Micronutrients and HIV-1 disease progression.

OBJECTIVE: To determine whether nutritional status affects immunological markers of HIV-1 disease progression. DESIGN: A longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. METHODS: Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. RESULTS: Development of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P = 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by zidovudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P = 0.041) and the AIDS index (P = 0.005). CONCLUSIONS: These data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Specific nutrient abnormalities in asymptomatic HIV-1 infection.

OBJECTIVE: To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DESIGN: A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SETTING: The study was performed on an outpatient basis at the University of Miami School of Medicine. PARTICIPANTS: One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. MAIN OUTCOME MEASURES: Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. RESULTS: Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. CONCLUSION: Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.

Electroencephalographic changes and periodontal status during short-term vitamin B-6 depletion of young, nonpregnant women.

As part of a larger investigation to determine the effect of animal vs. plant proteins on the vitamin B-6 requirement of young women, clinical changes during vitamin B-6 depletion were documented. Eight healthy young women were confined to a metabolic unit and fed a defined formula diet nearly devoid of vitamin B-6 (less than 0.05 mg/d). Serial electroencephalographic (EEG) tracings, peripheral nervous system tests, periodontal evaluations, and biochemical measures of vitamin B-6 status were conducted. Within 12 d on the depletion diet, two of the eight women exhibited abnormal EEG tracings. These changes were readily reversed by repletion of vitamin B-6 at the 0.5-mg/d level. Biochemical measures reflected lowered vitamin B-6 status but were not predictive of the onset of EEG changes. No detectable alterations in oral or periodontal status were found, nor did plaque flora change markedly. This study is the first report of EEG changes occurring in women undergoing vitamin B-6 depletion and the first report to document EEG changes in adults within 12 d on a vitamin B-6-depletion regimen.

Influence of dietary intakes of erythorbic acid on plasma vitamin C analyses.

D-Erythorbic acid is an epimer of L-ascorbic acid, but lacks antiscorbutic activity. It is commonly used as a food additive, particularly in processed meat items. Except for high-performance liquid chromatography (HPLC) methodology, the commonly used analytical procedures to measure vitamin C do not distinguish between the two isomers. A study with seven adult women demonstrated that the concentration of erythorbic acid present in food items commonly consumed was sufficient to produce interference in plasma vitamin C analyses. With the meals used, 7-23% of the apparent vitamin C in plasma obtained 2 h after the ingestion of the meals was actually erythorbic acid when analyzed by HPLC. To avoid falsely high plasma-serum vitamin C values as a result of erythorbic acid ingestion, the analyses should be conducted on overnight fasting blood specimens or with the use of an HPLC-amperometric method.

Vitamin B-6 requirement and status assessment: young women fed a depletion diet followed by a plant- or animal-protein diet with graded amounts of vitamin B-6.

The vitamin B-6 requirement of young women consuming a high-protein diet (1.55 g/kg body wt) and the effect of protein quality on this requirement was studied. In addition, the response of clinical, functional, and biochemical measures of vitamin B-6 nutriture to short-term depletion and step-wise repletion of vitamin B-6 were evaluated. Eight healthy young women resided in a metabolic unit and were fed a formula depletion diet (< 0.05 mg vitamin B-6/d) for 11-28 d followed by either an animal-protein (AP) or plant-protein (PP) diet with successively increasing vitamin B-6 intakes (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21 d. Animal proteins were primarily from dairy and poultry sources and plant proteins were primarily from legumes. Vitamin B-6 status measures were assessed at weekly intervals. Results showed that a PP diet does not elevate the vitamin B-6 requirement over that required for an AP diet given the high amount of dietary protein used in this study. It was also found that 0.015 mg vitamin B-6/g protein intake normalized most biochemical indexes of vitamin B-6 status (including those indicative of functional status), and that 0.020 mg/g protein normalized all biochemical measures except total urinary vitamin B-6. Adding a margin of safety to either the 0.015 or 0.020 mg/g protein intake would raise the vitamin B-6 requirement for young women above the currently recommended dietary allowance of 0.016 mg/g protein.

Folate requirement and metabolism in nonpregnant women.

Folate metabolism and requirements were studied in 10 adult nonpregnant women maintained for 92 d in a metabolic unit. After a folate depletion period of 28 d, the subjects received increasing supplements of folate from food items or as pteroylmonoglutamic acid (PGA). Plasma folate levels fell 60% during the depletion period and continued to fall until 200 micrograms/d of naturally occurring food folates were provided. Supplements of 300 micrograms/d of naturally occurring folates produced a small rise in plasma folate levels although erythrocyte folate levels continued to fall. Lymphocyte deoxyuridine suppression, neutrophil hypersegmentation, and other measurements related to folate metabolism were performed. When compared with PGA, dietary folates appeared to be no more than 50% available. A daily intake of 200-250 micrograms of dietary folates appears to meet the folate requirements of nonpregnant adult women whereas an intake of 300 micrograms/d provides an allowance for storage.

