SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults.

BACKGROUND: The effect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the effects of these within the context of a high-fat meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid profiles in healthy adults in the U.S. METHODS: Subjects (n = 393) between 18-66 years of age with BMIs ranging from 18.5-45 kg/m2 were enrolled the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men: 48%; women: 52%) gave consent for genotyping. SNPs in APOA5, APOB, APOC3, APOE, and LDLR were assessed. The association between lipid markers and genotypes was tested separately for each SNP with analysis of variance (ANOVA), adjusted for sex, age, and BMI. We also examined two-factor interactions between SNPs and sex, age, or BMI. RESULTS: Women carrying the C allele of rs3135506 in APOA5 or men carrying the C allele of rs429358 in APOE had reduced HDL-cholesterol levels during fasting and postprandially. The C allele in APOE was also correlated to increased LDL-C levels. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive effect of the risk alleles of APOA5 and APOE or APOC3 and APOE was detected. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. We found no significant effects of SNPs in APOB (rs1042034) or LDLR (rs2228671) on triglycerides, cholesterol, or free fatty acid levels. CONCLUSIONS: In healthy adults, fasting and postprandial cholesterol levels are strongly correlated with the tested APOA5, APOE, and APOC3 genotypes. Sex contributes to the genetic impact of the tested SNPs on lipid profiles. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02367287. Registered February 20, 2015, https://clinicaltrials.gov/ct2/show/NCT02367287 .

Diet, Fecal Microbiome, and Trimethylamine N-Oxide in a Cohort of Metabolically Healthy United States Adults.

TMAO is elevated in individuals with cardiometabolic diseases, but it is unknown whether the metabolite is a biomarker of concern in healthy individuals. We conducted a cross-sectional study in metabolically healthy adults aged 18-66 years with BMI 18-44 kg/m2 and assessed the relationship between TMAO and diet, the fecal microbiome, and cardiometabolic risk factors. TMAO was measured in fasted plasma samples by liquid chromatography mass spectrometry. The fecal microbiome was assessed by 16S ribosomal RNA sequencing and recent food intake was captured by multiple ASA24 dietary recalls. Endothelial function was assessed via EndoPAT. Descriptive statistics were computed by fasting plasma TMAO tertiles and evaluated by ANOVA and Tukey's post-hoc test. Multiple linear regression was used to assess the relationship between plasma TMAO and dietary food intake and metabolic health parameters. TMAO concentrations were not associated with average intake of animal protein foods, fruits, vegetables, dairy, or grains. TMAO was related to the fecal microbiome and the genera Butyribrio, Roseburia, Coprobaciullus, and Catenibacterium were enriched in individuals in the lowest versus the highest TMAO tertile. TMAO was positively associated with α-diversity and compositional differences were identified between groups. TMAO was not associated with classic cardiovascular risk factors in the healthy cohort. Similarly, endothelial function was not related to fasting TMAO, whereas the inflammatory marker TNF-α was significantly associated. Fasting plasma TMAO may not be a metabolite of concern in generally healthy adults unmedicated for chronic disease. Prospective studies in healthy individuals are necessary.

Machine Learning Identifies Stool pH as a Predictor of Bone Mineral Density in Healthy Multiethnic US Adults.

BACKGROUND: A variety of modifiable and nonmodifiable factors such as ethnicity, age, and diet have been shown to influence bone health. Previous studies are usually limited to analyses focused on the association of a few a priori variables or on a specific subset of the population. OBJECTIVE: Dietary, physiological, and lifestyle data were used to identify directly modifiable and nonmodifiable variables predictive of bone mineral content (BMC) and bone mineral density (BMD) in healthy US men and women using machine-learning models. METHODS: Ridge, lasso, elastic net, and random forest models were used to predict whole-body, femoral neck, and spine BMC and BMD in healthy US men and women ages 18-66 y, with a BMI (kg/m2) of 18-44 (n = 313), using nonmodifiable anthropometric, physiological, and demographic variables; directly modifiable lifestyle (physical activity, tobacco use) and dietary (via FFQ) variables; and variables approximating directly modifiable behavior (circulating 25-hydroxycholecalciferol and stool pH). RESULTS: Machine-learning models using nonmodifiable variables explained more variation in BMC and BMD (highest R2 = 0.75) compared with when using only directly modifiable variables (highest R2 = 0.11). Machine-learning models had better performance compared with multivariate linear regression, which had lower predictive value (highest R2 = 0.06) when using directly modifiable variables only. BMI, body fat percentage, height, and menstruation history were predictors of BMC and BMD. For directly modifiable features, betaine, cholesterol, hydroxyproline, menaquinone-4, dihydrophylloquinone, eggs, cheese, cured meat, refined grains, fruit juice, and alcohol consumption were predictors of BMC and BMD. Low stool pH, a proxy for fermentable fiber intake, was also predictive of higher BMC and BMD. CONCLUSIONS: Modifiable factors, such as diet, explained less variation in the data compared with nonmodifiable factors, such as age, sex, and ethnicity, in healthy US men and women. Low stool pH predicted higher BMC and BMD. This trial was registered at www.clinicaltrials.gov as NCT02367287.

