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: This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults.

Design: The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded.

Results: In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1–2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD.

Conclusions: A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.

Objectives: We investigated the agreement between ¹⁵N in hair and RBCs and then evaluated the relations between hair ¹⁵N and RBC EPA and DHA. We also assessed the agreement in carbon isotope ratios (¹³C) between hair and RBCs, because ¹³C has been proposed as a dietary biomarker in other populations.

Design: We assessed relations between hair and RBC ¹⁵N and ¹³C in a community-based sample of 144 Yup'ik Eskimos and examined the correlations between ¹⁵N and RBC EPA and DHA in a subset of these participants (n = 44).

Results: We showed a 1:1 relation with good agreement between hair and RBC ¹⁵N (r = 0.91) and ¹³C (r = 0.87). Hair isotope ratios were greater than RBC ratios by 1.5 for ¹⁵N and by 2.3 for ¹³C. There were strong correlations between hair ¹⁵N and RBC EPA and DHA (r = 0.83 and 0.84, respectively).

Conclusions: These results support the use of hair ¹⁵N values as a biomarker of EPA and DHA intakes. Because hair collection is noninvasive and the samples require no special processing, studies of EPA and DHA intakes in large populations could use biomarkers rather than self-reports to assess these fatty acids.

Objective: Our objective was to assess the effects of this variant on lifestyle intervention–induced changes in glucose values and metabolic variables at 1- and 4-y follow-ups.

Design: The rs7903146 variant was genotyped in 335 nondiabetic, dysmetabolic participants in a randomized lifestyle intervention trial.

Results: Subjects with the unfavorable TT genotype showed higher fasting glucose and lower homeostasis model assessment of β cell function values at baseline. Lifestyle modifications were successful in the amelioration of metabolic traits in all genetic subgroups after 1 y. At 4-y follow-up most of the metabolic benefits had disappeared. In a multiple regression model, values for glucose and homeostasis model assessment of β cell function at 4 y were significantly associated with the T allele (for glucose and homeostasis model assessments, respectively: β = 6.6; 95% CI: 2.5, 10.7; P = 0.001; and β = –0.37; 95% CI: –0.54, –0.20; P < 0.001) but not with intervention. There was no interaction between genotype and intervention. After 1 y, impaired fasting glucose and diabetes incidence were inversely associated with intervention. After 4 y, the presence of a T allele was associated with impaired fasting glucose (odds ratio: 3.04; 95% CI: 1.53, 6.04; P = 0.001) and diabetes (odds ratio: 2.63; 95% CI: 1.00, 6.96; P = 0.05) but not with intervention.

Conclusions: Lifestyle modifications improved the metabolic pattern in all genetic subgroups. At the end of the trial, however, weight gain occurred, and carriers of the T allele developed first hyperglycemia and decreased insulin secretion, which suggests the need for different "after-care" preventive approaches tailored to each genotype’s metabolic risk.

Objective: The objective of this study was to determine the nutritional contribution of OH eating and related socioeconomic determinants in Vietnamese adolescents.

Design: A 24-h recall was used to collect food intake data in a cross-sectional study of 1172 adolescents living in urban and rural areas. Multilevel analysis compared the mean daily intakes of energy, energy density, energy from fat, food groups, vitamin A, iron, and zinc in low, middle, and high consumers of OH food. Socioeconomic associations of OH eating were analyzed in a subsample of 870 adolescents.

Results: OH foods contributed 42% of fruit and vegetables, 23% of sodium, 21% of energy, 21% of vitamin A, 21% of iron, and 21% of zinc consumed per day. OH eating was negatively associated with total energy intake and energy density and positively associated with dietary diversity, energy contribution from fat, and consumption of sugar products. In rural areas, OH eating was positively associated with iron, fruit, meat, poultry, and offal intake. Female sex (P < 0.001), residence in urban areas (P < 0.001), and amount of pocket money (P < 0.001) were positively associated with consumption of OH foods.

Conclusions: OH eating added a number of desirable foods and nutrients but was also associated with higher consumption of energy from fat and sugar products. Independent of household wealth and locality, pocket money and sex are important determinants of OH eating.

Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conducted a cost-efficient, double-blind, randomized trial among participants of 2 large prospective cohorts, the Health Professionals Follow-Up Study and the Nurses’ Health Study.

Design: Participants were randomly assigned to receive folic acid (1 mg/d) (n = 338) or placebo (n = 334) for 3–6.5 y. The primary endpoint was any new diagnosis of adenoma during the study period (May 1996–March 2004). Secondary outcomes were adenoma by site, stage, and number of recurrent adenomas. Associations were also examined by plasma folate concentrations at baseline.

