Objective: We examined whether vitamin C supplements (1000 mg) and multivitamins containing vitamin C (60 mg) are associated with the incidence of age-related cataract extraction in a population-based, prospective cohort of women.

Design: Our study included 24,593 women aged 49–83 y from the Swedish Mammography Cohort (follow-up from September 1997 to October 2005). We collected information on dietary supplement use and lifestyle factors with the use of a self-administrated questionnaire. Cataract extraction cases were identified by linkage to the cataract extraction registers in the geographical study area.

Results: During the 8.2 y of follow-up (184,698 person-years), we identified 2497 cataract extraction cases. The multivariable hazard ratio (HR) for vitamin C supplement users compared with that for nonusers was 1.25 (95% CI: 1.05, 1.50). The HR for the duration of >10 y of use before baseline was 1.46 (95% CI: 0.93, 2.31). The HR for the use of multivitamins containing vitamin C was 1.09 (95% CI: 0.94, 1.25). Among women aged ≥65 y, vitamin C supplement use increased the risk of cataract by 38% (95% CI: 12%, 69%). Vitamin C use among hormone replacement therapy users compared with that among nonusers of supplements or of hormone replacement therapy was associated with a 56% increased risk of cataract (95% CI: 20%, 102%). Vitamin C use among corticosteroid users compared with that among nonusers of supplements and corticosteroids was associated with an HR of 1.97 (95% CI: 1.35, 2.88).

Conclusion: Our results indicate that the use of vitamin C supplements may be associated with higher risk of age-related cataract among women.

Objective: We determined the relation between dietary n–6 (–6) and n–3 (–3) fatty acid intakes and n–6 and n–3 fatty acids in RBC EPGs and phosphatidylcholine in near-term pregnant women.

Design: The subjects were 105 healthy Canadian pregnant (36 wk gestation) women. Fatty acid intakes were estimated by food-frequency questionnaire, and fasting venous blood samples were collected.

Results: DHA and EPA intakes were positively associated with RBC EPG and phosphatidylcholine concentrations of DHA ( = 0.309 and 0.369, respectively; P < 0.001) and EPA ( = 0.391 and 0.228, respectively; P < 0.001) and inversely associated with RBC EPG 22:4n–6 and 22:5n–6 (P < 0.001). In RBCs, concentrations of linoleic acid (LA, 18:2n–6) were inversely associated with DHA, EPA, and ARA, respectively, in EPGs (r = –0.432, P < 0.01; r = –0.201, P < 0.04; and r = –0.303, P < 0.01) and phosphatidylcholine (r = –0.460, –0.490, and –0.604; P < 0.01 for all).

Conclusions: Membrane fatty acids are influenced by the amount and balance of fatty acid substrates. Our results suggest the competitive interaction of LA with ARA, EPA, and DHA, with no evidence that higher LA increases ARA. Biochemical indicators to suggest that DHA is limiting are present in our population. This trial was registered at clinicaltrials.gov as NCT00620672.

Objective: The objective was to determine the postprandial effects of intake of different fatty acids on the gene expression profiles of peripheral blood mononuclear cells (PBMCs).

Design: In a single-blind crossover study, 21 healthy male volunteers consumed shakes enriched in PUFAs, monounsaturated fatty acids (MUFAs), or saturated fatty acids (SFAs) in random order. Blood samples were collected before and at several time points after intake. Whole-genome gene expression profiles of PBMCs were examined before and 6 h after intake of the PUFA and SFA shakes. Additionally, ex vivo incubation of human PBMCs with different fatty acids was performed.

Results: Whole-genome expression analysis showed distinct differences between PUFA and SFA consumption. PUFA intake decreased the expression of genes in liver X receptor signaling, whereas SFA intake increased the expression of these genes. PUFA intake also increased the expression of genes related to cellular stress responses. MUFA intake had an intermediate effect on several genes. Ex vivo experiments showed a direct effect of free fatty acids on PBMC gene expression.

Conclusions: This study showed that PBMCs can reveal fatty acid–specific gene expression profiles in young healthy men after the consumption of different fatty acids, as evidenced by the opposite effects of PUFA and SFA intakes on the expression of genes involved in liver X receptor signaling. This trial was registered at www.clinicaltrials.gov as NCT01000194.

Objective: We evaluated the relation between UrMis in different tissues and the effect of folate supplementation on UrMis.

Design: We analyzed UrMis concentrations in rectal mucosa (n = 92) and white blood cells (WBCs; n = 60) among individuals randomly assigned to receive supplementation with 1 mg folate/d or placebo, who were then evaluated for colorectal adenoma recurrence.

