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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.

Dietary supplements are not regulated in the United States, meaning the Food and Drug Administration (FDA) does not approve them for safety and effectiveness before products are marketed. When possible, choose a supplement that has been tested by a trusted third party, such as USP, ConsumerLabs, or NSF.

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

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

Recommended Iodine Intake

  • 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

Upper Limits

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.

FREQUENTLY ASKED QUESTIONS

  • 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.

 

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

]]> GABA and L-theanine mixture Improves REM Sleep, Antidepressant, and Mood-stabilizing Study Says https://goodshepherdmedia.net/gaba-and-l-theanine-mixture-improves-rem-sleep-antidepressant-and-mood-stabilizing-study-says/ Sat, 08 Jan 2022 08:32:10 +0000 https://goodshepherdmedia.net/?p=4625 GABA and L-theanine mixture Improves
REM Sleep, Antidepressant, and Mood-stabilizing Study Says

Abstract

Context: γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABAA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits.

Objective: This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture.

Materials and methods: Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes.

Results: GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit.

Conclusions: GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour.

Keywords: γ-Aminobutyric acid, insomnia, pentobarbital-induced sleep test, electroencephalography

Introduction

Sleep loss and other related disturbances pose an important health problem, as they can lead to significant functional impairments. Sleep disturbances can affect daily life considerably and reduce the quality of life. The importance of a good night’s sleep is well-established, nevertheless many people suffering from sleep disorders prefer not to use hypnotic drugs, despite providing effective symptomatic relief.

Hypnotic drugs, such as benzodiazepine analogues, zolpidem and doxepin, can cause unexpected side effects and can lead to drug resistance and dependence (Longo and Johnson ; Victorri-Vigneau et al. ; Lichstein et al. ). These types of sleeping drugs are not suitable for the treatment of temporary anxiety or sleep disturbances due to the observed drug resistance and dependence that has been associated with their long-term use (Oh et al. ). However, herbal remedies have been reported as effective and with a relatively low side effect risk for the treatment of insomnia (Wheatley ). Therefore, it is necessary to develop new bioactive substances derived from natural sources that present with similar efficacy but fewer side effects than hypnotic drugs, for the successful treatment of sleep-related disturbances.

γ-Glutamylethylamine, also known as l-theanine, and γ-aminobutyric acid (GABA) are known agents for improving sleep disturbances (Khan et al. ). GABA is a non-proteinogenic amino acid and is the main inhibitory neurotransmitter in the mammalian brain. Hence GABAA receptors are a primary target in the search for natural anxiolytic compounds or sedatives (Khom et al. ; Trauner et al. ). There is an increasing interest in investigating the effect of GABA-mediated inhibitory neurotransmission, in respect to its potential benefit on counteracting sleep disruption caused by various conditions, such as stress, diseases and caffeine intake, etc. (Wong et al. ). Therefore, GABA is widely used in functional food and pharmaceutical industries, and various researches have been investigated for biosynthesis and their efficacy as metabolites of plants and microorganisms produced by the decarboxylation of glutamic acid (Coda et al. ; Dhakal et al. ; Yang et al. ) l-Theanine, an amino acid exclusively found in tea leaves, composes only 1–2% (w/w) of the weight of dried tea leaves (Graham ) and is chemically or biologically synthesized for use as an active ingredient that induces sedation (Juneja et al. ; Yan et al. ). There are several reports indicating that l-theanine exerts neuroprotective effects (Kim et al. ), modulates neurotransmitter activity (Kakuda ) and reduces psychological stress (Kimura et al. ) and sleep disturbances (Jang et al. ). Nathan et al. () also reported that l-theanine intake increases serotonin, dopamine and GABA levels in the brain.

In recent years, there have been numerous ‘relaxation beverages’ available on the market containing relaxation-inducing nutraceuticals, such as valerian, l-theanine, GABA, 5-hydroxytryptophan (5-HTP) and the sleep-aid, melatonin. Therefore, the combination of GABA and l-theanine may synergistically promote symptomatic relief for sleep disorders, despite the scarce experimental data supporting this process. The purpose of this study was to investigate whether the effect of GABA/l-theanine mixture on sleep disturbances is greater than GABA or l-theanine alone and to determine the most effective dosing combination.

