Gamma-Aminobutyric acid (GABA), discovered in 1950, is an amino acid produced naturally in the brain. GABA functions as a neurotransmitter, facilitating communication among brain cells. GABA’s big role in the body is to reduce the activity of neurons in the brain and central nervous system (CNS), which in turn has a broad range of effects on the body and mind, including increased relaxation, reduced stress, a more calm, balanced mood, alleviation of pain, and a boost to sleep.

Amino acid neurotransmitters are critical for the function of the CNS; they have fast actions, producing responses within few milliseconds playing an important role in brain functions and neurological diseases. 

Under stress conditions certain metabolites, like GABA, are depleted, therefore, additional nutrients are required to replace these metabolites. As the quantities of nutrition vary from one individual to another and the difficulties to obtain these nutrients from food so a better alternative is to consume the required additional nutrients as enriched functional food and/or food supplements.

GABA is synthesised in tissues from glutamic acid via the enzyme glutamic acid decarboxylase (GAD), with pyridoxal-5-phosphate (P5P) acting as a cofactor.

Outside of the CNS, GABA is synthesised by the colonic microflora. As the major inhibitory neurotransmitter, GABA counteracts over excitation in the brain, and has been described as acting like a ‘brake’ on the neuronal circuitry during times of increased stress. Following its release from GABAergic nerve terminals, it acts on both GABA-A and GABA-B receptors, with a net inhibitory effect.

The GABA-A receptors regulate brain excitability and are responsible for GABA’s immediate synaptic inhibitory effects. As low GABA levels are associated with anxiety, depression, insomnia and epilepsy, medications that target these GABA receptors have been developed. There are many pharmaceutical medications, alcohol and psychoactive drugs that produce their anxiolytic, analgesic, anticonvulsant, and sedative effects by modulating GABA-A receptor activity or by blocking the reuptake of GABA by GABA transporter (GAT) proteins.

In addition to its effect on the brain, high doses of GABA (5-10g single dose) have been shown to exert effects on the endocrine system, including increases in plasma growth hormone levels, although the clinical significance of these effects is currently unknown. 1 References: Abdou, A. M., Higashiguchi, S., Horie, K., Kim, M., Hatta, H., & Yokogoshi, H. (2006). Relaxation and immunity enhancement effects of γ-Aminobutyric acid (GABA) administration in humans. BioFactors, 26(3), 201–208. doi:10.1002/biof.5520260305 2 Reference: GABA. Natural Medicines monograph 2014. Viewed 10 Oct 2015, https://naturalmedicines.therapeuticresearch.com/

GABA is likely safe when taken in the amounts commonly found in foods. It is possibly safe when taken in larger amounts as medicine. Doses of up to 1.5 grams daily have been used for up to one month. 

1. Not recommended during pregnancy or lactation.
2. GABA may decrease blood pressure in hypertensive individuals. If you take GABA in addition to taking blood pressure medication, your blood pressure may drop too low.
3. Use with caution in patients taking synthetic GABA agonist medications or herbs that interact with the GABAergic system (e.g. Valeriana officinalis, Hypericum perforatum). If additional sedative/relaxant effects are required, start GABA supplementation slowly and at a low dose.

GABA agonist medications: Baclofen, Zolpidem, Progabide, AZD 3355, Tramiprosate, Gaboxadol, Adipiplon, Arbaclofen Placarbil, Lesogaberan, Muscimol, Phenibut, Zaleplon u.c.

1. Unlike synthetic GABA-agonist drugs, natural GABA is virtually without side effects.

Possible side effects

GABA oral supplements are generally well tolerated by healthy adults. Some people may experience negative side effects, including:

• Gastric distress.
• Nausea.
• Diminished appetite.
• Constipation.
• Burning throat.
• Drowsiness and fatigue.
• Muscle weakness.
• Shortness of breath, at very high doses.

