Objective: The objective was to test the hypothesis that temperature in a heat-dissipating region of the hand is elevated in obese adults.

Design: Obese [body mass index (in kg/m²) ≥ 30] and normal-weight (NW; body mass index = 18–25) adults were studied under thermoneutral conditions at rest. Core body temperature was measured by using ingested telemetric capsules. The temperatures of the third fingernail bed of the right hand and of abdominal skin from an area 1.5 cm inferior to the umbilicus were determined by using infrared thermography. Abdominal skin temperatures were also measured via adhesive thermistors that were placed over a prominent skin-surface blood vessel and over an adjacent nonvessel location. The groups were compared by analysis of covariance with age, sex, race, and room temperature as covariates.

Results: Core temperature did not differ significantly between the 23 obese and 13 NW participants (P = 0.74). However, infrared thermography–measured fingernail-bed temperature was significantly higher in obese subjects than in NW subjects (33.9 ± 0.7°C compared with 28.6 ± 0.9°C; P < 0.001). Conversely, infrared thermography–measured abdominal skin temperature was significantly lower in obese subjects than in NW subjects (31.8 ± 0.2°C compared with 32.8 ± 0.3°C; P = 0.02). Nonvessel abdominal skin temperatures measured by thermistors were also lower in obese subjects (P = 0.04).

Conclusions: Greater subcutaneous abdominal adipose tissue in obese adults may provide a significant insulating layer that blunts abdominal heat transfer. Augmented heat release from the hands may offset heat retention in areas of the body with greater adiposity, thereby helping to maintain normothermia in obesity. This trial was registered at clinicaltrials.gov as NCT00266500.

Objectives: We aimed to 1) replicate previous findings that showed preferential central accumulation of adipose tissue in recently weight-restored AN women compared with control subjects, 2) describe the change within patients with longer-term (1-y) weight maintenance, and 3) compare adipose tissue distribution after 1-y maintenance with that of control subjects.

Design: Body composition and adipose tissue distribution were assessed by whole-body magnetic resonance imaging in women with AN shortly after weight normalization (n = 30) and again 1 y after hospital discharge (n = 16) and in 8 female control subjects at 2 time points.

Results: With acute weight restoration, AN patients had significantly greater visceral and intermuscular adipose tissue compared with control women [visceral: 0.75 ± 0.26 compared with 0.51 ± 0.26 kg in AN patients and controls, respectively (P = 0.02); intermuscular: 0.46 ± 0.17 compared with 0.29 ± 0.13 kg in AN patients and controls, respectively (P = 0.01)]. With maintenance of normal weight for 1 y, visceral adipose tissue distribution in AN patients was not different from that in healthy control subjects.

Conclusions: In adult women with AN, normalization of weight in the short term is associated with a distribution of adipose tissue that is consistent with a central adiposity phenotype. This abnormal distribution appears to normalize within a 1-y period of weight maintenance. This research was registered at clinicaltrials.gov as NCT 00271921 and NCT 00368667.

Objective: This study examined the effects of ADF that is administered under controlled compared with self-implemented conditions on body weight and coronary artery disease (CAD) risk indicators in obese adults.

Design: Sixteen obese subjects (12 women, 4 men) completed a 10-wk trial, which consisted of 3 phases: 1) a 2-wk control phase, 2) a 4-wk weight loss/ADF controlled food intake phase, and 3) a 4-wk weight loss/ADF self-selected food intake phase.

Results: Dietary adherence remained high throughout the controlled food intake phase (days adherent: 86%) and the self-selected food intake phase (days adherent: 89%). The rate of weight loss remained constant during controlled food intake (0.67 ± 0.1 kg/wk) and self-selected food intake phases (0.68 ± 0.1 kg/wk). Body weight decreased (P < 0.001) by 5.6 ± 1.0 kg (5.8 ± 1.1%) after 8 wk of diet. Percentage body fat decreased (P < 0.01) from 45 ± 2% to 42 ± 2%. Total cholesterol, LDL cholesterol, and triacylglycerol concentrations decreased (P < 0.01) by 21 ± 4%, 25 ± 10%, and 32 ± 6%, respectively, after 8 wk of ADF, whereas HDL cholesterol remained unchanged. Systolic blood pressure decreased (P < 0.05) from 124 ± 5 to 116 ± 3 mm Hg.

Conclusion: These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD risk. This trial was registered at clinicaltrials.gov as UIC-004-2009.

Objective: The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients.

Design: Forty-two high-risk volunteers (19 men and 23 women; mean ± SD age: 69.7 ± 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated.

Results: Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake.

Conclusions: These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis. This trial was registered in the Current Controlled Trials at London, International Standard Randomized Controlled Trial Number, at controlled-trials.com as ISRCTN75176807.

Objective: The objective was to further develop and validate a fluorometric assay for pyridoxamine phosphate oxidase (PPO) activity as a measure of riboflavin status.

Design: A fluorometric assay was optimized for the flavin-dependent enzyme PPO in erythrocytes. Hemolysates from a previous riboflavin intervention study (2- and 4-mg riboflavin supplements) were used to investigate the responsiveness of the method to changes in riboflavin intake.

Results: PPO activity and the PPO activation coefficient (PPOAC) were used to assess riboflavin status. Both PPO activity and PPOAC responded to riboflavin supplements (P < 0.01), but only PPO showed a dose response (P < 0.001). The change from baseline to after the intervention in PPOAC and PPO enzyme activity was significantly inversely correlated (P < 0.001). Both PPO activity and PPOAC were strongly correlated with EGRAC (P < 0.001). Additionally, both PPOAC and EGRAC showed a significant inverse correlation with dietary riboflavin intake (P < 0.01); PPO activity was positively correlated with riboflavin intake (P < 0.01).

Conclusion: PPO activity could be used as a biomarker for measuring riboflavin status, especially in populations with a high prevalence of G6PD deficiency. This trial is registered at www.isrctn.org as ISRCTN35811298.

Objective: We assessed the relation between changes in dietary intake, specifically sugar and fiber intakes, with changes in adiposity and risk factors for type 2 diabetes in a longitudinal analysis of overweight Latino youth.

Design: Overweight Latino youth (n = 85; aged 11–17 y) underwent the following measures over 2 y [mean (±SD) time difference was 1.5 ± 0.5 y]: dietary intake by 2-d diet recalls, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and glucose and insulin indexes by oral- and intravenous-glucose-tolerance tests. Partial correlations and repeated-measures analysis of covariance assessed the relation between changes in dietary intake with changes in adiposity and glucose and insulin indexes, independent of the following a priori covariates: sex, Tanner stage, time between visits, and baseline dietary and metabolic variables of interest.

