Influence of HIV Infection on Vitamin Status and Requirements" M. K. BAUM,b.rG. SHOR-POSNER," P. BONVEHI,b I. CASSETTI,' Y. LU," E. MANTERO-ATIENZA,b R. s. BEACH,' AND H. E. SAUBERLICH~ bDepartment of Epidemiology and Public Health Uniuersity of Miami School of Medicine 1029 NW 15th Street Miami, Florida 33136 'Brownrd General Medical Center Neonatology Division Ft. Lauderdale, Florida 33316 dDiuision of Experimental Nutrition Department of Nutrition Sciences University of Alabama at Birmingham Birmingham, Alabama 35294

INTRODUCTION Malnutrition and wasting are prominent features of the later stages of HIV-1 infection, the acquired immunodeficiency syndrome (AIDS).1-3 In addition to generalized protein-energy malnutrition, AIDS patients exhibit alterations in a number of specific nutrients4-'0 that appear to be related to the degree of wasting and malnutrition evidenced in anthropometry and body composition ~ t u d i e s . ~A, ~ ' variety of gastrointestinal manifestations are involved in the pathogenesis of the dramatic weight loss and the nutritional changes associated with AIDS. Mucosal damage and resulting malabsorption and diarrhea may occur through the direct effects of HIV-I infection on the gut as well as through opportunistic infections, malignancies, and possibly HIV-1-related enteropathy.12 All of these conditions, in addition to poor dietary intake in HIV- 1-infected patients, have readily apparent consequences for host nutritional status. Once occurring, malnutrition leads to immunosuppression, infection, and rnucosal damage, with failure of normal intestinal mucosal turnover and healing, resulting in further ma1n~trition.l~ Investigation of the precise nature and characteristics of the wasting and malnutrition associated with the more advanced stages of HIV-1 infection has revealed that even in patients who have not lost considerable amounts of body weight, a significant alteration in total body potassium, which is known to be a surrogate indicator of change in total lean mass, re suit^.^ Moreover, the degree of depletion appears to be related to mortality, with those patients suffering from the greatest

This work was supported by NIMH Grant #lPSOMH42555 (M. K. Baum), Fogarty lnternational Training Grant #5D43 TWO0017 (M. K. Baum), and RCDA Grant #KO4 HL01862 NIH (M. K. Baum). Send correspondence to M. K. Baurn, Department of Epidemiology and Public Health, University of Miami School of Medicine, P.O. Box 016069 (R-669), Miami, Florida 33101. 165

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degree of wasting, experiencing the highest and the most rapid rate of m0rta1ity.l~ Of particular interest, this process has been shown to be reversed by nutrient and calorie rep1eti0n.I~ Although nutritional factors are not likely to be the most important etiological determinants, they may influence initial susceptibility to HIV- I infection and have a significant impact upon the rate and form of disease expresion.

NUTRITIONAL STATUS IN EARLY HIV-1 INFECTION Although severe wasting and malnutrition are frequent components of the later stages of HIV-I infection, it is doubtful that such changes occur precipitously. Our research group has focused on the impact of nutritional status on immune status, disease progression, and neuropsychological function during the early stages of HIV-I disease. The study population was composed of 112 HIV-1 seropositive homosexual men, ranging in age from 20-50 years. HIV-1 seropositivity was determined by ELISA and confirmed by Western blot.16 At the entry into the study. the majority of subjects were asymptomatic, other than generalized lymphadenopathy, and did not have any other risk factors for HIV-I transmission, such as intravenous drug use. None of the participants had a significant past medical history that could influence nutritional status, and no one was enrolled in antiviral chemotherapy protocols at the baseline evaluation. Nutritional status was evaluated by biochemical, dietary, anthropometric, and clinicA assessments. The biochemical determinations included measurements of serum proteins, vitamins, and trace elements in blood. Use of illicit drugs was determined by urine toxicology. The dietary assessment consisted of a semiquantitative food frequency questionnaire, validated by 24-hour recalls and four-day diaries in a subsample of participants. Anthropometric evaluations included measurements of height, weight, ponderal index, left arm circumference, arm muscle, and arm fat areas. Immunological assessment included measurements of lymphocyte subpopulations (CD4), immune activation (beta,-microglobulin), natural killer (NK) cell function, and lymphocyte proliferation in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). Cognition was evaluated using a battery of tests designed to measure a wide range of cognitive processes, including information processing speeds, visuospatial processes, language, memory, attention, and psychomotor reaction times. Psychosocial measures consisted of the Profile of Mood States (POMS) and Millon Clinical Multiaxial Inventory (MCMI 11) scale.