Materials and methods

Materials

GABA (90.8%) and l-theanine (99.3%) was supplied by Neo Cremar Co. Ltd (Seoul, Korea) and BTC Co. Ltd (Ansan, Korea), respectively. Caffeine was purchased from Sigma-Aldrich (St. Louis, MO) and pentobarbital sodium was purchased from Hypharm. Co. Ltd. (Gyeonggi-do, Korea). All other reagents were purchased at the highest commercial grade available.

Animals

Male ICR mice (4 weeks old, 18–20 g) and Sprague-Dawley (SD) rats (8 weeks old, 160–180 g) were purchased from Orient Bio (Orient Bio Inc., Seongnam, Korea). All animals were caged at 22 ± 2 °C and 55 ± 5% humidity with a 12 h light/dark cycle. Normal pellet diet and water were freely provided. Rodents were acclimatized for at least one week before starting pentobarbital-induced sleep testing and electroencephalography (EEG) analysis. The ages of the animals used in this study were to ensure the functional integrity of the brain and central nervous system, which usually does not occur in older animals, which normally have degraded morphological and functional characteristics (Verdú et al. ). In this study, all animal experimental protocols were approved by the Korean University Animal Care Committee (KUIACUC-2017-49, Seoul, Korea).

Pentobarbital-induced sleep test

Pentobarbital-induced sleep was performed according to previously established methods with slight modifications (Yang et al. ). Sodium pentobarbital (42 mg/kg) was administered intraperitoneally in each mouse 40 min after oral administration of GABA, l-theanine or both (GABA/l-theanine). The time elapsed from compound administration to the loss of righting reflex (sleep latency) and the time from the loss of righting reflex to its return (sleep duration) were measured in seconds. Mice that did not sleep 15 min after the injection were excluded from the experiment.

Electrophysiological analysis

Male SD rats were anesthetized with 2% isoflurane (Troikaa Pharmaceutical Ltd., Gujarat, India), using a gas anesthesia mask in a stereotaxic instrument frame (Stoelting Inc., Wood Dale, IL). For the EEG recording, EEG screw electrodes were implanted into the cortex, striatum and hippocampus, as previously described (Hong et al. ). All rats received antibiotics and were kept individually in cages under a temperature-controlled facility with water and food. The rats were randomly divided into control and treatment groups at 7 days after recovery. Experiments were conducted from 10 am to 5 pm for 9 days. GABA, l-theanine or GABA/l-theanine mixture was orally administered 1 h before EEG signal analysis. EEG signals were amplified, filtered (0.5–30 Hz), recorded and stored using Iox2 (version. 2.8.0.13, emka Technologies, Paris, France). EEG spectra were analyzed in 1 Hz frequency bins and standard frequency bands (β: 13–30 Hz; α: 8–13 Hz; θ: 4–8 Hz; δ: 0.5–4 Hz). After the EEG recording, fast Fourier transform (FFT) was performed every 2 sec. Based on the FFT average data obtained at 10-sec intervals in the range of 0–30 Hz, the ecgAUTO3 program (version. 3.3.0.20, emka Technologies) was used to calculate the awake and sleep time. Caffeine (10 mg/kg) was used to induce the arousal condition before the experiments.

Quantification of receptor mRNA levels

Total RNA was extracted from mouse brains using TRIzol® (Invitrogen, CA), while genomic DNA was removed using Direct-zolTM RNA Miniprep (ZYMO Research, CA) according to the manufacturer’s protocol. Quality-controlled RNA (1 μg) was reverse transcribed using SuperScript® III Reverse Transcriptase (Invitrogen) with oligo d(T) as the primer. The generated cDNA was subjected to quantitative real-time PCR (qRT-PCR) using a Power Taqman PCR Master Mix kit (Applied Biosystems, Foster City, CA). For qRT-PCR, cycling conditions were 50 °C for 2 min, 95 °C for 10 min, followed by 40 cycles at 95 °C for 15 s and 60 °C for 1 min. Quantitative analysis was conducted using StepOne plus Software version 2.0 (Applied Biosystems, Inc., Foster City, CA). The endogenous housekeeping gene, GAPDH (NM_008084.2), was used for result normalization. Information for the target genes used for qRT-PCR is as follows: GABAA receptor (NM_008076.3), GABAB receptor 1 (NM_01 9439.3), GABAB receptor 2 (NM_001081141.1), GluA1 (NM_00111 3325.2), GluN1 (NM_001177656.2) and GluN2A (NM_008170.2).

