Glutamine is a critical amino acid and the most abundant in the body. Although it’s more commonly known as a bodybuilding supplement, studies don’t quite support its efficacy for muscle building. Rather, it helps prevent leaky gut, boosts immune function, and prevents muscle wasting in sick people.
Read this post to learn how glutamine benefits health.
What Is Glutamine?
Glutamine is an amino acid used as:
- 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
It is also the most abundant amino acid in the body, suggesting that it is very important [R].
The naturally occurring form and the form that our body uses is L-glutamine.
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 use so much glutamine that it becomes necessary to obtain it from diet or supplements [R, R].
Skeletal muscle accounts for 70% of all glutamine production in the body [R].
The main organs that use glutamine are skeletal muscle, kidneys, liver, and small intestine [R].
Glutamine is a critical amino acid for the immune system and for keeping the nitrogen levels in your body in check. Moreover, glutamine makes up to 60% of the free amino acids in the bones, making it a good supplement for bodybuilders and gym enthusiasts [R].
L-Glutamine Benefits the Gut
1) L-Glutamine Is a Fuel for Gut Cell Growth and Digestive Functions
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 [R].
2) L-Glutamine Prevents and Repairs Leaky Gut
Many factors cause leaky gut (intestinal permeability), such as stress, radiation exposure, and chemotherapy. In many such instances, L-Glutamine helps prevent and repair leaky gut.
In rats, glutamine supplementation prior to radiation reduced the incidences of leaky gut. Seven out of the eight rats that didn’t receive glutamine in their diet had leaky guts (increased intestinal permeability), whereas all of the rats that did receive glutamine had intact guts [R].
In addition, glutamine also helps preserve intestinal villi in number and height [R].
Heat and oxidative damage from exercise impairs the gut lining and cause leaky gut [R].
In healthy subjects who underwent a 60-minute treadmill run, glutamine supplementation prevented the leaky gut seen in the placebo group.
In breast cancer patients, glutamine supplementation for 12 days prior to chemotherapy significantly decreased the leaky gut from chemotherapy [R].
3) L-Glutamine Improves Gut Flow
Glutamine has been shown to be helpful in improving gut flow in patients who have had part of their stomachs surgically removed. Daily glutamine supplementation (3 grams) for 12 days resulted in significantly greater improvement in flow to the small intestine compared to controls.
L-Glutamine Benefits the Immune System and Supports Healing
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 [R].
Therefore, events that require the immune system, including injuries, infections, cancer treatments, and surgeries deplete glutamine in the body. In addition, glutamine supplementation tends to help with recovery from these events.
4) L-Glutamine Supports the Immune System Against Infections
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 [R].
In 22 patients undergoing colorectal surgery, L-Glutamine supplementation increased T lymphocytes, cells that defend the body against bacterial invasion [R].
In a study (DB-RCT) of 45 patients undergoing bone marrow transplantation, those who received glutamine supplementation developed fewer infections [R].
Studies on 68 hospitalized very-low-birth-weight infants showed that glutamine supplementation reduced hospital-acquired sepsis (a life-threatening condition that occurs when the body injures its own tissues in response to an infection) 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 [R].
5) Glutamine for Wound Healing
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 [R].
The decreased concentrations of glutamine stimulate muscle cells to produce more glutamine for wound-healing and other processes [R].
6) Glutamine Decreases 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 [R].
When patients were given glutamine supplements, the level of mucositis decreased along with pain levels [R].
When rats were subject to stomach radiation, those that were given glutamine supplementation lost less weight [R].
However, cancer cells may use glutamine for fuel, so glutamine supplementation is often contraindicated in cancer patients [R].
However, because cancer cases vary and glutamine may be beneficial in supporting overall well-being in cancer patients, patients should consult their physicians before adding glutamine to their regimen.
7) Glutamine Helps with Surgery Recovery
Surgeries deplete glutamine in muscles and reduce muscle protein synthesis [R].
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 [R].
Daily glutamine supplementation a week before stomach surgery improved the postoperative antioxidant status and liver function compared to controls [R].
The patients who received glutamine saw less of a decrease in glutathione (the main anti-oxidant in the body) and a trend for a decrease in the length of hospital stay.
8) Glutamine Increases Nitrogen in the Body When It Is Being Depleted
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 [R].
In a study (DB-RCT) of 24 bone marrow transplant patients, glutamine supplementation improved the body’s ability to retain nitrogen [R].
Glutamine also improved the nitrogen retention in patients undergoing stomach surgery [R].
In rats, glutamine supplementation preserved the nitrogen content of the stomach and colon. Also, glutamine-fed rats had increased nitrogen in their small bowel [R].
9) Glutamine Prevents Decrease in Branched-Chain Amino Acids (BCAA) Levels
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 [R].
In a study of seven healthy patients, glucocorticoid treatment decreased the amount of glutamine in 24 hours [R].
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 the decreased glutamine levels [R].
BCAAs are essential amino acids, and deficits in these amino acids lead to compromised protein synthesis rates [R].
In other studies, by keeping glutamine levels constant in the blood, the levels of leucine oxidation decreased in adults, infants, and children with Duchenne muscular dystrophy as well as in dogs [R, R, R, R].
However, in healthy people or athletes that consume sufficient proteins, glutamine supplementation may not have significant muscle-preserving effects [R].
