L-glutamine

L-glutamine is a nutrient belonging to the non-essential amino acid class.

L-glutamine is known as glutamine or levo-glutamine.

L-glutamine is essential for many critical biological processes inside the human body. The body uses glutamine as a building block for the synthesis of proteins. It is also required for the production of glucose and other amino acids.

A deficiency of L-glutamine can cause metabolic problems, reduced gut health, and immunological dysfunction. Although it doesn't directly cause any specific disease, it can worsen several other health problems.

Proteins from plants and animals, juices from vegetables (especially cabbage), eggs, wheat, soybeans, and fermented foods like miso and yoghurt are some examples of sources of L-glutamine.

L-glutamine is mainly absorbed from the small intestine and distributed widely in tissues for varied functions. It promotes the production of nucleotides, amino acids, and energy through metabolism. Blood, urine, and respiratory excretion are the three main elimination methods.

The common side effects of L-glutamine include GI disturbances, nausea and muscle or joint pain.

L-glutamine is available in tablets, capsules, oral powders and injection solutions.

Biochemical action of L-glutamine

L-glutamine belonging to the supplement class acts in several physiological processes. It works via cellular growth and immune protection pathway.

The biological functions of l-glutamine in the human body are significant. It is a vital energy source for intestinal mucosal cells, hepatocytes, and rapidly increasing immune system cells, such as lymphocytes and monocytes. It also plays a role in the regulation of acid balance, preventing acidosis, serves as a nitrogen shuttle, protecting the body from high levels of ammonia, and is involved in the synthesis of amino acids, including l-glutamate, GABA, glutathione (a vital antioxidant), purine Moreover, it contributes to the protein synthesis and the production of energy.

Gastrointestinal protection/repair: L-glutamine helps gut cells grow and heal, giving enterocytes and colonocytes their main energy source. It maintains secretory IgA to inhibit bacterial adhesion and prevents microbe translocation, which is crucial for intestinal integrity.

Immunomodulation: Infection and trauma models in animals and human trauma have shown that l-glutamine has an immunomodulatory effect. In addition to being necessary for cell proliferation and serving as the lymphocytes' preferred respiratory fuel, l-glutamine can improve the performance of immune cells that have been activated.

Antioxidant: L-glutamine can help reduce oxidation under metabolic stress since it is a precursor to glutathione, along with cysteine and glycine. Because glutathione protects epithelial cell membranes from damage, its loss can significantly impact gut barrier performance and cause severe colonic and jejunal epithelial cell degeneration.

Anabolic/anticatabolic: The anticatabolic/anabolic effects of supplemented l-glutamine are probably caused by a protective effect on skeletal muscle reserves since l-glutamine is primarily stored in skeletal muscles and turns conditionally necessary under conditions of metabolic stress.

Peak plasma time: 30 min

Peak plasma concentration: 150 mcg/mL

The volume of distribution, Vd: ~200 mL/kg

Half-life: ~1 hr

L-glutamine is available in tablets, capsules, oral powders and injection solutions.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.
• Injection solutions: To be administered parenterally, as applicable.

L-glutamine can be used as a supplement when the amount of L-glutamine taken from the diet is insufficient.

Taking L-glutamine supplements orally may effectively treat L-glutamine deficiency caused by specific genetic diseases or other disorders.

L-glutamine supplements may help prevent sickle cell disease as it helps in reducing the complications of the disease.

L-glutamic acid is commonly used as a supplement in sports nutrition.

Supplemental L-glutamine supports the immune system and other bodily functions, particularly under stressful situations when the body utilizes more glutamine.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

L-glutamine can help to support as a supplement for the following health benefits:

• Deficiency: prevention and treatment: L-glutamine becomes conditionally necessary during times of increased demand. Depletion may cause sepsis, increase intestinal permeability, microorganism translocation, obstruct healing, and increase intestinal permeability. Potential advantages for certain illnesses enhancing glutamine requirements include enhanced immune response, decreased mortality, hospital stay, and infection risk.
• Critical care settings: Most research indicates that glutamine prevents bacteria from migrating from the colon and invading other areas of the body in the months following serious infections; however, not all findings are consistent. In severely ill patients, glutamine may also lower their chance of acquiring infections within the hospital. Giving glutamine intravenously (via IV) instead of through a feeding tube better protects against hospital-acquired illnesses. Overall, glutamine does not appear to lower the mortality risk in patients with severe diseases.
• Chemotherapy: Glutamine may enhance the quality of life for cancer patients undergoing chemotherapy by reducing possible side effects. Because of the tissue breakdown brought on by chemotherapy, mucositis may not be as severe. While some trials indicate alleviation, further study is required for conclusions.
• Burns: Muscle atrophy, weight loss, and infection are all outcomes of acute burn injuries that cause glutamine and plasma levels to decline. Increased plasma glutamine concentration and decreased immunosuppression resulted from a glutamine granules supplement. Glutamine accelerated the healing of wounds and shortened hospital stays by improving immunological function, particularly cellular immunity.