Statistical analysis

Testing results were evaluated for statistical differences using SPSS version 12.0 (SPSS, Chicago, IL) by one-way analysis of variance (ANOVA) followed by both Tukey’s multiple comparisons and Bonferroni post hoc test. Different letters indicate significant differences (p < 0.05) among groups by Tukey’s multiple comparison tests. All data are expressed as the means ± standard error (SE) comparisons between groups, n = 8.

Results

Effects of GABA and l-theanine on sleep latency and duration in the pentobarbital-induced sleep model

Sleep latency and duration time following GABA or l-theanine administration were measured in the pentobarbital-included sleep model to identify the optimal combination ratio for sleep enhancement (Figure 1). Sleep latency showed a tendency to decrease with increasing GABA concentration and sleep duration to increase with increasing GABA concentration (Figure 1(A,B)). Regarding sleep latency, there was a significant difference (p < 0.05) following the administration of 100 mg/kg of GABA (3.1 min), as compared to control (3.7 min), but no significant differences with other GABA concentrations were observed (Figure 1(A)). With regards to sleep duration, there was also a significant difference (p < 0.05) following 100 mg/kg of GABA, as compared to control. No significant differences of sleep duration were observed following the administration of any other GABA concentrations (Figure 1(B)). Pentobarbital-induced sleep testing was carried out to assess the potential sleep enhancement effect of l-theanine (Figure 1(C,D)). Following the administration of 20 or 30 mg/kg of l-theanine, sleep latency significantly decreased (2.8 and 2.7 min, respectively), as compared to controls (3.7 min) (p < 0.05 and p < 0.01, respectively). However, the administration of 40 mg/kg of l-theanine not decreased sleep latency (3.7 min). When compared to controls (39.9 min), total sleep time increased in l-theanine-treated animals at a dose of 20 mg/kg (55.2 min), but not with 30 or 40 mg/kg of l-theanine (Figure 1(D), p < 0.01). In summary, administration of 20 mg/kg of l-theanine in mice, resulted in a decrease in sleep latency (23.3%) and an increase in sleep duration time (38.1%).

 

Effects of GABA or l-theanine on sleep latency (A, C) and sleep duration (B, D) in mice administered with a hypnotic dosage of pentobarbital (42 mg/kg, i.p.). Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as **p < 0.01, *p < 0.05.

Effects of GABA/l-theanine combination on sleep latency and duration in the pentobarbital-induced sleep model

The induced changes in sleep latency and duration time by different ratio combinations of GABA (80 and 100 mg/kg) and l-theanine (20 and 30 mg/kg) were measured (Figure 2). The sleep latency of animals that were administered with either of the GABA/l-theanine dose combinations (80/30 and 100/20 mg/kg) was slightly lower than the control group (Figure 2(A)) (16.8 and 17.7%, respectively). With respect to sleep duration, sleep time showed a tendency increase in all dose combination groups (Figure 2(B)). In particular, the GABA/l-theanine mixture administered at a dose ratio of 100/20 mg/kg, evoked the highest sleep duration increase (100.6 min) (p < 0.01).

Effects of GABA/l-theanine mixture on sleep latency (A, C) and sleep duration (B, D) in mice administered with a hypnotic dosage of pentobarbital (42 mg/kg, i.p.). Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as **p < 0.01, *p < 0.05.

The effects of the best sleep-promoting GABA/l-theanine dose combination (100/20 mg/kg) were compared to the changes in sleep latency and duration induced by the single administration of GABA or l-theanine (Figure 2(C,D)). The combined use of GABA/l-theanine (100/20 mg/kg) showed a decrease in sleep latency (20.7% and 14.9%, respectively) and an increase in sleep duration (87.3% and 26.8%, respectively) compared to a single administration of GABA (100 mg/kg) or theanine (20 mg/kg). The combined use of GABA/l-theanine showed synergy effects on sleep latency and sleep duration time.