Healthy eating index patterns in adults by sex and age predict cardiometabolic risk factors in a cross-sectional study.

BACKGROUND: Associations between diet and cardiometabolic disease (CMD) risk may vary in men and women owing to sex differences in eating habits and physiology. The current secondary analysis sought to determine the ability of sex differences in dietary patterns to discriminate groups with or without CMD risk factors (CMDrf) in the adult population and if this was influenced by age. METHODS: Diet patterns and quality were evaluated using 24 h recall-based Healthy Eating Index (HEI-2015) in free-living apparently healthy men (n = 184) and women (n = 209) 18-65 y of age with BMIs of 18-44 kg/m2. Participants were stratified into low- and high-CMDrf groups based on the presence/absence of at least one CMDrf: BMI > 25 kg/m2; fasting triglycerides > 150 mg/dL; HDL cholesterol < 50 mg/dL-women or < 40 mg/dL-men; HOMA > 2; HbA1c > 5.7. Sex by age dietary patterns were stratified by multivariate analyses, with metabolic variable associations established by stepwise discriminant analysis. RESULTS: Diet quality increased with age in both sexes (P < 0.01), while women showed higher fruit, vegetable and saturated fat intake as a percentage of total energy (P < 0.05). The total-HEI score (i.e. diet quality) was lower in the high-CMDrf group (P = 0.01), however, diet quality parameters predicted CMDrf presence more accurately when separated by sex. Lower 'total vegetable' intake in the high-CMDrf group in both sexes, while high-CMDrf men also had lower 'total vegetables', 'greens and beans' intake, and high-CMDrf women had lower 'total fruits', 'whole-fruits', 'total vegetables', 'seafood and plant-proteins', 'fatty acids', and 'saturated fats' intakes (P < 0.05). Moreover, 'dairy' intake was higher in high-CMDrf women but not in men (sex by 'dairy' interaction P = 0.01). Sex by age diet pattern models predicted CMDrf with a 93 and 89% sensitivity and 84 and 92% specificity in women and men, respectively. CONCLUSIONS: Sex and age differences in dietary patterns classified participants with and without accepted CMDrfs, supporting an association between specific diet components and CMD risk that differs by sex. Including sex specific dietary patterns into health assessments may provide targeted nutritional guidance to reduce the burden of cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02367287 . ClinicalTrials.gov : NCT02298725 .

Effect of Manual Data Cleaning on Nutrient Intakes Using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24).

BACKGROUND: Automated dietary assessment tools such as ASA24® are useful for collecting 24-hour recall data in large-scale studies. Modifications made during manual data cleaning may affect nutrient intakes. OBJECTIVES: We evaluated the effects of modifications made during manual data cleaning on nutrient intakes of interest: energy, carbohydrate, total fat, protein, and fiber. METHODS: Differences in mean intake before and after data cleaning modifications for all recalls and average intakes per subject were analyzed by paired t-tests. The Chi-squared test was used to determine whether unsupervised recalls had more open-ended text responses that required modification than supervised recalls. We characterized food types of text response modifications. Correlations between predictive energy requirements, measured total energy expenditure (TEE), and mean energy intake from raw and modified data were examined. RESULTS: After excluding 11 recalls with invalidating technical errors, 1499 valid recalls completed by 393 subjects were included in this analysis. We found significant differences before and after modifications for energy, carbohydrate, total fat, and protein intakes for all recalls (P < 0.05). Limiting to modified recalls, there were significant differences for all nutrients of interest, including fiber (P < 0.02). There was not a significantly greater proportion of text responses requiring modification for home compared with supervised recalls (P = 0.271). Predicted energy requirements correlated highly with TEE. There was no significant difference in correlation of mean energy intake with TEE for modified compared with raw data. Mean intake for individual subjects was significantly different for energy, protein, and fat intakes following cleaning modifications (P < 0.001). CONCLUSIONS: Manual modifications can change mean nutrient intakes for an entire cohort and individuals. However, modifications did not significantly affect the correlation of energy intake with predictive requirements and measured expenditure. Investigators can consider their research question and nutrients of interest when deciding to make cleaning modifications.