Results: As expected, total homocysteine was significantly lower among the study participants who received active folate treatment (Wilcoxon's P = 0.003) than among those in the placebo group. The median UrMis concentration in rectal mucosa and WBCs among individuals treated with folate was not significantly lower than that in those who received placebo (Wilcoxon's P = 0.17). UrMis concentrations in both rectal mucosa and WBCs did not correlate significantly with folate measured in plasma and red blood cells. UrMis in rectal mucosa was marginally associated with an increased risk of adenoma recurrence (odds ratio per SD: 1.43; 95% CI: 0.91, 2.25).

Conclusions: UrMis measurements in WBCs are not a robust surrogate for UrMis measurements in the rectal mucosa (Spearman correlation coefficient = 0.23, P = 0.08). Furthermore, folate supplementation in an already replete population (half treated with folic acid supplements and all exposed to folic acid fortification of the food supply) was not significantly associated with reduced UrMis in rectal mucosa cells or WBCs. Large-scale studies are needed to evaluate whether excessive UrMis concentrations are an important risk factor for colorectal neoplasia. This trial was registered at clinicaltrials.gov as NCT00272324.

Objective: Our objective was to combine data on dietary folate (as measured by two 24-h recalls) and folic acid from dietary supplements (collected with a 30-d frequency questionnaire) with the use of the bias-corrected best power method to adjust for within-person variability.

Design: The National Health and Nutrition Examination Survey (NHANES) is a nationally representative, cross-sectional survey. Linear contrasts were constructed to determine differences in dietary and total folate intake for age and racial-ethnic groups by sex; prevalence of inadequate and excessive intakes is presented.

Results: In 2003–2006, 53% of the US population used dietary supplements; 34.5% used dietary supplements that contained folic acid. Total folate intake (in dietary folate equivalents) was higher for men (813 ± 14) than for women (724 ± 16) and higher for non-Hispanic whites (827 ± 19) than for Mexican Americans (615 ± 11) and non-Hispanic blacks (597 ± 12); 29% of non-Hispanic black women had inadequate intakes. Total folate and folic acid intakes are highest for those aged ≥50 y, and 5% exceed the Tolerable Upper Intake Level.

Conclusions: Improved total folate intake is warranted in targeted subgroups, which include women of childbearing age and non-Hispanic black women, whereas other population groups are at risk of excessive intake.

Objective: Our objective was to evaluate the reproducibility of ad libitum energy intake with the use of a computerized vending machine system.

Design: Twelve individuals (mean ± SD: 36 ± 8 y old; 41 ± 8% body fat) consumed a weight-maintaining diet for 3 d; subsequently, they self-selected all food with the use of a computerized vending machine system for an additional 3 d. Mean daily energy intake was calculated from the actual weight of foods consumed and expressed as a percentage of weight-maintenance energy needs (%WMEN). Subjects repeated the study multiple times during 2 y. The within-person reproducibility of energy intake was determined through the calculation of the intraclass correlation coefficients (ICCs) between visits.

Results: Daily energy intake for all subjects was 5020 ± 1753 kcal during visit 1 and 4855 ± 1615 kcal during visit 2. There were no significant associations between energy intake and body weight, body mass index, or percentage body fat while subjects used the vending machines, which indicates that intake was not driven by body size or need. Despite overconsumption (%WMEN = 181 ± 57%), the reproducibility of intake between visits, whether expressed as daily energy intake (ICC = 0.90), %WMEN (ICC = 0.86), weight of food consumed (ICC = 0.87), or fat intake (g/d; ICC = 0.87), was highly significant (P < 0.0001).

Conclusion: Although ad libitum energy intake exceeded %WMEN, the within-person reliability of this intake across multiple visits was high, which makes this a reproducible method for the measurement of ad libitum intake in subjects who reside on a research unit. This trial was registered at clinicaltrials.gov as NCT00342732.

Objective: To determine the influence of vitamin E on Plasmodium parasite development and murine CM outcome, -tocopherol transfer protein (-TTP), a regulator of vitamin E in the host circulation, was abrogated.

Design: -TTP knockout mice were infected with P. berghei ANKA, and survival rate, parasitemia, brain histologic alterations, and brain barrier permeability were assessed. In addition, mRNA expression of the cytokines and adhesion molecules involved in this neurologic pathology were monitored.

Results: -TTP knockout mice infected with P. berghei ANKA did not exhibit any clinical or pathologic signs of CM, and a histologic analysis of the brain tissues in these animals showed no alteration of blood-brain barrier integrity compared with that in control mice. Interestingly, protection of the blood-brain barrier in these infected -TTP knockout mice was lost when dietary supplementation with vitamin E was added to their diet. Moreover, interleukins and adhesion molecule transcripts in the brain of control mice were significantly up-regulated compared with those in the -TTP knockout mice.

Conclusion: It appears that a deficiency of -tocopherol in the circulation prevents CM and suggests that -TTP is a putative target for the early prevention of CM.