Results: Incidence of at least one recurrent adenoma was not significantly associated with folic acid supplementation [relative risk (RR): 0.82; 95% CI: 0.59,1.13; P = 0.22]. Among participants with low plasma folate concentrations at baseline (≤7.5 ng/mL), those randomly assigned to receive folic acid experienced a significant decrease in adenoma recurrence (RR: 0.61; 95% CI: 0.42, 0.90; P = 0.01), whereas for subjects with high folate concentrations at baseline (>7.5 ng/mL), supplemental folic acid had no significant effect (RR: 1.28; 95% CI: 0.82, 1.99; P = 0.27, P_interaction = 0.01). Contrary to findings from another clinical trial, there was no evidence for an increased risk of advanced or multiple adenomas.

Conclusions: Our results do not support an overall protective effect of folic acid supplementation on adenoma recurrence. Folic acid supplementation may be beneficial among those with lower folate concentrations at baseline. This trial was registered at clinical trials.gov as NCT00512850.

Objective: We examined the metabolic profiles of healthy human subjects after extended dietary standardization to see whether the inherent variation in the human metabolome could be decreased.

Design: A cohort of 10 healthy volunteers was admitted to a clinical research center for 2 wk of dietary standardization. Daily serum and urine samples and serum samples at a 2-wk follow-up visit were collected. The samples were analyzed by ¹H nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses.

Results: NMR spectra were collected to globally profile the higher-concentration metabolites (>µmol/L concentrations). Metabolic changes were observed in some serum samples after day 1 or the 2-wk follow-up visit. For each subject, the samples from all other days had similar profiles. The urinary metabolome reflected no effects from dietary standardization. Pooled 24-h urine samples were studied, which indicated that any normalization that does occur would do so in <24 h.

Conclusions: For both the urinary and serum metabolome, a single day of dietary standardization appears to provide all of the normalization that is achievable within the strict controls implemented in a clinical research setting. After 24 h, the subjects remain in their metabolic space; the remaining intra- and intersubject variations appear to be influenced by variables such as genetics, age, and lifestyle.

Objective: We present longitudinal data on age-related changes in leg composition, strength, and muscle quality (MQ) in ambulatory, well-functioning men and women. We hypothesized that muscle cross-sectional area (CSA) and strength would decrease and muscular fat infiltration would increase over 5 y.

Design: Midthigh muscle, subcutaneous fat (SF), and intermuscular fat (IMF) CSAs and isokinetic leg muscle torque (MT) and MQ (MT/quadriceps CSA) were examined over 5 y in the Health, Aging, and Body Composition study cohort (n = 1678).

Results: Men experienced a 16.1% loss of MT, whereas women experienced a 13.4% loss. Adjusted annualized decreases in MT were 2–5 times greater than the loss of muscle CSA in those who lost weight and in those who remained weight-stable. Weight gain did not prevent the loss of MT, despite a small increase in muscle CSA. Only those who gained weight had an increase in SF (P < 0.001), whereas those who lost weight also lost SF (P < 0.001). There was an age-related increase in IMF in men and women (P < 0.001), and IMF increased in those who lost weight, gained weight, or remained weight-stable (all P < 0.001).

Conclusions: Loss of leg MT in older adults is greater than muscle CSA loss, which suggests a decrease in MQ. Additionally, aging is associated with an increase in IMF regardless of changes in weight or SF.

Objective: We sought to study the association between multivitamin supplementation and allergic disease in 8-y-old children.

Design: Data were obtained from a Swedish birth cohort study. Information on lifestyle factors, including use of vitamin supplements, environmental exposures, and symptoms and diagnoses of allergic diseases, was obtained by parental questionnaires. In addition, allergen-specific IgE concentrations of food and airborne allergens were measured in blood samples collected at age 8 y. A total of 2423 children were included in the study. The association between use of vitamin supplements and the selected health outcomes was analyzed with logistic regression.

Results: Overall, no strong and consistent associations were observed between current multivitamin use and asthma, allergic rhinitis, eczema, or atopic sensitization at age 8 y. However, children who reported that they started taking multivitamins before or at age 4 y had a decreased risk of sensitization to food allergens (odds ratio: 0.61; 95% CI: 0.39, 0.97) and tendencies toward inverse associations with allergic rhinitis. In contrast, there was no consistent association among children who started to use multivitamins at or after age 5 y.

Conclusion: Our results show no association between current use of multivitamins and risk of allergic disease but suggest that supplementation with multivitamins during the first years of life may reduce the risk of allergic disease at school age.

Objective: This study aimed to examine the association between beverage consumption and 5-y body weight change in 2294 adolescents.

Design: Project EAT ("Eating Among Teens") is a 5-y longitudinal study of eating patterns among adolescents. Surveys were completed in 1998–1999 (time 1) and in 2003–2004 (time 2). Multivariable linear regression was used to examine the association between beverage consumption at time 2 and change in body mass index from time 1 to time 2, with adjustments for age, socioeconomic status, race, cohort, physical activity, sedentary behavior, coffee, tea, time 1 body mass index, and beverage variables.