References 1 Reference:https://www.webmd.com/vitamins/ai/ingredientmono-464/gamma-aminobutyric-acid-gaba 2 Reference:https://go.drugbank.com/categories/DBCAT000427 3 Reference:https://www.fxmedicine.com.au/blog-post/gamma-aminobutyric-acid-gaba-monograph

GABA (Gamma-Aminobutyric acid) Deficiency

People with certain medical conditions may have lower levels of GABA. Some of these conditions include:

• Seizure disorders
• Anxiety
• Chronic stress
• Depression
• Difficulty concentrating and memory problems
• Muscle pain and headaches
• Insomnia and other sleep problems
• Low GABA activity is also associated with substance use disorders.

Some people with these conditions take GABA supplements to help manage their symptoms, but GABA is found naturally in varieties of green, black, and oolong tea, as well as in fermented foods including kefir, yogurt, and tempeh. Other foods contain GABA or may boost its production in the body, including whole grains, fava beans, soy, lentils, and other beans; nuts including walnuts, almonds, and sunflower seeds; fish including shrimp and halibut; citrus, tomatoes, berries, spinach, broccoli, potatoes, and cocoa. However, these symptoms have many psychological and physical causes, so you should talk to your doctor before treating them with a supplement. 4 Reference: National Library of Medicine, GABA-transaminase deficiency; https://www.healthline.com/health/gamma-aminobutyric-acid#uses https://www.psychologytoday.com/us/blog/sleep-newzzz/201901/3-amazing-benefits-gaba

More than 300 million people are affected by major depressive disorder (MDD), and limitations in the access to and effectiveness

of MDD treatment have made it the leading cause of disability world-wide. Despite long-standing efforts to identify the pathophysiology of depression, the underlying neurobiological determinants remain largely undefined. The relatively low rate of heritability, approximately 37%, the absence of variants with substantial impact on depression risk, the polygenic nature of depression risk, and the heterogeneity of depression have contributed to the difficulty in identifying genetic determinants of susceptibility. 

Environmental factors, such as trauma and stressful life events, contribute to depression risk through altering brain structure, chemistry, and function. Chronic exposure to social, psychological, or physical stressors provides useful contexts for studying how the brain transduces environmental stress exposure into depression.

The mechanisms underlying the pathophysiology and treatment of depression and stress-related disorders remain unclear, but studies in depressed patients and rodent models are beginning to yield promising insights. These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients. Studies of the neurobiological basis of the these alterations have focused on both the principle, excitatory glutamate neurons, as well as inhibitory GABA interneurons. Dysfunction of the central gamma-aminobutyric system has long been associated with anxiety spectrum disorders. While GABA neurons make up a smaller fraction of the total neuronal population, approximately 15%–20% compared to glutamate, inhibitory neurotransmission and balance with excitatory transmission are critical for normal brain function.

Based on evidence of altered glutamate and functional connectivity, it is not surprising that there is also evidence of disrupted GABA neurotransmission that contributes to the neurobiology of MDD.

Briefly, depression is often associated with decreased GABAergic function, while various antidepressant (AD) manipulations tend to increase it; low GABA function is proposed to be an inherited biological marker of vulnerability for depression; positive modulators of GABA-A receptors can have AD actions, while GABA-A negative modulators often produce depression. There is a large body of evidence to confirm that GABAergic anxiolytic drugs do produce AD effects in patients.

Summarizing, it seems likely that there are overlapping GABAergic mechanisms of anxiety and depression due to: 

1. common neurochemical mechanisms;
2. similar brain structures involved in the regulation of anxiety and depression; 
3. common genetic origins of anxiety and depression; and 
4. overlapping or correlation in neuropsychopharmacological effects of drugs.

Numerous studies have demonstrated a direct correlation between major depressive disorders and significantly decreased GABA concentrations in the brain. This is not to say that GABA deficiency causes depression but that it plays an important role as part of the overall treatment of depression, PMS, ADHD, bipolar disorder, panic, fear, mental blocks, a racing mind and anxiety. Doctors frequently prescribe benzodiazepines for most of these conditions but the major drawback to their use is that they can be addictive. GABA supplementation is not addictive and it is one nutrient that can be used to help facilitate withdrawal from benzodiazepines.