Results: Increases in total dietary fiber (g/1000 kcal) and insoluble fiber (g/1000 kcal) were associated with decreases in visceral adipose tissue (VAT) (r = –0.29, P = 0.02, and r = –0.27, P = 0.03, for total dietary and insoluble fiber, respectively), independent of baseline covariates and change in subcutaneous abdominal adipose tissue. Participants who had decreased total dietary fiber (mean decrease of 3 g · 1000 kcal^–1 · d^–1) had significant increases in VAT compared with participants who had increased total dietary fiber (21% compared with –4%; P = 0.02). No other changes in dietary variables were related to changes in adiposity or metabolic variables.

Conclusion: Small reductions in dietary fiber intake over 1–2 y can have profound effects on increasing visceral adiposity in a high-risk Latino youth population.

Objective: The objective was to determine the plasma pharmacokinetics of DHBA and DHPPA in human subjects to estimate whether they show potential as biomarkers for whole-grain rye and/or wheat intake.

Design: Fifteen human volunteers followed a low-alkylresorcinol diet for 2 d before ingesting a single dose of high-fiber rye bread containing 45 mg alkylresorcinols. Plasma samples were collected for 25 h, and the alkylresorcinol metabolites were quantified by HPLC with coulometric electrode array detection.

Results: Maximum concentrations were reached at 6 h for both metabolites, although interindividual variation was found. The half-life was significantly (P < 0.0002) longer for DHPPA (16.3 h) than for DHBA (10.1 h). No significant differences were discovered between women and men in the half-life of each metabolite, which, from a pharmacokinetic point of view, is the most important parameter. The area under the curve differed significantly between DHBA and DHPPA (P < 0.0001) and between women and men (P = 0.03 for DHBA and P = 0.01 for DHPPA). However, when corrected for body weight, the difference between sexes was no longer significant.

Conclusions: Our results suggest that DHBA and DHPPA are both good candidate biomarkers for whole-grain rye and/or wheat intake; however, DHPPA is the better indicator because of its longer half-life. This could provide a practical tool when investigating the association between diet and diseases.

Objective: This prospective cohort study of 447 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with preexistent CKD examined the association between sugar-sweetened beverage consumption (<1 drink/wk, 1–6 drinks/wk, and ≥1 drink/d) and progression of CKD.

Design: β-Coefficients for continuous outcomes of changes in estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) were calculated by using linear regression. Odds ratios for binary outcomes of accelerated decline in eGFR, defined as >2 mL · min^–1 · 1.73 m^–2 per year, and clinically significant progression of albuminuria (defined as attainment of UACR ≥30 mg/g for participants without microalbuminuria at visit 1 or a ≥25% increase in UACR for participants with baseline microalbuminuria) were evaluated by using logistic regression.

Results: The mean (±SD) baseline eGFR was 52 ± 6 mL · min^–1 · 1.73 m^–2 per year, and median baseline UACR was 6.3 mg/g (interquartile range: 3.5–17.6). Univariate and multivariate analyses showed no association between sugar-sweetened beverage consumption and rate of eGFR decline or changes in urinary albumin to creatinine ratio. The multivariate odds ratios comparing participants who drank ≥1 sugary beverage daily with those who drank ≤1 beverage weekly were 0.62 (95% CI: 0.27, 1.41) for accelerated eGFR decline and 1.51 (95% CI: 0.49, 4.62) for clinically significant progression of albuminuria.

Conclusion: A higher consumption of sugar-sweetened beverages was not associated with disease progression, on the basis of either eGFR or the urinary albumin to creatinine ratio, in MESA participants with preexistent CKD.

Objective: This study evaluated the nutritional status, energy intake, and expenditure profile of PD patients with and without previous circulatory congestion.

Design: We conducted a cross-sectional study in 244 PD patients, of whom 92 had previous circulatory congestion. We estimated dietary energy intake by using a locally validated 7-d food-frequency questionnaire and by assessing resting energy expenditure (REE) and total energy expenditure (TEE) with indirect calorimetry and a locally validated physical activity questionnaire, respectively.

Results: In comparison with those without circulatory congestion, patients with previous circulatory congestion were more malnourished by subjective global assessment (59% compared with 36%; P < 0.001), had lower handgrip strength, had lower midarm muscle circumference, had lower dietary protein (0.98 ± 0.45 compared with 1.19 ± 0.44 g · kg^–1 · d^–1; P < 0.001), and had lower energy intake (92.5 ± 37.0 compared with 110.9 ± 35.7 kJ · kg^–1 · d^–1; P < 0.001) but had higher C-reactive protein (P = 0.025) and higher REE (P < 0.001). However, no difference in TEE was noted between the 2 groups, which indicated lower activity energy expenditure among patients with previous circulatory congestion. The resulting energy balance was significantly more negative for patients with previous circulatory congestion than for those without previous circulatory congestion (P = 0.050). Furthermore, the prevalence of malnutrition increased with increasing episodes of circulatory congestion (P = 0.017).

Conclusions: Patients with previous circulatory congestion had significantly more inflammation, more muscle wasting, and higher REE but lower activity energy expenditure and energy and protein intakes in keeping with an anorexia-cachexia syndrome. The mechanisms of increased REE and reduced energy intake among patients with previous circulatory congestion warrant further investigation.

Objective: The objective was to examine associations between objectively measured PA and its subcomponents [ie, time spent at light-intensity PA, moderate-intensity PA (MPA), vigorous-intensity PA (VPA), and moderate-plus-vigorous-intensity PA (MVPA)], independent of sedentary time, and self-reported leisure screen time (television and electronic game use) with indexes of adiposity in a population-based sample of British children.

Design: A cross-sectional study was conducted in 1862 UK children aged 9–10 y. PA and sedentary activity were measured by accelerometry, and indicators of adiposity were waist circumference, body mass index (BMI), and fat mass index calculated from bioimpedance measurements. Screen time was assessed by self-report. We examined the associations between PA subcomponents and adiposity by multilevel linear models adjusted for birth weight, maternal BMI, energy intake, and sleep duration.