Objective: The objective of this study was to evaluate the effect of oral isoflavone supplementation on endothelial function, as measured by flow-mediated dilation (FMD), in postmenopausal women.

Design: A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endothelial function in postmenopausal women. Trials were searched in PubMed, Embase, the Cochrane Library database, and reviews and reference lists of relevant articles. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effect models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity.

Results: A total of 9 trials were reviewed in the present meta-analysis. Overall, the results of the 9 trials showed that isoflavone significantly increased FMD (WMD: 1.75%; 95% CI: 0.83%, 2.67%; P = 0.0002). Meta-regression analysis indicated that the age-adjusted baseline FMD was inversely related to effect size. Subgroup analysis showed that oral supplementation of isoflavone had no influence on FMD if the age-adjusted baseline FMD was ≥5.2% (4 trials; WMD: 0.24%; 95% CI: –0.94%, 1.42%; P = 0.69). This improvement seemed to be significant when the age-adjusted baseline FMD levels were <5.2% (5 trials; WMD: 2.22%; 95% CI: 1.15%, 3.30%; P < 0.0001), although significant heterogeneity was still detected in this low-baseline-FMD subgroup.

Conclusions: Oral isoflavone supplementation does not improve endothelial function in postmenopausal women with high baseline FMD levels but leads to significant improvement in women with low baseline FMD levels.

Objective: We investigated the effect of c9,t11 CLA supplementation on aortic pulse wave velocity (a marker of atherosclerosis) and on cardiovascular risk factors in overweight and obese but otherwise apparently healthy subjects.

Design: In a double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned 401 subjects, aged 40–70 y and with a body mass index (in kg/m²) ≥ 25, to receive either 4 g CLA/d (2.5 g c9,t11 CLA/d and 0.6 g trans-10,cis-12 CLA/d) or placebo supplements for 6 mo. Aortic pulse wave velocity, blood pressure, anthropometric characteristics, and concentrations of fasting lipid, glucose, insulin, and C-reactive protein measured before and after supplementation.

Results: During the intervention, mean (±SE) pulse wave velocity did not change in the c9,t11 CLA group (0.00 ± 0.07) compared with the placebo group (0.09 ± 0.06). There was no effect of c9,t11 CLA supplementation on blood pressure, body composition, insulin resistance, or concentrations of lipid, glucose, and C-reactive protein.

Conclusion: This study does not support an antiatherosclerotic effect or an effect on cardiovascular risk factors of c9,t11 CLA. This trial was registered at www.clinicaltrials.gov as NCT00706745.

Objective: The objective was to determine whether the postprandial metabolic responses elicited by fat and protein were influenced by the insulin sensitivity of the subjects and whether fat and protein modulate glucose responses through different mechanisms.

Design: Healthy nondiabetic subjects aged 18–45 y took 50 g oral glucose with 0–30-g doses of canola oil and whey protein on 11 separate mornings after fasting overnight. The subjects were classified into 3 fasting serum insulin (FSI) groups: FSI < 40 pmol/L (n = 9), 40 ≤ FSI < 70 pmol/L (n = 8), and FSI ≥ 70 pmol/L (n = 8). The relative glycemic response was expressed as the incremental area under the curve (AUC) after each test meal divided by the mean AUC of the glucose control in each subject.

Results: Protein significantly decreased glucose (P < 0.0001) and hepatic insulin extraction (P <0.0001) and increased insulin (P < 0.0001) and glucagon-like peptide 1 (P = 0.004); however, protein had no significant effect on C-peptide (P = 0.69) or on the insulin secretion rate (P = 0.13). No significant FSI x fat (P = 0.19) or FSI x protein (P = 0.08) interaction effects on glucose AUC were observed. In addition, the changes in relative glycemic response per gram of fat (r = –0.05, P = 0.82) or protein (r = –0.08, P = 0.70) were not related to FSI.

Conclusions: The hypoglycemic effect of fat and protein was not blunted by insulin resistance. Protein increased insulin but had no effect on C-peptide or the insulin secretion rate, which suggests decreased hepatic insulin extraction or increased C-peptide clearance.

Objective: The objective was to assess the relations between obesity indicators and cardiometabolic risk factors in 324 Chilean children 4 y of age.

Design: We collected anthropometric measurements and calculated general indicators of obesity (weight, body mass index, sum of 4 skinfold thicknesses, percentage fat, and body fat index) and central obesity (waist circumference, waist-to-hip ratio, waist-to-height ratio, and truncal fatness based on skinfold thickness). We measured blood sample concentrations of C-reactive protein, interleukin-6, homeostasis model assessment of insulin resistance, triglycerides, and total, LDL, and HDL cholesterol. We used correlation and multiple linear regression analyses.

