Applied Nutritional InvestigationsGlutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial
Introduction
Significant weight loss commonly occurs in patients with human immunodeficiency virus (HIV) infection.1 The extent of loss of body cell mass (BCM), which is the metabolically active tissue of the body, correlates with length of survival.1 Attempts to reverse this erosion of protein-rich tissue with appetite stimulants, oral nutritional supplements, and enteral or parenteral nutrition have resulted in deposition of adipose tissue, with variable or no restoration of BCM.2, 3, 4, 5 Recombinant human growth hormone (rhGH) administration resulted in gain in lean tissue, but the effects were not sustainable once treatment was terminated.6
It has been hypothesized that the conditionally essential amino acid, l-glutamine (GLN), may be rate limiting for repletion of BCM.7 GLN is synthesized primarily in skeletal muscle and released into the circulation. Tissues that consume GLN, e.g., the immune system, gastrointestinal tract, kidney, and liver, extract GLN as needed from the circulation.8, 9, 10, 11 During stress and inflammation, consumption of GLN exceeds the ability of skeletal muscle to supply this amino acid. Blood and muscle GLN concentrations fall, and progressive muscle breakdown occurs in an attempt to satisfy the GLN demand.7
At present, standard parenteral nutrition solutions and most enteral feeding formulas do not contain GLN; therefore, repletion is not possible.
GLN plays a major metabolic role in the maintenance of visceral tissues. This amino acid is the primary fuel for enterocytes and colonocytes and for the body’s immune tissue.12, 13 It is used at sites of tissue repair and participates in renal acid-base balance.14 It also provides the glutamate necessary for glutathione production.15 The demand for GLN in all of these situations is greatly heightened during infection with HIV.7
Nutrients do not function in isolation. For example, all necessary amino acids and cofactors must be available to achieve protein synthesis. Moreover, the production of reactive oxygen species has been associated with AIDS wasting and weight loss.16 In an effort to provide an environment more favorable to anabolism, a mixture of antioxidant nutrients was provided along with glutamine.
This study was undertaken to determine whether GLN supplementation and select antioxidants could satisfy an increased GLN requirement as occurs with weight loss and thus reverse the loss of BCM in patients with AIDS.
Section snippets
Methods
Study participants were men and non-pregnant women, with HIV infection and without active opportunistic infections, recruited from private-practice physicians who specialize in HIV care in Broward County, Florida. The study was approved by the Human Ethics Committee of Pompano Beach Community Hospital, and signed informed consent was obtained from each volunteer before enrollment, with written approval from each patient’s physician. Eligible study patients were randomized to a placebo-control
Results
Twenty-six subjects were enrolled in the trial, and 21 subjects completed the study. Dropouts occurred for the following reasons: 1 control subject was placed on protease inhibitors, 1 control subject died, and 2 control and 1 GLN subjects dropped out because of study conflicts. Despite the loss of 5 individuals, the groups were well matched (Table I) ; there were no individuals who had a past history of intravenous drug abuse, and all but 3 individuals were taking antiretroviral medication.
Discussion
This study demonstrates for the first time that the provision of a specific nutrient supplement, when coupled with nutritional counseling, can improve weight and restore BCM. Patients who received the combination of GLN and antioxidants for 12 wk increased BW an average of >2 kg and BCM by 1.8 kg. In contrast, control subjects initially gained weight but were unable to maintain the increased BW. At 12 wk, these individuals demonstrated a non-significant gain of 0.3 kg in BW and 0.4 kg in BCM.
Summary
This randomized, double-blind, placebo-controlled trial demonstrates for the first time that supplementation of the amino acid GLN and the provision of adequate antioxidants and nutritional counseling to subjects with HIV wasting can improve BW and restore BCM. This low-cost and low-risk supplement may be the preferred method of initial nutritional support in patients with weight loss of >5%. Larger trials are needed to evaluate the clinical impact of this approach on reducing opportunistic
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