Glutamine, one of the most abundant non-essential amino acids present in the body, are mostly found in the muscle (35%). Glutamine appears to be a unique amino acid, serving as a preferred respiratory fuel for rapidly multiplying cells, such as enterocytes (cells in the small intestine) and lymphocytes (white blood cells), is an important precursor of DNA, is involved in the urea cycle, which helps break down ammonia. (1)
Glutamine has a protein sparing effect
Glutamine can be synthesized from metabolic intermediates using transamination (a process that changes one amino acid into another) such as branched-chained amino acids (BCAAs). Supplementing with glutamine will thus have a BCAA sparing effect.
During periods of starvation, severe carbohydrate restriction or exercise, leucine is oxidized to produce glutamine, which is then used in gluconeogenesis to produce glucose. Thus glutamine will save the BCAAs from being used to produce energy, and to be solely used for muscle protein synthesis. (R) As exercise commences, muscle glycogen diminishes and therefore fatty acid oxidation increases. Fatty acid oxidation promotes BCAA oxidation (due to the need of oxaloacetate, a TCA cycle intermediate), however, ketones prevent leucine oxidation during exercise.
Glutamine is anti-Catabolic
Glutamine increases the body’s nitrogen balance (NB), which is essential for building muscle. The increase in NB also prevents/partially reverse declines in myosin heavy chain (MHC) and muscle protein synthesis (MPS) during stressful/catabolic periods (R). Glutamine also significantly reduces muscle degeneration enzyme mRNA namely MuRF-1 and MAF-bx, thus reducing muscle catabolism, and favoring MPS (R).
A glutamine dose of 0.28 g·kg-1 body mass improved nitrogen balance and prevented the decline of muscle free glutamine, a sign of whole body protein catabolism (R). 0.175g/kg/day twice a day prevent muscle loss by 13% during short-term (12 days) severe calorie restriction (2000 total daily calories for first 6 days and 1000 total daily calories for the remaining 6 days) in wrestlers (R). Wrestlers expend more than 9000Kj energy per day, so this was a big energy deficit which I think makes the retention of muscle mass quite worth noting.
Also, 0.3g/kg/BW of glutamine suppress post-workout leucine oxidation and therefore inhibits muscle protein breakdown creating a more positive net protein synthesis. (R)
Glutamine is anabolic
Glutamine is an essential and rate-limiting factor for the activation of mTORC1. mTOR stimulates muscle protein synthesis.
Akt mRNA is significantly increased following glutamine supplementation. (R) Akt is a part of the MPS signaling pathway and more Akt mRNA would result in greater Akt stimulation by mTOR leading to better hypertrophy.
Intracellular glutamine is significantly positively associated with muscle protein synthesis in the absence of insulin and is further enhanced in the presence of insulin (in vitro study). (R) The mTOR directly senses the intracellular content of key amino acids, such as glutamine and leucine, in potentiating protein synthesis (R). mTOR is maximized because of the leucine sparing effect of glutamine and also because intracellular glutamine accumulation is needed for transporting leucine into the muscle. (R) So both glutamine and leucine are needed to maximally stimulate MPS.
Glutamine itself is also a more potent stimulator of insulin secretion than leucine, which will further aid in the transport of amino acids into muscle. (R)
In this study, glutamine supplementation provided a slight, but not significant advantage in strength and lean mass gained, and also speeding up muscle recovery. (R)
Glutamine increases plasma taurine (an osmolyte amino acid), which increases cellular hydration. (R) This hydrated state signals anabolism and a dehydrated state signals catabolism.
