N-acetylcysteine, Alpha-Lipoic Acid, L-Glutamine, and L-Carnitine - Nutrients and HIV, part 3

Alternative Medicine Review, August, 2000 by Lyn Patrick

N-acetylcysteine as a Glutathione Regenerator

N-acetylcysteine has been used successfully to treat hepatic and renal failure caused by glutathione depletion secondary to acetaminophen overdose.[41] It has an extensive history as a mucolytic and has been used in pulmonary diseases including emphysema, tuberculosis, chronic asthma, fibrosing alveolitis, and primary amyloidosis of the lung.[42] The mechanism of action in these respiratory conditions includes the restoration of reduced and total glutathione levels in lung cell fluid.[43] N-acetylcysteine has been demonstrated to have heavy metal chelating capacities for toxic metals, as well as for copper, zinc, and boron.[44] Several studies support evidence that NAC increases glutathione levels in vivo and in vitro;[45-48] there is also evidence NAC may boost cellular immunity directly.[49]

N-acetylcysteine in HIV/AIDS

CD4+ and CD8+ T-cells from HIV-infected individuals have an impaired ability to proliferate; they are also unresponsive to recall antigens and unable to secrete normal amounts of interleukin-2, exhibiting properties similar to a state of anergy.[50] This altered response appears to be the reason for the rebound of viral loads to pre-medication levels following discontinuation of triple anti-viral therapies even after one year of continuous and successful treatment.[51] NAC appears to be able to help restore CD4 cell function: in a study of 11 asymptomatic HIV-infected individuals with CD4+ counts of over 300/mL, N-acetylcysteine (at 5, 10 and 20 mM) restored normal CD4+ proliferative responses in 8 of 11 patient blood samples.[50]

N-acetylcysteine appears to be beneficial in HIV as a result of its ability to restore normal glutathione levels in lymphocytes and thereby reduce free radical production.[52] NAC also, however, acts directly as an antioxidant.[52] Preincubation with 15 mM concentration of NAC was able to partially protect lymphocytes from asymptomatic HIV-infected patients after exposure to menadione, an oxidizing agent. This study also found a significant relationship between CD4+ counts, plasma peroxidation, and the ability of NAC to preserve the structural characteristics of the lymphocytes. The patients with lower CD4+ counts also had higher levels of lipid peroxidation products and were less protected by the same amount of NAC. As a direct free radical scavenger, NAC reduces hypochlorous acid produced by neutrophils in order to kill target cells.[53] Because NAC has a direct antioxidant action in lymphocytes, concern has been expressed that NAC supplementation would inhibit the natural mechanism of cytolysis by neutrophils. Cell studies[54] have shown NAC actually enhances intracellular killing of bacteria by protecting neutrophils and macrophages from free radical damage generated during phagocytosis. Cell studies with HIV-infected monocytes and neutrophils have shown similar results: NAC (at 1 and 5 mM concentrations), enhanced their cytotoxicity.[53] Multiple cell studies have shown NAC acts as an antiviral in HIV-infected cell lines; both by direct inhibition of TNF-[Alpha][52,55-57] and direct inhibition of viral transcription.[55]