This excerpt is reprinted by permission of Jossey-Bass Inc. Publishers from Dr. Mary Romeyn's new book Nutrition and HIV: A New Model for Treatment. Dr. Romeyn is an internist on staff at Saint Francis Memorial Hospital in San Francisco, with a private practice specializing in HIV and nutrition.
To understand the role of vitamins and minerals, it helps to understand a little bit about the chemistry of your body. Living organisms rely on highly complex processes to perform and regulate those internal functions that are necessary to maintain life. Processes are in place to
- Build the cells that make up your body's structures
- Meet the separate needs of different types of cells
- Permit each of these different cell types to carry out its own specific functions
- Help maintain cellular structure and performance
- Alter the type and degree of cellular activity in the face of changing circumstances
- Communicate and coordinate each cell's activity with the activity of other cells and organs in the body
- Adjust cellular behavior, as needed, in ways that will permit a coordinated response of the whole organism to its environment
- Dispose of waste products
- Govern the disposal of cells when their job is done
The scientific term we use to describe all this is homeostasis.
Homeostasis can be defined, then, as the ability of a living organism to maintain its structure and function intact, separate from and invulnerable to the forces of its environment.
The maintenance of homeostasis is highly complex, requiring many series of chemical reactions, distinct and yet interrelated. Each step in each reaction requires the presence of specific substances, often in minute amounts. If these materials are not present, or are present in too small a quantity to perform their roles, the reactions that require them cannot proceed correctly.
Vitamins, minerals, and trace elements are among these necessary substances. With the exception of vitamin D, which can be made within the skin, they cannot be made in the body; they must be absorbed to be obtained. Some are produced for us within the gut, by bacteria that live there.
We don't need a lot of them. Given perfect health and a well-balanced diet, we can get what we need from the food we eat. Given states of altered metabolism, though, we may need more. And during or following an illness, the body's natural processes of healing and repair cannot go forward unless we have enough-sometimes more-of the vitamins required.
There is evidence which raises the possibility that higher amounts of some of these substances may actually improve our health even when we're not sick, by giving our bodies a richer source of materials to draw on in the face of normal stress. This view is controversial, but more and more research supports it.
HIV and Vitamin, Mineral, and Trace Element Deficiencies
In HIV, as in normal aging, some evidence suggests that we may benefit from more of some of these elements than we normally get from our diet or than was previously recommended. In addition, many people with HIV have been shown to have actual vitamin deficiencies-lower body stores of some vitamins than what is considered necessary even for a person in perfect health.
In some cases, the HIV virus itself can benefit directly from those deficiencies, increasing the rate of its production. That means it's critical to avoid these deficiencies. It also offers hope for increasing our gains in the battle against HIV production in our own bodies.
As we have seen, HIV infection can cause you to eat less. Also, you may absorb nutrients less well. This is part of the reason for HIV-associated vitamin and mineral depletion.
Many vitamins, minerals, and trace elements are found to be deficient or in low-normal range in people with HIV. This has been documented even early in the course of infection. Even people who eat an excellent, well-balanced diet are not immune to these deficiencies if they are HIV positive. Therefore, even apart from the possible benefits of higher levels in some specific cases, it makes sense to supplement.
The best place to start-as simple as it seems-is to eat well. As Dr. Bruce Bistrian, of the Harvard nutrition team, puts it, "When we eat what God gave us, we're eating what's good for us.... You got to do it the hard way." We'll look at food sources that are naturally rich in each particular vitamin as we discuss it below.
But I don't believe you should stop there. For you there is too much at stake. Therefore, the recommendations in this chapter will be for supplementation-for taking vitamins daily, in addition to maintaining a healthy diet. And if for some reason you aren't sure your diet is healthy, supplementing it can help to protect you anyway.
Before we look at supplementation or institute a program, though, it's important to talk about RDA.
The RDA, or recommended dietary allowance, is a baseline figure. It is used to suggest the lowest amount of a given substance that we should take in, daily, from our diet. You'll see references to the RDA on labels for vitamins and for many prepared foods.
It's important to understand that this is not a recommended intake level. Rather, it represents the minimum amount required to prevent an overt, frank deficiency-in healthy people with good absorption and the ability to maintain normal nutritional status. Thus the RDA holds very little meaning for you.
The RDA underestimates the requirements of an organism under stress. It is not a good guide for your nutritional or dietary intake. For vitamin C, for example, the RDA is 60 milligrams a day-just enough to prevent scurvy in a healthy sailor.
The RDA also does not take into account specific actions of a given vitamin that can be of special value in illness, or may promote your overall good health.
It's also important to define our goals for supplementation. First off, we don't want to compound the problems of HIV with the problems of vitamin deficiency-but we can do more than avoid that. We can improve our bodies' ability to fight the effects of injury, disease, and stress by knowing what can help, and taking it.
We already know which vitamins and trace elements tend to be reduced in HIV infection. We already have an idea of the benefits that higher levels of supplementation may offer. And we already know when it's too much of a good thing-when vitamin excess can work against your health. Popping a good multivitamin or two each day, along with a trace-element supplement, can be a good start. There is research in the literature which shows a real role for daily vitamin use. One study showed that people with HIV did better just by taking a multivitamin supplement every day.
If you want to consider more specific supplementation-and I believe you should-some suggestions follow. For certain vitamins in particular, high-dose supplementation is worth considering.
Vitamins Which May Be Deficient in People with HIV
Note that in many cases the appropriate supplementation amount simply has not been determined. Where we don't know how much of a particular vitamin can help you, the RDA is given-just to give you a rock-bottom floor. Where we know too much of a vitamin can hurt you, this is stated as well.
To understand the minute quantities that are needed, you have to know the relevant units of measure:
1,000 micrograms = 1 milligram
1,000 milligrams = 1 gram
28 grams = 1 ounce
Here are some of the vitamins you want to pay special attention to.
