Improvement of immune functions in HIV infection by sulfur supplementation: Two randomized trials

Abstract

To determine the therapeutic effect of sulfur amino acid supplementation in HIV infection we randomized 40 patients with antiretroviral therapy (ART; study 1) and 29 patients without ART (study 2) to treatment for 7 months with N-acetyl-cysteine or placebo at an individually adjusted dose according to a defined scheme. The main outcome measures were the change in immunological parameters including natural killer (NK) cell and T cell functions and the viral load. Both studies showed consistently that N-acetyl-cysteine causes a marked increase in immunological functions and plasma albumin concentrations. The effect of N-acetyl-cysteine on the viral load, in contrast, was not consistent and may warrant further studies. Our findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency. Because immune reconstitution is a widely accepted aim of HIV treatment, N-acetyl-cysteine treatment may be recommended for patients with and without ART. Our previous report on the massive loss of sulfur in HIV-infected subjects and the present demonstration of the immunoreconstituting effect of cysteine supplementation indicate that the HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination.

Antioxidant Activity of Sulfur and Selenium: A Review of Reactive Oxygen Species Scavenging, Glutathione Peroxidase, and Metal-Binding Antioxidant Mechanisms

“…Additional investigations related to the harmful effects of homocysteine have been extensively reviewed [136,138]. In contrast, improved immune function for patients with HIV infection was observed with NAC supplementation [141]. Lead toxicity, associated with neurological, immunological, reproductive, and circulatory pathologies, has been reduced with the sulfur antioxidants N-acetylcysteine and lipoic acid [124].…”

Effect of oral N-acetyl cysteine supplementation in type 2 diabetic patients on intracellular glutathione content and innate immune responses to Burkholderia pseudomallei

“…For example, high dose oral NAC treatment was found to reduce neutrophil infiltration and elastase release in cystic fibrosis patients [31]. Another study in HIV infected patients, who had been documented to have GSH deficiency, reported an improvement in viral loads, and NK and T cell function after NAC therapy [44]. However, it is not clear if the immune functions and inflammation parameters restored in these studies were in direct response to an improvement in the GSH ratio, total thiol levels, total GSH levels, or an indirect effect of NAC supplementation.…”

Sulfur

“…Sulfur excretion was more than three-fold higher than in HIV-negative patients. In addition to an increased cysteine level following N-acetylcysteine and cysteine treatment, an improvement in immune function has also been observed (Breitkreuz et al 2000).…”