Abstract
This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter randomized controlled trial resulted in increased mortality in the glutamine-supplemented group. Within this context, defining the contribution of glutamine to the production of citrulline, and thus to de-novo arginine synthesis, has become a pressing issue. The beneficial effects of glutamine supplementation may be partially mediated by the effects of glutamine on citrulline synthesis by the gut and the de-novo synthesis of arginine by the kidney and other tissues. Although there is no strong evidence to support that glutamine is a major precursor for citrulline synthesis in humans, glutamine has the potential to increase overall gut function and in this way increase citrulline production.
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