Toenail and plasma levels as biomarkers of selenium exposure

PURPOSE: Both blood and toenail selenium are used to assess selenium exposure in epidemiologic studies. Little is known about the relationship of these biomarkers with each other or about whether there are differences in the relationships of these biomarkers with diet, supplement use, or participant characteristics. METHODS: Data are from 220 participants in a large cohort study of supplement use and cancer risk. Measures of selenium exposure included supplement use (current and 10-year) from a self-administered questionnaire, an inventory of currently used supplements (multivitamins and single supplements), dietary intake from a food frequency questionnaire (FFQ), and selenium concentration in toenails and plasma. RESULTS: Plasma and toenail selenium concentrations were significantly correlated (r=.56 [95% confidence interval: .46, .64]). Supplemental selenium was the strongest predictor of both selenium biomarkers, and these associations were slightly stronger when based on the supplement inventory and 10-year self-reported use compared to current self-reported use. Correlations of current and 10-year questionnaire dose and inventory dose with toenail selenium were .26, .36, and .33; for plasma selenium, these were .27, .36, and .36. Neither dietary selenium nor any participant characteristics, except smoking, was related to either biomarker. Current smokers had lower toenail, but not plasma, selenium levels compared to nonsmokers (.89 versus 1.03 microg/g, p = .03); however, the difference was not significant after control for supplement use (p = .09). CONCLUSIONS: Both toenail and plasma selenium levels similarly reflect selenium intake exposure. There do not appear to be independent associations of toenail or plasma selenium with FFQ-derived selenium intakes, health-related behaviors, or demographic characteristics.     

Association of diet with serum insulin-like growth factor I in middle-aged and elderly men

BACKGROUND: Insulin-like growth factor I (IGF-I) has been implicated in several chronic diseases, including cancer, heart disease, and osteoporosis. OBJECTIVE: Our aim was to assess whether intakes of total energy, alcohol, vitamins, minerals, and foods rich in protein and minerals (including red meat, fish and seafood, poultry, and milk) are associated with serum IGF-I concentrations in middle-aged and elderly men. DESIGN: We measured serum IGF-I concentrations in 226 free-living healthy men aged 42-76 y. The average of fourteen 24-h dietary telephone interviews performed over 1 y was used to estimate long-term dietary intake. RESULTS: We observed statistically significant positive associations between intakes of protein (P for trend = 0.001) and zinc (P for trend = 0.002) and serum IGF-I concentrations after adjusting for age. The difference in mean IGF-I concentrations for the highest compared with the lowest quintile of intake was approximately 17% (162 microg/L compared with 139 microg/L) for protein and approximately 16% (166 microg/L compared with 143 microg/L) for zinc. Consumption of red meat (P for trend = 0.05) and fish and seafood (P for trend = 0.07) was modestly positively associated with IGF-I concentrations. Other dietary factors were not associated with IGF-I concentrations. CONCLUSION: In this population of healthy well-nourished men, greater dietary intakes of protein, zinc, red meat, and fish and seafood were associated with higher IGF-I concentrations.     

Zinc intakes and plasma concentrations in men with osteoporosis: the Rancho Bernardo Study

BACKGROUND: Low zinc intakes and reduced blood zinc concentrations have been reported to be associated with osteoporosis in women. OBJECTIVE: The objective was to examine the independent association between dietary zinc and plasma zinc and the association of each with bone mineral density (BMD) and 4-y bone loss in community-dwelling older men. DESIGN: Of the original Rancho Bernardo Study subjects, 396 men (age: 45-92 y) completed BMD measurements at baseline in 1988-1992 and 4 y later. Osteoporosis was defined as a BMD > or = 2.5 SDs below the mean for young women (a T-score < or = -2.5). At baseline, dietary intake data were collected by using a standard food-frequency questionnaire, and plasma zinc concentrations were measured by using inductively coupled plasma spectroscopy. RESULTS: The mean dietary zinc intake was 11.2 mg, and the mean plasma zinc concentration was 12.7 micromol/L. Plasma zinc was correlated with total zinc intake (diet plus supplements). Dietary zinc intake and plasma zinc concentrations were lower in men with osteoporosis at the hip and spine than in men without osteoporosis at those locations. BMDs for the hip, spine, and distal wrist were significantly lower in men in the lowest plasma zinc quartile (<11.3 micromol/L) than in men with higher plasma zinc concentrations. The association between plasma zinc and BMD was cross-sectional, longitudinal, and independent of age or body mass index. However, plasma zinc did not predict bone loss during the 4-y interval. CONCLUSION: Dietary zinc intake and plasma zinc each have a positive association with BMD in men.     

