Restoration of blood total glutathione status and lymphocyte function following α-lipoic acid supplementation in patients with HIV infection

Objectives: To determine whether supplementation with alpha-lipoic acid (ALA), a glutathione-replenishing disulfide, modulates whole blood total glutathione (GSH + GSSG) levels and improves lymphocyte function in human immunodeficiency virus (HIV)-infected subjects with history of unresponsiveness to highly active antiretroviral treatment (HAART). Design and setting: Randomized, double-blinded, placebo-controlled trial conducted at two study sites: an eye clinic at a county hospital in San Jose and a research clinic in San Francisco, California. Subjects: A total of 33 HIV-infected men and women with viral load > 10,000 copies/cm(3), despite HAART, aged 44-47 years, approximately 36% nonwhite, were enrolled. Intervention: Patients were randomly assigned to receive either ALA (300 mg three times a day) or matching placebo for 6 months. Main outcome measures: The change over 6 months in blood total glutathione status, lymphocyte proliferation response to T-cell mitogens, CD4 cell count, and viral load in patients receiving ALA compared to placebo. Results: The mean blood total glutathione level in ALA-supplemented subjects was significantly elevated after 6 months (1.34 +/- 0.79 vs. 0.81 +/- 0.18 mmol/L) compared to insignificant change (0.76 +/- 0.34 vs. 0.76 +/- 0.22 mmol/L) in the placebo group (ALA vs. placebo: p = 0.04). The lymphocyte proliferation response was significantly enhanced or stabilized after 6 months of ALA supplementation compared to progressive decline in the placebo group (ALA vs. placebo: p < 0.001 with phytohemagglutinin; p = 0.02 with anti-CD3 monoclonal antibody). A positive correlation was seen between blood total glutathione level and lymphocyte response to anti-CD3 stimulation (R-2 = 0.889). There was no significant change in either HIV RNA level or CD4 count over 6 months in the ALA-supplemented compared to the control group. Conclusion: Supplementation with alpha-lipoic acid may positively impact patients with HIV and acquired immune deficiency syndrome by restoring blood total glutathione level and improving functional reactivity of lymphocytes to T- cell mitogens.