Challenges in Designing and Delivering Diets and Assessing Adherence: A Randomized Controlled Trial Evaluating the 2010 Dietary Guidelines for Americans.

BACKGROUND: Controlled-feeding trials are challenging to design and administer in a free-living setting. There is a need to share methods and best practices for diet design, delivery, and standard adherence metrics. OBJECTIVES: This report describes menu planning, implementing, and monitoring of controlled diets for an 8-wk free-living trial comparing a diet pattern based on the Dietary Guidelines for Americans (DGA) and a more typical American diet (TAD) pattern based on NHANES 2009-2010. The objectives were to 1) provide meals that were acceptable, portable, and simple to assemble at home; 2) blind the intervention diets to the greatest extent possible; and 3) use tools measuring adherence to determine the success of the planned and implemented menu. METHODS: Menus were blinded by placing similar dishes on the 2 intervention diets but changing recipes. Adherence was monitored using daily food checklists, a real-time dashboard of scores from daily checklists, weigh-backs of containers returned, and 24-h urinary nitrogen recoveries. Proximate analyses of diet composites were used to compare the macronutrient composition of the composite and planned menu. RESULTS: Meeting nutrient intake recommendations while scaling menus for individual energy intake amounts and food portions was most challenging for vitamins D and E, the sodium-to-potassium ratio, dietary fiber, and fatty acid composition. Dietary adherence for provided foods was >95%, with no differences between groups. Urinary nitrogen recoveries were ∼80% relative to nitrogen intake and not different between groups. Composite proximate analysis matched the plan for dietary fat, protein, and carbohydrates. Dietary fiber was ∼2.5 g higher in the TAD composite compared with the planned menu, but ∼7.4 g lower than the DGA composite. CONCLUSIONS: Both DGA and TAD diets were acceptable to most participants. This conclusion was supported by self-reported consumption, quantitative weigh-backs of provided food, and urinary nitrogen recovery. Dietary adherence measures in controlled-feeding trials would benefit from standard protocols to promote uniformity across studies. The trial is registered at clinicaltrials.gov as NCT02298725.

Association of Lactase Persistence Genotypes (rs4988235) and Ethnicity with Dairy Intake in a Healthy U.S. Population.

Lactase persistence (LP) is a trait in which lactose can be digested throughout adulthood, while lactase non-persistence (LNP) can cause lactose intolerance and influence dairy consumption. One single nucleotide polymorphism (SNP ID: rs4988235) is often used as a predictor for dairy intake, since it is responsible for LP in people in European descent, and can occur in other ethnic groups. The objective of this study was to determine whether rs4988235 genotypes and ethnicity influence reported dairy consumption in the United States (U.S.). A food frequency questionnaire (FFQ) and multiple Automated Self-Administered 24-h recalls (ASA24®) were used to measure habitual and recent intake, respectively, of total dairy, cheese, cow's milk, plant-based alternative milk, and yogurt in a multi-ethnic U.S. cohort genotyped for rs4988235. Within Caucasian subjects, LP individuals reported consuming more recent total dairy and habitual total cow's milk intake. For subjects of all ethnicities, LP individuals consumed more cheese (FFQ p = 0.043, ASA24 p = 0.012) and recent total dairy (ASA24 p = 0.005). For both dietary assessments, Caucasians consumed more cheese than all non-Caucasians (FFQ p = 0.036, ASA24 p = 0.002) independent of genotype, as well as more recent intake of yogurt (ASA24 p = 0.042). LP subjects consumed more total cow's milk than LNP, but only when accounting for whether subjects were Caucasian or not (FFQ p = 0.015). Fluid milk and alternative plant-based milk consumption were not associated with genotypes or ethnicity. Our results show that both LP genotype and ethnicity influence the intake of some dairy products in a multi-ethnic U.S. cohort, but the ability of rs4988235 genotypes to predict intake may depend on ethnic background, the specific dairy product, and whether intake is reported on a habitual or recent basis. Therefore, ethnicity and the dietary assessment method should also be considered when determining the suitability of rs4988235 as a proxy for dairy intake.

