Nutrition and HIV
Good nutrition is key to a healthy lifestyle, regardless of whether one is living with HIV/AIDS. Optimal nutrition can help boost immune function, maximize the effectiveness of antiretroviral therapy, reduce the risk of chronic illnesses such as diabetes and cardiovascular disease, and contribute to a better overall quality of life.
In the early years of the AIDS epidemic, many people with HIV were dealing with wasting and opportunistic infections (OIs) linked to unsafe food or water. While these problems are less common today in developed countries with widespread access to highly active antiretroviral therapy (HAART), many HIV positive people have traded these concerns for worries about body shape changes, elevated blood lipids, and other metabolic complications associated with antiretroviral therapy.
Fortunately, maintaining a healthy diet can help address these problems. As HIV positive people live longer thanks to effective treatment, good nutrition can also help prevent problems (such as bone loss) associated with normal aging. But there is no single, optimal eating regimen appropriate for every person living with HIV/AIDS. Instead, HIV positive people should adopt a sensible balanced diet and consult an experienced nutrition specialist for individualized recommendations.
Food for LifeFood is essential for life, providing the fuel the body needs to function and the building blocks that make up cells, tissues, and organs. The energy provided by food is expressed in terms of calories. The body requires a certain number of calories simply to carry out its basic metabolic functions such as respiration and maintenance of body temperature. Additional calories are needed to support physical activity, fight infection, and rebuild damaged tissues.
If a person does not take in enough calories, fat is broken down to provide fuel. Once the fat is consumed -- or if an individual's metabolism is disrupted due to illness -- lean body mass (muscles and organs) is then used for fuel and raw materials. Conversely, if a person takes in more calories than needed, the extra energy will be stored as fat. The average person needs about 10-20 calories per pound (depending on physical activity level and other factors) to maintain a stable body weight; this requirement is likely to be higher for people with HIV, especially those with advanced disease.
But all food is not equal. While all contain calories, different foods vary widely in the nutrients they provide. A balanced diet is comprised of the following components.
Protein: Protein provides the building blocks of lean body mass. When a protein-rich food is consumed, it is broken down into amino acids, which are reassembled to create enzymes, hormones, and bodily tissues. Most nutrition experts recommend that protein should contribute about 15-20% of the total calories in a person's diet. Good sources include meat, poultry, fish, eggs, dairy products, tofu, nuts, and legumes (e.g., dried beans, lentils).
Carbohydrates: Carbohydrates, which are converted to glucose in the body, are a primary source of energy. Carbohydrates are classified as simple or complex; complex carbohydrates take more time to break down, and thus provide fuel over a longer period of time. Despite the recent popularity of "low carb" diets, most nutrition experts recommend that carbohydrates -- primarily complex ones -- should make up at least 50% of one's total daily calorie intake. Simple carbohydrates are found in processed sugar, honey, fruit and juice, and lactose (milk sugar). Complex carbohydrates are found in grain products such as bread, pasta, and rice; legumes; and starchy foods such as corn, potatoes, winter squash, and root vegetables.
Fats: Fat in food is a source of energy and has a high concentration of calories. Excess energy from any source -- not just fatty food -- is converted to fat in the body and stored for later use. Cholesterol (found in animal products like meat and eggs) and triglycerides are present in food, but are also produced when the body metabolizes sugar and saturated fat. Everyone needs some dietary fat, but getting too little is rarely a problem. More important is the type of fat. Saturated fats promote elevated blood levels of low-density lipoprotein (LDL) "bad" cholesterol, which can clog arteries and increase the risk of cardiovascular disease. Saturated fat is found in meat, butter, tropical oils (e.g., coconut, palm), and "trans" fats or hydrogenated oils (which are chemically altered to make them solid at room temperature). Polyunsaturated fats (found in safflower, sunflower, corn, and soybean oils) are generally considered more healthful, and monounsaturated fats (found in olive and canola oils, nuts, seeds, and avocados) can help raise levels of high-density lipoprotein (HDL) "good" cholesterol, which protects against heart disease. A balanced diet also contains essentially fatty acids, including omega-3 (found in flax and cold-water fish). Most experts say fats should make up no more than 25-30% of total calorie intake, with less than 10% being saturated fat.
Fiber: Also known as "roughage," fiber is indigestible plant matter such as cellulose. Insoluble fiber plays an important role in digestion, helping food move smoothly through the colon (large intestine); this type of fiber is found in the skin and pulp of many fruits and vegetables, whole grains, popcorn, and seeds. Soluble fiber helps stabilize blood sugar and may reduce LDL cholesterol levels; this type of fiber is found in oatmeal and oat bran, legumes, nuts, and fruits such as apples, oranges, pears, and grapes.
Vitamins and minerals: Along with the "macronutrients" described above, a balanced diet also contains many "micronutrients," organic and inorganic substances necessary for proper biological functioning. Water-soluble vitamins (B and C) are excreted in the urine and must be consumed more often; fat-soluble vitamins (A, D, E, and K) are stored in the liver and can reach toxic levels if taken in large doses. Most vitamins must be obtained from food, although the body manufactures vitamin D when the skin is exposed to sunlight and others are produced by bacteria in the gut. Minerals (including the electrolytes chloride, potassium, and sodium) are inorganic substances found in the environment. The body needs several trace elements in tiny amounts, including boron, chromium, cobalt, copper, iodine, manganese, molybdenum, selenium, and zinc. Cooking and processing can destroy some vitamins and minerals. For information on the function and food sources of specific vitamins and minerals, see the chart below.
