Glutamine is the most abundant amino acid in the body. Although it’s commonly used as a bodybuilding supplement, studies don’t support its efficacy for muscle building. It is also being researched for its effects on leaky gut, immune function, and muscle wasting in sick people.
Read this post to learn about the science behind glutamine.
What Is Glutamine?
Glutamine is the most abundant amino acid in the body. The naturally occurring form and the form that our body uses is L-glutamine .
As a supplement, glutamine is popular among gym enthusiasts and athletes, though science doesn’t back up the use of glutamine for enhancing exercise performance or post-exercise recovery.
Additionally, glutamine supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
Glutamine is not an essential amino acid, but it is considered to be conditionally essential. Usually, glutamine is produced in sufficient amounts in the body. However, in some cases of stress, inflammation, and injuries, some bodily functions may use much more glutamine than usual [2, 3].
Our muscles account for 70% of all glutamine production in the body .
The main organs that use glutamine are muscle, kidneys, liver, and small intestine .
Scientists think glutamine is a critical amino acid for the immune system and for keeping the nitrogen levels in your body in check. It makes up to 60% of the free amino acids in the bones .
Overview of Glutamine Uses
- A building block for body proteins
- Fuel for cells that line the gut
- Fuel for immune cells, such as macrophages
- Maintaining nitrogen balance
- Preventing the burning of other amino acids for energy
L-Glutamine Purported Benefits
1) Sickle Cell Disease
L-glutamine was recently approved by the FDA for the management of sickle cell anemia. It reduces acute complications of sickle cell disease in adults and children 5 years of age and older .
Possibly Effective for:
Glutamine given through a feeding tube or intravenously (IV) likely reduces the risk of developing severe infections in people with severe burns. Through a feeding tube, it may also reduce the chance of death in this population. IV glutamine likely does not decrease the risk of death [8, 9].
3) Health Complications in Critically-ill People
Evidence suggests that glutamine likely prevents the spreading of bacteria from the gut to other parts of the body after major injuries or surgery. It might also reduce the risk of hospital-acquired infections in people who are critically ill, particularly when given intravenously (IV). However, it probably does not reduce the risk of death in this population [10, 11].
Heat shock proteins (HSPs) are a group of proteins that are released in response to cellular stress and help protect other proteins from being damaged or restructure already damaged proteins. They are an integral part of the stress response and are found in nearly every organism.
In trauma patients, increased HSP-70 levels are associated with reduced death rates .
In a study of 29 critically ill patients, glutamine supplementation increased HSP-70 levels 3.7-fold from baseline .
Animal models of stress have shown that glutamine supplementation increased levels of key heat shock proteins in multiple studies. However, proper human studies are completely lacking [14, 15, 16].
Moreover, the magnitude of HSP-70 increase was correlated to a decrease in ICU length of stay.
4) Muscle Wasting in People with HIV
Oral glutamine likely improves nutrient absorption and weight gain in people with HIV/AIDS. High doses (about 40 grams per day) are likely the most effective [17, 18].
5) Recovery After Surgery
Intravenous (IV) glutamine combined with intravenous nutrition likely reduces the number of days people spend in the hospital after surgery, especially major abdominal surgery. It also probably reduces infection rates after surgery in hospitals but doesn’t affect the risk of death after any type of surgery [11, 19].
Hospital Stay & Recovery Research
Surgeries deplete glutamine in muscles and reduce muscle protein synthesis .
In post-abdominal surgery patients, the glutamine-supplemented group saw a smaller decrease in muscle glutamine than the control group. Moreover, protein synthesis was unchanged in the treatment group, whereas in the control group it decreased .
Daily glutamine supplementation a week before stomach surgery improved the postoperative antioxidant status and liver function compared to controls .
The patients who received glutamine saw less of a decrease in glutathione (an antioxidant in the body) and a trend for a decrease in the length of hospital stay.
Infections, surgeries, radiation, and chemotherapy deplete nitrogen levels in the body by destroying proteins. In patients receiving a bone marrow transplant, factors that retain nitrogen in the body lead to fewer clinical infections, shorter hospital stays, and fewer formation of harmful microbial colonies .
In a study of 24 bone marrow transplant patients, glutamine supplementation improved the body’s ability to retain nitrogen. However, not all people who receive bone marrow transplants experience improvements .