Results: Objectively measured sedentary time was positively associated with waist circumference (P = 0.04) and fat mass index (P = 0.05), independent of age and sex. However, this association was attenuated after adjustment for MVPA and other covariates. VPA (all P < 0.0001), combined MVPA (all P < 0.01), and total activity (counts/min) (all P < 0.001) were all inversely associated with each of the adiposity indexes, independent of sedentary time and other important covariates. Associations were weaker for MPA: P = 0.05, 0.87, and 0.1 for waist circumference, BMI, and fat mass index, respectively.

Conclusions: Time spent in VPA appears to be more strongly associated with adiposity than sedentary time. Interventions may therefore need to incorporate higher intensity–based activities to curb the growing obesity epidemic.

Objective: The objective was to investigate body composition during a high-altitude expedition by using non–empirically derived methods, experimentally manipulating energy intake, and investigating the influence of initial body composition.

Design: Forty-one participants completed a 21-d expedition in the Himalayas. Energy intake was manipulated with a double-blind, placebo-controlled, randomized trial of carbohydrate energy supplementation. Body composition was assessed before and after the expedition by using a 4-component model including fat mass, total body water, bone mineral mass, and residual mass (principally protein and glycogen). Data were analyzed by repeated-measures analysis of variance.

Results: Participants allocated to receive carbohydrate were given an additional 15,058 ± 6211 kcal over the 21-d expedition (>6 kcal · kg^–1 · d^–1). Nevertheless, the functionally important residual mass decreased in both groups by 6% (main effect of time: P = 0.021), with no effect of allocation (interaction effect: P = 0.116). Similar decreases were observed for fat mass (11%) and total body water (3%), which were also unabated by allocation. Furthermore, high initial fat mass (by median split) did not preserve residual mass (high-fat compared with low-fat participants: residual loss = 5% compared with 8%; P = 0.990).

Conclusions: High-altitude exposure decreased body mass, including the functionally important residual component. These losses were not abated by increasing energy intake or an initially high fat mass. Factors other than negative energy balance must contribute to body-composition changes with chronic hypoxia. This trial was registered at clinicaltrials.gov as NCT00731510.

Objective: The objective was to investigate whether macronutrient dietary composition plays a role in weight maintenance and in improvement of cardiovascular disease risk factors.

Design: The study comprised 2 phases. Phase 1 featured a very-low-energy diet for 3 mo. In phase 2, the subjects were randomly assigned to an HP or an HC diet for 12 mo. The diets were isocaloric, tightly controlled, and individually prescribed for weight maintenance. The subjects were overweight or obese but otherwise healthy men and women.

Results: The subjects lost an average of 16.5 kg during phase 1 and maintained a mean (±SEM) weight loss of 14.5 ± 1.2 kg (P < 0.001) during phase 2; no significant differences between groups were observed. By the end of the study, reductions in systolic blood pressure were 14.3 ± 2.4 mm Hg for the HP group and 7.7 ± 2.2 mm Hg for the HC group (P < 0.045). Forty-seven percent of the 180 subjects who began the study completed both phases.

Conclusions: The results indicate that the protein or carbohydrate content of the diet has no effect on successful weight-loss maintenance. A general linear model analysis indicated that dietary treatment (HP or HC) was a significant factor in systolic blood pressure change and in favor of the HP diet. This trial was registered at www.clinicaltrials.gov as NCT 00625236.

Objectives: Our aims were to investigate the effect of exercise performed in the heat on energy intake in the subsequent meal and to determine concentrations of circulating appetite-related hormones.

Design: In a randomized, counterbalanced design, 11 active male participants completed 3 experimental trials in a fasted state: exercise in the heat (36°C), exercise in a neutral temperature (25°C), and a resting control (25°C). The exercise trials consisted of treadmill running for 40 min at 70% O_2peak. After each trial, participants were presented with a buffet-type breakfast of precisely known quantity and nutrient composition, which they could consume ad libitum.

Results: Energy intake was greater after exercise in the neutral temperature compared with the control (P = 0.021) but was similar between exercise in the heat and the control and between the 2 exercise trials. When accounting for the excess energy expended during exercise, relative energy intake during exercise in the heat was lower than the control (P = 0.002) but was similar between exercise in the neutral temperature and the control and between exercise in the heat and in the neutral temperature. The lower relative energy intake after exercise in the heat was associated with an elevated tympanic temperature and circulating concentrations of peptide YY (P < 0.05).

Conclusion: Exercise in a neutral environmental temperature is associated with higher energy intake in the subsequent meal compared with a control, whereas exercise in the heat is not.

Objectives: We examined the effects of a combined 7-d low–glycemic index (low-GI) diet and exercise training intervention on insulin sensitivity in older obese humans.

Design: Participants [n = 32; mean (±SEM) age: 66 ± 1 y; body mass index (in kg/m²): 33.8 ± 0.7] were randomly assigned to a parallel, double-blind, controlled-feeding trial and underwent supervised aerobic exercise (EX; 60 min/d at 80–85% maximum heart rate) in combination with either a low-GI (LoGI + EX: 41.1 ± 0.4) or a high-GI (HiGI + EX: 80.9 ± 0.6) diet. All meals were provided and were isocaloric to individual energy requirements. Insulin sensitivity and hepatic glucose production were assessed with a 40–mU ⋅ m^–2 · min^–1 hyperinsulinemic euglycemic clamp combined with a [6,6-²H₂]-glucose infusion.

Results: After the intervention, small decreases were observed in body weight (–1.6 ± 0.2 kg; P < 0.0001) and fat mass (–1.7 ± 0.9%; P = 0.004) in both groups. Maximal aerobic capacity ( O₂max) also improved slightly (0.06 ± 0.02 L/min; P = 0.004). Resting systolic blood pressure, fasting glucose, insulin, triglycerides, and cholesterol all decreased after the study (all P < 0.05). Larger changes in systolic blood pressure and O_2max were seen in the LoGI + EX group. Insulin-stimulated glucose disposal (P < 0.001), insulin suppression of hepatic glucose production (P = 0.004), and postabsorptive fat oxidation (P = 0.03) improved equally in both groups after the intervention.

Conclusions: These findings suggest that the metabolic improvements after short-term exercise training in older obese individuals are dependent on increased physical activity and are not influenced by a low-GI diet. However, a low-GI diet has added benefit in alleviating hypertension, thus reducing the risk of diabetic and vascular complications.

Objective: Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women.

Design: Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation.

Results: Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002).

Conclusions: In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at clinicaltrials.gov as NCT00183001.

Objective: Our aim was to examine the effects of prebiotic supplementation on satiety and related hormones during a test meal for human volunteers by using a noninvasive micromethod for blood sampling to measure plasma gut peptide concentrations.

