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

J Altern Complement Med. 2008 Mar;14(2):139-46. doi: 10.1089/acm.2006.6397.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Antioxidants / administration & dosage*
  • CD4 Lymphocyte Count
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glutathione / blood*
  • HIV Infections / blood*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • Humans
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / drug effects*
  • Thioctic Acid / administration & dosage*
  • Vitamin B Complex / administration & dosage*


  • Antioxidants
  • Vitamin B Complex
  • Thioctic Acid
  • Glutathione