Effects of GABA and l-theanine mixture on sleep architecture

EEG parameters were recorded to more accurately confirm the synergistic effect of GABA/l-theanine mixture observed in the pentobarbital-induced sleep model (Figure 3). The changes in sleep time and architecture were measured after a single administration of GABA 100 mg/kg or l-theanine 20 mg/kg and after GABA/l-theanine mixture (100/20 mg/kg). Figure 3 depicts the longest sleep time recorded following the oral administration of GABA/l-theanine. However, no significant difference in sleep time was detected between GABA/l-theanine mixture and l-theanine alone (Figure 3(A)). The most reduced awake time was detected after oral administration of GABA/l-theanine mixture (1.2 h) and was significantly different from control (2.2 h) (Figure 3(B), p < 0.001). Single GABA administration (100 mg/kg) significantly increased rapid-eye-movement (REM) sleep time, as compared to the control group (71.5%) (p < 0.01), but there was no significant difference in non-REM (NREM) sleep time compared to the control group (Figure 3(C,D)). Single l-theanine administration (20 mg/kg) significantly increased REM time, when compared to controls (88.6%) (p < 0.01), but there was no significant difference in NREM sleep time compared to the control group. NREM (20.7%) and REM (99.6%) were also significantly increased than control levels, after GABA/l-theanine mixture was orally administered (Figure 3(C,D), p < 0.05 and p < 0.001, respectively). The oral administration of GABA/l-theanine mixture improved sleep time and quality, as compared to GABA or l-theanine alone.

Effects of the GABA, l-theanine, and GABA/l-theanine mixture on sleep quantity and quality. Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences at ***p < 0.001, **p < 0.01, *p < 0.05 by Bonferroni test. NS: not significant.

The θ wave was significantly increased after GABA (1.8 h) or l-theanine (2.2 h) single infusion, as well as after GABA/l-theanine combined administration (2.5 h) (Figure 3(E)). The δ wave showed a tendency to decrease when GABA or l-theanine was separately administered and after GABA/l-theanine, but there were no significant differences between groups (Figure 3(F)).

Effects of GABA and l-theanine combination on sleep architecture during three sleep periods

Figure 4 depicts the sleep pattern measured for 9 days divided into 3 periods. Total sleep time increased and awakening time decreased from 1st to 3rd period in all sample groups (Figure 4(A,B)). NREM sleep was significantly increased in the GABA/l-theanine mixture group, as compared to controls during all three periods (Figure 4(C); 1st period: p < 0.05, 2nd period: p < 0.05, 3rd period: p < 0.001). REM sleep was significantly increased at all periods compared to control levels in the GABA or l-theanine alone groups, as well as the GABA/l-theanine mixture group (Figure 4(D)).

Effects of GABA, l–theanine, and GABA/l-theanine mixture on sleep quantity and quality during administration periods. Values are presented as the means ± standard error (SE) for each group, n = 8. Symbols indicate significant differences by Bonferroni test, as ***p < 0.001, **p < 0.01, *p < 0.05.

NREM sleep consists of θ and δ waves, with 4.0–8.0 and 0.5–4.0 Hz bandwidths, respectively. The use of l-theanine alone and GABA/l-theanine mixture increased θ waves over the ones detected in the control group during all periods. Single l-theanine administration led to a significant decrease in δ waves during the 1st period (2.0 h) (p < 0.01), which gradually increased in the 3rd period (3.1 h). When GABA/l-theanine mixture was administered, δ wave oscillations also gradually increased from 1st (2.2 h) to 3rd period (2.7 h) (Figure 4(E,F)). In conclusion, the combined treatment with GABA and l-theanine led to a significant increase in sleep time (22.4%), especially NREM (28.8%), when administered over a long period. In addition, the use of GABA/l-theanine mixture increased θ wave and decreased δ wave oscillations in NREM sleep, when compared to the control group. Nevertheless, δ waves gradually increased with long-term administration. Therefore, the longer the administration of GABA/l-theanine mixture the better the sleep quality and the longer the sleep duration, induced.

