People with HIV often take micronutrient supplements, but the research has not yet proven what the most useful dosages are for these individuals. Certain nutrients may directly influence the immune system's ability to fight infection. For example, cells that are supplemented with vitamin D appear to prevent Mycobacterium avium complex (MAC) from growing in macrophages from HIV-positive patients. This article will briefly review selected micronutrients and their known functions in the complex immune system.
Malnutrition and Immune Function
It has long been known that malnourished individuals are at higher risk for infectious disease due to an inadequate immune response. Infection then leads to inflammation and worsening nutritional status, which further compromises the immune system. This has been called the "vicious cycle." The outcomes of certain infectious diseases, including HIV and tuberculosis, are worse when the host is malnourished. Protein-calorie malnutrition has a significant negative effect on various components of the immune system. Studies have shown decreased function of the organs (thymus, spleen, lymph nodes) of the immune system in malnourished humans. The branch of the immune system that produces antibodies is depressed in malnutrition, specifically with a decreased number of circulating B-cells and antibody responses. As for the other branch of the immune system, malnourished humans exhibit decreased CD4+ and CD8+ T-cell counts, and the cells have less ability to multiply or respond to infectious organisms such as viruses that live inside of them. Other mechanisms that kill infectious organisms are also depressed in malnutrition. The functions of cytokines, chemicals that act as cell messengers, are altered in malnourished individuals. Replenishment of calories and protein is a difficult but essential intervention for people living with HIV/AIDS to mount as effective an immune response as possible to fight opportunistic infections.
Selected Vitamins and Immunity
Various studies have demonstrated that HIV-positive individuals have lower blood concentrations of certain vitamins, particularly vitamins A, B6, B12, C, E and folate. Vitamin A deficiency can interfere with how epithelial cells function, which is vital in maintaining tissue structure. The ability of certain immune cells to kill infectious organisms and the production of B-cells and T-cells are also dependent on vitamin A status. Blood levels of vitamin A have been shown to be lower in HIV-positive individuals compared to healthy individuals in both developing and developed countries. This is especially true in HIV-positive individuals with an opportunistic infection or cancer. Beta-carotene, a predecessor to vitamin A, has also been shown to be deficient in HIV-positive individuals despite vitamin supplementation. Since beta-carotene is a strong antioxidant, supplementation may improve CD4+ counts and natural killer cell activity.
The immune-related roles of vitamin C include collagen synthesis, phagocyte oxidative burst activity, and the ability of B-cells and T-cells to work properly. Only a few clinical studies have been conducted to determine the usefulness of vitamin C supplementation in HIV/AIDS. One small study of eight people demonstrated increased CD4+ cells and decreased HIV viral load levels after six days of high dosages of vitamin C (3 grams every 6 hours) and N-acetylcysteine (NAC). In the body, NAC can turn into glutathione, which protects cells against early death. This effect was only seen in people with initial CD4+ counts of less than 200. Other studies have shown that high doses of vitamin C can actually speed up the progression of infection, so it's still too early to give a blanket recommendation to megadose with vitamin C.
Low blood levels of vitamin B12 appear to be widespread in HIV infection. Vitamin B12 supplementation has been shown to improve both T-cell counts and natural killer cell activity in people with significant vitamin B12 deficiency. Vitamin B12 and folate are both involved in the production of genetic material. Deficiencies of vitamin B6 can occur as a result of certain medications, such as Isoniazid (for tuberculosis). Vitamin B6 deficiency has been reported in HIV-positive individuals and appears to decrease T-cell responsiveness and natural killer cells' ability to kill infectious organisms. Vitamin B6 deficiency has also been associated with an increased risk for certain cancers.
Vitamin E plays a key role as an antioxidant in cell membranes. Because of this function, vitamin E has been deemed an "anti-viral" nutrient, but this has only been shown in the laboratory, not clinically. Supplementation with vitamins E and A together in animals has demonstrated an enhanced function of neutrophil cells, which can kill infectious organisms. Vitamin E is rarely deficient in humans, although low blood concentrations have been reported in people with HIV.
Selected Minerals and Immunity
Investigations into which minerals are deficient in HIV infection are contradictive. Zinc, selenium and magnesium have been shown to be deficient in some studies. Even a mild zinc deficiency has been shown to reduce thymic hormone production and activity; decrease the numbers of CD4+ cells; harm the function of T-cells, natural killer cells and neutrophils; increase cell death; impair the ability of cells to kill infectious organisms; and interfere with cytokine production. When zinc was supplemented with vitamin A, an increased number of immune cells were seen in humans. Blood levels of zinc in an HIV-positive individual may not accurately reflect how much zinc is stored in the body or immune function, so supplementation is controversial. Furthermore, because of the complex interplay between nutrients in the body, excessive intake of zinc may interfere with copper absorption.
Magnesium's role in the immune system is also unclear; however, low magnesium levels are frequently reported in the HIV/AIDS population. Copper levels are usually normal or elevated during serious illness or trauma in people with HIV. Iron deficiency anemia may be seen in people with chronic disease/infection, but supplementation with this mineral is controversial due to its role as fuel for infectious organisms.
Selenium is a significant cellular antioxidant. Certain viruses become stronger and hardier in selenium-deficient people. Similarly, selenium-deficient animals are more susceptible to cardiac damage from viruses. Animals with selenium and copper or iron deficiency have neutrophils that are less able to kill infectious organisms. Selenium supplementation may be protective against cancer in animals and humans. When vitamin E and selenium are supplemented together in animals, there is an increase in the number of immune cells. In T-cells, the supplementation of selenium suppresses HIV replication and decreases the production of cytokines that cause inflammation. Supplementation with selenium in deficient HIV-positive people has been shown to improve selenium status. Selenium deficiency correlates with viral progression and death in HIV infection more than any other micronutrient. In a few studies, blood selenium correlated with CD4+ counts, although supplementation doesn't always result in improvement in T-cell counts.
Other Nutrients and Immunity
Omega-3 (n-3) fatty acids, normally found in fish oils, have been shown to effect immune function. Two fatty acids, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), have been shown to decrease inflammation by modulating and influencing the cytokine production of T-cells. Other studies have shown that n-3 fatty acids reduce the ability of some immune cells to react to infectious organisms. DHA may also slow down natural killer cell activity. Alpha-lipoic acid, an antioxidant that has been studied in HIV infection, appears to be able to regenerate vitamins C and E, further enhancing the overall antioxidant effect. Certain amino acids, specifically glutamine and arginine, may also play immune-related roles. Glutamine is important in maintaining the structure of the intestinal wall, which prevents infectious organisms from migrating across and into the bloodstream. Arginine contributes to the production of nitric oxide, which appears to have the ability to kill certain infectious organisms' activities.
The countless and intricate relationships between nutritional status, specific nutrients, and the immune system is an exciting and ongoing area of biomedical research. Well-nourished individuals are better prepared immunologically to fight microorganisms. Several micronutrients have significant roles in the functions of the immune system. It's clear that maintaining a good nutritional status and adequate micronutrient stores in the body are essential for mounting an effective immune response to opportunistic infections. However, research has yet to identify specific recommendations for people with HIV. So in the meantime, a well-balanced and varied diet that includes all vitamins and minerals seems to be the best advice.
Jennifer Muir Bowers is a faculty member in the Department of Nutritional Sciences at the University of Arizona in Tucson, AZ. She is also a doctoral candidate, studying nutritional sciences with a minor in microbiology and immunology.