ALTERED NUTRITIONAL PROFILE IN EARLY HIV-1 INFECTION The results of these studies have indicated that despite adequate or even excessive dietary intakes of nutrients, 67% of the HIV-I seropositive participants had at least one biochemical deficiency, 36% had multiple biochemical abnormalities, and the proportion of participants with biochemical nutritional abnormalities increased over No clinical signs and symptoms of nutritional deficiencies, however, were observed during this early stage of HIV-1 infection. Only a small percentage of the HIV- 1-infected men (17%) experienced changes in anthropometric measures, including body mass index and triceps skinfold thickness along with

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a loss in body weight. Serum retinol-binding protein levels were depressed in many of these subjects, who did not demonstrate anthropornetric evidence of malnutrition, suggesting that this measure may be a sensitive indicator of early signs of maInutrition.I9 Alterations in nutritional status, as shown in FIGURE 1, were widespread among the HIV-1 seropositive men. A large proportion (30%) of the seropositive participants had inadequate vitamin B, status (activity coefficient > 1.85). Decreased plasma vitamin B,, levels (< 200 pg/mL) were observed in 11% of the HIV1-infected men. Sixteen percent of the subjects had vitamin A inadequacy (< 0.30 pg/dL plasma), and 20% of this group had vitamin E inadequacy (< 5 pg/mL plasma). Low plasma zinc levels (< 0.75 pg/mL) were documented in 30% of the

-

0 Vitamin

86

Vitamin 612

Vitamin

Vitamin

A

E

Zinc

FIGURE 1. Inadequate vitamin B, status and low plasma levels of vitamins Biz, A, and E, and zinc were exhibited in a large proportion of the HIV-I-seropositive homosexual men (n = 112).,

HIV-1-infected subjects. Other nutrient values, including plasma levels of iron, folate, vitamin C, and status of vitamins B, and B,, were within the normal range in the majority of the men.I7

ALTERED NUTRITIONAL STATUS AND IMMUNE FUNCTION IN EARLY HIV-1 INFECTION The nutritional alterations observed in the early stages of HIV-1 infection are of particular concern, as vitamins and trace elements have been demonstrated

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repeatedly to influence immunological function.*OOur recent studies indicate that vitamin B, status has a significant impact upon the functional parameters of immunity in HIV-I-infected subjects.21 Our investigation has revealed a significant multivariate relationship between vitamin B, status over the entire range of vitamin B, values, and lymphocyte proliferation response to mitogens phytohemagglutinin and pokeweed, and N K cytotoxicity. In addition, when vitamin B, status was treated as a categorical variable, all three functional measures of immunity were, as a \et, significantly lower in vitamin B,-deficient HIV-I-infected participants than in those with adequate status. Altered selenium status has also been shown to be associated with impairment of immune function during the early stages of HIV-I disease.?, Our findings indicate low levels of selenium in plasma appear to affect T cell-dependent immune function and N K activity, whereas elevated plasma selenium levels seem to influence the humoral response by decreasing immunoglobulin titers. In other studies, deficiency of the trace element zinc has been associated with impaired phagocytic function as well as cellular and immune d y s f ~ n c t i o n . ~Our ~.?~ preliminary analyses” indicate that low levels of plasma zinc are associated with alterations in lymphocyte response to mitogens and CD4 cell count in HIV-l-infected individuals. Longitudinal autoregression analysis revealed significant associations between lymphocyte blastogenesis and levels of plasma zinc measured six months previously (p < 0.01). When zinc levels were normalized, a marked increase in CD4 cell number (p < 0.05), and blastogenesis in response to mitogens phytohemagglutinin as well a5 pokeweed (p < 0.05), was Our preliminary studies also indicate a particularly strong relationship between vitamin B,, status and measures of disease progression.26 Analysis of longitudinal changes in plasma vitamin B,? levels, from biochemically deficient to adequate, or from adequate to deficient status, revealed significant associations with CD4 cell number in the same direction (p < 0.009). A similar significant relationship was also observed between vitamin BIz and the AIDS index (p < 0.005). The AIDS index is a composite of CD4 cell number and beta,-microglobulin and is considered to be a useful marker of disease p r o g r e ~ s i o nImprovement .~~ of low plasma vitamin B,, levels (< 200 pg/dL) to adequate levels during the course of the study was associated with a stable CD4 cell number count (p < 0.017) and AIDS index (p < 0.017). Continuing vitamin B,, deficiency over time was associated with a steeper slope of decline in CD4 count and AIDS index. Thus, whereas persisting vitamin B,, deficiency was associated with disease progression, normalization of plasma vitamin B,, levels was associated with a stable CD4 cell number and AIDS index over time.26 NUTRITION AND COGNITION