Glutamine also improved nitrogen retention in patients undergoing stomach surgery .
Scientists think that immune cells, such as lymphocytes, macrophages, and neutrophils require glutamine. The presence of glutamine in the surrounding of these cells allow these white blood cells to grow .
Glutamine somewhat increased levels of B and T lymphocytes in patients with systemic inflammatory response syndrome (SIRS, a severe and potentially life-threatening inflammatory response to infections, trauma, or burns). Glutamine supplementation reduced inflammation and improved recovery in a study of 30 SIRS patients .
In 22 patients undergoing colorectal surgery, L-Glutamine supplementation increased T lymphocytes, cells that defend the body against bacterial invasion .
In a study of 45 patients undergoing bone marrow transplantation, those who received glutamine supplementation developed fewer infections .
However, no clinical trials support the use of glutamate supplements for enhancing immune function in healthy people.
Often heart surgeries produce an injury to the heart muscle called ischemia/reperfusion (I/R). Ischemia is due to low oxygen levels, while reperfusion is the return of oxygen after low oxygen levels .
It has been shown that I/R injuries lead to elevated levels of troponin I, creatine kinase-MB, and myoglobin. Elevated levels of these proteins have been linked to increased death and morbidity .
In a study of 14 patients, those who underwent heart surgery showed decreased levels of troponin I and creatine kinase-MB at 24 and 48 hours. Myoglobin only decreased after 24 hours. These outcomes led to fewer heart injuries and fewer complications in those that took the glutamine .
However, large-scale clinical trials are lacking to support this use of glutamate in hospitals.
Insufficient Evidence for:
The following purported benefits are only supported by limited, low-quality clinical studies.
There is insufficient evidence to support the use of glutamine for any of the below-listed uses.
Remember to speak with a doctor before taking glutamine supplements. Glutamine should never be used as a replacement for approved medical therapies.
6) Side Effects of Chemotherapy
There is insufficient evidence to support the use of glutamine for reducing the side effects of chemotherapy.
Patients undergoing chemoradiotherapy for head and neck cancer commonly develop mucositis (inflammation of the mucous membranes) in the oral cavity, larynx, and pharynx. This leads to severe pain and discomfort .
When patients were given glutamine supplements, the level of mucositis decreased along with pain levels .
When rats were subject to stomach radiation, those that were given glutamine supplementation lost less weight .
More research is needed.
7) Branched-Chain Amino Acid (BCAA) Levels
There is no valid clinical evidence to support the use of glutamine for improving BCAA levels.
According to one theory, after an injury or stress-induced muscle wasting, glutamine levels decrease in the muscles. Glucocorticoids induce muscle wasting in healthy individuals, which leads to decreased levels of glutamine .
In a study of seven healthy patients, glucocorticoid treatment decreased the amount of glutamine in 24 hours .
Decreased glutamine levels also lead to decreased levels of branched-chain amino acids. Leucine decreased by 23%, valine by 27%, and isoleucine by 33%. The increased oxidation of leucine was directly related to decreased glutamine levels .
BCAAs are essential amino acids, and deficits in these amino acids are thought to lead to compromised protein synthesis rates .
Additionally, in healthy people or athletes that consume sufficient proteins, glutamine supplementation may not have significant muscle-preserving effects .
Possibly Ineffective for:
8) Exercise Performance
The majority of studies show that taking glutamine orally likely doesn’t enhance exercise performance or immunity post-exercise.
Immunity & Exercise
Exercise is a stress on the body that reduces immune function in the hours following exercise. As a result, many endurance athletes develop frequent colds after long training. Short exercise sessions (under one hour) does not decrease glutamine in the blood, but may slightly increase it. According to some researchers, this could be because glutamate is converted into glutamine .
However, for prolonged and intense exercise (e.g., three hours), glutamine levels fall substantially and remain lowered even 4.5 hours post-exercise. Some scientists believe that this is likely because the liver uses glutamine for making glucose, to make more proteins, and to buffer the acidity from high carbon dioxide levels .
Glutamine levels appear to be lower in overtrained athletes that experience perpetual fatigue .
However, many studies find that preventing this drop in glutamine levels does not prevent the drop in immune function post-exercise. One exception to this is in extreme endurance exercises such as in marathon training. Glutamine supplementation (5 grams immediately and two hours after marathon races) significantly decreased the odds of developing colds in the following week .