• Infants: Enteral and parenteral glutamine supplementation has been demonstrated to benefit newborn morbidity and death in premature babies. However, these findings are controversial.
• HIV/AIDs: It has been demonstrated that ingesting glutamine increases glutathione levels and considerably increases lean body mass in HIV patients, and indicates enhanced food absorption in HIV/AIDS patients. The best results tend to come from doses of 40 grams per day.

• Gastrointestinal effects: According to studies, adding glutamine to chemotherapy helps minimize oral mucositis, a typical side effect of cancer treatment that causes discomfort, an increased risk of infection, and impaired function. For instance, oral glutamine (30 g/day) significantly decreased the occurrence of mucositis (9% vs 38% in control; P 0.001).
• Sickle cell disease: L-glutamine increases the NAD redox potential of sickle cell red blood cells when taken orally. Improvement in adherence to endothelial cells was consistently seen in a trial of five adult sickle cell anaemia patients receiving 30 g/day of l-glutamine compared to controls. These results suggest that l-glutamine has beneficial physiological effects on sickle cell disease.

L-glutamine supplementation may be administered orally and parenterally.

• Orally: L-glutamine supplements are available as tablets, capsules and powders that can be taken orally. The best time to take L-glutamine supplements is on an empty stomach, preferably about 15 minutes before a meal, as it might enhance absorption.
• Parenterally: L-glutamine supplements are generally taken by mouth but may have to be administered intravenously and intramuscularly.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 500 mg, 1000 mg, 5000 mg
• Capsules: 430 mg, 500mg, 1000mg, 5000 mg
• Powder, oral: 8 oz (226.8 g), 5g/packet (as L-glutamine)
• Injection solutions: 50ml, 100 ml, 250 ml

Dosage Adjustment for Adult Patients

Ideally, powdered formulas should be consumed immediately after mixing.

Gut repair: 7–21 g taken orally as a single dose or in divided doses.

Cancer therapy: 2–4 g twice daily swished in the mouth and swallowed (up to 45 g has been used in trials and given orally in divided doses).

Critical illness: 5 g/500 mL of enteral feeding solution.

HIV: 30 g/day taken orally as a single dose or in divided doses.

Infection: 12–30.5 g in an enteral feeding solution

Sickle Cell Disease

Endari: Indicated to lower the risk of sickle cell disease complications

<30 kg (<66 lb): 5 g orally BID

30-65 kg (66-143 lb): 10 g orally BID

≥65 kg (≥143 lb): 15 g orally BID

Short Bowel Syndrome

NutreStore: It is indicated for short bowel syndrome in patients receiving specialized nutritional support when used in conjunction with recombinant human growth hormone

30 g/day orally in divided doses (i.e., 5 g taken 6 times each day) for up to 16 weeks.

L-glutamine is available in tablets, capsules, oral powders and injection solutions.

L-glutamine should be used as a supplement that helps in several physiological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Limit foods and drinks with high L-glutamine content, sugars, caffeine, saturated fat, and sodium.

The dietary restriction should be individualized as per patient requirements.

Estimated NEAA(Non-Essential Amino acids) usage, mg/kg BW (Body Weight)

The estimated NEAA usage for L-glutamine is set at 21 mg/kg BW

Estimated NEAA(Non-Essential Amino acids) usage, in 70 kg BW

The estimated NEAA usage for L-glutamine in 70 kg is 1494 mg

L-glutamine supplementation may be contraindicated in the following conditions:

• Hypersensitivity; sensitive to L-glutamine.
• Chronic liver disease
• Kidney disease.
• Chronic renal failure
• Cirrhosis
• Hepatic encephalopathy
• Mania, a mental disorder
• Seizures

High-dose supplements should be used with caution in paediatrics.

High doses of l-L-glutamine supplements should be cautiously used in individuals with preexisting kidney or hepatic disease.

Individuals sensitive to Monosodium glutamate (MSG) should use l-glutamine supplements cautiously because the body converts glutamine to glutamate.

L-glutamine given intravenously (IV) can also increase the risk of mouth ulcers or death in people receiving bone marrow transplants. Avoid using L-glutamine supplements (iv) in this condition.