Vitamin B1 (Thiamine)
Thiamine is needed for conversion of carbohydrates into energy, for transmission of signals from your nerves to your muscles, and for maintaining the structure of membranes in the nervous system.
It is absorbed high in the small intestine and stored mainly in muscle tissue. Raw fish, coffee, and tea can break it down. Deficiency can occur quickly, as the body can't store this vitamin for long. Malabsorption, malnutrition, alcohol, diarrhea, and low folate levels can all contribute to B1 deficiency. Antacids and other medicines that reduce stomach acidity can destroy it.
Need is increased with fever, heavy exercise, or high caloric intake.
Deficiency can result in weight loss, irritability, poor appetite, and paresthesias-the burning or prickling sensations we associate with peripheral neuropathy-especially in the feet and lower legs. When deficiency is more severe there can be weakness and changes in mental status.
One to two milligrams a day is said to prevent frank deficiency. Excess thiamine goes out in the urine, so too much can't hurt you.
Most multivitamins contain 1.5 to 3 milligrams of thiamine. High-potency pills and B-complex supplements contain 50 to 100 milligrams.
Dietary sources of thiamine include red meat, whole grains, potatoes, peas, beans, nuts, and yeast. As this nutrient is water-soluble, it can be lost when food is cooked in liquids.
Vitamin B2 (Riboflavin)
Riboflavin is also absorbed in the small intestine. It is needed for many reactions in the body, and particularly for the metabolism-the energy economy-of amino acids, the basic units from which proteins are constructed. It is also needed to convert dietary vitamin B6 to its active form in the body.
Riboflavin deficiency can develop within a week. Some drugs can contribute to such deficiencies: Compazine, or prochlorperazine (used for nausea); major tranquilizers; and tricyclic antidepressants such as Elavil, or amitriptyline, often used for the treatment of foot pain in HIV, are among them.
Deficiency can result in burning and itching eyes, painful sensitivity to light, tongue and mouth pain, anemia, and personality changes. In addition, metabolism of drugs can be altered.
Three milligrams a day are recommended to prevent riboflavin deficiency. Again, if you don't need it, you excrete it.
Supplementation in standard multivitamins is in the range of 1.5 to 3.5 milligrams. High-potency sources and B-complex preparations contain 75 to 100 milligrams.
People who supplement their B2 notice that their urine shines a bright, fluorescent yellow. That's why you see this now, if you're taking a B-complex supplement.
Natural sources of riboflavin include dairy products, meat, fish, and green leafy vegetables. Whole grain cereals are also good sources, as are egg whites. Riboflavin is broken down by light, so exposure while cooking (by broiling, for instance) can deplete it.
Vitamin B6 (Pyridoxine)
Pyridoxine is also absorbed in the small intestine, and any excess is excreted in the urine. Deficiency can develop in two or three weeks. Like vitamin B2, it is active in the metabolism of amino acids. It also plays a role in making neurotransmitters-the chemicals that brain cells use to communicate with one another. It is essential to many enzyme reactions.
Vitamin B6 deficiency is relatively common in people with HIV. This has been reported in the early, asymptomatic phase of infection in particular. Isoniazid, or INH, commonly used to treat tuberculosis in people with HIV, further contributes to B6 deficiency.
Symptoms include irritability and depression, followed by skin rashes and tongue and mouth tenderness. Nausea and vomiting, as well as seizures, are late manifestations. B6 deficiency can also cause anemia, and it has been shown to further impair immune function in people with HIV.
One study reported that oral supplements of 20 milligrams or more a day successfully corrected deficiencies in people with HIV. Twenty-five to 50 milligrams a day is better if you're taking INH. Standard multivitamin preparations contain 2 to 5 milligrams. B-complex pills can have 5 to 100 milligrams.
Foods rich in B6 include meat, fish, egg yolks, beans, fruits, and vegetables. Liver is a good source, as are whole grain cereals. Losses occur during cooking.
Vitamin B12 (Cobalamin)
Absorption of vitamin B12 is more difficult than that of the other B vitamins. Cells in the stomach produce a factor which binds to B12 and permits it to be absorbed in the small intestine. Thus there are two points in its journey at which oral absorption can be impaired. On the other hand, the body can recycle some of what gets in, shuttling it back and forth between the intestine and the liver, for reuptake and reuse. It is stored in the liver in ample quantities, so B12 deficiency takes longer to occur than other B-vitamin deficiencies.
Nonetheless, B12 deficiency is common; some studies have found vitamin B12 levels to be low in 20 to 25 percent of people with HIV. Many of these people showed no obvious symptoms of deficiency. Also, it's harder to detect clinically.
Most HIV-negative people with B12 deficiency have changes in their red blood cells-bigger cells, more hemoglobin per cell-which show up easily on a complete blood count, alerting their doctors to test B12 levels. HIV-positive people don't show this pattern. If their doctors are not looking specifically for B12 deficiency, they may never know it's there. Doctors may also not consider the enormous contribution of malabsorption to HIV nutritional status and disease progression, which might otherwise encourage them to check B12 levels automatically. Thus, when not checked routinely, B12 deficiency can often be missed.
A low level of vitamin B12 is especially important in the setting of HIV, because of its potential role in problems with nerve conduction or function (neuropathy) and spinal cord abnormalities (myelopathy). These conditions are seen with some frequency in the HIV-positive population, and they have substantial impact on quality of life. One study looked at people with relatively advanced HIV disease who were referred to a university neurology clinic. These people presented either with neuropathy or myelopathy. Of those who had both conditions, vitamin B12 was found to be low in more than half.
Vitamin B12 deficiency has also been associated with early, subtle changes in mental function in people with HIV. Those changes include the speed with which we process information, and our performance on tasks requiring visual-spatial coordination. Because they are subtle, we may not pick these changes up.
Vitamin B12 is provided in the diet by meat, fish, and eggs, so vegetarians are particularly at risk. It can be obtained in lesser amounts from milk and milk products. Generally, it is not destroyed by cooking.
