Seattle Treatment Education Project (STEP) Perspective, Vol. 7, No. 1 - Spring 1995; A Publication of the Seattle Treat- ment Education Project, 127 Broadway E. Ste. 200, Seattle, WA 98102 * (206) 329-4857. Published 3 times a year
Brad S. Lichtenstein

In the January 1995 issue of Nutritional Biochemistry, the concept of malnutrition in those infected with HIV was discussed.[1] The authors note that nutritional status directly affects the "immune competence" of the individual. Another study concluded that in early HIV infection, multiple nutritional deficiencies were assessed, and moreover many of these result from inadequate intake, further implicating diet as an essential component to health.[2] Many of the nutrients listed below have dual roles: directly affecting the immune system, and hence important for those with HIV, and fostering regeneration and integrity of the microvilli of the gastrointestinal (GI) mucosa (lining). Before beginning any supplementation program, it would be wise to speak to one's health care provider to obtain a thorough assessment of the status of the digestive system. Remember, the studies listed below are conducted with the goal of gaining information on single nutrients alone. Although suggested dosages as determined by these studies are mentioned, be aware that the action of a single vitamin occurs not in isolation but in concert with everything an individual consumes.

Vitamin A and Beta Carotene

The first class of fat soluble vitamins to be discussed is vitamin A. Vitamin A refers to the class of compounds known as retinoids, and applies to those natural sources of retinol or its synthetic derivatives. Natural sources of vitamin A are solely animal sources. These include organ meats (liver and kidney) and fats (butter and yolk of eggs). The carotenes are a class of compounds that give plants their yellow color. Beta carotene is the most important of these, for it is the main precursor to vitamin A in the body. Sources of beta carotene are mainly yellow and green vegetables and fruits (carrots, spinach, broccoli, and cabbage). An intact intestinal mucosa is necessary for the conversion of beta carotene to its physiologically active form in the human body. The physiological functions of retinol in the body are many, but it is of main importance in vision, epithelial tissue (respiratory tract, gastrointestinal tract, genitourinary tract, skin, cornea), reproduction and growth. It should be noted that beta carotene, regardless of its conversion to retinol, possesses the ability to function as an antioxidant. No known toxicity levels have been reported regarding beta carotene, however vitamin A levels exceeding 50,000 IU per day or greater have been linked to headache, nausea, hair loss, blurred vision and chronic joint pain. If continued excess ingestion occurs, liver damage may occur.

Severe deficiency in carotenoids are seen in those with HIV infection, and this is believed to not simply be the result of inadequate nutritional intake, although that factor does exist.[3] Most literature supports the need for supplementation of beta carotene for its antioxidant properties, either on its own or upon its conversion to vitamin A. The importance of antioxidants lie in their ability to prevent or delay the breakdown of oxygen by the body's own mechanism resulting in tissue destruction. Carotenes are essential for their role of inactivating the free radical (compounds which cause tissue damage). Some research suggests that the changes which occur in HIV infection are the result of "oxidizing agents." If this is the case, the use of antioxidants can be the first line of defense in effective treatment for those with HIV.[4] The works of Coodley [5,6] and Alexander,[7] suggest increases in CD4 cell counts after supplementation of beta carotene, however these trials were short, ranging from 14 days to 1 month. This is in opposition with Garewal's study which suggested that no change in CD4, CD8 or total T cells occurred after supplementation for a 4 month period, yet an increase in natural killer cells were reported.[8] Another point of contention among the studies involved dosages. The studies reporting increase in cell counts used levels three times the amounts as the Garewel study had, somewhere around 180mg, or 300,000 IU, of beta carotene per day.

