated by B and T cells as well as plasma cells, macrophages and M cells. APCs in Peyer’s patches take IgA antigen from epithelial cells to activate T cells and also transport it to lymphoid tissue of the lamina propria and mesenteric lymph nodes. M cells present in Peyer’s patches of the small intestine transport antigens, macromolecules, micro-organisms and inert peptides from the gut lumen into the tissue via adsorptive endocytosis. These antigens may then activate the innate and adaptive immune systems.

As alluded to in the previous sections, Lactobacilli play an immunological role within the GI tract of the host, strengthening the intestinal barrier and conferring protection from potential pathogens. Lactobacilli can interact with both the innate and adaptive immune response systems via micro-organism-associated molecular patterns (MAMPs) interacting with pattern recognition receptors such as Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors and C-type lectins expressed on immune cells or on tissues including intestinal epithelium (120). The Lactobacillus cell envelope comprises several types of molecules which act as MAMPs including the peptidoglycan multi-layer, teichoic acids (lipoteichoic acid (LTA) bound to the cell membrane and wall teichoic acid bound to the peptidoglycan layer), exopolysaccharides (EPS) along with cell surface adhesion molecules previously discussed (see Figure 2). The immunomodulatory effect of Lactobacilli is achieved with the release of cytokines, including interleukins (IL), tumour necrosis factors (TNF), interferons (IFN), transforming growth factor (TGF), and chemokines from immune cells (121). The inflammatory process depends on pro-inflammatory versus anti-inflammatory cytokines and in this way probiotics may act in an immunoregulatory or immunostimulatory manner. Immunoregulatory probiotics decrease inflammatory responses protecting the host against autoimmune diseases, inflammatory bowel disease and allergy and are characterised by IL-10 and regulatory T cell (Treg) production. IL-10 is an anti-inflammatory cytokine produced by monocytes, T cells, B cells, macrophages, NK cells and DCs to inhibit pro-inflammatory cytokines, chemokines and chemokine receptors protecting against intestinal inflammation. Immunostimulatory probiotics defend the host against infection and cancer development activating NK cells and developing Th1 cells via IL-12 production, and also defend the host against allergy by balancing Th1 and Th2 production. Mounting evidence would suggest that probiotic Lactobacilli have the potential to prevent or treat certain inflammatory conditions (122).

The activation of specific immune receptors by MAMPs on Lactobacillus species has been characterized to an extent. Peptidoglycan of L. casei Shirota, L. johnsonii JCM 2012 and L. plantarum ATCC 14917 has been shown to down-regulate IL-12 production via TLR2 (123). Peptidoglycan from L. rhamnosus CRL1505 demonstrated an enhancement of innate and adaptive immune responses ameliorating the Th2 response when administered nasally in mice (124). LTA of L. plantarum has been shown to elicit an anti-inflammatory response in both human and porcine intestinal epithelial cells via inhibition of IL-8 (125, 126). The knockout mutant for the SpaCBA pilus of L. rhamnosus GG demonstrated that not only are these pili essential for adhesion but also the knockout demonstrated an increase in IL-8 likely via LTA TLR2 signalling which suggests an immunomodulatory role for this adhesion molecule (127). The protective exopolysaccharide layer has also demonstrated immunomodulatory capabilities with EPS from L. rhamnosus RW-9595M inducing macrophage production of IL-10 and no induction of TNF-α, IL-6, or IL-12 (128) and L. plantarum 14 EPS decreasing the IL-6 and IL-8 production in response to an enterotoxigenic E. coli challenge in porcine epithelial cells (129). In mice, EPS derived from L. delbrueckii subsp.bulgaricus OLL1073R-1 fermented yogurt had an immunostimulatory effect, activating natural killer (NK) cells and inducing IFN-γ production in the spleen (130).

Some immunomodulatory effects are mediated by the metabolites of Lactobacillus, such as SCFAs, in particular, propionate, acetate, and butyrate. These postbiotics bind to specific receptors on intestinal epithelial cells to inhibit pro-inflammatory activity and Treg suppressive effects of neutrophils and macrophages (131–133). Indeed butyrate enemas have demonstrated efficacy and become an accepted treatment for diversion colitis though this is believed to be due to a relaxation effect on smooth muscle (134).Lactobacilli are also capable of producing antioxidants like glutathione (GSH) and can induce reductions in oxidative stress. Two strains of L. bulgaricus (L. delbrueckii subsp. bulgaricus B3 and A13) have been demonstrated to reduce lipid peroxidation, increase measurements of antioxidant enzymes, and reduce oxidative stress in a rat model of colitis (135). In a mouse model of gastric damage L. fermentum Suo significantly reduced malondialdehyde (MDA; a measure of oxidative damage) concentrations and serum concentrations of IL-6, IL-12, TNF-α, and IFN-γ (136). L. casei 114001 administered to rats increased the antioxidant capacity of plasma, liver and intestines and decreased MDA plasma concentration (137). In healthy human subjects, L. casei capsules administered with prebiotic inulin significantly decreased MDA and glutathione disulphide (GSSG; another measure of oxidation) concentrations and increased concentrations of antioxidant indicators: GSH, total GSH (GSHt) and free sulfhydryl group (-SH) in the plasma (138). Pre-treatment with L. acidophilus NCDC15 with inulin and L. rhamnosus GG MTCC 1408 with inulin in a model of colon cancer in mice lead to a reduction in MDA and an increase in antioxidants GSH-reductase, GSH-peroxidase and superoxide dismutase as well as fewer dysplastic changes (139).

Lactobacilli may also modulate the immune system by secretion of proteinaceous compounds. Proteins p40 and p75 released from L. rhamnosus GG ATCC 53103 both activated the Akt signalling pathway, inhibiting TNF-a –induced apoptosis in human and murine colonic epithelial cells and murine colon explants (140). Pre-treatment with L. rhamnosus GG milk prior to induction of dextran sulphate sodium –induced colitis in mice significantly reduced colonic inflammation and injury, suppressing cytokine-induced apoptosis and reducing H₂O₂-induced disruption of TJs. Depletion of two soluble proteins found in L. rhamnosus milk, p40 and p75, abolished these anti-inflammatory effects (141). L. rhamnosus GG ATCC 53103 increased production of the heat-shock proteins HSP25 and HSP72 in murine colon cells via secretion of soluble peptides which function via activation of MAPK signal transduction pathway (142).

There have been many reports of Lactobacilli influencing the immune system while also enhancing the intestinal barrier. In vitro, L. acidophilus PZ1138, L. fermentum PZ1162, and L. paracasei LMG P-17806 induced expression of human β-defensin-2 gene in Caco-2 cells via modulation of nuclear factor kB (NF-kB) and the activator protein 1 (AP-1) resulting in IL-8 expression (42). L. salivarius Ls33 peptidoglycan induced anti-inflammatory IL-10 production, and stimulated Treg responses via NOD2 rescuing symptoms in a tri-nitrobenzene sulfonic acid (TNBS) -induced colitis murine model (143). Enteral administration of L. rhamnosus GG decreased inflammation in the developing mouse colon, attenuating pro-inflammatory MIP-2 and TNF-α concentrations in an IL-10 receptor-dependent manner (144). In Caco-2 cells L. plantarum WCSF1 has been shown to enhance ZO-1 trafficking to TJ regions in a toll-like receptor (TLR)-2-dependent manner (65). In a porcine intestinal cell line, L. rhamnosus GG ATCC 7469 pre-treatment increased ZO-1 and occludin protein expression in a TLR-2-dependent mechanism and also attenuated enterotoxigenic E. coli –induced increases in TNF-α via a partly TLR-2-mediated mechanism (145).

Lactobacilli may interact with enterocytes, DCs, Th1, Th2 and Treg cells in their immunomodulatory capacity in the intestine. Studies in vitro and in vivo demonstrated that L. paracasei and L. acidophilus strains induced early innate and adaptive immune responses in developing mice and rats in terms of phagocytosis, polymorphonuclear cell recruitment and TNF-α, IL-6, IL-10, IFN-γ production in a TLR-dependent mechanism (146). Homogenates prepared from several probiotics including L. rhamnosus GG ATCC53103, L. rhamnosus LC-705, L. acidophilus NCFB-Lb1748, and L. bulgaricus ATCC 11842 have demonstrated the ability to suppress peripheral blood mononuclear cell proliferation and L. acidophilus homogenates also down-regulated expression of IL-2 and IL-4 (147). In a mouse model of colitis where IL-10-deficient mice were infected with H. hepaticus, the combination of L. paracasei 1602 and L. reuteri 6798 reduced mucosal inflammatory cytokines TNF-α and IL-12 and also reduced intestinal inflammation (148). In an in vitro model, L. sakei LTH681 induced the inflammatory cytokines IL-1β, IL-8 and TNF-α in Caco-2 cells while L. johnsonii La1 failed to induce pro-inflammatory cytokines and instead induced production of anti-inflammatory TGF-β (149). Co-culture of ileal explants from patients with Crohn’s disease with L. casei DN-114001 and L. bulgaricus LB10 resulted in decreased TNF-α expression as well as decreased numbers of CD4+ T cells within the inflamed mucosa (150). CFCS from L. acidophilus ATCC 4356, L. casei ATCC 334, L. lactis ATCC 11454 and L. reuteri ATCC 55148 down-regulated IL-8 expression in human HT-29 cells and had differing strain-dependent efficacies in decreasing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and in increasing anti-inflammatory IL-10 production in LPS-stimulated monocyte-derived macrophages (151).

Inflammatory bowel disease (IBD) is an example of an intestinal inflammatory disease which may be modulated by Lactobacilli probiotics. IBD is a chronic, relapsing and remitting disorder characterised by inflammation of the GI tract with two main classifications: Crohn’s disease and ulcerative colitis. Although the cause of IBD is unclear, dysbiosis of the GI microbiota is a feature of the disorder and it is believed probiotics may have a therapeutic benefit by restoring microbial balance and also by immunomodulation (152). Data from both in vitro and in vivo studies in animal models of colitis are extremely promising in terms of reducing inflammatory markers and decreasing colitis severity (153–155), however the same cannot be said for clinical trials of probiotics in IBD. Although it would appear that probiotics have beneficial effects in inducing remission and increasing remission times in UC (156) this has not yet been demonstrated for CD (157). A meta-analysis recently showed that L. rhamnosus GG displayed no beneficial effects in IBD patients, though VSL#3 (a combination of eight lactic acid bacteria strains – of which four are Lactobacilli) was better than placebo in terms of a higher remission rate and lower relapse rate (158). Similarly, another recent meta-analysis and systematic review concluded that a combination of Lactobacillus probiotics and prebiotics were effective in UC, although probiotics in general were not effective in CD (159). Further randomised, placebo controlled, clinical trials will be required to clarify the role of Lactobacilli in IBD and to elucidate the most beneficial strain, dose, and mode of administration.

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Conclusion and Future Perspectives

There is increasing evidence to suggest that commercial and clinical use of probiotics is outpacing proven science. A recent study in healthy human subjects given probiotic supplements indicated that the colonisation of the GI tract featured person, region and strain -specific differences. In some individuals colonisation did not occur with the GI tract demonstrating colonisation resistance to the probiotics. The authors conclude that considering the transient, individualised effect of probiotics, the development of new personalised probiotic approaches is merited (160).

Despite the ever-increasing prevalence of probiotic use, there are also many limitations and unknowns (161–163). Data from research trials on efficacy of probiotics in the treatment and prevention of disease can often have conflicting results with similar studies pointing to opposing conclusions. These confusing data are somewhat to be expected and may be accounted for given the extremely complex nature of host – probiotic – microbiota interactions. One must allow for the unique individual differences in human microbiota composition, due to age, health, diet etc., which may affect the response to the intervention and may even account for adverse effects. Risks associated with probiotic use are generally concerned with the safety of vulnerable patient cohort such as the elderly or the immunocompromised. Thorough elucidation of mechanistic properties and host interactions will required in order to determine the probiotic strains and required intake levels required to achieve the desired health outcomes. It is also of note particularly for probiotic use in healthy individuals, and indeed for mechanisms requiring microbe-host interaction, that evidence indicates that probiotics are unlikely to be capable of maintaining colonisation in the host with any differences in microbiota composition being transient and dependent on continued probiotic intake. In terms of study design, it is often the case that mechanistic observations are founded in in vitro cell populations which cannot give the full picture of host and microbiota interactions. These are not always supported by in vivo observations in animal models which themselves may be flawed given incompatibilities or inconsistencies between human and animal microbiomes. On top of this the variety of available and potential new probiotics is vast and, as we have seen, beneficial effects can be species or strain specific and may require combination with other probiotics or prebiotics to be effective. Additionally, it is often the case that probiotic trials are initiated and funded by components of the probiotic industry who have commercial interests and may have a motive to downplay adverse effects. Although systematic reviews and meta-analyses of existing studies go some way in trying to overcome biased or underpowered research and allow for observation of overall trends, they are not themselves immune from the introduction of bias. Large, long-term, multicentre randomised controlled trials of probiotics chosen based on mechanistic information with specific beneficial outcomes for specific human cohorts in mind and involving collaborations with non-affiliated groups should be the aim to truly separate the good from the ineffective or bad.

It is clear that we have a long way to go in understanding all of the complexities of the microbiota and the effects of probiotic bacteria for health. Far more in-depth clinical testing will be required in order to substantiate the health claims of commercially available probiotic health supplements. Further elucidation of the modes of action of beneficial probiotics in clearly defined subsets of populations will hopefully allow us to make better predictions about efficacy, improve clinical trial design and enable improvement in development of probiotic health strategies. Expansion in the field of bacterial-derived products i.e. postbiotics signals a more precise, effective and safer future for the probiotic health market. In the interim, those looking to improve their overall health by enhancing their GI microbial complexity might find it more advantageous to focus on consuming a healthy varied diet of grains, fruit, vegetables and fermented foods such as miso, nattō, kimchi and sauerkraut.

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Author Contributions

Writing—original draft preparation, ED; writing—review and editing, ED and SC; Conceptualization, ED and SC; Funding acquisition, SC. All authors have read and agreed to the published version of the manuscript.

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Funding

Funding for the Corr Lab is provided by Science Foundation Ireland [grant 19/FFP/6499].

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Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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References

1. Metchnikoff E. The Prolongation of Life; Optimistic Studies. London: Heinemann; (1907). [Google Scholar]

2. Hammes WP, Hertel C. Lactobacillus. In: Whitman WB, Rainey F, Kämpfer P, Trujillo M, Chun J, DeVos P, et al., editors. Bergey’s Manual of Systematics of Archaea and Bacteria. (Hoboken USA: John Wiley & Sons, Inc.) In Association With Bergey’s Manual Trust (2015). p. 1–76. doi: 10.1002/9781118960608.gbm00604 [CrossRef] [Google Scholar]

3. Ibrahim SA. Lactic Acid Bacteria: Lactobacillus Spp.: Other Species. Reference Module in Food Science: Elsevier; (2016). [Google Scholar]

4. Zheng J, Wittouck S, Salvetti E, Franz C, Harris HMB, Mattarelli P, et al.. A Taxonomic Note on the Genus Lactobacillus: Description of 23 Novel Genera, Emended Description of the Genus Lactobacillus Beijerinck 1901, and Union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol (2020) 70(4):2782–858. doi: 10.1099/ijsem.0.004107 [PubMed] [CrossRef] [Google Scholar]

5. De Angelis M, Gobbetti M. Lactobacillus SPP.: General Characteristics☆. In: Reference Module in Food Science. Amsterdam, Netherlands: Elsevier; (2016). [Google Scholar]

6. Heeney DD, Gareau MG, Marco ML. Intestinal Lactobacillus in Health and Disease, a Driver or Just Along for the Ride? Curr Opin Biotechnol (2018) 49:140–7. doi: 10.1016/j.copbio.2017.08.004 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

7. Matos RC, Leulier F. Lactobacilli-Host Mutualism: “Learning on the Fly”. Microb Cell Fact (2014) 13 Suppl 1(Suppl 1):S6–S. doi: 10.1186/1475-2859-13-S1-S6 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

8. FAO/WHO . Guidelines for the Evaluation of Probiotics in Food.: Food and Agriculture Organization of the United Nations and World Health Organization Working Group Report. London, Ontario, Canada: Joint FAO/WHO Working Group; (2002). [Google Scholar]

9. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al.. The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Scope and Appropriate Use of the Term Probiotic. Nat Rev Gastroenterol Hepatol (2014) 11(8):506–14. doi: 10.1038/nrgastro.2014.66 [PubMed] [CrossRef] [Google Scholar]

10. Probiotics Market Size, Share & Trends Analysis Report By Product (Food & Beverages, Dietary Supplements), By Ingredient (Bacteria, Yeast), By End Use (Human, Animal), By Distribution Channel, And Segment Forecasts, 2021 – 2028: Grand View Research (2021). Available at: https://www.grandviewresearch.com/industry-analysis/probiotics-market.

11. George Kerry R, Patra JK, Gouda S, Park Y, Shin H-S, Das G. Benefaction of Probiotics for Human Health: A Review. J Food Drug Anal (2018) 26(3):927–39. doi: 10.1016/j.jfda.2018.01.002 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12. Tang X, Zhao J. Commercial Strains of Lactic Acid Bacteria With Health Benefits. In: Chen W, editor. Lactic Acid Bacteria: Omics and Functional Evaluation. Singapore: Springer Singapore; (2019). p. 297–369. [Google Scholar]

13. Binda S, Hill C, Johansen E, Obis D, Pot B, Sanders ME, et al.. Criteria to Qualify Microorganisms as “Probiotic” in Foods and Dietary Supplements. Front Microbiol (2020) 11:1662. doi: 10.3389/fmicb.2020.01662 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

14. Reid G, Anukam K, Koyama T. Probiotic Products in Canada With Clinical Evidence: What can Gastroenterologists Recommend? Can J Gastroenterol (2008) 22(2):169–75. doi: 10.1155/2008/843892 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

15. Montalban-Arques A, De Schryver P, Bossier P, Gorkiewicz G, Mulero V, Gatlin DM, 3rd, et al.. Selective Manipulation of the Gut Microbiota Improves Immune Status in Vertebrates. Front Immunol (2015) 6:512. doi: 10.3389/fimmu.2015.00512 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

16. Dronkers TMG, Ouwehand AC, Rijkers GT. Global Analysis of Clinical Trials With Probiotics. Heliyon (2020) 6(7):e04467. doi: 10.1016/j.heliyon.2020.e04467 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

17. Tsai YT, Cheng PC, Pan TM. The Immunomodulatory Effects of Lactic Acid Bacteria for Improving Immune Functions and Benefits. Appl Microbiol Biotechnol (2012) 96(4):853–62. doi: 10.1007/s00253-012-4407-3 [PubMed] [CrossRef] [Google Scholar]

18. Capurso L. Thirty Years of Lactobacillus Rhamnosus GG: A Review. . J Clin Gastroenterol (2019) 53(Suppl 1):S1–41. doi: 10.1097/MCG.0000000000001170 [PubMed] [CrossRef] [Google Scholar]

19. Goldenberg JZ, Yap C, Lytvyn L, Lo CKF, Beardsley J, Mertz D, et al.. Probiotics for the Prevention of Clostridium Difficile-Associated Diarrhea in Adults and Children. Cochrane Database Syst Rev (2017) 12. doi: 10.1002/14651858.CD006095.pub4 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

20. Sung JJY, Wong SH. What Is Unknown in Using Microbiota as a Therapeutic? J Gastroenterol Hepatol (2022) 37(1):39–44. doi: 10.1111/jgh.15716 [PubMed] [CrossRef] [Google Scholar]

21. Kothari D, Patel S, Kim S-K. Probiotic Supplements Might Not be Universally-Effective and Safe: A Review. Biomed Pharmacother (2019) 111:537–47. doi: 10.1016/j.biopha.2018.12.104 [PubMed] [CrossRef] [Google Scholar]

22. Committee ES, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, et al.. Guidance on the Assessment of the Biological Relevance of Data in Scientific Assessments. EFSA J (2017) 15(8):e04970. doi: 10.2903/j.efsa.2017.4970 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

23. Kleerebezem M, Binda S, Bron PA, Gross G, Hill C, van Hylckama Vlieg JET, et al.. Understanding Mode of Action can Drive the Translational Pipeline Towards More Reliable Health Benefits for Probiotics. Curr Opin Biotechnol (2019) 56:55–60. doi: 10.1016/j.copbio.2018.09.007 [PubMed] [CrossRef] [Google Scholar]

24. Nataraj BH, Ali SA, Behare PV, Yadav H. Postbiotics-Parabiotics: The New Horizons in Microbial Biotherapy and Functional Foods. Microb Cell Fact (2020) 19(1):168. doi: 10.1186/s12934-020-01426-w [PMC free article] [PubMed] [CrossRef] [Google Scholar]

25. Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al.. The International Scientific Association of Probiotics and Prebiotics (ISAPP) Consensus Statement on the Definition and Scope of Postbiotics. Nat Rev Gastroenterol Hepatol (2021) 18(9):649–67. doi: 10.1038/s41575-021-00440-6 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

26. Piqué N, Berlanga M, Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci (2019) 20(10):2534. doi: 10.3390/ijms20102534 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

27. Teame T, Wang A, Xie M, Zhang Z, Yang Y, Ding Q, et al.. Paraprobiotics and Postbiotics of Probiotic Lactobacilli, Their Positive Effects on the Host and Action Mechanisms: A Review. . Front Nutr (2020) 7:570344. doi: 10.3389/fnut.2020.570344 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

28. Vicariotto F, Mogna L, Del Piano M. Effectiveness of the Two Microorganisms Lactobacillus Fermentum LF15 and Lactobacillus Plantarum LP01, Formulated in Slow-Release Vaginal Tablets, in Women Affected by Bacterial Vaginosis: A Pilot Study. J Clin Gastroenterol (2014) 48 Suppl 1:S106–12. doi: 10.1097/MCG.0000000000000226 [PubMed] [CrossRef] [Google Scholar]

29. Huang R, Ning H, Shen M, Li J, Zhang J, Chen X. Probiotics for the Treatment of Atopic Dermatitis in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Cell Infect Microbiol (2017) 7:392. doi: 10.3389/fcimb.2017.00392 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

30. Zhang H, Yeh C, Jin Z, Ding L, Liu BY, Zhang L, et al.. Prospective Study of Probiotic Supplementation Results in Immune Stimulation and Improvement of Upper Respiratory Infection Rate. Synth Syst Biotechnol (2018) 3(2):113–20. doi: 10.1016/j.synbio.2018.03.001 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

31. Vancamelbeke M, Vermeire S. The Intestinal Barrier: A Fundamental Role in Health and Disease. Expert Rev Gastroenterol Hepatol (2017) 11(9):821–34. doi: 10.1080/17474124.2017.1343143 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

32. Boirivant M, Strober W. The Mechanism of Action of Probiotics. Curr Opin Gastroenterol (2007) 23(6):679–92. doi: 10.1097/MOG.0b013e3282f0cffc [PubMed] [CrossRef] [Google Scholar]

33. Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of Action of Probiotics. Adv Nutr (Bethesda Md) (2019) 10(suppl_1):S49–s66. doi: 10.1093/advances/nmy063 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

34. Sartor RB. Probiotic Therapy of Intestinal Inflammation and Infections. Curr Opin Gastroenterol (2005) 21(1):44–50. [PubMed] [Google Scholar]

35. Panpetch W, Phuengmaung P, Cheibchalard T, Somboonna N, Leelahavanichkul A, Tumwasorn S. Lacticaseibacillus Casei Strain T21 Attenuates Clostridioides Difficile Infection in a Murine Model Through Reduction of Inflammation and Gut Dysbiosis With Decreased Toxin Lethality and Enhanced Mucin Production. Front Microbiol (2021) 12:745299. doi: 10.3389/fmicb.2021.745299 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

36. Shekels LL, Lyftogt CT, Ho SB. Bile Acid-Induced Alterations of Mucin Production in Differentiated Human Colon Cancer Cell Lines. Int J Biochem Cell Biol (1996) 28(2):193–201. doi: 10.1016/1357-2725(95)00125-5 [PubMed] [CrossRef] [Google Scholar]

37. Mattar AF, Teitelbaum DH, Drongowski RA, Yongyi F, Harmon CM, Coran AG. Probiotics Up-Regulate MUC-2 Mucin Gene Expression in a Caco-2 Cell-Culture Model. Pediatr Surg Int (2002) 18(7):586–90. doi: 10.1007/s00383-002-0855-7 [PubMed] [CrossRef] [Google Scholar]

38. Martín R, Chamignon C, Mhedbi-Hajri N, Chain F, Derrien M, Escribano-Vázquez U, et al.. The Potential Probiotic Lactobacillus Rhamnosus CNCM I-3690 Strain Protects the Intestinal Barrier by Stimulating Both Mucus Production and Cytoprotective Response. Sci Rep (2019) 9(1):5398. doi: 10.1038/s41598-019-41738-5 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

39. Ahl D, Liu H, Schreiber O, Roos S, Phillipson M, Holm L. Lactobacillus Reuteri Increases Mucus Thickness and Ameliorates Dextran Sulphate Sodium-Induced Colitis in Mice. Acta Physiol (2016) 217(4):300–10. doi: 10.1111/apha.12695 [PubMed] [CrossRef] [Google Scholar]

40. Caballero-Franco C, Keller K, De Simone C, Chadee K. The VSL3 Probiotic Formula Induces Mucin Gene Expression and Secretion in Colonic Epithelial Cells. Am J Physiol Gastrointest Liver Physiol (2007) 292(1):G315–22. doi: 10.1152/ajpgi.00265.2006 [PubMed] [CrossRef] [Google Scholar]

41. Gaudier E, Michel C, Segain JP, Cherbut C, Hoebler C. The VSL# 3 Probiotic Mixture Modifies Microflora But Does Not Heal Chronic Dextran-Sodium Sulfate-Induced Colitis or Reinforce the Mucus Barrier in Mice. J Nutr (2005) 135(12):2753–61. doi: 10.1093/jn/135.12.2753 [PubMed] [CrossRef] [Google Scholar]

42. Schlee M, Harder J, Köten B, Stange EF, Wehkamp J, Fellermann K. Probiotic Lactobacilli and VSL3 Induce Enterocyte Beta-Defensin 2. Clin Exp Immunol (2008) 151(3):528–35. doi: 10.1111/j.1365-2249.2007.03587.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]

43. Terada T, Nii T, Isobe N, Yoshimura Y. Effects of Probiotics Lactobacillus Reuteri and Clostridium Butyricum on the Expression of Toll-Like Receptors, Pro- and Anti-Inflammatory Cytokines, and Antimicrobial Peptides in Broiler Chick Intestine. J Poult Sci (2020) 57(4):310–8. doi: 10.2141/jpsa.0190098 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

44. Alakomi HL, Skytta E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM. Lactic Acid Permeabilizes Gram-Negative Bacteria by Disrupting the Outer Membrane. Appl Environ Microbiol (2000) 66(5):2001–5. doi: 10.1128/AEM.66.5.2001-2005.2000 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

45. Atassi F, Servin AL. Individual and Co-Operative Roles of Lactic Acid and Hydrogen Peroxide in the Killing Activity of Enteric Strain Lactobacillus Johnsonii NCC933 and Vaginal Strain Lactobacillus Gasseri KS120.1 against enteric, uropathogenic and vaginosis-associated pathogens. FEMS Microbiol Lett (2010) 304(1):29–38. doi: 10.1111/j.1574-6968.2009.01887.x [PubMed] [CrossRef] [Google Scholar]

46. Dicks LMT, Dreyer L, Smith C, Van Staden Ad. A Review: The Fate of Bacteriocins in the Human Gastro-Intestinal Tract: Do They Cross the Gut–Blood Barrier? Front Microbiol (2018) 9(2297). doi: 10.3389/fmicb.2018.02297 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

47. Jack RW, Tagg JR, Ray B. Bacteriocins of Gram-Positive Bacteria. Microbiol Rev (1995) 59(2):171–200. doi: 10.1128/mr.59.2.171-200.1995 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

48. Feng Y, Wang Y, Wang P, Huang Y, Wang F. Short-Chain Fatty Acids Manifest Stimulative and Protective Effects on Intestinal Barrier Function Through the Inhibition of NLRP3 Inflammasome and Autophagy. Cell Physiol Biochem (2018) 49(1):190–205. doi: 10.1159/000492853 [PubMed] [CrossRef] [Google Scholar]

49. Todorov SD. Bacteriocins From Lactobacillus Plantarum – Production, Genetic Organization and Mode of Action: Produção, Organização Genética E Modo De Ação. Braz J Microbiol (2009) 40(2):209–21. doi: 10.1590/S1517-83822009000200001 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

50. Corr SC, Li Y, Riedel CU, O’Toole PW, Hill C, Gahan CG. Bacteriocin Production as a Mechanism for the Antiinfective Activity of Lactobacillus Salivarius UCC118. Proc Natl Acad Sci USA (2007) 104(18):7617–21. doi: 10.1073/pnas.0700440104 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

51. O’ Shea E, O’ Connor P, Raftis EJ, O’ Toole P, Stanton C, Cotter PD, et al.. Subspecies Diversity in Bacteriocin Production by Intestinal Lactobacillus Salivarius Strains. Gut Microbes (2012) 3(5):468–73. doi: 10.4161/gmic.21417 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

52. Cerutti A, Rescigno M. The Biology of Intestinal Immunoglobulin A Responses. Immunity (2008) 28(6):740–50. doi: 10.1016/j.immuni.2008.05.001 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

53. Pabst O, Slack E. IgA and the Intestinal Microbiota: The Importance of Being Specific. Mucosal Immunol (2020) 13(1):12–21. doi: 10.1038/s41385-019-0227-4 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

54. Peterson DA, McNulty NP, Guruge JL, Gordon JI. IgA Response to Symbiotic Bacteria as a Mediator of Gut Homeostasis. Cell Host Microbe (2007) 2(5):328–39. doi: 10.1016/j.chom.2007.09.013 [PubMed] [CrossRef] [Google Scholar]

55. Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL. Role of Commensal Bacteria in Development of Gut-Associated Lymphoid Tissues and Preimmune Antibody Repertoire. J Immunol (2004) 172(2):1118–24. doi: 10.4049/jimmunol.172.2.1118 [PubMed] [CrossRef] [Google Scholar]

56. Pasquier B, Launay P, Kanamaru Y, Moura IC, Pfirsch S, Ruffie C, et al.. Identification of FcalphaRI as an Inhibitory Receptor That Controls Inflammation: Dual Role of FcRgamma ITAM. Immunity (2005) 22(1):31–42. doi: 10.1016/S1074-7613(04)00377-2 [PubMed] [CrossRef] [Google Scholar]

57. Yanagibashi T, Hosono A, Oyama A, Tsuda M, Suzuki A, Hachimura S, et al.. IgA Production in the Large Intestine is Modulated by a Different Mechanism Than in the Small Intestine: Bacteroides Acidifaciens Promotes IgA Production in the Large Intestine by Inducing Germinal Center Formation and Increasing the Number of IgA+ B Cells. Immunobiology (2013) 218(4):645–51. doi: 10.1016/j.imbio.2012.07.033 [PubMed] [CrossRef] [Google Scholar]

58. Arai S, Iwabuchi N, Takahashi S, J-z X, Abe F, Hachimura S. Orally Administered Heat-Killed Lactobacillus Paracasei MCC1849 Enhances Antigen-Specific IgA Secretion and Induces Follicular Helper T Cells in Mice. PloS One (2018) 13(6):e0199018. doi: 10.1371/journal.pone.0199018 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

59. Sakai F, Hosoya T, Ono-Ohmachi A, Ukibe K, Ogawa A, Moriya T, et al.. Lactobacillus Gasseri SBT2055 Induces TGF-β Expression in Dendritic Cells and Activates TLR2 Signal to Produce IgA in the Small Intestine. PloS One (2014) 9(8):e105370. doi: 10.1371/journal.pone.0105370 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