Prospective study of zinc intake and the risk of age-related macular degeneration

PURPOSE: Zinc is found in high concentrations in the retina and is hypothesized to reduce the risk of age-related macular degeneration (AMD). Any long-term benefit associated with dietary zinc intake has not been evaluated. METHODS: We followed 66,572 women and 37,636 men who were > or = 50 years old and had no diagnosis of AMD or cancer. Zinc intake from food, multivitamins, and supplements was assessed with a semiquantitative food-frequency questionnaire at baseline (in 1984 for women and in 1986 for men) and repeated during follow-up (twice for women, once for men). RESULTS: During 10 years of follow-up for women and 8 years of follow-up for men, we confirmed 384 incident cases of AMD (195 cases of the early form and 189 cases of the late form) associated with a visual acuity loss of 20/30 or worse. After multivariate adjustment for potential risk factors, the pooled relative risk was 1.13 (95% confidence interval [CI], 0.82 to 1.57; p-value, test for trend, 0.74) among participants in the highest quintile of total zinc intake (energy-adjusted median; 25.5 mg/day for women and 40.1 mg/day for men) compared with those in the lowest quintile (energy-adjusted median; 8.5 mg/day for women and 9.9 mg/day for men). The relative risk for highest compared with lowest quintile was 1.04 (95% CI, 0.59 to 1.83; p-value, test for trend, 0.54) for zinc intake from food. Subjects who took zinc supplements had a pooled multivariate relative risk of 1.04 (95% CI, 0.75 to 1.45). CONCLUSIONS: In these two large prospective studies, moderate zinc intake, either in food or in supplements, was not associated with a reduced risk of AMD.     

Seasonal variations of antioxidant imbalance in Cuban healthy men

OBJECTIVE: To determine the antioxidant imbalance in healthy Cuban men 2y after the end of the epidemic neuropathy (50 862 cases from 1991 to 1993) and to evaluate its change over 1 y. DESIGN: Prospective study. SETTING: La Lisa health centres (Havana, Cuba). SUBJECTS: One-hundred and ninety-nine healthy middle-aged men were selected and 106 completed the study. Subjects were studied at 3 month intervals over 1 year. INTERVENTIONS: No invervention. MAIN OUTCOME MEASURES: An assessment of dietary intake and the determination of blood lipid peroxides (TBARS), glutathione, diglutathione, glutathione peroxidase, superoxide dismutase, vitamin E, carotenoids, copper, zinc and selenium were performed at each period. RESULTS: While dietary zinc, vitamins C and E, carotenoids and fat dietary intakes and blood concentrations were low for adult men compared to international reference ranges, serum TBARS concentrations were high at every period. Some significant seasonal variations were observed. The lowest carotenoids (P < 0.002) and vitamin C(P = 0.0001) intakes, serum beta-carotene (P = 0.0001) and lutein/zeaxanthin (P < 0.05) concentrations, and the highest blood TBARS (P = 0.0001) and diglutathione (P < 0.001) concentrations were observed at the end of the rainy season (October). This period seemed to pose the greatest risk of antioxidant imbalance. CONCLUSIONS: Cuban men still represent a vulnerable population in terms of antioxidant imbalance. A national program of vegetable growing and increase in fruit and vegetable consumption is now evaluated in Cuba.     