Design: This study was a randomized, double-blind, parallel, placebo-controlled trial. A total of 10 healthy adults (5 men and 5 women) were randomly assigned to groups that received either 16 g prebiotics/d or 16 g dextrin maltose/d for 2 wk. Meal tolerance tests were performed in the morning to measure the following: hydrogen breath test, satiety, glucose homeostasis, and related hormone response.

Results: We show that the prebiotic treatment increased breath-hydrogen excretion (a marker of gut microbiota fermentation) by 3-fold and lowered hunger rates. Prebiotics increased plasma glucagon-like peptide 1 and peptide YY concentrations, whereas postprandial plasma glucose responses decreased after the standardized meal. The areas under the curve for plasma glucagon-like peptide 1 and breath-hydrogen excretion measured after the meal (0–60 min) were significantly correlated (r = 0.85, P = 0.007). The glucose response was inversely correlated with the breath-hydrogen excretion areas under the curve (0–180 min; r = –0.73, P = 0.02).

Conclusion: Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.

Objective: The objective was to assess effects of IF on intermediary metabolism and energy expenditure.

Design: Glucose, glycerol, and valine fluxes were measured after 2 wk of IF and a standard diet (SD) in 8 lean healthy volunteers in a crossover design, in the basal state and during a 2-step hyperinsulinemic euglycemic clamp, with assessment of energy expenditure and phosphorylation of muscle protein kinase B (AKT), glycogen synthase kinase (GSK), and mammalian target of rapamycine (mTOR). We hypothesized that IF selectively increases peripheral glucose uptake and lowers proteolysis, thereby protecting protein stores.

Results: No differences in body weight were observed between the IF and SD groups. Peripheral glucose uptake and hepatic insulin sensitivity during the clamp did not significantly differ between the IF and SD groups. Likewise, lipolysis and proteolysis were not different between the IF and SD groups. IF decreased resting energy expenditure. IF had no effect on the phosphorylation of AKT but significantly increased the phosphorylation of glycogen synthase kinase. Phosphorylation of mTOR was significantly lower after IF than after the SD.

Conclusions: IF does not affect whole-body glucose, lipid, or protein metabolism in healthy lean men despite changes in muscle phosphorylation of GSK and mTOR. The decrease in resting energy expenditure after IF indicates the possibility of an increase in weight during IF when caloric intake is not adjusted. This study was registered at www.trialregister.nl as NTR1841.

Objective: The aim was to determine the most current distribution of serum vitamin C concentrations in the United States and the prevalence of deficiency in selected subgroups.

Design: Serum concentrations of total vitamin C were measured in 7277 noninstitutionalized civilians aged ≥6 y during the cross-sectional, nationally representative NHANES 2003–2004. The prevalence of deficiency was compared with results from NHANES III.

Results: The overall age-adjusted mean from the square-root transformed (SM) concentration was 51.4 µmol/L (95% CI: 48.4, 54.6). The highest concentrations were found in children and older persons. Within each race-ethnic group, women had higher concentrations than did men (P < 0.05). Mean concentrations of adult smokers were one-third lower than those of nonsmokers (SM: 35.2 compared with 50.7 µmol/L and 38.6 compared with 58.0 µmol/L in men and women, respectively). The overall prevalence (±SE) of age-adjusted vitamin C deficiency was 7.1 ± 0.9%. Mean vitamin C concentrations increased (P < 0.05) and the prevalence of vitamin C deficiency decreased (P < 0.01) with increasing socioeconomic status. Recent vitamin C supplement use or adequate dietary intake decreased the risk of vitamin C deficiency (P < 0.05).

Conclusions: In NHANES 2003–2004, vitamin C status improved, and the prevalence of vitamin C deficiency was significantly lower than that during NHANES III, but smokers and low-income persons were among those at increased risk of deficiency.

Objective: The objective was to determine whether supplementing mildly iodine-deficient children with iodine improves cognition.

Design: A randomized, placebo-controlled, double-blind trial was conducted in 184 children aged 10–13 y in Dunedin, New Zealand. Children were randomly assigned to receive a daily tablet containing either 150 µg I or placebo for 28 wk. Biochemical, anthropometric, and dietary data were collected from each child at baseline and after 28 wk. Cognitive performance was assessed through 4 subtests from the Wechsler Intelligence Scale for Children.

Results: At baseline, children were mildly iodine deficient [median urinary iodine concentration (UIC): 63 µg/L; thyroglobulin concentration: 16.4 µg/L]. After 28 wk, iodine status improved in the supplemented group (UIC: 145 µg/L; thyroglobulin: 8.5 µg/L), whereas the placebo group remained iodine deficient (UIC: 81 µg/L; thyroglobulin: 11.6 µg/L). Iodine supplementation significantly improved scores for 2 of the 4 cognitive subtests [picture concepts (P = 0.023) and matrix reasoning (P = 0.040)] but not for letter-number sequencing (P = 0.480) or symbol search (P = 0.608). The overall cognitive score of the iodine-supplemented group was 0.19 SDs higher than that of the placebo group (P = 0.011).

Conclusions: Iodine supplementation improved perceptual reasoning in mildly iodine-deficient children and suggests that mild iodine deficiency could prevent children from attaining their full intellectual potential. The trial was registered with the Australia New Zealand Clinical Trials Register as ACTRN12608000222347.

Objective: The present study evaluated serum lutein, zeaxanthin, and macular pigment optical density (MPOD) responses at 0.25°, 0.5°, and 1° retinal eccentricities to the consumption of 2 and 4 egg yolks/d by older adults taking cholesterol-lowering medications.

Design: Subjects consumed foods containing 2 followed by 4 egg yolks/d for 5 wk each with a 4-wk egg-free period at baseline and between the 2 interventions.

Results: Changes in MPOD (n = 37) with egg yolk consumption were inversely associated (P < 0.05) with baseline MPOD. Subjects with low-baseline MPOD (defined as MPOD ≤0.5 at 0.25°, ≤0.4 at 0.5°, and ≤0.35 at 1°) showed increases of ≤50% (P < 0.05) with 4 egg yolks at the 3 retinal eccentricities. MPOD increased by 31% (P = 0.059) at 0.5° with 2 egg yolks. Serum lutein increased by only 16% and 24% (P < 0.05) compared with increases of 36% and 82% (P < 0.001) in serum zeaxanthin (n = 52) after consumption of 2 and 4 egg yolks, respectively. Serum HDL cholesterol increased by 5% (P < 0.05) after consumption of 2 and 4 egg yolks. Serum LDL cholesterol did not change with either egg yolk treatment.