60. Kikuchi Y, Kunitoh-Asari A, Hayakawa K, Imai S, Kasuya K, Abe K, et al.. Oral Administration of Lactobacillus Plantarum Strain AYA Enhances IgA Secretion and Provides Survival Protection Against Influenza Virus Infection in Mice. PloS One (2014) 9(1):e86416. doi: 10.1371/journal.pone.0086416 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

61. Kusumo PD, Bela B, Wibowo H, Munasir Z, Surono IS. Lactobacillus Plantarum IS-10506 Supplementation Increases Faecal Siga and Immune Response in Children Younger Than Two Years. Benefic Microbes (2019) 10(3):245–52. doi: 10.3920/BM2017.0178 [PubMed] [CrossRef] [Google Scholar]

62. Ulluwishewa D, Anderson RC, McNabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components. J Nutr (2011) 141(5):769–76. doi: 10.3945/jn.110.135657 [PubMed] [CrossRef] [Google Scholar]

63. Orlando A, Linsalata M, Notarnicola M, Tutino V, Russo F. Lactobacillus GG Restoration of the Gliadin Induced Epithelial Barrier Disruption: The Role of Cellular Polyamines. BMC Microbiol (2014) 14:19. doi: 10.1186/1471-2180-14-19 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

64. Johnson-Henry KC, Donato KA, Shen-Tu G, Gordanpour M, Sherman PM. Lactobacillus Rhamnosus Strain GG Prevents Enterohemorrhagic Escherichia Coli O157:H7-Induced Changes in Epithelial Barrier Function. Infect Immunity (2008) 76(4):1340–8. doi: 10.1128/IAI.00778-07 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

65. Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJ, et al.. Regulation of Human Epithelial Tight Junction Proteins by Lactobacillus Plantarum In Vivo and Protective Effects on the Epithelial Barrier. Am J Physiol Gastrointest Liver Physiol (2010) 298(6):G851–9. doi: 10.1152/ajpgi.00327.2009 [PubMed] [CrossRef] [Google Scholar]

66. Qin H, Zhang Z, Hang X, Jiang YL. Plantarum Prevents Enteroinvasive Escherichia Coli-Induced Tight Junction Proteins Changes in Intestinal Epithelial Cells. BMC Microbiol (2009) 9:63. doi: 10.1186/1471-2180-9-63 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

67. Anderson RC, Cookson AL, McNabb WC, Park Z, McCann MJ, Kelly WJ, et al.. Lactobacillus Plantarum MB452 Enhances the Function of the Intestinal Barrier by Increasing the Expression Levels of Genes Involved in Tight Junction Formation. BMC Microbiol (2010) 10(1):316. doi: 10.1186/1471-2180-10-316 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

68. Cario E, Gerken G, Podolsky DK. Toll-Like Receptor 2 Enhances ZO-1-Associated Intestinal Epithelial Barrier Integrity via Protein Kinase C. Gastroenterology (2004) 127(1):224–38. doi: 10.1053/j.gastro.2004.04.015 [PubMed] [CrossRef] [Google Scholar]

69. Hummel S, Veltman K, Cichon C, Sonnenborn U, Schmidt MA. Differential Targeting of the E-Cadherin/beta-Catenin Complex by Gram-Positive Probiotic Lactobacilli Improves Epithelial Barrier Function. Appl Environ Microbiol (2012) 78(4):1140–7. doi: 10.1128/AEM.06983-11 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

70. Mujagic Z, de Vos P, Boekschoten MV, Govers C, Pieters H-JHM, de Wit NJW, et al.. The Effects of Lactobacillus Plantarum on Small Intestinal Barrier Function and Mucosal Gene Transcription; a Randomized Double-Blind Placebo Controlled Trial. Sci Rep (2017) 7:40128. doi: 10.1038/srep40128 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

71. Celebioglu HU, Svensson B. Dietary Nutrients, Proteomes, and Adhesion of Probiotic Lactobacilli to Mucin and Host Epithelial Cells. Microorganisms (2018) 6(3):90. doi: 10.3390/microorganisms6030090 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

72. Yadav AK, Tyagi A, Kumar A, Panwar S, Grover S, Saklani AC, et al.. Adhesion of Lactobacilli and Their Anti-Infectivity Potential. Crit Rev Food Sci Nutr (2017) 57(10):2042–56. doi: 10.1080/10408398.2014.918533 [PubMed] [CrossRef] [Google Scholar]

73. Jensen H, Roos S, Jonsson H, Rud I, Grimmer S, van Pijkeren JP, et al.. Role of Lactobacillus Reuteri Cell and Mucus-Binding Protein A (CmbA) in Adhesion to Intestinal Epithelial Cells and Mucus In Vitro. Microbiol (Read) (2014) 160(Pt 4):671–81. doi: 10.1099/mic.0.073551-0 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

74. Hynönen U, Palva A. Lactobacillus Surface Layer Proteins: Structure, Function and Applications. Appl Microbiol Biotechnol (2013) 97(12):5225–43. doi: 10.1007/s00253-013-4962-2 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

75. Prado Acosta M, Geoghegan EM, Lepenies B, Ruzal S, Kielian M, Martinez MG. Surface (S) Layer Proteins of Lactobacillus Acidophilus Block Virus Infection via DC-SIGN Interaction. Front Microbiol (2019) 10. doi: 10.3389/fmicb.2019.00810 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

76. Tytgat HLP, Douillard FP, Reunanen J, Rasinkangas P, Hendrickx APA, Laine PK, et al.. Lactobacillus Rhamnosus GG Outcompetes Enterococcus Faecium via Mucus-Binding Pili: Evidence for a Novel and Heterospecific Probiotic Mechanism. Appl Environ Microbiol (2016) 82(19):5756–62. doi: 10.1128/AEM.01243-16 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

77. Jeffery CJ. Protein Moonlighting: What Is It, and Why Is It Important? Philosophical Transactions of the Royal Society of London Series B. Biol Sci (2018) 373(1738):20160523. doi: 10.1098/rstb.2016.0523 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

78. Saad N, Urdaci M, Vignoles C, Chaignepain S, Tallon R, Schmitter JM, et al.. Lactobacillus Plantarum 299v Surface-Bound GAPDH: A New Insight Into Enzyme Cell Walls Location. J Microbiol Biotechnol (2009) 19(12):1635–43. doi: 10.4014/jmb.0902.0102 [PubMed] [CrossRef] [Google Scholar]

79. Patel DK, Shah KR, Pappachan A, Gupta S, Singh DD. Cloning, Expression and Characterization of a Mucin-Binding GAPDH From Lactobacillus Acidophilus. Int J Biol Macromol (2016) 91:338–46. doi: 10.1016/j.ijbiomac.2016.04.041 [PubMed] [CrossRef] [Google Scholar]

80. Zhang W-M, Wang H-F, Gao K, Wang C, Liu L, Liu J-X. Lactobacillus Reuteri Glyceraldehyde-3-Phosphate Dehydrogenase Functions in Adhesion to Intestinal Epithelial Cells. Can J Microbiol (2015) 61(5):373–80. doi: 10.1139/cjm-2014-0734 [PubMed] [CrossRef] [Google Scholar]

81. Ramiah K, van Reenen CA, Dicks LM. Surface-Bound Proteins of Lactobacillus Plantarum 423 That Contribute to Adhesion of Caco-2 Cells and Their Role in Competitive Exclusion and Displacement of Clostridium Sporogenes and Enterococcus Faecalis. Res Microbiol (2008) 159(6):470–5. doi: 10.1016/j.resmic.2008.06.002 [PubMed] [CrossRef] [Google Scholar]

82. Sherman PM, Johnson-Henry KC, Yeung HP, Ngo PS, Goulet J, Tompkins TA. Probiotics Reduce Enterohemorrhagic Escherichia Coli O157:H7- and Enteropathogenic E. coli O127:H6-induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect Immun (2005) 73(8):5183–8. doi: 10.1128/IAI.73.8.5183-5188.2005 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

83. Singh TP, Kaur G, Kapila S, Malik RK. Antagonistic Activity of Lactobacillus Reuteri Strains on the Adhesion Characteristics of Selected Pathogens. Front Microbiol (2017) 8(486). doi: 10.3389/fmicb.2017.00486 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

84. Hirano J, Yoshida T, Sugiyama T, Koide N, Mori I, Yokochi T. The Effect of Lactobacillus Rhamnosus on Enterohemorrhagic Escherichia Coli Infection of Human Intestinal Cells In Vitro. Microb Immunol (2003) 47(6):405–9. doi: 10.1111/j.1348-0421.2003.tb03377.x [PubMed] [CrossRef] [Google Scholar]

85. Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, McKay DM, et al.. Probiotics Prevent Bacterial Translocation and Improve Intestinal Barrier Function in Rats Following Chronic Psychological Stress. Gut (2006) 55(11):1553–60. doi: 10.1136/gut.2005.080739 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

86. Luyer MD, Buurman WA, Hadfoune M, Speelmans G, Knol J, Jacobs JA, et al.. Strain-Specific Effects of Probiotics on Gut Barrier Integrity Following Hemorrhagic Shock. Infect Immun (2005) 73(6):3686–92. doi: 10.1128/IAI.73.6.3686-3692.2005 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

87. Schoster A, Kokotovic B, Permin A, Pedersen PD, Dal Bello F, Guardabassi L. In Vitro Inhibition of Clostridium Difficile and Clostridium Perfringens by Commercial Probiotic Strains. Anaerobe (2013) 20:36–41. doi: 10.1016/j.anaerobe.2013.02.006 [PubMed] [CrossRef] [Google Scholar]

88. Saint-Cyr MJ, Haddad N, Taminiau B, Poezevara T, Quesne S, Amelot M, et al.. Use of the Potential Probiotic Strain Lactobacillus Salivarius SMXD51 to Control Campylobacter Jejuni in Broilers. Int J Food Microbiol (2017) 247:9–17. doi: 10.1016/j.ijfoodmicro.2016.07.003 [PubMed] [CrossRef] [Google Scholar]

89. Carter A, Adams M, La Ragione RM, Woodward MJ. Colonisation of Poultry by Salmonella Enteritidis S1400 is Reduced by Combined Administration of Lactobacillus Salivarius 59 and Enterococcus Faecium PXN-33. Vet Microbiol (2017) 199:100–7. doi: 10.1016/j.vetmic.2016.12.029 [PubMed] [CrossRef] [Google Scholar]

90. Chingwaru W, Vidmar J. Potential of Zimbabwean Commercial Probiotic Products and Strains of Lactobacillus Plantarum as Prophylaxis and Therapy Against Diarrhoea Caused by Escherichia Coli in Children. Asian Pac J Trop Med (2017) 10(1):57–63. doi: 10.1016/j.apjtm.2016.12.009 [PubMed] [CrossRef] [Google Scholar]

91. Sikorska H, Smoragiewicz W. Role of Probiotics in the Prevention and Treatment of Meticillin-Resistant Staphylococcus Aureus Infections. Int J Antimicrob Agents (2013) 42(6):475–81. doi: 10.1016/j.ijantimicag.2013.08.003 [PubMed] [CrossRef] [Google Scholar]

92. De Montijo-Prieto S, Moreno E, Bergillos-Meca T, Lasserrot A, Ruiz-Lopez MD, Ruiz-Bravo A, et al.. A Lactobacillus Plantarum Strain Isolated From Kefir Protects Against Intestinal Infection With Yersinia Enterocolitica O9 and Modulates Immunity in Mice. Res Microbiol (2015) 166(8):626–32. doi: 10.1016/j.resmic.2015.07.010 [PubMed] [CrossRef] [Google Scholar]

93. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, et al.. Global Prevalence of Helicobacter Pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology (2017) 153(2):420–9. doi: 10.1053/j.gastro.2017.04.022 [PubMed] [CrossRef] [Google Scholar]

94. Waldum HL, Kleveland PM, Sørdal ØF. Helicobacter Pylori and Gastric Acid: An Intimate and Reciprocal Relationship. Ther Adv Gastroenterol (2016) 9(6):836–44. doi: 10.1177/1756283X16663395 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

95. Sykora J, Valeckova K, Amlerova J, Siala K, Dedek P, Watkins S, et al.. Effects of a Specially Designed Fermented Milk Product Containing Probiotic Lactobacillus Casei DN-114 001 and the Eradication of H. pylori in Children: A Prospective Randomized Double-Blind Study. J Clin Gastroenterol (2005) 39(8):692–8. doi: 10.1097/01.mcg.0000173855.77191.44 [PubMed] [CrossRef] [Google Scholar]

96. Sahagun-Flores JE, Lopez-Pena LS, De La Cruz-Ramirez Jaimes J, Garcia-Bravo MS, Peregrina-Gomez R, De Alba-Garcia Je. [Eradication of Helicobacter Pylori: Triple Treatment Scheme Plus Lactobacillus vs. Triple Treatment Alone]. Cirugia Y Cirujanos (2007) 75(5):333–6. [PubMed] [Google Scholar]

97. Canducci F, Armuzzi A, Cremonini F, Cammarota G, Bartolozzi F, Pola P, et al.. A Lyophilized and Inactivated Culture of Lactobacillus Acidophilus Increases Helicobacter Pylori Eradication Rates. Aliment Pharmacol Ther (2000) 14(12):1625–9. doi: 10.1046/j.1365-2036.2000.00885.x [PubMed] [CrossRef] [Google Scholar]

98. Cremonini F, Di Caro S, Covino M, Armuzzi A, Gabrielli M, Santarelli L, et al.. Effect of Different Probiotic Preparations on Anti-Helicobacter Pylori Therapy-Related Side Effects: A Parallel Group, Triple Blind, Placebo-Controlled Study. Am J Gastroenterol (2002) 97(11):2744–9. doi: 10.1111/j.1572-0241.2002.07063.x [PubMed] [CrossRef] [Google Scholar]

99. Myllyluoma E, Veijola L, Ahlroos T, Tynkkynen S, Kankuri E, Vapaatalo H, et al.. Probiotic Supplementation Improves Tolerance to Helicobacter Pylori Eradication Therapy–a Placebo-Controlled, Double-Blind Randomized Pilot Study. Aliment Pharmacol Ther (2005) 21(10):1263–72. doi: 10.1111/j.1365-2036.2005.02448.x [PubMed] [CrossRef] [Google Scholar]

100. Szajewska H, Albrecht P, Topczewska-Cabanek A. Randomized, Double-Blind, Placebo-Controlled Trial: Effect of Lactobacillus GG Supplementation on Helicobacter Pylori Eradication Rates and Side Effects During Treatment in Children. J Pediatr Gastroenterol Nutr (2009) 48(4):431–6. doi: 10.1097/MPG.0b013e318182e716 [PubMed] [CrossRef] [Google Scholar]

101. Francavilla R, Lionetti E, Castellaneta SP, Magista AM, Maurogiovanni G, Bucci N, et al.. Inhibition of Helicobacter Pylori Infection in Humans by Lactobacillus Reuteri ATCC 55730 and Effect on Eradication Therapy: A Pilot Study. Helicobacter (2008) 13(2):127–34. doi: 10.1111/j.1523-5378.2008.00593.x [PubMed] [CrossRef] [Google Scholar]

102. Pantoflickova D, Corthesy-Theulaz I, Dorta G, Stolte M, Isler P, Rochat F, et al.. Favourable Effect of Regular Intake of Fermented Milk Containing Lactobacillus Johnsonii on Helicobacter Pylori Associated Gastritis. Aliment Pharmacol Ther (2003) 18(8):805–13. doi: 10.1046/j.1365-2036.2003.01675.x [PubMed] [CrossRef] [Google Scholar]

103. Gotteland M, Cruchet S. Suppressive Effect of Frequent Ingestion of Lactobacillus Johnsonii La1 on Helicobacter Pylori Colonization in Asymptomatic Volunteers. J Antimicrob Chemother (2003) 51(5):1317–9. doi: 10.1093/jac/dkg227 [PubMed] [CrossRef] [Google Scholar]

104. Le Moal VL, Fayol-Messaoudi D, Servin AL. Compound(s) Secreted by Lactobacillus Casei Strain Shirota YIT9029 Irreversibly and Reversibly Impair the Swimming Motility of Helicobacter Pylori and Salmonella Enterica Serovar Typhimurium, Respectively. Microbiol (Reading England) (2013) 159(Pt 9):1956–71. doi: 10.1099/mic.0.067678-0 [PubMed] [CrossRef] [Google Scholar]

105. Coconnier MH, Lievin V, Hemery E, Servin AL. Antagonistic Activity Against Helicobacter Infection In Vitro and In Vivo by the Human Lactobacillus Acidophilus Strain LB. Appl Environ Microbiol (1998) 64(11):4573–80. doi: 10.1128/AEM.64.11.4573-4580.1998 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

106. Sgouras DN, Panayotopoulou EG, Martinez-Gonzalez B, Petraki K, Michopoulos S, Mentis A. Lactobacillus Johnsonii La1 Attenuates Helicobacter Pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice. Clin Diagn Lab Immunol (2005) 12(12):1378–86. doi: 10.1128/CDLI.12.12.1378-1386.2005 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

107. Michetti P, Dorta G, Wiesel PH, Brassart D, Verdu E, Herranz M, et al.. Effect of Whey-Based Culture Supernatant of Lactobacillus Acidophilus (Johnsonii) La1 on Helicobacter Pylori Infection in Humans. Digestion (1999) 60(3):203–9. doi: 10.1159/000007660 [PubMed] [CrossRef] [Google Scholar]

108. Andersen LP, Rasmussen L. Helicobacter Pylori-Coccoid Forms and Biofilm Formation. FEMS Immunol Med Microbiol (2009) 56(2):112–5. doi: 10.1111/j.1574-695X.2009.00556.x [PubMed] [CrossRef] [Google Scholar]

109. Reshetnyak VI, Reshetnyak TM. Significance of Dormant Forms of Helicobacter Pylori in Ulcerogenesis. World J Gastroenterol (2017) 23(27):4867–78. doi: 10.3748/wjg.v23.i27.4867 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

110. Avonts L, De Vuyst L. Antimicrobial Potential of Probiotic Lactic Acid Bacteria. Mededelingen (Rijksuniversiteit Te Gent Fakulteit Van Landbouwkundige En Toegepaste Biologische Wetenschappen) (2001) 66(3b):543–50. [PubMed] [Google Scholar]

111. Ottemann KM, Lowenthal AC. Helicobacter Pylori Uses Motility for Initial Colonization and to Attain Robust Infection. Infect Immunity (2002) 70(4):1984–90. doi: 10.1128/IAI.70.4.1984-1990.2002 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

112. Isobe H, Nishiyama A, Takano T, Higuchi W, Nakagawa S, Taneike I, et al.. Reduction of Overall Helicobacter Pylori Colonization Levels in the Stomach of Mongolian Gerbil by Lactobacillus Johnsonii La1 (LC1) and its In Vitro Activities Against H. pylori Motility and Adherence. Biosci Biotechnol Biochem (2012) 76(4):850–2. doi: 10.1271/bbb.110921 [PubMed] [CrossRef] [Google Scholar]

113. Barbut F, Meynard JL. Managing Antibiotic Associated Diarrhoea. BMJ (Clinical Res ed) (2002) 324(7350):1345–6. doi: 10.1136/bmj.324.7350.1345 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

114. Zhou FF, Wu S, Klena JD, Huang HH. Clinical Characteristics of Clostridium Difficile Infection in Hospitalized Patients With Antibiotic-Associated Diarrhea in a University Hospital in China. Eur J Clin Microbiol Infect Dis (2014) 33(10):1773–9. doi: 10.1007/s10096-014-2132-9 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

115. Mekonnen SA, Merenstein D, Fraser CM, Marco ML. Molecular Mechanisms of Probiotic Prevention of Antibiotic-Associated Diarrhea. Curr Opin Biotechnol (2020) 61:226–34. doi: 10.1016/j.copbio.2020.01.005 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

116. Moayyedi P, Yuan Y, Baharith H, Ford AC. Faecal Microbiota Transplantation for Clostridium Difficile-Associated Diarrhoea: A Systematic Review of Randomised Controlled Trials. Med J Aust (2017) 207(4):166–72. doi: 10.5694/mja17.00295 [PubMed] [CrossRef] [Google Scholar]

117. Kale-Pradhan PB, Jassal HK, Wilhelm SM. Role of Lactobacillus in the Prevention of Antibiotic-Associated Diarrhea: A Meta-Analysis. Pharmacotherapy (2010) 30(2):119–26. doi: 10.1592/phco.30.2.119 [PubMed] [CrossRef] [Google Scholar]

118. Cai J, Zhao C, Du Y, Zhang Y, Zhao M, Zhao Q. Comparative Efficacy and Tolerability of Probiotics for Antibiotic-Associated Diarrhea: Systematic Review With Network Meta-Analysis. United Eur Gastroenterol J (2018) 6(2):169–80. doi: 10.1177/2050640617736987 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

119. Szajewska H, Hojsak I. Health Benefits of Lactobacillus Rhamnosus GG and Bifidobacterium Animalis Subspecies Lactis BB-12 in Children. Postgrad Med (2020) 132(5):441–51. doi: 10.1080/00325481.2020.1731214 [PubMed] [CrossRef] [Google Scholar]

120. Lebeer S, Vanderleyden J, De Keersmaecker SC. Host Interactions of Probiotic Bacterial Surface Molecules: Comparison With Commensals and Pathogens. Nat Rev Microbiol (2010) 8(3):171–84. doi: 10.1038/nrmicro2297 [PubMed] [CrossRef] [Google Scholar]

121. Wells JM. Immunomodulatory Mechanisms of Lactobacilli. Microb Cell Fact (2011) 10(1):S17. doi: 10.1186/1475-2859-10-S1-S17 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

122. Azad MAK, Sarker M, Wan D. Immunomodulatory Effects of Probiotics on Cytokine Profiles. BioMed Res Int (2018) 2018:8063647. doi: 10.1155/2018/8063647 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

123. Shida K, Kiyoshima-Shibata J, Kaji R, Nagaoka M, Nanno M. Peptidoglycan From Lactobacilli Inhibits Interleukin-12 Production by Macrophages Induced by Lactobacillus casei Through Toll-Like Receptor 2-Dependent and Independent Mechanisms. Immunology (2009) 128(1pt2):e858–e69. doi: 10.1111/j.1365-2567.2009.03095.x [PMC free article] [PubMed] [CrossRef] [Google Scholar]

124. Kolling Y, Salva S, Villena J, Alvarez S. Are the Immunomodulatory Properties of Lactobacillus Rhamnosus CRL1505 Peptidoglycan Common for All Lactobacilli During Respiratory Infection in Malnourished Mice? PloS One (2018) 13(3):e0194034. doi: 10.1371/journal.pone.0194034 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

125. Noh SY, Kang SS, Yun CH, Han SH. Lipoteichoic Acid From Lactobacillus Plantarum Inhibits Pam2CSK4-Induced IL-8 Production in Human Intestinal Epithelial Cells. Mol Immunol (2015) 64(1):183–9. doi: 10.1016/j.molimm.2014.11.014 [PubMed] [CrossRef] [Google Scholar]

126. Kim KW, Kang S-S, Woo S-J, Park O-J, Ahn KB, Song K-D, et al.. Lipoteichoic Acid of Probiotic Lactobacillus Plantarum Attenuates Poly I:C-Induced IL-8 Production in Porcine Intestinal Epithelial Cells. . Front Microbiol (2017) 8:1827. doi: 10.3389/fmicb.2017.01827 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

127. Lebeer S, Claes I, Tytgat HLP, Verhoeven TLA, Marien E, Ossowski Iv, et al.. Functional Analysis of Lactobacillus Rhamnosus GG Pili in Relation to Adhesion and Immunomodulatory Interactions With Intestinal Epithelial Cells. Appl Environ Microbiol (2012) 78(1):185–93. doi: 10.1128/AEM.06192-11 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

128. Bleau C, Monges A, Rashidan K, Laverdure J-P, Lacroix M, Van Calsteren M-R, et al.. Intermediate Chains of Exopolysaccharides From Lactobacillus Rhamnosus RW-9595M Increase IL-10 Production by Macrophages. J Appl Microbiol (2010) 108(2):666–75. doi: 10.1111/j.1365-2672.2009.04450.x [PubMed] [CrossRef] [Google Scholar]

129. Murofushi Y, Villena J, Morie K, Kanmani P, Tohno M, Shimazu T, et al.. The Toll-Like Receptor Family Protein RP105/MD1 Complex is Involved in the Immunoregulatory Effect of Exopolysaccharides From Lactobacillus Plantarum N14. Mol Immunol (2015) 64(1):63–75. doi: 10.1016/j.molimm.2014.10.027 [PubMed] [CrossRef] [Google Scholar]

130. Makino S, Sato A, Goto A, Nakamura M, Ogawa M, Chiba Y, et al.. Enhanced Natural Killer Cell Activation by Exopolysaccharides Derived From Yogurt Fermented With Lactobacillus Delbrueckii Ssp. Bulgaricus OLL1073R-1. J Dairy Sci (2016) 99(2):915–23. doi: 10.3168/jds.2015-10376 [PubMed] [CrossRef] [Google Scholar]

131. Sadler R, Cramer JV, Heindl S, Kostidis S, Betz D, Zuurbier KR, et al.. Short-Chain Fatty Acids Improve Poststroke Recovery via Immunological Mechanisms. J Neurosci (2020) 40(5):1162–73. doi: 10.1523/JNEUROSCI.1359-19.2019 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

132. Vinolo MAR, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. Suppressive Effect of Short-Chain Fatty Acids on Production of Proinflammatory Mediators by Neutrophils. J Nutr Biochem (2011) 22(9):849–55. doi: 10.1016/j.jnutbio.2010.07.009 [PubMed] [CrossRef] [Google Scholar]

133. Park JS, Lee EJ, Lee JC, Kim WK, Kim HS. Anti-Inflammatory Effects of Short Chain Fatty Acids in IFN-Gamma-Stimulated RAW 264.7 murine macrophage cells: involvement of NF-kappaB and ERK signaling pathways. Int Immunopharmacol (2007) 7(1):70–7. doi: 10.1016/j.intimp.2006.08.015 [PubMed] [CrossRef] [Google Scholar]

134. Tominaga K, Kamimura K, Takahashi K, Yokoyama J, Yamagiwa S, Terai S. Diversion Colitis and Pouchitis: A Mini-Review. World J Gastroenterol (2018) 24(16):1734–47. doi: 10.3748/wjg.v24.i16.1734 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

135. Şengül N, Işık S, Aslım B, Uçar G, Demirbağ AE. The Effect of Exopolysaccharide-Producing Probiotic Strains on Gut Oxidative Damage in Experimental Colitis. Digest Dis Sci (2011) 56(3):707–14. doi: 10.1007/s10620-010-1362-7 [PubMed] [CrossRef] [Google Scholar]

136. Suo H, Zhao X, Qian Y, Sun P, Zhu K, Li J, et al.. Lactobacillus Fermentum Suo Attenuates HCl/Ethanol Induced Gastric Injury in Mice Through Its Antioxidant Effects. Nutrients (2016) 8(3):155. doi: 10.3390/nu8030155 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

137. Uskova MA, Kravchenko LV. [Antioxidant Properties of Lactic Acid Bacteria–Probiotic and Yogurt Strains]. Voprosy Pitaniia (2009) 78(2):18–23. [PubMed] [Google Scholar]

138. Kleniewska P, Pawliczak R. Influence of Synbiotics on Selected Oxidative Stress Parameters. Oxid Med Cell Longev (2017) 2017:9315375. doi: 10.1155/2017/9315375 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

139. Verma A, Shukla G. Synbiotic (Lactobacillus Rhamnosus+Lactobacillus Acidophilus+Inulin) Attenuates Oxidative Stress and Colonic Damage in 1,2 Dimethylhydrazine Dihydrochloride-Induced Colon Carcinogenesis in Sprague-Dawley Rats: A Long-Term Study. Eur J Cancer Prev (2014) 23(6):550–9. doi: 10.1097/CEJ.0000000000000054 [PubMed] [CrossRef] [Google Scholar]

140. Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB. Soluble Proteins Produced by Probiotic Bacteria Regulate Intestinal Epithelial Cell Survival and Growth. Gastroenterology (2007) 132(2):562–75. doi: 10.1053/j.gastro.2006.11.022 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

141. Yoda K, Miyazawa K, Hosoda M, Hiramatsu M, Yan F, He F. Lactobacillus GG-Fermented Milk Prevents DSS-Induced Colitis and Regulates Intestinal Epithelial Homeostasis Through Activation of Epidermal Growth Factor Receptor. Eur J Nutr (2014) 53(1):105–15. doi: 10.1007/s00394-013-0506-x [PMC free article] [PubMed] [CrossRef] [Google Scholar]

142. Tao Y, Drabik KA, Waypa TS, Musch MW, Alverdy JC, Schneewind O, et al.. Soluble Factors From Lactobacillus GG Activate MAPKs and Induce Cytoprotective Heat Shock Proteins in Intestinal Epithelial Cells. Am J Physiol-Cell Physiol (2006) 290(4):C1018–C30. doi: 10.1152/ajpcell.00131.2005 [PubMed] [CrossRef] [Google Scholar]

143. Macho Fernandez E, Valenti V, Rockel C, Hermann C, Pot B, Boneca IG, et al.. Anti-Inflammatory Capacity of Selected Lactobacilli in Experimental Colitis is Driven by NOD2-Mediated Recognition of a Specific Peptidoglycan-Derived Muropeptide. Gut (2011) 60(8):1050–9. doi: 10.1136/gut.2010.232918 [PubMed] [CrossRef] [Google Scholar]

144. Mirpuri J, Sotnikov I, Myers L, Denning TL, Yarovinsky F, Parkos CA, et al.. Lactobacillus Rhamnosus (LGG) Regulates IL-10 Signaling in the Developing Murine Colon Through Upregulation of the IL-10R2 Receptor Subunit. PloS One (2012) 7(12):e51955. doi: 10.1371/journal.pone.0051955 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

145. Zhang W, Zhu Y-H, Yang J-C, Yang G-Y, Zhou D, Wang J-F. A Selected Lactobacillus Rhamnosus Strain Promotes EGFR-Independent Akt Activation in an Enterotoxigenic Escherichia Coli K88-Infected IPEC-J2 Cell Model. PloS One (2015) 10(4):e0125717–e. doi: 10.1371/journal.pone.0125717 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

146. Kourelis A, Zinonos I, Kakagianni M, Christidou A, Christoglou N, Yiannaki E, et al.. Validation of the Dorsal Air Pouch Model to Predict and Examine Immunostimulatory Responses in the Gut. J Appl Microbiol (2010) 108(1):274–84. doi: 10.1111/j.1365-2672.2009.04421.x [PubMed] [CrossRef] [Google Scholar]

147. Kankaanpää P, Sütas Y, Salminen S, Isolauri E. Homogenates Derived From Probiotic Bacteria Provide Down-Regulatory Signals for Peripheral Blood Mononuclear Cells. Food Chem (2003) 83(2):269–77. doi: 10.1016/S0308-8146(03)00090-6 [CrossRef] [Google Scholar]

148. Peña JA, Rogers AB, Ge Z, Ng V, Li SY, Fox JG, et al.. Probiotic Lactobacillus Spp. Diminish Helicobacter Hepaticus-Induced Inflammatory Bowel Disease in Interleukin-10-Deficient Mice. Infect Immun (2005) 73(2):912–20. doi: 10.1128/IAI.73.2.912-920.2005 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

149. Haller D, Bode C, Hammes WP, Pfeifer AM, Schiffrin EJ, Blum S. Non-Pathogenic Bacteria Elicit a Differential Cytokine Response by Intestinal Epithelial Cell/Leucocyte Co-Cultures. Gut (2000) 47(1):79–87. doi: 10.1136/gut.47.1.79 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