Our studies in early HIV-I infection have demonstrated an important role for nutritional status in cognitive function. Vitamin B,, status appeared to be particularly important in maintaining cognitive performance, as levels of vitamin B,, were associated with measures of information processing speed and visuospatial problem-solving As reflected by low plasma vitamin B,, levels, vitamin B , , deficiency appeared to account for a significant portion of the delay in the speed of retrieving highly overlearned name codes, and in the speed of visual scanning and discrimination. These findings suggest that concurrent vitamin B,, deficiency may be a cofactor in subtle cognitive changes observed during the early stages of HIV-I infection.

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Inadequate vitamin B6 status may also be an important factor in neurological dysfunction. Our preliminary findings have demonstrated significant associations between vitamin B, status and measures of cognition involving reaction time in HIV-1-infected subjects.30 Specifically, a decline in vitamin B, status over time was significantly associated with less improved or stable response time to a twochoice reaction time task, and to the nonsearch (zero intercept) of the Sternberg short-term memory search task. By contrast, when vitamin B6 status remained adequate, the reaction time on these tests improved over time. Psychosocial measures from the profile of mood states (POMS), specifically tensiordanxiety, were also significantly related to vitamin B, ~ t a t u s . ~Moreover, ' normalization of vitamin B, status was associated with a significant decrease in the POMS scale of depression (p < 0.02). It should be noted that these findings are the result of a longitudinal observational study and do not imply causality, but rather strong associations. Only a controlled clinical trial of vitamin/mineral supplementation will be able to determine whether normalizing nutrient status can affect brain function and/or slow disease progression.

NUTRITIONAL STATUS/DIETARY INTAKE IN EARLY HIV-1 INFECTION The above findings indicate that nutritional status may influence immune status and cognitive function, suggesting that nutritional manipulation may help to maintain physiological and functional integrity of the systems affected by HIV-I infection. In order to derive recommendations for dietary intake of nutrients, consistent with normal plasma levels in early HIV-1 infection, we have evaluated nutritional status in relationship to patterns of intake in HIVI-infected individuals. Our earlier studies indicated that dietary changes occur at the time of HIV-I seropositivity diagnosis, with participants decreasing their consumption of animal products and alcohol and increasing their intake of vegetables and vitamin/mineral s ~ p p l e m e n t s .The ~ ~ overall dietary patterns following diagnosis are more consistent with the recommendations for reducing the risk of coronary heart disease than patterns observed prior to diagnosis. In the absence of HIV-I dietary guidelines from the scientific community, other than to maintain a balanced diet and consume nutrients in the levels of recommended dietary allowances (RDA)," the HIV- I-positive patients often turn to recommendations for the prevention of other diseases3* and frequently, in desperation, to unorthodox therapies.34 Analysis of dietary intake patterns has revealed that the majority of HIVI-seropositive individuals generally consume dietary amounts that are equal to, or greater than, the RDA for the various nutrients. Consummatory patterns are shown in TABLE1, which indicates that most subjects consumed at least the RDA, and many consumed more than the RDA for vitamins B,, B,* and A. A significant proportion of individuals consumed less than RDA amounts, however, of vitamin E and zinc. The majority of the HIV-1-infected participants consumed dietary supplements of specific nutrients. Despite the high intake, nutritional inadequacies were prevalent, nevertheless, among the HIV-1-infected men. TABLE2 indicates the proportion of participants with inadequate plasma levels in relationship to nutrient consumption at various RDA levels. Intake of vitamin B6 was associated