As with the above vitamins, there is no specific recommendation for supplementing in HIV-positive people; the studies just haven't been done. Your basic multivitamin has 6 to 18 micrograms of B12. B-complex preparations include from 12 to 500 micrograms. Separate B12 oral supplements are also available, in doses from 25 micrograms to 1 milligram. An excess of B12 won't hurt you, but it may not be necessary.
We'll talk more about vitamin B12 supplementation later. Because absorption is so frequently a factor in B12 deficiency, you may need some help from your doctor.
Folate changes into its active form after it has been absorbed by the body. It is excreted through the gastrointestinal tract. It is necessary for making red blood cells and for neurological function. Thus deficiencies in folate, as with vitamin B12 deficiencies, are associated with neurologic symptoms. This can be particularly important to people with HIV. More folate is needed in the presence of severe infection, cancer, and pregnancy.
One report measured folate in the cerebrospinal fluid -- the fluid that bathes the brain and spinal cord -- in children infected with HIV. Results showed a lower level of folate in that fluid than in the blood. Thus we may be folate-deficient where we need it most, even when we test in the normal range. And, as is found with vitamin B12 deficiencies, the red-blood-cell changes normally associated with folate deficiency are often not seen in the presence of HIV.
AZT has been shown to contribute to folate deficiency. People taking AZT are therefore at greater risk. This is also true of other commonly used drugs. Trimethoprim, for example, part of the drug trimethoprim-sulfamethoxazole (Bactrim or Septra), which is widely used to protect against pneumocystis pneumonia, is a folate antagonist-it directly blocks folate. So do pyrimethamine, used for toxoplasmosis, and methotrexate, a common chemotherapy agent. Phenytoin, or Dilantin, a popular antiseizure medicine, blocks absorption of folate. So do barbiturates, used by some doctors for pain control or to help you sleep.
Alcohol is a special villain. It also blocks folate absorption, and people who regularly use substantial amounts of alcohol are often seriously deficient. Vitamin B12 deficiency can also lower available folate levels, as it is needed to change folate into its active form.
Loss of appetite, nausea, diarrhea, hair loss, and mouth and tongue pain can all be symptoms of folate deficiency. Fatigue is common too. As things get worse, changes in blood cells may be seen.
Folate deficiencies are treated with 1 to 2 milligrams a day. One milligram or less a day is given thereafter for maintenance. Oversupplementation is not thought to be dangerous.
Leafy vegetables, organ meats, and yeast are good dietary sources.
Multivitamin folate levels are usually set at 4 milligrams. Folate is not normally included in B-complex preparations.
Vitamins Not Frequently Requiring Supplementation in HIV
You'll see these vitamins listed on the labels of the multivitamin supplements you buy, as well as for sale separately. It's important that you know their role. Supplementing in large quantities is unnecessary, and can in some cases be harmful. Supplementation in the small quantities used in standard multivitamin preparations won't hurt you, though.
Niacin is needed for the metabolism of proteins, carbohydrates, and fats. It is absorbed throughout the intestine and excreted in the urine. In large doses, in HIV-negative people, it can have beneficial effects on cholesterol and triglyceride levels. But lowering these levels is not helpful if you are HIV-positive.
Without serious malnutrition, we rarely see nutritionally based niacin deficiency. Classically, deficiency has been found only in people who eat a corn-based and otherwise unbalanced diet.
Five to 20 milligrams a day are enough to protect against niacin deficiency, and large amounts may not be good for you. What you get in your diet should go a long way toward meeting your needs. Beyond that, my patients stick to what they get in their multivitamin pills.
Symptoms of niacin deficiency include generalized weakness and indigestion. Headaches and insomnia can follow. Severe deficiency can cause characteristic skin rashes, massive and bloody diarrhea, and even dementia.
Symptoms of supplementation include flushing and temporary tingling and burning sensations. Oversupplementation can cause vomiting, diarrhea, and even fainting, due to a fast heart rate and low blood pressure. At very high doses ulcers, liver damage, and high blood sugar can also result. This is not a vitamin to play around with.
Standard preparations contain 20 to 30 milligrams, which is a minimal amount. B-complex supplements can contain up to 100 milligrams. Even at that dose you may get some flushing and a characteristic prickling feeling.
If you can tolerate this, it won't hurt you; doses totaling up to 300 milligrams or so a day are probably okay. But there's no reason to take it on its own. In particular, you should avoid the time-release preparations. They are more likely to damage your liver.
As an HIV doctor, I also prefer that my patients not take niacin in substantial quantities because it changes the lab values I use to monitor their health. Large amounts of niacin, even if tolerated, will lower cholesterol and triglyceride levels-so those levels no longer tell me what I need to know.
Sound sources for obtaining sufficient niacin in the diet include meat, fish, eggs, and beans.
Biotin is found in most foods and is absorbed throughout the gut. Bacteria in the colon make more. Therefore, less biotin will be available if gut bacteria are destroyed by powerful antibiotics. It is needed for metabolism of fats and carbohydrates. Raw egg whites contain a substance which inactivates biotin. Still, biotin deficiency has only been seen in severe malnutrition.
Rashes, muscle pain, and hair loss are symptoms of biotin deficiency, as are nausea and anemia. However, even in patients maintained entirely on total parenteral nutrition or TPN (food delivered through the veins for people who can't be fed otherwise), reports of deficiency are rare. For anybody who can eat, the amount in a normal multivitamin, about 30 to 300 micrograms, should suffice. B-complex vitamins contain 30 to 100 micrograms.
Easily absorbed and readily available in the diet, pantothenic acid contributes to the metabolism of carbohydrates and fats and to making steroids. Deficiencies are rare and have only been described in association with other vitamin deficiencies.
When deficiency has been caused experimentally, the result has been foot pain-the so-called "burning foot syndrome." For this reason, investigators have tried to treat those symptoms with 10 milligrams a day. Success has been limited, however.
No role has yet been found for individual supplementation with this vitamin. You'll get a little, about 10 milligrams, in most routine supplements. Vitamin B combinations can have 5 to 75 milligrams.