Zinc and vitamin A intake and status in a national sample of British young people aged 4-18 y

OBJECTIVE: To examine zinc and vitamin A intake and status and associated dietary, socio-demographic, lifestyle and physiological factors in British young people. DESIGN: National Diet and Nutrition Survey of young people aged 4-18 y. SETTING: Great Britain, 1997. SUBJECTS: Complete 7-day weighed dietary records were provided by 1520 participants, while 1193 provided blood samples. RESULTS: A total of 13 and 11% of participants respectively reported low dietary intakes of zinc and vitamin A (retinol equivalents), relative to the UK lower reference nutrient intake. These percentages were not altered significantly by including contributions to intake from supplements, mainly containing vitamin A (as retinol). Likelihood of low zinc and/or vitamin A intake was more often associated with age, sex and likely under-reporting of food consumption than with other socio-demographic and lifestyle factors. Low zinc and vitamin A intakes were generally less likely in those with higher consumption of dairy foods (mainly milk). Zinc and vitamin A status (assessed by plasma zinc and retinol concentrations) were adequate in almost all participants. Plasma zinc concentration was not significantly associated with zinc intake. Plasma retinol concentration was correlated with vitamin A intake (overall r=0.17, P<0.001; adjusted for age and plasma alpha(1)-antichymotrypsin concentration) and increased significantly with age (P<0.001) in both sexes. A significant association was found between plasma zinc and retinol concentrations in boys only (r=0.17, P=0.001). CONCLUSION: Zinc and vitamin A intakes and status were generally adequate in this national sample of British young people.     

Association between the intake of vitamins and trace elements from supplements and C-reactive protein: results of the MONICA/KORA Augsburg study

OBJECTIVE: To examine the association between plasma concentrations of C-reactive protein (CRP) and the intake of vitamins and trace elements from supplements possibly related to inflammation such as vitamin C, vitamin E, carotenoids, selenium and zinc. DESIGN: Cross-sectional study using data from the Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg (MONICA/KORA) Survey 1994/95. SETTING: Region of Augsburg, Southern Germany. SUBJECTS: Population-based sample of 2045 women and 2172 men, aged 25-74 years. RESULTS: Intake of dietary supplements containing vitamins and trace elements was associated with lower CRP levels in women. Especially vitamin E in combination with other vitamins like vitamin C, vitamin B(1), B(2), B(6), B(12), niacin, folic acid, pantothenic acid and selenium, was significantly associated with lower CRP levels. Odds ratios for elevated CRP levels (>3.0 mg/l) after multivariable adjustment were 0.57 (95% confidence interval (CI): 0.37, 0.89) for the intake of vitamin E and 0.57 (95% CI: 0.35, 0.91) for the intake of multivitamins, defined as taking three or more different vitamins. These associations were not seen in men. Intake of vitamin C, carotenoids or zinc was not significantly associated with levels of CRP in both men and women. CONCLUSIONS: Our data indicate that the intake of certain vitamins and trace elements from supplements is associated with lower CRP concentrations in women. Thus, intake of these micronutrients could influence the inflammatory process underlying the pathogenesis of atherosclerosis. Specific dose response relationships and the best combinations of vitamins and trace elements have to be determined in further studies.     

Plasma changes in micronutrients following a multivitamin and mineral supplement in healthy adults