Vitamin B-6 depletion followed by repletion with animal- or plant-source diets and calcium and magnesium metabolism in young women.

An 84-98-d study was conducted in young women to determine the effect of vitamin B-6-deficient diets on calcium and magnesium metabolism. A vitamin B-6-deficient formula diet fed initially was followed by either animal- or plant-source protein food diets containing four increasing amounts of vitamin B-6. Calcium balance was negative during vitamin B-6 depletion. Serum calcium was higher and calcium balance negative with the plant protein diets. Magnesium balance was negative during vitamin B-6 depletion due to increased urinary magnesium excretion. Urinary calcium decreased during vitamin B-6 depletion and increased as dietary vitamin B-6 increased. Urinary oxalate was significantly higher at the end than at the beginning of vitamin B-6 depletion and was higher with plant than animal protein diets. The results suggest that vitamin B-6 depletion may alter calcium and magnesium metabolism and that dietary components associated with the protein source may influence calcium retention.

Effects of erythorbic acid on vitamin C metabolism in young women.

Erythorbic acid, an epimer of L-ascorbic acid, is used in the United States as a food additive. Studies were conducted to determine whether the ingestion of erythorbic acid in the diet had any beneficial or adverse effects on the human requirement for vitamin C. Young women were fed diets that contained controlled amounts of erythorbic acid and ascorbic acid. In pharmacokinetic evaluations, erythorbic acid and ascorbic acid were rapidly absorbed with little interaction. Erythorbic acid cleared from the body more rapidly than ascorbic acid. Some subjects received diets deficient in vitamin C for periods < or = 30 d. Increasing intakes of erythorbic acid or prolonged intakes of < or = 1 g erythorbic acid/d did not indicate any interactions with ascorbic acid. Consumption of erythorbic acid resulted in the presence of erythorbic acid in mononuclear leukocytes. Ascorbic acid concentrations in these cells were not affected by the presence of erythorbic acid. Erythorbic acid disappeared quickly from these cells with cessation of erythorbic acid supplements. Prolonged ingestion of erythrobic acid by young women neither antagonized nor spared their vitamin C status.

Thiamin requirement of the adult human.

Young adult male subjects maintained on a metabolic ward were fed diets providing controlled intakes of thiamin and either 2800 or 3600 kcal. The higher level of calories was attained by an increased intake of carbohydrates. Constant weights were maintained by the subjects by adjusting daily activity and exercise schedules. Thiamin requirements were evaluated in terms of erythrocyte transketolase activity and urinary excretion of the vitamin. The results of the study revealed that a relationship exists between thiamin requirement and caloric intake and expenditure. Thus, when the calories being utilized were derived primarily from carbohydrate sources, the minimum adult male requirement for thiamin appeared to be 0.30 mg of thiamin per 1000 kcal. Urinary excretion of thiamin and erythrocyte transketolase activity appear to be reasonably reliable reflections of thiamin intakes and thiamin nutritional status. The use of these measurements in nutrition surveys appears justified. The microbiological assay (Lactobacillus viridescens) for measuring thiamin levels in urine samples appears to be a somewhat more sensitive but valid procedure as an alternate for the thiochrome method. Judged from the results of this study, the recommended intake for the adult human of 0.40 mg of thiamin per 1000 kcal by FAO/WHO and the recommended allowance of 0.5 mg per 1000 kcal by the Food and Nutrition Board of the NAS-NRC appear reasonable and amply allow for biological variations and other factors that may influence the requirement for this vitamin.

Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects.

We performed the deoxyuridine suppression test (dUST) along with assessment of folate and vitamin B-12 status in blood specimens from 136 normal women and 109 women with cervical dysplasia. All tests were repeated at 2, 4, and 6 mo in subjects with dysplasia during a randomized, double-blind intervention trial in which 50 received a 10-mg daily oral folic acid supplement (F group) and 59 received a placebo (P group). Median folate concentration increased fivefold in plasma and threefold in erythrocytes of F group beginning at the second months and remained elevated whereas concentrations of the P group remained unchanged. Vitamin B-12 values did not vary significantly in either group. The dUST value decreased from 10.4 +/- 4.6% (means +/- SD) pretreatment to 4.5 +/- 4.7% in F group after 2 mo (p less than 0.001). The dUST values had significant negative correlation with plasma and erythrocyte folate concentrations. However, erythrocyte folate had the greatest power to distinguish P group from F group.