Regardless of the disparity involving the possible effect on CD4 cell counts, beta carotene has been shown repeatedly to be a potent antioxidant, preventing lipid peroxidation and cellular damage which seems increased in those infected with HIV. The use of beta carotene for strengthening the immune system lies in the function of vitamin A. Vitamin A is essential in maintaining the integrity of the epithelium(intestine & lung lining), the first barrier between outside invading organisms and the body's own internal system. By strengthening the mucosal layer (lining) of the GI tract, lungs and skin, the ability of the body to resist invading organisms increases. It could be argued that based on the simple assumptions that a) serum carotenoid levels are depressed in HIV infection, and b) vitamin A and carotenoids play a major role in the body's immune functioning, either as an antioxidant or epithelial stabilizer that the need for supplementation does exist. For those with HIV infection, the use of beta carotene at doses between 100,000 to 300,000 IU per day as a source of vitamin A is a safe and non-toxic approach . Much lower levels of pure vitamin A should be used to avoid liver toxicity; nothing exceeding 25,000 IU per day. Although no toxic doses are known, beta carotene has been shown to cause a change in skin pigment, an orange coloring of the palms and soles, in high doses. Those with certain conditions, hypothyroidism or diabetes may not be able to convert beta carotene in the GI mucosa, and therefore may experience a skin coloring change at lower doses.

Vitamin C

Vitamin C is a water-soluble vitamin. Like vitamin A and beta carotene, it has strong antioxidant properties. The role of vitamin C is an important one in the human body, imperative in what is known as hydroxylation reactions, or reactions that involve the removal and addition of water. These include the synthesis of steroid hormones, bile acids, carnitine, and proline. Carnitine is essential to help the body utilize and mobilize fats, a problem often seen in those infected with HIV. Proline, an amino acid, is unique to collagen. Without the synthesis of proline, the basic ground substance of collagen would not be formed properly, which occurs in scurvy. The collagen in the vascular system becomes weak and fragile, resulting in readily rupturing capillaries with diffuse bleeding. Proline is also necessary in the synthesis of dopamine, a potent neurochemical transmitter in the brain. Without proper dopamine synthesis, the adrenal glands would not be able to secrete norepinephrine, as dopamine is the precursor to norepinephrine and vitamin C is a cofactor in this pathway. This vitamin is also required by red blood cells for removing iron from its storage form in the body (ferritin) and making it available for hemoglobin synthesis.

The work of those who studied the effects of vitamin C on HIV is primarily based upon the information supporting the effectiveness of ascorbic acid in treating viruses. Vitamin C has been shown to inactivate a host of viruses upon exposure. Yet, at the same time, during active infection this nutrient is quickly depleted, thus increasing the body's need. In light of this, Harakeh and Jariwalla showed in their work that vitamin C can, in vitro, lead to a suppression of HIV.[9] However, they found that high levels of ascorbic acid and a prolonged duration, greater than 30 days, were necessary for the effect to occur. Once the dose was stopped, replication of the virus returned to pre-treatment levels. In 1994, Harakeh concluded that the effect of ascorbic acid on HIV was a post translational inhibition affecting enzymatic activity. This means the effect of vitamin C was not on direct replication of the virus, but on the activity of already replicated viruses. Once again, this was done in the lab and not done with human subjects.[10]

Regardless of its effect on HIV, vitamin C is a good candidate for supplementation. Its function as a powerful antioxidant is well established, as well as its need for maintaining proper hemoglobin concentration in the body. The work on increased levels of supplemented vitamin C upon the enzymatic activity of HIV may appear promising, but in vivo studies are warranted. The role of nutrition for the HIV-infected individual does not lie solely in its direct action upon the virus, but also upon its ability to stimulate the health and well being of the individual. One's ability to protect against opportunistic infections and maintain accurate functioning of all the body's systems, such as fat absorption and bile acid synthesis is essential. Without these two processes operating precisely, not only is digestion impaired, but the absorption of required nutrients is impaired as well. It has been shown that long term survivors have often taken between 12 - 30 grams of vitamin C per day in divided doses.[11] Bowel tolerance has often been the gauge for determining requirement and need. However, in those patients with GI complaints, it is often difficult to assess when vitamin C is affecting the softening and loosing the stools. When taking vitamin C, precautions should be given. First, the body's rate of absorption is often not greater than 1g hour, so divided doses are important. Second, if taking large doses, rebound scurvy can develop if the individual abruptly stops taking the vitamin.