The optimal dose of GABA varies with the need and the individual. The usual anti-anxiety doses for most adults are between 500 and 5000 mg daily in divided doses. 1 Reference: Ronald S. Duman, Gerard Sanacora and John H. Krystal; Department of Psychiatry, Yale University School of Medicine;  Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficit and Reversal by Novel Treatments; DOI:https://doi.org/10.1016/j.neuron.2019.03.013 2 Reference: Kalueff, A. V., & Nutt, D. J. (2007). Role of GABA in anxiety and depression. Depression and Anxiety, 24(7), 495–517. doi:10.1002/da.20262 3 Reference: Dr. Zoltan P. Rona, M.D., M.Sc. Defuse Stress and Calm Nerves Naturally

1. Alcohol is believed to mimic GABA's effect in the brain, binding to GABA receptors and inhibiting neuronal signaling.
2. Alongside GABAergic mechanisms, GABA has also been detected in other peripheral tissues including intestines, stomach, Fallopian tubes, uterus, ovaries, testes, kidneys, urinary bladder, the lungs and liver, albeit at much lower levels than in neurons.
3. In 1883, GABA was first synthesized, and it was first known only as a plant and microbe metabolic product.
4. GABA is also found in plants. It is the most abundant amino acid in the apoplast of tomatoes. Evidence also suggests a role in cell signalling in plants.
5. GABA tea is tea that has undergone a special oxygen-free fermentation process, and as a result has accumulated GABA in tea leaves. This technology has been created in Japan. 

L-theanine (γ-glutamylethylamide) is a derivative of L-glutamic acid, an amino acid most associated with tea leaves (Camellia sinensis L.). It has a similar chemical structure to glutamate (a neurotransmitter involved in more than 90% of all synaptic connections in the human brain). Upon reaching the brain, L-theanine turns into an active neurotransmitter, which ensures the transmission of intercellular nerve impulses and effectively affects the processes of inhibition and relaxation. In other words, your mood, concentration, sleep pattern, appetite and alertness are mainly influenced by various neurotransmitters - endogenous chemicals that transmit a signal from a neuron to a target cell through a synapse, including GABA (gamma-amino butyric acid), serotonin and dopamine, as well as brain function inhibitory hormones such as cortisol and corticosterone. When you're under stress, cortisol and corticosterone levels rise, resulting in reduced brain function.1

To prevent this, L-theanine enhances the action of neurotransmitters such as GABA, thus reducing the level of excitatory brain chemicals - cortisol and corticosterone - and promoting relaxation. Elevated levels of cortisol and corticosterone not only cause anxiety, but also affect various other brain functions such as spatial learning and memory.

Currently, four types of electromagnetic waves are known in the human brain: beta, alpha, theta and delta waves. Each has its own frequency range and is associated with a different activity, for example theta waves are associated with sleepiness and alpha waves with relaxation. Alpha brain waves are considered a measure of relaxation. Their action is associated with increased creativity, better performance under stress, better learning and concentration, and reduced anxiety. L-theanine increases the activity of alpha waves, thereby relaxing the activity of the brain.1; 2As you continue to relax, alpha waves begin to dominate the entire brain. The lack of these waves is caused by stress, illness, anxiety. 1 Atsauces: 1) Eschenauer, G. (2006). Pharmacology and therapeutic uses of theanine. American Journal of Health-System Pharmacy, 63(1), 26–30. doi:10.2146/ajhp050148 2) Gomez-Ramirez, M., Kelly, S. P., Montesi, J. L., & Foxe, J. J. (2008). The Effects of l-theanine on Alpha-Band Oscillatory Brain Activity During a Visuo-Spatial Attention Task. Brain Topography, 22(1), 44–51. doi:10.1007/s10548-008-0068-z

L-theanine is generally considered safe to use. It is not associated with serious adverse effects.

The most common side effects of L-theanine are headache, nausea, and irritability.1 However, nausea appears to be primarily associated with L-theanine intake through green tea rather than supplements. Similarly, the side effect of irritability has been associated with the double use of caffeine and L-theanine. 1 Atsauce: 1) Giesbrecht T, Rycroft JA, Rowson MJ, De bruin EA. The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutr Neurosci. 2010;13(6):283-90.