Ascorbic acid and erythorbic acid metabolism in nonpregnant women.

Ascorbic acid (AA) metabolism and requirements were studied in 11 adult nonpregnant women maintained in a metabolic unit and fed a formula diet devoid of AA for 54 d. After depletion for 24 d, the subjects received increasing supplements of AA in the presence or absence of 600 mg/d of erythorbic acid (EA). Various analytical procedures were used to measure AA concentrations in blood components. The depletion period resulted in a marked decrease in AA in all blood indices. During the study scorbutic signs developed in some of the subjects. AA supplements of 30 mg/d for 10 d failed to increase plasma ascorbate concentrations; 60 mg/d for 10 d produced a small increase; 90 mg/d resulted in a mean AA concentration of 29 mumol/L. EA did not present any adverse effects, but rather had a small sparing effect. Vitamin C requirements for adult nonsmoking, nonpregnant women would be marginally met by an intake of 60 mg/d of AA whereas 90 mg/d would provide an allowance for body storage.

Protein utilization by young women consuming animal or plant protein diets at various levels of vitamin B-6 intake.

Eight young women consumed a vitamin B-6 depletion diet (egg albumen formula, less than 0.05 mg vitamin B-6/d) for 11-28 d. Subjects (n = 4) then consumed either animal protein (AP, mainly dairy and poultry products) or plant protein (PP, mainly various types of beans) diets with increasing vitamin B-6 intake (0.5, 1.0, 1.5, and 2.0 mg/d) for periods of 14-21 d. All diets provided 1.55 g protein/kg body wt. Apparent protein digestibility of AP (94.6%) was significantly higher than that of PP (88.4%) diets (p less than 0.001). Protein digestibility was not significantly affected by vitamin B-6 intake. Apparent nitrogen balance of subjects consuming AP diets was slightly, though not significantly, higher than that of subjects fed PP diets. N balance was not influenced by vitamin B-6 intake. Data suggest that short-term low vitamin B-6 intake does not affect protein utilization in humans as determined by digestibility and N balance.

A stable-isotope study of zinc, copper, and iron absorption and retention by young women fed vitamin B-6-deficient diets.

A 98-d study was conducted in young women to determine the effect of vitamin B-6-deficient diets on zinc, copper, and iron metabolism. Young women were fed vitamin B-6-deficient formula initially, followed by food diets containing four increasing amounts of vitamin B-6. Zinc, copper, and iron absorption, retention, and status were determined at intervals throughout the study. Zinc absorption and retention were greater during vitamin B-6 depletion but serum zinc declined, suggesting that absorbed zinc was not available for utilization. Copper absorption was lower during vitamin B-6 depletion but serum copper was not affected and balance was positive. Iron absorption was not impaired significantly by vitamin B-6-deficient diets but status may have declined. The results suggest that vitamin B-6 depletion of young women may alter zinc metabolism, inhibit copper absorption, and affect iron status. The effects of vitamin B-6 depletion differ markedly among these elements.

Zinc concentration in plasma and erythrocytes of subjects receiving folic acid supplementation.

It has been suggested that oral supplements of folic acid interfere with the intestinal absorption of zinc and may have toxic side effects. The concentrations of Zn and folate in blood were monitored in a group of women with cervical dysplasia randomly assigned to receive 10 mg/d of either folic acid (pteroylglutamic acid) or ascorbate. Fifty subjects were evaluated after 2 mo; 21 of the same subjects were evaluated again after 4 mo. No untoward clinical effects were observed. Significant elevation of erythrocyte folate above the baseline value was observed in the supplemented group but not in the placebo group (p less than 0.001). The concentration of Zn in plasma and erythrocytes did not change significantly in either the folate-treated or placebo groups after 2 and 4 mo. It is concluded that carefully controlled clinical intervention trials of this type do not impose a risk of depleting the concentration of Zn in erythrocytes and plasma.

Vitamin A status of children in Sri Lanka.

A representative country-wide rural nutrition status survey determined the extent and distribution of vitamin A deficiency in Sri Lanka in children 6 through 71 months of age. Trained paramedical personnel recorded the presence or absence of selected ophthalmological signs and symptoms associated with vitamin A deficiency in 13,450 children. The results of the country-wide clinical survey indicate that a vitamin A deficiency problem of public health importance may exist in two of 15 health areas. Serum vitamin A levels were determined on 346 survey children from two of 15 health areas and compared with clinical findings for these areas. The lowest mean serum vitamin A, 26.3 microgram/100 ml, occurred in children with clinical eye findings. A high prevalence of clinical eye findings, 34%, and the low mean serum vitamin A value, 28.2 microgram/100 ml, were found in the group of chronically undernourished children--children who are less than 90% of their expected height for age. The survey results enabled planned redirection of the distribution of vitamin A capsules to preschool children in Sri Lanka to areas shown to have the highest prevalences of ophthalmological signs and symptoms and/or the highest prevalence of chronic undernutrition.

