HIV and the Role of Nutritional Supplements

Photograph © Colin Dunn

Understanding How They Help (and When They Might Harm) 

By Dennis Sifris, MD and James Myhre

Updated September 06, 2016

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Proper nutrition is as important to the long-term health and well-being of a person living with HIV as it is to anyone else. But oftentimes, dietary needs require adjustments as the body responds to different medications or the disease itself.

Vitamins and minerals can often be depleted during severe or prolonged bouts of diarrhea, the condition of which can induced by certain infections or medications.

Changes in body fats, also associated with treatment or HIV infection, can demand marked changes to one’s diet.

Far more concerning, however, is the impact on malnutrition on people with HIV. Vitamin A and B-12 deficiency, for example, has been associated with faster disease progression in both resource-rich and resource-poor settings. Low serum levels of micronutrients, commonly seen in malnourished individuals, demand greater vitamin intake—often in the way of nutritional supplements.

Without question, nutritional supplements have their place in the treatment of malnutrition or a diagnosed deficiency, whether it be caused by an HIV-related condition or poor nutrition itself. This is particularly true in late-stage disease when weight loss and HIV wasting are frequently seen.

But what about everyone else? Do people with HIV inherently need nutritional supplements? Do these products complement therapy in a way that either reduces the incidence of infection, delays disease progression, or reconstitutes a person’s key immune functions?

Or are we just hoping they will?

Putting the Supplements Industry into Context

According to the U.S. Centers for Disease Control and Prevention (CDC), nearly half of all Americans consume dietary supplements, including vitamins, minerals and herbals. This expansive range of products is regulated by the U.S.

Food and Drug Administration (FDA), which defines dietary supplements simply as products “intended to add further nutritional value to (supplement) the diet.”

In accordance with this definition, multivitamins and other nutritional supplements are regulated as a category of food, rather than as a pharmaceutical product. They neither have to go through stringent, pre-market safety and effectiveness testing, nor does the FDA have the authority to require such testing.

Instead, the FDA relies primarily on post-market surveillance—monitoring consumer complaints and requiring manufacturers to maintain of a roster of adverse events. However, these adverse event reports (AERs) are only sent in instances of serious to life

threatening side effects. Mild to moderate events, such as headache or gastrointestinal distress, are not reported unless the manufacturer voluntarily chooses to do so.

This is in stark contrast to the pharmaceutical industry, which spends an average of $1.3 billion dollar per drug in research & development costs in order to obtain FDA approval.

In 2011, sales of dietary supplements hit $30 billion in the U.S., more than twice the size of the global HIV drugs market.

Can Supplements "Boost" Immunity?

Good nutrition by means of a balanced diet can help ensure proper immune function in conjunction with the timely and informed use of antiretroviral medications. The role of vitamins and other nutritional supplements, by contrast, remains debatable.

Confusion is rife in the consumer marketplace, often fueled by manufacturer claims about products which are thinly supported by research. And while the FDA tries to regulate these claims, a 2012 assessment by the Department of Health and Human Services reported that as much as 20% of the supplements reviewed made wholly prohibited claims, oftentimes around the issue of “immune support.”

It’s not so much that these claims are patently false. It simply that the evidence referred to is generally inconclusive or anecdotal at best.

A number of manufacturers, for instance, regularly point to a 2004 study by the Harvard School of Public Health, which looked at the effect of multivitamins on disease progression in 1,097 HIV-positive, pregnant women in Tanzania. At the end of the trial, 31% who had taken the supplements had either died or acquired an AID-defining illness versus 25% in placebo group.

Based on this evidence, the researchers concluded that the daily use of a multivitamins (specifically B, C and E) not only delayed HIV progression, but provided “an effective, low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women.”

Upon publication of the research, a number of manufacturers pointed to the study as “scientific proof” of their product’s immune-boosting properties. What most failed to do, however, is contextualize the study, ignoring the numerous co-factors that contributed to the results—not least of which are the high levels of poverty, hunger and malnutrition that exist within an indigent African population.

Ultimately, nothing in the study suggested that multivitamins, in and of themselves, would demonstrate the same benefits—or afford the same conclusions—in the resource-rich settings like the U.S. or Europe.

Results from follow-up studies have been largely inconsistent, including a 2012 study which showed that high-dose multivitamins might actually increase the risk of death in severely malnourished individuals. Others clinical studies have shown benefits only in those with advanced disease (CD4 counts under 200 cell/mL), while others still have shown no benefit at all.

What most studies have supported is the safety of multivitamins in recommended daily doses, particularly for people with HIV who are either undernourished or in advanced stages of disease.  

When Supplements Do More Harm Than Good

Far less is known about the benefits of individual vitamins, minerals, and other trace elements. A number of studies in recent years have focused on the role of selenium, a non-metal mineral with known antioxidant properties. Research seems to suggest that the loss of selenium in early HIV infection parallel the loss of CD4 cells at a time when malabsorption and malnutrition are generally not seen to be factors.