Antioxidants: Free radicals are unstable oxygen molecules that contain unpaired electrons. This allows them to set off damaging chain reactions when they bind with and "steal" electrons from other molecules in the body -- a process known as oxidative stress. Antioxidants scavenge and neutralize free radicals. By disrupting the oxidation process, antioxidants help protect cells from damage. Antioxidants include vitamins C and E, beta-carotene, the minerals selenium and zinc, and glutathione.
Phytochemicals: Among the advantages of obtaining nutrients from a balanced diet rather than supplements is that there are substances in whole foods that may offer unrecognized benefits. While most vitamins and minerals were isolated early in the 20th century, plant compound called phytochemicals are just now being discovered. Among these are allyl sulfides (found in garlic and onions), anthocyanins (in blueberries and blackberries), carotenoids (including beta-carotene in orange fruits and vegetables, lycopene in tomatoes, and lutein in dark green leafy vegetables), catechins (the tannins in green and black tea), flavonoids (in dark chocolate, red wine, tea, and many fruits), isothiocyanates (in broccoli and other cruciferous vegetables), limonoids (in citrus fruits), and sulforaphane (also in cruciferous vegetables). Some phytochemicals work as antioxidants, but others appear to have different mechanisms of action.
How HIV Impacts Nutrition ... and Vice VersaIn the early years of the epidemic, healthcare providers soon learned that people with AIDS commonly experienced both overt protein/calorie malnutrition and deficiencies of specific nutrients. But nutrient depletion may also begin to occur earlier in the course of HIV disease, even among individuals with relatively intact immune systems. Several factors can contribute to nutritional problems in people with HIV/AIDS.
Malabsorption: HIV or associated infections can damage the lining of the gastrointestinal tract, which can interfere with absorption of nutrients. Some HIV positive people experience specific problems, such as fat malabsorption, which can impair absorption of fat-soluble vitamins.
Opportunistic infections: Various bacterial, viral, fungal, and parasitic infections can interfere with proper nutrition. Malignancies (cancers) and mycobacterial illnesses such as tuberculosis are often characterized by wasting. Several OIs cause vomiting and diarrhea, which can lead to poor absorption or loss of nutrients. Other infections -- such as thrush (oral candidiasis), gingivitis (gum inflammation), and cytomegalovirus esophagitis (throat inflammation) -- can make eating painful.
Medications: Antiretrovirals, OI drugs, and other medications can contribute to nutrient deficiencies and imbalances, either due to direct drug-nutrient interactions or drug side effects. Vomiting and diarrhea can lead to dehydration and depletion of nutrients. Loss of appetite (anorexia), fatigue, and taste alterations can make it difficult to eat enough. Antibiotics may interfere with nutrition by killing off beneficial bacteria in the gut. Food requirements -- the need to take medications either on a full or an empty stomach or with specific types of food -- can disrupt normal eating patterns. Finally, some antiretroviral medications are associated with metabolic changes such as blood lipid and glucose abnormalities.
Inadequate intake: Ill people often experience anorexia. OI symptoms and medication side effects -- nausea, diarrhea, sore mouth or throat, altered sense of taste or smell -- can further reduce the desire or ability to eat. This may be compounded by lack of money, depression, or feeling too fatigued to shop and prepare food.
Altered nutritional requirements: By altering metabolism (how the body processes and uses nutrients), acute or chronic illness -- including HIV disease and OIs -- and the resulting immune response can increase the body's energy needs. People with HIV/AIDS may require more calories, macronutrients, and specific vitamins and minerals. Chronic illness may also alter hormone and cytokine levels, which may have nutritional implications.
Conversely, nutritional deficiencies can impair immune function, potentially worsening HIV disease progression. Research has shown that depletion of vitamins A, C, and E, the B-complex vitamins, and the minerals selenium and zinc can interfere with cell-mediated immunity (CD4 cell, natural killer cell, and neutrophil proliferation and activation), antibody production, and normal cytokine signaling.
Studies looking at the prevalence of nutritional deficiencies in people with HIV/AIDS have produced conflicting data, but on the whole, depletion of nutrients (e.g., vitamins A and E, and minerals including magnesium, selenium, and zinc) appears to be common, especially among individuals with advanced disease. In particular, having HIV seems to decrease the body's store of antioxidants, as they are needed to offset increased oxidative stress. Researchers have uncovered evidence of subtle nutritional deficiencies among people who appear to be eating an adequate diet and are not suffering from frank protein/calorie malnutrition.
Experts don't yet understand the clinical significance -- if any -- of subtle changes in laboratory values relative to the norms seen in the HIV negative population, nor do they know how much of any given nutrient people with HIV/AIDS need for optimal immune function and overall health. Due to a lack of research on nutritional status in the setting of HIV disease, and because nutritional requirements vary dramatically from person to person, there are few definitive recommendations for nutritional supplementation in the HIV positive population.
Waste Not, Want NotWasting -- also known as cachexia -- was a prominent feature of AIDS in the early years of the epidemic; even today, AIDS is referred to as "slim disease" in Africa. Experts define wasting as involuntary or unwanted loss of 10% or more of body weight. As Steven Grinspoon, MD, and Kathleen Mulligan, MD, discuss in an April 2003 special issue of Clinical Infectious Diseases (CID) devoted to nutrition and HIV, "wasting ... has been associated with increased mortality, accelerated disease progression, loss of muscle protein mass, and impairment of strength and functional status." Even a 5% loss has been linked to increased illness and death.
In classic HIV-related wasting, lost weight is in the form of lean body mass rather than fat, especially in men. People with HIV/AIDS (and other chronic illnesses) require more calories simply to maintain their weight, due to increased metabolism, higher energy demands, hormone and cytokine imbalances, inefficient absorption and utilization of nutrients, and/or accelerated tissue breakdown (catabolism).