150. Borruel N, Carol M, Casellas F, Antolín M, de Lara F, Espín E, et al.. Increased Mucosal Tumour Necrosis Factor Alpha Production in Crohn’s Disease can be Downregulated Ex Vivo by Probiotic Bacteria. Gut (2002) 51(5):659–64. doi: 10.1136/gut.51.5.659 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

151. De Marco S, Sichetti M, Muradyan D, Piccioni M, Traina G, Pagiotti R, et al.. Probiotic Cell-Free Supernatants Exhibited Anti-Inflammatory and Antioxidant Activity on Human Gut Epithelial Cells and Macrophages Stimulated With LPS. Evid Based Complement Alternat Med (2018) 2018:1756308–. doi: 10.1155/2018/1756308 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

152. Islam SU. Clinical Uses of Probiotics. Medicine (2016) 95(5):e2658. doi: 10.1097/MD.0000000000002658 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

153. Alard J, Peucelle V, Boutillier D, Breton J, Kuylle S, Pot B, et al.. New Probiotic Strains for Inflammatory Bowel Disease Management Identified by Combining In Vitro and In Vivo Approaches. Benefic Microbes (2018) 9(2):317–31. doi: 10.3920/BM2017.0097 [PubMed] [CrossRef] [Google Scholar]

154. Le B, Yang SH. Efficacy of Lactobacillus Plantarum in Prevention of Inflammatory Bowel Disease. Toxicol Rep (2018) 5:314–7. doi: 10.1016/j.toxrep.2018.02.007 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

155. Park J-S, Choi JW, Jhun J, Kwon JY, Lee B-I, Yang CW, et al.. Lactobacillus Acidophilus Improves Intestinal Inflammation in an Acute Colitis Mouse Model by Regulation of Th17 and Treg Cell Balance and Fibrosis Development. J Med Food (2018) 21(3):215–24. doi: 10.1089/jmf.2017.3990 [PubMed] [CrossRef] [Google Scholar]

156. Mallon P, McKay D, Kirk S, Gardiner K. Probiotics for Induction of Remission in Ulcerative Colitis. Cochrane Database Syst Rev (2007) 4):Cd005573. doi: 10.1002/14651858.CD005573.pub2 [PubMed] [CrossRef] [Google Scholar]

157. Rahimi R, Nikfar S, Rahimi F, Elahi B, Derakhshani S, Vafaie M, et al.. A Meta-Analysis on the Efficacy of Probiotics for Maintenance of Remission and Prevention of Clinical and Endoscopic Relapse in Crohn’s Disease. Digest Dis Sci (2008) 53(9):2524–31. doi: 10.1007/s10620-007-0171-0 [PubMed] [CrossRef] [Google Scholar]

158. Jia K, Tong X, Wang R, Song X. The Clinical Effects of Probiotics for Inflammatory Bowel Disease: A Meta-Analysis. Medicine (2018) 97(51):e13792–e. doi: 10.1097/MD.0000000000013792 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

159. Ganji-Arjenaki M, Rafieian-Kopaei M. Probiotics are a Good Choice in Remission of Inflammatory Bowel Diseases: A Meta Analysis and Systematic Review. J Cell Physiol (2018) 233(3):2091–103. doi: 10.1002/jcp.25911 [PubMed] [CrossRef] [Google Scholar]

160. Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al.. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated With Unique Host and Microbiome Features. Cell (2018) 174(6):1388–405.e21. doi: 10.1016/j.cell.2018.08.041 [PubMed] [CrossRef] [Google Scholar]

161. Suez J, Zmora N, Segal E, Elinav E. The Pros, Cons, and Many Unknowns of Probiotics. Nat Med (2019) 25(5):716–29. doi: 10.1038/s41591-019-0439-x [PubMed] [CrossRef] [Google Scholar]

162. Lerner A, Shoenfeld Y, Matthias T. Probiotics: If It Does Not Help It Does Not Do Any Harm. Really? Microorgan (2019) 7(4):104. doi: 10.3390/microorganisms7040104 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

163. Teshale A, Belete A, Tilahun A, Tsehaye H, Berhanu H, Minwuyelet A. Bacterial Probiotics Their Importances and Limitations: A Review. . J Nutr Health Sci (2017) 4. doi: 10.15744/2393-9060.4.202 [CrossRef] [Google Scholar]

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The Functional Roles of Lactobacillus acidophilus in Different Physiological and Pathological Processes

Abstract

Probiotics are live microorganisms that can be consumed by humans in amounts sufficient to offer health-promoting effects. Owing to their various biological functions, probiotics are widely used in biological engineering, industry and agriculture, food safety, and the life and health fields. Lactobacillus acidophilus (L. acidophilus), an important human intestinal probiotic, was originally isolated from the human gastrointestinal tract and its functions have been widely studied ever since it was named in 1900. L. acidophilus has been found to play important roles in many aspects of human health. Due to its good resistance against acid and bile salts, it has broad application prospects in functional, edible probiotic preparations. In this review, we explore the basic characteristics and biological functions of L. acidophilus based on the research progress made thus far worldwide. Various problems to be solved regarding the applications of probiotic products and their future development are also discussed.

Keywords: Probiotics, Lactobacillus acidophilus, intestinal flora, cholesterol, immunity

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Introduction

The Food and Agriculture Association (FAO) and World Health Organization (WHO) have highlighted that probiotics are live strains of microorganisms that have been carefully selected. When administered in sufficient amounts, probiotics can bring health benefits to the host [1]. There are a large number of probiotic bacteria that colonize the human intestine, which can also interact and co-evolve with the human body. They help the host to digest and absorb nutrients in food, metabolize toxic waste products, and produce amino acids and short-chain fatty acids necessary for normal human activities. They can provide definite health effects such as improving the host microecological balance while exerting other beneficial effects on the intestinal tract [2].

Since the early 1990s, a plethora of “probiotic” health products have swept throughout the global market. In the meantime, “probiotics” have become a hot international research topic. Probiotics have been extensively studied in a variety of diseases and have been demonstrated to produce a range of potential health effects. The most studied species include lactobacilli, bifidobacteria, and yeasts [3]. Among them, L. acidophilus, an important intestinal probiotic in the lactic acid bacteria (LAB) family, has had a great deal of focus placed upon it in terms of research and development, especially as it is so closely linked to human health. As such, L. acidophilus is widely considered to have probiotic effects and is one of the most commonly recommended microorganisms for dietary use [4]. Compared with many other probiotics, L. acidophilus has better resistance to both acid and bile salt. These characteristics facilitate the survival and proliferation of L. acidophilus in the harsh environment of the gastrointestinal tract. Its ability to survive under these conditions provides further opportunities for its products to successfully function in the human body. When the total amount of L. acidophilus reaches a certain threshold value, health promotion can be achieved. L. acidophilus has multiple effects on the human body, including nutritional effects, regulation of intestinal flora balance, enhancement of immunity, age-delaying and anti-cancer effects, and support of cholesterol reduction [5, 6].

In this review, the basic characteristics of L. acidophilus are summarized, its biological functions in various diseases are discussed, and future research directions and applications in the form of probiotic products are explored. We hope to unveil the relationships between L. acidophilus and various life activities and disease development so as to provide a theoretical basis for later research and application direction.

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Basic Features and Functional Mechanisms of L. acidophilus

L. acidophilus was initially isolated from infant feces in 1900 and was officially named Lactobacillus acidophilus. Subsequently, a series of biological characteristics and functions have been studied. L. acidophilus is subdivided into many strain types, including L. acidophilus LA-1, LA-5, NCFM, and ATCC4356, DDS-1 [7]. Different strains also confer differing probiotic properties and functions. Since a strain may have multiple names, it is easy to confuse the strains during the process of understanding them and when undertaking research. Fortunately, most of the work on L. acidophilus, especially the work relating to its probiotic effects, has been done on particular strains.

Basic Features of L. acidophilus

L. acidophilus, within the genus Lactobacillus in the family Lactobacillaceae, is a gram-positive bacillus that does not form spores. They present as slender rods with a circular end, measuring 2-10 μm long. Most L. acidophilus strains are microaerobic bacteria, which grow better in anaerobic environments, or in 5~10% CO₂, rather than in aerobic environments. Their optimum culture temperature is generally 35~38°C, and they basically do not grow in temperatures below 20°C. L. acidophilus has poor heat resistance and its optimum pH is 5.5~6.0. The growth characteristics of different strains are also slightly different from each other. L. acidophilus is eosinophilic and has good resistance toward acids and bile [8, 9]. It can grow and reproduce in environments where other LAB cannot grow. It can also use glucose, fructose, lactose and sucrose to carry out homotype fermentation and can produce DL-lactic acid via fermentation [10].

L. acidophilus is a species of beneficial microbial flora and has been proven to have many good probiotic characteristics that can be roughly divided into two categories. The first category covers the essential probiotic properties of L. acidophilus which have been demonstrated in vitro and include tolerance to low pH, bile resistance, adhesion to human colon cells in cell culture, antibiotic production, lactase activity, and product stability [11–17]. The second category includes the overall probiotic effects that have been observed in animal-level feeding studies, such as regulation of host immune responses, reduction of host serum cholesterol, improvement of host lactose metabolism, and prevention or treatment of infection [18–20]. Here, we summarize the basic probiotic properties and main biological functions of L. acidophilus (Fig. 1).

Fig. 1

Probiotic properties and biological functions of Lactobacillus acidophilus.L. acidophilus is a species of beneficial microbial flora and has been proven to play an important role in many pathological and physiological processes. It has been shown to improve CVD and lactose intolerance, prevent and treat cancer, regulate immunity, and improve gastrointestinal diseases.

Functional Mechanisms of L. acidophilus

According to current studies, L. acidophilus participates in the host intestinal tract mainly through the production of metabolites and regulation of intestinal microbiota [21, 22].

First, L. acidophilus can regulate the balance of intestinal flora by reducing the intestinal pH and producing metabolites [21, 23]. The optimal pH of many intestinal pathogenic bacteria is neutral or slightly alkaline. Lactic acid produced by L. acidophilus metabolism can reduce pH, thus inhibiting the growth and reproduction of pathogenic bacteria [23]. In addition, some pathogenic microorganisms produce enzymes that can catalyze the conversion of carcinogenic precursors to carcinogens, such as azo reductase, nitro reductase, and β-glucosidase [24, 25]. L. acidophilus can not only inhibit the growth of these pathogenic microorganisms and reduce the production of these enzymes, but can also inhibit enzyme activity [25, 26]. Second, competition for adhesion sites with pathogenic bacteria is an important mechanism for L. acidophilus to inhibit the function of pathogenic bacteria, thereby interfering with their invasion into cells [27]. Surface the S-layer protein, extracellular polysaccharide and lipoteichoic acid of many strains can compete for adhesion with pathogenic bacteria [21, 28]. Third, the role of L. acidophilus in many diseases also depends on its ability to reduce serum cholesterol level [29, 30]. L. acidophilus can absorb and assimilate cholesterol [31, 32].

Although some mechanisms have been found, neither these mechanisms nor the influencing factors of L. acidophilus in the host have been fully studied and efforts should be made to explore them further.

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Biological Functions of L. acidophilus

Risk Reduction of Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for about one third of global deaths [33]. The occurrence of CVD is related to many factors [34–36]. Increasing blood cholesterol is one risk factor that directly impacts CVD. In the 1970s, Mann and Shaper found that populations of particular African tribes generally possessed lower incidences of high serum cholesterol [37]. After investigation, they found that the residents of these tribes regularly drank yogurt fermented by L. acidophilus, suggesting that this bacteria might regulate blood lipids [37]. Since then, more researchers have paid attention to the uses of L. acidophilus and other probiotics relevant to cholesterol reduction and the cholesterol-lowering effects of L. acidophilus have been confirmed. In addition, studies have investigated the effects of L. acidophilus intervention on cholesterol reduction and atherosclerosis development in animal models.

Harrison and Peat reported that the addition of L. acidophilus to baby feed reduced infant serum cholesterol from 147 mg/100 ml on the 5th day down to 119 mg/100 ml by the 8th day of intervention [38]. This decrease in serum cholesterol levels was accompanied by a significant increase in the number of LAB. The number of Escherichia coli present in fecal samples also decreased [38]. Stepankova et al. found that supplementation of L. acidophilus ATCC 4356 also promoted the proliferation of bifidobacteria [39]. Gilliland and Walker showed that L. acidophilus NCFM was able to remove cholesterol from laboratory growth media [40, 41]. NCFM has been reported to ingest cholesterol in the presence of bile and in the absence of oxygen, both of which occur in the gut. The researchers tested these effects on young pigs and the results showed that feeding L. acidophilus to pigs significantly inhibited the increased serum cholesterol levels that are usually observed in individuals fed a high-cholesterol diet. Park and colleagues have reported that adding L. acidophilus 43121 to a high-cholesterol diet given to rats resulted in reduced serum cholesterol [42, 43]. Song et al. showed that L. acidophilus NS1 can reduce plasma LDL-C by increasing the expression of LDLR and SREBP2 in the liver [44].

Huang et al. found that L. acidophilus ATCC 4356 had a significant cholesterol-lowering effect on rats fed with a high-cholesterol diet by inhibiting the expression of NPC1L1 in the small intestine [31, 45]. Chen and colleagues found that L. acidophilus ATCC 4356 alleviated atherosclerotic lesions in ApoE^−/− mice[46]. L. acidophilus ATCC 4356 inhibited oxidative stress by regulating the production of MDA, oxLDL and SOD, suppressed inflammation via regulations of TNF-α and IL-10 levels, and improved intestinal flora, resulting in blocked progression of atherosclerosis. However, it did not significantly reduce cholesterol levels. In different experimental models, many studies have produced different results due to inconsistent experimental methods. Therefore, the role and functional mechanism of L. acidophilus in reducing cholesterol and alleviating atherosclerosis require further detailed exploration.

Improvement of Gastrointestinal Disease Outcomes

Studies have shown that probiotics can regulate intestinal flora, play a beneficial role in inflammatory diseases such as ulcerative colitis (UC), and have been used effectively to treat and suppress human intestinal infections. Lightfoot and colleagues described the role of L. acidophilus NCFM surface layer protein A as a key effector in the prevention of colitis in mice [47] . Chandhni et al. also showed that the surface proteins in NCFM strains could reverse histopathological damage caused by colitis [48], thus providing a potentially safer option for the treatment of inflammatory bowel disease.

In the normal intestinal flora in humans, L. acidophilus plays a key role in inhibiting the growth of pathogens such as Salmonella enteritidis, Staphylococcus aureus, and Shigella dysenteriae. Therefore, studies have shown that L. acidophilus exhibited strong anti-inflammatory activities [49]. Moshiri et al. reported that L. acidophilus PTCC 1643 could affect the expression of TLR2 and TLR4 in HT29 intestinal epithelial cells under the action of Salmonella enterica serovar Enteritidis (SesE), and inhibit the inflammatory response caused by SesE infection [50]. Small intestinal bacterial overgrowth (SIBO) refers to the changes in the number or types of flora in the small intestine. It is considered to be a condition that can exist for many years without causing obvious symptoms although it is related to chronic digestive problems. Studies by Simenhoff and colleagues have shown that NCFM can inhibit the overgrowth of small intestinal bacteria, reduce the levels of toxic metabolites such as dimethylamine and nitrosodimethylamine in the blood, and positively affect intestinal colonization [51, 52], thus improving the nutritional status of patients. These observations support the use of L. acidophilus for the prevention and treatment of intestinal diseases. Further in vivo and in vitro studies are needed to elucidate the detailed mechanisms of these anti-inflammatory effects.

Improvement of Lactose Intolerance

Lactose intolerance, also known as lactose indigestion or lactose malabsorption, refers to the state in which the human body does not produce the enzyme lactase. After consuming milk or dairy products, some people might have diarrhea and other symptoms of intestinal discomfort due to the osmotic effect of the undecomposed lactose.

Previously, many studies have proved that LAB have the ability to be a source of lactase in the small intestine, which helps people with lactase deficiency to digest lactose. Related fermented dairy products may also enhance lactose tolerance [53].

Some probiotic studies have shown that L. acidophilus can improve lactose digestion or symptoms in lactose-intolerant patients [54, 55]. Among these studies, in vitro evaluation of the lactase levels of various probiotics has shown that the lactase levels of L. acidophilus NCFM were high when compared to all of the probiotics tested. Multiple studies have also shown that NCFM can improve lactose digestion and relieve symptoms of lactose intolerance such as bloating and diarrhea [56, 57]. A study speculated that the bacteria might metabolize lactose during digestion and transport it through the gastrointestinal tract. The study by Pakdaman et al. found that L. acidophilus DDS-1, a unique and edible strain, can improve lactose intolerance symptoms such as diarrhea, cramps, and vomiting [58]. However, a number of studies have shown the opposite effects. For example, Newcomer et al. demonstrated that dairy products containing L. acidophilus NCFM did not significantly improve human lactose intolerance [59–61]. The reason for these contradictory results has been associated with the levels of NCFM of L. acidophilus. Therefore, in order to better apply the functional properties of L. acidophilus and to improve lactose intolerance, it is essential to explore and adjust the probiotics levels and the formula with each product.

Prevention and Treatment of Cancer

Probiotics are considered a safe and cost-effective way to prevent or treat a variety of cancers, including colon and liver cancer. Several studies have suggested that consumption of cultured dairy products may reduce colon cancer risk, since the effects of diet are mediated by metabolic effects of intestinal organisms. The activities of β-glucuronase, nitroreductase, azoreductase and other microbial enzymes have been used to monitor colon cancer changes. Goldin and Gorbach observed that adding live L. acidophilus into the diet of carnivorous rats significantly reduced azoreductase, nitroreductase and glucuronidase activity [24, 25]. The incidence of colon cancer in rats with L. acidophilus NCFM was also lower. Their later study found that NCFM alongside antibiotics inhibited the growth of colon tumors in rats. In human, daily consumption of milk containing NCFM reduced the activity of these three fecal enzymes by a factor of two- to four-fold and reduced the incidence of colon cancer [24, 25]. In addition, they found that nitroreductase activity continued to decrease even three weeks after fermented milk intake was stopped, thus indicating a long-term change in colonic flora [24, 25].

Studies have shown that the extracellular polysaccharides (EPSs) synthesized by L. acidophilus have exerted health benefits by stimulating the immune response and fighting tumor cells [62]. The anticancer and immunomodulatory activities of EPSs synthesized by L. acidophilus have been proven to combat colon cancer and inflammatory liver cancer. Khedr and colleagues used male rats as a model and confirmed that L. acidophilus ATCC 4356 EPSs had immunomodulatory effects on liver cancer induced by diethylnitrosamine (DEN) and gamma radiation (IR) [63]. They proposed that L. acidophilus ATCC 4356 EPSs might be used as a safe and effective probiotic to prevent and treat liver cancer.

Regulation of Immune Capacity

The immune function of L. acidophilus is mainly conducted via regulating the body’s immune system, limiting pathogen colonization within the body, and controlling metabolic disorders and enteritis. Probiotics are used clinically to treat diseases caused by immune system disorders. This can significantly reduce infection time and respiratory tract infection frequency and also improve the therapeutic effects for allergic asthma.

The role of L. acidophilus in regulating the body’s ability to respond to immune responses has been demonstrated in previous studies. Wagner et al. confirmed that NCFM induced antibody- and cell-mediated responses to Candida albicans in immunodeficient mice [64]. The serum levels of IgG, IgA, and IgM were higher in euthymic immunocompromised mice and were thought to reduce the severity of candidiasis. Yoghurt prepared with yoghurt cultures containing NCFM, Streptococcus thermophilus, Lactobacillus bulgaricus and Bifidobacterium were tested for their effects on mucosal and systemic IgA and IgG responses in mice immunized orally with cholera toxin. The results showed that IgA against the cholera toxin was higher in the intestine and serum of the mice fed the formulated yogurt than that observed in the mice fed skim milk [65]. These results suggest that coculture including NCFM may increase immune responses to oral antigens.

Other Functions

We summarized the biological functions, processes, and effects of L. acidophilus– related strains in pathological and physiological processes (Table 1). However, the biological functions of L. acidophilus are far more extensive than what we have mentioned. The role of L. acidophilus in many other diseases is constantly being explored and new discoveries are being made. Studies have shown that kidney tissue damage can be alleviated by reducing oxidative stress, inflammation, and cell death [66]. Zhang et al. first explored the relationship between ATCC 4356 and renal ischemia-reperfusion injury (IRI) [67]. They found that L. acidophilus ATCC 4356 alleviated renal IRI through antioxidant stress and anti-inflammatory responses and improved intestinal microbial distribution in renal IRI mice. In the following treatment with ATCC 4356, the levels of anti-inflammatory factors (IL-4 and IL10) were upregulated, whereas the levels of pro-inflammatory factors (IL-1β, IL-8, TNF-α and IFN-γ) were downregulated. In addition, renal tissue apoptosis in IRI mice was reduced [67].

Table 1

The main biological effects of related strains of L. acidophilus.

Type of strain	Function	Major biological processes and their effects	Reference
L. acidophilus ATCC 4356	Inhibit CVD progression	Inhibit oxidative stress by modulating the productions of MDA, oxLDL and SOD; suppress inflammatory status by regulating TNF-α and IL-10 levels; inhibit NPC1L1 expression in the small intestine; improve intestinal microflora; inhibit the development of atherosclerosis.	[31, 40, 45, 46]
L. acidophilus NCFM		Assimilate cholesterol and control cholesterol levels.	[40, 41]
L. acidophilus 43121		Affect cholesterol metabolism and reduce blood cholesterol levels.	[40, 42, 43]
L. acidophilus NS1		Reduce plasma LDL-C by increasing hepatic LDLR and SREBP2 expression.	[44]
L. acidophilus NCFM	Improve gastrointestinal diseases	Strain surface layer proteins play an important role; alleviate Tcell-induced colitis by significantly reducing the proinflammatory response; preserve microbiome composition and intestinal barrier function; reverse histopathological damage caused by colitis; reduce the level of toxic metabolites.	[47, 48, 51, 52]
L. acidophilus PTCC 1643		Modulate the expression of TLR2 and TLR4 in HT29 intestinal epithelial cells challenged with SesE; enhance anti-inflammatory effects.	[50]
L. acidophilus NCFM	Improve lactose intolerance	Strain has a higher level of lactase, which metabolizes lactose during digestion and transits through the gastrointestinal tract, thereby improving lactose digestion.	[56, 57]
L. acidophilus DDS-1		Assist in breaking down lactose; improve lactose intolerance symptoms such as diarrhea, cramps and vomiting.	[58]
L. acidophilus ATCC 4356	Prevent and treat colon cancer, liver cancer and other cancers	The exopolysaccharides of the strain have immunomodulatory and antitumor activities; regulate the TLR2/STAT-3/P38-MAPK pathway associated with inflammation against HCC.	[63]
L. acidophilus NCFM		Stimulate the immune response; reduce the activities of β-glucuronase, nitroreductase, azoreductase and other microbial enzymes; produce compounds that inhibit tumor proliferation; reduce the incidence of colon cancer and inhibit the growth of colon tumors.	[24, 25]
L. acidophilus NCFM	Regulate immune capacity	Reduce levels of pro-inflammatory cytokines significantly and mobilize a systemic immune response; limit pathogen colonization in the body, control metabolic disorders.	[47, 64, 65]
L. acidophilus ATCC314	Manage inflammatory disorders	Regulate the secretion of inflammatory cytokines; reduce oxidative stress.	[70]

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Studies have shown that oral L. acidophilus can improve heart function in mice with myocardial infarction. Sadeghzadeh and co-researchers found that L. acidophilus was able to improve the hemodynamic and histopathological indicators of the ISO-induced myocardial injury rat model [68], providing obvious myocardial protection. In the future, probiotic supplements may become a new option for patients with ischemic heart disease.

L. acidophilus has been shown to have potential applications in the prevention and control of genitourinary and vaginal infections. Reid et al. precultured L. acidophilus NCFM with urinary and vaginal epithelial cells from healthy women and subsequently exposed them to different urinary tract pathogens. Results showed that NCFM competitively excluded these pathogens and effectively prevented and suppressed urinary tract and vaginal infections [69].

Rheumatoid arthritis (RA) is a common inflammatory joint disease. It has been reported that the ingestion of L. acidophilus ATCC 314 exerted anti-inflammatory and potent antioxidant properties in a collagen-induced arthritis (CIA) rat model [70, 71]. This suggests that L. acidophilus is a promising treatment that should be tested further in RA patient preclinical trials.

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Applications and Future Prospects of L. acidophilus

As people pay more and more attention to health issues, it is of great importance that different kinds of probiotics within food are able to play a healthy role. Of these probiotics, L. acidophilus is one of the most commonly used microorganisms, as it is thought to have various beneficial effects on human health. These advantageous effects include lowering blood cholesterol, improving gastrointestinal diseases, and reducing the risk of lactose intolerance and carcinogenicity [72, 73]. Research and development into L. acidophilus has received widespread attention. It is referred to as the third-generation yogurt starter strain. L. acidophilus has good acid and bile salt resistance and produces a variety of antibacterial substances during metabolism. Due to these attributes, L. acidophilus strains have broad application prospects as functional, edible bacteria.

Despite these favorable characteristics, through our analysis of studies on L. acidophilus which highlighted our present understanding of the current application status, we found that there are also many problems and limitations in the research and application of L. acidophilus. First, due to different naming methods, the same strain may have multiple names. This may lead to confusion during literature searches and research. Important findings could be missed, resulting in incomplete information collection. Second, due to the different research methods used to investigate probiotics, results from different research groups may deviate from each other. Different concentrations and ratios of probiotics have been shown to have different effects, therefore the health benefits of certain disease symptoms remain to be proven. Further research on the optimal strains, doses and dosing algorithms are of key importance for future research. In addition, different species of L. acidophilus can exhibit similar probiotic effects in vitro, but their properties differ significantly when evaluated in vivo.

Currently, probiotic regulation of intestinal flora is recognized as an interesting way to prevent certain diseases. Recent studies have proposed many mechanisms by which probiotics function, but the effectiveness of many probiotics has not been proven in different conditions, which has presently limited the promotion and application of probiotics. There are probably several main reasons why these research limitations occur, including too many low-quality studies, variability within the microbiome, and great diversity between the probiotic strains used. However, some studies have reported reasonable and encouraging results that support further research into probiotics. With this in mind, we should put more effort into overcoming the difficulties. First, because most studies have, so far, focused on animal studies or small human research groups, it is difficult to assess the possible health effects of these probiotics in the general population. Therefore, we need to conduct more extensive epidemiological evaluations which take into account the variability between patients. Due to the high cost of such interventions, it is necessary to characterize strains well to select the strains that are most effective for a particular application. Second, we should identify bacterial markers of the microbiome in related diseases in order to gain sufficient clinical trial capacity. Furthermore, new methods for analyzing the microbiome and its function will greatly facilitate the research when studying large numbers of samples. Probiotics could serve as a low-cost, low-risk alternative to antibiotic treatment in order to prevent infection. We believe that the development of probiotics will open up another impressive field of research. Further research in this area may provide exciting avenues for healthcare strategies, as well as creating more economic and social benefits.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 91849209) and Shandong Provincial Natural Science Foundation, China (Grant No. ZR2020QH016).

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Footnotes

Conflict of Interest

The authors have no financial conflicts of interest to declare.

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REFERENCES

1. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014;11:506–514. doi: 10.1038/nrgastro.2014.66. [PubMed] [CrossRef] [Google Scholar]

2. Butel MJ. Probiotics, gut microbiota and health. Med. Mal. Infect. 2014;44:1–8. doi: 10.1016/j.medmal.2013.10.002. [PubMed] [CrossRef] [Google Scholar]

3. Saini R, Saini S, Sugandha Probiotics: the health boosters. J. Cutan. Aesthet. Surg. 2009;2:112. doi: 10.4103/0974-2077.58530. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

4. Shah NP. Functional cultures and health benefits. Int. Dairy J. 2007;17:1262–1277. doi: 10.1016/j.idairyj.2007.01.014. [CrossRef] [Google Scholar]

5. Mital BK, Garg SK. Anticarcinogenic, hypocholesterolemic, and antagonistic activities of Lactobacillus acidophilus. Crit. Rev. Microbiol. 1995;21:175–214. doi: 10.3109/10408419509113540. [PubMed] [CrossRef] [Google Scholar]

6. Saxelin M, Tynkkynen S, Mattila-Sandholm T, de Vos WM. Probiotic and other functional microbes: from markets to mechanisms. Curr. Opin. Biotechnol. 2005;16:204–211. doi: 10.1016/j.copbio.2005.02.003. [PubMed] [CrossRef] [Google Scholar]

7. Bull M, Plummer S, Marchesi J, Mahenthiralingam E. The life history of Lactobacillus acidophilus as a probiotic: a tale of revisionary taxonomy, misidentification and commercial success. FEMS Microbiol. Lett. 2013;349:77–87. doi: 10.1111/1574-6968.12293. [PubMed] [CrossRef] [Google Scholar]

8. Altermann E, Russell WM, Azcarate-Peril MA, Barrangou R, Buck BL, McAuliffe O, et al. Complete genome sequence of the probiotic lactic acid bacterium Lactobacillus acidophilus NCFM. Proc. Natl. Acad. Sci. USA. 2005;102:3906–3912. doi: 10.1073/pnas.0409188102. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Azcarate-Peril MA, Altermann E, Hoover-Fitzula RL, Cano RJ, Klaenhammer TR. Identification and inactivation of genetic loci involved with Lactobacillus acidophilus acid tolerance. Appl. Environ. Microbiol. 2004;70:5315–5322. doi: 10.1128/AEM.70.9.5315-5322.2004. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

10. Claesson MJ, van Sinderen D, O’Toole PW. The genus Lactobacillus–a genomic basis for understanding its diversity. FEMS Microbiol. Lett. 2007;269:22–28. doi: 10.1111/j.1574-6968.2006.00596.x. [PubMed] [CrossRef] [Google Scholar]

11. Azcarate-Peril MA, McAuliffe O, Altermann E, Lick S, Russell WM, Klaenhammer TR. Microarray analysis of a twocomponent regulatory system involved in acid resistance and proteolytic activity in Lactobacillus acidophilus. Appl. Environ. Microbiol. 2005;71:5794–5804. doi: 10.1128/AEM.71.10.5794-5804.2005. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12. Pfeiler EA, Klaenhammer TR. Role of transporter proteins in bile tolerance of Lactobacillus acidophilus. Appl. Environ. Microbiol. 2009;75:6013–6016. doi: 10.1128/AEM.00495-09. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

13. Khaleghi M, Kermanshahi RK, Yaghoobi MM, Zarkesh-Esfahani SH, Baghizadeh A. Assessment of bile salt effects on s-layer production, slp gene expression and some physicochemical properties of Lactobacillus acidophilus ATCC 4356. J. Microbiol. Biotechnol. 2010;20:749–756. [PubMed] [Google Scholar]

14. Buck BL, Altermann E, Svingerud T, Klaenhammer TR. Functional analysis of putative adhesion factors in Lactobacillus acidophilus NCFM. Appl. Environ. Microbiol. 2005;71:8344–8351. doi: 10.1128/AEM.71.12.8344-8351.2005. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

15. Sanders ME, Klaenhammer TR. Invited review: the scientific basis of Lactobacillus acidophilus NCFM functionality as a probiotic. J. Dairy Sci. 2001;84:319–331. doi: 10.3168/jds.S0022-0302(01)74481-5. [PubMed] [CrossRef] [Google Scholar]

16. Sanders ME, Walker DC, Walker KM, Aoyama K, Klaenhammer TR. Performance of commercial cultures in fluid milk applications. J. Dairy Sci. 1996;79:943–955. doi: 10.3168/jds.S0022-0302(96)76445-7. [PubMed] [CrossRef] [Google Scholar]

17. Shah NP. Probiotic bacteria: selective enumeration and survival in dairy foods. J. Dairy Sci. 2000;83:894–907. doi: 10.3168/jds.S0022-0302(00)74953-8. [PubMed] [CrossRef] [Google Scholar]