Results: In prospective analyses, consumption of beverages was not associated with weight gain, except for consumption of low-calorie soft drinks (positive association, P = 0.002) and white milk (inverse association, P = 0.03), but these associations did not appear to be a monotonic linear dose-response relation. The positive association with low-calorie soft drinks was no longer present after adjustment for dieting and parental weight-related concerns, which suggests that the use of low-calorie soft drinks is a marker for more general dietary behaviors and weight concerns.

Conclusions: We showed no association between sugar-sweetened beverage consumption, juice consumption, and adolescent weight gain over a 5-y period. A direct association between diet beverages and weight gain appeared to be explained by dieting practices. Adolescents who consumed little or no white milk gained significantly more weight than their peers who consumed white milk. Future research that examines beverage habits and weight among adolescents should address portion sizes, adolescent maturation, and dieting behaviors.

Objective: We undertook this study to test the hypothesis that in patients undergoing automated peritoneal dialysis, an arterial pH of 7.43–7.45, as compared with a pH of 7.36–7.38, is associated with more-positive nitrogen balances.

Design: Eight stable subjects (5 men) aged 43.1 ± 15.3 y completed a randomized, crossover nitrogen balance study for ≥42 d. Arterial pH was varied by changing the daily doses of sodium citrate/citric acid and ammonium chloride.

Results: The subjects attained mean (±SD) arterial pH values of 7.37 ± 0.01 and 7.44 ± 0.02 during the low-normal and high-normal pH phases, respectively. The higher arterial pH was associated with higher net nitrogen balances (3.22 ± 1.37 compared with 2.29 ± 2.18 g/d; P = 0.06), lower serum urea nitrogen (54.1 ± 13.7 compared with 64.4 ± 20.2 mg/dL; P = 0.01), higher fasting leucine flux (P = 0.02), and increased fasting total-body protein synthesis (P = 0.01) and degradation (P = 0.02). In 7 of 8 study subjects, nitrogen balances were more positive at the higher arterial pH (P = 0.004). There were no significant changes in anthropometric measurements, other biochemical measurements, and the mRNA content of selected proteins in skeletal muscle.

Conclusion: This study suggests that in most stable automated peritoneal dialysis patients, a mean arterial pH of 7.44, as compared with 7.37, is associated with more-positive nitrogen balances. This trial was registered at clinical trials.gov as NCT00586131.

Objective: The effect of a dietary intervention plus n–3 (–3) fatty acid supplementation on serum triglycerides and markers of insulin sensitivity was investigated.

Design: Fifty-four persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were recruited for a dietary intervention in which total fat, type of fat, fiber, and glycemic load were controlled along with supplementation with n–3 fatty acids to achieve an intake of 6 g/d. The subjects were randomly assigned to an intervention or control group, and serum lipids, markers of insulin sensitivity, and serum phospholipid fatty acids were measured in both groups at baseline, 3 wk, and 13 wk.

Results: Triglycerides in the intervention group decreased from a median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile range: 84, 169) from baseline to 3 wk, whereas they remained stable in the control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (% nmol; P ≤ 0.001) in the intervention group. At 3 wk, the insulin area under the curve decreased but not significantly.

Conclusions: Diet and n–3 fatty acid supplementation dramatically reduced serum triglycerides, decreased arachidonic acid in the phospholipids fraction, and appeared to decrease the de novo lipogenesis associated with the metabolic syndrome in the intervention group.

Objective: We aimed to test the hypothesis that acute sleep loss decreases physical activity while increasing food intake, thereby shifting 2 crucial behavioral components of energy homeostasis toward weight gain.

Design: In 15 healthy, normal-weight men, spontaneous physical activity was registered by accelerometry during the entire experiment, and food intake as well as relevant hormones were assessed during a 15-h daytime period after 2 nights of regular sleep (bed time: 2245–0700) and after 2 nights of restricted sleep (bed time: 0245–0700). Experiments were performed in a crossover design.

Results: Sleep restriction significantly decreased physical activity during the daytime spent under free-living conditions after the first night of sleep manipulation (P = 0.008). Also, intensities of physical activity were shifted toward lower levels, with less time spent with intense activities (P = 0.046). Total energy intake, feelings of hunger, and appetite as well as ghrelin and leptin concentrations during day 2 remained unaffected by acute sleep restriction.

Conclusions: In contrast to our expectation, short-term sleep loss neither increased food intake nor affected concentrations of the hunger-regulating hormones leptin and ghrelin. However, the observed decrease in daytime physical activity may point to another potentially important behavioral mechanism for the health-impairing influence of sleep loss.