While effective antiretroviral therapy has dramatically reduced the incidence of severe wasting, moderate weight loss is still a prominent feature of HIV disease. For example, as reported in the September 1, 2005 Journal of Acquired Immune Deficiency Syndromes (JAIDS), Alice Tang, MD, from Tufts University Medical School and colleagues found a steady increase in the rate of 5% or greater loss of body weight between 1995-1997 (pre-HAART) and 1998-2003 (HAART era). In an analysis of 713 HIV positive participants in the Nutrition for Healthy Living cohort, 53% lost at least 5% of their body weight during any six-month period. Weight loss was significantly associated with nausea, diarrhea, thrush, poverty, history of drug use, CD4 cell count below 200 cells/mm3, and HIV viral load above 100,000 copies/mL. The authors were unable to pinpoint the reasons for the increased rate of wasting in the HAART era.
In another study (reported in the October 15, 2005 issue of CID), Adriana Campa, PhD, from Florida International University and colleagues found that 17.6% of 119 HIV positive, mostly homeless drugs users in Miami showed evidence of HIV-related wasting. In this study, wasting was associated with cocaine and heavy alcohol use, "food insecurity" (not eating for one or more days in the past month), and higher HIV viral load. Participants taking HAART were more likely to experiencing wasting than those not receiving anti-HIV treatment (86% vs 67%).
Rather than dramatic whole-body weight loss, today many HIV positive people on HAART experience lipoatrophy, or fat loss in the face, limbs, and buttocks. Paradoxically, this may coincide with fat accumulation in other areas of the body (discussed below). Lipoatrophy is most strongly associated with use of nucleoside reverse transcriptase inhibitors (NRTIs), especially d4T (stavudine or Zerit). For this reason, U.S. government treatment guidelines no longer recommend d4T as part of a first-line regimen for people starting HAART.
Since HIV positive people and their clinicians may not recognize the early signs of wasting, it is important to monitor weight regularly to detect subtle changes. Underlying factors contributing to weight loss -- such as OIs or hormone imbalances -- should be promptly addressed. But, as Grinspoon and Mulligan point out, "no therapeutic guidelines currently exist for the management of weight loss and wasting in HIV-infected patients."
When it comes to weight loss, prevention is often easier than cure. To add calories, focus on proteins and complex carbohydrates rather than "junk food" that contains mostly sugar and fat. Consider eating several small meals and snacks throughout the day rather than two or three large meals. Nutritional supplements such as Ensure or Boost may benefit individuals who find it difficult to eat solid foods. Some cities offer food delivery programs for people with HIV/AIDS who are unable to shop or prepare meals (e.g., Project Open Hand in San Francisco, God's Love We Deliver in New York City, Moveable Feast in Baltimore).
The appetite stimulant megestrol acetate (Megace) tends to promote fat rather than muscle gain and can cause side effects including edema (swelling). Certain antidepressants and other medications may also enhance appetite. Some patients swear by medical cannabis or dronabinol (Marinol), a pill that contains a synthetic version of marijuana's active ingredient, THC.
While recombinant human growth hormone (HGH, Serostim) is FDA-approved for the treatment of HIV-related wasting, it is extremely expensive and can cause side effects including carpal tunnel syndrome, joint pain, and insulin resistance. Anabolic (muscle-building) steroids such as testosterone and oxandrolone (Oxandrin) help some patients gain weight, but can also cause adverse effects. Hormone replacement therapy is most useful for individuals who have low levels; there is little evidence that "supraphysiological" doses (higher than the natural physiological range) are beneficial, and they may be harmful (see "HIV and Hormones" in the Summer 2004 issue of BETA). Research has shown that anabolic steroids work better when combined with resistance exercise; in fact, some studies suggest resistance exercise works better than steroids, without the cost or side effects.
Too Much of a Good ThingFor many HIV positive people in the developing world today, severe overall wasting due to protein/calorie malnutrition is not a major concern. In fact, some research suggests obesity may be a bigger problem. For example, Valerianna Amorosa, MD, and colleagues from the University of Philadelphia reported in the August 15, 2005 issue of JAIDS that in a cohort of nearly 1,700 HIV positive individuals, 31% of men and 30% of women were overweight, and 11% and 28%, respectively, were obese (in contrast, just 9% overall experienced wasting). Obesity was not associated with age, income, employment status, education, history of injection drug use, HIV treatment, or viral load, but in women it was more common among African-Americans. In Tang's study discussed above, the proportion of patients categorized as overweight was greater in the HAART era than before the advent of effective antiretroviral therapy (35% vs 30%). And HIV positive people are hardly alone: the National Center for Health Statistics reports that two-thirds of all Americans are overweight and nearly one-third of adults are obese -- double the proportion in 1980.
While "garden variety" obesity remains common, HIV positive people on HAART may also experience accumulation of fat in specific areas of the body including the belly, breasts, and back of the neck ("buffalo hump"). This abdominal or truncal lipohypertrophy is composed of deep visceral fat surrounding the internal organs. Both lipoatrophy (described above) and lipohypertrophy are features of lipodystrophy syndrome; however, as discussed in an article by Denise Jacobson, PhD, and colleagues from Tufts in the June 15, 2005 issue of CID, experts now recognize that these are two distinct processes, not simply redistribution of fat from one area to another.