If your usual answer to the question “How are you?” is “Tense –work never ends” or “I can't get anything done”, you may want to supplement your daily routine with L-theanine to reduce your stress and anxiety symptoms.1

L-theanine is associated with anti-anxiety effects by inhibiting the excitation of cortical neurons. Stress is our body's natural response to danger. For example, when you see a bear in the forest, your sympathetic nervous system is activated, hormones are released, your heart beats faster, your hands sweat, your mouth becomes dry, etc. However, you can also activate your sympathetic nervous system accidentally, so to speak, “unnecessarily”, and this can become a problem.

At best, the effects of stress can result in unpleasant, sweaty palms. At worst, you may suffer from chronic stress and related physiological reactions, such as increased heart rate and blood pressure, or weakened immunity.

Students are also under regular stress. Stress increases the level of the hormone corticosterone, and as a result, the brain cannot function as it is supposed to. Consequently, learning becomes ineffective. It was proven in the study2 that the use of L-theanine ensured a faster simple reaction time, faster numerical working memory reaction time, and improved sentence test accuracy. Self-assessments of persons such as “headache” and “fatigue” were reduced.

This proves that by reducing levels of the hormone corticosterone, L-theanine protects cognitive abilities from potential disorders that could occur due to high levels of the stress hormone.

Researchers have established3 that L-theanine helps in regulating high blood pressure, thus helping people to keep it at a healthy level in stressful situations.

If you suffer from stress-induced insomnia, L-theanine can help. A team of researchers conducted a study4 to investigate the ability of L-theanine to improve sleep quality. A study shows that taking 200 mg of L-theanine before bed improves sleep quality, not sedation, but anxiolysis. As L-theanine does not induce daytime drowsiness; its use can be beneficial at any time of the day.

L-theanine improves sleep quality in a number of ways. First, the amino acid enables a person to relax better and become less anxious. With the stimulation of relaxation and reduced stress, you can fall asleep easier and faster. By reducing anxiety and promoting relaxation, L-theanine helps you go through the entire normal sleep cycle, including the much-needed deep REM phase, for complete mind and body rejuvenation. 1 Atsauce: 1) Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). l-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39–45. doi:10.1016/j.biopsycho.2006.06.006 2) Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., & Scholey, A. B. (2008). The effects of l-theanine, caffeine and their combination on cognition and mood. Biological Psychology, 77(2), 113–122. doi:10.1016/j.biopsycho.2007.09.008 3) Rogers, P. J., Smith, J. E., Heatherley, S. V., & Pleydell-Pearce, C. W. (2007). Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology, 195(4), 569–577. doi:10.1007/s00213-007-0938-1 4) Rao, T. P., Ozeki, M., & Juneja, L. R. (2015). In Search of a Safe Natural Sleep Aid. Journal of the American College of Nutrition, 34(5), 436–447. doi:10.1080/07315724.2014.926153

L-tyrosine is a replaceable (non-essential) aromatic amino acid that serves as a raw material in the body for the synthesis of various other substances, for example, it is a precursor for the synthesis of the thyroid gland hormone thyroxine (T4) (produced by iodination of tyrosine), the pigment melanin and other biologically active substances such as catecholamines - epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. These are very important biologically active substances that are synthesised in the neuron and released in the synapse; binding to the receptors of another cell, they transmit a nerve impulse from the synapse to the cell (neurotransmitters), which are closely related to the corresponding concentration of L-tyrosine in the body.

L-tyrosine is part of many natural proteins, including enzymes. In the body, L-tyrosine is synthesised from phenylalanine with the help of the enzyme phenylalanine-4-hydroxylase.

How does tyrosine work in our body? First, the thyroid gland absorbs iodine from food. Once these iodine molecules are oxidised, they are ready to attach to the tyrosine found in thyroglobulin (a protein produced by the thyroid gland). When iodine and tyrosine combine, they create thyroid gland hormone precursors, monoiodotyrosine (T1) and diiodotyrosine (T2). T1 and T2 then combine to form the thyroid gland hormones triiodothyronine (T3; thyroglobulin with three iodine molecules) and thyroxine (T4, thyroglobulin with four iodine molecules). T4 and T3 are the primary thyroid gland hormones that are essential for regulating metabolic processes throughout the body.