Vitamin E

Vitamin E, like vitamin A, is another fat-soluble vitamin. Vitamin E is the name given to a group of compounds called the tocopherols, of which alpha tocopherol is the most important for human use. Tocopherols naturally occur in plants and can be found in vegetable oils such as wheat germ and cotton seed. Vitamin E can also be found in milk, eggs, fish, leafy green vegetables, meats and cereals. It is considered one of the most potent fat soluble antioxidants due to its ability to donate electrons, hence interfering with the damaging effects of the oxidation process. It has been shown to effectively reverse the likelihood of oxidation of red blood cells.[12] In addition to its antioxidant properties, vitamin E increases the immune response by increasing antibody and mitogen response, increasing phagocytic activity, and fostering host resistance to viral and infectious diseases.[13] Odeleye and Watson discuss how immune dysfunction in vitamin E deficiency is rarely seen since most healthy individuals receive the adequate amount of vitamin E. However, they report that with decreased levels of vitamin E a decrease in the responsiveness of the immune system is seen.[14]

Multiple studies have shown that in HIV-infected individuals, serum tocopherol levels are decreased. The variance in the literature involves the stage in which the levels go down. The majority of information supports the notion that serum vitamin E and tocopherol levels decrease in those who experience symptoms.3 Wang and Watson report that vitamin E should be considered for supplementation due to its ability to minimize the stimulation for replication of HIV. They discuss the concept that vitamin E can decrease serum levels of tumor necrosis factor alpha (TNF-a) and protein kinase C. TNF-a increases the activity of phospholipase A2. In monocytes, phospholipase A2 stimulates the replication of HIV. Protein kinase C activates the replication of HIV in lymphocytes, so a latent infection becomes active.[13] The study by Geissler demonstrates how vitamin E can reverse or minimize many of the damaging effects of AZT and other medications. AZT inhibits blood cell production in the bone marrow, thus resulting in low white blood cell counts and anemia. In vitro studies suggest that this can be reversed with supplementation of Vitamin E.[15]

As can be seen from an evaluation of the literature and from an understanding of the basic physiological activities of vitamin E, supplementation would be beneficial in the immune-compromised individual. If the individual is on AZT or other pharmacological agents that incite the generation of free radicals, vitamin E is further warranted. Toxicity of this vitamin is not well researched and at present no known toxic levels are established. It has been reported that transient GI discomfort is possible in those taking megadoses. In those with rheumatic heart disease, vitamin E in high doses is contraindicated.[16] In the April 1991 edition of the Journal of American Dietetics Association, the debate over accepted dosages ranged from 300 mg per day to 800 mg per day, with the majority of studies being conducted using this range without complications. Again, vitamin E is a potent antioxidant with multiple benefits for strengthening the immune system and should be considered in a comprehensive supplement protocol.

Selenium

When supplementing with vitamin E, one should always consider selenium. These two nutrients act synergistically. Selenium is essential in another antioxidant pathway, that involving the glutathione peroxidase enzyme. Glutathione is a compound comprised of the amino acids L-cysteine, L- glutamine, and glycine. This enzyme splits glutathione into oxidized glutathione and water. This is done by utilizing H2O2 (perioxidase) and other hydroperoxides. For this enzyme to function properly, selenium is needed as a cofactor. In selenium deficiency, the enzyme fails to function properly, and hence increased free radical damage can ensue. Deficiencies have been linked to an increased risk of cancers of many forms: colon, lung, prostate, and skin, to name a few. In the review of the studies on selenium, Schrauzer reports that many viral conditions have been protected against by the use of supplemental selenium.[17] This study mentions that selenium in decreased amounts has been shown to effect the immune system's antibody response by lowering it. Additionally, the rate of the hepatitis infection was decreased by selenium supplementation. In light of this information, these authors conclude that selenium's antioxidant and immune-modulating activity might not rest solely with its glutathione activity. Vitamin E and selenium work in conjunction with one another as both are essential in blocking the rate of lipid peroxidation. These two nutrients have often been given together for a variety of conditions, such as angina and breast cancer.

Many authors report decreased serum selenium levels in those who have HIV and are symptomatic. The studies reviewed for this article showed that selenium had a positive effect when supplemented. Although increase in CD4 counts occurred during the studies, improvements were many: less severity of GI disturbances, less diarrhea and cramping, maintenance of weight, improvement of epithelial conditions (skin) and less frequency of illnesses.[17,18,19] Selenium supplementation is well tolerated, dosages in these studies ranged from 100 to 400 g per day, suggesting that selenium can easily be added to any treatment protocol. Cirelli concludes that selenium should be supplemented as early as possible.