Lipodystrophy syndrome also includes elevated blood lipid levels and blood glucose abnormalities (see "Insulin Resistance and Diabetes" in the Winter 2004 issue of BETA). While most research indicates that lipodystrophy is associated with antiretroviral therapy -- in particular protease inhibitors (PIs) -- it is likely a multifactorial condition related to long-term HIV infection or immune reconstitution, since some people who develop the syndrome have never taken HAART. In a recent study by Peter Bacchetti, PhD, and colleagues, for example, abdominal fat accumulation was not linked to HAART, and was actually more common among HIV negative than HIV positive men (see "News Briefs," in this issue.)
Obesity, and in particular visceral abdominal fat, has been linked to increased risk of cardiovascular disease in the general population. While it is still uncertain whether HIV positive people on HAART have higher rates of heart attacks and strokes (studies have yielded mixed data), it is likely that traditional cardiovascular risk factors -- advancing age, male sex, cigarette smoking, high LDL cholesterol and triglyceride levels, insulin resistance, elevated blood pressure, and being overweight -- are as important for HIV positive people as for anyone else (see "Cardiovascular Disease in People with HIV" in the Summer/Autumn 2002 issue of BETA).
While early nutritional guidelines for people with AIDS often emphasized packing on the calories -- adding cream, cheese, peanut butter, gravy, and the like to foods -- many HIV positive people today would be better served by adopting a balanced, low-fat diet.
Lifestyle changes, including diet modification, weight loss (if needed), exercise, and smoking cessation, are the first line of defense against cardiovascular disease. In order to lose weight, HIV positive people must follow the same rules as everyone else: burn more calories than one takes in. But reducing the amount of fat and cholesterol in the diet is not always enough to reverse fat accumulation or bring blood lipids within a healthy range, and exercise may not have much effect on visceral fat. When this is the case, lipid-lowering medications (including the statin and fibrate classes) are often used. Altering one's antiretroviral regimen to include drugs less linked to high blood fat -- such as substituting atazanavir (Reyataz) for another PI -- is often effective. Researchers have tried treating lipodystrophy with human growth hormone and anabolic steroids, with mixed results. Although it is not yet clear what are the best interventions to address increased cardiovascular risk among HIV positive people on HAART, experts agree that a healthy diet certainly can't hurt, and is likely to be part of the solution.
Healthy Diet BasicsA healthy diet provides adequate nutrition without a lot of empty calories. "Balanced" means eating a variety of foods from all the important food groups, since no food alone provides all the nutrients the body needs. The traditional Food Guide Pyramind offers guidelines about how much to eat from each food group. (The traditional food pyramid was replaced in 2005 with a new pyramid, an online tool at www.MyPyramid.com. Because the new pyramid is more difficult to interpret, however, many nutrition experts continue to use the traditional version.) It recommends 6-11 servings per day of grain products such as bread, cereal, rice, and pasta; 3-5 servings of vegetables; 2-4 servings of fruit; 2-3 servings of dairy products such as milk, yogurt, and cheese; 2-3 servings of high-protein foods such as meat, poultry, fish, eggs, and legumes; and small amounts of fat, oil, and sugar.
This may seem like a lot, but a "serving" is smaller than many people realize. A "serving" as per the guidelines would be, for example, a 3-ounce portion of cooked meat (about the size of a deck of playing cards), one chicken leg, a 2-inch cube of cheese, an 8-ounce glass of milk, a single tortilla or slice of bread, 5-6 crackers, one-third cup of cooked pasta, one-half cup of cooked vegetables, or one medium-size apple or orange. The amount of food typically served in restaurants, therefore, actually accounts for multiple "servings."
The 2005 revision of the food pyramid focuses less on quantity and more on quality, while also emphasizing the importance of physical activity. At least half of one's daily consumption of bread and cereal products should be comprised of whole grains; as a rule, less processed foods contain more nutrients. Simple carbohydrates tend to make blood glucose spike soon after eating and then fall, while complex carbohydrates tend to promote more stable levels over time. But what really matters is a food's "glycemic index," a measure of how quickly it is broken down in the body. Foods with a high glycemic index are broken down rapidly, causing blood sugar to rise sharply, while low glycemic index foods help the body maintain a steadier glucose level.
Eat vegetables of various colors -- including dark green and deep orange -- since these contain different vitamins, minerals, and phytochemicals. Whole fruit is preferable to juice, which is high in sugar and calories and typically lacks fiber. Since cooking can destroy vitamins, it is usually recommended to eat vegetables raw or lightly steamed. However, this may not be the best advice for people with severely compromised immunity who are at risk of infection with microorganisms that can be killed by cooking.
In the dairy group, select low-fat or non-fat products. People who choose not to consume dairy foods should be sure to obtain enough calcium from other sources. In the protein group, the new pyramid recommends eating more legumes, nuts, seeds, and fish -- which contains heart-healthy omega-3 fatty acids. When eating meat or poultry, remove visible fat and skin. Broiling, baking, and grilling are healthier cooking methods than frying.
In terms of fats, avoid animal-derived fats and chemically altered hydrogenated oils, instead substituting plant-derived monounsaturated and polyunsaturated oils. This is good advice even for people who do not need to lose (or could stand to gain) weight, since animal fats increase the risk of cardiovascular disease. Fortunately, thanks to consumer demand, it is easier than ever to find commercial baked goods, snack foods, salad dressings, and the like that do not contain saturated fats. Another boon for the heart: a low-sodium diet can help keep blood pressure under control.
In addition to eating a balanced diet, it is also important to consume enough fluids. Experts traditionally recommend eight 8-ounce glasses of water per day. Herbal tea, broth, and fruit or vegetable juices can also be good fluid sources. But beverages that contain caffeine or alcohol have a diuretic effect, and can cause loss of water due to increased urination. It is especially important to drink enough fluid to prevent dehydration when suffering prolonged vomiting or diarrhea. People with very low CD4 cell counts concerned about infections such as cryptosporidiosis due to contaminated tap water should use filtered or bottled water.