Increased cytokine production by monocytes from human subjects who consumed grape powder was not mediated by differences in dietary intake patterns.

Recently, in a randomized, double-blind crossover study, we reported that consumption of grape powder by obese human subjects increased the production of the proinflammatory cytokines interleukin (IL)-1ß and IL-6 by peripheral blood monocytes after ex vivo stimulation with bacterial lipopolysaccharide compared with the placebo treatment. We hypothesized that dietary grape powder increased the production of these cytokines by stimulated monocytes. To test this hypothesis, we used 24-hour dietary recall data to determine if differences in dietary patterns played a role in increased cytokine production. No differences in total energy, protein, carbohydrates, or fat intake in the diets were observed between the grape powder and placebo intervention periods. There were no differences observed in consumption of meats and poultry, eggs, fish, vegetables, grains, total dairy, or nuts and seeds by the participants between the 2 intervention periods. When participants received the grape powder, the recall data showed decreased intakes of butyric and capric acids (P<.05), and a possible trend toward decreased intake of cheese and total fruit (P<.1). Positive associations between the intakes of margaric acid, butter, total dairy, or whole grain and IL-6 production were observed (P<.05). However, path analysis showed that total energy, protein, carbohydrates, and fats, and individual fatty acids did not influence the production of cytokines by monocytes. The path analysis indicated that the increased cytokine production by lipopolysaccharide-stimulated monocytes from obese human subjects was caused by the grape powder and not mediated by differences in dietary intake.

Design and implementation of a cross-sectional nutritional phenotyping study in healthy US adults.

BACKGROUND: Metabolic imbalance is a key determinant of risk of chronic diseases. Metabolic health cannot be assessed solely by body mass calculations or by static, fasted state biochemical readouts. Although previous studies have described temporal responses to dietary challenges, these studies fail to assess the environmental factors associated with certain metabolic phenotypes and therefore, provide little scientific rationale for potentially effective intervention strategies. METHODS/DESIGN: In this phenotyping study of healthy US adults, we are evaluating lifestyle, biological and environmental factors in addition to metabolic parameters to determine the factors associated with variations in metabolic health. A series of practical fitness, dietary, and emotional challenges are introduced and temporal responses in various areas of specialization, including immunology, metabolomics, and endocrinology, are monitored. We expect that this study will identify key factors related to healthy or unhealthy metabolic phenotypes (metabotypes) that may be modifiable targets for the prevention of chronic diseases in an individual. DISCUSSION: This study will provide novel insights into metabolic variability among healthy adults in balanced strata defined by sex, age and body mass index. Usual dietary intake and physical activity will be evaluated across these strata to determine how diet is associated with health status defined using many indicators including immune function, metabolism, body composition, physiology, response to exercise andmeal challenges and neuroendocrine assessment. A principal study goal is to identify dietary and other personal factors that will differentiate different levels of "health" among study participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02367287.

Postprandial Inflammatory Responses and Free Fatty Acids in Plasma of Adults Who Consumed a Moderately High-Fat Breakfast with and without Blueberry Powder in a Randomized Placebo-Controlled Trial.

BACKGROUND: Saturated fatty acids (FAs) released from triglyceride-rich lipoproteins (TGRLs) activate Toll-like receptor 2 (TLR-2) and induce the expression of proinflammatory cytokines in monocytes. Certain plant polyphenols inhibit TLR-mediated signaling pathways. OBJECTIVE: We determined whether plasma free FAs (FFAs) after a moderately high-fat (MHF, 40% kcal from fat) breakfast modulate the inflammatory status of postprandial blood, and whether blueberry intake suppresses FFA-induced inflammatory responses in healthy humans. METHODS: Twenty-three volunteers with a mean ± SEM age and body mass index (in kg/m(2)) of 30 ± 3 y and 21.9 ± 0.4, respectively, consumed an MHF breakfast with either a placebo powder or 2 or 4 servings of blueberry powder in a randomized crossover design. The placebo powder was provided on the first test day and the blueberry powder doses were randomized with a 2-wk washout period. Plasma concentrations of lipids, glucose, and cytokines were determined. To determine whether FFAs derived from TGRL stimulate monocyte activation, and whether this is inhibited by blueberry intake, whole blood was treated with lipoprotein lipase (LPL). RESULTS: The median concentrations of FFAs and cytokines [tumor necrosis factor-α, interleukin (IL)-6 and IL-8] in postprandial plasma (3.5 h) decreased compared with fasting plasma regardless of the blueberry intake (P < 0.001 for FFAs and P < 0.05 for cytokines). However, concentrations of FFAs and cytokines including IL-1ß increased in LPL-treated whole blood compared with untreated blood samples from participants who consumed the placebo powder. Blueberry intake suppressed IL-1ß and IL-6 production in LPL-treated postprandial blood compared with the placebo control when fasting changes were used as a covariate. CONCLUSIONS: The plasma FFA concentration may be an important determinant affecting inflammatory cytokine production in blood. Supplementation with blueberry powder did not affect plasma FFA and cytokine concentrations; however, it attenuated the cytokine production induced by ex vivo treatment of whole blood with LPL. This trial was registered at clinicaltrials.gov as NCT01594008.

