OBJECTIVES: There have been claims that l-ornithine alpha-ketoglutarate (OKG) exerts anticatabolic, anabolic, and immunomodulating properties. This study aimed at quantifying the effects of OKG on muscle force, body composition, and immune function in outpatients infected with the human immunodeficiency virus (HIV) and presenting weight loss. METHODS: Forty-six HIV(+) patients were included in a double-blind, prospective, randomized, controlled trial for 12 wk (10 g/d of OKG or isonitrogenous placebo and nutritional counseling). Podometry, handgrip strength, step test, triceps skinfold thickness, 50-kHz bioelectrical impedance, 3-d diet record, CD4 cell count, HIV-1 RNA concentration (viral load), and gastrointestinal symptoms were assessed at 0, 4, 8, and 12 wk. RESULTS: At baseline, patients (OKG, n = 22; placebo, n = 24) has similar CD4 counts (338 +/- 172 and 310 +/- 136 cells/mL), viral load (3.6 +/- 1.3 and 3.5 +/- 1.3 log(10) copies/mL), body mass index (20.0 +/- 2.4 and 20.6 +/- 3.0 kg/m(2)), weight loss (9.0 +/- 3.12 and 9.4 +/- 3.0 kg), and food intake (2509 +/- 962 and 2610 +/- 808 kcal/d). Twenty-nine patients completed the protocol. Both groups increased their body mass index (P = 0.02 versus baseline) and triceps skinfold thickness (P < 0.01 versus baseline). They showed a similar positive correlation between handgrip strength and fat-free mass. Frequency of gastrointestinal symptoms increased in the OKG group (86% versus 54% in the placebo group, P = 0.025). No other differences were observed between groups. CONCLUSIONS: All patients increased their body mass index and triceps skinfold thickness due to food supplementation and diet counseling. Oral OKG failed to improve nutritional, functional, or immunologic status in these weight-losing HIV(+) patients and had important gastrointestinal side effects.