Vitamin D is available in the diet, but the major portion is produced by skin synthesis. It is important for calcium and phosphate metabolism, and may have a role in immune function. Vitamin D deficiencies are rare, occurring only with inadequate exposure to sunlight. There are no reported cases of vitamin D deficiency in people with HIV. Too much vitamin D can raise your calcium level, weaken your bones, and lead to kidney stones. If you want to ensure that you have enough vitamin D, don't look to your vitamins; just go to the park and lie in the sun.
Vitamin K occurs in two forms. It can be obtained in the diet from green leafy vegetables and liver. Bacteria in the gut provide another form, which is less active. Vitamin K is stored in limited amounts in the liver, where it is used to make factors that promote blood clotting. Thus a vitamin K deficiency can result in anticoagulation. If the liver is damaged, it may not be able to use vitamin K, even when present or provided in adequate amounts.
Malabsorption or the long-term use of powerful antibiotics, which sterilize the gut, can lead to a vitamin K deficiency. So can long-term use of TPN. Such deficiencies respond to injections of vitamin K, if the liver is healthy. There is no report of vitamin K deficiency peculiar to HIV, and I know of no need to supplement it on your own. Multivitamins don't generally contain it.
When a deficiency is documented in people with long-term malabsorption and diarrhea, it sometimes will respond to oral treatment. This you should discuss with your doctor.
Antioxidant vitamins play a central role in regulating homeostasis. They are especially interesting, because it is possible that increasing levels of supplementation may, in some cases, be of benefit.
To understand what an antioxidant is, we need to learn a little more about the way our bodies work. I'll try to keep this simple.
How Antioxidants Work
The body is made up of molecules, combinations of atoms constructed in a particular way to do a specific job.
The molecules that take part in or regulate processes in your body are held together by the forces between their electrons, which have a sort of magnetic attraction to one another, and fit together based on that attraction.
Many molecules within your body exist periodically in what is called an oxidized state. This means that they have one or more unpaired electrons. They are looking for molecular partners, often at the expense of other important molecular relationships. When they are in this state, they are called free radicals.
These free radicals can react much more with their surroundings, often in ways that are damaging. They can interact with and disrupt many finely tuned processes which are needed to maintain the body.
In some cases, the presence of these active molecules, or free radicals, can be helpful. Cells of your immune system, for example, rely on the destructive power of free radicals and use them as ammunition, discharging them where infection is present in order to kill the invaders. But along with the destruction of unwelcome cells or organisms, there can be damage to nearby tissues and processes your body needs.
In other cases, however, free radicals are simply an unavoidable by-product of body processes -- the leftovers, so to speak, of necessary reactions -- and serve no useful purpose. In these cases they are like static on the radio: they mess things up a little, but the music keeps on playing.
All of this is true for every living body.
Our bodies contain natural substances, called antioxidants, which can gather up and neutralize free radicals, limiting their capacity for destruction. Often there are not enough to do the whole job.
There are stages or circumstances in our lives in which free radicals and their damage are increased. Much of the deterioration we see in aging, for example, results from the presence of an increased amount of these reactive molecules. Our natural stores of antioxidants cannot successfully overcome the increase. In states of illness or infection, free radical presence is also increased and results in many of our symptoms. This is of special concern for people with HIV, in whom the normal antioxidant defense system is compromised.
Alcohol and other substances increase the number of free radicals, and hence the damage they do to the body. We'll talk more about that later, when we look at alcohol and HIV.
What makes all this very important is that, given the chance, the HIV virus uses free radicals to establish itself. Free radicals activate the critical step in the actual copying of genetic material needed to reproduce the virus. And the virus itself stimulates their increased presence. The more we can swamp them with extra antioxidants, the harder it is for HIV to grow.
This has been proven, and is currently the subject of substantial research around the world. We already know:
- If you add antioxidants to a culture dish in which HIV is growing, activity of the virus is profoundly reduced, and HIV production is inhibited.
- If antioxidants are removed from a culture dish in which HIV is growing, production of the virus is increased.
- The amount of certain natural antioxidants is decreased in the blood of people with HIV, and antioxidant levels decrease progressively with increasing illness.
- The results of some studies suggest that antioxidant supplementation may slow the progression of HIV.
We can help our system to protect and repair itself by increasing its antioxidant supply. This chapter will look at some of the natural antioxidants our body uses, which we can easily increase with supplementation.
There are also some antioxidants not found naturally in the body, which are being studied for their possible role in fighting HIV.
Vitamin C (Ascorbic Acid)
Vitamin C is the best known, the most studied, and the most frequently supplemented antioxidant. It is easily absorbed in the small intestine, as it is a simple carbohydrate, and it is excreted in the stool and urine. The kidney reabsorbs it from the urine when supplies are low. Absorption, both in the kidney and the small intestine, is reduced when intake is greater than 200 milligrams per day.
The bulk of its impact on wound healing is due to its role in making collagen, the building block of new tissue formation. Thus it helps maintain our very structure. It also may offer special protection to the lung, by reducing damage to delicate lung tissues caused by activation of the cells of the immune system.
Vitamin C is involved in the manufacture of hormones, steroids, and neurotransmitters -- the substances by which our nerve cells speak to one another. It is necessary for the conversion of folate into its active form. It also assists in iron absorption.
Our need for and utilization of vitamin C increases in the presence of infection or injury. With inflammation and fever we consume more. Major burns increase requirements by a hundredfold. And if we are malabsorbing, we must take in a lot to get in a little.
Frank vitamin C deficiencies are rare; they manifest as poor wound healing, easy bruising and bleeding, and anemia.
Vitamin C has been studied in the medical literature, and it is touted in the lay literature for its effects on the common cold -- a viral infection -- both for prevention and recovery. One study treated patients newly infected with colds, using either vitamin C (6 grams a day for five days) or a placebo. (A placebo is an inactive substance made to look like the pill being studied, so that neither the doctor nor the patient can tell who gets the real thing.) Improvement was so striking in those receiving vitamin C that it was not possible to hide their identity from the doctors who observed them.