Facts Versus FadsThe traditional dietary guidelines are not free of controversy. Some critics contend that in putting together the recommendations, the federal government has been unduly influenced by the food industry. They argue, for example, that adults really do not need to consume cow's milk at all. Some believe the pyramid recommends more protein than most people need, while others argue that humans evolved to eat a "hunter-gatherer" diet much lower in carbohydrates.
"Low carb" diets (related to the Atkins plan) containing small amounts of carbohydrates and larger amounts of protein and fat have gained considerable popularity in recent years -- so much so that many people have come to believe that carbohydrates per se are "fattening." While such diets may produce temporary weight loss, they are usually short on fiber, can stress the liver and kidneys, and may lead to dangerously elevated blood lipid levels.
More people are also adopting vegetarian or vegan diets, which have been linked to reduced risk of cardiovascular disease and cancer. Most people can obtain adequate nutrition from a diet that contains little or no meat or other animal products, though this may be more challenging for growing children or people with chronic illness who have increased energy needs. The trick is to learn how to combine proteins from different sources (such as grains, legumes, nuts, and soy) to obtain a full complement of essential amino acids; vitamin B12 supplementation may also be needed.
An increasing number of healthcare providers now recommend a "Mediterranean diet" -- including olive oil, tomatoes, garlic, and red wine -- since people from areas that consume such a diet tend to have lower rates of heart disease. A Japanese-style diet that contains lots of fish and soy products is also a healthy option.
Notwithstanding these caveats, the consensus recommendation to eat a range of foods from a variety of categories remains sound. Most experts suggest a breakdown of about 50-60% carbohydrates, 15-20% protein, and no more than 25-30% fat. But because individual nutritional needs vary widely, it is difficult to recommend a specific diet suitable for all people with HIV/AIDS. A trained dietitian who has experience working with HIV positive people can help devise an appropriate individualized eating plan.
What About Supplements?As a rule, it's usually best to obtain nutrients from food. Swallowing handfuls of pills will not make up for a poor diet. But even HIV positive people who eat well can have low levels of various important nutrients -- at a time when their nutritional needs may be increased -- and thus may benefit from supplementation. The U.S. government's Daily Values (formerly known as Recommended Dietary Allowances) for nutrients do not necessarily reflect the amount required for optimal health, just the minimum needed to stave off deficiency symptoms in the average healthy person. It is not yet known whether accepted recommended nutrient levels for the general population are adequate for people with HIV/AIDS.
Dietary supplements are products such as vitamins, minerals, amino acids, herbs, and antioxidants; they are usually taken orally in the form of tablets, capsules, powders, or liquids. Due to the lack of strict quality control and labeling requirements, marketed products can vary widely in contents, strength, and purity. Although regulated by the U.S. Food and Drug Administration (FDA), supplements do not need to undergo rigorous clinical trials of safety and efficacy as required for approval of pharmaceutical drugs. In fact -- because there is little financial incentive to spend money developing products that cannot be patented -- there have been few rigorous, controlled studies on the use of nutritional supplements in people with HIV.
In the mid-1980s, Barbara Abrams, DrPH, and colleagues from the University of California at Berkeley began a large observational study of dietary intake in 296 HIV positive men; results were reported in the August 1993 issue of JAIDS. By one measure, the risk of developing AIDS decreased as consumption of 11 different micronutrients increased -- significantly so for riboflavin, vitamin E, and iron, and approaching significance for thiamin, niacin, and vitamin C. This study was susceptible to selection bias, however, since people who ate healthier diets or took supplements might have had healthier lifestyles overall.
More recently, researchers in Thailand showed that a low-cost multivitamin and mineral supplement improved the survival of HIV positive people who were not taking HAART. As reported in the November 21, 2003 issue of AIDS, Sukhum Jiamton, MD, and colleagues conducted a double-blind, placebo-controlled trial in which nearly 500 HIV positive individuals with CD4 cell counts of 50-550 cells/mm3 were randomly assigned to receive either a placebo or a supplement containing 12 vitamins, eight minerals, and the amino acid cysteine twice daily. After 48 weeks, about twice as many people died in the placebo arm compared with the supplement arm (15 vs 8 deaths); among those with baseline CD4 counts below 200 cells/mm3, the mortality rate was significantly lower in the supplement arm. On the other hand, an earlier study in Zambia found that multivitamin supplementation had no effect on CD4 cell count or mortality.
In the July 1, 2004 New England Journal of Medicine, Wafaie Fawzi, DrPH, from Harvard School of Public Health and colleagues reported on a double-blind, placebo-controlled study in which 1,078 HIV positive pregnant women in Tanzania received either daily supplements of vitamin A; a multivitamin supplement containing vitamins B, C, and E; or both. After a median follow-up of 71 months, 67 out of 271 women (24.7%) who received the multivitamin either died or progressed to advanced HIV disease (stage IV as defined by the World Health Organization), compared with 83 out of 267 women (31.1%) who received the placebo. Women in the multivitamin arm -- but not those receiving vitamin A alone -- also had significantly lower HIV viral load, higher CD4 and CD8 cell counts, and improved birth outcomes.