Postpartum thiamine deficiency in a Karen displaced population.

BACKGROUND: Before its recognition, infantile beriberi was the leading cause of infant death in camps for displaced persons of the Karen ethnic minority on Thailand's western border. OBJECTIVE: This study aimed to document thiamine status in the peripartum period to examine the current supplementation program and the correlation between the clinical manifestations of thiamine deficiency and a biochemical measure of thiamine status. DESIGN: Women were enrolled prospectively at 30 wk of gestation and were followed up weekly until delivery and at 3 mo postpartum. Thiamine supplementation during pregnancy was based on patient symptoms. RESULTS: At 3 mo postpartum, thiamine deficiency reflected by an erythrocyte transketolase activity (ETKA) > or = 1.20% was found in 57.7% (15/26) of mothers, 26.9% (7/26) of whom had severe deficiency (ETKA > 1.25%). No significant associations between ETKA and putative maternal symptoms or use of thiamine supplements were found. CONCLUSIONS: Biochemical postpartum thiamine deficiency is still common in Karen refugee women. This situation may be improved by educating lactating women to reduce their consumption of thiaminase-containing foods and by implementing an effective thiamine supplementation program.

Hematopoietic studies in vitamin A deficiency.

Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease.

High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with angiographically demonstrated CAD, and 108 white male, similarly aged, control subjects living in the same community as the patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0, 2.0). The OR change per quartile increase of folate concentration was 0.8 (95% CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy adjustment. No difference in the geometric mean of vitamin B-12 concentration was found between patients and control subjects, both 5.8 nmol/L. However, after Hcy and the other CAD risk factors were controlled for, the OR per quartile increase in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy by interventions to increase plasma folate concentration may decrease CAD risk.

Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males.

Chemotherapeutic regimens frequently interact with and may influence nutritional factors. To determine the possible effects of zidovudine (ZDV) treatment on nutrient status, this study examined and compared the nutritional, immunological, and hematological status of asymptomatic, CDC stage III, HIV-1-seropositive males (n = 15) provided with ZDV (500-1,200 mg/day) and 22 nontreated, CD4-matched HIV-1-seropositive subjects. Prior to ZDV administration, hematological and plasma nutrient levels were similar in both groups. Following ZDV treatment, drug-treated subjects demonstrated alterations in hematological and nutritional parameters. A large proportion of the ZDV-treated participants exhibited decreased levels of zinc and copper along with a significant increase in red cell folate. The level of plasma zinc appeared to be particularly important in maintaining immune function in the ZDV-treated group. Whereas ZDV-treated subjects with adequate zinc levels displayed a significant increase in the response of peripheral blood lymphocytes to mitogens, this enhancement was not demonstrated in zinc-deficient, ZDV-treated participants or in untreated individuals whose lymphocyte response significantly declined over time, despite adeqaute zinc status. The findings of this study reveal a zidovudine-induced effect on nutritional parameters, indicating the importance of monitoring nutritional status with drug therapeutic regimens.

Association of vitamin B6 status with parameters of immune function in early HIV-1 infection.

Nutritional deficiencies have been documented to affect immune function. The present study indicates that vitamin B6 deficiency is prevalent in CDC stage III HIV-1-infected subjects, despite adequate dietary vitamin B6 intake. As vitamin B6 deficiency has been previously shown to affect immune function, these relatively asymptomatic HIV-1-infected patients were examined for evidence of a relationship between vitamin B6 deficiency and immune dysregulation. Vitamin B6 status in HIV-1-infected subjects was significantly associated with functional parameters of immunity [multivariate F(3,36) = 3.70, p less than or equal to 0.02]. Additional analyses indicated that overtly deficient participants exhibited significantly decreased lymphocyte responsiveness to the mitogens phytohemagglutinin and pokeweed, and reduced natural killer cell cytotoxicity, compared to subjects with clearly adequate vitamin B6 status (chi 2 = 8.78, df = 3, p less than 0.04). Vitamin B6 status was not related to immune cell subpopulations, e.g., CD4, CD8 cell number, or level of serum immunoglobulins. The results of this study indicate that while vitamin B6 status is not a primary etiological factor in HIV-1-related immunological dysregulation, it appears to be an important cofactor of immune function.