EEG acquisition and analysis in a caffeine-induced wakefulness model

EEG was performed to assess the sleep-inducing effects of GABA, l-theanine or the combination of both (GABA/l-theanine mixture) in a caffeine-induced awakening animal model (Figure 5). A significant difference (p < 0.001) in sleeping and awakening times were observed between the arousal group, which was orally administered 10 mg/kg of caffeine and the control group which was orally administered with saline (Figure 5(A,B)). Administration of GABA, l-theanine, or the combination of both, in the caffeine-induced awakening model led to significant differences in sleep and awakening times, when compared to the arousal group (p < 0.001). In the wakefulness model, the use of l-theanine alone or GABA/l-theanine mixture restored NREM sleep time to the control group level (Figure 5(C)). However, the use of GABA/l-theanine mixture in the wakefulness model had a tendency to restore REM sleep time, but there was no significant difference to arousal group. The administration of GABA/l-theanine mixture increased θ wave (1.9 h) and increased δ wave (2.0 h) oscillations in NREM sleep, when compared to the arousal group (1.4 and 2.5 h, respectively) (Figure 5(E,F), p < 0.01). These results suggest that the combined use of GABA and l-theanine rather than GABA or l-theanine alone restores sleep time and quality to normal levels, in the arousal animal model.

Effects of the GABA, l-theanine, and GABA/l-theanine mixture on caffeine-induced wakefulness in rats at a dosage of caffeine (10 mg/kg). Values are presented as the means ± standard error (SE) for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as ***p < 0.001, **p < 0.01 compared with arousal group.

Effects of GABA and l-theanine combination on the mRNA levels of neurotransmitter receptors

To investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture mediates neurotransmitter receptor expression changes, the mRNA levels of GABA and glutamate receptors were evaluated (Figure 6). Transcript levels for the GABAA receptor following the combined administration of GABA/l-theanine were 1.53-fold higher than control levels (Figure 6(A), p < 0.01). Moreover, GABA/l-theanine combined infusion led to significant changes in the mRNA levels of GABAB-R2 (21.4%), as compared to controls (Figure 6(C), p < 0.001). However, there was no significant difference in the mRNA levels of GABAB-R1 compared to the control group (Figure 6(B)).

Effects of the GABA/l-theanine mixture on GABA and glutamate receptors mRNA expression in the mouse brain. Values are presented as mean ± standard error of the mean (SEM) for the brain regions of 8 mice and for each group, n = 8. Different letters indicate significant differences (p < 0.05) among samples by Tukey’s multiple range test. Symbols indicate significant differences by Bonferroni test, as ***p < 0.001, **p < 0.01, *p < 0.05. NS: not significant.

GABA/l-theanine mixture significantly increased the mRNA levels of the GluN1 glutamate receptor subunit, as compared to control (13.8%) (Figure 6(E), p < 0.05). However, administration of l-theanine alone also altered the GluR1 glutamate receptor (12.5%) and GluN1 glutamate subunit (7.2%) expressions when compared to controls (Figure 6(D,E), p < 0.05). These results indicate that increased expression of GABA receptors GABAA, GABAB-R1 and GABAB-R2, and the GluN1 glutamate receptor subunit observed with GABA/l-theanine, may possibly lead to improved sleep behaviour and neurological regulation.

Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models

Abstract

The aim of this study was to investigate the sleep-promoting effect of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) on sleep quality and quantity in vertebrate models. Pentobarbital-induced sleep test and electroencephalogram (EEG) analysis were applied to investigate sleep latency, duration, total sleeping time and sleep quality of two amino acids and GABA/5-HTP mixture. In addition, real-time PCR and HPLC analysis were applied to analyze the signaling pathway. The GABA/5-HTP mixture significantly regulated the sleep latency, duration (p<0.005), and also increased the sleep quality than single administration of the amino acids (p<0.000). Long-term administration increased the transcript levels of GABAA receptor (1.37-fold, p<0.000) and also increased the GABA content compared with the control group 12h after administration (1.43-fold, p<0.000). Our available evidence suggests that the GABA/5-HTP mixture modulates both GABAergic and serotonergic signaling. Moreover, the sleep architecture can be controlled by the regulation of GABAA receptor and GABA content with 5-HTP.