Other studies did not show a reduction in the number of colds contracted, but did show that colds were shorter and less severe with vitamin C supplementation. And fewer superimposed bacterial infections -- which often follow colds when resistance is down -- have been reported.
There has been considerable interest, in the HIV-positive community, in the role of vitamin C supplementation. So let's look at the nature of vitamin C. We know that, except for guinea pigs, humans are the only mammals who can't make it. We know that, pound for pound, the average mammal makes the equivalent of up to ten grams a day for an organism our size. We know that this production is not static, but increases when an animal is stressed (for example, by infection). Rats, when stressed, have been shown to increase their production tenfold. We know that the amount of supplementation required to cause diarrhea, a side effect of high supplementation, increases when we have an infection -- suggesting that we use more, if we have it, when we need it. Interestingly, levels of vitamin C have been found to be reduced in humans during infection with the common cold. We use more when we're sick, and we can't make more to replace it.
Part of the role of vitamin C in infection is to react with and neutralize free radicals. Cells of the immune system release toxic substances to kill an invading germ or virus; surrounding tissues are also damaged; and the free radicals which result can extend that damage further. This is particularly worrisome in people with HIV, because the virus needs just such an environment -- one with excess free radicals, in an oxidized state -- to reproduce itself. And vitamin C is a powerful antioxidant.
Vitamin C also helps increase the net antioxidant action of vitamin E. Some of vitamin E's actions can actually oppose its antioxidant effect, but in the presence of vitamin C this does not happen.
Perhaps because of its antioxidant properties, vitamin C use is associated with a reduced risk not only of infection, but also of heart disease, cataracts, and some cancers. It helps protect against the ravages of cigarette smoke and city smog. Preliminary data suggest a role for vitamin C in treating or helping prevent heart attacks, adult-onset diabetes, some long-term side effects of psychiatric drugs, and other chronic disorders.
Some cells in the immune system contain up to fifty times as much vitamin C as is found in the blood. This may help protect these cells against the kind of damage they cause their surroundings, from the compounds they make to fight infection.
While there can be problems with oversupplementation of vitamin C, most of them occur only at very high doses. Diarrhea is the most common. It rarely occurs at doses of less than 4 grams, or 4,000 milligrams, a day, and it resolves when amounts are reduced. In fact, those who take high doses of this vitamin often choose their dose by increasing their intake daily until diarrhea appears. And, as we have said, that diarrhea is not present at the same dose during times when their system is stressed. It's a natural way to ask your body how much vitamin C it can handle.
There are people, some of them doctors, who advocate massive doses of vitamin C -- up to 10 or more grams a day. But such doses are not without risk. Kidney stones can precipitate at very high intake levels.
At this point, until the results are in, I recommend an intermediate dose of 1 to 3 grams a day, as tolerated. During periods of active infection you can double or triple this dose; but I suggest no more, for now, than 6 grams a day. For those who are committed to higher doses, consider taking baking soda, to keep your urine alkaline and to reduce the risk of stones. Drinking large quantities of water can help prevent kidney stones, too.
Remember that we have no proof of what constitutes the perfect dose. But you and I just don't have time to wait. To quote a 1994 editorial in the Journal of the American College of Nutrition: "Antioxidant nutrients appear remarkably benign, even at high supplementary intakes.... [R]ecommendations to wait until every conceivable study has been designed and conducted to achieve a level of absolute certainty will result in the continuing cost of the disease to the individual and to society" (Hemila, 1992).
Basic multivitamin preparations contain 60 to 180 milligrams of vitamin C. You'll find some vitamin C in your B stress, or B-complex, vitamins. You need not count this in your total.
Vitamin E (Tocopherol)
Vitamin E is absorbed in and with fat; it requires pancreatic and biliary enzymes for absorption. Its antioxidant properties serve to protect and stabilize cell membranes. It is found in vegetable oils, and to a lesser degree in eggs, whole grain cereals, and butter. You can get a little from vegetables. Frank deficiency is rare and takes a long time to occur, but can be seen when there is lasting, severe fat malabsorption. It can also be seen after long-term TPN administration. Effects of vitamin E deficiency include peripheral neuropathy, poor position sense and balance, and a reduction in knee-jerk and other reflexes. Deficiency of this vitamin alone in those who are not HIV positive can result in the same immune system abnormalities found in people with HIV infection.
Cell membranes have a fat, or lipid, layer. Free radicals in these membranes react with oxygen and initiate a chain reaction forming new free radicals at every step in the chain. Vitamin E counters this process by entering the lipid membrane and uniting with the free radical. The molecule which results has a different shape; it sticks its head out of the membrane, where it becomes visible to vitamin C. When attacked by vitamin C, it can be reduced back to a stable molecule, and the chain of damage is halted.
It's important to know what kind of vitamin E you're taking. If its not alpha tocopherol, which is naturally produced, Vitamin C won't recognize it, and you won't get all of this effect. If it's gamma tocopherol, such as is found in soybean oil, it will be excreted quickly. So you should try to find supplements which contain alpha tocopherols. These have the most activity. Most vitamin E is sold in the alpha form.
Vitamin E is used in a variety of circumstances for its antioxidant effects. It is under study in combination with vitamin C and beta-carotene, for example, as supportive treatment for those with cholesterol disorders, along with appropriate cholesterol-lowering drugs. Its supplementation has been shown to increase cell-mediated immunity in healthy elderly people. This is exactly the type of immune response which is impaired, and eventually destroyed, by HIV disease. In each of these studies, the dosage used has been eight hundred units a day. Vitamin E is also one of the vitamins which can be taken in relatively large doses without toxicity.
Dietary supplementation of vitamin E is thought to increase AZT's effectiveness in fighting the virus. And, in the presence of HIV infection, vitamin E intake may decrease the speed of progression to AIDS.
