Glutamine Function and Dosing

Glutamine is a conditionally essential amino acid and endogenous production of glutamine is usually sufficient to meet physiologic needs except during times of metabolic stress.^1,2 Oral glutamine supplementation can maintain glutamine status or augment levels for therapeutic purposes. The dosing of glutamine varies widely among clinical trials and in practice. This article highlights some of the dosing options for glutamine and the function and risks of different dosage protocols.

Glutamine Function

Glutamine serves as the primary source of energy for lymphocytes and enterocytes.*³ It is therefore a foundational nutrient to support both immune and gastrointestinal health.* In the gastrointestinal tract, glutamine not only fuels enterocytes, but also helps to maintain tight junctions, supporting the integrity of gut barrier function.*^4,5 Glutamine is a precursor for nucleotides in DNA synthesis and a precursor to glutathione.^6,7

Increased Need for Glutamine

The demand for glutamine increases when the body is under physical or even emotional stress. The excess cortisol associated with stress leads to production of cytokines, increased oxidative stress, and a higher demand for glutathione—effectively draining endogenous glutamine supply. Endurance exercise that extends longer than 2 hours decreases serum glutamine levels and potentially damages lymphocytes, which rely on glutamine for energy.⁸ Glutamine may be in higher demand for any person with compromised intestinal barrier function.* Finally, individuals eating a low-protein or vegan diet may have an increased need for glutamine supplementation.

Dosing: Efficacy Studies

Studies show that glutamine is equally bioavailable when taken as free glutamine in supplement form as it is when taken as part of a complete protein.⁹ It has also been confirmed that oral glutamine supplementation does effectively increase plasma glutamine levels.¹⁰

Many clinical trials have dosed glutamine in amounts measured in mg/kg of body weight. A dosage of 500 mg/kg (34 grams for a 150-lb person) improved intestinal barrier and other situational effects.*^11,12 A dosage of 80 mg/kg (5.4 grams for a 150-lb person) effectively supported a subdomain of subjects during exercise.*¹³

The most typical dosages used in clinical practice range from 5 to 30 grams per day.

Dosing: Safety Studies

There is some concern that long-term dosing of glutamine may lead to increased serum ammonia, as this was observed in a pediatric study at a dosage of 750 mg/kg (51 grams for a 150-lb person).¹⁴ Concerns have also been raised about the potential for glutamine to enter neurons and convert to glutamate via glutaminase. This would suggest that caution should be used in individuals with conditions related to the neurological system. There is a dearth of evidence suggesting that oral glutamine is neurotoxic, and it is important to note that accumulation of glutamine outside of the nervous system is not a safety issue. What remains is either a theoretical concern or unpublished anecdotal experience.

The highest oral dosages that have been evaluated in clinical trials are 50 to 60 grams of glutamine per day. A randomized controlled trial demonstrated safety of a single dose of 50 grams of glutamine, and no adverse effects were observed when glutamine was dosed at 50 to 60 grams per day for several weeks.^15,16

The “observed safety limit” for glutamine has been set at 14 grams per day, meaning that it is deemed safe to take this amount on a long-term basis with no adverse effect.¹⁷

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