L-Glutamine and Exercise
10) Prolonged and Intense Exercise Use Up L-Glutamine
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 rather slightly increases it. This could be because glutamate is converted into glutamine [R].
However, for prolonged and intense exercise (e.g., three hours), glutamine levels fall substantially and remain lowered even 4.5 hours post-exercise. 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 [R].
Glutamine levels appear to be lower in overtrained athletes that experience perpetual fatigue [R].
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 developing colds in the following week [R].
11) L-Glutamine Use and Muscle Building
Glutamine is used by many bodybuilders to support the muscle building process and reduce soreness. However, the studies have not supported 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 [R].
- 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 [R].
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 [R].
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 [R].
Glutamine and Growth Hormone
Growth hormone increases by 4-fold 90 minutes after ingesting 2 grams of L-Glutamine. However, moderate to high-intensity exercise for one hour increases growth hormone by 20-fold [R].
While this might be helpful for the general population, glutamine supplementation has a much less significant effect on growth hormone levels among people who exercise at moderate to high intensity.
Glutamine and Exercise Recovery
Adding 8 grams glutamine to a glucose solution with 61 grams of glucose helped muscle recover its glycogen reserve faster than glucose alone. However, the mechanism is still unclear [R].
Other Health Benefits of Glutamine
12) Glutamine Protects Against Stress
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 [R].
In a study (DB-RCT) of 29 critically ill patients, glutamine supplementation increased HSP-70 levels 3.7-fold from baseline [R].
Moreover, the magnitude of HSP-70 increase was correlated to a decrease in ICU length of stay.
13) Glutamine Protects the Heart During Heart Attacks and Surgeries
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 [R].
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 [R].
In a study (DB-RCT) 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 [R].
In cell studies, when cells underwent I/R and were given glutamine, less glutamine-fed cells were killed than controls [R].
Also, the contractile function of the heart cells was recovered in all glutamine-fed cells, while none of the cells without glutamine were able to recover that function [R]
14) Glutamine Prevents Non-Alcoholic Fatty Liver Disease
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 [R].
Other studies have shown that glutamine decreases the uptake of fat by the liver [R].
What to Consider When Supplementing with Glutamine
Because glutamine is used up during times of stress or injury, simply taking glutamine supplements during a period of physical trauma or stress should maintain the glutamine concentrations and keep muscles from decaying [R].
However, glutamine is an unstable molecule and has limited solubility, making its effectiveness as a supplement not as useful as one might expect [R].
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 [R].
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.
Glutamine Side Effects
1) Glutamine Supplementation Interferes with the 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 increase glutamine concentrations to the point where other amino acid transport and absorption suffer [R].
2) Glutamine Supplementation Reduces Internal Glutamine Production
Excessive glutamine supplementation impairs your body’s own production of glutamine. This causes the body to instead create more harmful molecules such as glutamate and ammonia [R].
3) Glutamine Supplementation Impairs Ammonia Detoxification
Glutamine supplementation impairs the body’s ability to detoxify harmful molecules such as ammonia. This also leads to decreased transport of ammonia by glutamine between tissues [R].
4) Withdrawing from Glutamine Supplementation Causes Side Effects
Long-term glutamine supplementation reduces the body’s own production of glutamine. Then, when glutamine supplementation is ceased, the body is not able to produce enough glutamine, which causes a wide range of side effects such as increased nitrogen levels [R].
5) Other Side Effects of Glutamine Supplementation
Although these effects of glutamine supplementation have not been fully corroborated, there may be a link between glutamine supplementation and these side effects [R]:
- Damaged immune system
- Increased risk of cancer
- Tumor growth
- Increased levels of other amino acids in the blood leading to acidic conditions
Other Glutamine Risks: Cancer
Cancer cells feed on glutamine. In many cases, the cancer cells depend on glutamine for survival [R].
Therefore, glutamine supplementation is often contraindicated for cancer patients. However, as indicated above, glutamine supplementation helps with many other aspects of health that maintain well-being and recovery from cancer. Some clinicians believe that glutamine supplementation is beneficial for cancer patients [R].
Patients should, therefore, consult their physicians before using glutamine as part of their cancer treatment program.
Glutamine Supplementation 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 [R, R].
Due to the relatively harmless nature of natural supplements, there are not many studies that test the effectiveness of glutamine with other drugs [R].
However, there are cases where glutamine supplementation does more harm than good. One case is when glutamine is used with irinotecan/5-fluorouracil (5-FU) when treating colon carcinoma [R].
The combination of 5-FU with glutamine being harmful would not have been known with our current understanding, and so additional testing is vital before supplementation when taking any sort of drug [R].
Glutamine, when used in conjunction with omega-3 fatty acid treatments, has also been shown to be less effective than individual treatments. Glutamine and omega-3 fatty acids both produce similar effects in chemotherapy patients. However, when chemotherapy was done with both glutamine and n-3 fatty acids, the effects of both treatments seemed to cancel and the combined treatment fared way worse than individual treatment [R].
Many of the helpful responses seen in individual treatment such as anti-tumor effects were lost in the combined treatment [R].
In conclusion, patients should absolutely consult a doctor before glutamine supplementation use when taking other drugs.
Glutamine Supplementation Dosage
5 g per serving for many of the muscle recovery effects seen through supplementation. However, many of the clinical trials above have seen effects using less than 5 g. For instance, the systemic inflammatory response syndrome study in Section 1 saw an improvement in health using only 1 g of glutamine supplements [R]