There is insufficient evidence to support the use of glutamine for improving muscle building in healthy people.
Glutamine is used by many bodybuilders to increase muscle-building and reduce soreness. However, the studies do not support this use of L-Glutamine.
L-Glutamine supplementation increases glutamine in the blood, while muscle free glutamine remains unchanged. However, simultaneous consumption of glutamine with glucose decreases free glutamine inside muscle cells because this reduces the production of glutamine inside the body .
Acute glutamine supplementation at typical doses (3-6 grams per day) does NOT significantly affect [32, 33]:
- Exercise performance
- Buffering capacity (reducing acidity in the body)
- Immune function maintenance (with the exception of marathon training)
- Muscle soreness after exercise
- Body composition improvement or fat mass reduction
In some studies, the use of supplement stacks that contain glutamine along with other supplements (e.g., BCAAs and whey proteins) seemed to increase muscle mass and exercise performance. However, these effects were not observed on glutamine supplementation on its own .
Does L-glutamine Reduce Muscle Soreness?
High-dose glutamine supplementation (0.3 g/kg of body weight, or 18 grams for a 60 kg individual) increased leg strength and reduced soreness after exercise .
These effects were higher in men than in women. However, in another study in young adults, glutamine supplementation at a dose of 0.9 g/kg of body weight did not significantly improve strength or reduce muscle soreness from squatting or bench pressing .
Therefore, l-glutamine likely doesn’t improve muscle soreness. Large-scale studies are needed to determine its effects.
Glutamine and Growth Hormone
Growth hormone increased by 4-fold 90 minutes after ingesting 2 grams of L-Glutamine in nine healthy people. No conclusions can be drawn from such a small sample. Additionally, moderate to high-intensity exercise for one hour alone actually increases growth hormone by 20-fold .
Therefore, glutamine supplementation probably has an insignificant effect on growth hormone levels among people who regularly exercise at moderate to high intensity.
Adding 8 grams of glutamine to a glucose solution with 61 grams of glucose helped muscle recover its glycogen reserve faster than glucose alone. However, this study only involved six people and the findings and proposed mechanism are under question .
9) Low Infant Weight
Based on the available evidence, glutamine likely doesn’t improve growth or prevent illness and early death in premature infants .
Only one study on 68 hospitalized very-low-birth-weight infants suggested that glutamine supplementation reduced hospital-acquired sepsis (a life-threatening complication of blood poisoning) and bacteremia (bacterial infection of the blood) .
Only 11% of the infants receiving glutamine supplementation developed an infection compared to 30% of the infants who did not receive supplementation .
10) Duchenne Muscular Dystrophy
Glutamine likely doesn’t improve muscle strength in children with muscular dystrophy.
In some studies, by keeping glutamine levels constant in the blood, the levels of leucine oxidation decreased in adults, infants, and children with Duchenne muscular dystrophy [39, 40, 41, 42].
However, clinical studies show that oral glutamine (0.5-0.6 grams per kilogram of bodyweight) does not significantly improve muscle strength or whole body protein breakdown in children with Duchenne muscular dystrophy .
Popular Uses Lacking Evidence
No clinical evidence supports the use of glutamine for any of the conditions listed in this section.
Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
Gut Health & Gut Flow
Evidence is lacking to support the use of glutamine for gut disorders.
Limited evidence suggests that glutamine may support gut health, but proper clinical trials are lacking.
Glutamine is one of the three major sources of fuel (the other two being glutamate and aspartate) for cells in the small intestine. In the gut, glutamine is needed for cellular production and cell growth, and to assist in the absorption and transport of nutrients .
Many factors are thought to cause “leaky gut” (intestinal permeability), such as stress, radiation exposure, and chemotherapy. Holistic practitioners often claim that l-Glutamine helps prevent and repair leaky gut, though no clinical trials have been carried out.
In rats, glutamine supplementation prior to radiation reduced the incidences of leaky gut. Most rats that didn’t receive glutamine in their diet developed leaky gut (increased intestinal permeability), whereas the rats that did receive glutamine had intact guts .
However, findings in lab animals cannot be translated to humans.
Some scientists consider that glutamine helps preserve intestinal villi in number and height .