Results: The prevalence of obesity (BMI-for-age z score >2, World Health Organization 2006), central obesity (≥90th percentile, third National Health and Nutrition Examination Survey), and lipid disorders was high (13%, 11%, and ≥ 20%, respectively), and 70% of the children had at least one cardiometabolic risk factor. Most correlations between obesity and central obesity indicators were moderate to strong (0.40 < r < 0.96). Obesity was positively but weakly associated with C-reactive protein in both sexes and with homeostasis model assessment of insulin resistance only in girls (all r < 0.3, P < 0.05). Obesity indicators were unrelated to interleukin-6 and lipid concentrations (P > 0.05). Overall, obesity indicators explained, at most, 8% of the variability in cardiometabolic risk factors.

Conclusions: Obesity and central obesity were common, and most of the children had at least one cardiometabolic risk factor, particularly lipid disorders. Obesity and central obesity indicators were highly intercorrelated and, overall, were weakly related to cardiometabolic status. At this age, body mass index and waist circumference were poor predictors of cardiometabolic status.

Objective: To present a picture of global obesity and examine the shifts in BMI in children, I examined BMI data for men and women at the upper ends of the BMI distributions in Australia, China, the United Kingdom, and the United States.

Design: As representative data, I used directly measured weight and height for children aged 6–18 y and for men and women aged ≥19 y. Quantile regression analysis with BMI was used to determine the outcome, and the coefficients of age, age squared, and age cubed represented the explanatory variables plotted to determine mean BMI at the 95th centile for each age group. Overweight and obesity measures across all selected countries, with the use of nationally representative surveys and the 95th centile mean BMI, were determined.

Results: Among women, much larger increases were found in mean BMI at the 95th percentile in Australia (+5.7 BMI units) and the United Kingdom (+3.7 BMI units) than in the United States (+2.7 BMI units) in one-half the time. In contrast, among children, younger Chinese children experienced the largest increase. For example, the mean BMI at the 95th centile for 6-y-old Chinese children is 24.8 (a 5.0 increase), which is 2.6 BMI units more than the BMI at the 95th centile for children in the United States.

Conclusions: Among children, BMIs for US children at the 95th centile are below those in China, whereas among women, Australian and UK women are rapidly approaching BMIs found in US women.

Objective: We sought to determine the effect of vitamin D status on health outcomes.

Design: Healthy community-dwelling women (n = 1471) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation. 25(OH)D was measured at baseline in all women. Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline.

Results: Fifty percent of women had a seasonally adjusted 25(OH)D concentration <50 nmol/L. These women were significantly older, heavier, and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration ≥50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration <50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities. Women with a seasonally adjusted 25(OH)D concentration <50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome, including fracture, falls, bone density, or grip strength or any nonskeletal outcomes, including death, myocardial infarction, cancer, heart failure, diabetes, or adverse changes in blood pressure, weight, body composition, cholesterol, or glucose.

Conclusions: Vitamin D insufficiency is more common in older, frailer women. Community-dwelling older women with a seasonally adjusted 25(OH)D concentration <50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities. Randomized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes. This trial was registered at www.anzctr.org.au as ACTRN 012605000242628.

Objective: We examined the efficacy of isoflavones (extracted from soy protein) on bone mineral density (BMD) in nonosteoporotic postmenopausal women. We hypothesized that isoflavone tablets would spare BMD, with biological (age, body weight, serum 25-hydroxyvitamin D) and lifestyle (physical activity, dietary intake) factors modulating BMD loss.

Design: Our double-blind, randomized controlled trial (36 mo) included healthy postmenopausal women (aged 45.8–65.0 y) with intent-to-treat (n = 224) and compliant (n = 208) analyses. Treatment groups consisted of a placebo control group and 2 soy isoflavone groups (80 compared with 120 mg/d); women received 500 mg calcium and 600 IU vitamin D₃. Outcomes included lumbar spine, total proximal femur, femoral neck, and whole-body BMD.

Results: Analysis of variance for intent-to-treat and compliant (≥80%) models, respectively, showed no treatment effect for spine (P = 0.46, P = 0.21), femur (P = 0.86, P = 0.46), neck (P = 0.17, P = 0.14), or whole-body (P = 0.86, P = 0.78) BMD. From baseline to 36 mo, BMD declined regardless of treatment. In intent-to-treat and compliant models, respectively, BMD decreases were as follows: spine (–2.08%, –1.99%), femur (–1.43%, –1.38%), neck (–2.56%, –2.51%), and whole body (–1.66%, –1.62%). Regression analysis (compliant model) indicated that age, whole-body fat mass, and bone resorption were common predictors of BMD change. After adjustment for these factors, 120 mg (compared with placebo) was protective (P = 0.024) for neck BMD. We observed no treatment effect on adverse events, endometrial thickness, or bone markers.