In a June 10, 2005 AIDS editorial reviewing the current state of knowledge about micronutrient supplementation in people with HIV/AIDS, Tang and colleagues concluded that "a combination of vitamins may afford some benefits to undernourished HIV-infected populations, particularly those with more advanced disease," but conceded that "the role of individual micronutrients ... is less clear." Most healthcare providers agree that HIV positive people can benefit from a daily multivitamin and mineral supplement. (Due to the potential harmful effects of iron, many recommend an iron-free supplement for anyone other than menstruating women and people with iron deficiency). But when it comes to specific nutrients, expert opinion -- and the little relevant research conducted to date -- remains sharply divided.
Higher amounts of various substances have been proposed to improve immune response, ameliorate symptoms and drug side effects, and slow HIV disease progression, on the basis of theoretical understandings about how an agent is expected to behave, laboratory research looking at the effects of a substance in vitro, cross-sectional studies showing specific nutritional deficiencies in a population, or -- less commonly -- controlled trials. Several nutrients that have received the most attention with regard to HIV/AIDS are discussed below.
Vitamin ARichard Semba, MD, from Johns Hopkins and colleagues reported in 1993 that among a cohort of 179 HIV positive and HIV negative injection drug users in Baltimore, vitamin A deficiency was linked to lower CD4 cell counts and increased risk of mortality. Two years later, he reported that vitamin A deficiency among pregnant HIV positive women in Malawi was associated with increased risk of mother-to-child HIV transmission (32% among deficient women vs 7% among women with normal levels) and higher infant mortality. Similarly, a U.S. study found that vitamin A-deficient women were about five times more likely to transmit HIV to their babies. Some studies have found vitamin A deficiency to be associated with greater vaginal shedding of HIV and higher levels of virus in breast milk -- although Fawzi's study described above actually found a significantly higher rate of mother-to-child transmission via breast-feeding in women given vitamin A supplements.
Several large controlled studies looking at supplementation with vitamin A or beta-carotene (a vitamin A precursor) for HIV positive pregnant women in parts of Africa where frank deficiency is common, however, have failed to detect decreased rates of mother-to-child transmission; results have been mixed concerning reductions in miscarriages, premature births, and infant morbidity and mortality. In Fawzi's Tanzanian study, vitamin A alone did not produce outcomes significantly different from those seen in the placebo arm, and adding vitamin A to the multivitamin seemed to reduce its beneficial effects. Since the benefits are unclear and high doses can cause liver toxicity and other problems, most experts do not recommend vitamin A supplementation -- beyond the amount found in a typical multivitamin pill -- for people with HIV/AIDS.
Vitamin CIn laboratory studies, vitamin C has been shown to inhibit viral replication in vitro; it also plays an important role in tissue repair. Thus, it is not surprising that megadoses of this vitamin have been touted as a cure for everything from the common cold to cancer to HIV/AIDS. Controlled clinical trials comparing vitamin C to placebo for the treatment of colds and flus have yielded mixed results, and the data have been even less promising concerning HIV disease. While vitamin C deficiency does appear to impair various aspects of the immune response, research has not provided evidence that supplementation delays HIV disease progression or improves survival.
Vitamin EVitamin E plays a role in metabolism and proper immune function, and laboratory studies suggest it has an antiviral effect. For example, Alonso Heredia, PhD, from the University of Maryland and colleagues reported in the May 20, 2005 issue of AIDS that addition of vitamin E to cell cultures from 10 HIV positive individuals significantly reduced HIV production, as indicated by p24 antigen levels. The authors suggested that supplementation might slow HIV replication enough to inhibit the emergence of drug-resistant virus in resting cells and to delay viral rebound after treatment interruption. But while low (or decreasing) levels of vitamin E have been linked to CD4 cell declines and HIV disease progression, this does not imply causality.
The jury is still out on the benefits and risks of high-dose vitamin E supplementation, but data from recent large studies in the HIV negative population do not look good. In the Women's Health Study (a primary prevention trial that included nearly 40,000 healthy, HIV negative women), subjects randomly assigned to receive 600 IU of vitamin E every other day not only did not have reduced rates of cancer or cardiovascular disease relative to women in the placebo arm, but actually showed a nonsignificant increase in total mortality. Results of a meta-analysis of 19 clinical trials with a total of nearly 136,000 subjects published in the January 4, 2004 Annals of Internal Medicine led authors Edgar Miller, MD, and colleagues to conclude that, "High-dosage [400 IU or more daily] vitamin E supplements may increase all-cause mortality and should be avoided." In the absence of large controlled studies in the HIV positive population, the same advice is sound for people with HIV/AIDS as well.
SeleniumThe trace element selenium -- also known to play a role in proper immune function -- has received considerable attention as a treatment for HIV/AIDS and a variety of other diseases. Some in vitro research indicates that HIV requires selenium in order to replicate. A study of 125 HIV positive injection drug users by Marianna Baum, PhD, and colleagues from the University of Miami (published in 1997) revealed that after adjusting for various factors including CD4 cell count, selenium deficiency was significantly associated with increased mortality. "When all nutrient factors that are associated with survival are considered together," Baum concluded in a later review article, "only selenium deficiency is a significant predictor of mortality." And in a study of 670 HIV positive pregnant women in Tanzania (reported in the June 1, 2005 issue of JAIDS), Roland Kupka, DSc, from Harvard School of Public Health and colleagues found that low plasma selenium levels were associated with increased risk of miscarriage, infant death, and mother-to-child HIV transmission.
But the fact that low selenium levels are linked to worse disease progression does not necessarily mean supplementation will improve matters. HIV nutrition expert Mary Romeyn, MD, has reported anecdotal evidence that selenium supplementation leads to clearance of thrush. On the other hand, while low selenium levels were linked to increased likelihood of cervical dysplasia (precancerous cell changes) among HIV positive women in one study, selenium supplements did not reduce the risk.