Conclusions: Consumption of 4 egg yolks/d, and possibly of 2 egg yolks/d, for 5 wk benefited macular health in older adults with low MPOD. Serum HDL cholesterol increased without an increase in LDL cholesterol in this study population, most of whom were taking cholesterol-lowering statins.

Objectives: With the use of iron stable isotopes, we aimed to determine whether circulating hepcidin predicts dietary iron bioavailability, to quantify the amount of absorbed iron after oral iron loading, and to measure the plasma hepcidin response.

Design: In the first study, young women (n = 98) with an iron status varying from iron deficiency anemia to iron sufficiency (women with serum ferritin concentrations 25–40 µg/L were not included) were given stable isotope–labeled test meals (n = 196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after which plasma hepcidin and iron bioavailability were measured. In the second study, iron-sufficient men (n = 4) were given 3.8- and 60-mg oral doses of labeled ferrous sulfate. The stable isotope appearance curve was determined, and the plasma hepcidin response was measured over 6 h.

Results: In study 1, plasma hepcidin and plasma ferritin were strongly correlated (r = 0.79, P < 0.001). Plasma hepcidin significantly, but modestly, predicted iron bioavailability from ferrous sulfate and ferrous fumarate (r = –0.51 and –0.46, respectively; P < 0.0001) but not from ferric pyrophosphate (r = –0.30, P = 0.056, respectively). In study 2, the 3.8-mg dose increased mean circulating absorbed iron to a peak of 0.42 µmol/L at 60 min but did not increase plasma hepcidin, The 60-mg dose increased mean circulating absorbed iron to a peak of 5.9 µmol/L at 120 min and produced an 30% increase in mean plasma hepcidin at 6 h (P < 0.01).

Conclusions: Plasma hepcidin is only a modest predictor of dietary iron bioavailability in humans. Oral iron loading, measured by stable-isotope appearance curves, increases circulating hepcidin.

Objectives: The objectives were to investigate whether, within BMI categories, the GWG with the lowest risks to mother and infant varied with parity and to describe these risks in short (<160 cm), young (<20 y), and smoking women.

Design: Of 27,030 primiparous and 31,407 multiparous women with term births within the Danish National Birth Cohort, self-reported GWG was divided into 6 categories (<5, 5–9, 10–15, 16–19, 20–24, and ≥25 kg). Population-based registers provided information about birth outcomes. GWG-specific absolute adjusted risks for emergency cesarean delivery, birth of a small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infant, and postpartum (6 mo) weight retention (PPWR) were compared across different types of women.

Results: The risk of SGA decreased with increasing GWG in both parity groups, but SGA risk <10% was reached at 2–3 GWG categories lower in multiparae than in primiparae. An excess risk of LGA was present only in obese primiparae and multiparae, but the PPWR risk increased with increasing GWG irrespective of BMI and parity. Young primiparae had better outcomes than other primiparae. Short women had a higher risk of emergency cesarean delivery that varied minimally with GWG. Smokers had a higher SGA risk and had a PPWR risk similar to that of nonsmokers.

Conclusions: The tradeoff in risk between mother and infant is reached at lower GWG in multiparae than in primiparae; therefore, a lower GWG may be needed among multiparae. Differential guidelines seem unnecessary for short or young women or smokers.

Objective: The aim was to determine whether periconceptional iron supplementation reduces anemia during pregnancy.

Design: A randomized, double-blind, controlled trial was conducted in rural Bangladesh. Married, nulliparous women were randomly assigned to receive daily iron and folic acid (IFA; 60 mg ferrous fumarate and 400 µg folic acid) (n = 134) or folic acid (FA; 400 µg) (n = 138) in the form of a powdered supplement added to food. Women were followed until pregnancy or the end of 9 mo. Primary outcomes included hemoglobin, plasma ferritin, and plasma transferrin receptor concentrations.

Results: Among 88 pregnant women, periconceptional IFA in comparison with FA did not affect anemia or iron status at 15 wk gestation. However, each 1% increase in adherence was associated with a 10-g/L increase in change in hemoglobin from baseline (P = 0.03), and those who initiated supplementation at a mean (±SD) time of 72.9 ± 57.8 d before conception showed a 7.3-g/L increase in change in hemoglobin from baseline compared with those who initiated supplementation at 26.3 ± 12.3 d after conception (P = 0.01). Among 146 nonpregnant women, IFA decreased anemia (odds ratio: 0.19; 95% CI: 0.04, 0.95) and improved iron stores (P = 0.001) more than did FA.

Conclusion: Good adherence and initiation of supplementation before conception are needed to reduce anemia during early pregnancy. This trial was registered at www.clinicaltrials.gov as NCT00953134.

Objective: The objective was to examine the perinatal risk factors related to childhood obesity.

Design: In a prospective study, 89 women with normal glucose tolerance (NGT) or gestational diabetes mellitus (GDM) and their offspring were evaluated at birth and at 8.8 ± 1.8 y. At birth, obstetrical data, parental anthropometric measures, and neonatal body composition were assessed; at follow-up, diet and activity were assessed and laboratory studies were conducted. Weight was classified by using weight for age and sex, and body composition was measured by using dual-energy X-ray absorptiometry. In childhood, data were analyzed as tertiles and prediction models were developed by using logistic and stepwise regression.

Results: No significant differences in Centers for Disease Control and Prevention weight percentiles, body composition, and most metabolic measures were observed between children of mothers with NGT and GDM at follow-up. Children in the upper tertile for weight had greater energy intake (P = 0.02), skinfold thickness (P = 0.0001), and leptin concentrations (P < 0.0001) than did those in tertiles 1 and 2. Children in the upper tertile for percentage body fat had greater waist circumference (P = 0.0001), insulin resistance (P = 0.002), and triglyceride (P = 0.009) and leptin (P = 0.0001) concentrations than did children in tertiles 1 and 2. The correlation between body fat at birth and follow-up was r = 0.29 (P = 0.02). The strongest perinatal predictor for a child in the upper tertile for weight was maternal pregravid body mass index (BMI; kg/m²) >30 (odds ratio: 3.75; 95% CI: 1.39, 10.10; P = 0.009) and for percentage body fat was maternal pregravid BMI >30 (odds ratio: 5.45; 95% CI: 1.62, 18.41; P = 0.006).

Conclusion: Maternal pregravid BMI, independent of maternal glucose status or birth weight, was the strongest predictor of childhood obesity.

