The Role of Dietary Supplements in HIV
There's a lot more to life than viral load and CD4 counts. And increasing evidence shows that taking a few extra supplements a day may help in a variety of ways.
Vitamins and Minerals
All the food we eat to stay alive and healthy is made up of various chemicals. Those that are required in small amounts are known as micronutrients. They're considered essential because, for the most part, the body can't manufacture them. These include vitamins and minerals.
Vitamins are small, complex organic substances that the body needs for the chemical reactions involved in metabolism and growth. Vitamins can be divided broadly into two categories: fat-soluble (vitamins A, D, E and K) and water-soluble (the B-vitamins, folic acid, biotin and vitamin C). To illustrate the difference, vitamin E mixes up well in oil, while a powder of vitamin C mixes up nicely in water. Fat-soluble vitamins wind up being stored in the liver, and some can be toxic if taken in excessive quantities.
Minerals are inorganic solid substances not composed of plant or animal matter. They are as important as vitamins in maintaining health and essential to survival. For example, the movement of minerals across cell membranes supports our body's most primary functions, such as the regulation of our heart beat, electrical activity of nerve cells, and water balance inside and outside of cells. Macrominerals that are required in relatively large amounts daily include phosphorus, calcium, and magnesium. Other macrominerals include the electrolytes, which are ionized salts such as sodium, potassium and chloride (found in some sports drinks to help replenish levels after a sweaty workout). Trace elements, or microminerals, refer to those minerals that are also considered essential, but needed only in tiny amounts by the body. These include boron, manganese, selenium, copper, iron, iodine, chromium, molybdenum, cobalt, vanadium, nickel, silicon and zinc. Excessive amounts of some minerals can also cause toxic reactions.
Other Dietary Supplements
In addition to the micronutrients, our bodies require macronutrients to function. Macronutrients include fats, simple and complex carbohydrates, and proteins that the body uses for fuel in the form of calories. Of course, consuming more calories than the body will utilize may result in fat deposits. However, data from researchers at the British Columbia Center of Excellence in HIV/AIDS at St. Paul's Hospital have shown that people with HIV need to consume greater numbers of calories than uninfected individuals. The trick is assuring that the quality of those calories is carefully -- pardon the expression -- weighed.
Eating a healthy, balanced diet is the first essential component of a comprehensive HIV management strategy. This includes consuming plenty of clean water, fresh fruit and vegetables, whole grains, beans and other varied sources of protein (meat, dairy, fish). A well balanced diet should also emphasize sources of healthy fats -- omega-3 fatty acids from fish, monounsaturated fats found in nuts, avocados, olive oil -- while cutting down on processed foods and beverages and the greasy, fried foods that may add calories but are otherwise problematic from a health standpoint. And of course, exercise is necessary to preserve lean muscle and help transform as much of our nutritional intake as possible into lean tissue!
Many other substances are also extremely important for their health benefits. These include amino acids, which are the chemicals that make up proteins. Examples include carnitine and its nerve-improving cousin, acetylcarnitine, N-acetylcysteine (NAC), taurine and glutamine, as well as chemicals such as coenzyme Q10, alpha lipoic acid, choline, inositol, various flavonoids and omega-3 fatty acids.
When these various nutrients aren't contained in food or medications, the Food and Drug Administration (FDA) refers to them as dietary supplements, which the agency defines as substances not considered either foods or drugs. Dietary supplements include vitamins, minerals, fatty acids, single or mixed amino acids, protein supplements (powders and drinks) and herbs used for non-cooking purposes.
How Does HIV Affect Nutritional Status?
Directly, HIV disease can cause damage to the gastrointestinal tract. This is not surprising considering the fact that HIV infects T-cells and a significant majority of those cells reside in the Gut-Associated Lymphoid Tissue (GALT). As a result, the lining of the intestinal tract deteriorates during the immune system's battle against HIV, possibly resulting in such problems as diarrhea and villous atrophy. Villous atrophy is a condition in which the tiny hair-like lining of the inside of the small intestine becomes stunted. These villi help the intestines to absorb nutrients. If they can't function properly, the intestines are unable to absorb nutrients properly. This may lead to malabsorption.