Conclusion: Our results do not show a bone-sparing effect of extracted soy isoflavones, except for a modest effect at the femoral neck. This trial was registered at clinicaltrials.gov as NCT00043745.

Objectives: This study aimed to examine demographic disparities and 5-y longitudinal and secular trends (1999–2004) in whole-grain intake among 2 cohorts of Minnesota adolescents.

Design: Whole-grain intake was examined among 996 adolescent males and 1222 adolescent females who were Project EAT (Eating Among Teens) participants in 1999 and 2004. Multinomial logistic regression models were used to examine demographic differences in whole-grain intake. Mixed linear regression models were used to estimate 1) longitudinal trends among 2 cohorts of adolescents during developmental transitions and 2) age-matched secular trends between the cohorts at middle adolescence.

Results: In 1999, 11% of adolescent males and 13% of adolescent females reported that they consumed more than one daily serving of whole grains. Whole-grain intake was lowest among youth of the Native American and white races and among youth of high socioeconomic status. During the transition from middle to late adolescence, whole-grain intake increased by a mean of 0.14 daily servings among adolescent males and 0.09 daily servings among adolescent females. No significant changes in whole-grain intake were shown among either sex during the transition from early to middle adolescence. Yeast breads, popcorn, and ready-to-eat breakfast cereals were major sources of whole grains in 1999 and 2004.

Conclusion: Findings suggest the need to advance efforts that target improvements in the amount of whole-grain foods selected by adolescents.

Objective: The objective was to perform a systematic review and meta-analysis of RCTs of GTCs on anthropometric variables, including body mass index (BMI), body weight, waist circumference (WC), and waist-to-hip ratio (WHR).

Design: A systematic literature search of MEDLINE, EMBASE, CENTRAL, and the Natural Medicines Comprehensive Database was conducted through April 2009. RCTs that evaluated GTCs with or without caffeine and that reported BMI, body weight, WC, or WHR were included. The weighted mean difference of change from baseline (with 95% CIs) was calculated by using a random-effects model.

Results: Fifteen studies (n = 1243 patients) met the inclusion criteria. On meta-analysis, GTCs with caffeine decreased BMI (–0.55; 95% CI: –0.65, –0.40), body weight (–1.38 kg; 95% CI: –1.70, –1.06), and WC (–1.93 cm; 95% CI: –2.82, –1.04) but not WHR compared with caffeine alone. GTC ingestion with caffeine also significantly decreased body weight (–0.44 kg; 95% CI: –0.72, –0.15) when compared with a caffeine-free control. Studies that evaluated GTCs without concomitant caffeine administration did not show benefits on any of the assessed anthropometric endpoints.

Conclusions: The administration of GTCs with caffeine is associated with statistically significantly reductions in BMI, body weight, and WC; however, the clinical significance of these reductions is modest at best. Current data do not suggest that GTCs alone positively alter anthropometric measurements.

Objective: This study evaluated the effect of calcium supplementation on the change in the ratio of HDL to LDL cholesterol (primary endpoint) and on changes in cholesterol fractions, triglycerides, blood pressure, and body composition (secondary endpoints).

Design: We carried out a randomized controlled trial of calcium supplementation in 323 generally healthy men over a period of 2 y. Subjects were randomly assigned to take placebo, 600 mg Ca/d, or 1200 mg Ca/d.

Results: There was no significant treatment effect on the ratio of HDL to LDL cholesterol (P = 0.47) nor on weight, fat mass, lean mass, triglycerides, or total, LDL, or HDL cholesterol (P > 0.28 for all). There were downward trends in systolic and diastolic blood pressures within the calcium-supplemented groups, but there were no significant treatment effects over the whole trial period (P > 0.60). In a post hoc analysis of those with baseline calcium intakes below the median value (785 mg/d), blood pressures showed borderline treatment effects (P = 0.05–0.06 for changes at 2 y in those who received 1200 mg Ca/d compared with placebo: systolic, –4.2 mm Hg; diastolic, –3.3 mm Hg). Low magnesium intake showed a similar interaction. No treatment effects on weight or body composition were found.

Conclusions: These data do not show significant effects of calcium supplementation on serum lipids or body composition. Calcium supplementation in those with low dietary intakes may benefit blood pressure control. This trial was registered with the Australian Clinical Trials Registry as ACTRN 012605000274673.

Objective: We examined the way in which glucose kinetics and related factors change after breakfast as a result of colonic fermentation.

Design: In a crossover design, 10 healthy men ingested as an evening meal white wheat bread (WB) or cooked barley kernels (BA) that were rich in nondigestible carbohydrates. In the morning after intake of 50 g ¹³C-enriched glucose, the dual-isotope technique was applied to determine glucose kinetics. Plasma insulin, free fatty acid, interleukin-6, tumor necrosis factor-, and short-chain fatty acid concentrations and breath-hydrogen excretion were measured.