According to one theory, heat and oxidative damage from exercise impairs the gut lining and cause leaky gut. This theory remains unproven. Only one clinical study is available: in healthy subjects who underwent a 60-minute treadmill run, glutamine supplementation prevented the leaky gut seen in the placebo group .
Chemotherapy has also been shown to increase intestinal permeability. In breast cancer patients, glutamine supplementation for 12 days prior to chemotherapy significantly decreased the leaky gut from chemotherapy. We can’t draw any conclusions from a single, small trial. Large-scale studies in humans are needed [46, 47, 48].
Wound Healing Research
Evidence is lacking to support the use of glutamine for wound healing.
Glutamine provides energy for cells that are important for the wound healing processes like macrophages, lymphocytes, and connective tissue [49, 50].
When an injury occurs, the tissue and immune cells surrounding the injury use up glutamine faster. In rats, glutamine levels decreased by 50% five days after the injury .
The decreased concentrations of glutamine stimulate muscle cells to produce more glutamine for wound-healing and other processes .
Some people use glutamate to “support liver health.” It’s also a part of some “detox” supplements. However, clinical data are completely lacking to support the use of glutamine for liver health.
Only animal data are available, and we can’t extrapolate the findings from lab animals to humans.
Rats given a diet without the glutamine had a large buildup of fat in their livers (hepatic steatosis) .
Rats on glutamine-supplemented diets showed 47% less fat in their livers. Their livers were also 12% lighter than those without the glutamine most likely due to the decreased amount of fat .
Other animal studies have shown that glutamine decreases the uptake of fat by the liver .
Clinical research is needed.
Supplementing with Glutamine
Glutamine is an unstable molecule and has limited solubility, making its effectiveness as a supplement not as useful as one might expect .
Scientists suggest that attaching another amino acid such as alanine or glycine in order to create dipeptides (two amino acids bonded together) improves the stability of glutamine without side effects .
Reviews of glutamine seem to be pretty mixed. Clinically, glutamine is not widely used as a supplement because of its instability. However, glutamine is used by many bodybuilders to restore muscle mass.
Reviewers of glutamine supplements found that glutamine supplements decreased recovery time.
On the other hand, other forums have criticized glutamine as a supplement, saying that it didn’t seem to produce any beneficial effects.
The opinions expressed in this section are solely those of the users who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.
Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
In general, glutamine is tolerated well.
Side effects occurring most frequently in clinical trials of glutamine included nausea, heart-unrelated chest pain, fatigue, and musculoskeletal pain.
Other Theoretical Considerations
Absorption and Transportation of Other Amino Acids
Oftentimes, different amino acids compete with one another for transport into tissues or absorption into the gut and kidneys. Glutamine supplementation may, in theory, increase glutamine concentrations to the point where other amino acid transport and absorption suffer .
Internal Glutamine Production
Excessive glutamine supplementation may impair the body’s own production of glutamine, according to some unproven theories .
Some scientists consider that glutamine supplementation may impair the body’s ability to detoxify harmful molecules such as ammonia. This may lead to decreased transport of ammonia by glutamine between tissues in the long term .
Other Side Effects
Although these effects of glutamine supplementation have not been fully corroborated, there may be a link between glutamine supplementation and these side effects :
- Damaged immune system
- Increased risk of cancer
- Tumor growth
- Increased levels of other amino acids in the blood leading to acidic conditions
Contraindications and Drug Interactions
Contraindications to glutamine supplementations usually exist only when the patient cannot take in nutrients such as glutamine through enteral nutrition, which is when nutrients are given through the patient by a feeding tube. This is mainly due to problems in the gut that keep the patient from being able to take in the nutrients. In these cases, the nutrients are given parenterally or through the veins [55, 56].
Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
- For burns: 0.35-0.5 grams per kilogram of body weight per day or 4.3 grams every four hours.
- For critical illness: liquid feed at 0.2-0.6 grams per kilogram of body weight each day or 20 grams per day.
- For sickle cell disease: 5-15 grams twice daily for 48 weeks in people with sickle cell disease 5 years of age or older.
- Involuntary weight loss in people with HIV/AIDS: 14-40 grams per day.
Commercially-available supplements intended for general health recommend much lower doses on the label (usually 1-3 g/day). Some popular blogs recommend up to 30 g/day for “leaky gut,” but no clinical data supports them.