We have already noted that, in laboratory cultures of HIV, addition of antioxidants slows the rate of growth of the virus. With high enough doses of vitamin E, growth may actually be halted; those doses, however, are so high that they kill the cells in which the virus has been cultured. Thus, the toxicity of vitamin E at super-high doses limits the extent of its effect. In moderately high doses, however, it may stimulate, and perhaps protect, some of the immune cells the virus is known to destroy.
Low levels of vitamin E have been found to correlate with the presence of HIV and other infections, particularly in immigrants from developing countries. The Italian studies which reported this finding did not investigate which abnormality-infection or vitamin E deficiency-might have come first. They did report, however, that vitamin E was found to be deficient in study subjects with AIDS, and in about a third of intravenous drug users who did not have evidence of HIV infection. This association of vitamin E deficiency with migrants from developing countries, and with intravenous drug users, was also reported in another Italian study, raising the possibility that low levels of vitamin E and other antioxidants might actually play a role in initial infection, as well as in progression to AIDS in those already infected.
In another study, blood levels of vitamin E were found to be low in 27 percent of HIV-positive men-four to five times as many as those who are deficient in vitamin A or C.
Thus, we know that vitamin E helps slow the growth of the virus; we know that your vitamin E level may be deficient if you are infected; and we know that moderately high doses won't hurt you. Given these facts, it makes sense to supplement vitamin E.
Based on recommendations for other health conditions, I recommend 800 to 1,200 milligrams of vitamin E a day.
Your standard multivitamin has only about 30 milligrams of vitamin E. Centrum contains none.
Like vitamin E, vitamin A is a fat-soluble vitamin. It occurs in its active form in milk products, meat, and saltwater fish. Green leafy vegetables, carrots and other yellow root vegetables, and yellow and orange fruits contain beta-carotene, which the body can convert to vitamin A. Depletion results from malabsorption of fats, or from the use of mineral oil as a laxative. Alcohol use can also contribute. Beta-carotene conversion to active vitamin A in the body can be defective in people with diabetes or hypothyroidism. Long-term TPN can promote deficiency, too.
Dry eyes, night blindness, and other eye conditions are symptoms of vitamin A deficiency. In extreme cases, blindness can result. Also, white cells can be reduced, as can red blood cells. Resistance to infection is impaired. Thus vitamin A deficiency can result in more, and more severe, diseases of many types. Even a mild deficiency has been shown to increase the risk of pneumonia, diarrhea, and even death in children.
Supplementation with beta-carotene, the recommended form of vitamin A replacement, has been shown in one study to increase the number of T4 lymphocytes in healthy, HIV-negative people. This kind of immune cell-the kind you want to hold on to-is entered, taken over, and eventually destroyed by HIV. One of the fourteen participants in this study reported diarrhea. No other side effects were seen.
And what about the particular need for supplementation in people with HIV? In a study of over one hundred HIV-positive patients with no symptoms other than enlarged lymph nodes, 18 percent were found to be deficient in vitamin A. Another study, also showing lower levels of the vitamin in HIV patients, reported no effect on T-cell, or CD4, counts.
So once again, we find that higher levels of a vitamin may help protect against HIV's effects on the immune system. We know that lower levels are likely to be found in the presence of HIV, just when its support is most needed. We know this can happen early. We also know, however, that an excess of vitamin A is toxic and must be avoided.
Too much vitamin A -- called hypervitaminosis A -- can result in high levels of blood calcium, as calcium is pulled from bone. Vomiting and headache can result. Bone and joint pain are features also. In extreme cases there can be liver damage. A recent study showed increased lung cancer in smokers who supplemented their vitamin A intake. This is of less concern for you, but it does point to the fact that inappropriate use of vitamin A, even as beta-carotene, can actually promote free radicals.
Hypervitaminosis A is one of the more common types of vitamin excess. You can monitor yourself for it by watching the color of your palms, and by looking for yellow coloration in the places where you sweat. But the best way is to monitor your intake.
Doctors have a shared joke: an alcoholic, they say, is a person who drinks more than her or his doctor. In my office we define a patient with hypervitaminosis A as someone whose palms are yellower than mine.
One of the ways we avoid vitamin A toxicity is to supplement in the form of beta-carotene. I do not recommend taking a direct vitamin A supplement. Nor do I recommend cod liver oil.
Even in the form of beta-carotene you shouldn't go overboard. I suggest 15 to 30 milligrams a day, which will give you the equivalent of twenty-five thousand to fifty thousand units of vitamin A. If you drink carrot juice most days, you can skip supplementation entirely. Hypervitaminosis A can even be seen in people who take no supplements, if they live their life on carrot juice.
You'll find about 3 milligrams, or five thousand units, of vitamin A in most multivitamins. High-dose preparations can have up to three times this much.
The regulation of mineral balance in the body is essential to survival. Like the body itself, each cell is a living organism and must maintain its internal environment. And it must interact with its surroundings in order to perform the functions assigned to it. The movement of minerals across cell membranes, between the extracellular and intracellular fluid, forms the basis for the body's most primary functions. Electrical activity is initiated; hearts beat, nerve cells signal. Muscles respond. Blood vessels tighten or relax. Water balance is maintained.
Here is a look at how some of these processes work, and a survey of the need to supplement in the setting of HIV.
Sodium and Potassium
These minerals, as they flow back and forth across cell membranes in controlled fashion, maintain homeostasis in the cell, and in the organ and the body that it is part of.
The body's ability to regulate and maintain its stores of sodium and potassium is impressive. Except in the case of severe illness, or the use of certain medications or intravenous fluids, there should be no special need to supplement. In those cases, your doctor will monitor your levels.
Calcium and Phosphorus
While there is a recommended dietary intake for calcium and phosphorus, deficiencies are rarely a problem. Calcium will be found in your multivitamins in varying amounts; about 30 to 150 milligrams of phosphorus will be present in your daily vitamin, and it's commonly present in foods. If levels are low in the blood, it will be because you're sick, and your doctor will be watching them.