Results: The plasma glucose response after the glucose drink was 29% lower after the BA evening meal (P = 0.019). The insulin response was the same, whereas mean (±SEM) tissue glucose uptake was 30% higher (20.2 ± 1.9 compared with 15.5 ± 1.8 mL/2 h; P = 0.016) after the BA evening meal, which indicated higher peripheral insulin sensitivity (P = 0.001). The 4-h mean postprandial interleukin-6 (19.7 ± 5.1 compared with 5.1 ± 0.7 pg/mL; P = 0.024) and tumor necrosis factor- (7.8 ± 2.1 compared with 5.3 ± 1.6 pg/mL; P = 0.008) concentrations after the glucose drink were higher after the WB evening meal. Butyrate concentrations (P = 0.041) and hydrogen excretion (P = 0.005) were higher in the morning after the BA evening meal.

Conclusion: In healthy subjects, factors related to colonic fermentation of nondigestible carbohydrates increase peripheral insulin sensitivity and moderate glucose-associated inflammation.

Objective: The aim was to identify and characterize the effects of MC4R variants in Hispanic children.

Design: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits.

Results: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81.

Conclusion: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure.

Objective: The objective of this study was to evaluate the acute effects of a dairy-rich diet on oxidative and inflammatory stress in overweight and obese subjects in the absence of adiposity changes.

Design: Twenty subjects (10 obese, 10 overweight) participated in a blinded, randomized, crossover study of dairy- compared with soy-supplemented eucaloric diets. Two 28-d dietary periods were separated by a 28-d washout period. Inflammatory and oxidative stress biomarkers were measured on days 0, 7, and 28 of each dietary period.

Results: The dairy-supplemented diet resulted in significant suppression of oxidative stress (plasma malondialdehyde, 22%; 8-isoprostane-F₂, 12%; P < 0.0005) and lower inflammatory markers (tumor necrosis factor-, 15%, P < 0.002; interleukin-6, 13%, P < 0.01; monocyte chemoattractant protein-1, 10%, P < 0.0006) and increased adiponectin (20%, P < 0.002), whereas the soy exerted no significant effect. These effects were evident by day 7 of treatment and increased in magnitude at the end of the 28-d treatment periods. There were no significant differences in response to treatment between overweight and obese subjects for any variable studied.

Conclusion: An increase in dairy food intake produces significant and substantial suppression of the oxidative and inflammatory stress associated with overweight and obesity. This trial was registered at clinicaltrials.gov as NCT00686426.

Objective: The objective was to assess the validity and reliability of the Recent Physical Activity Questionnaire (RPAQ), which assesses usual physical activity (PA) in 4 domains (work, travel, recreation, and domestic life).

Design: Total energy expenditure (TEE) was measured for 14 d by using the doubly labeled water (DLW) technique combined with a measure of resting metabolic rate to yield PA energy expenditure (PAEE) in 25 men and 25 women. Simultaneously, intensity of activity was measured by using combined heart rate and movement sensing for 11 d. Repeatability of the RPAQ was assessed in an independent sample of 71 women and 60 men aged 31–57 y.

Results: Estimated TEE and PAEE were significantly associated with criterion measures (TEE: r = 0.67; PAEE: r = 0.39) with mean (±SD) biases of –3452 ± 2025 kJ/d and –13 ± 24 kJ · d^–1 · kg^–1. The correlation between self-reported and measured time spent was significant for vigorous PA (r = 0.70) and marginally insignificant for sedentary time (r = 0.27, P = 0.06). The mean biases were relatively small for sedentary time and vigorous PA: 0.7 ± 2.8 h/d and + 12 ± 24 min/d, respectively. The intraclass correlation coefficient for repeatability of total PAEE (kJ/d) was 0.76 (P < 0.0001).

Conclusion: The RPAQ is the first questionnaire with demonstrated validity for ranking individuals according to their time spent at vigorous-intensity activity and overall energy expenditure.

Objective: This study aimed to systematically review the present literature and to quantify the effect of multiple micronutrients on cognitive performance in schoolchildren.

Methods: The Institute for Scientific Information Web of Knowledge and local medical databases were searched for trials published from 1970 to 2008. Randomized controlled trials that investigated the effect of ≥3 micronutrients compared with placebo on cognition in healthy children aged 0–18 y were included following protocol. Data were extracted by 2 independent researchers. The cognitive tests used in the trials were grouped into several cognitive domains (eg, fluid and crystallized intelligence), and pooled effect size estimates were calculated per domain. Heterogeneity was explored through sensitivity and meta-regression techniques.

