Glutamine amino acid benefit and side effects, dosage, use for sports and immune support
December 21 2016 by
Ray Sahelian, M.D.

L Glutamine is traditionally considered a nonessential amino acid but may be conditionally essential in patients with catabolic (loss of muscle tissue due to disease) conditions. Glutamine -supplemented foods in these patients have been shown to prevent deterioration of gut permeability, protect against the development of intestinal mucosal atrophy, and improve nitrogen balance. Levels in plasma and skeletal muscle are decreased in those with cancer. Glutamine supplementation can attenuate loss of protein in the muscle and protect immune and gut-barrier function during radiochemotherapy in patients with advanced cancer.
     L-glutamine is the most prevalent amino acid in the blood. Human cells readily manufacture it and under normal circumstances dietary intake and production is sufficient. However, in times of stress or increased energy output, the body's tissues need more than usual.

Benefit of glutamine - in sports - research review
Short-term ingestion of glutamine does not enhance weightlifting performance in resistance-trained men.
   Heavy exercise induces impairment of lymphocyte function. Ten male athletes participated in a randomized, placebo-controlled, double-blind crossover study. Each athlete performed bicycle exercise for 2 h at 75% of maximum O(2) consumption on 2 separate days. Glutamine or placebo supplements were given orally during and up to 2 hours post-exercise. Most lymphocyte subpopulations decreased 2 h after exercise. Glutamine supplementation abolished the post-exercise decline in plasma glutamine concentration but had no effect on lymphocyte trafficking, Natural killer cell activities, T cell proliferation, catecholamines, human growth hormone, insulin, or glucose. This study does not support the idea that glutamine plays a mechanistic role in exercise-induced immune changes.

Bodybuilding and strength
The combination of glutamine and creatine increases muscle mass and power.

The effects of 8 weeks of creatine monohydrate and glutamine supplementation on body composition and performance measures.
J Strength Cond Res. 2003.
Twenty-nine (17 men, 12 women) collegiate track and field athletes were randomly divided into a creatine monohydrate (CM) group, creatine monohydrate and glutamine (CG) group, or placebo group. The CM group received 0.3 g creatine per kg body mass per day for 1 week, followed by 0.03 g body mass per day for 7 weeks. The CG group received the same creatine dosage scheme as the CM group plus 4 g glutamine /day. All 3 treatment groups participated in an identical periodized strength and conditioning program during preseason training. Body composition, vertical jump, and cycle performances were tested before and after the 8-week supplementation period. Our results suggest CM and creatine-glutamine significantly increase body mass, lean body mass, and initial rate of power production during multiple cycle ergometer bouts.

Burn patients
The influence of combined supplementation of glutamine and recombinant human growth hormone on the protein metabolism in severely burned patients
Zhonghua Shao Shang Za Zhi 2004.
Sixty severely burned patients were enrolled in the study and were randomly divided into control and glutamine with recombinant human growth hormone (glutamine + rhGH groups. The total hospital stay days in glutamine + rhGH group were less than that in the control and glutamine groups. Combined administration of glutamine and rhGH could be beneficial to the elevation of plasma glutamine level in severely burned patients and the systemic protein synthesis was therefore enhanced and the wound healing rate was improved.

Hospitalized critically ill patients
Cochrane Database Syst Rev. 2014. Glutamine supplementation for critically ill adults. Glutamine is a non-essential amino acid which is abundant in the healthy human body. There are studies reporting that plasma glutamine levels are reduced in patients with critical illness or following major surgery, suggesting that glutamine may be a conditionally essential amino acid in situations of extreme stress. In the past decade, several clinical trials examining the effects of glutamine supplementation in patients with critical illness or receiving surgery have been done, and the systematic review of this clinical evidence has suggested that glutamine supplementation may reduce infection and mortality rates in patients with critical illness. However, two recent large-scale randomized clinical trials did not find any beneficial effects of glutamine supplementation in patients with critical illness.

Glutamine - antioxidant nutrient supplementation can increase body weight, body cell mass, and intracellular water when compared with placebo in HIV patients. It is helpful in those with HIV who are receiving certain types of anti-viral medicines.

L-glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals.
HIV Clin Trials. 2003.
HIV-infected patients with nelfinavir-associated diarrhea for >1 month were randomized to receive L-glutamine 30 g/day or placebo for 10 days in a prospective, double-blind, crossover study. In this population of HIV-positive participants, L-glutamine 30 g/day significantly reduced the severity of nelfinavir-associated diarrhea and produced improved quality of life compared with placebo.

