Focus on: L-glutamine


Used by sports enthusiasts to boost performance, and recommended by nutritional therapists to restore the gastrointestinal wall, what are the mechanisms and evidence to support the use of l-glutamine? Mémé Watanabe who is a nutritional therapist with a focus on gastrointestinal health, examines this popular nutrient.

The most abundant amino acid

Glutamine is the most abundant amino acid in human blood, skeletal muscle and the free amino acid pool, and with a rapid turnover, it plays a key role in the growth of lymphocytes, fibroblasts and enterocytes. Glutamine is also a precursor to nucleotides, glutathione homeostasis, protein synthesis, glucose biosynthesis and oxidative energy and acts as a main transporter of ammonia (1). Glutamine has two forms:

  • l-glutamine and d-glutamine, which are mirror images of each other. However, it is l-glutamine that has the important role in the body (2). Although glutamine is a non-essential amino acid, if its use exceeds its production, then glutamine becomes an essential amino acid.
  • The glutamine-glutamate/GABA cycle metabolises glutamine using the enzyme glutaminase (2) to produce glutamate, which is a precursor to gamma-amino butyric acid (GABA). In the brain, GABA is an inhibitory neurotransmitter and in contrast, glutamate is an excitatory neurotransmitter. 

In some studies, glutamine supplementation has been shown to improve mood, but other studies have shown that excess glutamine in the plasma may be correlated with reduced mental health conditions such as low cognition and Alzheimer’s Disease (3).

Exercise performance

It has been suggested that intense exercise and training can render athletes more susceptible to infection and colds (4). One suggested reason may be decreased levels of plasma glutamine because of skeletal muscles use during exercise, which reduces the availability of glutamine for cells in the immune system. In addition, glutamine may inhibit the expression of nuclear factor-kB in the intestines, which is a key regulator of the immune system (5).

Glutamine has also been investigated as having ergogenic properties to reduce fatigue in athletes because glutamine stimulates glycogen synthesis, is a precursor to the antioxidant glutathione, and may reduce muscle damage (6). However, certain early studies have found no positive effect on exercise performance from taking glutamine (7,8).

Gastrointestinal tract

Glutamine is the primary fuel for intestinal epithelial cells, with about 30 per cent of total body glutamine as the main nutrient in the intestines. Intestinal epithelial cells renew every 4-5 days and are amongst the fastest renewing cells in the body.

Glutamine encourages cell regulation and proliferation through protein kinases and growth factors. A review on glutamine and the intestine byKim and Kim (9) included in-vivo studies, which demonstrated the modulating effect of glutamine on tight junctions in the small intestine and used the schematic diagram on the proposed mechanisms of glutamine in the gut (9) – top right.

meme gluthamine graphic

Secretory immunoglobulin A (sIgA) is an antibody found in the intestinal lumen, protecting the intestinal epithelium by preventing adhesion of pathogens, and facilitating removal from the gut. Glutamine supplementation has been shown to enhance sIgA secretion through a number of possible pathways. Since low sIgA is implicated in gastrointestinal diseases, there may be potential in using glutamine supplementation, although more clinical studies are needed to confirm this.

In 2013, a small human study found reduced exercise induced intestinal permeability with the use of 0.9 g/kg of fat free mass per day of glutamine for seven days prior to 60 minutes of exercise (15). In 2017, a similar study was conducted with the same results (16). A meta-analysis published in 2017 on the effects of glutamine and radiation enteritis found higher efficacy in patients with enteritis compared to control; however, these differences were not statistically significant (10). In terms of illness, a meta-analysis and systematic review found no or little effect of glutamine on infection, reduced length of stay in hospital, or risk of mortality (11,12). Currently, glutamine is given to chemotherapy patients for mucositis; systematic reviews have showed positive effects of glutamine on mucositis in chemotherapy patients with an average dose of 20-30g per day, divided into three doses (13,14).

Past studies have found glutamine intake to be safe; however, few studies have looked at the effects of long-term glutamine supplementation. A review in 2012 discussed how long-term, high-dose supplementation could potentially result in glutamine competing with other amino acids for shared transporters, impairment of endogenous glutamine, alterations in the important role glutamine plays as a transporter of ammonia, and other side effects (17).


Like all supplements, glutamine should be used as a short-term strategy to supplement dietary nutrient intake. Recommended doses from supplement companies range from 500mg to 10 grams a day, divided into three doses, depending on the reasons for use such supporting exercise or gastrointestinal health. The excitatory effect of glutamine to glutamate conversion on mood is possible, but rare and therefore supplementation should be taken with the guidance of a qualified practitioner, especially for those with mood disorders.
• References upon request