Even very early in HIV disease, the levels of certain vitamins and minerals begin to become depleted in many people. This happens notably with carotenoids, which are pigments related to vitamin A, vitamin E, vitamins B12 and thiamin (B vitamins), ascorbates (vitamin C), selenium, and zinc, among others. Many of these deficiencies worsen as the disease progresses. In 1996, researchers at University of Medicine and Dentistry of New Jersey noted lower levels of many antioxidants and minerals even in some people who took supplements, although the deficiency was not as marked as in people who did not use supplements. Lower levels of various nutrients -- due to inadequate dietary intake, malabsorption, diarrhea, or altered metabolism -- may be a sign of more rapid disease progression. Antioxidants are important because they can offset some of the damage caused by free radicals that are produced by HIV, some medications, and the body's inflammatory responses to HIV. Vitamins C and E (tocopherols), bioflavonoids, selenium, carotenoids, coenzyme Q10, and alpha lipoic acid act directly as antioxidants, while the B vitamins, NAC, and other substances are critical for maintaining the reduction-oxidation balance (redox) that occurs inside cells.
As HIV disease progresses, opportunistic infections such as cryptosporidiosis, microsporidiosis and other intestinal parasites, cytomegalovirus (CMV), Kaposi's sarcoma (KS) and candidiasis (thrush) can cause further inflammation and severe damage to the small intestine. The loss of the intestinal ability to absorb necessary nutrients may be compounded by medication side effects.
In summary, nutrient status can be impaired by HIV's damage to gut function, other infections leading to malabsorption and intestinal damage, hormonal imbalance (declining testosterone levels in both women and men, for example), diminished appetite, and diarrhea. These and other problems individually and collectively conspire to make it hard to get the nutrition that your body needs -- let alone to make up for the metabolic losses sustained in the ongoing struggle with HIV.
What Can Be Done?
Thankfully, a lot! The first step is to aggressively seek a diagnosis for any infection that may be causing symptoms such as diarrhea or weight loss. This can be difficult since some infections, especially certain parasites, are hard to diagnose. Some of the diagnostic procedures may be uncomfortable. But if an infection is found, treatment should be started.
Aside from diagnosing and managing infections, it's critical to establish a good diet. The first line of defense against any disease is maintaining adequate nutrient intake. That must come first from the food we eat. As Hogg and his colleagues noted in a 1995 article in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology, people with HIV need to take in substantially more calories than their HIV-negative counterparts.
A healthful diet is a smart part of a complete HIV-fighting program. However, in the case of HIV disease, food alone is probably inadequate to sustain the body's needs. Even the healthiest of diets may not provide adequate levels of vitamins, minerals and other important nutrients to offset the damage.
Data: Many Questions Remain
We still have no consensus on the best dosages of vitamins, partly due to the lack of clinical studies that can properly answer the questions. How potent should a multivitamin be? Researchers at the University of Medicine and Dentistry of New Jersey have noted micronutrient deficiencies persisting in a subset of supplement-using HIV-positive people.
Further research is unquestionably needed. Too often, mainstream medicine doesn't fully address or consider the use of supplements, let alone endeavor to study them. Although this is changing in some good ways, the changes are slow to happen. Fortunately, more people are becoming activist and demanding that good clinical studies be conducted of these types of interventions.
One problem with all clinical studies, however, is that broad and sometimes inappropriate generalizations are made for everyone based on a study of relatively few people or based upon an ill-conceived study design. For example, a study of long-term, heavy smokers received a lot of press when it found that smokers supplementing with beta-carotene and vitamin A actually had a slightly increased risk of lung cancer compared to those who did not use the supplements. The media blitz following the release of the study results in 1996 suggested that beta-carotene was generally harmful. But beta-carotene is only one antioxidant in a tightly controlled system, and later animal studies showed that an excess of beta-carotene combined with the oxidizing effects of cigarette smoke apparently wreaked havoc with this fine-tuned system. So, rather than proving that beta-carotene can prevent cancer in smokers, this study showed that the combination of beta-carotene and heavy smoking is potentially dangerous.
