Glutamine excess

Glutamine is abundant. There are mechanisms by which glutamine is transferred throughout the body based on the needs of the moment. Even with the body's innate ability to deal with large amounts of glutamine, one might theorize that a critical concentration could be reached that could cause harm. In the rodent, increased levels of body glutamine from exogenous sources results in increased expression of intestinal glutaminase and an increase in glutamine metabolism [72]. Whether a similar mechanism exists in humans is unclear. Nevertheless, it appears that the human body is well equipped to safely deal with any excess.

A review of available data concerning the safety of glutamine supplementation reveals that in most circumstances it is quite safe [85]. There are certain circumstances wherein glutamine has been the cause of untoward side effects. Oral glutamine may cause or worsen hepatic encephalopathy in patients with cirrhosis, possibly as a result of its conversion to glutamate and ammonia [72]. This may also explain the fact that it may be unsafe in patients with liver or kidney disease. However, there is some evidence to suggest that glutamine degradation to glutamate and ammonia does not produce neurotoxic effects in humans [85]. A case report details a patient who suffered mania and hypomania as a result of ingesting 4 g of glutamine per day, which could potentially be attributed to the fact that glutamine is a precursor for GABA, a neurotransmitter [86].

Elderly individuals, patients with Alzheimer's dementia, or Down syndrome showed increased glutamine toxicity in peripheral lymphocytes compared to controls [72]. Aside from these sporadic and somewhat anecdotal reports of toxicity, glutamine appears to be quite safe. Even with high intakes of glutamine, the concentrations of ammonia and glutamate are not greatly increased, and the plasma concentrations of other amino acids, hormones, and electrolytes are not altered [85].

When dealing with issues of safety and efficacy, it is important to address such parameters as the form of delivery and route of delivery, as well as dose amount, timing, and duration. Glutamine is stable as a dry solid, but after a short time in solution, it breaks down into toxic by-products, including pyroglutamate and ammonia [69,85]. Recently, delivery has been enhanced by the use of aseptic processing, air-permeable bags for solution, and dipeptide preparations such as alanine-glutamine and glycine-glutamine [87]. Practically speaking, the route of delivery for supplementation is likely to depend on the patient's clinical status and feeding needs.

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