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Vitamin E (Tocopherol) in HIV/AIDSIntroductionVitamin E is a fat-soluble antioxidant that plays an important role in protecting the cell membrane, bone marrow toxicity (a well established side-effect of AZT[i]), fats, the immune system and vitamin A from oxidative stress. Low levels of vitamin E in the body have been associated with an increase in oxidative stress in persons living with HIV/AIDS. Vitamin E nutriture has been demonstrated to be significantly lower in HIV-positive patients than controls. In a dietary assessment study of 100 asymptomatic HIV+ men, 26 percent had a vitamin E intake of 50 percent or less of the RDA.[ii] In this same patient population, 27 percent had marginal or overtly low serum levels of vitamin E. In a study of 18 AIDS, 12 ARC, and 13 HIV-positive patients, 50, 58, and 38 percent of patients had vitamin E intakes at least 50 percent below the RDA, respectively.[iii] Even at RDA intakes, serum vitamin E deficiencies have been seen in HIV+ populations.[iv] A study of 296 HIV positive men followed over six years showed a decreased risk of progression to AIDS with a doubling of vitamin E intake. [v] Vitamin E Trials in HIV/AIDSAs mentioned earlier, AZT has been demonstrated to cause bone marrow toxicity. A study of the effects of d-alpha tocopherol on bone marrow cultures from stage IV (CDC) AIDS patients revealed similar findings.[vi] At a concentration of 1 to 100 micromol/L, d-a-tocopherol was able to significantly increase the growth of bone marrow cells in culture. When added to erythropoietin, the medication used to partially reverse AZT-induced anemia, AZT suppression of bone marrow cell growth was significantly reversed. In African setup AZT still remains the main medication used to reduce viral levels of HIV-1, and bone marrow failure with anemia, leukopenia, and/or thrombocytopenia are still a feature of progressed stages of HIV infection. [vii]The suppression of hematopoietic progenitor cells is not directly due to HIV infection, since only a minority of these cells become infected.[viii] It has been suggested this effect is instead mediated indirectly by cytokine-induced toxicity via oxidative damage.[ix] Anti-viral Mechanisms of Vitamin EThe main cause of CD4+ T-lymphocyte death in HIV is not due to direct viral invasion, but the process of apoptosis, a cell autonomous “suicide” initiated by several different mechanisms. [x] One of the main mechanisms which appears to trigger CD4+ cell death is oxidative stress.[xi] Reactive oxygen species (ROS) are involved in cell signaling mechanisms which cause cellular apoptosis and activate HIV-1 replication. Both of these processes can be initiated by inflammatory cytokines, particularly tumor necrosis factoralpha (TNF-á).[xii] TNF-á is produced as a result of macrophage stimulation and functions as part of the normal immune response, mediating inflammation and producing anti-tumor factors. Overproduction of TNF-á is associated with rheumatoid arthritis, inflammatory bowel disease, liver cirrhosis, and AIDS wasting syndrome, in addition to other aspects of AIDS pathology. As a result of increased production of TNF-á and other cytokines, immune cells release free radicals which cause cellular damage, initiate apoptosis, and further activate viral replication through the induction of a signaling messenger, nuclear factor kappa B (NF-kB).[xiii] Antioxidants, including vitamin E, reduced NF-kB levels in HIV-1-infected lymphocyte cell cultures and decreased production of oxidant compounds in lymphocytes, which would otherwise lead to viral activation or cell death.[xiv],[xv] Vitamin E is a lipophilic antioxidant which protects cell membranes from lipid peroxidation.[xvi] Packer has demonstrated that á-tocopheryl acetate (E acetate) almost completely blocked NF-kB activation in HIV-1-infected cell cultures, whereas á-tocopherol at the same concentration had a minimal effect.[xvii] Alpha-tocopheryl succinate (ATS) completely inhibited NF-kB binding, which was more effective than E acetate, alpha tocopherol, alpha lipoic acid, and Nacetylcysteine. References [i]
[ii]
Beach R, Mantero-Atienza E,
Shor-Posner G, et al. Specific nutrient abnormalities in asymptomatic HIV-1
infection. AIDS 1992;6:701-708. [iii]
Dworkin BD, Wormser GP,
Axelrod F, et al. Dietary intake in patients with acquired immunodeficiency
syndrome (AIDS), patients with AIDS-Related complex, and serologically
positive human immunodeficiency virus patients: correlations with
nutritional status. JPEN 1990;14:605-609. [iv]
Baum MK, Shor-Posner G, [v]
[vi]
[vii]
[viii]
[ix]
[x]
Gougeon ML, [xi]
[xii]
Matsuyama T, [xiii]
Duh EJ, Maury WJ, Folks TM, et
al. Tumor necrosis factor alpha activates human immunodeficiency virus type
1 through induction of nuclear factor binding to the NF-kB sites in the long
terminal repeat. [xiv]
Packer L. Inactivation of
NF-kB activation by vitamin E derivatives. [xv]
[xvi]
Packer L. Protective role of
vitamin E biological systems. Am J [xvii]
Packer L, |