OBJECTIVE: To estimate the micronutrient (riboflavin, folate, vitamin C, vitamin B(12), iron, zinc and copper) bioavailability in healthy adults from a multi-micronutrient dietary supplement to assess the possible influence on it by the tablet disintegration properties and by the relative intestinal permeability of subject. METHODS: The bioavailability of seven micronutrients from a single brand of multi-micronutrient dietary supplement was measured on two separate occasions in the presence of a standardized test meal in 15 healthy adult subjects. Each subject visited the Metabolic Research Unit on four separate randomized occasions for an absorption test. One test measured the intestinal permeability. The other three tests measured the postprandial changes in plasma or serum concentrations after consuming a test meal alone (control:placebo effect), or the test meal with either whole or crushed and powdered dietary supplements. 15 healthy Caucasian adult volunteers, aged 42 +/- 14 years. RESULTS: The 12 hour-post-dose AUC for riboflavin, folate and vitamin C (whole and crushed tablet), and that for vitamin B(12) (only for the crushed tablet treatment) and iron (only for the whole tablet treatment) were all significantly (p < 0.001) higher than after a test meal alone. In contrast there was no significant increase in the AUC after supplement intake for zinc and copper. Neither the form of the supplement for all micronutrients tested nor intestinal permeability of the subject for riboflavin, folate, vitamin C, iron, zinc and copper influenced the postdose nutrient AUC. In contrast, for vitamin B(12) the intestinal permeability of the subject influenced significantly the nutrient AUC (p = 0.003). CONCLUSION: Tablet disintegration characteristics of this dietary supplement did not limit absorption of these seven micronutrients. The intestinal permeability of subject was only positively correlated with the B(12) bioavailability. Results are suggestive of using multi-micronutrients dietary supplements as a vehicle to decrease the prevalence of multiple micronutrient deficiencies overall for vitamins in healthy adults.     

The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis

The potential exists for zinc to influence numerous metabolic functions and to impact a range of diseases. In the present review we examine the reported relationships between zinc and plasma lipids, haemostasis and other factors postulated to play a role in atherogenesis. Ecological studies that investigated zinc intake or status, and incidence of coronary heart disease (CHD) reveal no consistent pattern. The conflicting observations may be explained by differences in the extent of CHD, site of atherosclerosis, or confounding factors. In most studies the diurnal variation in serum zinc concentrations, and the lifestyle factors that affect cholesterol metabolism were not explicitly considered. Results of randomised controlled trials show that low-density lipoprotein (LDL) oxidation and the concentrations of LDL-cholesterol (c), total cholesterol and triglycerides in plasma are unaffected by supplementation with up to 150 mg Zn/d. In contrast, plasma high-density lipoprotein (HDL)-c concentrations decline when zinc supplements provide a dose >50 mg/d. Limited data suggest that sustained hyperzincaemia predisposes individuals to thrombogenesis, whereas acute zinc depletion impairs platelet aggregation and prolongs bleeding time. In addition, Zinc supplements have been shown in some studies to decrease Cu/Zn-superoxide dismutase activity, primarily due to the antagonistic relationship between high zinc intakes and copper absorption. Besides the demonstrated adverse effect of zinc supplementation on plasma HDL-c concentrations in apparently healthy men, there is insufficient evidence to determine the role of zinc supplementation in influencing other risk factors for CHD such as antioxidant status and thrombogenesis.     

Dietary antioxidants and plasma lipids: the CARDIA Study.

To determine if dietary antioxidants play a role in preventing coronary heart disease (CHD) by having an impact on lipid levels.

Data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to assess the associations of reported intake of vitamins A, C, E and beta carotene, and their use in supplements, with lipid levels in a black and white, healthy adult (18 to 30 years of age at the baseline examination) population.

After adjusting for age, education level, physical activity, body size, alcohol consumption and caloric intake, vitamin A, beta carotene, and vitamin C (white women) intake were directly associated with HDL-cholesterol levels among women who smoked cigarettes, with the strongest associations being observed for white women. Black men who took supplements of vitamins A and C and did not smoke cigarettes had significantly higher HDL-cholesterol levels compared to those in the lowest levels of dietary intake. Although vitamin E was associated with higher levels of HDL-cholesterol, the association was only of borderline significance among white men who smoked cigarettes (p = 0.06). We did not observe any consistent associations between antioxidants and other plasma lipids, including total cholesterol, LDL-cholesterol, or triglycerides.

We conclude that dietary antioxidants are associated with HDL-cholesterol levels in some subsets of the population, although these associations may be operating in conjunction with other lifestyle behaviors.     

Requirement of zinc in human subjects.