So, to summarise the roles of tyrosine in the body, the following should be mentioned:

A lack of tyrosine can cause thyroid gland dysfunction, such as hypothyroidism, as well as cause depression or increased nervousness due to impaired catecholamine synthesis.

L-Tyrosine is considered safe in most doses, but you should still consult your doctor before using it if you are taking any medications. It can interact with medications, including some medications used to treat thyroid gland disorders or depression.

Monoamine oxidase inhibitors (MAOIs) - Tyrosine can cause serious increases in blood pressure in people taking antidepressants known as MAOIs. This rapid rise in blood pressure, also called a “hypertensive crisis,” can lead to a heart attack or stroke. People taking MAOIs should avoid foods and supplements that contain tyrosine. For instance:

Levodopa - Tyrosine should not be used at the same time as levodopa, a medicine used to treat Parkinson's disease. Levodopa may interfere with the absorption of tyrosine.

In some cases, extra use of tyrosine can cause insomnia, restlessness, palpitations, headaches, stomach disorders and heartburn.

Because tyrosine is involved in the production of thyroid gland hormones, you should not take it if you have been diagnosed with a thyroid disorder such as hyperthyroidism or Graves' disease.

The recommended daily dietary allowance (RDA) for tyrosine is 25 mg per kilogram of body weight.1 Assuming that a person receives half of the required amino acid, this amounts to 12.5 mg per kg. Thus, a person weighing 70 kg should consume about 875 mg of tyrosine per day, which is the amount used to calculate the RDA. Tyrosine is found in a variety of foods, such as peanuts, fish, chicken, turkey, soy, eggs, and cottage cheese. It is also in pumpkin seeds, oats, wheat, beans, sesame seeds, avocados, and bananas. 1 Atsauce: George M. Kapalka, in Nutritional and Herbal Therapies for Children and Adolescents, 2010

Hypothyroidism, or reduced thyroid function, means that the thyroid gland produces insufficient amounts of important hormones that have an impact on all metabolic processes.  The most common causes of hypothyroidism are chronic autoimmune thyroiditis, the use of various medications, radiation therapy, and thyroid surgery. It should also be taken into account that people are reluctant to use sea vegetables, such as kelp, in their diet, as well as because of the taste, people prefer salt without iodine addition, which is also the reason why iodine deficiency is becoming more and more common.

The most common symptoms of hypothyroidism are fatigue, increased sensitivity to cold, dry skin, brittle hair, a person looking much older than they actually are. Women often have irregular menstruation, cognitive disorders, depression.

It has also been shown that people with thyroid disease, whether hyperthyroid or hypothyroid, have very fluctuating tyrosine levels in the blood serum, and those with hypothyroidism (low thyroid hormone levels) usually have lower than normal blood tyrosine levels.

Combined with the proven fact that the use of medications (for example, levothyroxine, a synthetic thyroid gland hormone used to treat thyroid diseases and disorders) improves the metabolism of tyrosine in the liver, it may be worth consulting a doctor and considering the possibility to supplement everyday life with both thyroid medication and tyrosine (either by following a special diet or using nutritional supplements).

If you choose to supplement your everyday life with L-tyrosine, remember that it is more effective to use it together with other minerals that can improve thyroid function, such as zinc and selenium. Zinc helps to improve the conversion of thyroxine (T4) to triiodothyronine (T3) in hypothyroid patients with insufficient thyroid function. Selenium, on the other hand, helps reduce thyroid antibodies and is also involved in the conversion of T4 to T3.