Objective: The objective was to study the associations of 5 CLOCK polymorphisms with MetS features by analyzing fatty acid (FA) composition from dietary and red blood cell (RBC) membrane sources.

Design: Participants (n = 1100) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Anthropometric and biochemical measurements and genotypes were determined. Postprandial lipids and the FA composition of RBC membranes were analyzed.

Results: CLOCK single nucleotide polymorphisms were significantly associated with obesity and individual components of MetS. For single nucleotide polymorphism rs4580704, minor allele carriers had a 46% lower risk of hypertension than did noncarriers. The monounsaturated fatty acid (MUFA) content of RBC membranes, particularly oleic acid, changed according to CLOCK genetic variants (P < 0.05). We identified significant gene-diet interactions associated with MetS at the CLOCK locus. By dichotomizing MUFA intake, we found different effects across rs4580704 genotypes for glucose (P = 0.020) and insulin resistance (P = 0.026). The protective effect of the minor allele on insulin sensitivity was only present when MUFA intake was >13.2% of energy. We also found different effects across CLOCK 3111T->C genotypes for saturated fatty acid intake (% of energy) (P = 0.017). The deleterious effect of gene variants on waist circumference was only found with high saturated fatty acid intakes (>11.8%).

Conclusions: CLOCK polymorphisms interact with FAs to modulate MetS traits. The dietary source and membrane content of MUFAs are implicated in the relations between alterations in the circadian system and MetS.

Objective: The objective was to determine the relative contributions of increased energy intake and reduced physical activity to the US obesity epidemic.

Design: We predicted the changes in weight from the changes in estimated energy intakes in US children and adults between the 1970s and 2000s. The increased US food energy supply (adjusted for wastage and assumed to be proportional to energy intake) was apportioned to children and adults and inserted into equations that relate energy intake to body weight derived from doubly labeled water studies. The weight increases predicted from the equations were compared with weight increases measured in representative US surveys over the same period.

Results: For children, the measured weight gain was 4.0 kg, and the predicted weight gain for the increased energy intake was identical at 4.0 kg. For adults, the measured weight gain was 8.6 kg, whereas the predicted weight gain was somewhat higher (10.8 kg).

Conclusions: Increased energy intake appears to be more than sufficient to explain weight gain in the US population. A reversal of the increase in energy intake of 2000 kJ/d (500 kcal/d) for adults and of 1500 kJ/d (350 kcal/d) for children would be needed for a reversal to the mean body weights of the 1970s. Alternatively, large compensatory increases in physical activity (eg, 110–150 min/d walking), or a combination of both, would achieve the same outcome. Population approaches to reducing obesity should emphasize a reduction in the drivers of increased energy intake.

Objective: Because FTO is highly expressed in hypothalamic regions that are important for appetite, FTO genotype may affect energy balance by influencing eating behavior. Loss of control (LOC) eating, a behavior commonly reported by overweight youth, predicts excessive weight gain in children. However, the relation between FTO genotype and LOC eating has not been previously examined.

Design: Two-hundred eighty-nine youth aged 6–19 y were genotyped for rs9939609, underwent body-composition measurements, and were interviewed to determine the presence or absence of LOC eating. A subset (n = 190) participated in a lunch buffet test meal designed to model an LOC eating episode. Subjects with AA and AT genotypes were grouped together for comparison with wild-type TT subjects.

Results: Subjects with at least one A allele (67.7%) had significantly greater body mass indexes, body mass index z scores (P < 0.01), and fat mass (P < 0.05). Of the AA/AT subjects, 34.7% reported LOC compared with 18.2% of the TT subjects (P = 0.002). Although total energy intake at the test meal did not differ significantly by genotype (P = 0.61), AA/AT subjects consumed a greater percentage of energy from fat than did the TT subjects (P < 0.01).

Conclusions: Children and adolescents with 1 or 2 FTO rs9939609 obesity-risk alleles report more frequent LOC eating episodes and select foods higher in fat at a buffet meal. Both LOC eating and more frequent selection of energy-dense, palatable foods may be mechanisms through which variant FTO alleles lead to excess body weight.

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: The objective was to investigate whether early life exposures influence the timing of puberty, as defined by both early and late markers, in healthy German girls and boys.

Design: Term participants (n = 215; 49.8% female) of the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) Study, with sufficient repeated anthropometric measurements between 6 and 13 y to allow estimation of age at take-off of the pubertal growth spurt (ATO) and information on a variety of early life exposures, including birth weight, breastfeeding status, velocity of weight gain, and parental characteristics, were studied. Age at peak height velocity (APHV) and menarche were also considered.