And, as reported in the December 15, 2004 issue of JAIDS, Scott McClellend, MD, from the University of Washington and colleagues found that in a study of 400 nonpregnant HIV positive women in Kenya, supplementation with a multivitamin plus selenium led to increased vaginal shedding of HIV, which has implications for sexual and perinatal transmission. Among women who started out with normal selenium levels, those who received supplements were more than twice as likely to shed HIV in their vaginal secretions and had higher vaginal HIV viral loads than women who received a placebo; a similar effect was not seen, however, in selenium-deficient women brought up to normal levels. While supplementation resulted in higher CD4 and CD8 cell counts, the authors concluded that, "The potential benefit of micronutrient supplementation in HIV-1-seropositive women should be considered in relation to the potential for increased infectivity."
ZincZinc deficiency has been linked to impaired immune function and supplementation has been suggested as a treatment for people with HIV/AIDS, but studies to date have produced conflicting results. While some suggest that zinc enhances the body's ability to fight HIV and improves disease symptoms, others have found it has a detrimental effect. In one study of injection drug users, lower zinc levels were associated with reduced CD4 cell counts, but this does not necessarily mean one caused the other. In an early nutritional survey of nearly 300 HIV positive men followed for seven years, high doses of zinc were associated with faster HIV disease progression. Some researchers have hypothesized that this may be related to the fact that HIV requires zinc-containing structures called "zinc fingers" to produce functional viral progeny.
More recently, Raziya Bobat, MD, and colleagues reported in the November 26, 2005 issue of The Lancet that in a randomized, placebo-controlled trial of 96 HIV positive South African children aged six months to five years, zinc supplementation for six months reduced the incidence of diarrhea and pneumonia, and did not appear to promote viral replication. Given the degree of uncertainty, most experts do not recommend zinc supplementation beyond the amount contained in a multivitamin and mineral pill.
AntioxidantsVitamin C, vitamin E, selenium, and zinc act as antioxidants, helping prevent cell damage caused by highly reactive free radicals (oxidative stress). While free radicals play a role in immune defense against invading pathogens, they can also harm surrounding cells. Research has shown that people with HIV and other chronic infections have higher levels of free radicals, which promote viral replication. Conversely, antioxidants appear to reduce oxidative stress, inhibit HIV activity, and possibly slow HIV disease progression. Antioxidants may also reduce liver fibrosis in people with hepatitis B or C and protect the liver from toxicity as it metabolizes drugs.
The body manufactures certain antioxidants as needed, but this process requires adequate amounts of several nutrients. Studies suggest that a major intracellular antioxidant, glutathione, may help reduce the rate of HIV disease progression. Nutrients that help raise glutathione levels include selenium, alpha-lipoic acid, N-acetyl-cysteine (NAC), acetyl-L-carnitine, L-glutamine, and coenzyme Q10. In one small study, high-dose NAC supplementation led to decreased HIV viral load. There have been several case reports and small studies in which supplementation with antioxidants or precursors including NAC, acetyl-L-carnitine, and coenzyme Q10 seemed to counter lactic acidosis (a sign of mitochondrial toxicity) related to antiretroviral therapy. What's more, Andrew Hart, MD, and colleagues from the Royal Free and University College Medical School reported in the July 23, 2004 issue of AIDS that acetyl-L-carnitine supplements helped reverse nerve damage and alleviated the pain of peripheral neuropathy associated with certain NRTI drugs.
But antioxidant supplements may also have deleterious effects. In a small pilot study by Grace McComsey, MD, and colleagues from Case Western Reserve University (reported in the August 15, 2003 issue of JAIDS), while supplementation with vitamin C, vitamin E, and NAC slightly reduced elevated LDL cholesterol levels and abdominal fat accumulation in 10 subjects with HIV-related lipodystrophy, the antioxidants also raised blood glucose levels and worsened insulin resistance. "We should never assume that high doses of vitamins are safe," the authors cautioned. "They are not safe until clinical studies prove them to be safe."
Omega-3 Fatty AcidsOmega-3 fatty acids, found in cold-water fish such as salmon and herring, have been associated with reduced cardiovascular disease risk in the general population; one study of more than 4,700 adults over age 65 showed that eating fish 3-4 times per week was associated with a 30% reduction in congestive heart failure. In the November 15 issue of CID, David Wohl, MD, from the University of North Carolina at Chapel Hill and colleagues reported that omega-3 may also help address one cardiovascular risk factor in people with HIV/AIDS. In this open-label study, 52 HIV positive individuals on HAART with fasting triglyceride levels above 200 mg/dL were randomly assigned to receive either omega-3 fish oil supplements (eicosapentaenoic acid and docosahexaemoic acid) plus nutritional counseling or else nutritional counseling alone. After 16 weeks, subjects receiving fish oil supplements experienced a 19.5% reduction in fasting triglyceride levels, compared with a 5.7% decrease in the counseling-only arm (though seemingly substantial, this difference was not statistically significant). However, LDL cholesterol levels increased by 22.4% in the fish oil arm, while remaining stable in the counseling-only arm; HDL levels did not change in either group. The authors acknowledged that "whether this increase [in LDL] attenuates any benefit in lowering triglyceride levels is unclear."