Glutamine boosts Growth hormone
Glutamine load, 2g, is capable of elevating alkaline reserves (bicarbonate) as well as plasma growth hormone 4 times higher than normal. (R) Also, a combination of glycine, glutamine and vitamin B3 enhanced serum GH by 70% after 3 weeks in middle-aged and elderly individuals, but the contribution of glutamine is unknown. (R)
Glutamine Help burn fat and improve insulin sensitivity
Glutamine induces insulin resistance in adipose tissue (thus reducing fat gain) and increase insulin sensitivity in liver and muscle (aiding in glucose and amino acid uptake in muscle). (R)
Indeed glutamine supplementation enhanced weight loss compared to placebo. (R)
Glutamine promotes Glycogen resynthesis
In this mice study, glutamine was more effective than glucose at recovering from hypoglycemia. (R) However, in this study, when taken 0.3g/kg glutamine with 1g/kg glucose post-workout was ineffective at enhancing muscle glycogen resynthesis than just the glucose alone. (R) We know glutamine is used to produce glucose via gluconeogenesis which is very effective at replenishing liver glycogen in mice and men, but not further enhance muscle glycogen resynthesis in men when combined with carbs, however, it serves as a good substitute as its also effective at restoring muscle glycogen on its own. (R) It helps at keeping the muscles insulin sensitive, which directly aids in muscle glycogen resynthesis.
In this study, 0.3g/kg glutamine increased muscle glycogen accumulation and muscle glycogen concentration was 3.5 times higher than the placebo group after 2 hours post-workout. No glucose was used in this study. (R)
Also, acute supplementation of glutamine and maltodextrin combination, 2 hours before exercise is more efficient in prevention of anaerobic power decrease than consumption of a pure carbohydrate or glutamine alone. (R) So it can be very useful at improving the physical performance of athletes during repeated competitions.
Glutamine boosts recovery post-exercise recovery and reduces DOMS
L-glutamine (0.3g/kg/day) supplementation resulted in faster recovery of peak torque and diminished muscle soreness (DOMS) following resistance exercise. (R)
Glutamine boosts Immunity
Glutamine is utilized at a high rate by cells of the immune system in culture and is required to support optimal lymphocyte proliferation and production of cytokines by lymphocytes and macrophages. (R)
Glutamine is also a precursor to glutathione, a very powerful antioxidant defense system in the body, which helps detoxify the body, reduce inflammation, boost immunity etc…
Pre-exercise glutamine supplementation (6g x3 a day) seemed to help enhance immune function and the defensive inflammatory reaction. It prevents a rise in IL-15, a cytokine that helps kill virally infected cells, which indicates glutamine is protecting against infection. (R) It also lowers creatine kinase and blood phosphorus post-workout when compared to BCAAs or placebo and therefore is able to enhance recovery and protect against inflammation. (R)
Glutamine supplementation may be able to restore immune function and reduce the immunosuppressive effects of heavy-load training by boosting white blood cell count. (R)
Glutamine also increases heat shock proteins which protect cells against stress.
a) Glutamine can also be converted to glutamate, which is an excitatory neurotransmitter, which will help with alertness and energy. Glutamine and glutamate are able to stimulate the release of pituitary gonadotropin-releasing hormone (GnRH) which then signals testosterone production in rats. (R) This is also very possible in men but needs further study. Glutamine is negatively correlated with leptin. (R) Leptin is inversely correlated with testosterone.
b) High doses, 28g/day is very well to tolerated and doesn’t result in abnormal plasma ammonia levels. (R)
c) Glutamine is necessary for intestinal mucosal integrity (R)
d) As much as 76% of ingested glutamine is taken up by the splanchnic tissue in the small intestine.
e) Glutamine transporter uptake in muscle is insulin dependent. Glutamine uptake in diabetes is reduced, showing that insulin sensitivity is important in glutamine uptake. Glucose does not further enhance glutamine uptake. (R)
f) Glutamine may not be as beneficial for all as it would be for some. It would be most beneficial during stressful times such as dieting/illness, carbohydrate restriction, overtraining etc…
g) High dose might need to be taken to reap its benefits, as shown in the studies, about 0.3g/kg/body weight seems to be effective.
I don’t think high dose glutamine is needed at all when you eat a high protein diet. Eating 150g daily will give you 21g of glutamine, making supplementation completely unnecessary.
But if you don’t eat a high protein diet, and you’re looking for a supplement, this is the one I would advise.