Keywords: 5-Hydroxytryptophan; Electroencephalogram; Pentobarbital; Sleep; Vertebrate; γ-Aminobutyric acid.

The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent

Abstract

L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.

A Novel Theanine Complex, Mg-L-Theanine Improves Sleep Quality via Regulating Brain Electrochemical Activity

Discussion

The pentobarbital-induced sleeping model was used to identify the optimal sleep enhancement dosing ratio for GABA and l-theanine. In this study, the combination of GABA and l-theanine (100/20 mg/kg) not only did it reduce sleep latency but also prolonged sleep duration in pentobarbital-induced sleep model. The key finding of this study is the confirmation of the synergistic action (p < 0.01, compared to control) of GABA and l-theanine on sleep behaviour, which significantly decreased sleep latency and increased sleep duration.

Amino acid neurotransmitters are important for the function of the central nervous system (CNS). They are fast-acting, inducing responses within milliseconds and play an important role in physiological brain function and neurological diseases (Krystal et al. ). Rapid neurotransmitter regulation and nerve function, facilitation of relaxation without drowsiness, stress relief (including physical stress), and l-theanine-mediated excitement are known strategies used for the improvement of sleep quality and for exhaustion recovery (Rao et al. ).

Sleep deprivation is known to cause serious illnesses such as cardiovascular disease, diabetes, and cancer (Davis and Mirick ; Laposky et al. ; Baron and Reid ). The pentobarbital-induced sleep test and the EEG measurement that have been performed usually in a study of sleep enhancement were used to confirm the synergy effect of GABA/l-theanine mixture in sleep enhancement (Jeon et al. ).

The combination of GABA and l-theanine (80/20 and 100/30 mg/kg) did not show a synergistic effect in sleep latency and sleep duration unlike the GABA/l-theanine mixture (100/20 mg/kg). Lin et al. () reported that the synergistic effects were different depending on the ratio of taurine and caffeine, and it is important to identify specific synergistic ratio in the study of combined sample administration. However, further research is needed to determine that synergistic effects are achieved only at a specific ratio with any pharmacokinetic mechanism.

GABA acts through GABA receptors. There are generally 2 types of GABA receptors: GABAA and GABAB. The most important receptor, with respect to sleep is the GABAA receptor (Gottesmann ). When GABA or another agonist binds to GABAA receptor, it triggers the influx of chloride ions in neuronal cells. This causes a negative membrane potential that inhibits action potential firing. In this way, GABA (and GABA-promoting compounds) reduce activity in brain cells through GABAA receptor activation. It is well-known that the activation of GABAA receptors is beneficial for sleep (Abdou et al. ). The structural similarity of l-theanine to the neurotransmitter glutamic acid has prompted researchers to study its potential competition binding on glutamate receptors in the nervous system (Shinozaki and Ishida ). l-Theanine rapidly induces changes in serotonergic and dopaminergic transmission (Yokogoshi et al. ). These components act as modulating receptors of the neurotransmitter GABA, which is the main inhibitory neurotransmitter in the CNS, and therefore, one of the main molecules responsible for sleeping behaviour (Zanoli and Zavatti ). The decreases in sleep latency, together with a slight improvement in sleep quality, are the possible reasons for the observed increase in sleep efficiency, in our study.

As characterized by EEG recordings, sleep is broadly divided into REM and NREM (Bersagliere et al. ). Combined oral administration of GABA and l-theanine significantly increased the amount of NREM sleep, as compared to controls (Figure 3, p < 0.05), via an increase in theta waves. Moreover, awake time was also significantly decreased following GABA/l-theanine administration, as compared to all other groups (p < 0.001, Figure 3). Brain waves can be classified into four types: α (less than 8–13 Hz), β (more than 13 Hz), θ (less than 4–8 Hz), and δ waves (less than 4 Hz) (Abdou et al. ). Each wave type is associated with a specific mental state. Delta and theta occur in the early stages of deep sleep and sleep, respectively (Ray and Cole ).