Other studies suffer from poor design. One randomized clinical study conducted by researchers from St. Bartholomew's and the Royal London School of Medicine and Dentistry evaluated the benefit of a combination of vitamins A, C and E, selenium and zinc in treating diarrhea. Participants received either albendazole, a drug used to treat some parasitic infections, or albendazole plus the supplements. The study found no added benefit to using the supplements over a two-week period. Aside from the fact that the study was too short, making generalizations based on these results is difficult since these people had diarrhea. Who knows how much of the supplements were actually absorbed? Indeed, the researchers concluded that despite a higher risk of death in those with low levels of the vitamins and minerals in their blood, little benefit was gained in giving people pills that simply passed through their systems.
A better designed study might have provided the amino acid, glutamine, to manage the diarrhea. Recent data have underscored the benefit of this intervention for managing protease inhibitor-related diarrhea, and there is a good deal of clinical data to support the benefits of glutamine in restoring gut function. Clearly, the albendazole study spent a lot of money to state the obvious -- even supplements won't be completely helpful if they don't stay in your body for long. The other lesson, not surprisingly, is that it is crucial to diagnose and treat diarrhea.
Fighting for Access
Millions of HIV-positive people do not have adequate access to food and clean water. Vitamin A deficiency and growth retardation are major public health problems in developing countries. In Africa, HIV infection, malaria, diarrhea, and respiratory infections are widespread, and their association with poor nutritional status accounts for a large number of deaths, particularly in infants and children. Various studies have shown that simple supplementation regimens can have a significant impact on suffering and death rates among people with HIV in places like Zambia, South Africa and Tanzania. Interventions such as a multivitamin and/or a B-complex are inexpensive. Even so, the cost remains beyond the reach of many, even in so-called developed nations like the United States. Activism is critical to secure access to these important interventions for people in developing nations and to ensure that they are covered by state Medicaid and AIDS Drug Assistance Programs (ADAPs) here at home.
Certain states, like New York, cover multivitamin supplements under their Medicaid and ADAP formularies. However, the ones that are provided are considered by many to be inadequate and, indeed, they provide considerably lower dosages than other brands. Some people compensate by simply taking more tablets each day, but this can be problematic in a disease that already has a high daily pill burden.
Supplementation: Can't Hurt, May Help
Observational studies of adults in the United States show an overall 30% reduction in the rate of progression to AIDS when just a multivitamin is used. This kind of study is difficult to accept on its own since there might be biases that a controlled clinical evaluation might help to minimize. With an epidemiological study of this sort, people who chose to take supplements may take better care of themselves generally and be in better health to begin with, representing a selection bias. Still, it isn't outrageous to conclude that a multivitamin may be a good idea in a disease that often results in nutritional deficiencies and a potentially fatal wasting.
A large double-blind placebo study published in The Lancet in 1998 described the effects of vitamin supplementation in 1,075 HIV-positive pregnant women in Tanzania, 34% of whom had vitamin A deficiency. The women were equally divided into four groups, receiving vitamin A alone, a multivitamin with vitamin A, a multivitamin without vitamin A, or placebo. Women taking a multivitamin -- with or without vitamin A -- had reduced risks of preterm birth, low birth weight, and fetal death compared to those taking placebo or vitamin A alone. They also had comparatively significant increases in CD4, CD8 and CD3 counts. In this study, researchers observed that taking vitamin A alone or adding vitamin A to the multivitamin did not seem to show any added benefit.
A recent report from Mercer University School of Medicine in Savannah, Georgia described a woman taking antiretroviral therapy and suffering from lactic acidosis. Mitochondrial toxicity, a potential side effect of the nucleoside analogues (Zerit, Videx, AZT, etc.), can create abnormally high levels of lactate, which, rarely, leads to lactic acidosis, a potentially life-threatening condition. The woman in Georgia had a very low level of the B vitamin, riboflavin and was given 50 mg of riboflavin a day. Within four days, her lactate levels were close to normal. This is only one case, of course, but there are many other case reports of lactic acidosis being treated with B vitamins, carnitine and coenzyme Q10. So it wouldn't hurt -- and it may very well help -- to use a B-complex. Although there are no data yet to show that a B-complex will prevent increases in lactate levels, it is an inexpensive and safe intervention. It may be reasonable to take that extra capsule or two a day, along with a potent multivitamin.