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TABLE 1. Consummatory Patterns in HIV-1-Positive Participants' Nutrientsb Vitamin B6 (2 mglday) Vitamin BI2 (2 &day) Vitamin A (3300 1U/day) Vitamin E (10 mgiday) Zinc (15 mglday)

< RDA RDA 2-5

X

RDA 6-10

X

RDA

11-25 x RDA

S-25 X RDA

6%

31%

46%

5%

2%

9%

0%

4%

30%

31%

24%

12%

0%

5%

42%

31%

19%

3%

14%

19%

32%

2%

3%

31%

25%

38%

22%

14%

1%

0%

Indicated is the proportion of HIV-1-seropositive participants (n = 112) with intake at various levels of the RDA. Value in parenthesis is the RDA for that nutrient.

'

with inadequate nutritional status in 56% of the men who consumed vitamin B, at the RDA level; 21% of those who consumed 2-5 times RDA vitamin B6 had inadequate status, and even some (3 out of 6) of those who consumed 6-10 times RDA had inadequate vitamin B6 status. Regarding vitamin B,, status, only those HIV-1-infected individuals consuming more than 25 times RDA demonstrated adequate vitamin B,, levels. Little evidence of biochemical deficiency was observed in HIV-I-seropositive men consuming 11-25 times RDA for vitamin A, although some participants with inadequate vitamin A status consumed even greater amounts of this nutrient. Consumption of vitamin E a t 2-5 times RDA was associated with adequate status in 27 out of 29 subjects. Inadequate vitamin E status was observed, however, in a small proportion of subjects (7%) who consumed vitamin E at levels > 25 times the RDA. The majority of HIV-1-infected men consuming 6-10 times the RDA for zinc had adequate zinc status. Thus, when the dietary intake of these nutrients was high, there was little evidence of biochemical inadequacy. Moreover, correlations between intake and plasma levels of nutrients indicated that plasma levels were

TABLE 2.

Inadequate Plasma Levels in Relationship to Dietary Intake" RDA 2-5 x RDA 6-10 X RDA 11-25 x RDA > 25 x RDA

Nutrients'

Vitamin B, (2 mg/day) Vitamin B,z (2 @g/day) Vitamin A (330 lU/day) Vitamin E (10 mglday) Zinc ( I5 mg/day)

18/32 (56%) 114 (25%) 1/3 (33%) XI 19 (42%) 10136 (28%)

10148 (21%) 613 I (19%) 9/43 (21%) 3/29 (10%)

6124 (25%)

316 (50%) 2/32 (6%)

1/32 (3%) 1/2 (50%) 1/13 (8%)

012 (0%) 4/26 (15%) 3/18 ( 17%) 0/3 (0%) l/l (100%)

0110 (0%) 0/13 (0%) 113 (33%) 2/30 (7%)

-

-

Given is the proportion of HIV-1-seropositive men (n = 112) with inadequate plasma nutrient levels at various levels of dietary intake. Value in parenthesis is the RDA for that nutrient. "

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significantly associated, at least in part, with dietary intake, which has important implications for dietary intervention strategies. The presence of abnormal nutrient blood values despite high levels of supplementation indicates the possible involvement of additional factors, including malabsorption and altered metabolism or excretion. The maintenance of adequate nutrient blood levels during the early stages of HIV-1 disease appears to require intakes above the RDA for vitamins B,, B,,, A, E, and zinc. The elevated doses that were compatible with adequate plasma nutrient levels were not associated with toxic effects. There are some concerns, nevertheless, that supplementation with high doses may produce adverse eff e c t ~ , indicating ~ ~ - ~ ~ the need for monitoring of blood levels when nutritional support is provided. As nutritional status may have a significant influence on disease processes, critical studies are urgently needed to determine whether restoration of adequate nutrient levels can be associated with improved cognitive function and slower HIV-1-disease progression. REFERENCES 1.

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6. 7. 8. 9. 10. 11. 12. 13.

14.