Objective: The objective was to evaluate different approaches to describing more extreme values of body mass index (BMI)-for-age by using simple functions of the CDC growth charts.

Design: Empirical data for the 99th and the 1st percentiles of BMI-for-age were calculated from the data set used to construct the growth charts and were compared with estimates extrapolated from the CDC-supplied LMS parameters and to various functions of other smoothed percentiles. A set of reestimated LMS parameters that incorporated a smoothed 99th percentile were also evaluated.

Results: Extreme percentiles extrapolated from the CDC-supplied LMS parameters did not match well to the empirical data for the 99th percentile. A better fit to the empirical data was obtained by using 120% of the smoothed 95th percentile. The empirical first percentile was reasonably well approximated by extrapolations from the LMS values. The reestimated LMS parameters had several drawbacks and no clear advantages.

Conclusions: Several approximations can be used to describe extreme high values of BMI-for-age with the use of the CDC growth charts. Extrapolation from the CDC-supplied LMS parameters does not provide a good fit to the empirical 99th percentile values. Simple approximations to high values as percentages of the existing smoothed percentiles have some practical advantages over imputation of very high percentiles. The expression of high BMI values as a percentage of the 95th percentile can provide a flexible approach to describing and tracking heavier children.

Objective: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes.

Design: Androgen and glucocorticoid metabolites were profiled by gas chromatography–mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3–12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios.

Results: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R² = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes.

Conclusions: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.

Objective: The objective was to assess the relation between alcohol consumption and urinary hydroxytyrosol concentrations.

Design: This was a cross-sectional study with baseline data from a subsample of the PREvención con DIeta MEDiterránea (PREDIMED) trial, an intervention study directed at testing the efficacy of the Mediterranean diet on the primary prevention of cardiovascular disease. Participants included 1045 subjects, aged 55–80 y, who were at high cardiovascular risk. Alcohol consumption was estimated through a validated food-frequency questionnaire. Urinary hydroxytyrosol and ethyl glucuronide, a biomarker of alcohol consumption, were measured.

Results: Urinary ethyl glucuronide concentrations were directly related to alcohol and wine consumption (P < 0.001) as well as to urinary hydroxytyrosol in both sexes (P < 0.001). The degree of alcohol consumption was directly associated with urinary hydroxytyrosol in male alcohol consumers (P < 0.001). Multivariate logistic regression analyses showed a significant linear trend (P < 0.05) for elevated hydroxytyrosol concentrations with an increase in alcohol consumption. Intakes of >20 g (2 drinks)/d and >10 g (1 drink)/d alcohol in men and women, respectively, were associated (P < 0.05) with elevated concentrations of hydroxytyrosol.

Conclusions: We report for the first time a direct association between urinary hydroxytyrosol and alcohol consumption at a population level. These findings reinforce previous work in human and animal models that examines wine as a source of hydroxytyrosol and alcohol as an indirect promoter of endogenous hydroxytyrosol generation. This trial was registered at controlled-trials.com/isrctn/ as ISRCTN 35739639.

Objective: The objective was to determine the association of activity-related energy expenditure with change in body mass and composition among older men and women.

Design: Total energy expenditure (TEE) was assessed over 2 wk by using the doubly labeled water method in 302 community-dwelling older adults aged 70–82 y. Resting metabolic rate (RMR) was measured by using indirect calorimetry, and the thermic effect of meals was estimated at 10% of TEE. Activity energy expenditure (AEE) was calculated as [TEE(0.9) – RMR]. Total body mass, fat-free mass (FFM), and fat mass (FM) were assessed by dual-energy X-ray absorptiometry annually over a mean (±SD) of 4.9 ± 1.3 y.

Results: In multivariate models adjusted for baseline age, smoking status, and race, men and women had a decline (in kg/y) in body mass (men: –0.34, 95% CI: –0.71, 0.02; women: –0.45, 95% CI: –0.71, –0.19) and FFM (men: –0.48, 95% CI: –0.67, –0.29; women: –0.14, 95% CI: –0.026, –0.03). No changes (in kg/y) were observed in FM (men: 0.14, 95% CI: –0.10, 0.38; women: –0.28, 95% CI: –0.49, –0.07). In men and women, higher AEE at baseline was associated with greater FFM. The average change in these outcomes (ie, slope), however, was similar across tertiles of AEE.

Conclusions: These data suggest that accumulated energy expenditure from all physical activities is associated with greater FFM, but the effect does not alter the trajectory of FFM change in late life.

Objectives: We tested the hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted in older subjects, together with blunted activation of Akt–protein kinase B (PKB).

Design: Groups of 8 young [mean (±SD) age: 24.5 ± 1.8 y] and older (65.0 ± 1.3 y) participants were studied during euglycemic (5 mmol/L), isoaminoacidemic (blood leucine 120 µmol/L) clamp procedures at plasma insulin concentrations of 5 and 15 µIU/mL for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of amino acid tracers), and muscle protein synthesis were measured with d₅-phenylalanine and [1,2-¹³C₂]leucine. The kinase activity of muscle Akt-PKB and the extent of phosphorylation of signaling proteins associated with the mTOR (mammalian target of rapamycin) pathway were measured before and after the clamp procedures.

Results: Basal LPB rates were not different between groups (66 ± 11 compared with 51 ± 10 nmol leucine · 100 mL leg^–1 · min^–1 and 30 ± 5 compared with 24 ± 4 nmol phenylalanine · 100 mL leg^–1 · min^–1 in young and older groups, respectively). However, although insulin at 15 µIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen in muscle protein synthesis or associated anabolic signaling phosphoproteins.

Conclusions: At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.

Objective: This study aimed to assess dietary information use among persons with chronic disease by using a nationally representative sample of the US population.

Design: A total of 5603 respondents aged ≥17 y from the 2005–2006 National Health and Nutrition Examination Survey participated in the study. This representative sample of US civilians were asked 17 questions regarding their awareness of federal nutrition information and their food label use and were given two 24-h recall dietary interviews. Participants were classified into 5 disease categories: 1) hypertension, 2) hypercholesterolemia, 3) diabetes/at risk of diabetes, 4) overweight, and 5) heart disease.

Results: Subjects with chronic diseases were more aware of nutritional recommendations, checked more often for specific nutrients, and used nutrition information on food labels more often than did participants without such diseases. Label use behavior was inconsistently associated with dietary guideline compliance.

