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]