PI Perspective #35

January 2003     View PDF     En español

Complementary Corner

Interest in nutritional health products stems from a number of observations. These include documented nutritional/vitamin deficiencies even in early stages of HIV infection and malnutrition associated with increased risk of HIV disease progression. There is great controversy, however, over whether or not using supplements is always a good idea and if it provides benefits in the long run. There has also been long-standing interest in complementary and alternative medicine (CAM) approaches to managing HIV infection and various conditions associated with HIV. The CAMs most commonly used by people living with HIV are not drugs, herbs or other pharmacologic agents, but rather things like meditation, massage, energy healing, acupuncture and the like. The following article contains summary highlights of studies of nutritional health products and CAM approaches in the setting of HIV presented at the World AIDS Conference in Barcelona.

Selenium and HIV
Several studies have suggested that deficiencies in selenium are associated with HIV disease progression. A small study of 24 children and a larger study of 125 adults living with HIV concluded that those with selenium deficiencies were at a greater risk for HIV disease progression and death. Whether or not selenium supplementation would make a difference, however, is not known, nor did the study clearly determine whether selenium deficiency was a cause or an effect of disease progression.

Observations of selenium toxicity have been noted among people using selenium supplements. This led to warnings noting that unusual diets and vitamin supplements are the most common causes of selenium toxicity in the United States. The U.S. RDA of selenium is generally 55µgs. the Institute of Medicine has proposed that The maximal daily intake of selenium before causing toxic effects is roughly 400µgs for adults.

A study conducted at the University of Miami compared the use of selenium supplementation (200µg/day) to placebo in 259 people living with HIV (147 men, 112 women). Information about CD4+ cell count, viral load and other parameters were collected at the initial study visit and then every six months thereafter for two years. While investigators concluded otherwise, it was not clear that selenium supplementation decreased the risk of hospitalization.

In a related study, investigators examined blood levels of selenium in the 112 women receiving anti-HIV therapy and looked for correlations between selenium levels and the risk for pre-cancerous cervical cells (cervical dysplasia). While selenium levels were lower in women who developed cervical dysplasia, supplementation made no difference in the risk of developing cervical dysplasia.

In another related presentation, investigators provided information on the impact of selenium supplementation on CD4+ cell count increases. It appears that those receiving supplements were more likely to have slightly higher CD4+ cell count increases, but problems with data reporting leave it unclear what other factors may have impacted these increases. Investigators note that heroin use appears to decrease general nutritional status and is associated with lower levels of selenium, but no information on the distribution of heroin users in the supplement vs. placebo group were provided.

In short, the most that can be concluded from these reports is that it remains unknown if selenium supplementation offers any beneficial or harmful effects, whatsoever. Risks for cervical dysplasia appear slightly increased when selenium levels are lower, but supplementation does not appear to lessen this risk. Well-designed research is critical to evaluating the potential benefits (and risks) of selenium supplementation.

Vitamin A (Beta Carotene and Retinoids)
and HIV Drug Interactions
Deficiencies in vitamin A (retinol and its precursor, beta-carotene) have been associated with advanced HIV disease. As in many similar situations, it is unclear if the deficiencies are a cause or effect of disease progression. It also remains unclear if supplementing vitamin A with retinoids or beta-carotene is helpful for people with HIV beyond correcting the deficiency. Moreover, questions remain as to whether or not vitamin A supplements cause vitamin-drug interactions. A team in Canada set out to evaluate whether or not a variety of forms of vitamin A supplements interact with the p450 enzyme system. This system is important for the breakdown and use of many anti-HIV drugs. Things that interact with the p450 system are highly likely to have interactions with anti-HIV drugs, particularly protease inhibitors, as well as with drugs to prevent and treat some opportunistic infection.

The Canadian team evaluated six different vitamin A (beta-carotene) supplement products (four tablets and two liquid filled soft gel capsule products). All of the products tested had lower beta-carotene content then what was indicated on the label. One product had ten-fold less beta-carotene then what was advertised.

All of the constituents of vitamin A (retinal, retinol, retinate and beta-carotene) as well as all of the products tested had moderate (45 to 65%) to strong (65 to 100%) inhibitory effect on the p450 enzyme system. Therefore, these products have a very strong likelihood of interacting with anti-HIV drugs. Studies, in people as opposed to the laboratory, to look at the impact of taking vitamin A supplements (like beta-carotene) in combination with anti-HIV medications, are needed to understand the extent and impact these findings.

Vitamin Supplements and HIV in Women
(Implications for Everyone)
A study in Tanzania, Africa of the use of multivitamins among HIV-positive pregnant women showed that multivitamin supplementation led to decreases in death of the unborn child (fetal death), increases in birth weight and decreases in pre-term births. While these findings were encouraging, trends were noted that children born to HIV-positive moms who received multivitamins during pregnancy were more likely to be infected with HIV. Because of this observation, another study was initiated in Kenya to examine the impact of daily multivitamin supplementation (or placebo) among 400 women who weren’t pregnant and evaluate their impact on vaginal and cervical shedding of HIV.

Women received either a daily multivitamin or placebo for six weeks. The use of multivitamins was associated with slightly higher CD4+ and CD8+ cell counts and no overall changes in HIV levels in the blood. However, multivitamin use was associated with increases in vaginal shedding of HIV, with about ½ log higher levels of HIV in vaginal swabs among those receiving multivitamins.

Researchers speculate that the use of daily multivitamins among women is unlikely to protect women from HIV infection and may increase the likelihood that they will transmit HIV to others.