Hopkins and Cole discovered tryptophan at the beginning of the twentieth century after isolating it from the casein protein, while Ellinger and Flamand determined its molecular structure shortly thereafter. L-tryptophan (i.e., tryptophan) is one of the eight essential amino acids (amino acids that cannot be synthesised by the human body and must be obtained from the diet). 1 Atsauces: Richard, D. M., Dawes, M. A., Mathias, C. W., Acheson, A., Hill-Kapturczak, N., & Dougherty, D. M. (2009). L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. International Journal of Tryptophan Research, 2, IJTR.S2129. doi:10.4137/ijtr.s2129

So L-tryptophan is a unique protein amino acid that has an indole ring. Indole is a typical nitrogen heterocyclic aromatic compound, widely distributed in our daily products and natural environment. The indole ring is present in many alkaloids, phytohormones, plant flower oils, pigments and proteins. Because the indole nucleus has a wide spectrum of biological activities, it is widely used in the pharmaceutical industry.

After L-tryptophan enters various tissues and cells of the body, it is included in protein metabolism and synthesis, and it can also participate in various metabolic processes depending on the expression of specific enzyme activities in the tissues. 2 Atsauces: Palego, L., Betti, L., Rossi, A., & Giannaccini, G. (2016). Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans. Journal of Amino Acids, 2016, 1–13. doi:10.1155/2016/8952520  

L-tryptophan is the only precursor of peripherally and centrally produced serotonin. 3 Atsauces: Jenkins, T., Nguyen, J., Polglaze, K., & Bertrand, P. (2016). Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8(1), 56. doi:10.3390/nu8010056 Serotonin regulates the balance of the nervous system, mental stability, mood and also sleep. On the other hand, melatonin is synthesised from serotonin. As the “output material” of melatonin, serotonin helps regulate sleep cycles and the internal clock. It has been proven that melatonin plays a decisive role in the quality of sleep.  Melatonin is a biologically active substance that is formed in our brain during the night (darkness) and regulates the biorhythms of our body - the cycle of sleep and wakefulness. 2 Atsauces: Palego, L., Betti, L., Rossi, A., & Giannaccini, G. (2016). Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans. Journal of Amino Acids, 2016, 1–13. doi:10.1155/2016/8952520 Both melatonin and serotonin are formed from the essential amino acid L-tryptophan, which we can only take in through food or food supplements. Significant amounts of L-tryptophan can be found in various types of cheese and meat.

Food supplements containing L-tryptophan are safe as long as they are not taken on a long-term basis. L-Tryptophan can cause someside effects such as drowsiness, stomach pain, vomiting, diarrhoea, headache, blurred vision, dizziness, palpitations and more.

L-tryptophan can interfere with the effects of many different drugs. Do not take L-tryptophan if you are taking antidepressants known as selective serotonin reuptake inhibitors (SSRIs), MAO inhibitors, tricyclic antidepressants, and atypical antidepressants. This can lead to a life-threatening condition called serotonin syndrome. Symptoms of serotonin syndrome include:

• • Extreme anxiety
• • Heart palpitations
• • Delirium
• • Severe muscle spasms
• • Increased body temperature

L-tryptophan supplements are not recommended for pregnant women.

Consult your doctor before taking L-tryptophan if you have cirrhosis of the liver.

Always tell your doctor about any food supplements you take, including natural and over-the-counter supplements. In this way, your doctor can check for possible side effects or interactions with any medications.

Atsauce Atsauce: https://www.webmd.com/vitamins-and-supplements/l-tryptophan-uses-and-risks

The main role of L-tryptophan in the human body is a part of protein synthesis. Because tryptophan is found in the lowest concentration of all the amino acids in the body, it is relatively lessavailable and it is considered to play a decelerating role in protein synthesis. Tryptophan is also a precursor of two important metabolic processes: kynurenine synthesis and serotonin synthesis (substance involved in the reaction resulting in the formation of the target substance - an intermediate member of the metabolic pathway). 1 Atsauce: Sainio EL, Pulkki K, Young SN. L-tryptophan: Biochemical, nutritional and pharmacological agents. Amino Acids. 1996;10:21–47.