NAC is a sulfur-containing amino acid. This nutrient has a history of use in bronchitis sufferers for its mucous dissolving properties. NAC has the ability to thin the mucous and allow better respiration, which can also be advantageous for those dealing with secondary infections. NAC has been shown to have an effect upon HIV replication. One potential rationale for this again involves glutathione. In HIV, decreased plasma and monocyte levels of glutathione and cysteine have been reported.[20] The NIH has demonstrated that levels of glutathione in the serum have been shown to be decreased by 70% and in the epithelium of the lung by 40%. The theory is that supplementation of NAC can restore glutathione levels. NAC has been observed to raise glutathione levels by acting upon TNF. Remember that TNF-a leads to increased phospholipase A2 activity, which in turn stimulates the replication of HIV in monocytes. However, this has not been seen across all studies. Another possibility is that NAC's antioxidant activity is responsible for its action. Despite the mechanism involved, NAC exerts an effect upon the replication of HIV in vitro. Thus, NAC helps decrease virus and mucous production in the lungs.[3,21,22] Like selenium, studies have not shown any adverse effects for supplementation, so this supplement can easily be added for maximal nutritional benefit to one's regime.

A discussion of nutrition and HIV would not be complete without the mention of the health of the digestive tract. For any individual with compromised immunity, the state of the digestive organ, one of the major sites of interaction between self and the external world, is paramount. For food to become fuel, proper digestion and absorption is rudimentary. This involves accurate movement of food through the tract, sufficient digestive enzymatic activity, intact lining of the mucosa permitting accurate absorption, and proper elimination. When these functions are not in balance, symptoms such as diarrhea, weight loss, and bloating are seen. MacDonald and Spencer point out that evidence exists that activated T cells in the GI mucosa have a pivotal role in enteropathies (intestinal illnesses). Studies show that HIV alone, and not opportunistic infections, may be responsible for some GI complaints. Marsh and Cummins have shown that those with HIV have similar findings, although to a lesser extent, to the changes seen in celiac disease.[24] Several authors have suggested gluten-free diets, citing the similarities of the mucosa of these two conditions. In a November 15, 1990 letter in Annals of Internal Medicine, Dr. Ruiz-Arguelles discussed his success with a gluten-free diet for individuals with HIV who had diarrhea and malabsorption problems.25 His clinical trials have proven effective in 93% of individuals. This is not to suggest that those with GI dysfunctions and HIV have celiac disease or a gluten allergy. What can be inferred from this information is that many people with HIV and with GI complaints need to consider diet to facilitate their immunity. By avoiding gluten and possibly some other food sources (namely dairy, corn, and sugar), in times of acute distress, the individual can possibly do much in the way of healing the intestinal lining, reducing inflammation and reactivity of the food, thereby improving absorption of the nutrients from food as well as supplements. In a clinical trial performed at Bastyr University by Dr. Guiltinan, a diet free of wheat and dairy was utilized in addition to the supportive measures focused at regenerating a healthy GI system and decreasing intestinal permeability. People in the study improved though it was not conclusive that elimination of wheat and dairy was responisble for the results.

Nutritional supplementation can be an effective and beneficial treatment addition for those with HIV. Individuals should be just as selective of their food and dietary intake as they are regarding the pills they put into their body. The supplements listed above can easily be included in any existing plan. The benefits of these supplements will not solely be isolated to the HIV infection. As mentioned above, many of these have a direct effect upon the intestinal tract and its integrity, and should be used with the goals of improving health.

Brad Lichtenstein is a fourth year student at Bastyr University and has been working as a student clinician in the Natural Health Clinic for two years.

BIBLIOGRAPHY

1. Gramlic, L. M. and Mascioli, (1995). Nutrition and HIV Infection. Nutritional Biochemistry 6, p. 2-11.

2. Baum, M., et al., (1994). Inadequate Dietary Intake and Altered Nutrition Status in Early HIV-1 Infection. Nutrition 10, p. 16-20.

3. Favier, A. et al., (1994) Antioxidant Status and Lipid Peroxidation in Patients Infected with HIV. Chemico-Biological Interactions 91, p. 165-180.

4. Schrauzer, G. N. et al. (1994). Selenium in the Maintenance and Therapy of HIV-Infected Patients. Chemico-Biological Interactions 91, p. 199-205..