18. Bron PA, van Baarlen P, Kleerebezem M. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat. Rev. Microbiol. 2011;10:66–78. doi: 10.1038/nrmicro2690. [PubMed] [CrossRef] [Google Scholar]

19. Gilliland SE. Acidophilus milk products: a review of potential benefits to consumers. J. Dairy Sci. 1989;72:2483–2494. doi: 10.3168/jds.S0022-0302(89)79389-9. [PubMed] [CrossRef] [Google Scholar]

20. Wang KY, Li SN, Liu CS, Perng DS, Su YC, Wu DC, et al. Effects of ingesting Lactobacillus– and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am. J. Clin. Nutr. 2004;80:737–741. [PubMed] [Google Scholar]

21. Tegegne BA, Kebede B. Probiotics, their prophylactic and therapeutic applications in human health development: a review of the literature. Heliyon. 2022;8:e09725. doi: 10.1016/j.heliyon.2022.e09725. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

22. Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin. Microbiol. Rev. 2003;16:658–672. doi: 10.1128/CMR.16.4.658-672.2003. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

23. Bennett A, Eley KG. Intestinal pH and propulsion: an explanation of diarrhoea in lactase deficiency and laxation by lactulose. J. Pharm. Pharmacol. 1976;28:192–195. doi: 10.1111/j.2042-7158.1976.tb04129.x. [PubMed] [CrossRef] [Google Scholar]

24. Goldin BR, Gorbach SL. Effect of Lactobacillus acidophilus dietary supplements on 1,2-dimethylhydrazine dihydrochlorideinduced intestinal cancer in rats. J. Natl. Cancer Inst. 1980;64:263–265. doi: 10.1093/jnci/64.2.263. [PubMed] [CrossRef] [Google Scholar]

25. Goldin BR, Gorbach SL. The effect of milk and lactobacillus feeding on human intestinal bacterial enzyme activity. Am. J. Clin. Nutr. 1984;39:756–761. doi: 10.1093/ajcn/39.5.756. [PubMed] [CrossRef] [Google Scholar]

26. Chang JH, Shim YY, Cha SK, Reaney MJT, Chee KM. Effect of Lactobacillus acidophilus KFRI342 on the development of chemically induced precancerous growths in the rat colon. J. Med. Microbiol. 2012;61:361–368. doi: 10.1099/jmm.0.035154-0. [PubMed] [CrossRef] [Google Scholar]

27. Singh VP, Sharma J, Babu S, Rizwanulla, Singla A. Role of probiotics in health and disease: a review. J. Pak Med. Assoc. 2013;63:253–257. [PubMed] [Google Scholar]

28. Kopp-Hoolihan L. Prophylactic and therapeutic uses of probiotics: a review. J. Am. Diet Assoc. 2001;101:229–238. doi: 10.1016/S0002-8223(01)00060-8. [PubMed] [CrossRef] [Google Scholar]

29. Oh JK, Kim YR, Lee B, Choi YM, Kim SH. Prevention of cholesterol gallstone formation by Lactobacillus acidophilus ATCC 43121 and Lactobacillus fermentum MF27 in lithogenic diet-induced mice. Food Sci. Anim. Resour. 2021;41:343–352. doi: 10.5851/kosfa.2020.e93. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

30. Lee NY, Shin MJ, Youn GS, Yoon SJ, Choi YR, Kim HS, et al. Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis. Clin. Mol. Hepatol. 2021;27:110–124. doi: 10.3350/cmh.2020.0125. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

31. Huang Y, Wang J, Quan G, Wang X, Yang L, Zhong L. Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice. Appl. Environ. Microbiol. 2014;80:7496–7504. doi: 10.1128/AEM.02926-14. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

32. Wang L, Zhou B, Zhou X, Wang Y, Wang H, Jia S, et al. Combined lowering effects of rosuvastatin and L. acidophilus on cholesterol levels in rat. J. Microbiol. Biotechnol. 2019;29:473–481. doi: 10.4014/jmb.1806.06004. [PubMed] [CrossRef] [Google Scholar]

33. Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation. 2010;121:1768–1777. doi: 10.1161/CIRCULATIONAHA.109.849166. [PubMed] [CrossRef] [Google Scholar]

34. Tan WQ, Wang JX, Lin ZQ, Li YR, Lin Y, Li PF. Novel cardiac apoptotic pathway: the dephosphorylation of apoptosis repressor with caspase recruitment domain by calcineurin. Circulation. 2008;118:2268–2276. doi: 10.1161/CIRCULATIONAHA.107.750869. [PubMed] [CrossRef] [Google Scholar]

35. Ding SL, Wang JX, Jiao JQ, Tu X, Wang Q, Liu F, et al. A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its ability to regulate the Puma protein in apoptosis. J. Biol. Chem. 2013;288:26865–26877. doi: 10.1074/jbc.M112.440453. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

36. Xue S, Liu D, Zhu W, Su Z, Zhang L, Zhou C, et al. Circulating MiR-17-5p, MiR-126-5p and MiR-145-3p are novel biomarkers for diagnosis of acute myocardial infarction. Front. Physiol. 2019;10:123. doi: 10.3389/fphys.2019.00123. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

37. Mann GV. Studies of a surfactant and cholesteremia in the Maasai. Am. J. Clin. Nutr. 1974;27:464–469. doi: 10.1093/ajcn/27.5.464. [PubMed] [CrossRef] [Google Scholar]

38. Harrison VC, Peat G. Serum cholesterol and bowel flora in the newborn. Am. J. Clin. Nutr. 1975;28:1351–1355. doi: 10.1093/ajcn/28.12.1351. [PubMed] [CrossRef] [Google Scholar]

39. Stepankova R, Tonar Z, Bartova J, Nedorost L, Rossman P, Poledne R, et al. Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet. J. Atheroscler. Thromb. 2010;17:796–804. doi: 10.5551/jat.3285. [PubMed] [CrossRef] [Google Scholar]

40. Gilliland SE, Walker DK. Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans. J. Dairy Sci. 1990;73:905–911. doi: 10.3168/jds.S0022-0302(90)78747-4. [PubMed] [CrossRef] [Google Scholar]

41. Gilliland SE, Nelson CR, Maxwell C. Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 1985;49:377–381. doi: 10.1128/aem.49.2.377-381.1985. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

42. Park YH, Kim JG, Shin YW, Kim SH, Whang KY. Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats. J. Microbiol. Biotechnol. 2007;17:655–662. [PubMed] [Google Scholar]

43. Park YH, Kim JG, Shin YW, Kim HS, Kim YJ, Chun T, et al. Effects of Lactobacillus acidophilus 43121 and a mixture of Lactobacillus casei and Bifidobacterium longum on the serum cholesterol level and fecal sterol excretion in hypercholesterolemiainduced pigs. Biosci. Biotechnol. Biochem. 2008;72:595–600. doi: 10.1271/bbb.70581. [PubMed] [CrossRef] [Google Scholar]

44. Song M, Park S, Lee H, Min B, Jung S, Park S, et al. Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in dietinduced obese mice. J. Dairy Sci. 2015;98:1492–1501. doi: 10.3168/jds.2014-8586. [PubMed] [CrossRef] [Google Scholar]

45. Huang Y, Wang J, Cheng Y, Zheng Y. The hypocholesterolaemic effects of Lactobacillus acidophilus American type culture collection 4356 in rats are mediated by the down-regulation of Niemann-Pick C1-like 1. Br. J. Nutr. 2010;104:807–812. doi: 10.1017/S0007114510001285. [PubMed] [CrossRef] [Google Scholar]

46. Chen L, Liu W, Li Y, Luo S, Liu Q, Zhong Y, et al. Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process. Int. Immunopharmacol. 2013;17:108–115. doi: 10.1016/j.intimp.2013.05.018. [PubMed] [CrossRef] [Google Scholar]

47. Lightfoot YL, Selle K, Yang T, Goh YJ, Sahay B, Zadeh M, et al. SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. EMBO J. 2015;34:881–895. doi: 10.15252/embj.201490296. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

48. Chandhni PR, Pradhan D, Sowmya K, Gupta S, Kadyan S, Choudhary R, et al. Ameliorative effect of surface proteins of probiotic Lactobacilli in colitis mouse models. Front. Microbiol. 2021;12:679773. doi: 10.3389/fmicb.2021.679773. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

49. Wu Z, Pan DD, Guo Y, Zeng X. Structure and anti-inflammatory capacity of peptidoglycan from Lactobacillus acidophilus in RAW-264.7 cells. Carbohydr. Polym. 2013;96:466–473. doi: 10.1016/j.carbpol.2013.04.028. [PubMed] [CrossRef] [Google Scholar]

50. Moshiri M, Dallal MMS, Rezaei F, Douraghi M, Sharifi L, Noroozbabaei Z, et al. The effect of Lactobacillus acidophilus PTCC 1643 on cultured intestinal epithelial cells infected with Salmonella enterica serovar enteritidis. Osong. Public Health Res. Perspect. 2017;8:54–60. doi: 10.24171/j.phrp.2017.8.1.07. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

51. Simenhoff ML, Dunn SR, Zollner GP, Fitzpatrick ME, Emery SM, Sandine WE, et al. Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus. Miner. Electrolyte Metab. 1996;22:92–96. [PubMed] [Google Scholar]

52. Dunn SR, Simenhoff ML, Ahmed KE, Gaughan WJ, Eltayeb BO, Fitzpatrick MED, et al. Effect of oral administration of freezedried Lactobacillus acidophilus on small bowel bacterial overgrowth in patients with end stage kidney disease: Reducing uremic toxins and improving nutrition. Int. Dairy J. 1998;8:545–553. doi: 10.1016/S0958-6946(98)00081-8. [CrossRef] [Google Scholar]

53. Shah N. Effectiveness of dairy-products in alleviation of lactose-intolerance. Food Aust. 1993;45:268–271. [Google Scholar]

54. Lin MY, Yen CL, Chen SH. Management of lactose maldigestion by consuming milk containing lactobacilli. Dig. Dis. Sci. 1998;43:133–137. doi: 10.1023/A:1018840507952. [PubMed] [CrossRef] [Google Scholar]

55. Mustapha A, Jiang T, Savaiano DA. Improvement of lactose digestion by humans following ingestion of unfermented acidophilus milk: influence of bile sensitivity, lactose transport, and acid tolerance of Lactobacillus acidophilus. J. Dairy Sci. 1997;80:1537–1545. doi: 10.3168/jds.S0022-0302(97)76083-1. [PubMed] [CrossRef] [Google Scholar]

56. Kim HS, Gilliland SE. Lactobacillus acidophilus as a dietary adjunct for milk to aid lactose digestion in humans. J. Dairy Sci. 1983;66:959–966. doi: 10.3168/jds.S0022-0302(83)81887-6. [PubMed] [CrossRef] [Google Scholar]

57. Montes RG, Bayless TM, Saavedra JM, Perman JA. Effect of milks inoculated with Lactobacillus acidophilus or a yogurt starter culture in lactose-maldigesting children. J. Dairy Sci. 1995;78:1657–1664. doi: 10.3168/jds.S0022-0302(95)76790-X. [PubMed] [CrossRef] [Google Scholar]

58. Pakdaman MN, Udani JK, Molina JP, Shahani M. The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance – a randomized, double-blind, placebo-controlled, crossover clinical trial. Nutr. J. 2016;15:56. doi: 10.1186/s12937-016-0172-y. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

59. Newcomer AD, Park HS, O’Brien PC, McGill DB. Response of patients with irritable bowel syndrome and lactase deficiency using unfermented acidophilus milk. Am. J. Clin. Nutr. 1983;38:257–263. doi: 10.1093/ajcn/38.2.257. [PubMed] [CrossRef] [Google Scholar]

60. McDonough FE, Hitchins AD, Wong NP, Wells P, Bodwell CE. Modification of sweet acidophilus milk to improve utilization by lactose-intolerant persons. Am. J. Clin. Nutr. 1987;45:570–574. doi: 10.1093/ajcn/45.3.570. [PubMed] [CrossRef] [Google Scholar]

61. Payne DL, Welsh JD, Manion CV, Tsegaye A, Herd LD. Effectiveness of milk products in dietary management of lactose malabsorption. Am. J. Clin. Nutr. 1981;34:2711–2715. doi: 10.1093/ajcn/34.12.2711. [PubMed] [CrossRef] [Google Scholar]

62. El-Deeb NM, Yassin AM, Al-Madboly LA, El-Hawiet A. A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-kappaB inflammatory pathways in human colon cancer. Microb. Cell Fact. 2018;17:29. doi: 10.1186/s12934-018-0877-z. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

63. Khedr OMS, El-Sonbaty SM, Moawed FSM, Kandil EI, Abdel-Maksoud BE. Lactobacillus acidophilus ATCC 4356 exopolysaccharides suppresses mediators of inflammation through the inhibition of TLR2/STAT-3/P38-MAPK pathway in DENinduced hepatocarcinogenesis in rats. Nutr. Cancer. 2021;74:1037–1047. doi: 10.1080/01635581.2021.1934490. [PubMed] [CrossRef] [Google Scholar]

64. Wagner RD, Pierson C, Warner T, Dohnalek M, Farmer J, Roberts L, et al. Biotherapeutic effects of probiotic bacteria on candidiasis in immunodeficient mice. Infect. Immun. 1997;65:4165–4172. doi: 10.1128/iai.65.10.4165-4172.1997. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

65. Tejada-Simon MV, Lee JH, Ustunol Z, Pestka JJ. Ingestion of yogurt containing Lactobacillus acidophilus and Bifidobacterium to potentiate immunoglobulin A responses to cholera toxin in mice. J. Dairy Sci. 1999;82:649–660. doi: 10.3168/jds.S0022-0302(99)75281-1. [PubMed] [CrossRef] [Google Scholar]

66. Yang Y, Song M, Liu Y, Liu H, Sun L, Peng Y, et al. Renoprotective approaches and strategies in acute kidney injury. Pharmacol. Ther. 2016;163:58–73. doi: 10.1016/j.pharmthera.2016.03.015. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

67. Zhang P, Han X, Zhang X, Zhu X. Lactobacillus acidophilus ATCC 4356 alleviates renal ischemia-reperfusion injury through antioxidant stress and anti-inflammatory responses and improves intestinal microbial distribution. Front. Nutr. 2021;8:667695. doi: 10.3389/fnut.2021.667695. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

68. Sadeghzadeh J, Vakili A, Sameni HR, Shadnoush M, Bandegi AR, Zahedi Khorasani M. The effect of oral consumption of probiotics in prevention of heart injury in a rat myocardial infarction model: A histopathological, hemodynamic and biochemical evaluation. Iran Biomed J. 2017;21:174–181. doi: 10.18869/acadpub.ibj.21.3.174. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

69. Reid G. In vitro testing of Lactobacillus acidophilus NCFM (TM) as a possible probiotic for the urogenital tract. Int. Dairy J. 2000;10:415–419. doi: 10.1016/S0958-6946(00)00059-5. [CrossRef] [Google Scholar]

70. Amdekar S, Singh V, Kumar A, Sharma P, Singh R. Lactobacillus casei and Lactobacillus acidophilus regulate inflammatory pathway and improve antioxidant status in collagen-induced arthritic rats. J. Interferon Cytokine Res. 2013;33:1–8. doi: 10.1089/jir.2012.0034. [PubMed] [CrossRef] [Google Scholar]

71. Paul AK, Paul A, Jahan R, Jannat K, Bondhon TA, Hasan A, et al. Probiotics and amelioration of rheumatoid arthritis: Significant roles of Lactobacillus casei and Lactobacillus acidophilus. Microorganisms. 2021;9:1070. doi: 10.3390/microorganisms9051070. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

72. Holzapfel WH, Schillinger U. Introduction to pre- and probiotics. Food Res. Int. 2002;35:109–116. doi: 10.1016/S0963-9969(01)00171-5. [CrossRef] [Google Scholar]

73. Marteau P, Boutron-Ruault MC. Nutritional advantages of probiotics and prebiotics. Br. J. Nutr. 2002;87 Suppl 2:S153–157. doi: 10.1079/BJN2002531. [PubMed] [CrossRef] [Google Scholar]

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Chia seed benefits: What you need to know

The Truth News — Wed, 29 May 2024 18:11:26 +0000

Chia seed benefits: What you need to know

Packed with fiber, protein, omega-3 fatty acids, and antioxidants, tiny chia seeds pack a nutritional punch. From adding them to prepared dishes or as a topping on oatmeal, cereals, or smoothies, you can easily incorporate chia seeds into many foods to give them a nutritious boost.

Chia seeds are frequently featured as the star ingredient in many healthy eating recipes, ranging from baked goods to protein bars to smoothies and beyond.

Why are chia seeds good for you? Apart from offering a pop of flavor and texture to your favorite foods, they also provide health perks, such as helping balance blood sugar and support heart health.

Keep reading for a complete list of chia seeds benefits and potential side effects, as well as preparation instructions and simple ways to add them to your diet with some clever chia seed recipes.

What Are Chia Seeds?

Chia seeds (Salvia hispanica) are tiny superfoods that are grow on a species of flowering plant that’s in the mint family. They are native to areas of Mexico and Guatemala but are commonly cultivated in many areas in North and South America.

Chia is typically easy t digest when prepared properly and can be a very versatile ingredient that works well in a variety of recipes. Plus, the seeds offer a long list of important nutrients, including:

Chia seeds are tiny black or white seeds derived from the Salvia hispanica plant, a member of the mint family native to Central America. These small seeds have been a part of human diets for over 5,000 years. Chia seeds were a staple food for the Aztecs and Mayans.

Where Do Chia Seeds Come From?

Originally grown in Mexico, chia has long been highly valued for its medicinal properties and nutritional value. In fact, it was even used as currency at one point.

Chia means “strength” in the Mayan language, and chia seeds were known as “runners’ food” because runners and warriors would use them as fuel while running long distances or during battle. Aztec warriors ate them to give them energy and endurance, claiming that just one spoonful could sustain them for 24 hours.

Salvia hispanica has also been used for its potent healing properties in many branches of traditional medicine for centuries. According to Ayurveda, chia seeds can help nourish the blood and promote digestive regularity thanks to their ability to absorb water in the gastrointestinal tract, forming a gel-like substance.

They can also reduce inflammation, promote kidney health and support proper hydration.

Health benefits of chia seeds

Chia seeds are packed with nutrients that may support numerous health benefits. Among them:

reducing blood pressure
lowering cholesterol levels
supporting digestive health
aiding in weight management
reducing inflammation
helping to control diabetes
protecting against chronic disease
improving anxiety and depression.

When chia seeds are ingested, they form a gel-like substance in the stomach that can increase your feeling of fullness and decrease your appetite and calorie intake.

Nutrition Facts

Chia is rich in protein (amino acids), fiber, manganese, phosphorus and calcium. Plus, as mentioned above, it’s a good source of omega-3s (polyunsaturated fatty acids), such as α-linolenic and linoleic acids.

Additionally, it’s rich in polyphenols and antioxidants, such as caffeic acid, rosmarinic acid, myricetin, quercetin and others. It’s also considered a low-carb food because the net carbs (total carbohydrate grams minus fiber grams) are relatively low.

Chia seeds: Nutritional heavyweights

fiber
protein
manganese
calcium
antioxidants
omega-3 fatty acids

Chia seeds contain a variety of nutrients including fiber, protein, omega-3 fatty acids, antioxidants, and various vitamins and minerals like calcium, magnesium, and phosphorus that are beneficial to your health.

Omega-3 fatty acids

Chia seeds are a powerhouse of omega-3 fatty acids. This type of fatty acid is primarily found in fatty fish, nuts, and seeds.

Omega-3 fatty acids play an important role in brain function, heart health, and reducing inflammation in the body. Incorporating omega-3s into the diet promotes overall well-being, benefiting cardiovascular and cognitive functions.

Chia seeds are rich in a type of omega-3 fatty acid known as alpha-linolenic acid (ALA). The body cannot produce ALA its own, so it must be obtained through food. Consuming ALA has been linked to a decreased heart disease risk.

Fiber

Incorporating chia seeds into your diet is also an excellent way to increase your intake of fiber. Just one ounce of chia seeds (two to three tablespoons) provides approximately 9.8 grams of dietary fiber.

Research has shown that adequate fiber intake is associated with a decreased risk of:

coronary heart disease
type 2 diabetes
several types of cancer
inflammation
digestive disorders.

On the heart health front, fiber helps lower LDL (“bad”) cholesterol and triglyceride levels, and helps increase levels of heart-protective HDL cholesterol.

The fiber in chia seeds can also aid healthy digestion by softening the stool and providing bulk to it. This allows the stool to pass more quickly through the intestines and can help alleviate constipation.

Antioxidants

Chia seeds are packed with antioxidants including tocopherols, phytosterols, carotenoids, and polyphenolic compounds. Antioxidants play a crucial role in protecting the body from damage caused by free radicals, which can build up in the body and lead to cell damage and disease.

Thanks in part to their antioxidant content, chia seeds may help protect against:

inflammation
diabetes
cancer
heart disease
Alzheimer’s disease.

Protein

Chia seeds are also a valuable source of protein. Chia seeds contain all nine essential amino acids. The protein in chia seeds can help stabilize blood sugar levels and provide a steady source of energy.

Chia seeds pack nutritional punch

Chia seeds are small round seeds, and can be black, brown and white in color. They are harvested from a flowering plant in the mint family known as Salvia hispanica. It’s native to parts of Mexico and Guatemala. Edible chia seeds are closely related to the chia plants made popular by Chia Pets, but they are not the same seed.

A gel forms around the chia seed when mixed with liquid, which gives chia beverages their distinctive texture. Chia seeds can absorb up to 12 times their weight in liquid, which makes them useful in keeping baked goods moist.

Chia Seeds Benefits: The Omega-3, Protein-Packed Superfood

Chia seeds have many nutritional benefits. They are high in omega-3 fatty acids and fiber. Chia provides a similar amount of omega-3 fatty acids as ground flaxseed in the form of alpha linolenic acid, or ALA. They can help with weight loss.

Chia seeds are an excellent source of fiber, which can improve heart health, reduce cholesterol levels and promote intestinal health. Fiber takes longer to digest and makes you feel satisfied longer, which is how it can help with weight loss and decrease your risk of developing diabetes or heart disease. Eating a diet rich in fiber also is shown to protect against colorectal cancer.

One serving of dried chia seeds is about 2.5 tablespoons. This has 140 calories, 5 grams of protein, 10 grams of fiber, 12 grams of carbohydrate and 9 grams of fat, of which 8 grams are heart-healthy fats.

A one-ounce serving of dried chia seeds (about 28.4 grams) contains approximately:

Calories: 137
Total Carbohydrates: 11.9 g
Fiber: 9.8 g
Total Fat: 8.7 g
Saturated Fat: 0.9 g
Polyunsaturated Fat: 6.7 g
Monounsaturated Fat: 0.7 g
Trans Fat: 0.04 g
Protein: 4.7 g
Sodium: 4.5 mg (0.2% DV)
Manganese: 0.8 mg (35% DV)
Copper: 0.3 mg (33% DV)
Phosphorus: 244 mg (20% DV)
Calcium: 179 mg (14% DV)
Zinc: 1.3 mg (12% DV)
Potassium: 115 mg (2% DV)

*Daily Value: Percentages are based on a diet of 2,000 calories a day.

In addition to the nutrients listed above, chia contains some vitamin A, vitamin B, vitamin E and vitamin D, plus minerals such as iron, iodine, magnesium, copper, niacin and thiamine.

Benefits

What are the benefits of eating chia seeds? Here are nine reasons to add more of them to your diet, including because they can decrease risk for several common diseases:

1. Support Healthy Skin

Chia is jam-packed with antioxidants, which are compounds that fight free radical damage and prevent oxidative stress while also promoting tissue repair and protecting against skin damage.

Interestingly enough, researchers from Mexico recently uncovered that they have a total antioxidant concentration nearly two times higher than previously reported. In fact, the antioxidant activity of Salvia hispanica seeds was shown to stop up to 70 percent of free radical activity.

As one of the most high-antioxidant foods on the planet, adding some to your diet may help fight premature aging and protect the skin cells from things like ultraviolet and environmental damage.

2. Promote Digestive Health

Chia is loaded with fiber, squeezing nearly 11 grams of fiber into a single ounce. This means that adding just one ounce to your daily meals my can supply a whopping 44 percent of your fiber needs for the entire day.

Because of their rich fiber content, chia seeds benefit digestive health by promoting regularity and increasing stool frequency to prevent constipation. The fiber also acts as a prebiotic to provide fuel for the beneficial bacteria in the gut, which plays a central role in many aspects of health and disease.

Fiber also absorbs a good amount of water and expands in the stomach, helping keep you feeling fuller for longer.

3. Improve Heart Health

Thanks to their high content of antioxidants, fiber and heart-healthy fats, chia seeds have been shown to help prevent cardiovascular disease in several ways.

One of the most powerful effects is it ability to reduce inflammation and decrease several risk factors of heart disease, such as high cholesterol and blood pressure. Inflammation can put extra strain on blood vessels and is thought to contribute to heart disease along with a slew of other chronic conditions.

Chia is high in omega-3 fatty acids, boasting even more omega-3s per gram than salmon. Omega-3s work to protect the heart by lowering blood pressure, cholesterol levels and inflammation. Meanwhile, the fiber found in chia seeds can help manage cholesterol levels and keep the arteries clear to minimize the risk of coronary heart disease.

A 2021 study also found that chia can help reduce high blood pressure/hypertension. In this study, adults with hypertension experienced significantly reduced blood pressure levels compared to a control group when they consumed 40 grams per day of chia seeds (about 1.5 ounces) for 12 weeks.

4. Balance Blood Sugar

Rich in both alpha-linolenic acid and fiber, evidence from several studies suggests that chia can help maintain normal blood sugar levels and fight development of type 2 diabetes and insulin resistance.

Animal and human studies have found that adding them to a high-sugar diet helps prevent changes in blood sugar and lipid levels. What’s more, human studies have also found that adding these seeds to white bread reduces the glycemic response and can help prevent spikes and crashes in blood sugar levels.

5. Boost Energy and Exercise Performance

Chia is often used by athletes for carb loading, a strategy that helps maximize the storage of glycogen in the muscles and liver to optimize endurance and boost exercise performance.

In fact, a study published in the Journal of Strength and Conditioning concluded that consuming chia seeds enhanced exercise performance for workouts that lasted 90 minutes the same way a sugar-laden sports drink would but without all the unhealthy sugar. In the study, half of the athletes drank 100 percent Gatorade, while the others consumed half Gatorade and half chia drink.

In the end, the runners’ times were matched, but the chia group consumed far less sugar.

Plus, studies show the protein content of these seeds is among the highest of all seeds and grains, giving it the ability to help build muscle mass and increase strength. Research shows that consuming protein as a post-workout meal can aid in the repair of muscle tissues and can also build new muscle to speed up recovery time between workouts.

6. Build Stronger Bones

Chia can help strengthen bone health and preserve bone density while reducing the risk of serious conditions like osteoporosis. This is because the seeds are loaded with calcium and manganese, two minerals that are needed to maintain bone health.

With about 99 percent of the calcium in your body stored in your bones, calcium serves an important role in maintaining bone strength and density. Manganese is also involved in bone metabolism, with studies showing that a deficiency in this key nutrient can impair bone resorption and decrease bone formation.

Impressively enough, a single ounce of chia seeds contains 18 percent of the calcium you need in a day while also meeting 30 percent of your daily manganese requirements.

7. Aid in Weight Loss

Chia seeds rank among the top plant-based protein foods, which is why they are great to consume for those trying to put on lean muscle, burn fat, and manage hunger and appetite.

How can chia seeds help you lose weight? Studies show that increasing your intake of protein can help promote weight loss by curbing cravings and cutting caloric intake.

One study published in the American Journal of Clinical Nutrition, for example, showed that increasing protein intake by just 15 percent of daily calories led to significant decreases in energy intake and appetite. Other research shows that chia may help reduce levels of ghrelin, the hormone responsible for stimulating hunger.

8. Fight Cancer Growth

Chia is rich in alpha-linolenic acid (ALA), a type of omega-3 fatty acid that gives it the potential to act as a cancer-fighting food.

One in-vitro study published in the Journal of Molecular Biochemistry found that ALA helped limit the growth of both breast and cervical cancer cells. Researchers also found that it caused cell death of the cancer cells without harming the normal healthy cells in the body.

While more research still needs to be done to find out the deeper implications of ALA on other types of cancer, this is a great discovery for women struggling with these increasingly common types of cancer.

9. Enhance Oral Health

Because chia is full of calcium, phosphorus, vitamin A and zinc, it helps promote dental and oral health.

Calcium is the building block of your teeth and necessary for maintaining oral health. Meanwhile, zinc prevents tartar by keeping plaque from mineralizing onto your teeth and has an antibacterial effect that keeps bad breath germs away.

Vitamin A and phosphorus are also important for strong teeth and a healthy mouth.

Risks and Side Effects

There are very few side effects associated with chia seeds when they’re eaten in moderation.

Occasionally, some people may experience stomach discomfort when consuming high amounts, mostly due to the high fiber content. As with any food, increase your intake slowly, and drink plenty of water.

If you have any concerns or experience any persistent side effects, consider decreasing your intake, and be sure to discuss with your doctor.

Can chia seeds make you gain weight? They shouldn’t, as long as you don’t eat too many. Stick to about two to three tablespoons daily.

Conclusion

The chia seed is a type of seed that comes from a flowering species in the mint family of plants and is native to Mexico and Guatemala.
The chia nutrition profile boasts a good amount of protein, fiber, omega-3 fatty acids, and important minerals like manganese, calcium and phosphorus — thus explaining why chia seeds benefits are so plentiful.
So what are chia seeds good for? Chia seeds benefits include increased weight loss, better blood sugar levels, improved heart health, enhanced regularity, increased weight loss and more.
From chia seed pudding to protein bars and baked goods, there are plenty of chia seeds recipe options that you can try to fit this nutrient-rich seed into your diet and get chia seeds benefits.
Soak, grind or enjoy whole for a nutritious and delicious way to boost the benefits of your diet and take advantage of the multitude of chia seeds benefits.

How to incorporate chia seeds into your diet (click here)

source source source

Benefits of Cloves

The Truth News — Fri, 24 May 2024 18:31:30 +0000

What are Cloves?

Cloves are dried flower buds from clove trees. Clove is a major spice that is used in many cooking methods around the globe. In India, it is one of the home remedies that can cure multiple health conditions. They are strong aromatic spices used in food to give it a distinct taste. These dark brown buds give spiciness to many dishes like curries, cookies, bread, etc. It can be used as clove powder or as a whole bud as well. It is similar to other spices or herbs like cinnamon and nutmeg. You can understand ‘laung ke fayde‘ in various ‘Dadi ke nuskhe’. It is hot, so it is used in winter to cure colds and throat soreness.

Nutritional Value of Clove

Cloves are full of nutrients like vitamins, minerals, and fiber. They are a good source of nutrients and add a lot of flavour to any dish.

As per FoodData Central, USDA, This table represents several nutrients and their amounts present in 2.1 grams of ground clove:

Nutritional Value of Clove
Nutrients (in 2 grams of Cloves)	Its amount
Calories	6Kcal
Carbs	1 gram
Fiber	1 gram
Sugar	Less than 1 grams
Manganese	55% of the Daily Value (DV)
Vitamin K	2% of the DV

Clove is high in manganese, an essential mineral for brain and bone health.

Apart from these nutrients, it is also a rich source of potassium, vitamin K, beta-carotene, iron, calcium, and eugenol. It is low in calories but has a fair amount of a few minerals.

Also Read: Health Benefits of Cinnamon

Glycemic Index and Glycemic Load of Clove

Cloves are low-calorie, low-carb foods with a low glycemic index. Cloves have a GI of 30. Cloves are good for blood sugar as their GI & GL are both low. Its Glycemic Load is 1.2/250, which is very low.