Dietary supplementation with purified citrus limonin glucoside does not alter ex vivo functions of circulating T lymphocytes or monocytes in overweight/obese human adults.

Overweight/obesity is associated with chronic inflammation and impairs both innate and adaptive immune responses. Limonoids found in citrus fruits decreased cell proliferation and inflammation in animal studies. We hypothesized that limonin glucoside (LG) supplementation in vivo will decrease the ex vivo proliferation of T cells and the production of inflammatory cytokines by monocytes and T cells. In a double-blind, randomized, cross-over study, 10 overweight/obese human subjects were served purified LG or placebo drinks for 56 days each to determine the effects of LG on immune cell functions. The percentage of CD14+CD36+ cells in whole blood was analyzed by flow cytometry. Peripheral blood mononuclear cells were isolated and activated with CD3 plus CD28 antibodies (T-lymphocyte activation) or lipopolysaccharide (monocyte activation). Interferon γ, tumor necrosis factor α, interleukin (IL) 2, IL-4, and IL-10 were measured in supernatants from activated T cells. Supernatants from activated monocytes were analyzed for the production of tumor necrosis factor α, IL-1ß, and IL-6. Peripheral blood mononuclear cells were prestained with PKH dye and activated with CD3 plus CD28 antibodies to determine the proliferative responses of CD4+ and CD8+ T lymphocytes by flow cytometry. No differences were observed for CD14+CD36+ monocyte populations, T-cell proliferation, or the production of T cell and monocyte cytokines between the 2 treatments. Thus, LG supplementation in vivo did not affect ex vivo functions of T cells and monocytes, whereas it decreased several circulating markers of hepatic inflammation as we previously reported.

Dietary grape powder increases IL-1ß and IL-6 production by lipopolysaccharide-activated monocytes and reduces plasma concentrations of large LDL and large LDL-cholesterol particles in obese humans.

Obese individuals are at an increased risk of developing CVD, hypertension, type 2 diabetes, and bacterial and viral infections when compared with the normal-weight population. In a 9-week randomised, double-blind, cross-over study, twenty-four obese subjects aged between 20 and 60 years and with a BMI between 30 and 45 kg/m2 were fed grape or placebo powder for 3-week intervals to determine the effects of dietary grapes on blood lipid profiles, plasma inflammatory marker concentrations and immune cell function. Blood samples were collected on days 1 and 8 for obtaining baseline information and at weeks 3, 4, 8 and 9. Comprehensive chemistry panels, lipid profile analyses by NMR, measurement of plasma inflammatory marker concentrations, and analyses of cytokine production by activated T lymphocytes and monocytes were performed for each blood draw. Dietary grape powder reduced the plasma concentrations of large LDL-cholesterol and large LDL particles compared with the placebo powder (P< 0·05). The concentrations of interferon-γ, TNF-α, IL-4 and IL-10 were measured in supernatants from peripheral blood mononuclear cells (PBMC) activated with anti-CD3/CD28 antibodies and those of TNF-α, IL-1ß, IL-6 and IL-8 were measured in supernatants from PBMC activated with lipopolysaccharide (LPS). No difference in the production of T-cell cytokines was observed between the two intervention groups. The production of IL-1ß and IL-6 was increased in supernatants from LPS-activated PBMC in the grape powder group compared with the placebo powder group (P< 0·05). These data suggest that dietary grapes may decrease atherogenic lipid fractions in obese individuals and increase the sensitivity of monocytes in a population at a greater risk of developing infections.

Effects of dietary strawberry powder on blood lipids and inflammatory markers in obese human subjects.