MALEBANCHI, R., E. ARMOUX, J. M. GUERINe r a / . 1983. Acquired immunodeficiency syndrome with severe gastrointestinal manifestation in Haiti. Lancet 11: 873877. D., R. D. MURGERWA, N. K. SEWANKAMBO et a / . 1985. Slim disease: SERWADDA, New disease in Uganda and its association with HTLV-Ill infection. Lancet 2: 849-852. KOTLER,D. P., J. WANG& R. N. PIERSONJR. 1985. Body composition studies in patients with the acquired immunodeficiency syndrome. Am. J. Clin. Nutr. 42: 1255-1265. FALUTZ,T., C. TSOUKAS& P. GOD. 1988. Zinc as a cofactor in human immunodeficiency virus-induced immunosuppression. J. Am. Med. Assoc. 259: 28502851. N., E. MOCCHEGIANI, M. GALLI& A . LAZZARIN. 1988. AIDS, zinc deficiency, FABRIS, and thymic hormone failure. J. Am. Med. Assoc. 259: 839-840. J. D., H. C. MILLARD & P. B. JOHNSON. 1988. Zinc in human immunodeSHOEMAKER, ficiency virus infection. J. Am. Med. Assoc. 260: 1881-1882. DWORKIN,H. B., W. S. ROSENTHAL, G. P. WORMSER & L. WEISS. 1986. Selenium deficiency in the acquired immunodeficiency syndrome. J. Parenter. Enteral Nutr. 10: 405-407. SMITH,J., D. W. HOWELLS,B. KENDALet a / . 1987. Folate deficiency and demyelination in AIDS. Lancet 2: 215. R. L., H. COHEN,M. KRAILOer a / . 1987. Low serum cobalamin levels occur BURKES, frequently in the acquired immunodeficiency syndrome and related disorder. Eur. J. Haematol. 38 141-147. HARRIMAN, G. R., P. D. SMITH,M. K. HORNEef a / . 1989. Vitamin B12malabsorption in patients with acquired immune deficiency syndrome. Arch. Intern. Med. 149: 2039-204 I . BRINSON,R. R. 1985. Hypoalbuminemia, diarrhea and the acquired immunodeficiency syndrome. Ann. Intern. Med. 102: 413. 1990. Nutritional aspects of AIDS. Annu. Rev. KEUSCH,G. T. & J. G. FARTHING. Nutr. 10: 475-501. T. K. & R. R. WATSON.1989. The AIDS-immunocompetence-nutriLEONARD-GEEN, tion-infection cycle. I n Cofactors in HIV-1 Infection and AIDS. R. R. Watson, Ed.: 187. CRC Press, Inc. Boca Raton, FL. JR. 1989. Magnitude of KOTLER,D. P., A. R. TIERNEY,J. WANG& R. N. PIERSON body cell mass depletion and the timing of death from wasting in AIDS. Am. J. Clin. Nutr. 50: 444-447.