Benefits of Cloves

Cloves have many potential health benefits, including:

Antioxidants – Cloves contain antioxidants that help fight free radicals, which can damage cells and lead to disease. This may help reduce the risk of developing heart disease, diabetes, and certain cancers.
Anti-inflammatory – Cloves have anti-inflammatory properties and can help improve the immune system, which can also reduce inflammation.
Antibacterial – Cloves have antibacterial properties that can help keep germs at bay. They’ve been used to treat toothaches, headaches, colds, and flu.
Antifungal – Cloves have antifungal properties that can help with acne-prone skin.
Hair health – Cloves can increase blood circulation in the scalp and promote hair growth.
Diabetes – Cloves can help manage diabetes by reducing inflammation and naturally lowering blood sugar levels.
Libido – Cloves have been used as an aphrodisiac for centuries and may improve testosterone levels and erectile health. They may also help treat premature ejaculation

1. Contain important nutrients

Cloves contain fiber, vitamins, and minerals, so using whole or ground cloves to add flavor to your food can provide some important nutrients.

One teaspoonTrusted Source (tsp) (2 grams (g)) of ground cloves contains:

Calories: 6
Carbs: 1 g
Fiber: 1 g
Manganese: 55% of the Daily Value (DV)
Vitamin K: 2% of the DV

Manganese is an essential mineralTrusted Source for maintaining brain function and building strong bones.

Apart from being a rich source of manganese, cloves are only used in small amounts and do not provide significant amounts of nutrients.

2. High in antioxidants

In addition to containing several important vitamins and minerals, cloves are rich in antioxidants.Trusted Source

Antioxidants are compounds that reduce oxidative stress, which can contribute to the development of chronic disease.

Cloves also contain a compound called eugenol, which has been shown to act as a natural antioxidant. Therefore, including cloves in your diet, along with other antioxidant-rich foods, can help improve your overall health.

3. May improve liver health

A 2022 animal studyTrusted Source found that clove extract improved liver damage caused by the toxic substance thioacetamide. In particular, the compound eugenol may beTrusted Source especially beneficial for the liver.

However, there isn’t enough research showing the benefit of cloves for liver health in humans, and high doses can actually damageTrusted Sourcethe liver.

4. May help protect against cancer

Some research suggests that the clove oil might help protect against cancer.

Specifically, eugenol has been shownTrusted Source to have anticancer properties. Specifically, test-tube researchTrusted Source suggests eugenol promotes cell death in breast cancer cells.

However, as stated, eugenol is toxic in high amounts, and overdosing on clove oilTrusted Source may cause liver damage, especially in children. Further research is needed to determine how lower amounts may affect humans.

5. Can kill bacteria

Cloves have been shownTrusted Source to have antimicrobial properties, meaning they can help stop the growth of microorganisms like bacteria.

What’s more, in combination with regular brushing and proper oral hygiene, the antibacterial effects of cloves may even benefit your oral health.

6. May help regulate blood sugar

The compounds found in cloves may help keep blood sugar under control. For example, in a 2019 studyTrusted Source, people with and without prediabetes who took 250 milligrams (mg) of clove extract daily for 30 days showed significantly less blood glucose after meals.

In another animal study, nigricin, a compound found in cloves, was foundTrusted Source to increase the uptake of sugar from the blood into cells, increase the secretion of insulin, and improve the function of cells that produce insulin in mice.

In combination with a balanced diet, cloves may help keep your blood sugar levels in check, though more research on humans is needed to confirm this.

7. May promote bone health

Low bone mass is a condition that affects an estimated 43 million AmericansTrusted Source, according to the most recent estimates from 2014.

It can lead to the development of osteoporosis, which may increase the risk of breaks and fractures.

Animal research suggests that eugenol may help improve bone mass. In addition, cloves contain manganese, which is involved in the formation of bone and is incredibly important to bone health.

That said, more research is needed to determine how cloves may affect bone in humans.

8. May reduce stomach ulcers

Some animal researchTrusted Source indicates that eugenol could help treat stomach ulcers.

Also known as peptic ulcers, stomach ulcers are painful sores that form in the lining of the stomach, duodenum, or esophagus.

Test tube research also suggests that clove oil may also have an effect against Helicobacter pylori (H. Pylori), a bacteria that can trigger stomach problems such as ulcers and even cancer.

Though the anti-ulcer effects of cloves and their compounds may be promising, further studies are needed on their effects in humans.

What are the side effects of clove?

These are the things to keep in mind in terms of the safety of clove:

Eating clove: Eating small amounts is not likely to cause you harm. In fact, The Food and Drug Administration (FDA) has approved clove buds and clove oil as Generally Recognized as Safe (GRAS) for use as an additive in food. That said, there isn’t enough evidence on the effect of ingesting clove in large amounts, especially for people who are pregnant or nursing. Stay on the safe side and stick to the amount recommended in the recipe.
Ingestion of clove oil: While both clove and clove oil contain eugenol, the compound is in much higher concentrationsTrusted Source when clove is distilled into oil. For this reason, clove oil is unsafe to take by mouth, especially for children. Even small amounts of clove oil can cause severe side effects such as seizures, liver damage, and fluid imbalances. It can also lead to bleeding in people with bleeding disorders or during surgery.
Topical: Clove oil or cream from clove flowers is generally safeTrusted Source for skin application. However, using clove oil on the gums can lead to irritation and damage.
Drug interactions: Be careful if you’re taking any medications to manage blood clotting or manage your blood sugar, such as for diabetes, as the eugenol in clove may interfereTrusted Source with these drugs. source

Clove Benefits: 8 Surprising Health Benefits and Uses

by Zahra Ijaz

You might have heard about the clove benefits for toothache and your dental health, but do you know that have other health benefits as well.

Originating from Indonesia, clove is a dried flower bud from the clove tree.

They are a popular spice that many individuals use in soups, stews, meats, sauces, and rice dishes.

Their name comes from a Latin word, Clavus, which means nail as the shape of a dried clove resembles that of a nail.

People all around the world have used it in cooking and traditional medicine for many years in raw form or as clove tea.

However, only recently, many scientists have begun studying their potential health benefits.

Moreover, studies suggest that the compounds in cloves have several health benefits.

These include supporting liver health, benefiting your immune system to stabilizing your blood sugar levels.

Keep on reading to learn more about the potential health benefits of clove and its uses.

Nutrients of Clove

Clove contains a number of nutrients including fiber, vitamins, and minerals.

Thus using them as whole or in ground form can provide you some important nutrients.

One teaspoon or 2 grams of ground cloves contains:

calories: 6
carbs: 1 gram
fiber 2 grams
manganese: 55% of the daily value or DV
vitamin K: 2% of the DV

Manganese is an essential mineral for maintaining your brain functions and building strong bones.

Other than being a rich source of manganese. you can use cloves in small amounts and do not provide significant amounts of other nutrients.

Clove Benefits: High in Antioxidants

Along with other important vitamins and minerals, cloves are rich in .

Antioxidants are compounds that help to reduce oxidative stress, which can contribute to the development of chronic diseases.

Clove contains Eugenal, that according to studies acts as a natural antioxidant.

According to a test tube study, eugenol helps to stop oxidative damage due to free radicals 5 times more effective than vitamin E, which is another potent antioxidant.

Thus, including cloves in your diet along with other antioxidant-rich foods can help to improve your overall health.

Learn more about Hydrafacial in Dubai here.

Protect Against Cancer

According to some research, the compounds found in cloves can help to protect against cancer.

One test-tube study suggests that clove extract helps to stop the growth of tumors and promotes cell death in cancer cells.

Another study suggests the same results, showing the in concentrated form, clove oil causes cell death in 80% of the esophageal cancer cells.

The eugenol present in cloves has anti-cancer properties.

However, bear in mind that these test-tube studies used very concentrated amounts of clove extract, clove oil, and eugenol.

Moreover, eugenol is toxic in high amounts and its overdose can cause liver damage, especially in children.

Further research is needed to determine how lower amounts can affect humans.

Clove Benefits: Kills Bacteria

Studies suggest that clove has antimicrobial properties, which means that they can help stop the growth of micro-organism like bacteria.

According to a test-tube study, clove essential oil helps to kill 3 common types of bacteria.

These include E. coli, which is a strain of bacteria that can cause food poisoning.

Moreover, the antibacterial properties of cloves can even help to promote oral health.

In another study, the compounds extracted from clovers were found to stop the growth of the above 2 types of bacteria.

These two types contribute to gum diseases.

Another study suggests that using an herbal mouthwash consisting of tea tree oil, cloves, and basil improves gum health.

Moreover, it helps to reduce the amount of plaque and bacteria in your mouth.

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Helps to Improve Liver Health

Studies suggest that the beneficial compounds in cloves can help promote liver health.

The compound eugenol is especially good for the health of your liver.

According to an animal study, clove oil or eugenol improves liver functions, reduces inflammation, and decreases oxidative stress.

Thus, reducing fatty liver disease.

Another animal study suggests that cloves help to reverse the signs of liver cirrhosis or scarring of the liver.

However, the effect of clove and eugenol on the liver of humans is limited.

But one study found that individuals who take eugenol supplements for 1 week show a decrease in glutathione-S-transferases, GSTs.

This is a family of enzymes that are involved in detoxification that is often a marker of liver diseases.

Moreover, cloves are high in antioxidants that can help prevent liver diseases.

This is due to their ability to decrease oxidative stress.

However, keep in mind that eugenol is toxic in high amounts.

One case study found that clove oil caused serious damage to a child, 2 years of age when ingested 5 to 10 mL of it.

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Regulates Blood Sugar

According to studies, compounds found in cloves can help and even regulate blood sugar levels.

An animal study suggests that clove extracts can help moderate blood sugar increases in mice with diabetes.

Moreover, cloves and nigericin that increase the uptake of sugar from the blood into the cells, increases the secretion of insulin.

Thus, helps to improve the function of cells that produce insulin.

Insulin is a hormone that is responsible for transporting sugar from your blood into the cells.

The proper functioning of the liver is important for maintaining steady blood sugar levels.

Along with a balanced diet, cloves can help you to keep your blood sugar levels in check.

Clove Benefits: May promote Bone Health

Low bone mass is a condition that affects about 43 million older adults in the United States alone.

Image the number worldwide.

It can lead to the development of osteoporosis, which can increase the risk of breaks and fractures.

In some animal studies, clove helps to preserve bone mass.

For instance, one animal study suggests that clove extract that is high in eugenol can help improve several markers of osteoporosis.

Moreover, it helps to increase bone density and strength.

Cloves are rich in manganese, providing an impressive 30% of the DV in just 1 tsp or 2 grams of ground cloves.

Manganese is a mineral that helps in the formation of bone and is also important for the health of your bones.

However, it is important to note that current research on the effects of clove on bone mass is limited to animal and test-tube studies.

More research is needed to determine how it affects bone formation.

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Clove Benefits: Reduce Stomach Ulcers

Some of the research suggests that the compounds present in cloves can help treat stomach ulcers.

Also known as peptic ulcers, stomach ulcers can b painful sores that form in the lining of your stomach, duodenum, or esophagus.

Moreover, they are due to reductions in the protective lining of the stomach.

This is often due to stress, infections, and genetics.

According to one animal study, essential oil from cloves shows to increase the production of gastric mucus.

Gastric mucus functions are a barrier and help to prevent erosion of the stomach lining from the digestive acids.

Although the anti-ulcer effects of cloves and their compounds may be promising, further studies are required on their effects in humans.

Potential Side Effects and Risks

According to the National Center for Biotechnology Information, there are different side effects associated with clove oil.

In some cases, it can cause skin, eye, and respiratory irritation or an allergic reaction on the skin.

Moreover, it is also flammable and can be fatal if you swallow it and it goes into the airway.

According to a case report, a 15-month-old child experienced liver failure after consuming 10 milliliters or ml of clove oil.

Another incident shows that a boy who drank 5 to 1o ml of clove oil experienced multiple medical conditions.

These include coma, liver damage, and problems with blood clotting.

Moreover, it can also increase your chance of bleeding or increase your body’s response to warfarin.

Thus, it is important to discuss the use of any herbal products with your medical professional, so that they can review potential side effects and interactions.

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Using Cloves

Cloves are popular for their strong taste and smell, and you can purchase them in ground form or in the whole form.

Many cuisines use cloves, and it is an important ingredient in certain condiments like ketchup and Worcestershire sauce.

Moreover, some perfumes even use it for the aroma and are also found as an essential oil.

You can use clove in similar ways as cinnamon and ginger and can also be used to flavor applesauce, oatmeal, muffins, and cookies.

It can also be used in tea along with certain other spices. source

AMAZING CLOVE OIL BENEFITS FOR YOUR SKIN, HAIR AND HEALTH

Clove is a powerhouse of health benefits. It has been used for centuries in Ayurveda and traditional Chinese medicine to cure various diseases. Apart from adding flavour and aroma to our food, clove benefits can be obtained from its oil, stem, leaves as well as dried buds. The anti-microbial, anti-fungal, antiviral and antiseptic properties of cloves make it an excellent home remedy for various ailments. A rich source of antioxidants, cloves can be used to address the most common skin, hair and health problems. One of the most common benefits of cloves is its ability to numb toothache.

Using cloves in its original form can be a lot of work, therefore its oil is preferred in Ayurveda and other DIY remedies. The benefits of clove oil are the same as the spice itself, so if you are looking to treat common skin, hair and health concerns, we suggest you get your hands on some pure clove oil.

Heals and prevents acne

The antibacterial and antiseptic properties of cloves kill acne-causing bacteria and keep breakouts at bay. Clove oil contains a compound called eugenol that helps in treating acne by reducing the inflammation and redness. To reap the benefits of clove, mix a few drops of clove essential oil with a carrier oil and use it as a spot treatment or add it to your daily moisturiser and apply all over the face. Avoid using clove oil if you have sensitive skin.

Fights the signs of ageing

Did you know clove oil is a powerful anti-ageing ingredient used in cosmetics? It works in reducing skin sagging and the appearance of fine lines and wrinkles. The application of clove oil improves blood circulation, which gives skin a youthful and radiant look. Mix a few drops of clove oil in your serum or moisturizer and apply on cleansed skin at night, before going to bed for the best results.

Fades dark spots and blemishes

Apart from healing and preventing acne, another clove oil benefit is that it also fades dark spots and blemishes left behind by acne and pimples. It has mild exfoliating properties that remove dead skin cells and ensure an even skin tone. Mix a few drops of clove essential oil with a carrier oil and massage onto your face in circular motions. Repeat every night for the best results.

Treats dandruff

While the exact cause of dandruff is unknown, many men and women face this common scalp problem. Dandruff can be an embarrassing problem, especially when it flakes and falls on your shoulders. Use the benefits of clove oil to treat this problem. As mentioned before, clove oil contains anti-fungal and anti-microbial properties, this helps fight dandruff and prevents the itchy sensation. To soothe a dry and irritated scalp that has dandruff, add 10-12 drops of clove essential oil to your regular shampoo and use it to wash your hair.

Promotes hair growth

The compound eugenol found in clove oil helps promote hair growth when applied to the roots. It can also repair, strengthen and add a healthy shine to the hair shaft when applied regularly. To use clove oil for stronger and healthier hair growth, add a teaspoon of clove oil to warm coconut oil and apply it to the roots of your hair using your fingertips. Wash off after 2-3 hours. This will improve blood circulation in the scalp and promote stronger hair growth.

Prevents premature ageing

Spotting a few grey strands in your thirties is normal, but if you have more grey hair than black, then it needs to be addressed. In fact, people in their late 20s have also started experiencing premature hair greying. Here’s how you can tackle the problem using the benefits of clove oil. It contains some unique elements that improve the production of the pigment responsible for keeping hair in its natural colour. Combine three tablespoons of eucalyptus oil with a teaspoon of clove oil and massage your scalp and hair twice a week.

Treats indigestion

Clove oil is one of the oldest remedies to fight stomach and digestion-related issues. The presence of eugenol in clove and clove oil helps treat gastric problems like indigestion. It can also be used to address motion sickness and hiccups. Avoid taking medicines, instead, simply chew on a clove to get relief from digestion related issues like acidity and heartburn. You can also add a few cloves to your tea to keep the problem of indigestion at bay.

Eases headaches

Before you reach out for that medicine box for your headache, head to the kitchen and use the benefits of clove to get relief from the headache. Clove oil is an excellent pain reliever, the flavonoids in clove oil have anti-inflammatory agents that have a cooling effect and relieve headaches. Simply mix four drops of clove oil with salt and apply it on your forehead for instant relief.

Strengthens immunity

A good immune system keeps several health issues at bay, therefore it is recommended to include immunity-boosting foods into our diet. The antioxidant property of cloves can help strengthen the immune system and protect it from heart ailments and viruses. It also improves the immune system by increasing the white blood cell count in the body. source

1. Antioxidant Properties

In a study quoted by NIH, it was found that cloves are a powerful antioxidant that aids in the treatment of various chronic health conditions. Antioxidants help reduce oxidative stress, inhibiting chronic diseases like heart disease, cancer, and diabetes. Clove is rich in eugenol, a natural antioxidant that fights 5 times more against free radicals than any other antioxidant. It stops cell damage, thus preventing the development of multiple diseases.

Including cloves in your diet with other antioxidant-rich foods can improve your health.

2. Anti-Inflammatory

The anti-inflammatory properties of cloves result from two essential and powerful phytonutrients, eugenol and isoeugenol. These phytonutrients reduce inflammation in the body and prevent the development of some conditions like arthritis or chronic conditions.

3. Anti-Cancer Properties

Cloves have anti-cancer properties because of eugenol. In a research article published in the Journal of Hindawi, eugenol oil has shown various anti-cancer properties. Some test-tube observations explain that eugenol has the capability of killing cancer cells, and it can also hinder tumour growth, majorly in cervical and oesophagus cancer. For these tests, cloves were used in concentrated amounts.

There is a need for thorough and further research about cloves to explain their anti-cancer properties. Eugenol is toxic in excess amounts that can impact health, especially liver health, significantly.

4. Anti-Diabetic

Cloves are also known for their anti-diabetic property. It is considered to control your blood sugar levels because of the presence of nigericin compounds. It helps in reducing insulin resistance and can promote moderate sugar levels.

Insulin is the hormone that manages blood sugar levels in the body by carrying it from the blood to the cells. Cloves help to improve the functions of insulin-producing cells and manage their levels. Some studies show its impact on test tubes and animal research. A study published by NIH shows the anti-diabetic effect of clove on rabbits, although more studies are needed.

5. Anti-Microbial Properties

Cloves have antimicrobial agents that reduce the development of bacteria-like microorganisms. It can act against bacteria and fungi like E. Coli., vaginal candidiasis, and staph aureus. Clove extracts and clove oil help in fighting against food poisoning and stomach infections.

This spice is popular for strengthening oral health. It fights against resting mouth bacteria and improves oral hygiene by reducing bad breath and gum infections. It is used in mouthwash and toothpaste to reduce oral bacteria and plaque on teeth

6. Suitable For The Liver

According to some studies, cloves help to improve liver health. The compound eugenol has antioxidant and anti-inflammatory properties that promote liver health. It reduces the risk of liver cirrhosis and fatty liver condition. It helps to strengthen liver health by decreasing oxidative stress. Some studies show that clove can help decrease the levels of glutathione-S-transferases (GSTs) responsible for liver diseases.

Although cloves can be identified as a good source for liver health, there is still a need for more human studies.

On the other hand, excess consumption of cloves can damage the liver because of eugenol toxicity.

7. Helps Reduce Ulcers

Stomach ulcers are the result of stress, infections, or genetics. These ulcers are caused by the depletion of the mucus layer in the stomach. This mucus layer helps to safeguard stomach walls from digestive acids. If these walls get thin, it results in stomach ulcers. Cloves have some compounds that help in thickening these walls.

According to WebMD, clove helps reduce the risks of developing new ulcers and also treats existing ulcers. Clove oil can help increase stomach mucus and decrease the probability of gastric ulcers.

8. Natural Painkiller And Anti-Cough Properties

As a traditional medicine, clove treats cough, sore throat, and toothache. It is a common home remedy used with hot beverages for treating cough. Clove oil is also an effective painkiller that has been used to treat toothache for centuries.

9. Good For Bone Health

A large population is at risk of low bone density, arthritis, and osteoporosis. Cloves are rich in manganese, which is important for bone health. Also, as per the findings of NIH, eugenol in clove helps increase bone density and strength. These benefits of clove eventually prevent conditions like osteoporosis, fractures, and breaks because of low bone mass. Although these studies are limited to animals, there is much room for human research and clove’s impact on human bone health. However, a small amount of clove powder fulfils almost 30% of the daily required manganese in the body.

10. Clove Benefits For Men

Cloves are very beneficial for men and impact men’s reproductive health. It is very useful in increasing men’s health in multiple ways, they are:

It increases testosterone levels, improves sex life, increases sperm count, removes infertility, increases libido, reduces the condition of early ejaculation, and strengthens reproductive organs.

Apart from these, using clove essential oil in bathing can also reduce the craving for smoking, thus keeping you free from smoking addiction.

11. Apart From These Benefits, Cloves Also Have Other Benefits Like

Treating cold, flu, cough, and chest congestion. Any hot beverage mixed with clove and cinnamon can help lower the symptoms of these conditions.

It is also good for the skin. Cloves can detoxify skin and reduce acne, blemishes, and dark circles. It is used in many herbal face packs for better results and glowing skin.

Way to Consume Clove

This is an omnipresent spice or herb that can be used year-long in food, medicines, and cosmetics. These dried flowers not only have a distinct aroma but flavour as well. You can consume it in many ways, including as a whole bud, with beverages, and in many dishes.

You can use it in multiple ways:

Clove Tea

Clove tea is the easiest recipe to enjoy the benefits of cloves. To make clove tea:

Use a tablespoon of grounded clove
Boil it for some minutes
Strain it and drink it as an effective clove tea.

Clove Water

Clove water is also a great way of consuming this magical spice.

Put 3-5 clove buds in a glass of water and leave them overnight.
Drink it in the morning to see amazing results.

Apart from clove tea and clove water, you can also mix this dried flower in many dishes for flavor and taste:

Use in curries and chutneys
Add in pickles
Masala Milk Tea with Clove
Add in Baking, Cookies, and Bread
Used to season meat
It can also be used as a natural preservative

Side-Effects of Clove

Cloves have many health benefits but can also affect health negatively and cause a few side effects. These strong spices can lower blood sugar and can cause hypoglycemia, where a person can feel dizziness and nausea. As per WebMD, clove’s compound, eugenol, can also react with some blood-thinning medicines and increase the chances of side effects. However, small amounts of clove can have more positive results than negatives, but always pay attention while consuming it in excess. Eugenol in excess amounts can be toxic and can cause dizziness.

According to the traditional medicine system, cloves are a hot spice that can cause nosebleeds, mouth ulcers, stomach burning or irritation, and throat rashes if consumed in excess.

Also, some people are allergic to cloves, so they should avoid them.

Can Diabetics Eat Cloves?

Many studies suggest that cloves are good for diabetes. It helps in controlling blood sugar levels and increases insulin production. This super spice helps cells secrete insulin, responsible for moderate blood sugar levels in the body.

Clove’s GI and GL are low. It’s also low on carbs and calories, which is a good factor in making it a diabetic-friendly spice. Clove oil helps maintain PP sugar levels and GRM. source

Everything You Need To Know About Magnesium And Sleep

The Truth News — Mon, 22 Jan 2024 20:31:33 +0000

Everything You Need To Know About Magnesium And Sleep

In the pecking order of natural sleep aids, magnesium seems to be steadily making its way to the top. This essential mineral plays multiple roles in the body, but what does it do for sleep? There is some evidence, both clinical and anecdotal, that magnesium may be helpful for better sleep, but details are still murky. To get a better idea of how exactly magnesium and sleep could be connected, we spoke with a certified sleep expert and a registered nutritionist.

What Is Magnesium?

“Magnesium is a mineral we need in our diet to stay healthy,” explains Dr. Chelsie Rohrscheib, a neuroscientist and the head sleep expert at Wesper. It’s classified as an electrolyte and involved in over 300 enzymatic processes in the body, including supporting bone health, regulating muscle function, and promoting energy production.

The body doesn’t make its own magnesium, which means we need to source sufficient amounts from the foods we eat or the supplements we take. The mineral is present in nutritious foods like fruits and vegetables, fish, nuts, seeds, legumes and whole grains. Still, a 2018 review found that an estimated 50 percent of Americans may be deficient. While it’s not necessarily life threatening, a magnesium deficiency can have unpleasant symptoms, such as muscle cramps, tremors and twitches — none of which make it easy to fall or stay asleep.

How Does Magnesium Affect Sleep?

Susan Schachter, MSRDN, calls magnesium a smooth muscle relaxer, which means it can help calm the nervous system. “It has been shown to increase levels of the neurotransmitter GABA, which helps calm the brain and reduce anxiety,” she explains. “Because of this, research has suggested that magnesium may help improve sleep quality, reduce insomnia, and increase sleep time in people with some sleep disorders.”

In fact, it’s often recommended to people who struggle with muscle cramps at night or those with restless legs syndrome, says Rohrscheib. But that’s not all.

“In addition to its involvement in reducing anxiety, relaxing muscle and increasing levels of GABA, magnesium helps to regulate the body’s production of melatonin, a hormone that’s important for sleep-wake cycles,” says Schachter.

While several small studies show a positive association between magnesium and improved sleep quality and duration, research about the actual impact of magnesium on sleep is still quite limited. What’s more, findings are mixed. A 2021 review of magnesium supplementation for insomnia in older adults found that sleep latency and total sleep time improved, but researchers called the results statistically insignificant and noted that outcomes were supported with poor quality of evidence.

How to Take Magnesium

As a potential sleep aid, magnesium can be taken as an oral supplement about 30 minutes to an hour before bed. It comes in several forms, including magnesium oxide, magnesium citrate and magnesium chloride, and absorption can vary based on the type used in a given supplement. Some studies have found that citrate and chloride forms of magnesium are more bioavailable than oxide — that means the body is able to more readily absorb those forms, which could mean greater efficacy.

Magnesium is also available in topical form, including lotions, sprays, and bath salts. While research is still needed to confirm the efficacy of topical magnesium as a sleep remedy, the application of a soothing magnesium lotion or a calming soak in a warm tub could still be a good addition to a bedtime routine.

How Much Magnesium Should I Take for Sleep?

Keep in mind that we get magnesium in our diets, and it’s an essential mineral for various bodily functions. The National Institutes of Health recommends that adults supplement with no more than 350 mg per day. That’s slightly at odds with dosages used in clinical studies of magnesium for sleep. “Some studies have shown that taking 200-400 mg before bed may help improve sleep quality and quantity, particularly in people who have difficulty falling asleep,” says Schachter.

Still, it’s best to err on the side of caution. “When supplementing one needs to be careful with dosing, as a high dose can cause diarrhea (because the intestines are smooth muscle) and/or upset stomach,” Schachter says.

Magnesium and Anxiety

There is research that suggests magnesium could be a viable treatment for anxiety, possibly because of the way it regulates neurotransmitters and brain function. Specifically, magnesium interacts with stress mediators like the hypothalamus, the part of the brain that manages stress and anxiety, by inhibiting the stress response. However, like magnesium as a sleep aid, more research is needed to clarify how exactly magnesium can help with anxiety.

How Can I Raise My Magnesium Levels Naturally?

Generally, you can increase magnesium levels through diet alone, because it’s present in a fairly wide range of foods. The federal government’s Dietary Guidelines for Americans outlines a healthy diet as one that includes a mix of vegetables, fat and low-fat dairy, beans and legumes, and nuts and seeds, all of which include magnesium.

Foods High In Magnesium

Schachter says that the amount of magnesium in specific foods can vary depending on how they’re processed and prepared, but the following are great sources:

Dark leafy greens: spinach, kale, Swiss chard, collard greens
Nuts and seeds: almonds, cashews, pumpkin seeds, sunflower seeds
Legumes: black beans, kidney beans, chickpeas, lentils
Whole grains: brown rice, quinoa (actually a seed but used like a grain), whole wheat products
Fish: halibut, salmon, mackerel
Dairy products: milk, yogurt, cheese
Soy Products: soy milk, soy beans
Dark chocolate

Is Magnesium Better Than Melatonin?

Magnesium is inherently different from melatonin. One is an essential mineral that we need to source from the foods we eat, while the other is a hormone that we produce naturally. Schachter says they can both potentially help with sleep, and the two substances share a deeper connection as well. “Magnesium has the benefit of helping with melatonin production, as well as decreasing anxiety and relaxing muscles,” she says.

It isn’t that one is necessarily better than the other, but rather that they offer different benefits. Melatonin supplements help jumpstart your natural melatonin production, which can make it easier to fall asleep in certain scenarios, like if you’re dealing with jet lag, trying to sleep in a new environment, or navigating short-term insomnia. Magnesium can be a better option if you need to shut down an anxious mind so that your body can relax into sleep.

The Last Word from Sleepopolis

Magnesium rivals melatonin as a popular natural sleep aid, and there is promising research to support its role in better sleep. However, more studies are needed to pinpoint exactly how magnesium supports sleep. If you’re considering this supplement to help you get a better night’s sleep, make sure to speak with your doctor first. “It’s always important to check with a healthcare professional to be sure magnesium is safe for you if you have any health conditions or are taking medication,” says Schachter. source

Learn about how sound can help aid your sleep process:

Why Walnuts Are A Good Snack To Eat Before Bed

The Right Noise – Pink, White ,Brown, Blue, Black, and Red Noise: Your Guide to a Good Night’s Sleep

How to Sleep Better: Your Guide for Good ZZZ

Everything You Need To Know About Magnesium And Sleep

Optimizing the Sleep-Wake Cycle

How to Reset Your Sleep Cycle When You Live With Insomnia

The Importance of Sleep with Alzheimer’s

What You Eat Affects How You Sleep

GABA & L-theanine mix Improves REM Sleep, Stabilizes mood and helps with depression

What Happens When Circadian Rhythm Is Off? Learn More

Do You Wake Up Every Night At The Same Time? Learn More

How to Reset Your Sleep Cycle When You Live With Insomnia Learn More

What You Eat Affects How You Sleep? Learn More

GABA / L-theanine mixture Improves REM Sleep, Antidepressant, and Mood-stabilizing Study Says Learn More

Magnesium Introduction

Magnesium, an abundant mineral in the body, is naturally present in many foods, added to other food products, available as a dietary supplement, and present in some medicines (such as antacids and laxatives). Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation [1-3]. Magnesium is required for energy production, oxidative phosphorylation, and glycolysis. It contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm [3].

An adult body contains approximately 25 g magnesium, with 50% to 60% present in the bones and most of the rest in soft tissues [4]. Less than 1% of total magnesium is in blood serum, and these levels are kept under tight control. Normal serum magnesium concentrations range between 0.75 and 0.95 millimoles (mmol)/L [1,5]. Hypomagnesemia is defined as a serum magnesium level less than 0.75 mmol/L [6]. Magnesium homeostasis is largely controlled by the kidney, which typically excretes about 120 mg magnesium into the urine each day [2]. Urinary excretion is reduced when magnesium status is low [1].

Assessing magnesium status is difficult because most magnesium is inside cells or in bone [3]. The most commonly used and readily available method for assessing magnesium status is measurement of serum magnesium concentration, even though serum levels have little correlation with total body magnesium levels or concentrations in specific tissues [6]. Other methods for assessing magnesium status include measuring magnesium concentrations in erythrocytes, saliva, and urine; measuring ionized magnesium concentrations in blood, plasma, or serum; and conducting a magnesium-loading (or tolerance) test. No single method is considered satisfactory [7]. Some experts [4] but not others [3] consider the tolerance test (in which urinary magnesium is measured after parenteral infusion of a dose of magnesium) to be the best method to assess magnesium status in adults. To comprehensively evaluate magnesium status, both laboratory tests and a clinical assessment might be required [6].