Results: Children who weighed between 2500 and <3000 g at birth were 7 mo younger at ATO than were the other children (β ± SE: –0.56 ± 0.20 y; P = 0.006). Children who had gained weight rapidly between birth and 24 mo (increase in weight SD score >0.67) experienced ATO 4 mo earlier than those who had gained weight normally (–0.34 ± 0.15 y; P = 0.02). Rapid weight gain was also associated with an earlier APHV (P = 0.0006) and, in girls, with an earlier menarche (P = 0.002). Adjustment for body mass index SD score or body fat percentage 1, 2, or 3 y before ATO did not account for these effects.

Conclusions: In both boys and girls, intrauterine and early postnatal growth factors appear to influence both early and later markers of puberty onset independently of prepubertal body composition.

Objective: The aim of this study was to investigate the relations between green tea consumption and depressive symptoms in elderly Japanese subjects who widely consumed green tea.

Design: We conducted a cross-sectional study in 1058 community-dwelling elderly Japanese individuals aged ≥70 y. Green tea consumption was assessed by using a self-administered questionnaire, and depressive symptoms were evaluated by using the 30-item Geriatric Depression Scale with 2 cutoffs: 11 (mild and severe depressive symptoms) and 14 (severe depressive symptoms). If a participant was consuming antidepressants, he or she was considered to have depressive symptoms.

Results: The prevalence of mild and severe and severe depressive symptoms was 34.1% and 20.2%, respectively. After adjustment for confounding factors, the odds ratios (95% CI) for mild and severe depressive symptoms when higher green tea consumption was compared with green tea consumption of ≤1 cup/d were as follows: 2–3 cups green tea/d (0.96; 95% CI: 0.66, 1.42) and ≥4 cups green tea/d (0.56; 95% CI: 0.39, 0.81) (P for trend: 0.001). Similar relations were also observed in the case of severe depressive symptoms.

Conclusion: A more frequent consumption of green tea was associated with a lower prevalence of depressive symptoms in the community-dwelling older population.

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.

Objective: This study examined the organ-tissue basis of the increased REE shown in HIV lipoatrophy.

Design: REE was measured in 29 HIV-infected patients with lipoatrophy and in 29 HIV-infected and 19 healthy control subjects. Five organ-tissue mass components (brain, bone, skeletal muscle, adipose tissue, and residual mass) were calculated with the use of DXA modeling and body weight.

Results: DXA modeling showed no significant differences in predicted REE between the 3 groups. However, measured REE was significantly greater in subjects with lipoatrophy than in control subjects. Measured REE remained significantly greater in lipoatrophy subjects after routine adjustment for lean body mass and after adjustment for each organ-tissue mass component. Finally, DXA and regression modeling of REE suggests that increased energy expenditure in skeletal muscle may account for the resting hypermetabolism of patients with HIV lipoatrophy.

Conclusions: Increased REE in subjects with HIV lipoatrophy cannot be explained by differences in organ-tissue mass as modeled by DXA. Instead, DXA and regression modeling of REE suggests that skeletal muscle is hypermetabolic in patients with HIV lipoatrophy. This may be a form of adaptive thermogenesis in response to an inability to store triglyceride fuel in a normal manner.

Objectives: The objectives were to determine the relation between C3 polymorphisms and MetS and whether interaction with plasma polyunsaturated fatty acids (PUFAs), a biomarker of dietary PUFA, modulate this relation.

Design: C3 polymorphisms (rs11569562, rs2250656, rs1047286, rs2230199, rs8107911, rs344548, rs344550, rs2241393, rs7257062, rs163913, and rs2230204), biochemical measurements, and plasma fatty acids were measured in the LIPGENE–SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study in MetS cases and matched controls (n = 1754).

Results: Two single nucleotide polymorphisms were associated with MetS. rs11569562 GG homozygotes had decreased MetS risk compared with the minor A allele carriers [odds ratio (OR): 0.53; 95% CI: 0.35, 0.82; P = 0.009], which was augmented by high plasma PUFA status (OR: 0.32; 95% CI: 0.11, 0.93; P = 0.04). GG homozygotes had lower C3 concentrations than those in AA homozygotes (P = 0.03) and decreased risk of hypertriglyceridemia compared with A allele carriers (OR: 0.54; 95% CI: 0.34, 0.92; P = 0.02), which was further ameliorated by an increase in long-chain n–3 (omega-3) PUFAs (OR: 0.46; 95% CI: 0.22, 0.97; P = 0.04) or a decrease in n–6 PUFAs (OR: 0.32; CI: 0.16, 0.62; P = 0.002). rs2250656 AA homozygotes had increased MetS risk relative to the minor G allele carriers (OR: 1.78; CI: 1.19, 2.70; P = 0.02), which was exacerbated by low n–6 PUFA status (OR: 2.20; CI: 1.09, 4.55; P = 0.03).

Conclusion: Plasma PUFAs may modulate the susceptibility to MetS that is conferred by C3 polymorphisms, which suggests novel gene-nutrient interactions. This trial was registered at clinicaltrials.gov as NCT00272428.