5. Coodley, G.O. et al., (1993) Beta-Carotene in HIV Infection. Journal of Acquired Immune Deficiency Syndromes 6, p. 272-276.

6. Coodley, G.O. (1991) Beta Carotene Therapy in Human Immunodeficiency Virus Infection. Clinical Research 39, p. 634.

7. Alexander, M. et al., (1985) Oral Beta Carotene Can Increase the Number of OKT4+ Cells in the Human Blood. Immunological Letters 9, p. 221-224.

8. Garewal, H.S. et al., (1992) A preliminary Trial of Beta Carotene in Subjects Infected with Human Immunodeficiency Virus. Journal of Nutrition 122, p. 728-732.

9. Harakeh, S. and Jariwalla, R. J. (1991) Comparative Study of the Anti-HIV Activities of Ascorbate and Thiol-Containing Reducing Agents in Chronically HIV-Infected Cells. American Journal of Clinical Nutrition 54, p. 1231S-1235S.

10. Harakeh, S., Niedzwiecki, A. and Jariwalla, R. J. (1994) Mechanistic Aspects of Ascorbate Inhibition of Human Immunodeficiency Virus. Chemico-Biological Interactions 91, p. 207-215.

11. Badgley, L. (1987). Healing AIDS Naturally. p. 112-114.

12. Oski, F.A. and Barness, L.A. (1967). Vitamin E Deficiency: A Previously Unrecognized Cause of Hemolytic Anemia in Premature Infant. Journal of Pediatrics 70, p. 211-215.

13. Wang, Y. and Watson, R.R. (1993) Is Vitamin E Supplementation A Useful Agent in AIDS Therapy? Progress In Food and Nutrition Science 17, p. 351-375.

14. Odeley, O.E. and Watson, R.R. (1991) The Potential Role of Vitamin E In the Treatment of Immunologic Abnormalities During Acquired Immune Deficiency Syndrome. Progress in Food and Nutrition Science 15, p. 1-19.

15. Geissler, R.G. et. al. (1994). In Vitro Improvement of Bone Marrow-Derived Hematopoietic Colony Formation in HIV-Positive Patients by Alpha-D-Tocopherol and Erythropoietin. European Journal of Haematology. 53. p. 201- 206.

16. Gerber, J.M. Handbook of Preventive and Therapeutic Nutrition. Aspen Publication, Gaithersburg, Maryland. 1993.

17. Schrauzer, G. N. et al. (1994). Selenium in the Maintenance and Therapy of HIV-Infected Patients. Chemico-Biological Interactions 91, p. 199-205.

18. Dworkin, B.M. (1994). Selenium Deficiency in HIV Infection and the Acquired Immunodeficiency Syndrome. (AIDS). Chemico-Biological Interactions 91, p. 199-205.

19. Cirelli, A. et al. (1991). Serum Selenium Concentration and Disease Progress in Patients with HIV Infection. Clinical Biochemistry 24, p. 211-214.

20. Buhl, R. et al. (1989). Systemic glutathione Deficiency in Symptom-Free HIV-Seropositive Individuals. Lancet. ii. p.1294-1298.

21. Kalebic, T. and Schien, P.S. (1994). Organic Thiophosphate WR-151327 Suppresses Expression of HIV in Chronically Infected Cells. AIDS Research and Human Retroviruses 10. p. 727-733.

22. Simon, G. et al. (1994). Effects of Glutathione Precursors on Human Immunodeficiency Virus Replication. Chemico-Biological Interactions 91. p. 217-224.

23. MacDonald, T.T. and Spencer, J. (1988) Evidence That Acitvated Mucosal T Cells Play a Role in the Pathogenesis of Enteropathy in Human Small Intestines. Journal of Experimental Medicine 167. p. 1341-1349.

24. Marsh, M.N. and Cummins, A. G. (1993). The Interactive Role of Mucosal T Lymphocytes in Intestinal Growth, Development and Enteropathy. Journal of Gastroenterology and Hepatology 8, p. 270-278.

25. Ruiz-Arguelles, G. J. (1990), Gluten-Free Diet for AIDS-Associated Enteropathy. Annals of Internal Medicine, 113. p. 806-807.

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