Abstract
Although several specific micronutrient deficiencies are associated with disease progression and increased mortality risk in HIV/AIDS, and even a simple multivitamin/mineral supplement can prolong survival, this is typically viewed merely as nutritional support of the immune system, and only necessary if there are deficiencies to be rectified. However, the reality is more complex. Several striking nutrient-related metabolic abnormalities have been consistently documented in HIV infection. One is chronic oxidative stress, including a drastic depletion of cysteine from the glutathione pool, and a progressive decline of serum selenium that is correlated with disease progression and mortality. Another is decreased blood levels of tryptophan, with an associated intracellular niacin deficiency. Tryptophan depletion or “deletion” by induction of indoleamine-2,3-dioxygenase (IDO), the first step in oxidative tryptophan metabolism, is a known mechanism for immune suppression that is of critical importance in cancer and pregnancy, and, potentially, in HIV/AIDS. Existing evidence supports the hypothesis that these nutrient-related metabolic abnormalities in HIV infection regarding antioxidants, selenium, sulfur, tryptophan and niacin are interrelated, because HIV-associated oxidative stress can induce niacin/NAD+ depletion via activation of poly(ADP-ribose) polymerase (PARP), which could lead to tryptophan oxidation for compensatory de novo niacin synthesis, thereby contributing to immune tolerance and T-cell loss via tryptophan deletion and PARP-induced cell death. This “oxidative stress-induced niacin sink” (OSINS) model provides a mechanism whereby the oxidative stress associated with HIV infection can contribute to immunosuppression via tryptophan deletion. This model is directly supported by evidence that antioxidants can counteract indoleamine-2,3-dioxygenase (IDO), providing the critical link between oxidative stress and tryptophan metabolism proposed here. The OSINS model can be used to guide the design of nutraceutical regimens that can effectively complement antiretroviral therapy for HIV/AIDS.
Highlights
The use of vitamins, minerals, amino acids and other dietary supplements is widespread in HIVinfected populations, and not surprisingly, many such products are promoted as complementaryalternative medicine therapies by some supplement manufacturers and vendors, and aggressively marketed on the Internet
These nutrients include B vitamins, antioxidant vitamins, zinc and selenium; similar correlations exist for nutritiondependent biomolecules like the antioxidant glutathione, which requires the amino acid cysteine, which becomes depleted in HIV infection (Droge, 1993, Eck et al, 1989)
An extensive body of evidence shows that certain nutrient deficiencies are associated with faster disease progression or increased mortality risk, and pilot studies suggest that micronutrient supplements can prolong survival in HIV/AIDS
Summary
The earliest noted antioxidant defect in HIV-infected patients was the apparent progressive decline in blood levels of the essential dietary antioxidant selenium (Se) that was first reported by Dworkin in the mid-1980s (Dworkin et al, 1985, Dworkin et al, 1986). This decline has been widely documented in many independent studies, as reviewed (Baum and ShorPosner, 1998, Campa et al, 2000, Constans et al, 1999, Taylor et al, 1997), and was generally found to be more severe in full-blown AIDS patients (Dworkin et al, 1988). Low serum selenium was eventually shown to be highly correlated with disease progression and increased mortality risk (e.g., Baum et al, 1997a, Campa et al, 1999, Constans et al, 1995)
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