The role of antioxidants in preventing apoptosis and viral activation in HIV is well documented. N-acetylcysteine, glutathione, and alpha-lipoic acid have been shown to interrupt the process of viral activation and CD4 cell death. L-glutamine has been shown to improve glutathione levels and significantly increase lean body mass in HIV infection. The literature on the use of L-carnitine and acetyl-L-carnitine in treating mitochondrial toxicity, both in muscle and nerve pathologies is relevant in nutritional treatment of HIV, given the mitochondrial toxicity of nucleoside analog reverse transcriptase inhibitor therapy. The current use of highly-active antiviral therapies, their toxicity, and significant failure rates have created the need for a more conservative reassessment of HIV treatment. The adjunctive use of nutrient therapy in the treatment of HIV is reviewed here.
(Altern Med Rev 2000;5(4):290-305)
The Importance of Redox Homeostasis in HIV
HIV infection and the progression to AIDS involves a long period of latent infection characterized by low levels of viral replication that slowly increase to the point of immunosuppression. This progression is accelerated if the latent (non-reproducing) provirus in the nuclei of the lymphocyte is activated. Oxidative stress induces both viral activation of HIV and DNA damage, leading to immunosuppression.[3-5] It is now generally accepted that a central pathologic feature of HIV disease involves oxidative stress, leading to programmed cell death (apoptosis) and depletion of CD4 cells.[6,7] It has been hypothesized by Montagnier and others[8,9] that the majority of T-helper (CD4+) cell loss (the cell most susceptible to fatal injury by HIV) actually occurs by apoptosis and not by direct HIV infection. This phenomenon has been seen in in vitro culture and in peripheral blood lymphocytes from HIV-infected patients.
Evidence of increased oxidation reactions, depletion of the glutathione-based antioxidant defense system, and increased levels of oxygen radicals have been demonstrated in the blood and tissues of HIV-infected individuals. Elevated levels of hydroperoxides, malondialdehyde, and deficiencies of the critical antioxidant enzymes manganese superoxide dismutase, glutathione peroxidase, thioredoxin, and catalase have been demonstrated in plasma, lung lining, erythrocytes, and lymphocytes in HIV-infected individuals.[4,7,13] Nutrient malabsorption, glutathione and selenium depletion, and reduction of total thiol (cysteine) levels have all been observed to be associated with the pathology of free radical overload that leads to the cellular apoptosis of T lymphocytes.
Glutathione: Antioxidant and Antiviral
Glutathione, the most abundant cellular thiol, provides the major antioxidant defense mechanism in all mammalian cells by neutralizing toxic peroxides. It also helps to maintain levels of ascorbate and tocopherol by acting as a reducing agent. Glutathione is necessary for maintaining immune mediated T-cell activation and phagocytosis, in addition to cellular and antibody mediated cytotoxicity, and a normal balance between the T-helper cell 1 (IL-2, IL-12, gamma-interferon) and the T-helper cell 2 (IL-6, IL-4, tumor necrosis factor-alpha, IL-10, IL-1) cytokine response profile. Glutathione conjugation is also the primary mechanism of eliminating electrophilic xenobiotics (some of which are carcinogens) in the liver.
Glutathione deficiency has been theorized to be the cause of the increased sensitivity HIV-infected individuals have to high doses...
This is a preview. Get the full text through your school or public library.