Results: Three trials were retrieved in children aged <5 y, and 17 trials were retrieved in children aged 5–16 y. For the older children, pooled random-effect estimates for intervention were 0.14 SD (95% CI: –0.02, 0.29; P = 0.083) for fluid intelligence and –0.03 SD (95% CI: –0.21, 0.15; P = 0.74) for crystallized intelligence, both of which were based on 12 trials. Four trials yielded an overall effect of 0.30 SD (95% CI: 0.01, 0.58; P = 0.044) for academic performance. For other cognitive domains, no significant effects were found.

Conclusions: Multiple micronutrient supplementation may be associated with a marginal increase in fluid intelligence and academic performance in healthy schoolchildren but not with crystallized intelligence. More research is required, however, before public health recommendations can be given.

Objective: The objective was to assess the relation of dietary and physical activity weight-control strategies, alone and together, with subsequent weight change.

Design: This was a prospective study of 4456 female adolescents and young adults aged 14–22 y in the ongoing Growing Up Today Study. Weight-control behaviors, including dietary approaches and physical activity, were self-reported in 2001 and were used to predict weight change from 2001 to 2005.

Results: In 2001–2002, 23.7% of female adolescents and young adults were trying to maintain their weight and another 54.4% were trying to lose weight. Approximately 25% used each of the following weight-control strategies: not eating snacks, following low-calorie or low-fat diets, and limiting portion sizes. In addition, 47.7% reported exercising at least occasionally for weight control. During 4 y of follow-up, participants gained an average of 3.3 kg. None of the dietary approaches to weight control predicted less weight change; however, females who exercised ≥5 d/wk gained significantly less weight than did their peers (–0.9 kg; 95% CI: –1.4, –0.4). The most successful strategy for weight-gain prevention among the females was to limit portion sizes (–1.9 kg; 95% CI: –2.6, –1.1) combined with frequent exercise.

Conclusions: Our results suggest that physical activity is a necessary strategy for long-term weight control among adolescents and young adult females. Combining dietary weight-control approaches with physical activity is the most effective method for reducing weight gain.

Objective: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism.

Design: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations.

Results: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P < 0.01) increased total fecal cholesterol excretion (36 ± 6% and 74 ± 10%, respectively) and biliary cholesterol excretion (38 ± 7% and 77 ± 12%, respectively) and reduced percentage intestinal cholesterol absorption (–10 ± 1% and –25 ± 3%, respectively). Serum LDL cholesterol declined significantly only with the highest phytosterol dose (–8.9 ± 2.3%); a trend was observed with the 459-mg/d dose (–5.0 ± 2.1%; P = 0.077).

Conclusions: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

Objective: Our objective was to examine the relation between dietary protein and risk of stroke in men who participated in the Health Professionals Follow-Up Study.

Design: A total of 43,960 men who were free of cardiovascular disease and cancer at baseline were included in the analysis. Dietary protein (total, animal, and vegetable) was assessed with the use of a food-frequency questionnaire at 5 time points during the follow-up period of 1986–2004. Cox proportional hazards models were used to calculate multivariate relative risks and 95% CIs, which represented the effect of the substitution of protein for an equal percentage of energy from carbohydrate.

Results: During 18 y of follow-up there were 1057 incident stroke events (638 ischemic, 171 hemorrhagic, and 248 of unknown type). For total stroke, the relative risk for the top quintile of percentage energy from protein compared with the bottom was 1.14 (95% CI: 0.90, 1.43; P for linear trend: 0.43) for total protein, 1.11 (95% CI: 0.87, 1.41; P for linear trend: 0.52) for animal protein, and 0.82 (95% CI: 0.60, 1.12; P for linear trend: 0.17) for vegetable protein. The results were similar when ischemic and hemorrhagic stroke subtypes were considered separately.

Conclusion: In contrast to studies in Japanese populations, this study did not show a statistically significant association between total, animal, or vegetable protein and risk of stroke in this population of US men.

Objective: The aim of this study was to compare the frequency of LM in healthy southern and northern Indian populations.

Design: A total of 153 healthy volunteers (76 from southern and 77 from northern India) were evaluated for LM by using a lactose tolerance test (LTT), a lactose hydrogen breath test (lactose HBT), and polymerase chain reaction–restriction fragment length polymorphism to identify the lactase gene C/T-13910 polymorphism (confirmed by sequencing).

Results: Volunteers from southern and northern India were comparable in age and sex. The LTT result was abnormal in 88.2% of southern Indians and in 66.2% of northern Indians (P = 0.001). The lactose HBT result was abnormal in 78.9% of southern Indians and in 57.1% of northern Indians (P = 0.003). The CC genotype was present in 86.8% and 67.5% (P = 0.002), the CT genotype was present in 13.2% and 26.0% (P = 0.036), and the TT genotype was present in 0% and 6.5% (P = 0.03) of southern and northern Indians, respectively. The frequency of symptoms after the lactose load (47.4% compared with 15.6%; P < 0.001) and peak concentrations of breath hydrogen (88.5 ± 71.9 compared with 55.4 ± 61.9 ppm; P = 0.003), both of which might indicate the degree of lactase deficiency, were higher in southern than in northern Indians.

