Thirty-eight patients (median age, 36 years) with AIDS-associated diarrhea and/or wasting were randomly assigned to receive, in double-blind fashion, one of the following treatments daily for seven days: 1) 46 g of glycine (control), 2) 30 g of glutamine plus 15 g of glycine, 3) 4 g of alanyl-glutamine plus 42 g of glycine, or 4) 44 g of alanyl-glutamine (which is equimolar to 30 g of glutamine). All regimens were isonitrogenous. Nineteen of 20 patients receiving glutamine or high-dose alanyl-glutamine improved, as compared with 38% of controls (p < 0.003). Low-dose alanyl-glutamine was also effective, but less so than high-dose alanyl-glutamine. Blood levels of antiretroviral drugs, which were universally low at baseline, increased in patients receiving high-dose alanyl-glutamine or glutamine by 113% (p = 0.02) and 14% (p = 0.01), respectively.

Comment: Glutamine plays an important role in both gastrointestinal function and immune function. The results of the present study indicate that glutamine is an effective treatment for AIDS-associated diarrhea and also increases antiretroviral drug levels to some extent. The mechanism of the increase in drug levels is probably related to an improvement in malabsorption. In previous studies of AIDS patients, supplementation with 30 g/day or more of glutamine was not associated with any serious adverse effects.

Alanyl-glutamine is a dipeptide that releases glutamine after being hydrolyzed in vivo. The fact that this peptide increased antiretroviral drug levels to a greater extent than did glutamine suggests that alanyl-glutamine is more effective than glutamine at reversing gastrointestinal pathology. However, the study lasted only seven days, and it is possible that the benefits of glutamine would have "caught up" to those of the dipeptide in a longer study. Alanyl-glutamine does not appear to be readily available at the present time, whereas glutamine is widely available and relatively inexpensive.

Bushen OY, et al. Diarrhea and reduced levels of antiretroviral drugs: improvement with glutamine or alanyl-glutamine in a randomized controlled trial in northeast Brazil. Clin Infect Dis. 2004;38:1764-1770.