Recommended Intakes

Intake recommendations for magnesium and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) [1]. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and sex, include the following:

Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals
Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA
Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals
Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects

Table 1 lists the current RDAs for magnesium [1]. For infants from birth to 12 months, the FNB established an AI for magnesium that is equivalent to the mean intake of magnesium in healthy, breastfed infants, with added solid foods for ages 7–12 months.

Table 1: Recommended Dietary Allowances (RDAs) for Magnesium [1]
Age	Male	Female	Pregnancy	Lactation
Birth to 6 months	30 mg*	30 mg*
7–12 months	75 mg*	75 mg*
1–3 years	80 mg	80 mg
4–8 years	130 mg	130 mg
9–13 years	240 mg	240 mg
14–18 years	410 mg	360 mg	400 mg	360 mg
19–30 years	400 mg	310 mg	350 mg	310 mg
31–50 years	420 mg	320 mg	360 mg	320 mg
51+ years	420 mg	320 mg

Sources of Magnesium

Food

Magnesium is widely distributed in plant and animal foods and in beverages. Green leafy vegetables, such as spinach, legumes, nuts, seeds, and whole grains, are good sources [1,3]. In general, foods containing dietary fiber provide magnesium. Magnesium is also added to some breakfast cereals and other fortified foods. Some types of food processing, such as refining grains in ways that remove the nutrient-rich germ and bran, lower magnesium content substantially [1]. Selected food sources of magnesium are listed in Table 2.

Tap, mineral, and bottled waters can also be sources of magnesium, but the amount of magnesium in water varies by source and brand (ranging from 1 mg/L to more than 120 mg/L) [8].

Approximately 30% to 40% of the dietary magnesium consumed is typically absorbed by the body [2,9].

Table 2: Magnesium Content of Selected Foods [10]
Food	Milligrams (mg) per serving	Percent DV*
Pumpkin seeds, roasted, 1 ounce	156	37
Chia seeds, 1 ounce	111	26
Almonds, dry roasted, 1 ounce	80	19
Spinach, boiled, ½ cup	78	19
Cashews, dry roasted, 1 ounce	74	18
Peanuts, oil roasted, ¼ cup	63	15
Cereal, shredded wheat, 2 large biscuits	61	15
Soymilk, plain or vanilla, 1 cup	61	15
Black beans, cooked, ½ cup	60	14
Edamame, shelled, cooked, ½ cup	50	12
Peanut butter, smooth, 2 tablespoons	49	12
Potato, baked with skin, 3.5 ounces	43	10
Rice, brown, cooked, ½ cup	42	10
Yogurt, plain, low fat, 8 ounces	42	10
Breakfast cereals, fortified with 10% of the DV for magnesium, 1 serving	42	10
Oatmeal, instant, 1 packet	36	9
Kidney beans, canned, ½ cup	35	8
Banana, 1 medium	32	8
Salmon, Atlantic, farmed, cooked, 3 ounces	26	6
Milk, 1 cup	24–27	6
Halibut, cooked, 3 ounces	24	6
Raisins, ½ cup	23	5
Bread, whole wheat, 1 slice	23	5
Avocado, cubed, ½ cup	22	5
Chicken breast, roasted, 3 ounces	22	5
Beef, ground, 90% lean, pan broiled, 3 ounces	20	5
Broccoli, chopped and cooked, ½ cup	12	3
Rice, white, cooked, ½ cup	10	2
Apple, 1 medium	9	2
Carrot, raw, 1 medium	7	2

*DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for magnesium is 420 mg for adults and children age 4 years and older [11]. FDA does not require food labels to list magnesium content unless magnesium has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

The U.S. Department of Agriculture’s (USDA’s) FoodData Central [10] lists the nutrient content of many foods and provides comprehensive list of foods containing magnesium arranged by nutrient content and by food name.

Dietary supplements

Magnesium supplements are available in a variety of forms, including magnesium oxide, citrate, and chloride [2,3]. The Supplement Facts panel on a dietary supplement label declares the amount of elemental magnesium in the product, not the weight of the entire magnesium-containing compound.

Absorption of magnesium from different kinds of magnesium supplements varies. Forms of magnesium that dissolve well in liquid are more completely absorbed in the gut than less soluble forms [2,12]. Small studies have found that magnesium in the aspartate, citrate, lactate, and chloride forms is absorbed more completely and is more bioavailable than magnesium oxide and magnesium sulfate [12-16]. One study found that very high doses of zinc from supplements (142 mg/day) can interfere with magnesium absorption and disrupt the magnesium balance in the body [17].

Medicines

Magnesium is a primary ingredient in some laxatives [18]. Phillips’ Milk of Magnesia, for example, provides 500 mg elemental magnesium (as magnesium hydroxide) per tablespoon; the directions advise taking up to 4 tablespoons/day for adolescents and adults [19]. (Although such a dose of magnesium is well above the safe upper level, some of the magnesium is not absorbed because of the medication’s laxative effect.) Magnesium is also included in some remedies for heartburn and upset stomach due to acid indigestion [18]. Extra-strength Rolaids, for example, provides 55 mg elemental magnesium (as magnesium hydroxide) per tablet [20], although Tums is magnesium free [21].

Magnesium Intakes and Status

Dietary surveys of people in the United States consistently show that many people consume less than recommended amounts of magnesium. An analysis of data from the National Health and Nutrition Examination Survey (NHANES) of 2013–2016 found that 48% of Americans of all ages ingest less magnesium from food and beverages than their respective EARs; adult men age 71 years and older and adolescent males and females are most likely to have low intakes [22]. In a study using data from NHANES 2003–2006 to assess mineral intakes among adults, average intakes of magnesium from food alone were higher among users of dietary supplements (350 mg for men and 267 mg for women, equal to or slightly exceeding their respective EARs) than among nonusers (268 mg for men and 234 for women) [23]. When supplements were included, average total intakes of magnesium were 449 mg for men and 387 mg for women, well above EAR levels.

No current data on magnesium status in the United States are available. Determining dietary intake of magnesium is the usual proxy for assessing magnesium status. NHANES has not determined serum magnesium levels in its participants since 1974 [24], and magnesium is not evaluated in routine electrolyte testing in hospitals and clinics [2].

Magnesium Deficiency

Symptomatic magnesium deficiency due to low dietary intake in otherwise-healthy people is uncommon because the kidneys limit urinary excretion of this mineral [3]. However, habitually low intakes or excessive losses of magnesium due to certain health conditions, chronic alcoholism, and/or the use of certain medications can lead to magnesium deficiency.

Early signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions and cramps, seizures, personality changes, abnormal heart rhythms, and coronary spasms can occur [1,2]. Severe magnesium deficiency can result in hypocalcemia or hypokalemia (low serum calcium or potassium levels, respectively) because mineral homeostasis is disrupted [2].

Groups at Risk of Magnesium Inadequacy

Magnesium inadequacy can occur when intakes fall below the RDA but are above the amount required to prevent overt deficiency. The following groups are more likely than others to be at risk of magnesium inadequacy because they typically consume insufficient amounts or they have medical conditions (or take medications) that reduce magnesium absorption from the gut or increase losses from the body.

People with gastrointestinal diseases

The chronic diarrhea and fat malabsorption resulting from Crohn’s disease, gluten-sensitive enteropathy (celiac disease), and regional enteritis can lead to magnesium depletion over time [2]. Resection or bypass of the small intestine, especially the ileum, typically leads to malabsorption and magnesium loss [2].

People with type 2 diabetes

Magnesium deficits and increased urinary magnesium excretion can occur in people with insulin resistance and/or type 2 diabetes [25,26]. The magnesium loss appears to be secondary to higher concentrations of glucose in the kidney that increase urine output [2].

People with alcohol dependence

Magnesium deficiency is common in people with chronic alcoholism [2]. In these individuals, poor dietary intake and nutritional status; gastrointestinal problems, including vomiting, diarrhea, and steatorrhea (fatty stools) resulting from pancreatitis; renal dysfunction with excess excretion of magnesium into the urine; phosphate depletion; vitamin D deficiency; acute alcoholic ketoacidosis; and hyperaldosteronism secondary to liver disease can all contribute to decreased magnesium status [2,27].

Older adults

Older adults have lower dietary intakes of magnesium than younger adults [21,28]. In addition, magnesium absorption from the gut decreases and renal magnesium excretion increases with age [29]. Older adults are also more likely to have chronic diseases or take medications that alter magnesium status, which can increase their risk of magnesium depletion [1,30].

Magnesium and Health

Habitually low intakes of magnesium induce changes in biochemical pathways that can increase the risk of illness over time. This section focuses on four diseases and disorders in which magnesium might be involved: hypertension and cardiovascular disease, type 2 diabetes, osteoporosis, and migraine headaches.

Hypertension and cardiovascular disease

Hypertension is a major risk factor for heart disease and stroke. Studies to date, however, have found that magnesium supplementation lowers blood pressure, at best, to only a small extent. A meta-analysis of 12 clinical trials found that magnesium supplementation for 8–26 weeks in 545 hypertensive participants resulted in only a small reduction (2.2 mmHg) in diastolic blood pressure [31]. The dose of magnesium ranged from approximately 243 to 973 mg/day. The authors of another meta-analysis of 22 studies with 1,173 normotensive and hypertensive adults concluded that magnesium supplementation for 3–24 weeks decreased systolic blood pressure by 3–4 mmHg and diastolic blood pressure by 2–3 mmHg [32]. The effects were somewhat larger when supplemental magnesium intakes of the participants in the nine crossover-design trials exceeded 370 mg/day. A diet containing more magnesium because of added fruits and vegetables, more low-fat or nonfat dairy products, and less fat overall was shown to lower systolic and diastolic blood pressure by an average of 5.5 and 3.0 mmHg, respectively [33]. However, this Dietary Approaches to Stop Hypertension (DASH) diet also increases intakes of other nutrients, such as potassium and calcium, that are associated with reductions in blood pressure, so any independent contribution of magnesium cannot be determined.

In 2022, FDA approved a qualified health claim for conventional foods and dietary supplements that contain magnesium [34]. One example of this claim states, “Consuming diets with adequate magnesium may reduce the risk of high blood pressure (hypertension). However, FDA has concluded that the evidence is inconsistent and inconclusive.” FDA also specifies that foods and dietary supplements carrying this claim on their labels must provide at least 84 mg of magnesium per serving and, for dietary supplements, no more than 350 mg.

Several prospective studies have examined associations between magnesium intakes and heart disease. The Atherosclerosis Risk in Communities study assessed heart disease risk factors and levels of serum magnesium in a cohort of 14,232 White and African-American men and women age 45 to 64 years at baseline [35]. Over an average of 12 years of follow-up, individuals in the highest quartile of the normal physiologic range of serum magnesium (at least 0.88 mmol/L) had a 38% reduced risk of sudden cardiac death compared with individuals in the lowest quartile (0.75 mmol/L or less). However, dietary magnesium intakes had no association with risk of sudden cardiac death. Another prospective study tracked 88,375 female nurses in the United States to determine whether serum magnesium levels measured early in the study and magnesium intakes from food and supplements assessed every 2 to 4 years were associated with sudden cardiac death over 26 years of follow-up [36]. Women in the highest compared with the lowest quartile of ingested and plasma magnesium concentrations had a 34% and 77% lower risk of sudden cardiac death, respectively. Another prospective population study of 7,664 adults age 20 to 75 years in the Netherlands who did not have cardiovascular disease found that low urinary magnesium excretion levels (a marker for low dietary magnesium intake) were associated with a higher risk of ischemic heart disease over a median follow-up period of 10.5 years. Plasma magnesium concentrations were not associated with risk of ischemic heart disease [37]. A systematic review and meta-analysis of prospective studies found that higher serum levels of magnesium were significantly associated with a lower risk of cardiovascular disease, and higher dietary magnesium intakes (up to approximately 250 mg/day) were associated with a significantly lower risk of ischemic heart disease caused by a reduced blood supply to the heart muscle [38].

Higher magnesium intakes might reduce the risk of stroke. In a meta-analysis of seven prospective trials with a total of 241,378 participants, an additional 100 mg/day magnesium in the diet was associated with an 8% decreased risk of total stroke, especially ischemic rather than hemorrhagic stroke [39]. One limitation of such observational studies, however, is the possibility of confounding with other nutrients or dietary components that could also affect the risk of stroke.

A large, well-designed clinical trial is needed to better understand the contributions of magnesium from food and dietary supplements to heart health and the primary prevention of cardiovascular disease [40].

Type 2 diabetes

Diets with higher amounts of magnesium are associated with a significantly lower risk of diabetes, possibly because of the important role of magnesium in glucose metabolism [41,42]. Hypomagnesemia might worsen insulin resistance, a condition that often precedes diabetes, or it might be a consequence of insulin resistance [43]. Diabetes leads to increased urinary losses of magnesium, and the subsequent magnesium inadequacy might impair insulin secretion and action, thereby worsening diabetes control [3].

Most investigations of magnesium intake and risk of type 2 diabetes have been prospective cohort studies. A meta-analysis of seven of these studies, which included 286,668 patients and 10,912 cases of diabetes over 6 to 17 years of follow-up, found that a 100 mg/day increase in total magnesium intake decreased the risk of diabetes by a statistically significant 15% [41]. Another meta-analysis of eight prospective cohort studies that followed 271,869 men and women over 4 to 18 years found a significant inverse association between magnesium intake from food and risk of type 2 diabetes; the relative risk reduction was 23% when the highest to lowest intakes were compared [44].

A 2011 meta-analysis of prospective cohort studies of the association between magnesium intake and risk of type 2 diabetes included 13 studies with a total of 536,318 participants and 24,516 cases of diabetes [45]. The mean length of follow-up ranged from 4 to 20 years. Investigators found an inverse association between magnesium intake and risk of type 2 diabetes in a dose-responsive fashion, but this association achieved statistical significance only in individuals who were overweight (body mass index [BMI] 25 or higher) but not in normal-weight individuals (BMI less than 25). Again, a limitation of these observational studies is the possibility of confounding with other dietary components or lifestyle or environmental variables that are correlated with magnesium intake.

Only a few small, short-term clinical trials have examined the potential effects of supplemental magnesium on control of type 2 diabetes and the results are conflicting [42,46]. For example, 128 patients with poorly controlled diabetes in a Brazilian clinical trial received a placebo or a supplement containing either 500 mg/day or 1,000 mg/day magnesium oxide (providing 300 or 600 mg elemental magnesium, respectively) [47]. After 30 days of supplementation, plasma, cellular, and urine magnesium levels increased in participants receiving the larger dose of the supplement, and their glycemic control improved. In another small trial in Mexico, participants with type 2 diabetes and hypomagnesemia who received a liquid supplement of magnesium chloride (providing 300 mg/day elemental magnesium) for 16 weeks showed significant reductions in fasting glucose and glycosylated hemoglobin concentrations compared with participants receiving a placebo, and their serum magnesium levels became normal [48]. In contrast, neither a supplement of magnesium aspartate (providing 369 mg/day elemental magnesium) nor a placebo taken for 3 months had any effect on glycemic control in 50 patients with type 2 diabetes who were taking insulin [49].

The American Diabetes Association states that there is insufficient evidence to support the routine use of magnesium to improve glycemic control in people with diabetes [46]. It further notes that there is no clear scientific evidence that vitamin and mineral supplementation benefits people with diabetes who do not have underlying nutritional deficiencies.

Osteoporosis

Magnesium is involved in bone formation and influences the activities of osteoblasts and osteoclasts [50]. Magnesium also affects the concentrations of both parathyroid hormone and the active form of vitamin D, which are major regulators of bone homeostasis. Several population-based studies have found positive associations between magnesium intake and bone mineral density in both men and women [51]. Other research has found that women with osteoporosis have lower serum magnesium levels than women with osteopenia and those who do not have osteoporosis or osteopenia [52]. These and other findings indicate that magnesium deficiency might be a risk factor for osteoporosis [50].

Although limited in number, studies suggest that increasing magnesium intakes from food or supplements might increase bone mineral density in postmenopausal and elderly women [1]. For example, one short-term study found that 290 mg/day elemental magnesium (as magnesium citrate) for 30 days in 20 postmenopausal women with osteoporosis suppressed bone turnover compared with placebo, suggesting that bone loss decreased [53].

Diets that provide recommended levels of magnesium enhance bone health, but further research is needed to elucidate the role of magnesium in the prevention and management of osteoporosis.

Migraine headaches

Magnesium deficiency is related to factors that promote headaches, including neurotransmitter release and vasoconstriction [54]. People who experience migraine headaches have lower levels of serum and tissue magnesium than those who do not.

However, research on the use of magnesium supplements to prevent or reduce symptoms of migraine headaches is limited. Three of four small, short-term, placebo-controlled trials found modest reductions in the frequency of migraines in patients given up to 600 mg/day magnesium [54]. The authors of a review on migraine prophylaxis suggested that taking 300 mg magnesium twice a day, either alone or in combination with medication, can prevent migraines [55].

In their evidence-based guideline update, the American Academy of Neurology and the American Headache Society concluded that magnesium therapy is probably effective for migraine prevention [56]. Because the typical dose of magnesium used for migraine prevention exceeds the UL, this treatment should be used only under the direction and supervision of a health care provider.

Health Risks from Excessive Magnesium

Too much magnesium from food does not pose a health risk in healthy individuals because the kidneys eliminate excess amounts in the urine [29]. However, high doses of magnesium from dietary supplements or medications often result in diarrhea that can be accompanied by nausea and abdominal cramping [1]. Forms of magnesium most commonly reported to cause diarrhea include magnesium carbonate, chloride, gluconate, and oxide [12]. The diarrhea and laxative effects of magnesium salts are due to the osmotic activity of unabsorbed salts in the intestine and colon and the stimulation of gastric motility [57].

Very large doses of magnesium-containing laxatives and antacids (typically providing more than 5,000 mg/day magnesium) have been associated with magnesium toxicity [58], including fatal hypermagnesemia in a 28-month-old boy [59] and an elderly man [60]. Symptoms of magnesium toxicity, which usually develop after serum concentrations exceed 1.74–2.61 mmol/L, can include hypotension, nausea, vomiting, facial flushing, retention of urine, ileus, depression, and lethargy before progressing to muscle weakness, difficulty breathing, extreme hypotension, irregular heartbeat, and cardiac arrest [29]. The risk of magnesium toxicity increases with impaired renal function or kidney failure because the ability to remove excess magnesium is reduced or lost [1,29].

The FNB has established ULs for supplemental magnesium for healthy infants, children, and adults (see Table 3) [1]. For many age groups, the UL appears to be lower than the RDA. This occurs because the RDAs include magnesium from all sources—food, beverages, dietary supplements, and medications. The ULs include magnesium from only dietary supplements and medications; they do not include magnesium found naturally in food and beverages.

Table 3: Tolerable Upper Intake Levels (ULs) for Supplemental Magnesium [1]
Age	Male	Female	Pregnant	Lactating
Birth to 12 months	None established	None established
1–3 years	65 mg	65 mg
4–8 years	110 mg	110 mg
9–18 years	350 mg	350 mg	350 mg	350 mg
19+ years	350 mg	350 mg	350 mg	350 mg

Interactions with Medications

Several types of medications have the potential to interact with magnesium supplements or affect magnesium status. A few examples are provided below. People taking these and other medications on a regular basis should discuss their magnesium intakes with their health care providers.

Bisphosphonates

Magnesium-rich supplements or medications can decrease the absorption of oral bisphosphonates, such as alendronate (Fosamax), used to treat osteoporosis [61]. Use of magnesium-rich supplements or medications and oral bisphosphonates should be separated by at least 2 hours [57].

Antibiotics

Magnesium can form insoluble complexes with tetracyclines, such as demeclocycline (Declomycin) and doxycycline (Vibramycin) as well as quinolone antibiotics, such as ciprofloxacin (Cipro) and levofloxacin (Levaquin). These antibiotics should be taken at least 2 hours before or 4–6 hours after a magnesium-containing supplement [57,62].

Diuretics

Chronic treatment with loop diuretics, such as furosemide (Lasix) and bumetanide (Bumex), and thiazide diuretics, such as hydrochlorothiazide (Aquazide H) and ethacrynic acid (Edecrin), can increase the loss of magnesium in urine and lead to magnesium depletion [63]. In contrast, potassium-sparing diuretics, such as amiloride (Midamor) and spironolactone (Aldactone), reduce magnesium excretion [63].

Proton pump inhibitors

Prescription proton pump inhibitor (PPI) drugs, such as esomeprazole magnesium (Nexium) and lansoprazole (Prevacid), when taken for prolonged periods (typically more than a year) can cause hypomagnesemia [64]. In cases that FDA reviewed, magnesium supplements often raised the low serum magnesium levels caused by PPIs. However, in 25% of the cases, supplements did not raise magnesium levels and the patients had to discontinue the PPI. FDA advises health care professionals to consider measuring patients’ serum magnesium levels prior to initiating long-term PPI treatment and to check magnesium levels in these patients periodically [64].

Magnesium and Healthful Diets

The federal government’s 2020–2025 Dietary Guidelines for Americans notes that “Because foods provide an array of nutrients and other components that have benefits for health, nutritional needs should be met primarily through foods. … In some cases, fortified foods and dietary supplements are useful when it is not possible otherwise to meet needs for one or more nutrients (e.g., during specific life stages such as pregnancy).”

For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for Americans and the USDA’s MyPlate.

The Dietary Guidelines for Americans describes a healthy dietary pattern as one that

Includes a variety of vegetables; fruits; grains (at least half whole grains); fat-free and low-fat milk, yogurt, and cheese; and oils.
- Whole grains and dark-green, leafy vegetables are good sources of magnesium. Low-fat milk and yogurt contain magnesium as well. Some ready-to-eat breakfast cereals are fortified with magnesium.
Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.
- Dried beans and legumes (such as soybeans, baked beans, lentils, and peanuts) and nuts (such as almonds and cashews) provide magnesium.
Limits foods and beverages higher in added sugars, saturated fat, and sodium.
Limits alcoholic beverages.
Stays within your daily calorie needs.

References

Institute of Medicine (IOM). Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride . Washington, DC: National Academy Press, 1997.
Rude RK. Magnesium. In: Coates PM, Betz JM, Blackman MR, Cragg GM, Levine M, Moss J, White JD, eds. Encyclopedia of Dietary Supplements. 2nd ed. New York, NY: Informa Healthcare; 2010:527-37.
Rude RK. Magnesium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, Mass: Lippincott Williams & Wilkins; 2012:159-75.
Volpe SL. Magnesium. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Ames, Iowa; John Wiley & Sons, 2012:459-74.
Elin RJ. Assessment of magnesium status for diagnosis and therapy. Magnes Res 2010;23:1-5. [PubMed abstract]
Gibson, RS. Principles of Nutritional Assessment, 2nd ed. New York, NY: Oxford University Press, 2005.
Witkowski M, Hubert J, Mazur A. Methods of assessment of magnesium status in humans: a systematic review. Magnesium Res 2011;24:163-80. [PubMed abstract]
Azoulay A, Garzon P, Eisenberg MJ. Comparison of the mineral content of tap water and bottled waters. J Gen Intern Med 2001;16:168-75. [PubMed abstract]
Fine KD, Santa Ana CA, Porter JL, Fordtran JS. Intestinal absorption of magnesium from food and supplements. J Clin Invest 1991;88:396-402. [PubMed abstract]
U.S. Department of Agriculture, Agricultural Research Service. FoodData Central , 2019.
U.S. Food and Drug Administration. Food Labeling: Revision of the Nutrition and Supplement Facts Labels. 2016.
Ranade VV, Somberg JC. Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther 2001;8:345-57. [PubMed abstract]
Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnes Res 2001;14:257-62. [PubMed abstract]
Mühlbauer B, Schwenk M, Coram WM, Antonin KH, Etienne P, Bieck PR, Douglas FL. Magnesium-L-aspartate-HCl and magnesium-oxide: bioavailability in healthy volunteers. Eur J Clin Pharmacol 1991;40:437-8. [PubMed abstract]
Lindberg JS, Zobitz MM, Poindexter JR, Pak CY. Magnesium bioavailability from magnesium citrate and magnesium oxide. J Am Coll Nutr 1990;9:48-55. [PubMed abstract]
Walker AF, Marakis G, Christie S, Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomized, double-blind study. Mag Res 2003;16:183-91. [PubMed abstract]
Spencer H, Norris C, Williams D. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. J Am Coll Nutr 1994;13:479-84. [PubMed abstract]
Guerrera MP, Volpe SL, Mao JJ. Therapeutic uses of magnesium. Am Fam Physician 2009;80:157-62. [PubMed abstract]
Phillips’®. Phillips’ Milk of Magnesia . 2020.
Rolaids®. 2012.
Tums®. 2012.
U.S. Department of Agriculture, Agricultural Research Service. Usual Nutrient Intake from Food and Beverages, by Gender and Age, What We Eat in America, NHANES 2013-2016 ; 2019.
Bailey RL, Fulgoni III VL, Keast DR, Dwyer JD. Dietary supplement use is associated with high intakes of minerals from food sources. Am J Clin Nutr 2011;94:1376-81. [PubMed abstract]
Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev 2012;70:153-64. [PubMed abstract]
Chaudhary DP, Sharma R, Bansal DD. Implications of magnesium deficiency in type 2 diabetes: a review. Biol Trace Elem Res 2010;134:119–29. [PubMed abstract]
Tosiello L. Hypomagnesemia and diabetes mellitus. A review of clinical implications. Arch Intern Med 1996;156:1143-8. [PubMed abstract]
Rivlin RS. Magnesium deficiency and alcohol intake: mechanisms, clinical significance and possible relation to cancer development (a review). J Am Coll Nutr 1994;13:416–23. [PubMed abstract]
Ford ES, Mokdad AH. Dietary magnesium intake in a national sample of U.S. adults. J Nutr 2003;133:2879-82. [PubMed abstract]
Musso CG Magnesium metabolism in health and disease. Int Urol Nephrol 2009;41:357-62. [PubMed abstract]
Barbagallo M, Belvedere M, Dominguez LJ. Magnesium homeostasis and aging. Magnes Res 2009;22:235-46. [PubMed abstract]
Dickinson HO, Nicolson D, Campbell F, Cook JV, Beyer FR, Ford GA, Mason J. Magnesium supplementation for the management of primary hypertension in adults. Cochrane Database of Systematic Reviews 2006: CD004640. [PubMed abstract]
Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr 2012;66:411-8. [PubMed abstract]
Champagne CM. Dietary interventions on blood pressure: the Dietary Approaches to Stop Hypertension (DASH) trials. Nutr Rev 2006;64:S53-6. [PubMed abstract]
U.S. Food and Drug Administration. RE: Petition for a qualified health claim for magnesium and reduced risk of high blood pressure (hypertension) (docket No. FDA-2016-Q-3770). January 10, 2022.
Peacock JM, Ohira T, Post W, Sotoodehnia N, Rosamond W, Folsom AR. Serum magnesium and risk of sudden cardiac death in the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J 2010;160:464-70. [PubMed abstract]
Chiuve SE, Korngold EC, Januzzi Jr JL, Gantzer ML, Albert CM. Plasma and dietary magnesium and risk of sudden cardiac death in women. Am J Clin Nutr 2011;93:253-60. [PubMed abstract]
Joosten MM, Gansevoort RT, Mukamal KJ, van der Harst P, Geleijnse JM, Feskens EJM, Navis G, Bakker SJL. Urinary and plasma magnesium and risk of ischemic heart disease. Am J Clin Nutr 2013;97:1299-306. [PubMed abstract]
Del Gobbo LC, Imamura F, Wu JHY, Otto MCdO, Chiuve SE, Mozaffarian D. Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 2013;98:160-73. [PubMed abstract]
Larsson SC, Orsini N, Wolk A. Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr 2012;95:362-6. [PubMed abstract]
Song Y, Liu S. Magnesium for cardiovascular health: time for intervention. Am J Clin Nutr 2012;95:269-70. [PubMed abstract]
Larsson SC, Wolk A. Magnesium intake and risk of type 2 diabetes: a meta-analysis. J Intern Med 2007;262:208-14. [PubMed abstract]
Rodriguez-Moran M, Simental Mendia LE, Zambrano Galvan G, Guerrero-Romero F. The role of magnesium in type 2 diabetes: a brief based-clinical review. Magnes Res 2011;24:156-62. [PubMed abstract]
Simmons D, Joshi S, Shaw J. Hypomagnesaemia is associated with diabetes: not pre-diabetes, obesity or the metabolic syndrome. Diabetes Res Clin Pract 2010;87:261-6. [PubMed abstract]
Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med 2007;167:956–65. [PubMed abstract]
Dong J-Y, Xun P, He K, Qin L-Q. Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies. Diabetes Care 2011;34:2116-22. [PubMed abstract]
Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Nwankwo R, Verdi CL, Urbanski P, Yancy WS Jr. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care 2013;36:3821-42. [PubMed abstract]
Lima MDL, Cruz T, Pousada JC, Rodrigues LE, Barbosa K, Canguco V. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care 1998;21:682-6. [PubMed abstract]
Rodriquez-Moran M, Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care 2003;26:1147-52. [PubMed abstract]
de Valk HW, Verkaaik R, van Rijn HJ, Geerdink RA, Struyvenberg A. Oral magnesium supplementation in insulin-requiring Type 2 diabetic patients. Diabet Med 1998;15:503-7 [PubMed abstract]
Rude RK, Singer FR, Gruber HE. Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr 2009;28:131–41. [PubMed abstract]
Tucker KL. Osteoporosis prevention and nutrition. Curr Osteoporos Rep 2009;7:111-7. [PubMed abstract]
Mutlu M, Argun M, Kilic E, Saraymen R, Yazar S. Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women. J Int Med Res 2007;35:692-5. [PubMed abstract]
Aydin H, Deyneli O, Yavuz D, Gözü H, Mutlu N, Kaygusuz I, Akalin S. Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women. Biol Trace Elem Res 2010;133:136-43. [PubMed abstract]
Sun-Edelstein C, Mauskop A. Role of magnesium in the pathogenesis and treatment of migraine. Expert Rev Neurother 2009;9:369–79 [PubMed abstract]
Schürks M, Diener H-C, Goadsby P. Update on the prophylaxis of migraine. Cur Treat Options Neurol 2008;10:20–9. [PubMed abstract]
Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults. Neurology 2012;78:1346-53. [PubMed abstract]
Natural Medicines Comprehensive Database . Magnesium. 2013.
Kutsal E, Aydemir C, Eldes N, Demirel F, Polat R, Taspnar O, Kulah E. Severe hypermagnesemia as a result of excessive cathartic ingestion in a child without renal failure. Pediatr Emerg Care 2007;23:570-2. [PubMed abstract]
McGuire JK, Kulkarni MS, Baden HP. Fatal hypermagnesemia in a child treated with megavitamin/megamineral therapy. Pediatrics 2000;105:E18. [PubMed abstract]
Onishi S, Yoshino S. Cathartic-induced fatal hypermagnesemia in the elderly. Intern Med 2006;45:207-10. [PubMed abstract]
Dunn CJ, Goa KL. Risedronate: A review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001;61:685-712. [PubMed abstract]
Arayne MS, Sultana N, Hussain F. Interactions between ciprofloxacin and antacids–dissolution and adsorption studies. Drug Metabol Drug Interact 2005;21:117-29. [PubMed abstract]
Sarafidis PA, Georgianos PI, Lasaridis AN. Diuretics in clinical practice. Part II: electrolyte and acid-base disorders complicating diuretic therapy. Expert Opin Drug Saf 2010;9:259-73. [PubMed abstract]
U.S. Food and Drug Administration. Proton Pump Inhibitor Drugs (PPIs): Drug Safety Communication—Low Magnesium Levels Can Be Associated With Long-Term Use. March 2, 2011.
sourced

How Rosemary Oil Can Help Your Hair

The Truth News — Wed, 03 May 2023 08:29:03 +0000

How Rosemary Oil Can Help Your Hair Grow

Studies show that the herby oil can lead to longer, healthier hair

The key to growing longer and healthier hair may come down to seasoning.