Objective: The aim of this study was to examine the prospective association between the Mediterranean-style dietary pattern and metabolic syndrome.

Design: The Mediterranean-style dietary pattern score (MSDPS) was used to characterize a Mediterranean-style dietary pattern in the Framingham Heart Study Offspring Cohort. We examined the longitudinal association between MSDPS and metabolic syndrome traits (including homeostasis model assessment–insulin resistance, fasting glucose, waist circumference, triglyceride, high-density lipoprotein cholesterol, and systolic and diastolic blood pressure) among 2730 participants of the Framingham Heart Study Offspring Cohort without type 2 diabetes (baseline median age: 54 y; 55% women), who were followed from the 5th (baseline) to the 7th study examinations (mean follow-up time: 7 y), and metabolic syndrome incidence (according to the National Cholesterol Education Program Adult Treatment Panel III definition) in 1918 participants free of the condition at baseline.

Results: A higher MSDPS was associated with lower homeostasis model assessment–insulin resistance (P = 0.02), waist circumference (P < 0.001), fasting plasma glucose (P = 0.03), and triglycerides (P < 0.001) and higher HDL cholesterol (P = 0.02) after adjustment for the corresponding baseline values and for several confounding factors associated with type 2 diabetes risk. Participants in the highest quintile category of the MSDPS had a lower incidence of metabolic syndrome than those in the lowest quintile category (38.5% compared with 30.1%; P = 0.01).

Conclusion: Our study suggests that the consumption of a diet consistent with the principles of the Mediterranean-style diet may protect against metabolic syndrome in Americans.

Objective: The objective was to assess the association between the amount and type of dietary fat and subsequent weight change (follow-up weight minus baseline weight divided by duration of follow-up).

Design: We analyzed data from 89,432 men and women from 6 cohorts of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Using country-specific food-frequency questionnaires, we examined the association between baseline fat intake (amount and type of total, saturated, polyunsaturated, and monounsaturated fats) and annual weight change by using the residual, nutrient density, and energy-partition methods. We used random-effects meta-analyses to obtain pooled estimates across centers.

Results: Mean total fat intake as a percentage of energy intake ranged between 31.5% and 36.5% across the 6 cohorts (58% women; mean ± SD age: 53.2 ± 8.6 y). The mean (±SD) annual weight change was 109 ± 817 g/y in men and 119 ± 823 g/y in women. In pooled analyses adjusted for anthropometric, dietary, and lifestyle factors and follow-up period, no significant association was observed between fat intake (amount or type) and weight change. The difference in mean annual weight change was 0.90 g/y (95% CI: –0.54, 2.34 g/y) for men and –1.30 g/y (95% CI: –3.70, 1.11 g/y) for women per 1 g/d energy-adjusted fat intake (residual method).

Conclusions: We found no significant association between the amount or type of dietary fat and subsequent weight change in this large prospective study. These findings do not support the use of low-fat diets to prevent weight gain.

Objective: Our objective was to investigate the effect of a saturated fatty acid (SFA)– and a monounsaturated fatty acid (MUFA)–rich diet on insulin sensitivity, serum lipids, and gene expression profiles of adipose tissue in subjects at risk of metabolic syndrome.

Design: A parallel controlled-feeding trial was conducted in 20 abdominally overweight subjects. Subjects received an SFA diet or an MUFA diet for 8 wk. Plasma and subcutaneous adipose tissue samples were obtained, and insulin sensitivity was measured by using a hyperinsulinemic-euglycemic clamp. Adipose tissue samples underwent whole-genome microarray and histologic analysis. Plasma and adipose tissue fatty acid composition and concentrations of serum cholesterol and plasma cytokine were determined.

Results: Consumption of the SFA diet resulted in increased expression of genes involved in inflammation processes in adipose tissue, without changes in morphology or insulin sensitivity. The MUFA diet led to a more antiinflammatory gene expression profile, which was accompanied by a decrease in serum LDL-cholesterol concentrations and an increase in plasma and adipose tissue oleic acid content.

Conclusions: Consumption of an SFA diet resulted in a proinflammatory "obesity-linked" gene expression profile, whereas consumption of an MUFA diet caused a more antiinflammatory profile. This suggests that replacement of dietary SFA with MUFA could prevent adipose tissue inflammation and may reduce the risk of inflammation-related diseases such as metabolic syndrome. This trial was registered at clinicaltrials.gov as NCT00405197.

Objective: Our objective was to determine the efficacy of an increased intake of red meat, or the consumption of iron-fortified milk, in improvement of iron status in toddlers at a population level.