Another study found that vitamin A deficiencies in the blood were associated with increased vaginal shedding of HIV during pregnancy, increased HIV in breast milk, higher rates of mother-to-child HIV transmission, lower CD4+ cell counts and more rapid HIV disease progression. These observations come from studies in the third world where dietary vitamin A deficiencies are notable and marked, regardless of HIV status. The same team that conducted the study of multivitamins noted above evaluated the use of vitamin A supplementation or placebo in 400 Kenyan women who were not pregnant and examined a variety of viral and immune parameters.

Women received either vitamin A (10,000 IU delivered as retinyl palmitate) or placebo, daily for six weeks. The dose of vitamin A used is the dose recommended by the World Health Organization for correcting symptomatic vitamin A deficiencies in women of childbearing potential. The study found that vitamin A supplementation had no effect (positive or negative), whatsoever, on vaginal shedding of HIV, blood levels of HIV, CD4+ or CD8+ cell counts compared to placebo. These observations held true even among women with notable vitamin A deficiencies at the start of the study (about 59% of the women). These findings suggest that while vitamin A deficiencies may be associated with poorer outcomes in mother-to-child HIV transmission and poorer outcomes of HIV disease in general, supplementation is unlikely to address these problems.

The women in these studies were not receiving anti-HIV therapies and thus the results are perhaps most relevant to settings where anti-HIV therapies are not available and/or to individuals who choose not to use them in conjunction with supplement approaches. Whether the increase in vaginal shedding of HIV associated with multivitamin supplements would be controlled with the concurrent use of anti-HIV therapy remains unknown.

Vitamin E, Vitamin A and Anti-HIV Therapies
Previous reports have suggested that vitamin E levels are decreased in people living with HIV and low levels of vitamin E in the blood have been associated with increased risk of HIV disease progression. Researchers in the United Kingdom sought to evaluate vitamin E levels among 33 people before and six weeks after starting anti-HIV therapy and compare them to levels observed in healthy HIV-negative people.

Investigators found that prior to starting anti-HIV therapy, vitamin E levels were lower among people with HIV compared to healthy HIV-negative people. Contrary to previous reports, people with HIV who had AIDS had slightly higher vitamin E levels (24µmol/liter) compared to people with HIV who did not have AIDS (19µmol/liter). After six weeks of anti-HIV therapy, vitamin E levels normalized among people with HIV (28µmol/liter) compared to HIV-negative people with vitamin E levels measured six weeks after the start of study (26µmol/liter).

Vitamin A levels were also evaluated before and six weeks after starting anti-HIV therapies. No differences were observed in vitamin A levels either before or after starting anti-HIV therapy. Moreover, vitamin A levels were in normal healthy ranges, roughly equivalent to those observed in HIV-negative individuals, both before and after six weeks of anti-HIV therapy use. Further, no differences were observed in vitamin A levels between healthy HIV-positive people and those with AIDS.

This study suggests that for people taking anti-HIV therapy, vitamin E supplementation is likely not necessary. Moreover, vitamin A deficiencies were not noted with HIV infection, regardless of stage of disease. It remains unknown if vitamin E supplementation among people not on anti-HIV therapy will provide benefits.

Nutrition and Exercise to Manage Lipodystrophy
A group in New York conducted a small study to evaluate the impact of individualized nutrition and exercise advice (delivered by a registered dietitian in accordance with recommendations by the American Heart Association) on lipid levels in people with HIV experiencing lipid elevations associated with the use of anti-HIV therapy. Twenty-five people were enrolled in the study (1 Asian, 10 African Americans, 7 Hispanics and 7 white/non-Hispanic), which included 10 women and 15 men.

Nutritional and exercise advice had little to no impact on lipid levels. Virtually no changes were seen in cholesterol levels (either HDL or LDL cholesterol). There were slight decreases in triglyceride levels, but not to healthy target levels defined by the National Cholesterol Education Program. While only a small study, the investigators propose that nutrition and exercise advice alone are unable to improve lipid abnormalities seen in people on anti-HIV therapy.

There are several limitations to this study that may confound conclusions. One is the relatively small size of the study. Another is that dietary assessments were not conducted (while people were given advice on nutrition and exercise, it’s unknown if they actually followed the advice). Despite underwhelming results from this study, improving nutrition and exercise habits and routines will likely benefit a person’s general overall health even if it has apparently little effect on lipid profiles.

Managing Side Effects of Anti-HIV Therapy with Acupuncture
Acupuncture is an ancient Chinese healing art, involving placing small, fine needles at various points through the skin. These points are believed to conduct an energy, called qi, between the surface of the body and internal organs. Putting fine needles in various points is believed to direct this energy and promote healing and balance. Acupuncture is sometimes used with Chinese herbal remedies, though not always. A Boston study evaluated acupuncture as a treatment for digestive side effects associated with anti-HIV medications.

The study included 26 people who were taking anti-HIV medication and experiencing digestive side effects of therapy. Half received symptom-specific acupuncture for three weeks and half received non-specific acupuncture for three weeks. At the end of three weeks the groups switched modes of acupuncture therapy.

Preliminary results were presented on the effect of symptom-specific and non-specific acupuncture for nausea, excessive gas and loss of appetite associated with the use of anti-HIV therapy.

Side Effect	% reporting symptom after symptom-specific acupuncture treatment	% reporting symptom after non-specific acupuncture treatment
Nausea	25%	37%
Excessive Gas	50%	63%
Appetite Improvements (only includes those reporting lack of appetite at study entry)	85%	58%

 

These results suggest that symptom-specific acupuncture may be more effective than non-specific acupuncture in managing digestive side effects of anti-HIV therapies. Of note, adherence to anti-HIV therapies improved following symptom-specific treatment (80%) compared to non-specific treatment (68%). Current plans are to expand the pilot study to see if these results hold true in a larger and more diverse group of people.

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