Accordingly, serotonin is synthesised from the irreplaceable amino acid in the human body - L-tryptophan, while serotonin regulates mood, improves sleep quality and appetite. It is important that serotonin also participates in the regulation of dopamine - if it is lacking, it promotes its release, if there is too much dopamine - it helps to slow down its release. Low serotonin levels are thought to be closely related to depression, anxiety, sleep disorders, weight gain, and other health problems. If there is a deficiency of serotonin in the body, then the person's mood deteriorates, pessimism and apathetic mood increases, as a result of which the desire to do something disappears.

Several laboratories have demonstrated the positive effect of L-tryptophan on sleep quality 2 Atsauce: Hartmann, E. (1982). Effects of L-tryptophan on sleepiness and on sleep. Journal of Psychiatric Research, 17(2), 107–113. doi:10.1016/0022-3956(82)90012-7 , as well as the fact that tryptophan reduces the time it takes to fall asleep in patients with mild insomnia or those who take a long time to fall asleep. 3 Atsauce: Simon N. Young:  Is tryptophan a natural hypnotic?; Journal of Psychiatry & Neuroscience; 2003 Mar; 28(2): 160; PMCID: PMC161739

Tryptophan has not been found to have any effect on next-day alertness. In patients with moderate to severe insomnia, tryptophan is not as effective as standard sleep aids.

In general, we can say that serotonin regulates the balance of the nervous system; mental stability, mood and also sleep, is the “raw material” for melatonin. In turn, it has been proven that melatonin plays a decisive role in the quality of sleep.  Both melatonin and serotonin are formed from the essential amino acid L-tryptophan, which we can only get through food or food supplements.

However, when tryptophan is ingested as part of the diet, it is joined by other large neutral amino acids that compete for the system that transports them all to the brain. As a result, dietary tryptophan intake, unlike tryptophan in the form of food supplements, does not increase tryptophan levels in the brain. Thus, the popular myth that a glass of milk before bed has a calming effect because it contains tryptophan is false. 3 Atsauce: Simon N. Young:  Is tryptophan a natural hypnotic?; Journal of Psychiatry & Neuroscience; 2003 Mar; 28(2): 160; PMCID: PMC161739

Glutamine is the most abundant and versatile free-form (already broken down and easily absorbed) α-amino acid in our bodies. In the body, glutamine is formed from glutamic acid by the action of the enzyme glutamine synthetase, which binds ammonia. Glutamine is an important component of nitrogen metabolism. Like arginine, glutamine is a biochemical nitrogen donor, forming other amino acids, purines and pyrimidines. 1 Ref.: https://en.wikipedia.org/wiki/Glutamine For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for tissue development and for the formation of the main new immune cells, lymphocytes. Glutamine helps produce cytokines – biochemically active protein molecules that are produced by cells of the immune system to affect other immune cells. These cytokines activate or modulate cells of the innate immune system (macrophages, dendritic cells, natural killer cells) and also epithelial cells. 2 Ref.: Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., & Newsholme, P. (2018). Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients, 10(11), 1564. doi:10.3390/nu10111564 The immune cells consume glutamine both when the body is healthy and during illness, and this consumption is similar to or greater than that of glucose.

Glutamine is involved in various biochemical processes. Some provide energy, serving as a precursor for amino acid synthesis, a nitrogen donor for nucleic acid formation, helping to synthesise intracellular proteins and acting as essential support in the acid-base balance. 3 Ref.: De Oliveira, D. C., da Silva Lima, F., Sartori, T., Santos, A. C. A., Rogero, M. M., & Fock, R. A. (2016). Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression. Nutrire, 41(1). doi:10.1186/s41110-016-0016-8

Glutamine is also a potential precursor for the synthesis of N-acetyl-glucosamine and N-acetyl-galactosamine, which may play a crucial role in the synthesis of intestinal mucin (a glycoprotein) and thus in maintaining a passive barrier against bacterial invasion. 4 Ref.: Khan J, Iiboshi Y, Cui L, Wasa M, Sando K, Takagi Y, Okada A. Alanylglutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine. JPEN J Parenter Enteral Nutr. 1999;23:24–31.