In addition, certain amino acids are proving their worth repeatedly and should probably be considered a core part of HIV management. These include, with a best estimate on the dose for adults, 1,500-2,000 mg of NAC, 5 grams (5,000 mg) of glutamine (unless diarrhea is present, in which case the dose can go up to 40 grams) and 3,000-6,000 mg (3-6 grams) of carnitine daily in divided doses. The recommended dose is 3 grams per day, as carnitine can cause diarrhea and body odor.
Another form of carnitine, acetyl-carnitine, crosses the blood-brain barrier and seems to help with neuropathy according to preliminary data from Dr. Michael Youle of the Royal Free Hospital in London. Plain old carnitine has the added advantage of helping to lower LDL (bad) cholesterol and possibly triglycerides. The ideal dose may be 3 grams of each form per day, but, frustratingly, there are no available data to support this theory yet.
To improve gut function, many people supplement with acidophilus and bifidus bacteria, which are found naturally in the gut. Diarrhea and antibiotics can destroy these normal intestinal companions. One of the functions of the pancreas is to secrete the enzymes the body uses to digest foods, and this activity can be disrupted in HIV disease. Some people take supplements that contain these enzymes (protease, amylase, lipase, and/or lactase).
Of course, none of the interventions described above represent a cure. However, the accumulating data strongly suggest that they can improve quality of life and reduce medication side effects and symptoms of HIV disease. Indeed, they may well improve the chances for a longer life.
What Makes A Good Study?
More studies to evaluate the benefits, costs and limitations of micronutrient therapy are needed. As researchers Friis and Michaelsen from The Royal Veterinary and Agricultural University in Denmark note, "The fact that multiple micronutrient deficiencies usually co-exist and often interact makes design of interventional [as opposed to observational] studies and interpretation and generalization of the results difficult. For example, zinc is required for mobilization of vitamin A from the liver stores, wherefore effects of vitamin A supplementation cannot necessarily be generalized to populations with a different zinc intake. Thus, it does not seem reasonable to evaluate a single micronutrient in the context of multiple co-existing and interacting deficiencies."
This points to a need to be a bit more clever about trial design when it comes to dietary supplements. The question must be framed carefully, the intervention selected intelligently and the trial design appropriate to the question at hand. Although some recent studies have focused on the effects of certain botanical interventions on the blood level of antiretrovirals, the clinical significance of the results are unclear since the studies involved HIV-negative volunteers using single drugs. A recent study showed that St. John's wort reduced blood levels of indinavir (Crixivan) in volunteers. The data certainly suggest caution -- avoid St. John's wort. Unfortunately, this leaves open the question about how to manage the mild-to-moderate depression that St. John's wort can safely treat, given the toxicities and potential for drug interactions with many antidepressant medications. To date, no cost/benefit/risk analysis comparing these interventions has been undertaken.
There is a profound need for more studies that examine supplements of all kinds in people with HIV. Studies have repeatedly shown that most people, both HIV-positive and negative, use dietary supplements. More information about these supplements will help people make more informed treatment decisions and allow for more sensible analyses of the costs, benefits, risks and limitations of these types of interventions.
Until There's More Data
Ultimately, each individual's health condition, age, gender, weight and other variables must be factored in to tailor a regimen suitable to that person's needs. And on top of all that, you have to be willing to take those few extra pills every day! For the health of the body and a decent quality of life, those extra pills may not be such a bad deal. At the very least, a potent multivitamin and B-complex daily can't hurt, and enough data exist to support their potential benefits. Other supplements should be carefully considered. Talk to your physician. He or she should want to work with you in designing the best program for you and not dismiss your concerns or your choices.
George M. Carter is the director of The Foundation for Integrative AIDS Research (FIAR), a new, not-for-profit organization that is dedicated to the clinical evaluation of dietary supplements used in HIV and chronic viral hepatitis.
This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.