Immune system health
Glutamine metabolism by lymphocytes, macrophages, and neutrophils: its importance in health and disease.
J Nutrional Biochemistry. 1999.
The high rate of glutamine utilization and its metabolism in such immune cells has raised the question of why glutamine is responsible for these functions. The macrophage has access to a variety of metabolic fuels both in vivo and in vitro. The quantitatively important role of glutamine in the processes of free radical and cytokine production has been established in our laboratories. Our current understanding of the rate of utilization and the pathway of metabolism of glutamine by cells of the immune system raises some intriguing questions concerning therapeutic manipulation of utilization of this amino acid, specifically the phagocytic and secretory capacities of cells of the defense system can be beneficially altered.

Effects of an oral mixture containing glycine, glutamine and niacin on memory, HGH and IGF-I secretion in middle-aged and elderly subjects.
Nutr Neuroscience. 2003.
Aging is associated with declining activity of the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis and with a decrease in cognitive function. The stimulatory effect of an orally administered nutritional supplement, mainly containing glycine, glutamine and niacin on the GH-IGF-I axis and on mood and cognition was investigated. Forty-two healthy subjects (14 men and 28 women, aged 40-76 years) were enrolled in a randomised, double blind, placebo-controlled trial. They received 5 g of a nutritional supplement or placebo, twice daily orally for a period of 3 weeks. The nutritional supplement ingestion for 3 weeks was found to increase serum GH levels with 70% relatively to placebo, whereas circulating IGF-I levels did not change. GH increase was not associated with improvement in mood or memory. Individual increases in IGF-I, but not GH, were associated with improved memory and vigor. It is concluded that an oral mixture of glycine, glutamine and niacin can enhance GH secretion in healthy middle-aged and elderly subjects.

Sickle cell anemia
Oral glutamine supplementation decreases resting energy expenditure in children and adolescents with sickle cell anemia.
J Pediatr Hematol Oncology. 2004.
Twenty-seven children and adolescents (13 boys, 14 girls), 5 to 17 years old, received orally administered glutamine (600 mg/kg per day) for 24 weeks. After 24 weeks, the patients' median REE (kcal/d) decreased by 6%. Patients with less than 90% ideal body weight had even greater declines in REE after 24 weeks. Improvements in nutrition parameters and in two amino acids in the plasma were observed. After 24 weeks of orally administered glutamine, children and adolescents with sickle cell anemia had a decrease in REE and improvement in nutritional parameters. Those who were underweight had a greater decrease in REE than those of normal body weight. Lowering REE may be an effective way to improve the growth of these children and adolescents.

L Glutamine side effects, safety, danger
Glutamine has few side effects except in massive doses. We are not aware of any glutamine side effects when used in low dosages. As to long term daily use of glutamine in high doses, we really don't know what potential danger, if any, it would have in the long run.

You state that there are no side effects of glutamine except in high doses. I learned that glutamine converts to glutamate, the major excitatory neurotransmitter. Have you heard that there could be dangers of taking glutamine because of the risk for the neurotoxicity of glutamate? Personally i have found creatine to be much more effective for muscle gains and i have noticed stimulating effects when trying glutamine.
   Perhaps we should have clarified that there are no known short term glutamine side effects. As to long term daily use in high doses, we really don't know what potential danger, if any, it would have.

Glutamine appears be helpful in those with cancer, HIV, or other medical conditions that lead to a catabolic state, but does not seem to play a significant role (by itself) in those who are healthy or provide any significant enhancement in athletic performance.

Glutamine and glutamate with proline, histidine, arginine and ornithine, make up 25% of the dietary amino acid intake and form the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals glutamine is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated calcium transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to alpha-ketoglutarate, an important component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue.

Glutamine research, combining with other supplements
I take tribulus sexual herbal enhancer and yohimbe for erectile function benefit, just wondering if the amino acid interferes with their function. Any problems with pygeum africanum extract used for prostate or also saw palmetto extract.
   Not that I know of. I don't think there should be a problem with
quercetin use or with sitosterol as long as dosages are low.

Other forms of the amino acid
How is L-Alanyl-L-Glutamine Dipeptide different than glutamine in a practical sense? I have seen ads for it in a muscle magazine.
   I have not seen any studies comparing L-Alanyl-L-Glutamine Dipeptide to glutamine itself.