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R. FERRARO el a / . 1991. Enteral alimentation and 15. KOTLER,D. P., A. R . TIERNEY, repletion of body cell mass in malnourished patients with acquired immune deficiency syndrome. Am. J. Clin. Nutr. 53: 149-154. & R. C. GALLO.1984. M. G., M. POPOVIC,L. BRACH,J . SCHUPBACH 16. SARNGADHARAN, Antibodies reactive with human T-lymphotragic retroviruses (HTLV-111). Science 224: 506-507. G. SHOR-POSNER ef a / . 1992. Specific nutrient 17. BEACH,R. S., E. MANTERO-ATIENZA, abnormalities in asymptomatic HIV-1 infection. AIDS 6: 701-708. J. J., G. SHOR-POSNER, E. MANTERO-ATIENZA, R. S. BEACH& M. K. BAUM. 18. JAVIER, 1990. Nutritional abnormalities associated with HIV infection. Neuroscience (Abst) 16: 614. 19. MANTERO-ATIENZA, E., R. S. BEACH,M. A. FLETCHER et a / . 1989. Measures Of nutritional status in early HIV infection. Arch. AIDS Res. 3: 275-285. M. E., R. S. BEACH& L. S . HURLEY.1985. Nutrition and Immunity. 20. GERSHWIN, Academic Press. Orlando, FL. G . SHOR-POSNER et a / . 1991. Association of 21. BAUM,M. K., E. MANTERO-ATIENZA, vitamin BAstatus with parameters of immune function in early HIV-1 infection. J. AIDS 4: 1122-1132. E.. M. C. GAVANCHO-SOTOMAYOR, G. SHOR-POSNER et a / . 1991. 22. MANTERO-ATIENZA. Selenium status and immune function in asymptomatic HIV-I seropositive men. .~ Nutr. Res. 11: 1236-1250. P. J.. M. E. GERSHWIN. R. A. GOOD& 0. PRASAD.1986. Interrelationships 23. FRAKER. between zinc and immune function. Fed. Proc. Fed. Am. SOC. Exp. Biol. 45: 1474. S . , R. S. BOCKMAN, A. LINef d.1990. Physiological and 24. CUNNINGHAM-RUNDLES, pharmacological effects of zinc on immune response. In Micronutrients and Immune Functions. A. Bendich & R. K. Chandra, Eds.: Annals of the New York Academy of Sciences. New York. 587: 113-122. E. MANTERO-ATIENZA ef a / . 1991. Effect ofzinc normalizaR. S., C. CABREJOS, 25. BEACH, tion on immunological function in early HIV-I infection. VII Int. Conf. on AIDS. MC 3128, 330. ef a / . 1991. Predictors of change 26. BAUM.M. K.. R. S . BEACH.E . MANTERO-ATIENZA in immune function: Longitudinal analysis of nutritional status in early HIV-I infection. VII. Int. Conf. on AIDS. MC 3127, 329. J. L., J. M. G. TAYLOR, R. DETELSet a/. 1990. The prognostic value ofcellular 27. FAHEY, and serological markers in infection with human immunodeficiency virus type 1. N. Engl. J. Med. 322: 166-172. 28. BEACH,R. S., R. MORGAN & F. WILKIE.1992. Plasma cobalamin levels as a potential cofactor in studies of HIV-I related cognitive changes. Arch. Neurol. (Chicago) 49: 501-506. E., M. K. BAUM,R. MORGANet a / . 1991. Vitamin B12in early 29. MANTERO-ATIENZA, human immunodeficiency virus 1 infection. Arch. Int. Med. 151: 1019-1020. E. MANTERO-ATIENZA e r a / . 1991. Association of vita30. WILKIE,F., G. SHOR-POSNER, min B6 status and reaction time in early HIV-I infection. Neuroscience of HIV Infection. Int. Conf. on Neuroscience of HIV Infection. Padova, Italy. Abst. 67. G., N. BLANEY, D. FEASTER ct a / . 1992. Anxiety and depression in 31. SHOR-POSNER, early HIV-I infection and its association with vitamin B6 status. VIII Int. Conf on AIDS. POB 3711, 209. E., M. K. BAUM,J. J. JAVIER e t a / . 1991. Nutritional knowledge, 32. MANTERO-ATIENZA, beliefs and practices in the HIV infected patient. Nutr. Res. 11: 33-40. 33. WINICK,M., R. I. ANDRASSAY, D. ARMSTRONG et a / . 1989. Guideline for nutrition support in AIDS. Nutrition 5: 39-46. D. & A . GALVIN.1989. Nourishing the HIV-1 infected adult. Holistic Nurs. 34. RAKOWER, Practice 4: 26-37. 35. CHANDRA, R. K. 1984. Excessive intake of zinc impairs immune responses. J. Am. Med. Assoc. 252: 1443-1446. 36. COHEN,M. & A. BENDICH.1986. Safety of pyridoxine-a review of human and animal studies. Toxicol. Lett. 34: 129-139.

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37. BENDICH, A. & L. LANGSETH. 1989. Safety of vitamin A. Am. J. Clin. Nutr. 4 9 358-371.

H. K. 1989. Comparative assessment of the toxicology of vitamin A and 38. BIESALSKI, retinoids in man. Toxicology 57 117-161.