Design: In this 20-wk randomized placebo-controlled trial, 225 healthy nonanemic 12–20-mo-old children were assigned to 1 of 3 groups: red meat (toddlers encouraged to consume 2.6 mg iron from red meat dishes daily), fortified milk [toddlers' regular milk replaced with iron-fortified (1.5 mg iron/100 g prepared milk) cow milk], or control [toddlers' regular milk replaced with nonfortified (0.01 mg iron/100 g prepared milk) cow milk]. Blood samples were collected at baseline and at 20 wk for hemoglobin, serum ferritin, serum transferrin receptor, and C-reactive protein. The prevalence of suboptimal iron status (ie, depleted iron stores, iron-deficient erythropoiesis, and iron deficiency anemia) was determined, and body iron was calculated.

Results: No intervention effects were shown on the prevalence of suboptimal iron status. Serum ferritin increased by 44% (95% CI: 14, 82%; P = 0.002) in the fortified milk group, did not change (+10%) in the red meat group (95% CI: –7, 30%; P = 0.241), and tended to decrease (–14%) in the control group (95% CI: –27, 1%; P = 0.063). By 20 wk, in comparison with the control group, serum ferritin and body iron were significantly higher in the fortified milk group (both P < 0.001) and serum ferritin was significantly higher in the red meat group (P = 0.033).

Conclusions: Consumption of iron-fortified milk can increase iron stores in healthy nonanemic toddlers, whereas increased intakes of red meat can prevent their decline. This trial was registered at actr.org.au as ACTRN12605000487617.

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.

Objective: The aim of the present study was to measure REE and its main components longitudinally during the first weeks of life to quantify their significant determinants.

Design: REE was investigated longitudinally over a period of 6 wk in healthy, stable, and growing preterm infants and over 5 wk in full-term neonates by means of indirect calorimetry.

Results: A total of 197 infants, including 183 premature infants and 14 full-term neonates, were recruited for the study. REE values increased in all gestational age groups from the first week to 5–6 wk of postnatal age, with the most pronounced increase in the smallest infants (+140%) and the smallest increase in the full-term neonates (+47%). Univariate calculations showed that for each postnatal week, REE increased by 6.93–9.64 kcal · kg^–1 · d^–1 with each additional kcal administered, for an average increase of 0.701 kcal, and increased by 1.78 kcal for each 1 g gain in weight. Postnatal age was the strongest predictor to influence REE (r² = 0.727, P < 0.0001).

Conclusions: This study provides comprehensive data on longitudinally determined REE values of healthy premature and full-term infants. Results may serve as a basis for comparative studies that address various disease states as well as different nutritional protocols.

Objective: The objective was to determine whether a prenatal MMN-fortified food supplement (FFS) improves anthropometric measures at birth compared with supplementation with an MMN pill alone.

Design: We conducted a nonblinded, individually randomized controlled trial in 1296 pregnant women in 2 villages in rural Burkina Faso. Supplements were provided on a daily basis, and compliance was closely verified by using a community-based network of home visitors.

Results: Anthropometric measures at birth were available for analysis for 87% of the 1175 live singleton deliveries enrolled. After adjustment for gestational age at birth, the FFS group had a significantly higher birth length (+4.6 mm; P = 0.001). FFS supplementation resulted in a modestly higher birth weight (+31 g; P = 0.197). Subgroup analyses showed clinically important treatment effects on birth length (+12.0 mm; P = 0.005) and on birth weight (+111 g; P = 0.133) for underweight [body mass index (in kg/m²) <18.5] pregnant women. Women with early pregnancy anemia who received FFS gave birth to taller newborns (+7.3 mm; P = 0.002) than did those who received MMN supplementation.

Conclusions: The provision of FFS to pregnant women resulted in higher birth length than did MMN supplementation. For women with a suboptimal prepregnancy nutritional status, MMN supplementation should be complemented with a balanced energy and protein supplement to produce a clinical effect on birth size. The trial was registered at clinicaltrials.gov as NCT00909974.

Objectives: We sought to estimate the means and percentile cutoffs of PBF, TBF, and FFM and to assess the differences by sex, age, race-ethnicity, and body mass index in US adults.

Design: Data from the National Health and Nutrition Examination Survey, which were collected during the 6-y period from 1999 to 2004 and comprise a large nationally representative sample of the US population, were analyzed (n = 6559 men and 6507 nonpregnant women). TBF and FFM were measured by using dual-energy X-ray absorptiometry. PBF was calculated as TBF divided by total mass multiplied by 100.

Results: There were large differences between men and women in unadjusted mean PBF (28.1% compared with 40.0%, P < 0.001), TBF (25.4 compared with 30.8 kg, P < 0.001), and FFM (62.3 compared with 44.0 kg, P < 0.001); the sex differences persisted across all body mass index categories after adjustment for age and race-ethnicity (all P < 0.001). The common percentile cutoffs of PBF, TBF, and FFM were estimated by sex, race-ethnicity, and age groups. Equations for the estimation of PBF (R² = 0.85), TBF (R² = 0.94), and FFM (R² = 0.94) according to demographic characteristics and simple anthropometric measures were generated.

