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


METHODS
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.


METHODS
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.


METHODS
Patients were randomly assigned to receive either ALA (300 mg three times a day) or matching placebo for 6 months.


METHODS
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.


CONCLUSIONS
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.
Jariwalla
Raxit J
RJ
California Institute for Medical Research, San Jose, CA, USA. r.jariwalla@drrath.com
Lalezari
Jacob
J
Cenko
Diane
D
Mansour
Sam E
SE
Kumar
Abha
A
Gangapurkar
Bhakti
B
Nakamura
Daniel
D
D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000097:blood*; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D008063:Thioctic Acid / Q000008:administration & dosage*; D014803:Vitamin B Complex / Q000008:administration & dosage*
D000975:Antioxidants; D014803:Vitamin B Complex; D008063:Thioctic Acid; D005978:Glutathione