Conclusions: People with chronic disease generally reported better nutrition awareness and food label use and checking behaviors compared with those without chronic disease, but this did not translate into unequivocally better eating behaviors. New strategies are needed to improve the actual nutritional behaviors of persons with chronic disease.

Objective: The purpose of this study was to formally investigate the current relation of iron status and food security status among children aged 3–19 y (n = 11,247).

Design: Participants of the National Health and Nutrition Examination Survey 1999–2004 were classified for food security status by using the US Children's Food Security Scale and the US Household Food Security Scale. Iron deficiency was defined as ≥2 abnormal values for transferrin saturation, serum ferritin, and erythrocyte protoporphyrin, with the addition of abnormal hemoglobin to classify iron deficiency anemia.

Results: The odds of iron deficiency anemia among children aged 12–15 y were 2.95 times (95% CI: 1.18, 7.37; P = 0.02) those for children in households with food insecurity among children compared with children in households with food security among children.

Conclusions: The results of this study indicate a continuing need for successful interventions to reduce iron deficiency anemia among food-insecure children and to improve food security among children.

Objective: We assessed whether nutritional supplementation in children aged <7 to 15 y affected their children's nutritional status 29–38 y later.

Design: We studied 791 children 0–12 y who were offspring of 401 Guatemalan women who had participated as children in a nutritional supplementation trial in which 2 villages were randomly assigned to receive a nutritious supplement (atole) and 2 were assigned to receive a less-nutritious supplement (fresco). We compared anthropometric indicators between the offspring of mothers exposed to atole and the offspring of mothers exposed to fresco.

Results: Compared with the offspring of women exposed to fresco, the offspring of women exposed to atole had a 116-g (95% CI: 17, 215 g) higher birth weight, were 1.3-cm (0.4, 2.2 cm) taller, had a 0.6-cm (0.4, 0.9 cm) greater head circumference, had a 0.26 (0.09, 0.43) greater height-for-age z score, and had a 0.20 (0.02, 0.39) greater weight-for-age z score. The association for height differed by offspring sex. Sons of women exposed to atole were 2.0-cm (95% CI: 1.0, 3.1 cm) taller than the sons of women exposed to fresco. Supplementation was not associated with 6 other offspring anthropometric indicators that reflect measures of adiposity. Supplementation in boys did not affect their children's anthropometric measures.

Conclusion: Nutritional supplementation in girls is associated with substantial increases in their offsprings' (more for sons) birth weight, height, head circumference, height-for-age z score, and weight-for-age z score.

Objectives: We examined plasma folate (P-folate) concentration in relation to genotypes of the folate-metabolizing enzyme methylenetetrahydrofolate reductase [MTHFR 677C->T (rs1801133) and 1298A->C (rs1801131)]. We also explored whether P-folate was associated with risk of postmenopausal breast cancer overall and in subgroups with genetic variants of the MTHFR single nucleotide polymorphisms (SNPs).

Design: This nested case-control study included 313 cases (age 55–73 y at baseline) with invasive breast cancer and 626 control subjects, matched on age and blood-sample date, from the population-based Malmö Diet and Cancer cohort. P-folate and MTHFR genotypes were determined for 310 cases and 611 controls. P-folate according to genotype was calculated by using analysis of variance. Odds ratios were obtained by using logistic regression. All tests were 2-sided.

Results: The variant 677T allele was associated with lower P-folate. In women with the 677T allele, a high P-folate concentration was associated with increased breast cancer risk (P for trend across P-folate tertiles = 0.03). Interaction was seen between the 677C->T SNP and P-folate (P = 0.002). A positive association, which was seen between P-folate and breast cancer risk in 1298AA women (P = 0.01), was probably due to linkage between the 2 SNPs. Overall, and in women with other genotypes, no significant associations were observed.

Conclusions: Our results suggest an association of high P-folate concentration with increased risk of postmenopausal breast cancer in carriers of the 677T allele. The findings underline the importance of genetic variation of MTHFR in the complex relation between folate and cancer.

Objective: Our aim was to clarify whether green tea consumption is associated with lower psychological distress.

Design: We analyzed cross-sectional data for 42,093 Japanese individuals aged ≥40 y from the general population. Information on daily green tea consumption, psychological distress as assessed by the Kessler 6-item psychological distress scale, and other lifestyle factors was collected by using a questionnaire. We used multiple logistic regression analyses adjusted for age, sex, history of disease, body mass index, cigarette smoking, alcohol consumption, time spent walking, dietary factors, social support, and participation in community activities to investigate the relation between green tea consumption and psychological distress.

Results: We classified 2774 (6.6%) of the respondents as having psychological distress (Kessler 6-item psychological distress scale ≥13/24). There was an inverse association between green tea consumption and psychological distress in a model adjusted for age and sex. Although the relation was largely attenuated when possible confounding factors were adjusted for, a statistically significant inverse association remained. The odds ratio (with 95% CI) of developing psychological distress among respondents who consumed ≥5 cups of green tea/d was 0.80 (0.70, 0.91) compared with those who consumed <1 cup/d. These relations persisted when respondents were stratified by social support subgroups or by activities in communities.

Conclusion: Green tea consumption was inversely associated with psychological distress even after adjustment for possible confounding factors.

Objective: The objective of this study was to show the methodologic weakness of comparing energy density with energy cost.

Design: The relation between energy density and energy cost was replicated in a random-number data set. Additionally, observational data were collected for produce and snacks from an online supermarket. Variables included total energy (kcal), total weight (g), total number of servings, serving size (g/serving), and energy density (kcal/g). Price measures included energy cost ($/kcal), total price ($), unit price ($/g), and serving price ($/serving). Two-tailed t tests were used to compare price measures by food category. Relations between energy density and price measures within food categories were examined with the use of Spearman rank correlation analysis.

Results: The relation between energy density and energy cost was shown to be driven by the algebraic properties of these variables. Food category was strongly correlated with both energy density and food price measures. Energy cost was higher for produce than for snacks. However, total price and unit price were lower for produce. Serving price and serving size were greater for produce than for snacks. Within food categories, energy density was uncorrelated with most measures of food price, except for a weak positive correlation with serving price within the produce category.

Conclusion: The findings suggest the relation between energy density and food price is confounded by food category and depends on which measure of price is used.

Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots.

Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders.

Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, -carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for ≥median compared with <median servings per week of high–vitamin C fruit and vegetables, citrus fruit, and green leafy vegetables were 0.61 (0.43, 0.86), 0.64 (0.46, 0.89), and 0.59 (0.43, 0.81), respectively. The strongest inverse association was observed for ≥median compared with <median combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food: 0.27 (0.14, 0.55).