As compelling as this relationship might seem, research has not yet been able to support any true benefit of selenium supplementation, either in the avoidance of HIV-related illness or the reconstitution of CD4.  Similar results have been seen with magnesium and zinc supplements, whereby increases in plasma levels have had no correlative association to either disease progression or outcome.

The prolific use of supplements by some HIV-positive people is underpinned by the belief that “natural” products provide natural immune support that can readily complement HIV therapy.

This is often not the case. In fact, a number of supplements can have a profoundly negative impact on people with HIV, either by interfering with the metabolism of their drugs or by causing toxicities that mitigate any possible benefit of supplementation.

Among the potential concerns:

• Megadose Vitamin A – High doses of vitamin A (above 25,000 IUs daily) can increase the risk of liver toxicities, internal bleeding, spontaneous fractures, and weight loss. The World Health Organization (WHO) does not recommend the use of vitamin A supplements in pregnant, HIV-positive women, with research showing that a daily 5,000 IU dose might actually increased the risk of mother-to-child transmission.
   
• Megadose Vitamin C – While some research has suggested that high doses of vitamin C may play a significant role in cellular immunity, evidence is highly contradictory.  What we do know is that high doses of vitamin C can cause gastrointestinal distress and diarrhea (the latter of which can impact absorption of certain HIV medications). Vitamin C doses above 1000 mg per day are also known to reduce Crixivan (indinavir) levels in some.
   
• Vitamin B6 (pyridoxine) – Excessive intake of vitamin B-6 (above 2,000 mg per day) can cause reversible nerve damage, exacerbating peripheral neuropathy in HIV-positive patients already affected by the condition.
   
• Vitamin E – High doses of vitamin E (above 1,500 IUs) can interfere with blood clotting, while prolonged, excessive use can result in diarrhea, muscular weakness, and nausea.
   
• St. John’s Wort (hypericin) – An herbal preparation popularly used to treat mild depression, St. John’s Wort is known to reduce the levels of all protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-class drugs, putting the patient at risk of drug resistance and treatment failure.
   
• Garlic – Garlic pills and supplements have been shown to reduce serum levels of certain HIV drugs, particularly Invirase (saquinavir) which can be reduced by half when taken concurrently with garlic supplements. By contrast, fresh or cooked garlic are not seen to affect serum drug levels.
   
• Grapefruit Juice – An 8 oz. glass of fresh grapefruit juice taken with Crixivan can reduce serum drug levels by 26%, while a similar size glass can increase Invirase levels by up to 100% (increasing potential side effects). While grapefruit juice should not necessarily be omitted from one’s diet, it should not be taken either two hours before or two hours after a drug dose.

Take Home Messages

The importance of proper nutrition and healthy, balanced diet cannot be overstressed. Nutritional counseling may help those with HIV better understand their dietary needs in order to better:

• Achieve and maintain a healthy body weight.
• Maintain healthy lipids levels, including cholesterols and triglycerides.
• Foresee dietary complications that may result from some antiretroviral medications.
• Address dietary complications that may arise from HIV-related symptoms.
• Implement food measures to avoid possible food-borne opportunistic infections.

The role of exercise cannot be ignored, with benefits to both physical and mental health (including a reduction in the risk in HIV-associated neurocognitive impairment).

In terms of supplementation, a daily multivitamin can help ensure that micronutrient needs are met, particularly in those unable to achieve nutritional goals.

However, taking vitamins in excess of their recommended daily allowance is not advised. There is also no data to support the use of herbal supplements in either treating HIV infection or increasing the efficacy of antiretroviral drugs by reducing the HIV viral load.

Please advise your doctor of any supplements you may be taking when discussing the management and treatment of your HIV.

Sources:

U.S. Centers for Disease Control and Prevention (CDC). “Dietary Supplement Use Among U.S. Adults Has Increased Since NHANES III (1999-1994).” NCHC Data Brief. National Center for Health Statistics; Hyattsville, Maryland; April 2011; Number 1.

 Fawzi, W.; Msamanga, G.; Spiegelman, D.; et al. “A randomized trial of multivitamin supplements and HIV disease progression and mortality.” New England Journal of Medicine. July 2004; 351(1):23-32.

Isanaka, S.; Mugusi, F.; Hawkins, C; et al. “Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial.” Journal of the American Medical Association. October 17, 2012; 308(15):1535-1544.

 Constans, J.; Delmas-Beauvieux, M.; Sergeant, C.; et al. “One-year antioxidant supplementation with beta-carotene or selenium for patients infected with human immunodeficiency virus: a pilot study.” Clinical Infectious Diseases. September 1996; 23(3):654-656. 

 Villamor E.; Msamanga, G.; Spiegelman, D.; et al. “Effect of multivitamin and vitamin A supplements on weightgain during pregnancy in HIV-1-infected women.” American Journal of Clinical Nutrition. December 7, 2001; 76(5):1082-1090.

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Read more articles from Very Well, here.

 You can also find some really good information about Vitamins and Supplements if you visit The Well Project, here.