There is no sufficient scientific evidence traceable regarding the use and safety of L-glutamine for use in special populations.

There is no sufficient scientific evidence traceable regarding the use and safety of L-glutamine for use in special populations.

Limit the consumption of foods and beverages higher in added sugars, processed foods, caffeine, alcohols and high protein foods as these substances could hinder L-glutamine absorption.

The adverse reactions related to L-glutamine can be categorized as-

• Common: GI disturbances like bloating, gas, nausea, or diarrhoea, especially with high doses.
• Less Common: Muscle or joint pain, headache or dizziness.
• Rare: Allergic reactions (rash, itching), seizures and high ammonia levels in the blood (hyperammonemia).

The clinically relevant drug interactions of L-glutamine are briefly summarized here:

• Radiation and chemotherapy: The intake of l-glutamine during radiation and chemotherapy is beneficial.
• Indomethacin/NSAIDs: L-glutamine (7 g three times per day) and indomethacin taken together could mitigate the increased intestinal permeability caused by indomethacin. Misoprostol's addition to this mixture may have a synergistic impact, making a favourable interaction probable.
• Human growth hormone: In patients with severe short-bowel syndrome, concomitant l-glutamine and human growth hormone may enhance nutrient absorption.

The common side of L-glutamine includes the following:

• Nausea
• Diarrhoea
• Headaches
• Dizziness
• Abdominal pain.
• Vomiting
• Fatigue
• Bloating, gas
• Muscle or joint pain

L-glutamine should be prudent in the following group of special populations.

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of L-glutamine for use in special populations.

• Paediatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of L-glutamine for use in special populations.

Dosage Adjustment for Paediatric Patients

Sickle Cell Disease

Endari: It is indicated to lower the risk of sickle cell disease complications in adults and children aged more or equal to 5 years

less than 5 years: There is safety and efficacy

Less or equal to 5 years

less than 30 kg (<66 lb): 5 g orally BID

30 to 65 kg (66-143 lb): 10 g orally BID

More or equal to 65 kg (≥143 lb): 15 g orally BID

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of L-glutamine for use in special populations.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of L-glutamine for use in special populations.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of L-glutamine. Overconsumption of L-glutamine may lead to symptoms of that might include gastrointestinal discomfort, nausea, and vomiting.

There is no specific antidote or treatment for excessive intake of supplemental L-glutamine. L-glutamine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after L-glutamine supplement use or dietary intake. Increase fluid intake and supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of L-glutamine

The molecular structure of L-glutamine consists of a central carbon atom which is bonded to an amino group, a carboxyl group, a side-chain amide group, and two hydrogen atoms. Because of its diverse roles, L-glutamine, a -amino acid, plays a vital role in biochemistry. It contributes to cellular structure and functions as a necessary component in protein synthesis. Besides its position in protein synthesis, L-glutamine is a vital nitrogen transporter between tissues, facilitating metabolic activities like amino acid metabolism and urea generation.

L-glutamine's metabolic importance applies to energy production, particularly during catabolic states or periods of high demand. It acts as a readily available substrate for energy generation, contributing to maintaining cellular energy homeostasis. Notably, L-glutamine plays a critical function in antioxidant defence by working as a cofactor for glutathione, a potent cellular protector against oxidative stress.

Kinetic profile:

• Absorption: L-glutamine is absorbed predominantly in the small intestine through specialized transporters. This process of absorption is essential for ensuring a consistent flow of glutamine throughout various tissues.
• Distribution: L-glutamine is extensively distributed throughout the body after absorption. Cells absorb it and utilize it for various physiological functions, including protein synthesis, production of energy, and immune cell activity.
• Metabolism: L-glutamine is a variable substrate used in many metabolic processes. It may be converted into energy via the citric acid cycle, help produces other amino acids, have nucleotides and act as an antioxidant.
• Elimination: L-glutamine is utilized by cells, then it is metabolized, and the byproducts that result can be excreted in various ways. The carbon skeletons of glutamine molecules can be released into circulation and utilized by various tissues, while some are eliminated in the urine. A small amount could be expelled as carbon dioxide through the respiratory system.

1. Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4th Edition Vol-2. Australia. Elsevier.
2. National Institute of Nutrition. 2011. Dietary guidelines for Indians; 2nd Edition. Hyderabad. India
3. https://pubmed.ncbi.nlm.nih.gov/31187867/

4. Tessari P. 2019. Nonessential amino acid usage for protein replenishment in humans: a method of estimation; American Society for Nutrition. Department of Medicine, University of Padova, Padova, Italy