Obesity is a strong risk factor for the development of CVD, hypertension and type 2 diabetes. The overall goal of the present pilot study was to feed strawberries, in the form of freeze-dried powder, to obese subjects to determine whether dietary strawberries beneficially altered lipid profiles and reduced blood markers of inflammation compared with a control intervention. A total of twenty healthy subjects (thirteen females and seven males) aged between 20 and 50 years with a BMI between 30 and 40 kg/m2 completed the present 7-week double-blind, randomised, cross-over trial. Each subject received a prepared diet 7 d/week for 7 weeks consisting of approximately 35 % of energy from fat, 20 % protein, 45 % carbohydrate and 14 g fibre. Blood was collected on days 1 and 8 for baseline information. After the first week, subjects were randomly assigned to the strawberry powder (equivalent to four servings of frozen strawberries) or control (strawberry-flavoured) intervention for 3 weeks. For the remaining 3 weeks, subjects crossed over to the opposite intervention. Blood was collected again at the end of weeks 3, 4, 6 and 7. A comprehensive chemistry panel, lipid profile analyses and measurement of inflammatory mediators were performed for each blood draw. A 3-week dietary intervention with strawberry powder reduced plasma concentrations of cholesterol and small HDL-cholesterol particles, and increased LDL particle size in obese subjects (P < 0·05). Dietary strawberry powder reduced risk factors for CVD, stroke and diabetes in obese volunteers, suggesting a potential role for strawberries as a dietary means to decrease obesity-related disease.

High-selenium yeast supplementation in free-living North American men: no effect on thyroid hormone metabolism or body composition.

In a prior study, we observed decreased serum 3,3',5-triiodothyronine (T(3)), increased serum thyrotropin and increased body weight in five men fed 297 microg/d of selenium (Se) in foods naturally high in Se while confined in a metabolic research unit. In an attempt to replicate and confirm those observations, we conducted a randomized study of high-Se yeast supplements (300 microg/d) or placebo yeast administered to 42 healthy free-living men for 48 weeks. Serum thyroxine, T(3) and thyrotropin did not change in supplemented or control subjects. Body weight increased in both groups during the 48-week treatment period and remained elevated for the 48-week follow-up period. Body fat increased by 1.2 kg in both groups. Energy intake and voluntary activity levels were not different between the groups and remained unchanged during the treatment period. Dietary intakes of Se, macronutrients and micronutrients were not different between groups and remained unchanged during the treatment period. These results suggest that our previous observation of a hypothyroidal response to high-Se foods was confounded by some aspect of the particular foods used, or were merely chance observations. Because of the high dose and long administration period, the present study suggests that the effects of Se supplements on thyroid hormone metabolism and energy metabolism in healthy North American men with adequate Se status do not represent a significant risk for unhealthy weight gain.

Response of selenium status indicators to supplementation of healthy North American men with high-selenium yeast.

The essential nutrient selenium is required in microgram amounts [recommended dietary allowance (RDA) = 55 microg/day, 699 nmol/day] and has a narrow margin of safety (upper tolerable intake limit = 400 microg/day, 5 micromol/day). We conducted a randomized placebo-controlled study of high-selenium yeast, the form used in most supplements (300 microg/day, 3.8 micromol/day), administered to 42 free-living healthy men for 48 weeks. Dietary intakes of selenium, macronutrients, and micronutrients were not different between groups and did not change during the study. Supplementation more than doubled urinary selenium excretion from 69 to 160 microg/day (876 to 2,032 nmol/day). Urinary excretion was correlated with recent selenium intake estimated from 3-day diet records: urinary selenium excretion = 42 microg/day (533 nmol/day) + 0.132 x dietary selenium intake, p < 0.001. Dietary selenium intake was not significantly correlated with the other indicators of selenium status, presumably because urinary selenium excretion reflected recent intake, and tissue selenium was homeostatically controlled. After 48 weeks of supplementation, plasma selenium was increased 60% from 142 to 228 microg/l (1.8 to 2.9 micromol/l), and erythrocyte selenium was approximately doubled from 261 to 524 microg/l (3.3 to 6.6 micromol/l). Selenium concentrations increased more modestly in hair (56%) and platelets (42%). Platelets were the only blood component in which glutathione peroxidase activity was significantly related to selenium content. Selenium levels decreased rapidly after the end of supplementation, and there were no significant differences in selenium status indicators between groups by week 96. The absorption, distribution, and excretion of selenium from high-Se yeast were similar to selenium in foods.