I noticed you had a question on your website about the differences between L-Alanyl-L-Glutamine and Glutamine. Glutamine is extremely unstable when added to water or solutions and its content will be degraded over a short time period. L-Alanyl-L-Glutamine is a dipeptide that provides a stable form of glutamine as well as additional hydration benefits. I would be happy to forward on the stability data and our recent clinical study. Karen E. Todd, RD, CISSN, CSCS, Registered Dietitian, Director of Marketing, Kyowa Hakko U.S.A., Inc.

Study in mice
J Nutr Biochem. March 2014. Oral supplementations with free and dipeptide forms of l-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia.

I developed an intestinal infection when traveling abroad. I was given several courses of antibiotics which did not resolve my condition. I consequently developed leaky gut and reduction in beneficial intestinal flora. I took myself off the antibiotics and took about 10-20 grams of glutamine. Slowly but surely my symptoms resolved themselves. I've read that long term intake of high amounts of glutamine is peripherally associated with cancer growth, because cancer cells have a higher need for glutamine. I've also read about feedback loops - where oral supplementation reduces endogenous production of glutamine - thus depleting cancer cells of glutamine. this is the mechanism behind the use of whey protein as an anticancer agent.
   The long term benefits and risk of high dose glutamine supplementation are not fully clear to me.

Would taking glutamine pills or powder increase my height (18 year old)?
   There is no evidence that the use of this amino acid supplement increases height.

I am a medical doctor. Today, I received the following verbiage in an email from NewsMax reporting the opinion of Russell Blaylock, MD: "Blaylock Tip of the Week, High-Protein Diets Can Increase Dementia Risk. A diet high in protein actually may damage your brain. In one study, meat consumption was associated with a 300 percent increased risk of dementia. The increase could be because of pesticides dissolved in the animalís fat or the high concentration of proteins, which contain glutamate. High-protein diets increase the risk of a number of diseases. One of the leading experts in excitotoxicity found that eating a diet high in meats increased blood glutamate levels. The levels were 100 percent higher if the person had a neurodegenerative disease. Meats especially beef and other red meats are naturally high in glutamate, the amino acid that causes the excitotoxicity. The juices are especially high in glutamate. Because glutamine is converted into glutamate in the brain, I would advise against taking glutamine supplements. Studies have shown that high glutamine intake increases excitotoxicity, especially in people with a neurodegenerative disease. Some nutritionists advocate taking glutamine to repair the GI tract, but recent studies have shown this is not effective." For about 5 years, I have advised my patients to use L-Glutamine to reduce cravings for EtOH, sugar, and starch with variable response, but many times excellent results. My alcoholic patients may notice tremendous relief of cravings using only 500 mg daily, other weight loss patients notice relief of carbohydrate cravings using 5,000 mg of L-Glutamine powder mixed in water or better in hot tea once or twice daily. In your opinion, am I causing harm to my patients?
    If the period of use of the glutamine supplements is for a few weeks or months, I don't think there is major harm. I would not feel comfortable using high dosages for several years. Also, I think reasonable amounts of meat consumption are acceptable. It is only when people go overboard than health problems occur.

I was impressed with your website, your in-put is forthright and honest, Is it safe to take tryomine which has L-Tyrosine 225mg and L-Glutamine 475mg? and if yes, can i still take multivitamin and thyroid complex supplement with it?
   There are many factors that are involved in supplementation including age, weight, health condition, dosage, diet, activity level, etc. It is not possible to give an answer that applies to everyone without doing a full review of the medical history and physical exam.

I only take 500 mg of l-glutamine once/day, but of course there is also plenty of it in my diet (nuts & seeds, etc.). One thing I never see mentioned in this whole Blaylock issue of excitotoxins is the advantage of having lots of l-glut available as precursors for glutathione production (along, of course, w/ NAC etc.).
   A. It depends why you are taking l-glutamine. For antioxidant purposes I prefer using low doses of NAC.

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A growing body of evidence suggests that during certain stressful times, the body may require more glutamine than it can produce. Under these circumstances it may be considered a "conditionally essential" amino acid.  Glutamine is involved in maintaining a positive nitrogen balance (an anabolic state) and also aids rapidly growing cells (immune system lymphocytes and intestinal cell enterocytes). In addition, it is a regulator of acid-base balance and a nitrogen transporter.

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Supplement Facts
Serving Size  1 Capsule
  Amount Per Serving %Daily Value
L-Glutamine (Free-Form) 1.0 g (1,000 mg) *
* Daily Value not established.

Serving Size: 1 capsule of 1000 mg per pill

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Suggested Use: As a dietary supplement, take 1 glutamine capsule 1-3 times daily, preferably with meals, or as directed by your health care provider.