Conclusion: High combined intakes of vitamins C and E, β-carotene, β-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons.

Objective: The objective was to determine whether GST genotypes modify the association between dietary vitamin C and serum ascorbic acid.

Design: Nonsmoking men and women (n = 905) between 20 and 29 y of age were participants in the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for deletion polymorphisms in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. A 196-item food-frequency questionnaire was used to estimate vitamin C intake.

Results: A gene-diet interaction on serum ascorbic acid was observed for GSTM1 (P = 0.04) and GSTT1 (P = 0.01) but not for GSTP1 (P = 0.83). The odds ratio (95% CI) for serum ascorbic acid deficiency (<11 µmol/L) was 3.20 (1.88, 5.44) for subjects who did not meet the Recommended Dietary Allowance of vitamin C compared with those who did. The corresponding odds ratios (95% CIs) were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42), respectively, for individuals with the GSTT1*1/*1 +*1/*0 (functional) and GSTT1*0/*0 (null) genotypes and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09), respectively, for the GSTM1*1/*1+GSTM1*1/*0 and GSTM1*0/*0 genotypes.

Conclusions: The recommended intake of vitamin C protects against serum ascorbic acid deficiency, regardless of genotype. Individuals with GST null genotypes had an increased risk of deficiency if they did not meet the Recommended Dietary Allowance for vitamin C, which suggests that the GST enzymes protect against serum ascorbic acid deficiency when dietary vitamin C is insufficient.

Objective: The aim was to examine whether dietary factors (macronutrient and fiber intakes) and leisure-time physical activity modify the association between genetic variation in FTO and body mass index (BMI; in kg/m²).

Design: A cross-sectional study examined 4839 subjects in the population-based Malmö Diet and Cancer study with dietary data (from a modified diet history method) and information on the genetic variant FTO (rs9939609). Direct anthropometric measures were made, and leisure-time physical activity was determined from the duration participants spent on 18 different physical activities.

Results: Significant interactions between energy-adjusted fat intake and FTO genotype (P = 0.04) and between carbohydrate intake and FTO genotype (P = 0.001) on BMI were observed. The observed increase in BMI across FTO genotypes was restricted to those who reported a high-fat diet, with a mean BMI of 25.3 (95% CI: 24.9, 25.6) among TT carriers and of 26.3 (95% CI: 25.8, 26.8) among AA carriers (P = 0.0001). The FTO variant was not associated with a higher BMI among subjects with lower fat intakes (BMI = 25.7 and 25.9 in TT carriers and AA carriers, respectively; P = 0.42). Among individuals with a low-carbohydrate intake, we observed a mean BMI of 25.4 for TT carriers and of 26.8 for AA carriers. The increase in BMI across genotypes was mainly restricted to individuals who reported low leisure-time physical activity (P for trend = 0.004, P for interaction = 0.05).

Conclusion: Our results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant.

Objective: The objective was to determine whether postprandial responses in hunger and satiety are associated with rs9939609, taking interactions with other relevant candidate genes into account.

Design: Sixty-two women and 41 men [age: 31 ± 14 y; body mass index (in kg/m²): 25.0 ± 3.1] were genotyped for 5 SNPs in FTO, DNMT1, DNMT3B, LEP, and LEPR. Individuals received fixed meals provided in energy balance. Hunger and satiety were determined pre- and postprandially by using visual analog scales.

Results: A general association test showed a significant association between postprandial responses in hunger and satiety with rs9939609 (P = 0.036 and P = 0.050, respectively). Individuals with low postprandial responses in hunger and satiety were overrepresented among TA/AA carriers in rs9939609 (FTO) compared with TT carriers (dominant and additive model: P = 0.013 and P = 0.020, respectively). Moreover, multifactor dimensionality reduction showed significant epistatic interactions for the postprandial decrease in hunger involving rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR). Individuals with a low postprandial decrease in hunger were overrepresented among TA/AA (dominant), CC/CA (recessive), and AG/GG (dominant) carriers in rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR), respectively (n = 39), compared with TT, AA, and/or AA carriers in these SNPs, respectively (P = 0.00001). Each SNP had an additional effect.

Conclusions: Our results confirm a role for FTO in responsiveness to hunger and satiety cues in adults in an experimental setting. The epistatic interaction suggests that DNA methylation, an epigenetic process, affects appetite.

Objective: Our aim was to test the effect of soy isoflavone supplementation on bone health.

Design: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed.

Results: After study site, soy intake, and pretreatment values were controlled for, subjects receiving a daily supplement with 120 mg soy isoflavones had a statistically significant smaller reduction in whole-body BMD than did the placebo group both at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole-body BMD T score were observed among this group of women at 1 y (P < 0.03) but not at 2 y of treatment. When compared with the placebo, soy isoflavone supplementation had no effect on changes in regional BMD, BMC, T scores, or biochemical markers of bone metabolism.

Conclusion: Daily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

Objective: Our objective was to investigate whether low serum B vitamins are associated with altered structural and biomechanical properties of human bone.

Design: Femoral heads of 94 men and women who underwent hip arthroplasty were analyzed by using dual-energy X-ray absorptiometry (DXA), biomechanical testing (indentation method), and histomorphometry. In addition, blood was collected to measure serum concentrations of homocysteine, folate, vitamin B-6, vitamin B-12, the bone formation marker osteocalcin, and the bone resorption marker tartrate-resistant acid phosphatase (TRAP). Measurement outcomes were grouped according to subjects with high and low serum concentrations, respectively, of folate, vitamin B-6, and vitamin B-12 (n = 47 for each group).

Results: Histomorphometric analysis showed a significantly lower trabecular thickness and trabecular area in subjects with low serum folate concentrations than in those with high serum folate concentrations and a significantly lower trabecular number in subjects with low serum vitamin B-6 concentrations than in those with high serum vitamin B-6 concentrations. In contrast, we found a comparable trabecular structure in subjects with high and low serum vitamin B-12 concentrations. DXA and biomechanical testing did not show significant differences between subjects with high and low serum B vitamin concentrations. Osteocalcin was significantly lowered in subjects with a low serum B vitamin concentration, whereas there was no association between serum B vitamins and TRAP.

Conclusion: The results of the present study indicate that low serum folate and vitamin B-6 concentrations, but not low serum vitamin B-12 concentrations, are associated with an altered morphology of human bone.