Special SupplementsVarious functional supplements have been developed to augment levels of particular compounds thought to have specific beneficial effects. For example, two small studies presented at the 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV in November 2005 showed that a supplement called NucleomaxX -- a sugar cane extract containing the nucleoside uridine -- helped reverse lipoatrophy in individuals taking NRTIs. Jussi Sutinen, MD, and colleagues from Finland reported than in a study of 20 patients taking d4T or AZT (zidovudine, Retrovir), those taking NucleomaxX three times daily for 10 days gained significantly more arm and leg fat (about 900 grams) than subjects taking placebo; the NucleomaxX group also gained visceral abdominal fat. Likewise, McComsey reported that both patients and their physicians reported significant improvement in lipoatrophy in a study of 14 subjects taking d4T who received NucleomaxX three times daily every other day for 16 weeks. (An open-label Phase II study of NucleomaxX for lipoatrophy is currently enrolling; see "Open Clinical Trials," in this issue).
More Is Not Always BetterWith all this conflicting data, it can be difficult for HIV positive people to make informed decisions about supplements. The bottom line, according to Judith Nerad, Mary Romeyn, and colleagues in the April 2003 CID special issue: "
People with HIV/AIDS commonly have subtle nutritional deficiencies, and research to date has shown that daily multivitamin use is safe and at least potentially beneficial in this population. Different experts have suggested various supplementation regimens. For example, Romeyn -- in her book Nutrition and HIV: A New Model for Treatment -- suggests a basic regimen that includes:
Others, such as nutritionist Margaret Davis, RD, recommend only the multivitamin, plus increased consumption of fruits and vegetables.
As previously noted, nutritional needs vary widely from person to person, and there is no one diet or supplement regimen appropriate for all people with HIV/AIDS. Further, the presence of a nutrient deficiency does not necessarily mean supplementation is the solution, since poor absorption, underlying infections, metabolic changes, or hormone imbalances could be contributing to the problem.
When using supplements, do not take more than the recommended dose on the label unless advised to do so by a knowledgeable healthcare provider. As some of the studies discussed above illustrate, more is not necessarily better. A recent case underscores this warning. As reported in the September 2005 International Journal of STD and AIDS, an HIV positive man in London developed severe liver inflammation with skyrocketing ALT levels after taking more than a dozen dietary supplements, many at high doses -- as much as 67 times the recommended daily value; fortunately, once he stopped taking the supplements, his liver function returned to normal.
Certain vitamins and minerals (including the fat-soluble vitamins A, D, and E) can be toxic at high doses, and they may cause deleterious effects even at lower doses beyond what is provided in a typical multivitamin pill. Remember that "natural" does not necessarily mean "safe." Beware of any supplement touted as a "cure" for a range of ailments -- if something sounds too good to be true, it probably is. Verify that health claims are supported by reliable research. Some supplements may not be harmful, but simply a waste of money. Seek medical advice before starting a new supplement or beginning any unusual diet. Tell healthcare providers about any use of supplements (as well as over-the-counter medications, recreational drugs, and herbal remedies), since these can potentially interact with antiretroviral drugs.
Eat Right for LifeNutritional management should be a regular part of HIV/AIDS care. Even if an HIV positive person has no obvious nutritional problems such as wasting, a healthy diet can still help stave off illness and improve quality of life. But, as Tang and colleagues noted in their review, dealing with nutritional issues "may not be part of the traditional care or thought process of the HIV care provider." A registered dietitian (RD) who has experience working with people with HIV/AIDS can be an invaluable resource.
The American Dietetic Association recommends a baseline nutritional and body composition assessment soon after HIV diagnosis. Follow-up assessments should be conducted at least once annually for asymptomatic individuals with well-controlled HIV disease, and every few months for patients with AIDS or known nutritional problems. Tasmin Knox, MD, from Tufts recommends anthropometric measurements of body composition (see "Weights and Measurements" above for an explanation of various methods); laboratory tests of protein and micronutrient levels in the blood; tests of metabolic parameters such as blood lipids, blood glucose, and liver enzymes; and clinical assessment of eating patterns, supplement use, functional status, physical symptoms, and psychological or socioeconomic issues that may impede adequate nutrient intake. Some experts recommend that people keep a daily diary of everything they eat, along with any dietary problems they encounter.
Once such an assessment is complete, promptly address any underlying problems -- such as infections, hormone imbalances, or metabolic disorders -- that may be interfering with proper nutrition. The next step is to develop an appropriate, individualized nutrition plan. Seniors, growing children, pregnant or breast-feeding women, and people with active OIs are among the many groups that have special nutritional needs. While supplements can offer important benefits, they do not replace a well-balanced diet. When it comes to good nutrition, there is no "quick fix." It's better to develop long-term healthy eating habits, such as cutting back on saturated fat and consuming more fruits, vegetables, and whole grains. But set realistic goals: it's fine to splurge occasionally if one normally adheres to a healthy diet. Fortunately, small changes in eating habits can often make a big difference in terms of health.
Since many people with HIV/AIDS use dietary supplements in addition to HAART, it's crucial to learn more about how nutritional supplementation impacts HIV disease and vice versa. According to Tang and colleagues, areas ripe for further research include the role of micronutrient supplementation in people with well-controlled HIV disease, whether micronutrients can enhance CD4 cell responses, the role of antioxidants in countering increased oxidative stress due to HIV infection or its treatment, whether micronutrient supplementation can help reduce morbidity associated with coinfections such as hepatitis B or C, the role supplements might play in addressing metabolic manifestation such as lipodystrophy and bone loss, and the appropriate doses of supplements for HIV positive people at various stages of disease.
"Attempts to improve dietary quality and micronutrient status may play an overall role in maximizing health for the HIV-infected individual, particularly in undernourished populations," Tang and colleagues concluded, "and may also play a role in the more subtle management of HIV infection in the future."
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This article was provided by San Francisco AIDS Foundation. It is a part of the publication Bulletin of Experimental Treatments for AIDS. Visit San Francisco AIDS Foundation's Web site to find out more about their activities, publications and services.