Conclusion: The estimates of means and percentile cutoffs for PBF, TBF, and FFM, on the basis of National Health and Nutrition Examination Survey 1999–2004 dual-energy X-ray absorptiometry data, provide a reference in the US adult population.

Objective: We aimed to define ranges for optimal GWG with respect to the risk of either small- or large-for-gestational-age offspring by using a new statistical approach.

Design: For the purpose of an observational study, data on n = 177,079 mature singleton deliveries in Bavaria between 2004 and 2006 were extracted from a standard data set that is regularly collected for national benchmarking of obstetric units in terms of clinical performance. Joint predicted risks of either small- or large-for-gestational-age births in relation to GWG (continuous measurement) were estimated by logistic regression models with adjustment for potential confounders.

Results: The estimated optimal GWG ranges as defined by joint predicted risk of ≤20% were substantially wider than those recommended by the Institute of Medicine for underweight (8–25 compared with 12.5–18.0 kg) and normal-weight (2–18 compared with 11.5–16.0 kg) women. Overweight and obese women’s optimal GWG ranged from –7 to 12 and –15 to 2 kg, respectively (Institute of Medicine recommendations: 7.0–11.5 and 5.0–9.0 kg, respectively). We observed considerable effect modifications by parity and smoking in pregnancy. In normal-weight primiparae, for example, the optimal GWG range was 10–26 kg for nonsmokers compared with 23–27 kg for smokers.

Conclusions: Considerably wider optimal GWG ranges than recommended by the Institute of Medicine might be tolerated with respect to avoidance of adverse birth weight outcome. Stratification by maternal body mass index category alone might not be sufficient.

Objective: The aim of our study was to compare the effect of a high-protein (HP) with a normal-protein (NP) diet on renal hemodynamics and selected clinical-chemical factors.

Design: We prospectively studied the effect of an HP diet (2.4 g · kg^–1 · d^–1) with that of an NP diet (1.2 g · kg^–1 · d^–1) on the glomerular filtration rate (assessed on the basis of sinistrin—an inulin analog—clearance) and renal plasma flow (para-aminohippuric acid clearance) by using the constant infusion technique. Filtration fraction and renal vascular resistance were calculated. Twenty-four healthy young men followed the 2 diet protocols for 7 d each in a crossover design. They were individually advised by a dietitian to achieve the planned protein intake by selecting normal foods under isocaloric conditions. Serum and urinary variables and renal hemodynamics were measured on day 7 of both diets.

Results: The glomerular filtration rate (NP: 125 ± 5 mL/min; HP: 141 ± 8 mL/min; P < 0.001) and filtration fraction (NP: 23 ± 5%; HP: 28 ± 5%; P < 0.05) increased significantly with the HP diet. Renal plasma flow was not significantly different between the HP (496 ± 25 mL/min) and NP (507 ± 18 mL/min) phases. Renal vascular resistance was not significantly different between the NP (94 ± 6 mm Hg · mL^–1 · min^–1) and HP (99 ± 8 mm Hg · mL^–1 · min^–1) phases. Blood urea nitrogen, serum uric acid, glucagon, natriuresis, urinary albumin, and urea excretion increased significantly with the HP diet.

Conclusions: A short-term HP diet alters renal hemodynamics and renal excretion of uric acid, sodium, and albumin. More attention should be paid to the potential adverse renal effects of HP diets.

Objective: We investigated whether –3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD.

Design: We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on –3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit.

Results: Participants who reported the highest –3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P ≤ 0.02) and 0.68 (95% CI: 0.49, 0.94; P ≤ 0.02).

Conclusions: The 12-y incidence of CGA and NV AMD in participants at moderate-to-high-risk of these outcomes was lowest for those reporting the highest consumption of –3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.

Objective: The purpose was to compare metabolic indicators of vitamin B-12 status, cognitive function, and depressive symptoms among elderly Latinos with elevated and nonelevated plasma folate.

Design: Cross-sectional data were analyzed for 1535 subjects (age: ≥60 y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or ≥148 pmol/L) and folate (≤ or >45.3 nmol/L). Homocysteine, methylmalonic acid, holotranscobalamin, ratio of holotranscobalamin to vitamin B-12, Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were compared between the groups.

Results: Individuals with low vitamin B-12 and elevated folate (n = 22) had the highest concentrations of homocysteine and methylmalonic acid and the lowest concentration of holotranscobalamin and ratio of holotranscobalamin to vitamin B-12 when compared with all other groups (P ≤ 0.003). No differences in Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were observed between the low vitamin B-12 and elevated-folate group compared with other groups.

Conclusions: Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the potential costs, risks, and benefits of folic acid and vitamin B-12 fortification programs.