Conclusion: The frequency and degree of LM is higher in southern than in northern Indian healthy populations because of genetic differences in these populations.

Objective: The objective was to estimate usual folic acid intake above the UL and adjusted serum and red blood cell folate, vitamin B-12, methylmalonic acid, and homocysteine concentrations among US adults by 3 major folic acid intake sources—enriched cereal-grain products (ECGP), ready-to-eat cereals (RTE), and supplements (SUP)—categorized into 4 mutually exclusive consumption groups.

Design: We used data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 (n = 8258).

Results: Overall, 2.7% (95% CI: 1.9%, 3.5%) of adults consumed more than the UL of folic acid. The proportions of those who consumed folic acid from ECGP only, ECGP+RTE, ECGP+SUP, and ECGP+RTE+SUP were 42%, 18%, 25%, and 15%, respectively. Of 60% of adults who did not consume supplements containing folic acid (ECGP only and ECGP+RTE), 0% had intakes that exceeded the UL. Of 34% and 6% of adults who consumed supplements with an average of ≤400 and >400 µg folic acid/d, <1% and 47.8% (95% CI: 39.6%, 56.0%), respectively, had intakes that exceeded the UL. Consumption of RTE and/or supplements with folic acid was associated with higher folate and vitamin B-12 and lower homocysteine concentrations, and consumption of supplements with vitamin B-12 was associated with lower methylmalonic acid concentrations (P < 0.001).

Conclusion: At current fortification levels, US adults who do not consume supplements or who consume an average of ≤400 µg folic acid/d from supplements are unlikely to exceed the UL in intake for folic acid.

Objective: Our aim was to examine the differences in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) between white and African American adults.

Design: The sample included 1967 adults aged 18–84 y, including 790 white women, 435 African American women, 606 white men, and 136 African American men. Total body fat was measured by using dual-energy X-ray absorptiometry, whereas abdominal VAT and SAT cross-sectional areas (L4–L5 level) were measured by using computed tomography. Sex-specific differences in SAT and VAT between racial groups were analyzed by the use of general linear models, which controlled for age and total body fat. Additional models tested for racial differences in VAT and SAT and controlled for age, total body fat, smoking, and menopausal status. Statistical significance was accepted at P < 0.05.

Results: Abdominal VAT was significantly higher in white than in African American men and women, even after adjustment for covariates. White women had significantly lower SAT than did African American women, both before and after adjustment for covariates. White men had significantly higher SAT than did African American men, but after adjustment for covariates, their SAT was lower than that of African American men.

Conclusions: Abdominal visceral adiposity is significantly greater in white men and women. After adjustment for covariates, white men and women had significantly lower SAT than did African American men and women. The results of this study highlight the heterogeneity of human body fat distribution across racial groups.This trial was registered at clinicaltrials.gov as NCT00959270.

Objectives: We examined associations and compared effect sizes of these newly identified obesity susceptibility loci with various anthropometric traits and assessed their cumulative effects and predictive value for obesity risk.

Design: We genotyped 12 single nucleotide polymorphisms (SNPs) from each locus in 20,431 individuals (age: 39–79 y) from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk cohort. General linear model and logistic regression were used to examine associations, and the area under the receiver operating characteristic curve (AUC) was used to assess the predictive value of these variants for obesity risk.

Results: Effect sizes of the risk alleles ranged between 0.058 and 0.329 for BMI (in kg/m²), between 0.094 and 0.866 kg for weight, and between 0.085 and 0.819 cm for waist circumference, with rs1121980 (FTO locus) showing the largest effect. Risk alleles of rs7132908 (FAIM2 locus) and rs17782313 (MC4R locus) were also associated with taller height. On average, each additional risk allele was associated with increases of 0.149 in BMI (P = 1.54E-22), 0.444 kg in body weight (P = 9.88E-22), and 0.357 cm in waist circumference (P = 1.10E-18) and 10.8% (P = 9.83E-16) and 5.5% (P = 3.38E-10) increased risks of obesity and overweight, respectively. All SNPs combined explained 0.9% of BMI variation, with an AUC of 0.574 (95% CI: 0.559, 0.590) for prediction of obesity.

Conclusions: Common variants for BMI have small effects on obesity measures and show different association patterns with anthropometric traits, with the largest effect shown for the FTO locus. These variants have cumulative effects, yet their predictive value for obesity risk is limited.