Using rosemary oil for hair growth exploded as a TikTok trend over the past year. Nearly a billion people on the social media app have watched hair-flipping testimonials on the benefits of the extract.

So, are those TikTokers onto something or should the savory herb be left as a dinner seasoning? Let’s comb through what’s fact or fiction with dermatologist Shilpi Khetarpal, MD.

Can rosemary oil help regrow hair?

The answer appears to be yes — and there’s scientific proof behind it.

Researchers found rosemary oil to be as effective at encouraging hair regrowth as minoxidil, a medication better known as Rogaine®, says Dr. Khetarpal. The 2015 study focused on people with androgenic alopecia (male pattern baldness or female pattern baldness).

Using rosemary oil instead of minoxidil also led to fewer issues with itchy scalp at the three-month and six-month check-ins.

“The bottom line is, yes, it does seem to work,” says Dr. Khetarpal. “The study really prompted people to look at rosemary oil for hair growth. It became much more common in over-the-counter products after that, too.”

The 2015 study built on findings from 2013 and 2010 that hinted at rosemary’s potential to combat hair loss.

What makes rosemary oil effective for hair growth?

So, why does rosemary oil act like Miracle-Gro® when rubbed onto your scalp as a highly concentrated extract? Much of the credit goes to carnosic acid, a phenolic chemical compound in the plant.

Carnosic acid carries anti-inflammatory and antioxidant properties that can help rejuvenate damaged nerves and tissue in your body. Applying it to your scalp creates an environment where your hair can thrive.

“If you increase blood flow to the scalp, you give your hair the nutrients it needs to shed less, grow more and just be a bit healthier,” explains Dr. Khetarpal.

Other benefits of rosemary oil

Aside from promoting a hair growth spurt, rosemary oil has been linked to hair benefits such as:

Dandruff control. Rosemary oil’s ability to limit skin inflammation and irritation also helps reduce dandruff (seborrheic dermatitis). “It helps calm things down on your scalp, which certainly assists with dandruff,” says Dr. Khetarpal.
Limiting premature graying. There’s some evidence that rosemary can help reduce stress, which has been shown to turn hair gray. “It’s a potential benefit, but more studies need to be done to determine its effect,” she adds.

How to use rosemary oil in your hair care routine

If you want to give rosemary oil a try to grow a thicker head of hair, Dr. Khetarpal offers these six tips and recommendations:

Focus on your scalp. Putting a coat of rosemary oil on your hair isn’t going to do anything aside from giving you a greasy look. “You want to apply it to the scalp as a treatment,” instructs Dr. Khetarpal. “Really focus on working it in.”
Give rosemary oil time to work. Let the rosemary oil sit and do its thing for at least a few hours. Dr. Khetarpal suggests using rosemary oil at night and then washing your hair in the morning.
Avoid fragranced products. Products with added fragrance may diminish the effectiveness of the rosemary oil or cause skin irritation. “Try to find something that’s 100% rosemary oil,” she says.
Start slow. Try rosemary oil on a small area of your scalp before coating your whole head with it. “That’s a good way to test to see if it causes a reaction on your skin.”
A little goes a long way. A few drops of rosemary oil may be all it takes for an application. It can be added to your shampoo or conditioner, too.
Be patient. One use of rosemary oil isn’t going to give you a bushy head of hair. “You’re going to need to use it two or three times a week for six months to see meaningful improvement,” notes Dr. Khetarpal. “Stay consistent and give it time.”

Does your hair type make a difference?

Coarse hair may be better able to handle an application of rosemary oil. But people with finer hair might find that using the product makes their locks look greasy or weighed down.

“Everyone can use rosemary oil, but you might need to modify how often you use it depending on your hair type,” suggests Dr. Khetarpal. “Some people might be able to use it daily. Others may see that one or twice a week works best.”

Are there side effects to using rosemary oil?

Although considered relatively safe to use, rosemary oil isn’t recommended if you’re pregnant or breastfeeding (chestfeeding). Warning labels on some 100% rosemary products warn that use could affect the fetus or lead to a miscarriage.

Final thoughts

Rosemary oil may be able to help if you’re dealing with hair loss. But Dr. Khetarpal cautions against expecting dramatic results.

“You want to be realistic,” she says. “If you’ve had hair loss for over 20 years, don’t expect it to work wonders. It might help a bit, particularly if your hair loss is just starting, but the extent of the improvement is variable. There are no guarantees.” source

Topically applied rosemary oil may help support hair growth and prevent hair loss. But applying too much can cause side effects.

Rosemary essential oil and hair

Rosemary is a culinary and healing herb. This woody perennial is native to the Mediterranean region, where it’s been used as food and medicine for centuries.

Much like oregano, peppermint, and cinnamon, rosemary is frequently found in essential oil form. Essential oils are highly concentrated and distilled extracts of volatile plant compounds. These are used for cooking, cleaning, beauty, health, and other purposes.

Rosemary essential oil is a common variety you can purchase and use as a home remedy. The oil’s health uses range from antioxidant benefits and anti-inflammation to memory enhancement and more.

In recent years, there have been claims that the oil may be great for hair growth. Some say it could even prevent hair loss, pointing to Mediterranean cultures’ use of rosemary in hair rinses to promote hair growth for hundreds of years as supporting evidence.

Can rosemary oil treat hair loss?

The idea that rosemary oil encourages hair growth may come from the rosemary’s basic health benefits. The plant in essential oil form is said to:

have anti-inflammatory properties
promote nerve growth
improve circulation

Like peppermint essential oil (also used to promote hair growth), rosemary essential oil strengthens circulation. As a result, it could prevent hair follicles from being starved of blood supply, dying off, and leading to hair loss.

Beyond stimulating hair growth, rosemary essential oil is used to prevent premature graying and dandruff. It may also help dry or itchy scalp.

Do studies support the claims?

According to some scientific evidence, rosemary may benefit nerve tissue.

Carnosic acid, an active ingredient in the plant, healed tissue and nerve damage in one study. This ability to heal nerve endings may rejuvenate nerves in the scalp too, in turn possibly restoring hair growth.

More revealing recent studies show that rosemary directly helps protect against hair loss. One 2015 trialTrusted Source pitted the essential oil against minoxidil, commercially known as Rogaine. Both were used on human subjects with androgenetic alopecia (male or female pattern baldness).

Results showed that rosemary essential oil was just as effective a minoxidil. During the process, it helped the side effect of itchy scalp more successfully than minoxidil.

Another studyTrusted Source of rosemary leaf extract (different from the essential oil) showed it stimulated hair growth. This occurred when hair loss was triggered by testosterone (as in pattern baldness). This study was performed on mice, however.

Two separate clinical reviews — one from 2010Trusted Source and one from 2011 — also acknowledge rosemary’s hair growth potential. The former cites a study with successful hair regrowth in people with alopecia who used essential oils. One of these essential oils was rosemary.

In the latter review, rosemary essential oil was described as a hair loss restorative. This was due to its circulation-improving effects.

How should I use rosemary oil for hair loss?

Here are a few ways to try using rosemary essential oil as a hair restorative and thickener. Try any of these treatments one to two times per week to start out. Use them more often when desired or you’ve become comfortable using them.

1. Massage it directly into your scalp

After mixing about 5 drops of rosemary essential oil with a teaspoon of carrier oil (like jojoba oil or coconut oil), massage evenly into your scalp after bath or shower. Rinsing out the oil afterward is optional — though if you do rinse, let the oil sit on your scalp for at least 5 to 10 minutes beforehand.

2. Mix it into your shampoo

This can also apply to conditioners, lotions, or creams. Play it safe and don’t add too much. Keep to about five drops per ounce of product. Afterward, use the product like usual. You can also add 2 to 3 drops directly to any hair product when you apply a dollop of it on your palm before use.

3. Add it to your own homemade shampoo

There are many recipes online for a shampoo base. You can also add essential oils for your preferred health and beauty benefits. These may incorporate a mixture of baking soda, coconut oil, essential oil, and possibly other oils. Try this one at Tiny Apothecary.

What should I know before using rosemary oil?

Avoid getting essential oil in your eyes. If contact occurs, quickly rinse your eyes with cold water.

Likewise, be careful not to apply too much to your scalp. Rosemary essential oil has been known to irritate the skin. It may cause discomfort, but no health dangers. To avoid skin irritation, dilute the oil with a carrier oil or other product before applying it.

Not enough is known about the safety of using rosemary essential oils while pregnant or breastfeeding. Though using the essential oil for hair loss is only done topically, be cautious — its effects in this regard are still unknown.

The bottom line

Rosemary has been used by many to promote hair growth successfully. Using rosemary essential oil could very well do the same for you.

Science and personal experience together both strongly suggest the essential oil does protect against hair loss, particularly that related to male or female pattern baldness. It may even be effective for alopecia.

Rosemary essential oil is a simple remedy that you can use at home, and it may even be competitive with commercial products. What’s more, it’s quite safe when used correctly and yields very few side effects. source

What to Know About Rosemary Oil for Hair Growth, According to Experts

While seasoning a winter soup with a sprinkle of dried rosemary, you probably don’t think of the herb as a hair-transforming ingredient. But, in oil form, rosemary is on the rise as a staple for hair growth, strength, and shine. Curious to learn how it works? Ahead, dermatologists and hair stylists explain the benefits of rosemary oil for hair, how to use it, potential side effects, and more.

Rosemary oil for hair benefits

Rosemary oil is most touted as an encourager of hair growth. “It has been clinically shown to increase hair growth similar to minoxidil, the main active ingredient in Rogaine,” says Ramya Garlapati, M.D., a board-certified dermatologist based in Los Angeles. “It stimulates hair growth by blocking the effects of DHT, a type of testosterone that is normally responsible for shrinking hair follicles that can lead to hair loss.”

Dr. Garlapati adds that rosemary oil also stimulates blood flow to the hair follicles, “which increases the delivery of oxygen and nutrients, promoting hair growth,” and it has naturally anti-inflammatory and antimicrobial properties, making it ideal for helping irritation caused by flaking and dandruff.

As an oil, it also inherently provides a bit of moisture and shine, which can help prevent breakage, adds Sabrina Rowe Holdsworth, celebrity hairstylist and founder of NTRL by Sabs.

What are the side effects of rosemary oil on hair?

Because it’s a pretty potent ingredient, for some, excess use of rosemary oil may lead to some itching and burning, says Holdsworth. “It can cause mild irritation of the scalp and should be discontinued if this is experienced,” adds Garlapati.

With that being said, Dr. Garlapati says the oil is safe for all hair types, including color-treated hair.

How to dilute rosemary oil for hair

To DIY your own diluted rosemary oil hair treatment, Dr. Doyle recommends mixing two tablespoons of your carrier oil of choice (she recommends jojoba) with two to three drops of rosemary oil. Apply the mixture to the scalp and “leave on for an hour before washing,” Doyle adds.

How often should I put rosemary oil in my hair?

Holdsworth says rosemary oils and infused shampoos may be used a few times a week, unless you have an adverse reaction. “I suggest starting with two to three times a week and if well tolerated, working up to daily,” adds Schmidt. “Consistent use always yields the best results.”

source

Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial

Yunes Panahi, Mohsen Taghizadeh, Eisa Tahmasbpour Marzony, Amirhossein Sahebkar

PMID: 25842469

Abstract

Rosmarinus officinalis L. is a medicinal plant with diverse activities including enhancement microcapillary perfusion. The present study aimed to investigate the clinical efficacy of rosemary oil in the treatment of androgenetic alopecia (AGA) and compare its effects with minoxidil 2%. Patients with AGA were randomly assigned to rosemary oil (n = 50) or minoxidil 2% (n = 50) for a period of 6 months. After a baseline visit, patients returned to the clinic for efficacy and safety evaluations every 3 months. A standardized professional microphotographic assessment of each volunteer was taken at the initial interview and after 3 and 6 months of the trial. No significant change was observed in the mean hair count at the 3-month endpoint, neither in the rosemary nor in the minoxidil group (P > .05). In contrast, both groups experienced a significant increase in hair count at the 6-month endpoint compared with the baseline and 3-month endpoint (P < .05). No significant difference was found between the study groups regarding hair count either at month 3 or month 6 (> .05). The frequencies of dry hair, greasy hair, and dandruff were not found to be significantly different from baseline at either month 3 or month 6 trial in the groups (P > .05). The frequency of scalp itching at the 3- and 6-month trial points was significantly higher compared with baseline in both groups (P < .05). Scalp itching, however, was more frequent in the minoxidil group at both assessed endpoints (P < .05). The findings of the present trial provided evidence with respect to the efficacy of rosemary oil in the treatment of AGA.

Cited by

Rosmarinus officinalis and Skin: Antioxidant Activity and Possible Therapeutical Role in Cutaneous Diseases.

Li Pomi F, Papa V, Borgia F, Vaccaro M, Allegra A, Cicero N, Gangemi S.Antioxidants (Basel). 2023 Mar 9;12(3):680. doi: 10.3390/antiox12030680.PMID: 36978928 Free PMC article. Review.
Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss.

Natarelli N, Gahoonia N, Sivamani RK.J Clin Med. 2023 Jan 23;12(3):893. doi: 10.3390/jcm12030893.PMID: 36769541 Free PMC article. Review.
Complementary Strategies to Promote Hair Regrowth in Post-COVID-19 Telogen Effluvium.

Popescu MN, Berteanu M, Beiu C, Popa LG, Mihai MM, Iliescu MG, Stănescu AMA, Ionescu AM.Clin Cosmet Investig Dermatol. 2022 Apr 22;15:735-743. doi: 10.2147/CCID.S359052. eCollection 2022.PMID: 35497690 Free PMC article. Review.
Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics.

Nestor MS, Ablon G, Gade A, Han H, Fischer DL.J Cosmet Dermatol. 2021 Dec;20(12):3759-3781. doi: 10.1111/jocd.14537. Epub 2021 Nov 6.PMID: 34741573 Free PMC article. Review.
The Use of Natural Ingredients in the Treatment of Alopecias with an Emphasis on Central Centrifugal Cicatricial Alopecia: A Systematic Review.

Ezekwe N, King M, Hollinger JC.J Clin Aesthet Dermatol. 2020 Aug;13(8):23-27. Epub 2020 Aug 1.PMID: 33178378

source

What Is Iodine? – Uses, Side Effects, and More

The Truth News — Sat, 15 Jan 2022 21:07:09 +0000

What Is Iodine? – Uses, Side Effects, and More

Iodine is an essential mineral, meaning your body needs it to function properly. You can’t produce it independently and must ingest it through your diet or as a supplement.

Iodine is important for thyroid function. The thyroid is a butterfly-shaped organ in your neck that produces hormones that regulate bodily activities, like metabolism (the conversion of food to energy).

You can find iodine in foods, but amounts can be hard to identify. Iodized salt is the primary source of this mineral in the United States. Most people should regularly use salt enriched with iodine to get enough in their diet.1

What is Iodine and How Does the Supplement Work?

This article discusses the benefits of iodine and how much iodine you need. It also covers what happens when you get too little or too much iodine.

However, even if supplements are third-party tested, that doesn’t mean that they are necessarily safe for all people or effective in general. It is important to talk to your healthcare provider about any supplements you plan to take and to check in about any potential interactions with other supplements or medications.

Supplement Facts

Active ingredient(s): Potassium iodide, sodium iodide
Alternate name(s): N/A
Legal status: Available over the counter (OTC) and by prescription
Suggested dose: 90-130 micrograms per day for children, 150 micrograms per day for adults (and teens 14-18), 220 micrograms per day during pregnancy
Safety considerations: Excessive iodine can impact the thyroid and lead to goiter, high TSH levels, and hypothyroidism; supplements can interact with some thyroid medications, ACE inhibitors, and diuretics

Uses of Iodine

Iodine is an essential part of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) made by your thyroid gland. Both of these hormones contain iodide (a form of iodine).2 Thyroid hormones have the following functions in the body:3

Help cells make protein
Regulate activity of enzymes (proteins that create chemical reactions in the body)
Determine metabolism

For the most part, people take iodine to prevent or treat iodine deficiency, which can cause problems with fetal development, cognitive function, and thyroid function. In addition, some people use iodine for fibrocystic breasts and to prevent thyroid cancer when exposed to radiation. Some of these uses are better supported by research than others.

Fetal Development

Since 50% more iodine is required during pregnancy to meet fetal developmental needs, some research has examined how iodine deficiency impacts fetal development.3

For example, in a 2013 study published in Lancet, researchers evaluated the effect of insufficient iodine in pregnancy on cognitive outcomes in children.4 Researchers measured urinary iodine concentration in 1,040 pregnant participants during the first trimester. Later, they also measured the children’s intelligence quotient (IQ) at age 8.

Compared to those with adequate iodine, those with mild-to-moderate iodine deficiency were more likely to have the lowest scores for verbal IQ, reading accuracy, and reading comprehension.

In addition, a 2019 study published in Nutrients evaluated educational outcomes in adolescents whose gestational parents had mild iodine deficiency in pregnancy.5

First, researchers assessed the iodine concentration of 266 pregnant people attending antenatal clinics at the Royal Hobart Hospital in Australia from 1999 to 2000. Then, researchers compared their children’s standardized test scores in literacy and math when they were ages 8–9, 10–11, 12–13, and 14–15 years.

The study found that even mild iodine deficiency in pregnancy had long-term cognitive effects. However, these effects did not resolve with sufficient iodine intake during childhood. For example, children whose parents had iodine deficiency in pregnancy had reduced scores in reading, spelling, and grammar, independent of other factors known to impact learning.

Fibrocystic Breasts

Fibrocystic breasts are a benign condition where breast tissue is lumpy. Since breast tissue has a high concentration of iodine, some research has evaluated whether the mineral could be helpful in fibrocystic breasts.3

For example, in a 2018 study published in the Journal of Women’s Health, researchers evaluated whether a nutritional supplement including iodine could decrease cyclical breast pain and nodules.6 The randomized, multi-center, controlled, double-blind trial included 188 participants.

Researchers randomized participants to receive either a nutritional formula containing 1 gram (g) gamma-linolenic acid (GLA), 750 micrograms (mcg) iodine, and 70 mcg selenium, or a placebo daily for three menstrual cycles. While breast pain decreased in both groups, nodules decreased in the supplement group but not in the control group.

Radiation-Induced Thyroid Cancer

Nuclear accidents can release radioactive iodine (Iodine-131) into the environment, increasing the risk of thyroid cancer in those exposed. Therefore, some research has evaluated whether iodine supplementation could reduce cancer risk in high-risk populations following some historic nuclear disasters.

For example, in 1993, the American Journal of Medicine published a study examining the benefits and risks of iodide supplements in Poland following the 1986 Chernobyl nuclear power plant meltdown.7 That study found that where potassium iodide was widely used, thyroid cancer rates did not increase substantially in the following years. On the other hand, in Belarus and Ukraine, where people did not use iodine supplements, thyroid cancer increased significantly among children and adolescents.

FDA Recommendations

The FDA recommends potassium iodide as a thyroid blocking agent in nuclear emergencies.8

Other

Other uses mainly include managing thyroid conditions caused by an iodine deficiency. Those uses are explored more below.

Iodine Deficiency

If your iodine intake falls below 10–20 mcg/day, you may become deficient. Iodine deficiency leads to problems with thyroid hormone production, which can result in thyroid disease, including goiter (enlarged thyroid) and hypothyroidism (underactive thyroid).

In addition, iodine deficiency can lead to cognitive disabilities in children whose gestational parents did not have adequate intake during pregnancy.1

What Causes an Iodine Deficiency?

Since the body does not make iodine on its own, you need to obtain enough of it in your diet. If you do not get enough iodine through diet or supplements, you may become deficient.

Since the introduction of iodized salt, iodine deficiency has been rare in the U.S. However, some groups are at increased risk for a deficiency, including:3

People who don’t use iodized salt
Pregnant people
Vegans
Those with marginal iodine status who eat goitrogens (foods that interfere with the uptake of iodine in the thyroid)

Some goitrogens include broccoli, cabbage, cauliflower, kale, and strawberries. If you have normal thyroid function and iodine intake, you don’t need to worry about these foods causing an iodine deficiency.

How Do I Know If I Have an Iodine Deficiency?

Goiter is often the first clinical sign of iodine deficiency. A goiter is an enlarged thyroid that is sometimes visible or palpable through the neck. This enlargement happens because the thyroid grows so it can try to absorb as much iodine as possible.

Goiter symptoms include:9

Neck lump
Throat tightness
Coughing
Hoarseness
Trouble breathing or swallowing

In addition, if you have iodine deficiency, you may develop hypothyroidism. This happens because the thyroid has too little iodine to make thyroid hormone.

Hypothyroidism can cause a variety of symptoms, including:10

Weight gain
Diminished energy
Sleepiness
Dry skin
Trouble concentrating
Depression
Constipation
Feeling cold all the time

Children with hypothyroidism may experience the same effects as adults and additional symptoms, including slow physical growth, mood problems, trouble concentrating, and learning difficulties.11

Newborn screening tests can detect iodine deficiency in infants. Deficiency may cause babies to develop congenital hypothyroidism. Symptoms may include trouble eating, being excessively sleepy, or having constipation. Sometimes, it may not cause any symptoms at all.12

What Are the Side Effects of Iodine?

Your provider may recommend you take iodine during pregnancy or for deficiency. However, consuming a supplement like iodine may have potential side effects. These side effects may be common or severe.

Common Side Effects

In general, moderate iodine consumption from iodized salt or the food in your diet shouldn’t cause problems. That is because the body eliminates extra iodine through the urine.3

Allergies and sensitivities to iodine have been reported. However, more recent research suggests that iodine allergies may actually be due to another substance and not iodine. Usually, this occurs with exposure to iodine contrast material for medical testing, not from iodine supplements.

For example, a 2021 review in the American Journal of Health System Pharmacy looked at common misperceptions of iodine allergy.13 Researchers found that among 81 articles, iodine was not seen as the allergen responsible for allergic reactions to iodinated contrast media, amiodarone (a drug that regulates heart rate), povidone-iodine (antiseptic skin disinfectant used before surgery), and other iodine-containing compounds.

Mild allergic reactions to iodine contrast materials include:14

Headache
Nausea
Hives
Rash
Sweating

Severe Side Effects

Although rare, allergic reactions can also be severe. Anaphylaxis is a life-threatening emergency that can occur without warning due to exposure to an allergen. Symptoms include:15

Hives
Throat swelling
Wheezing
Unconsciousness
Hoarseness
Trouble swallowing
Vomiting
Diarrhea
Face flushing

If you experience any of the above symptoms, it is critical to seek emergency medical care immediately.

Precautions

Iodine supplements may interact with some medications, including:3

Anti-thyroid drugs used to treat hyperthyroidism (overactive thyroid)
Angiotensin-converting enzyme (ACE) inhibitors used to treat high blood pressure and heart disease
Potassium-sparing diuretics, such as Aldactone (spironolactone) and Midamor (amiloride)

If you take any medications, talk to a healthcare provider or pharmacist about the safety of any supplements you consider taking.

Dosage: How Much Iodine Should I Take?

Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs.

Since your body produces thyroid hormones on an ongoing basis, all children and adults need to consume iodine regularly. In addition, pregnant people need higher amounts to support the developing fetus.

The United States Institute of Medicine recommends the amount of iodine a person should ingest daily.3

110 micrograms (mcg) per day for infants birth-6 months
130 mcg per day for infants 7-12 months
90 mcg per day for kids 1-8 years
120 mcg per day for kids 9-13
150 mcg per day for adults and teens over 14
220 mcg per day during pregnancy
290 mcg during lactation

You can not measure iodine levels in the blood, but you can measure it in the urine. Normal urinary iodine concentrations range between 100 and 200 micrograms per liter. Values lower than 20 micrograms per liter suggest inadequate iodine intake.3

Medical Use

Radioactive iodine is a medical treatment for conditions like thyroid cancer or goiter. It works by destroying overactive thyroid tissue or thyroid cancer cells.16

This treatment comes as a prescription pill and requires a special low iodine diet one to two weeks before starting treatment.

Radioactive iodine can be harmful to others, so healthcare providers recommend precautions to protect other people. Precautions include maintaining distance from other people while your body gives off radiation.

What Happens If I Take Too Much Iodine?

You can consume more iodine than your body can handle by using supplements that contain high doses of iodine. Chronic iodine overdose is associated with goiter, hyperthyroidism (overactive thyroid), thyroiditis (thyroid inflammation), and thyroid cancer.3

Toxicity is rare but can occur from consuming heavy doses (usually many grams) of iodine supplements. Signs of iodine poisoning include:

Mouth, throat, or stomach burning
Fever
Abdominal pain
Nausea
Vomiting
Diarrhea
Weak pulse
Coma

To avoid toxicity, be aware of the appropriate dosage (above) and stay below the safe upper limit established by the Institute of Medicine.3

200 mcg for children 1-3 years

300 mcg for children 4-8 years

600 mcg for kids 9-13 years

900 mcg for teens 14-18 years

1,100 mcg for all adults, including those who are pregnant and lactating

If you consume more than these amounts or more than what is recommended by your healthcare provider, you may want to go to the emergency room.

How to Store Iodine

Store iodine in a cool, dry place. Keep it away from direct sunlight. Discard after one year or as indicated on the packaging.

What is an iodine solution?

An iodine solution is a topical iodine preparation that sterilizes the skin to prevent infection. Potassium iodide (KI), used in radioactive emergencies, is also available as a solution.17

Learn More: How Is Radiation Sickness Treated?
Can iodine deficiency cause low energy levels?

Iodine deficiency can affect your thyroid hormone levels, causing low energy. However, iodine deficiency does not independently affect energy levels. Instead, the lack of iodine reduces the thyroid’s ability to produce thyroid hormone, which can cause a range of symptoms, including low energy.

Learn More: Thyroid Blood Tests
Can eating salty foods cause iodine toxicity?

Eating salty foods should not cause iodine toxicity. The body will automatically eliminate excess iodine when you urinate. However, consuming excess iodine supplements is not safe and can lead to toxicity. Signs of iodine poisoning include an upset stomach, mouth and throat burning, diarrhea, and vomiting.

Sources of Iodine and What To Look For

Iodine is found in food sources and is also available as a supplement. Most people can meet their iodine needs through food sources.

Food Sources of Iodine

The most common source of iodine is iodized salt, which contains 76 mcg (51% of the daily recommended intake for adults) in a quarter teaspoon. However, this concentration may differ depending on the manufacturer. For precise amounts, check the label’s nutritional information.

In addition, plenty of foods contain iodine. Fish and seaweed are the foods richest in iodine. For example, one 3-ounce serving of cod contains about 158 mcg of iodine, and one serving of seaweed contains about 116 mcg of iodine. Other iodine-rich foods include:3

Bread made with iodate dough
Oysters
Yogurt
Milk
Enriched pasta boiled in iodized salt
Eggs

Supplements

Vitamins and supplements vary in their iodine content. You can find the specific amount of iodine on the label. Talk with your healthcare provider before taking a supplement.

Iodine supplements most often come as potassium iodide or sodium iodide. Some iodine supplements are also sourced from kelp (seaweed).3 They are available in drops, capsules, and tablets. If you are vegan or have food allergies, read labels carefully to ensure there are no animal products or allergens.

Iodine is quickly absorbed in the stomach and small intestine. Next, it travels through the bloodstream. From there, iodine receptors located in the thyroid bind to it and take it in.

Do not use iodine supplements unless you are diagnosed with iodine deficiency. If you need iodine supplements, your healthcare provider will give you a prescription. You might be able to use an OTC supplement. If so, verify that the dose is exactly as prescribed by your healthcare provider.

Summary

Iodine is a mineral your body needs for producing thyroid hormones. These hormones have essential roles in regulating body weight and maintaining energy.

Iodine deficiency can lead to hypothyroidism, where the thyroid doesn’t produce enough hormones. It can also cause an enlarged thyroid, called a goiter.

Common sources of iodine include salt, supplements, and foods like vegetables and seafood. Consult a healthcare provider before taking any supplements.

A Word From Verywell

Iodine deficiency is rare in countries where iodized salt is regularly used. However, if you have a thyroid problem, a healthcare provider may instruct you to maintain a low iodine diet or supplement your diet with iodine.

If you’ve had an iodine deficiency in the past, check with your doctor about regular monitoring of your thyroid hormone levels. Regular check-ups are the best way to know whether you are getting enough iodine.

10 Uses for Iodine: Do Benefits Outweigh the risks?

What is iodine?

Also called iodide, iodine is a type of mineral that’s naturally found in the earth’s soil and ocean waters. Many salt water and plant-based foods contain iodine, and this mineral is most-widely available in iodized salt.

It’s important to get enough iodine in the diet. It regulates hormones, fetal development, and more.

If your iodine levels are low, your doctor might recommend supplementation. You shouldn’t take supplements without checking with your doctor first.

Read on to learn more about the uses and side effects of iodine, plus recommended daily amounts by age.

10 uses of iodine

Iodine is considered an essential mineral for our bodies. It’s particularly important during pregnancy, and exposure in the womb may even help prevent certain health conditions later in life.

The following is a list of some of the most important uses and how they benefit the body.

1. Promoting thyroid health

Iodine plays a vital role in thyroid health. Your thyroid gland, which is located at the base of the front of your neck, helps regulate hormone production. These hormones control your metabolism, heart health, and more.

To make thyroid hormones, your thyroid takes up iodine in small amounts. Without iodine, thyroid hormone production can decrease. A “low” or underactive thyroid gland can lead to a condition called hypothyroidism.

Given the wide availability of iodine in western diets, thyroid health isn’t typically impacted by low iodine levels in the United States.

You can get enough iodine from your diet by eating dairy products, fortified foods, and salt water fish. Iodine is also available in plant foods that grow in naturally iodine-rich soil. You also can get the mineral by seasoning your food with iodized salt.

While iodine promotes overall thyroid health, too much iodine can have a negative effect on the thyroid gland. That’s why you shouldn’t take iodine supplements without your doctor’s recommendation.

2. Reducing risk for some goiters

A goiter is an enlarged thyroid gland. Your thyroid may become enlarged as a result from either hypothyroidism or hyperthyroidism. Hyperthyroidism is an overactive thyroid gland.

Non-cancerous thyroid nodules (cysts) can also cause thyroid gland enlargement.

Sometimes a goiter develops as a direct response to iodine deficiency. This is the most common cause of goiter worldwide, though it’s not as common a cause in the United States and other countries with access to iodine-rich foods.

Iodine-induced goiters may be reversed by adding iodine-rich foods or supplements in the diet.

3. Managing overactive thyroid gland

Your doctor may recommend a special type of iodine called radioactive iodine to treat an overactive thyroid gland. Also called radioiodine, this medication is taken by mouth. It’s used to destroy extra thyroid cells to help reduce excessive amounts of thyroid hormone.

The risk with radioactive iodine is that it can destroy too many thyroid cells. This can decrease the amount of hormone production, leading to hypothyroidism. For this reason, radioactive iodine is usually only recommended after anti-thyroid drugs have failed.

Radioactive iodine is not the same thing as iodine supplements. You should never take iodine supplements for hyperthyroidism.

4. Treating thyroid cancer

Radioiodine may also be a possible treatment option for thyroid cancer. It works in much the same way as hyperthyroid treatment.

When you take radioactive iodine orally, the medication destroys thyroid cells, including cancerous ones. It may be used as a treatment following thyroid surgery to make sure all cancerous cells have been removed from the body.

According to the American Cancer SocietyTrusted Source, radioactive iodine treatments significantly improve the chances of survival for people with thyroid cancer.

5. Neurodevelopment during pregnancy

You need more iodine in pregnancy. That’s because iodine intake during pregnancy is linked to brain development in fetuses. One reviewTrusted Source found that babies whose birth mothers had an iodine deficiency during pregnancy were more likely to grow up with lower IQ’s and other intellectual delays.

The recommended daily intakeTrusted Source of iodine during pregnancy is 220 mcg. By comparison, the recommended amount in non-pregnant adults is 150 mcg a day.