Basically, it is “food” for enterocytes (the cells that make up the small intestine), helping to heal intestinal inflammation. It is ideal for autoimmune diseases, which are often aggravated by inflammatory bowel disease. Additional use of glutamine has been shown to relieve psoriasis, eczema and joint pain. If inflammatory markers are detected in a gut microbiome test, glutamine may help.

Medications used to prevent seizures (Anticonvulsants) interact with glutamine.

Glutamine may increase the risk of seizures in some people. Therefore, taking glutamine may decrease the effects of medications used to prevent seizures.

When taken orally, glutamine is likely safe when used in doses of up to 40 grams daily. Side effects are generally mild and might include bloating, nausea, dizziness, heartburn, and stomach pain.

Glutamine can increase the risk of brain function issues in people with advanced liver disease. Consult your healthcare professional if you have any advanced liver disease.

Bipolar disorder: glutamine might increase the risk of mania or hypomania in people with this condition.

Monosodium glutamate (MSG) sensitivity: if you are sensitive to MSG, you might also be sensitive to glutamine because the body converts glutamine to glutamate.

Nutrients can impact and regulate cellular metabolism and cell function which is particularly important for the activation and function of diverse immune subsets. Among the critical nutrients for immune cell function and fate, glutamine is possibly the most widely recognised immune-nutrient, playing key roles in the TCA cycle (tricarboxylic acid cycle – cellular respiration involving a series of chemical reactions that release stored energy), heat shock protein responses and antioxidant systems.

If speaking of immunity, we must not forget the intestinal tract. Why? For many years, the gut was only studied as an organ for digestion, nutrient absorption and fermentation. However, now we know that the intestinal tract is a complex organ performing a variety of critical physiological functions. The intestinal mucosa not only contains a secretion but also immune and neuroendocrine cell-absorbing enterocytes (an epithelial cell in the intestinal mucosa that mainly absorbs nutrients). One layer of epithelium covering the gastrointestinal tract creates a selective barrier to prevent harmful substances such as toxins, allergens and pathogens from entering the large circulatory tract. 1 Ref.: De Oliveira, D. C., da Silva Lima, F., Sartori, T., Santos, A. C. A., Rogero, M. M., & Fock, R. A. (2016). Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression. Nutrire, 41(1). doi:10.1186/s41110-016-0016-8

From this perspective, we can understand the important role of glutamine. Glutamine is the main energy substance of enterocytes. Rapidly dividing cells need glutamine, which serves as a nitrogen donor, for amino acids, purine and pyrimidine by acting on carbamoyl phosphate synthetase. 2 Ref.: Lobley GE, Hoskin SO, McNeil CJ. Glutamine in animal science and production. J Nutr. 2001;131:2525S–31

Based on this, glutamine is generally included on the list of “immune elements” that have biological effects.

Conclusion: glutamine is required by the cells of the immune system both as a primary fuel and as a carbon and nitrogen donor for nucleotide precursor synthesis. In vivo studies have demonstrated that glutamine is essential for optimal immune cell functioning for monocytes, lymphocytes and neutrophils. A number of studies of patients have shown improved infectious morbidity when receiving glutamine. 3 Ref.: Andrews, F. J., & Griffiths, R. D. (2002). Glutamine: essential for immune nutrition in the critically ill. British Journal of Nutrition, 87(S1), S3. doi:10.1079/bjn2001451

1. Cabbage and beetroot contain high concentrations of glutamine. Other dietary sources include fish, beans and dairy products.
2. Unlike protein or creatine, glutamine does not directly help build muscle mass.
3. If you happen to spend more time in the gym, glutamine helps in recovering from muscle soreness and fatigue, thus reducing the “recovery” time between workouts.
4. Having enough glutamine in your body promotes good ‘mucosal integrity’ of the gut – which means it has a strong defence against irritants, such as from alcohol or drugs such as aspirin.
5. It is best to take L-glutamine about 10-15 minutes before a meal on an empty stomach and take it 2–3 times per day (so before meals 2–3 per day) to provide support evenly and consistently.
6. However, glutamine should not be taken with anything hot such as coffee, tea, soup or broth. The main reason is that high temperatures can denature (take away the natural properties) or damage the amino acids.