DISCUSSION D. ROE(Cornell University, Ithaca, N Y ) : Do you see any relationship between the vitamin status of these persons and their intake of drugs? M. K. BAUM(Uniuersity of Miami, Miami, FL): We recently had an article published in the Journal of AIDS showing that patients who consume AZT are at a risk for zinc deficiency. There was a significant decrease in levels of zinc in persons who were taking AZT. Those with decreased levels of zinc did not respond to the mitogens as opposed to those who had normal zinc. UNIDENTIFIED SPEAKER: In your reference to toxicity, did you refer to toxic levels or toxic symptoms? BAUM:Toxic symptoms. In particular, we saw patients who were taking 100 times the RDA for vitamin A and had hypertriglyceridemia. When they stopped taking the vitamin A for six months, they did not have the hypertriglyceridemia anymore. J . LEKLEM (Oregon State University, Corvallis, OR): What did you use to assess vitamin B,? BAUM:Erythrocyte transaminase. LEKLEM: I think that it is not a very sensitive indicator. Another question has to do with the population that was taking vitamin B,. Were they taking only vitamin B6, or were they taking other vitamins along with the B,? BAUM:It varied. This was an observational study. We were not able to intervene at all. Some people were taking multiple supplements; some people were taking single supplements. Mostly, however, they were taking multiple supplements. LEKLEM: So there is really no way to distinguish the effect of one vitamin or the other on some of the indices that you were measuring. Is that correct? BAUM:That's correct, other than in the statistical analyses where we always controlled for the other nutrients. LEKLEM: I think that we have to be very cautious about making recommendations to increase the intake of vitamins as you've done with multiple vitamins. First, trying to understand whether the subjects, in fact, are taking those vitamins and then whether they're taking them on a regular basis makes these kinds of studies very difficult. BAUM:I agree. L. C. ABBEY(East Windsor, N J ) : What effects did you see from vitamin supplementation? BAUM:Let me again explain that we did not give supplements to these participants-they took supplements themselves, and we tried our best to find out what they were doing. We then looked statistically at how, over time, the levels of nutrients were associated with immunity and the other factors that were studied. We told the participants when they had deficient levels, and still only about half of the ones that were told took supplements. That allowed us to make a comparison

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between those who remained vitamin-deficient and those that became supplemented. Even though our group was small, we saw very strong statistical differences. ABBEY:Were the differences in a positive direction for those with supplements? BAUM:Yes. F. COLBY ( N e w Yurk, N Y ) : I didn't hear any information about the composition of your cohort. How representative were they of the homosexual community, relative to socioeconomic status, race, and alcohol consumption? BAUM:We have been recruiting from the screening clinics of Margaret Fischl, where she sees several thousand patients a year. Second, we have information on alcohol intake, and we have toxicology screens at all visits as well as smoking information. All of this is always controlled for in the analyses. For example, the vitamin B, results were published in the November issue of the Journal o f A l D S , and controlling for alcohol was extremely important in those analyses. COLBY:How about prohibited substances, such as marijuana? BAUM:We have them on the toxicological screens, and if a subject uses them again, that is entered into the analysis. That's the only way we are using this information. L. BENITEZ(Uniuersity of Mexico, Mexico Ciry): Do you think nutritional status in some way influences infectivity with the HJV virus? BAUM:The only kind of information we have is with the HIV-negative cohort. There was a tremendously high prevalence of low levels of copper in this group. We hypothesize that perhaps there are some nutritional factors in these homosexual males that make them more predisposed to being infected, but we have no evidence for that. We have also found that both low plasma levels of selenium and high plasma levels of selenium are associated with immunosuppression. So, I think that caution for oversupplementation with minerals is always there. J.-P. CURTAY(Paris, France): I would like to thank Dr. Baum for her very helpful recommendations. We have very respectable scientists like Dr. Roe and Dr. Leklem giving words of caution about giving supplementation without enough data. We are in a position, however, where we are also at risk of excessive caution when treating people who are at risk of dying of HIV. Life is very risky; we have a good chance of getting cancer, cardiovascular disease, and being exposed to pollution and drugs. One has to weigh the beneficial effects of products like betacarotene and vitamin E against the dangers. UNIDENTIFIED SPEAKER: What is the likelihood that the low copper levels were a result of the zinc supplementation. BAUM:There was no correlation between the zinc supplementation and the lower copper levels.

Influence of HIV infection on vitamin status and requirements.

Influence of HIV Infection on Vitamin Status and Requirements" M. K. BAUM,b.rG. SHOR-POSNER," P. BONVEHI,b I. CASSETTI,' Y. LU," E. MANTERO-ATIENZA,b...
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