If in fact you have lost a lot of weight, have recently been ill, or are now ill, you might want to monitor your phosphorus level. It's found on a routine chemistry panel.
Magnesium, however, is a different matter. It plays an active role in the metabolism of sodium, potassium, and calcium. It acts on your heart and blood vessels, your nerves and muscles, and your gut. Most of it is concentrated in tissue, so levels in the blood don't tell us much.
Kidneys spill magnesium. Losses also occur in the stool and through the skin. Malabsorption can reduce its availability from the diet. High alcohol use reduces it. Diuretics and some antibiotics deplete it.
Levels are often low in states of severe infection, and often then rise in that setting, suggesting that tissue damage and cell death cause its release. Then it's carried out of the body and lost. Thus illness can deplete you rapidly; and your doctor may not know it, even if she or he tests you. Calcium deficiency results from magnesium depletion, and may not respond to treatment without magnesium supplementation.
Unlike calcium, there are no reserves in bone to draw on if magnesium supplies get low. But also unlike calcium, you cannot get too much.
Recent studies show that magnesium supplementation can reduce lung injury from oxygen toxicity. It blocks blood vessel constriction, so it can augment blood flow. It has been shown to increase the speed of recovery from open heart surgery, and to improve the likelihood of recovery from severe, life-threatening infection.
Since it can be hard to get magnesium in and easy to lose it, since it's so important, since you can't get too much, and since too much can't hurt you, it makes sense to supplement.
The only time you shouldn't supplement your magnesium is in the case of kidney failure. If you can't excrete it in the urine, it can build up. Otherwise, you're safe.
One hundred to 125 milligrams are found in most multivitamins. Theragram M has only 24 milligrams. Trace element combinations generally contain 100 to 500 milligrams. The RDA for magnesium is 400 milligrams.
Given the exciting results of all the new research described above, you may want to beef up your program with a separate magnesium supplement. There's no way to know how much is enough. For now I suggest 500 extra milligrams a day, on top of whatever's in your combination pills.
These are other elements whose quantities are small but whose contribution is enormous and essential. There are seven essential trace elements described in humans: chromium, copper, cobalt, iodine, iron, selenium, and zinc.
There is no known use for cobalt except as part of vitamin B12. No deficiency of manganese has ever been reported. Iodine is important in thyroid metabolism, but has no known potential role in HIV in the absence of thyroid disease. It's present in small amounts in combination pills. Supplementing this element aggressively may meddle with your thyroid levels, so I don't recommend it.
The remaining trace elements are discussed below.
Chromium helps insulin perform, so it's needed by your cells to take up glucose. Thus when it is deficient, blood sugar levels can be elevated. Cholesterol and triglyceride levels rise too. Peripheral neuropathy has been reported, as has weight loss. Heavy exercise, infection, and injury increase its use, and hence its loss.
Chromium is found in good supply in brewer's yeast and in meats and cheeses.
The normal American diet is said to contain only about half of what we should have, but deficiencies have rarely been reported. And the above effects are the only ones we've seen.
The RDA, which is all we have to go by here, is fifty to two hundred micrograms. There are no studies reported on its importance in HIV.
Multivitamins contain from 15 to 100 micrograms of chromium. Trace element supplements can add another 100 micrograms or so.
Copper is a necessary part of some of the enzymes which help inactivate free radicals. Thus it plays a part in antioxidant protection. It is also used for making blood cells. It is active in the metabolism of iron. Copper-containing enzymes are involved in immune function.
Absorption can be reduced by critical illness, by high-dose zinc supplementation, and by antacids. Deficiencies are rare. Measurement is difficult. Excesses can be harmful and can lead to liver failure.
Copper supplementation is not normally recommended, except for those on TPN. However, copper deficiencies have been reported in people with HIV, and it is further reduced with AZT treatment. One study, though, showed higher levels of copper in people with HIV.
There is no RDA for copper. Two to 3 milligrams are generally found in daily multivitamins.
Iron is needed to make red blood cells. It can function as an antioxidant. Vitamin C promotes its absorption. When your body needs more iron, it absorbs more from your diet.
Deficiency leads to anemia. Malabsorption can result as well. When present in excess, though, iron can work against you. Iron is frequently sequestered in the body to prevent its use by bacteria as a source of fuel. Increasing iron inappropriately might lead to increased infection.
Iron attaches to proteins; it is first stored and then carried throughout the body by these proteins. But in states of chronic illness, the supply of these proteins is reduced. Storage capacity is thus limited. And when the body runs out of safe places to put its iron, what's left is deposited in tissues. The function of these tissues can be harmed by this process, particularly in the liver and the heart.
When present in excess, iron can actually stimulate free radical formation.
Unless you're menstruating, or otherwise losing blood regularly, there's no way to get rid of excess iron. And while insufficient iron can cause anemia, anemia may not mean that you need iron.
In one study, higher levels of iron were found in HIV-positive subjects than in HIV-negative subjects.
Low levels of iron should be interpreted by your doctor in the context of other tests, before you supplement your intake. These tests show not only what your level is, but also whether you have a safe place to park it.
Supplementation in documented deficiency states is prescribed at 325 milligrams, one to three times a day.
You'll get about 18 milligrams in most vitamin supplements, and the same in trace and mineral combinations. If your multivitamin specifically advertises iron, in its name or loudly on its label, it may contain more. I suggest you stay with a regular multivitamin.
Iron is found in red meats, liver, beans, and peas. The RDA ranges from 7 milligrams a day to 14 for women who menstruate.
Because of its potential for harm when oversupplied, and until we can better interpret its role in people with HIV, I recommend not supplementing on your own beyond what you get in combinations.
Selenium is an especially important antioxidant for you. It has been found to be depleted in both the tissues and the blood of people with AIDS, suggesting a deficiency of long standing. Selenium deficiency has been found in patients with or without diarrhea and malabsorption. Eighteen percent of the men in one HIV study, all asymptomatic, were found to be selenium deficient.