Essentiality of zinc in nutrition of higher animals was established in 1934. Dietary zinc deficiency in humans was recognized in 1961. Dietary requirements for zinc have been estimated factorially and by balance studies. Factors that influence dietary zinc requirement include dietary and other substances that either facilitate or inhibit absorption and retention of zinc; and metabolic phenomena that influence retention or excretion of the element. These determinants must be considered in estimating the requirement and the recommended dietary allowance for this essential element. An approach that has been used to assess requirement is the measurement of dietary zinc retention by men fed diets providing sufficient energy to meet the needs of each individual and containing other nutrients in proportion to energy content. By measurement of chemical balance and subsequent analysis of the data by multiple regression, dietary factors influencing requirement have been identified and amounts of dietary zinc essential for needs calculated. Using this approach, 83% of the variance (P less than 0.0001) in requirement was accounted for by the dietary content of phosphorus and nitrogen when data from 157 twenty-eight to thirty day studies were analyzed. The equation, Intake = 1.466 + 0.23 (Zn balance) + 5.19 (P intake) + 0.40 (N intake) ? 0.30 (P intake ? 1.389) (N intake - 14.646), was used to estimate zinc requirement of persons who participated in the most recent USDA Food Consumption Survey. For all age groups, ages 9 to greater than 75y, males and females, the mean (range) difference between the estimated intakes and calculated requirements were: males 1.5% (?6.5 to + 8.1), females 11.3% (? 1.1 to + 20.3). Thus, mean intakes were generally within the 95% confidence limits of the estimated requirements. Of some interest was the finding that the mean intake of none of the groups was equivalent to the Recommended Dietary Allowance. The mean intake of males ranged from 9.32 mg in men 75y and older to 13.53 mg in persons 15–18y. The mean intake of the females ranged from 7.04 mg in women 75y and older to 9.22 mg in persons 12–14 y.     

Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women.

The authors investigated the association of diet and other factors with the plasma concentrations of carotenoids, retinol and tocopherols in a sample of 121 men and 186 women participating in two prospective investigations of dietary etiologies of chronic diseases. Lycopene (mean concentration, 0.82 mumol/L in men, 0.76 mumol/L in women), beta-carotene (mean 0.46 mumol/L in men, 0.58 mumol/L in women) and lutein (mean 0.28 mumol/L in men, 0.27 mumol/L in women) were the major circulating carotenoids. Among nonsmokers, dietary carotenoid, as typically calculated in epidemiologic studies, was significantly correlated with plasma beta-carotene (r = 0.34 in men, r = 0.30 in women), alpha-carotene (r = 0.52 in men, r = 0.37 in women) and lutein (r = 0.36 in men, r = 0.19 in women), but not with plasma zeaxanthin (r = 0.11 and r = 0.02) or lycopene (r = 0.13 and r = 0.01) after adjusting for plasma cholesterol and triglycerides, body mass index and energy intake. Total vitamin E intake was positively associated with plasma concentrations of alpha-tocopherol (r = 0.51 in men, r = 0.41 in women) and inversely associated with plasma concentrations of gamma-tocopherol (r = -0.51 in men r = -0.42 in women), but this was primarily due to use of vitamin E supplements. Measurements of specific carotenoids can provide independent information beyond the usual calculation of carotene intake in epidemiologic studies.     

Predictors of selenium concentration in human toenails

To assess the validity of the selenium concentration in human toenails as a measure of selenium intake and to determine other correlates of toenail selenium level, the authors examined the predictors of toenail selenium within two subgroups of a large cohort study of US women. Mean toenail selenium was higher among 38 consumers of selenium supplements (0.904 micrograms/g, standard deviation (SD) 0.217) than among 96 nonusers (0.748 micrograms/g, SD 0.149; p less than 0.001), and a dose-response relation was observed among supplement users (Spearman's r = 0.32; p = 0.05). In a second subgroup of 677 women, selenium supplement use was also associated with higher mean toenail selenium (0.906 micrograms/g, SD 0.214, among 18 users and 0.801 micrograms/g, SD 0.148, among 659 nonusers; p = 0.02), and the dose-response relation was also significant (Spearman's r = 0.50; p = 0.03). The geographic variation in toenail selenium levels was consistent with the geographic distribution of selenium in forage crops. Toenail selenium declined with age and was significantly reduced among cigarette smokers (mean = 0.746, SD 0.124, among 146 current smokers and mean = 0.817, SD 0.159, among 311 never smokers; p less than 0.001) but was not materially affected by alcohol consumption. A dietary selenium score calculated from a food frequency questionnaire failed to predict toenail selenium level, demonstrating the suspected inability of diet questionnaires to measure individual selenium intake because of the highly variable selenium composition of different samples of the same food.(ABSTRACT TRUNCATED AT 250 WORDS)     