We observed a tendency for NREM sleep to increase with increasing dosing periods during the combined oral administration of GABA and l-theanine, probably due to l-theanine (Figure 4). This change in NREM is likely due to changes in delta waves after GABA/l-theanine administration. EEG frequency estimation revealed increased delta and decreased beta activity in the NREM state. Caffeine causes a variety of sleep disturbances, including total sleep time reduction, prolonged sleep onset latency and increased arousal in humans and rats through adenosine receptor blockade (Deckert and Gleiter ).

In Figure 5, caffeine decreased sleep time, especially NREM and increased the awake time in rats. The results indicate that GABA and l-theanine combined intake can reverse caffeine-induced sleep reduction, especially NREM, in rats (Figure 5). Administration of l-theanine has been reported to inhibit caffeine’s convulsive action and to increase GABA brain levels in mice (Kimuraand Murata 1971). l-Theanine is known to decrease norepinephrine levels in the rat brain and suppress caffeine-induced serotonin and 5-hydroxyindoleacetic acid increases in rats (Kimura and Murata ). Furthermore, the neuroprotective effect of theanine has been shown to be mediated via glutamate receptors, as theanine acts as a glutamate receptor antagonist (Kakuda et al. ). The above results suggested that the GABA/l-theanine mixture was significantly superior to GABA or l-theanine alone, for reducing sleep latency, awake time and extending NREM sleep duration. The l-theanine seems to play a major role in the synergistic effect of GABA and l-theanine combination. A trend for prolonged NREM with increasing l-theanine dosing was observed, which was similar to the delta wave increasing trend. In the caffeine-induced arousal model, combined GABA and l-theanine led to a similar synergistic effect on sleep enhancement. The combination of GABA and l-theanine is an attractive NREM sleep-promoting regimen as it increases delta wave oscillations.

As shown in Figure 6, GABAA receptor expression levels were significantly changed in mice with administration GABA/l-theanine mixture compared with the control group (p < 0.01). The GABAA receptor complex is a chloride ionophore, which consists primarily of GABA, barbiturate, benzodiazepine, steroid and picrotoxin binding sites (MacDonald and Olsen ). Parisky et al. () demonstrated that GABAA receptor over expression increases total sleep time, while down-regulation of the receptor decreases sleep duration. The metabotropic GABAB receptor can influence the activation of Ca+2 and K+ ion channels via G-protein coupled second messengers. The affinity of GABA to GABAB receptors is lower than that for GABAA receptors (Chu et al. ). The sedative or sleep-inducing effect of GABA is most likely mediated via GABA receptors. GABA receptor expression in the rat brain was significantly increased following the combined administration of GABA and l-theanine but not after GABA infusion alone. l-Theanine has a similar chemical structure to glutamate and l-theanine has micromolar affinities for kainate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) glutamate receptors (Kakuda et al. ). l-Theanine can act as a competitive glutamate antagonist. The mRNA level of the NDMA receptor subunit GluN1 was slightly higher following GABA/l-theanine infusion than after l-theanine treatment alone (Figure 6).

In conclusion, our results demonstrate that the combined use of GABA and l-theanine increase sleep activity to more than a single administration of either amino acid or these synergistic sleep-promoting effects are likely mediated via changes in GABA and/or glutamate receptor expression in the brain. In summary, this result suggests that GABA/l-theanine mixture could be used for treatment for insomnia and sleep disorders as a concept of nonpharmacological management of sleep.

Funding Statement

This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (R0004012).

Disclosure statement

No potential conflict of interest was reported by the authors.

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cited https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366437/

https://pubmed.ncbi.nlm.nih.gov/27150227/

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

 

]]> Top 7 Vitamins for Stroke Recovery Based on the Latest Clinical Evidence https://goodshepherdmedia.net/top-7-vitamins-for-stroke-recovery-based-on-the-latest-clinical-evidence/ Thu, 06 Jan 2022 11:05:27 +0000 https://goodshepherdmedia.net/?p=11259

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

 

always consult with your physician!

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