Levels go down as the disease progresses. Selenium levels correlate with albumin levels, with lean body mass, and with total lymphocyte count-all markers of immune function. Supplementation has been shown to improve symptoms and blood levels, but not these other markers. Further studies of its use, in combination with other antioxidants, are underway.
Infection and increased metabolic rates compound the loss of selenium.
Selenium deficiency is associated with heart disease and with anemia. Thrush is more common, and CD4s drop. Some patients report that their thrush goes away when they start selenium supplementation.
Current trials will tell us more about the value of selenium supplementation. For now, I recommend it. The 10 to one 100 micrograms you'll get in your daily vitamin and trace element supplements is a start. I recommend an additional 50 micrograms from one to four times a day.
I don't advise huge amounts. Selenium functions with -- and very much like -- vitamin E. We know more about vitamin E, and we know it's safe to push the dose. We don't yet know that about selenium.
There is as yet no RDA for selenium.
Zinc can be shuttled from blood to tissue in times of stress or illness. Thus plasma levels may not reflect its true concentration in the body. Zinc is absorbed in the small intestine. High-fiber diets and the presence of parasites can limit its absorption. Only 25 percent of what's ingested is absorbed, at best; with poor intestinal absorption, the amount can be even less.
Wound healing and the maintenance of membranes are among its tasks. It also plays a role in antibody production, and other aspects of immune response.
With zinc deficiency, immune response is impaired. Hair loss can result. Night vision is lost. We may think less clearly. Wound healing is slowed, and protein metabolism impaired.
Diarrhea can be both a cause and a result of zinc deficiency, and thus can compound the problem. Zinc should always be supplemented in people with severe, chronic diarrhea.
A reduction or change in our sense of taste can also result from zinc deficiency. This can be especially disturbing, as it affects both appetite and absorption.
Levels of testosterone, a male hormone, drop in states of zinc deficiency. This is particularly interesting to men with HIV, of which up to 20 percent are said to have low testosterone levels. In my own practice, I don't tend to see that so often-but I certainly see it in 10 percent of my male patients, and particularly in those with advanced illness. Loss of sexual desire and a decreased ability to lay down lean body mass are associated.
Some, but not all, studies have shown reduced zinc levels in people with HIV. Remember, though, that these are blood levels. They may not reflect tissue levels. AZT lowers zinc levels.
Some investigators report improvement of symptoms with supplementation. When taken in excess, though, zinc can weaken immune system function and lower calcium levels.
I'm particularly concerned about the results of a study set up in 1984. Two hundred eighty-eight HIV-positive men were asked what supplements they took, at the time they entered the study. They were then monitored for seven years for progression to AIDS. High daily intakes of vitamin C, biotin, and niacin were associated with slower progression to AIDS. High zinc intakes, however, were associated with faster progression-in a pattern consistent with the amount of intake. The authors concluded that high levels of zinc supplementation may have harmed immune status in these men.
It's hard to rely too much on this study, as other factors may have been involved. Still, it raises concern about zinc.
So we know we need some zinc, and we know we may have less in the setting of HIV infection. We also know a little bit of it may help reduce symptoms. And we know too much may be bad for us.
Multivitamins usually contain about 15 milligrams of zinc. Trace element supplements have 20 to 25 milligrams. Separate zinc supplements usually contain 50 to 60 milligrams. You'll get about 50 milligrams, then, if you take two multivitamins and a trace element supplement each day. I think that should be enough.
The RDA for zinc is 15 milligrams.
What to Do
Now that you have all this information, you have to decide what to do with it-just how aggressive, how committed you want to be.
To start with, you see how important it is to eat a healthy, varied diet, including the foods we've mentioned, to help supply these nutrients. Everyone should do that.
It is worth mentioning that even routine daily use of one multivitamin pill has been associated with a longer delay in progression from HIV to AIDS. We recommend this to all our patients.
The simplest schedule, then, is as follows:
- A multivitamin, without extra iron, twice a day
- A trace element supplement once a day
- An antioxidant supplement once a day
While this may not offer you all of the possible benefits of the high-dose supplementation described below, it should help prevent frank deficiencies. And if it's hard for you to eat or to get pills down, or if money is a problem, this will give you a safe, supportive regimen that is easy and inexpensive.
If you want to do more, here's my recipe:
- A multivitamin, without extra iron, twice a day.
- A trace element supplement once a day.
- A vitamin C supplement, 1,000 to 3,000 milligrams (as tolerated), once a day; or 3,000 to 6,000 milligrams (as tolerated), once a day during periods of active illness.
- A vitamin E supplement (alpha tocopherol preferred), 800 to 1200 units, once a day.
- A beta-carotene supplement, 15 milligrams (with 25,000 units of vitamin A), twice a day.
- A vitamin B stress complex supplement twice a day. (These offer higher doses than an average B-complex supplement. They have a little added vitamin C, to promote their absorption. You needn't count this vitamin C toward your recommended vitamin C total.)
- A magnesium supplement, 250 milligrams, twice a day.
- A selenium supplement, 50 micrograms, one to four times a day.
This is imprecise, because these studies are in their infancy. But it's a good place to start. And it takes into account the dangers of oversupplementing.
If your own regimen currently calls for more than what I've outlined, or calls for different substances, be sure to consider the dangers we've looked at above. You don't want too much of a good thing.
It's a good idea to take your vitamins with food, if you can.
Here in the United States, vitamins are easy to buy. There are health food stores in every town; even supermarkets and drug stores routinely carry a supply of the basics. But in other countries, where attention to nutrition is less a part of the popular culture, they're harder to find.
I was surprised, in speaking with AIDS activists and with educators associated with the French HIV information service SIDA, to find that access to vitamins was so limited, and their cost so high, in Europe.
If you can't obtain vitamins where you live, a list of sources for reasonably priced, good vitamin supplements is included in Appendix IV.
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