Review of nutrient actions on age-related macular degeneration

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression.     

Nutrient intake and body weight in a large HIV cohort that includes women and minorities

OBJECTIVE: Evaluate the baseline nutrient intake of an HIV positive population that includes significant representation from women and minorities, and determine the relationship between state of disease and nutritional intake. DESIGN: Baseline data from a prospective study (Nutrition for Healthy Living). SUBJECTS: Individuals with HIV in the Boston and Rhode Island area (n = 516); 25% were women and 30% were minorities. METHODS: Nutrient intakes from 3-day food records, which included vitamin/mineral supplements, were estimated by gender and nonwhite vs white categories, after grouping by CD4 lymphocyte counts. STATISTICAL ANALYSES: Spearman correlation coefficients, Wilcoxon signed rank test, Wilcoxon rank sum test, chi2 test, and restricted cubic spline model were used for data analyses as indicated. RESULTS: Macronutrient but not micronutrient intake was statistically and inversely associated with decreasing CD4 cell counts. The median intake of micronutrients was higher in the study sample compared with the same age and gender group in NHANES III data; however, 25% to 35% of the women in our study sample had dietary intakes of less than 75% of the DRIs for vitamins A, C, E and B-6, and iron and zinc. White men had statistically higher values of all micronutrients compared with nonwhite men. Body mass index for men and women ranged from 23 to 25. CONCLUSIONS/APPLICATIONS: Median values for micronutrient intake from food plus vitamin/mineral supplements were adequate in the overall population studied, but a large percent of women and minorities had inadequate nutrient intakes and would benefit from dietary assessment and counseling.     

Basal urinary zinc/creatinine ratio as an indicator of dietary zinc intake in healthy adult women

OBJECTIVE: To study, in healthy women, the correlation between the basal urinary zinc/creatinine ratio and dietary zinc intake. SUBJECTS: A group of 36 healthy female University students was evaluated. Mean age and body weight were, respectively, 25.6+/-3.3 years and 54.4+/-7.0 kg. METHODS: Basal urine was collected; Zn was determined by AAS and Creatinine (Creat) by the Jaffe method. A nutritional survey of seven days was recorded. Mean daily dietary intake of energy (DE) and zinc (DZn) were calculated according to the INCAP and English or German Food Composition Tables, respectively. RESULTS: Mean dietary daily intake were as follows (x +/- SD): Energy (kcal): 1606+/-570; zinc (mg): 9.1+/-3.8; basal urine Zn/Creat ratio: 0.41+/-0.24. Individual values of the Zn/Creat ratio correlated with dietary Zn (r=0.481, p=0.0339); data grouped according to ranges of dietary Zn fit the following equation: Zn/Creat=0.160+/-0.034 DZn (mg/day); (r=0.870, p=0.00497). CONCLUSIONS: These results showed that the basal urinary Zn/Creat ratio could be a useful indicator of dietary Zn intake in healthy adult women.     

Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population

BACKGROUND: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy. OBJECTIVE: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area. DESIGN: We performed observational analyses of baseline and 2-4-mo follow-up data collected in a study designed to test the feasibility of conducting a large-scale clinical trial of vitamin supplements by mail. The study population consisted of 151 women and 109 men with a median age of 64 y. At baseline, each participant completed a food-frequency questionnaire. At follow-up, fasting serum tHcy was measured. RESULTS: In multivariable linear regression and generalized linear models, there was an independent, inverse dose-response relation between dietary protein and In tHcy (P = 0.002) and a positive, significant dose-response relation between coffee consumption and In tHcy (P for trend = 0.01). Other significant predictors of In tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B vitamins (inverse; P = 0.03). In stratified analyses restricted to persons receiving standard multivitamin therapy, the association of 1n tHcy with dietary protein and coffee persisted. CONCLUSIONS: These results support the hypothesis that increased protein intake and decreased coffee consumption may reduce tHcy and potentially prevent atherosclerotic cardiovascular disease and other disease outcomes.     

Iron supplement use and iron status among US adults: results from the third National Health and Nutrition Examination Survey

BACKGROUND: Patients with hemochromatosis are instructed to avoid taking supplemental iron. Whether supplemental iron intakes lead to higher iron status among healthy persons remains less clear. OBJECTIVE: The objective was to ascertain whether supplemental iron intakes are associated with increases in iron transport (transferrin saturation) and stores (serum ferritin) among US adults aged > or = 19 y. DESIGN: We analyzed data for 5948 adults from whom a fasting serum sample was collected during the third National Health and Nutrition Examination Survey. We used multivariable linear regression and analysis of variance to assess the association of supplemental iron intake with iron transport and stores among men (aged 19-30 y or > 30 y) and women (nonpregnant premenopausal or postmenopausal); multiple comparison tests were also performed. RESULTS: Healthy adults who took supplements containing average daily amounts of iron at < or = 3 times the recommended dietary allowance (RDA) did not have significantly higher iron transport or stores than did those who did not take supplements. In younger men, the intake of > 32 mg Fe/d (> 4x RDA) was associated with mean transport iron concentrations that were significantly higher than those in persons who took 0 to < or = 24 mg Fe/d. In older men, the intake of > 32 mg Fe/d (> 4x RDA) was associated with mean iron stores that were significantly higher than those in persons who took 0 to < or = 24 mg Fe/d; a similar result was observed in postmenopausal women, but it was of borderline statistical significance. CONCLUSION: Supplement users should be made aware of the amount of iron necessary to satisfy dietary requirements and informed of the possible influence that excess iron intake can have on body iron stores and health.     

Correlates of serum alpha- and gamma-tocopherol in the Women's Health Initiative

PURPOSE: There is increasing evidence that vitamin E (primarily alpha- and gamma-tocopherol) may reduce the risk of cardiovascular disease and some cancers, therefore it is important to understand factors that influence blood levels.METHODS: The correlates of serum alpha- and gamma-tocopherol were investigated among participants in the Women's Health Initiative (WHI), a 40-site disease prevention trial. Subjects were 1047 postmenopausal women aged 50-79 years, who provided fasting blood specimens and detailed information on diet, supplement use, and other factors at entry to the study (1994-96).RESULTS: Total serum cholesterol and triglycerides were highly correlated with serum alpha- and gamma-tocopherol concentrations and were controlled for in all analyses along with age, ethnicity and body mass index (BMI). Alpha and gamma-tocopherol were strongly negatively correlated (partial r = -0.69). The strongest predictor of serum tocopherols was average daily intake of vitamin E from supplements (partial r = 0.60 for alpha, r = -0.54 for gamma). Other factors associated with increased alpha- and/or decreased gamma-tocopherol concentrations were serum retinol and carotenoids, supplemental vitamin C, alpha-tocopherol intake from food, dietary fiber, and Hispanic ethnicity. Factors associated with lower alpha- and/or higher gamma-tocopherol concentrations included gamma-tocopherol intake from food, total fat intake, and BMI. Age, income, hormone use, and geographic location were "spuriously" associated with serum tocopherol levels through their association with supplement use, i.e., there was no such association among the subset of women not taking supplements.CONCLUSIONS: Vitamin E intake from supplements and BMI are the major independent predictors of serum tocopherol levels in women, whereas dietary factors only play a small role.