If you’re pregnant, ask your doctor about iodine supplementation, especially if your prenatal vitamin doesn’t have iodine (many do not). Iodine supplements may also be necessary if you’re deficient in the mineral.

You’ll also need to continue monitoring your iodine intake if you’re breastfeeding. The recommended daily amount of iodine while nursing is 290 mcg. That’s because the iodine you take up from diet and supplementation is transferred via breast milk to your nursing infant. This is a crucial brain developmental period, so infants need 110 mcg per day until they’ve reached 6 months of ageTrusted Source.

6. Improving cognitive function

The same neurological benefits of iodine during pregnancy may extend to healthy brain function during childhood. This also includes a reduced riskTrusted Source of intellectual disability.

It is likely your child gets all the iodine they need through their diet, but if you have any questions about their iodine intake, talk to their pediatrician.

7. May help treat fibrocystic breast disease

It’s possible that iodine supplements or medications can help treat fibrocystic breast disease. This non-cancerous condition is most common in women of reproductive age, and it can cause painful breast lumps.

Although there is some promise that iodine might help with fibrocystic breast cysts, you shouldn’t attempt self-treatment. Only take iodine for this condition if your doctor specifically recommends it. Otherwise, you could be at risk of side effects from iodine toxicity.

8. Disinfecting water

Iodine is just one method of water disinfection. This may be especially helpful if you don’t have access to potable water due to traveling or effects from a natural disaster.

Two percent liquid iodine tincture may be added to water in five-drop increments per one quart of clear water. If the water is cloudy, add ten drops per quart.

Iodine tablets may also be used, but the instructions can vary by manufacturer.

Despite the role iodine can play in disinfecting drinking water, there’s also some concerns that it can increase total iodine intake in humans and lead to adverse health effects. Total iodine intake shouldn’t exceed 2 mg per dayTrusted Source.

9. Protection from nuclear fallout

In the case of nuclear emergencies, the Centers for Disease Control and Prevention recommends the use of potassium iodide (KI) to protect the thyroid gland from radiation injuries. These are available in tablet and liquid formulas.

While not completely foolproof, the sooner KI is taken, the better the thyroid is thought to be protected in the event of this kind of emergency.

There are serious risks associated with KI, including gastrointestinal upset, inflammation, and allergic reaction. You’re also at increased risk for thyroid disease. Your risk for complications is higher if you already have thyroid disease.

10. Treating infections

Iodine can be used topically in a liquid form to help treat and prevent infections. It works by killing bacteria in and around mild cuts and scrapes.

Topical iodine should not be used on newborn babies. It should also not be used for deep cuts, animal bites, or burns.

Follow directions on the packaging for dosage information, and do not use for more than 10 days unless directed by your doctor.

How much iodine do you need?

To reduce our risk for iodine deficiency, the National Institutes of HealthTrusted Source (NIH) has the following recommendations for daily intake based on age:

Age	Daily recommended amount in micrograms (mcg)
birth–6 months	110 mcg
infants between 7–12 months	130 mcg
children 1–8 years old	90 mcg
children 9–13 years old	120 mcg
adults and teens, 14 and older	150 mcg
pregnant women	220 mcg
nursing women	290 mcg

Side effects of iodine

Possible side effects from too much iodine include:

nausea or vomiting
diarrhea
fever
burning sensations in the throat and mouth
stomach pain

In more severe cases, iodine toxicity may lead to coma.

You shouldn’t take iodine if you have a thyroid condition, unless recommended by your doctor.

Young children and the elderly are more prone to iodine side effects.

Micronutrient Testing is REQUIRED to know if you are deficientm consult a doctor !

Symptoms of iodine deficiency

Iodine deficiency can only be diagnosed via urine tests.

The symptoms of low iodine levels are primarily detected through thyroid symptoms, such as:

a visible goiter
thyroid gland that’s painful or tender to the touch
breathing difficulties, especially when lying down
difficulty swallowing
fatigue
extreme feelings of coldness, despite normal temperatures
hair loss
depression
brain fog
unintentional weight gain

Who should take iodine?

Your doctor might recommend iodine supplements if your levels are low. The only way to know for certain is by checking your levels through a urine test. After that point, your doctor may recommend a supplement.

Iodine is available in stronger formulas through a prescription. However, these are used for serious health conditions only. For example, your doctor may recommend prescription-strength iodine if you’ve been exposed to radiation or have an overactive thyroid gland.

If you suspect you need iodine support, check with your doctor to see if you’re a candidate.

Takeaway

Iodine is an essential nutrient. People with access to iodized salt, seafood, and certain vegetables are able to get enough iodine from their diet.

In some cases, you may need iodine supplementation to help reduce your risk for iodine deficiency, or as a treatment for certain medical conditions, such as underactive thyroid or goiter.

Talk to your doctor about your specific iodine needs.

Overview

Iodine is an element that is used by the thyroid. Humans cannot produce iodine, so it must be consumed. It is added to some foods and also to salt.

Iodine reduces thyroid hormone and can kill fungus, bacteria, and other microorganisms such as amoebas. Iodine deficiency is one of the most common and preventable world health problems. Most iodine is found in the ocean, where it is concentrated by sea life, particularly in seaweed.
Iodine is taken by mouth to prevent and treat iodine deficiency and its consequences, including goiter and some thyroid disorders. A specific kind of iodine called potassium iodide is also US FDA approved to prevent thyroid damage after a radioactive accident. Iodine is also used for pink eye, gum infections, wound healing, and many other conditions, but there is limited scientific evidence to support many of these uses.

CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.

This copyrighted material is provided by Natural Medicines Comprehensive Database Consumer Version. Information from this source is evidence-based and objective, and without commercial influence. For professional medical information on natural medicines, see Natural Medicines Comprehensive Database Professional Version.
© Therapeutic Research Faculty 2020.

Soruce 1 Soruce 2 Source 3 Source 4

9 Health Benefits of Ashwagandha; What is it?

The Truth News — Sat, 08 Jan 2022 07:41:07 +0000

Ashwagandha

Ashwagandha is a nontoxic herb gaining attention in the U.S. for its ability to modulate stress and anxiety. The herb is an important part of centuries-old Ayurveda, the traditional system of medicine in India, and is used to treat a range of conditions, such as rheumatism and insomnia^[1].

“[Its] physiologic effects… are interrelated,” says Andrea Fossati, M.D., an integrative healthcare specialist in Vermont. “For example, less stress equals lower cortisol levels, which equals better blood sugar control.”

Still, many clinical trials have tested the herbal substance on a relatively small number of participants. Further and more expansive studies are needed to establish ashwagandha’s claimed benefits, especially over the long term.

What Is Ashwagandha?

Ashwagandha is part of a class of plants called adaptogens known for their health benefits when ingested as teas, powders, tinctures and supplements, or in their raw forms.

Also known as Indian ginseng, winter cherry or by its scientific name Withania somnifera, ashwagandha is a herbal shrub whose roots and berries are used for their medicinal properties.

Risks and Side Effects of Ashwagandha

Ashwagandha is a safe and nontoxic plant, but there are a few factors to consider before adding it to your diet.

Do you take other medications? It’s a good idea to let your doctor(s) know if you want to add something new to your health routine, including ashwagandha. If you’re already taking other medications, ashwagandha may enhance or weaken their effects.

Are there other conditions to consider? Ashwagandha may be unsafe if you are pregnant, breastfeeding, immunocompromised, soon undergoing surgery or have a thyroid condition. It’s also worth noting that some people who are allergic to nightshades or have certain grass allergies don’t tolerate ashwagandha well. If any of these situations apply to you, talk to your doctor or an integrative health specialist to determine whether it’s safe for you to take ashwagandha.

What dosage should I take? Experts say that bodies may not absorb all of a 300-milligram dose of ashwagandha, for example. Larger doses may even trigger unwanted side effects, such as vomiting and diarrhea. Instead, take smaller doses more frequently to benefit most from its balancing effects.

Where did this ashwagandha come from? Always check the source of your herbs, especially if you’re buying supplement capsules. Start by asking staff members at natural foods or supplements stores for recommendations. If they say any brand will work, do your own research on each company’s certifications, testing practices and product standards. You especially want to check for the presence of any heavy metals, including arsenic, cadmium, lead and mercury, in their products^[19]. Exposure to these metals can result in damage to the liver, kidneys, central nervous system, immune system and reproductive system^[20].

Buy Now: Available on Amazon.

How to Take Ashwagandha

Ashwagandha roots and berries can be consumed for their medical properties, but typically, you find ashwagandha in supplement capsules or in tablet, gummy, powder, tincture and tea form. SOURCE

9 Health Benefits of Ashwagandha

Potential benefits of ashwagandha include better athletic performance and sleep. Some research suggests this herb may help people with conditions like anxiety and infertility, but stronger studies are needed.

Ashwagandha is one of the most important herbs in Ayurveda, which is a traditional form of alternative medicine based on Indian principles of natural healing.

People have used ashwagandha for thousands of years to relieve stress, increase energy levels, and improve concentration (1).

“Ashwagandha” is Sanskrit for “smell of the horse,” which refers to both the herb’s scent and its potential ability to increase strength (2).

Its botanical name is Withania somnifera, and it’s also known by several other names, including “Indian ginseng” and “winter cherry.”

The ashwagandha plant is a small shrub with yellow flowers that’s native to India and Southeast Asia. Extracts or powder from the plant’s root or leaves are used to treat a variety of conditions, including anxiety and fertility issues (3).

Here are 9 potential benefits of ashwagandha, based on research.

1. May help reduce stress and anxiety

Ashwagandha is perhaps best known for its ability to reduce stress. It’s classified as an adaptogen, a substance that helps the body cope with stress.

Ashwagandha appears to help control mediators of stress, including heat shock proteins (Hsp70), cortisol, and stress-activated c-Jun N-terminal protein kinase (JNK-1) (4).

It also reduces the activity of the hypothalamic-pituitary-adrenal (HPA) axis, a system in your body that regulates the stress response (4, 5).

Several studies have shown that ashwagandha supplements may help relieve stress and anxiety.

In a small study with 58 participants, those who took 250 or 600 mg of ashwagandha extract for 8 weeks had significantly reduced perceived stress and levels of the stress hormone cortisol compared with those who took a placebo.

What’s more, the participants who took the ashwagandha supplements experienced significant improvements in sleep quality compared with the placebo group (4).

Another study in 60 people found that those who took 240 mg of ashwagandha extract per day for 60 days had significant reductions in anxiety compared with those who received a placebo treatment (5).

Thus, early research suggests ashwagandha may be a helpful supplement for stress and anxiety.

However, a recent review of studies concluded that there’s not enough evidence to form a consensus on the most appropriate dosage and form of ashwagandha for treating stress-related neuropsychiatric disorders such as anxiety (6).

2. May benefit athletic performance

Research has shown that ashwagandha may have beneficial effects on athletic performance and may be a worthwhile supplement for athletes.

One analysis of research included 12 studies in men and women who took ashwagandha doses between 120 mg and 1,250 mg per day. The results suggest the herb may enhance physical performance, including strength and oxygen use during exercise (7).

An analysis of five studies found that taking ashwagandha significantly enhanced maximum oxygen consumption (VO₂ max) in healthy adults and athletes (8).

VO₂ max is the maximum amount of oxygen a person can use during intense activity. It’s a measurement of heart and lung fitness.

Having optimal VO₂ max is important for athletes and nonathletes alike. Low VO₂ max is associated with increased mortality risk, while higher VO₂ max is associated with a lower risk of heart disease (8).

Additionally, ashwagandha may help increase muscle strength.

In one study, male participants who took 600 mg of ashwagandha per day and participated in resistance training for 8 weeks had significantly greater gains in muscle strength and size compared with a placebo group (9).

SUMMARYAshwagandha may help improve measures of physical performance in athletes and healthy adults, including VO₂ max and strength.

3. May reduce symptoms of some mental health conditions

Some evidence suggests that ashwagandha may help reduce symptoms of other mental health conditions, including depression, in certain populations.

In one study, researchers looked at the effects of ashwagandha in 66 people with schizophrenia who were experiencing depression and anxiety.

They found that participants who took 1,000 mg of ashwagandha extract daily for 12 weeks had greater reductions in depression and anxiety than those who took a placebo (10).

What’s more, findings from another study suggest that taking ashwagandha may help improve total symptoms and perceived stress in people with schizophrenia (11).

Limited research from 2013 also suggests that ashwagandha may help improve cognitive impairment in people with bipolar disorder. However, more research is needed (12).

Additionally, a study from 2012 found that stressed adults who took 600 mg of ashwagandha extract per day for 60 days reported a 77% reduction in symptoms of depression, while the placebo group reported a 5% reduction (13).

However, only one of the participants in this study had a history of depression, so the relevance of the results is unclear.

Although some findings suggest that ashwagandha may have some antidepressant effects in certain people, you should not try to use it as a substitute for antidepressant medication.

If you’re experiencing symptoms of depression, talk with a healthcare professional so you can get any help or treatment you may need.

SUMMARYThe limited research available suggests that ashwagandha may help reduce symptoms of depression and benefit people with some mental health conditions. However, more research is needed.

4. May help boost testosterone and increase fertility in men

Ashwagandha supplements have been shown in some studies to benefit male fertility and increase testosterone levels.

In one study, 43 overweight men ages 40–70 who had mild fatigue took tablets containing ashwagandha extract or a placebo daily for 8 weeks.

The ashwagandha treatment was associated with an 18% greater increase in DHEA-S, a sex hormone involved in testosterone production. Participants who took the herb also had a 14.7% greater increase in testosterone than those who took the placebo (14).

Additionally, a review of four studies found that ashwagandha treatment significantly increased sperm concentration, semen volume, and sperm motility in men with low sperm count.

It also increased sperm concentration and motility in men with normal sperm count (15).

However, the researchers concluded that there’s currently not enough data to confirm the potential benefits of ashwagandha for male fertility and that more high quality studies are needed (15).

SUMMARYAshwagandha may help increase testosterone levels and may have some potential benefits for male fertility. However, more research is needed.

5. May reduce blood sugar levels

Limited evidence suggests that ashwagandha may have some benefits for people with diabetes or high blood sugar levels.

A review of 24 studies, including 5 clinical studies in people with diabetes, found that treatment with ashwagandha significantly reduced blood sugar, hemoglobin A1c (HbA1c), insulin, blood lipids, and oxidative stress markers (16).

It’s believed that certain compounds within ashwagandha, including one called withaferin A (WA), have powerful antidiabetic activity and may help stimulate your cells to take in glucose from your bloodstream (17).

However, research is limited at this time, and more well-designed studies are needed.

SUMMARYLimited evidence suggests that ashwagandha may reduce blood sugar levels through its effects on insulin secretion and cells’ ability to absorb glucose from the bloodstream.

6. May reduce inflammation

Ashwagandha contains compounds, including WA, that may help reduce inflammation in the body (18).

Researchers have found that WA targets inflammatory pathways in the body, including signal molecules called nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2).

Animal studies have shown that WA may also help reduce levels of inflammatory proteins such as interleukin-10 (IL-10) (18).

There’s some evidence that ashwagandha may help reduce inflammatory markers in humans too.

In one study from 2008, adults experiencing stress took ashwagandha extract for 60 days. As a result, they had significant reductions in C-reactive protein — an inflammatory marker — compared with those who consumed a placebo (19).

In another study, researchers gave people with COVID-19 an Ayurvedic drug containing 0.5 grams of ashwagandha and other herbs twice per day for 7 days. This reduced participants’ levels of inflammatory markers CRP, IL-6, and TNF-α compared with a placebo (20).

The treatment formulation also contained:

1 gram of giloy ghanvati (Tinospora cordifolia)
2 grams of swasari ras (a traditional herbo-mineral formulation)
0.5 grams of tulsi ghanvati (Ocimum sanctum)

Even though these findings are promising, research on ashwagandha’s potential effects on inflammation is limited at this time.

SUMMARYAshwagandha may help reduce inflammatory markers in the body. However, more research is needed.

7. May improve brain function, including memory

Taking ashwagandha may benefit cognitive function.

One review that included five clinical studies noted there was early evidence that ashwagandha could improve cognitive functioning in certain populations, including older adults with mild cognitive impairment and people with schizophrenia.

Cognitive functions it may benefit included (21):

executive functioning
attention
reaction time
performance on cognitive tasks

A study in 50 adults showed that taking 600 mg of ashwagandha extract per day for 8 weeks led to significant improvements in the following measures compared with taking a placebo (22):

immediate and general memory
attention
information-processing speed

Researchers note that compounds found in ashwagandha, including WA, have antioxidant effects in the brain, which may benefit cognitive health (22).

However, more research is needed before experts can draw strong conclusions.

SUMMARYAshwagandha supplements may improve memory, reaction time, and the ability to perform tasks in certain populations. However, more research is needed.

8. May help improve sleep

Many people take ashwagandha to promote restful sleep, and some evidence suggests it may help with sleep issues.

For example, a study in 50 adults ages 65–80 found that taking 600 mg of ashwagandha root per day for 12 weeks significantly improved sleep quality and mental alertness upon waking compared with a placebo treatment (23).

Additionally, one review of five high quality studies found that ashwagandha had a small but significant positive effect on overall sleep quality.

Taking ashwagandha reduced people’s anxiety levels and helped them feel more alert when they woke up (24).

The researchers noted that results were more pronounced in people with insomnia and in those who took more than 600 mg daily for 8 weeks or longer (24).

SUMMARY: Recent evidence suggests that ashwagandha may be an effective natural remedy to improve sleep and may especially help people with insomnia.

9. Relatively safe and widely available

Ashwagandha is a safe supplement for most people, although its long-term effects are unknown.

A review of 69 studies found that ashwagandha root appears to be safe and effective for managing certain health conditions, including stress, anxiety, and insomnia (1).

One study in 80 healthy men and women showed that taking 600 mg of ashwagandha daily for 8 weeks was safe and did not cause any adverse health effects in participants (25).

However, certain people should not take it. For example, pregnant people should avoid it because it may cause pregnancy loss if used in high doses (26).

Also, those with hormone-sensitive prostate cancer and those taking certain medications, such as benzodiazepines, anticonvulsants, or barbiturates, should avoid taking ashwagandha (26).

Some side effects have been reported in people taking ashwagandha supplements, including upper gastrointestinal discomfort, drowsiness, and diarrhea (26).

Additionally, ashwagandha may affect the thyroid, so those with thyroid disease should check with a healthcare professional before taking it (27).

Dosing recommendations for ashwagandha vary. For example, doses ranging from 250–1,250 mg per day have been shown to be effective for different conditions. Consult a healthcare professional if you have questions regarding ashwagandha dosing.

Research findings suggest that ashwagandha’s effects aren’t immediate, so keep in mind that you may have to take it for several months before you start noticing its effects.

You can take ashwagandha in many ways, in either a single dose or multiple doses per day. And you can take it either with meals or on an empty stomach.

Several supplement manufacturers produce it and various retailers sell it, including health food stores and vitamin shops.

SUMMARYAlthough ashwagandha is safe for most people, it’s not safe for everyone. It’s important to check with a healthcare professional before taking ashwagandha.

The bottom line

Ashwagandha is an ancient medicinal herb with multiple possible health benefits.

Study findings suggest that it may help reduce anxiety and stress, support restful sleep, and even improve cognitive functioning in certain populations.

Ashwagandha is considered relatively safe for most people. However, it’s not appropriate for everyone, so it’s important to talk with a healthcare professional before adding ashwagandha to your routine. SOURCE

Overview

Ashwagandha is an evergreen shrub that grows in Asia and Africa. It is commonly used for stress. There is little evidence for its use as an “adaptogen.”

Ashwagandha contains chemicals that might help calm the brain, reduce swelling, lower blood pressure, and alter the immune system.

Since ashwagandha is traditionally used as an adaptogen, it is used for many conditions related to stress. Adaptogens are believed to help the body resist physical and mental stress. Some of the conditions it is used for include insomnia, aging, anxiety and many others, but there is no good scientific evidence to support most of these uses. There is also no good evidence to support using ashwagandha for COVID-19.

Don’t confuse ashwagandha with Physalis alkekengi. Both are known as winter cherry. Also, don’t confuse ashwagandha with American ginseng, Panax ginseng, or eleuthero. SOURCE

Top 7 Vitamins for Stroke Recovery Based on the Latest Clinical Evidence

The Truth News — Thu, 06 Jan 2022 11:05:27 +0000

Top 7 Vitamins for Stroke Recovery Based on the Latest Clinical Evidence

Vitamins for stroke recovery can help boost brain health, but beware that no single pill fits all.

Supplements that enhance one person’s recovery from stroke may worsen recovery in someone else. To avoid this mistake, learn why some stroke supplements can be dangerous for you.

Then, we’ll share an updated list of the best vitamins to enhance stroke recovery.

Take Supplements for Stroke Recovery with Extreme Caution

Before we dig into the list of science-backed vitamins and supplements for stroke recovery, you need to proceed with caution.

It is imperative that you consult with your physician before adding supplements to your regimen. Some supplements can interfere with certain medications to worsen your health status and cause complications.

For example, ginko biloba is an herb that is used to help prevent ischemic stroke (the type of stroke caused by a clot) because it’s a natural blood thinner…

However, it can also put people with a history of hemorrhagic stroke (the type of stroke caused by a bleed) at an increased risk of suffering a second stroke. Additionally, complications can arise if you’re already taking blood thinning medication.

Other supplements that contain natural blood thinning properties include: turmeric, ginger, cayenne pepper, vitamin E, garlic, cassia cinnamon, grape seed extract, omega 3s, and bromelain.

Now, let’s dig into the list of the top supplements and vitamins for stroke recovery.

Want 20 pages of stroke recovery tips in an illustrated PDF? Download our free ebook by clicking here (link opens a pop up for uninterrupted reading)

The Best Science-Backed Vitamins for Stroke Recovery

Based upon relevant clinical research, here are the best supplements and vitamins for stroke recovery:

1. Vitamin D

Research studies show that vitamin D is one of the best vitamins for stroke recovery.

Low levels of vitamin D are associated with worse outcomes after ischemic stroke, which account for 87% of all strokes in America. Furthermore, vitamin D deficiency is associated with the stroke risk factors like hypertension, obesity, and diabetes. (Source: Current Opinion in Clinical Nutrition and Metabolic Care)

Fortunately, after supplementing with vitamin D, “there is a significant improvement in stroke outcomes after 3 months.” (Source: Journal of Clinical and Diagnostic Research)

Getting enough vitamin D can also provide neuroprotective, neuromuscular, and osteoprotective benefits which can reduce cognitive and functional impairments in individuals after a stroke. (Source: Current Drug Targets)

By getting your daily dose of vitamin D, you can reduce your risk of another stroke while aiding your brain’s recovery.

How to get vitamin D naturally:

Your body can produce Vitamin D, known as the sunshine vitamin, from daily amounts of sun exposure. As always, be cautious about your exposure during peak hours (generally 10am-4pm) when the sun’s rays are the strongest.

If you can’t get sun exposure due to medical restrictions (like heightened risk of skin cancer), then consume it through foods that are high in Vitamin D, like fatty fish, cheese, and egg yolks.

Quick Summary

Vitamin D deficiency is associated with poor outcomes after stroke, whereas daily supplementation is associated with better outcomes.

2. Probiotics

Probiotics aren’t a vitamin or mineral. Rather, probiotics are the “good” bacteria that comprise your microbiome, the 100 trillion microbes that live inside your gut.

The bacteria living inside your body serve an important role – they even have a nervous system of their own called the enteric nervous system.

Through this internal ecosystem, the bacteria in your gut communicate with your brain through the gut-brain axis. This connection is bidirectional, which means that it goes both ways. (Source: Annals of Gastroenerology)

Since gut health plays a key role in brain health, probiotics make the list of top supplements for stroke recovery.

How to get probiotics naturally:

Great dietary sources of probiotics include fermented foods like yogurt, kefir, tempeh, kimchi, and miso.

Quick Summary

You need “good” bacteria to support your microbiome, which influences brain health and function via the gut-brain axis.

3. Vitamin B12

Vitamin B12 deficiency is associated with a type of inflammation that damages the blood vessels. When blood vessels become damaged, excess deposits can develop and interrupt blood flow. If this happens to an artery in the brain, it can lead to a stroke. (Source: VeryWell Health)

Supplementing with vitamin B12 can enhance stroke recovery by boosting the function and development of the brain and nerve cells. (Source: Viatcheslav Wlassoff, PhD)

This encourages neuroplasticity, which is the brain’s ability to reorganize itself, create new neural pathways, and rearrange existing ones.

How to get vitamin B12 naturally:

Vitamin B12 can be found in animal products like fish, meat, poultry, eggs, and milk. If you have a history of stroke risk factors like high cholesterol or atherosclerosis, consume lean sources of protein such as fish or poultry.

Quick Summary

Vitamin B12 provides essential support for both brain and blood vessel health.

4. Vitamin B3 (Niacin)

Vitamin B3, also known as niacin, can encourage recovery of brain function after stroke for two main reasons:

First, niacin directly affects neuroplasticity, which is the primary driver of recovery from stroke. Secondly, niacin has been proven to improve “good” cholesterol levels, which are statistically low in stroke survivors. (Source: MedicineNet)

Although experts have yet to link “good” cholesterol levels with stroke recovery, reducing one’s risk of a second stroke is a significant accomplishment.

How to get niacin naturally:

You can find vitamin B3 in tuna, chicken, turkey, and salmon. For meatless options, you can find lesser quantities of niacin in peanuts and brown rice.

Quick Summary

Vitamin B3 positively affects neuroplasticity, which is driving mechanism of stroke recovery.

5. DHA (Docosahexaenoic acid)

DHA is an omega-3 fatty acid that is critical for healthy brains. While omega-3s are not vitamins, they still made the list for their positive effects on stroke recovery.

DHA is essential for brain growth in infants and maintenance of normal brain function in adults. Some studies suggest that DHA can reduce stroke risk factors like hypertension and atherosclerosis. (Source: Pharmacological Research)

Be aware that fish oil is contraindicated for some blood thinners, such as Warfarin. Check with your physician to see if this supplement is safe for you. (Source: Annals of Pharmacotherapy)

How to get DHA:

DHA is an essential fatty acid, meaning your body cannot produce it on its own – you must get it from your diet (or supplements).

Fatty fish, like salmon, contain healthy amounts of DHA. If you are on a strict heart healthy diet, then consider taking fish oil supplements to obtain your daily amount of DHA.

Quick Summary

DHA can improve healthy brain function and must be consumed through diet or supplements.

6. Coenzyme Q10 (CoQ10)

CoQ10 is most famous for improving heart health – but it holds incredible benefits for your brain, too. This is why CoQ10 made the list of top vitamins for stroke recovery, even though it’s a nutrient and not a vitamin.

CoQ10 is a powerful antioxidant that provides protection from free radicals, which are toxic molecules associated with disease. Free radicals are believed to play a role in cardiovascular disease, which is a precursor to stroke.

By supplementing with CoQ10, you can improve your heart health and, therefore, reduce your risk of a second stroke.

Also, low CoQ10 levels have been associated with greater tissue damage to the brain during stroke.

How to get CoQ10 naturally:

CoQ10 can be found in most liver organ meats like heart, liver, and kidney. However, these meats also contain high amounts of cholesterol and saturated fats that exacerbate cardiovascular disease.

Small amounts of CoQ10 can be found in spinach, broccoli, and cauliflower. Due to this, supplementation may be more suitable for individuals recovering from a stroke.

Quick Summary

CoQ10 can boost recovery from stroke by protecting you from damaging free radicals associated with cardiovascular disease.

7. Vitamin C

Vitamin C deficiency may be a stroke risk factor, especially in individuals with a history of hemorrhagic strokes (the type of stroke caused by a burst artery in the brain).

In a study from the American Academy of Neurology, 65 survivors of hemorrhagic stroke were compared to 65 healthy people. On average, those who suffered a stroke had depleted levels of vitamin C while healthy people did not.

Study author Stephane Vannier, MD, concluded that “vitamin C deficiency should be considered a risk factor for this severe type of stroke.”

How to get vitamin C naturally:

Although oranges are well-known for their nutritional benefits, other fruits and vegetables, like papaya, bell peppers, broccoli, and strawberries, contain higher amounts of vitamin C.

Dr. Stephane Vannier, from Pontchaillou University Hospital in Rennes, does not recommend supplementing vitamin C if you are not deficient.

Quick Summary

People with a history of hemorrhagic stroke should pay attention to their vitamin C levels to promote overall health and wellness.

How to Get These Stroke Supplements without Breaking Your Budget

Consider obtaining these supplements through your diet as opposed to costly pills and herbal remedies.

Eat a variety of whole foods every day, especially foods that help stroke recovery, in order to avoid developing a nutritional deficiency. Prioritize meals with minimal processing, which can strip foods of essential vitamins and minerals.

If you are unable to consume these vitamins and minerals through your diet, then consult with your physician prior to adding supplement to your medication regimen.

Medically reviewed by Andrew Tran PT, DPT, NCS, CSCS source

Herbs & Supplements Archives - Good Shepherd News - Fastest Growing Religious, Free Speech & Political Content

Foods to help balance fatty liver

Foods to help balance fatty liver

1. What is fatty liver disease?

Fatty liver is a common disease with an increasing incidence. Fatty liver disease, if not detected and treated early, can lead to hepatitis, cirrhosis, and even liver cancer. Therefore, it is best to prevent disease with foods that help balance fatty liver.

2. Fatty liver eat what?

3. Lifestyle changes in fatty liver disease

The BEST Drink for a Fatty Liver

Discover the Mutual Impact of Olive Oil and Lemon on liver

Olive oil and Lemon Juice Liver Cleanse Recipe

Ingredients:

Instructions:

How do you know that this combination is best for you?

Cleansing and Detoxification Ideas

Weight Loss

Health Benefits of using Liver oil and Lemon Cleanse

How might a liver cleanse cause side effects?

How to liver cleanse at home?

How much olive oil for detox?

Conclusion

Cleanse Your Liver

Water

Teas

Grapefruit Juice

Turmeric Water

Lemon Water

Ginger Water

DRINK 1 CUP PER DAY to Remove Fat from Your Liver – Dr. Berg

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

Abstract

1. Introduction

2. Materials and Methods

2.1. Chemicals and Reagents

2.2. Materials

2.3. Animal Study

2.4. Measurement of Biochemical Parameters in the Serum

2.5. Measurement of TG and Antioxidant Enzyme Activities in the Liver

2.6. Measurement of Lipid Peroxidation Levels in the Liver

2.7. Liver Histopathological Assessment

2.8. Ferric-Reducing Antioxidant Power (FRAP) Assay

2.9. Trolox Equivalent Antioxidant Capacity (TEAC) Assay

2.10. Determination of TPC

2.11. Determination of TFC

2.12. Statistical Analysis

3. Results

3.1. Effects of Lemon Juice on the Levels of ALT and AST in Serum

3.2. Effects of Lemon Juice on the Levels of TG in Serum and Liver

3.3. Effects of Lemon Juice on Liver Lipid Peroxidation Levels

3.4. Effects of Lemon Juice on Liver Antioxidant Enzyme Activities

Table 1

3.5. Histopathological Evaluation

3.6. The In Vitro Antioxidant Activity, Total Phenolic Contents (TPC), and Total Flavonoid Contents (TFC) of Lemon Juice

4. Discussion

5. Conclusions

Acknowledgments

Conflicts of Interest

Authors’ Contributions

References

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References

Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver

Abstract

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Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure

Abstract

1. Introduction

2. Materials and Methods

2.1. Chemicals

2.2. Plant Material

2.3. Phytochemical Analysis

Identification and Quantification of Polyphenolic Compounds by HPLC-DAD-ESI MS

2.4. Animals and Experimental Design

2.5. Biochemical Serum Analysis

2.6. Histological Assessment

2.7. Immunohistochemical Analysis of 3-Nitrotyrosine

2.8. Statistical Analysis

3. Results

3.1. Phytochemical Analysis