Background: In low-birth-weight girls, obesity increases the risk of premature adrenarche and metabolic complications. However, the consistency of this association in normal-birth-weight children and its potential mediators remain unknown.

Objectives: The objectives were to assess the associations between obesity indicators and dehydroepiandrosterone sulfate (DHEAS) at 7 y of age and to evaluate the role of hormonal markers on these associations.

Design: We assessed in 969 participants (6.9 y; 48% girls; all Tanner I) in the Growth and Obesity Chilean Cohort Study the associations between DHEAS and weight, BMI, waist circumference (WC), waist-to-height ratio, skinfold thickness, and percentage total fat (bioimpedance) and determined whether these associations were related to insulin, insulin-like growth factor I (IGF-I), and leptin. We also compared BMI and height growth from 0 to 7 y of age in nonobese and obese children with normal and high DHEAS (≥75th percentile) at 7 y.

Results: DHEAS concentrations were similar between girls (30.3 ±1.86 μg/dL) and boys (29.4 ±1.73 μg/dL) (P > 0.05); 17.3% of children were obese (BMI-for-age z score ≥2 SD). Adiposity indicators were positively and similarly associated with DHEAS [ie, BMI, β standardized regression coefficient: 0.23 (95% CI: 0.17, 0.29); WC, β standardized regression coefficient: 0.23 (95% CI: 0.16, 0.30)]; these associations were only partially related to IGF-I and leptin. Obese children had twice the risk of high DHEAS (OR: 2.16; 95% CI: 1.51, 3.09); at 7 y, obese children with high DHEAS were fatter and more centrally obese than their counterparts (P < 0.05), although their previous growth was similar (P > 0.05). None of the results differed by sex (P > 0.05).

Conclusion: In children of normal birth weight, obesity is positively associated with DHEAS at 7 y of age.

Background: It has been suggested that dietary patterns are associated with future risk of depressive symptoms. However, there is a paucity of prospective data that have examined the temporality of this relation.

Objective: We examined whether adherence to a healthy diet, as defined by using the Alternative Healthy Eating Index (AHEI), was prospectively associated with depressive symptoms assessed over a 5-y period.

Design: Analyses were based on 4215 participants in the Whitehall II Study. AHEI scores were computed in 1991–1993 and 2003–2004. Recurrent depressive symptoms were defined as having a Center for Epidemiologic Studies Depression Scale score ≥16 or self-reported use of antidepressants in 2003–2004 and 2008–2009.

Results: After adjustment for potential confounders, the AHEI score was inversely associated with recurrent depressive symptoms in a dose-response fashion in women (P-trend < 0.001; for 1 SD in AHEI score; OR: 0.59; 95% CI: 0.47, 0.75) but not in men. Women who maintained high AHEI scores or improved their scores during the 10-y measurement period had 65% (OR: 0.35%; 95% CI: 0.19%, 0.64%) and 68% (OR: 0.32%; 95% CI: 0.13%, 0.78%) lower odds of subsequent recurrent depressive symptoms than did women who maintained low AHEI scores. Among AHEI components, vegetable, fruit, trans fat, and the ratio of polyunsaturated fat to saturated fat components were associated with recurrent depressive symptoms in women.

Conclusion: In the current study, there was a suggestion that poor diet is a risk factor for future depression in women.

Background: Intestinal damage and malabsorption caused by chronic environmental enteropathy are associated with growth faltering seen in infants in less-developed countries. Evidence has suggested that supplementary omega-3 (n−3) long-chain PUFAs (LC-PUFAs) might ameliorate this damage by reducing gastrointestinal inflammation. LC-PUFA supplementation may also benefit cognitive development.

Objective: We tested whether early n−3 LC-PUFA supplementation improves infant intestinal integrity, growth, and cognitive function.

Design: A randomized, double-blind, controlled trial [200 mg DHA and 300 mg EPA or 2 mL olive oil/d for 6 mo] was conducted in a population of 172 rural Gambian infants aged 3–9 mo. The primary endpoints were anthropometric measures and gut integrity [assessed by using urinary lactulose:mannitol ratios (LMRs)]. Plasma fatty acid status, intestinal mucosal inflammation (fecal calprotectin), daily morbidity, and cognitive development (2-step means-end test and an attention assessment) were secondary endpoints.

Results: PUFA supplementation resulted in a significant increase in plasma n−3 LC-PUFA concentrations (P < 0.001 for both DHA and EPA) and midupper arm circumference (MUAC) (effect size: 0.31 z scores; 95% CI: 0.06, 0.56; P = 0.017) at 9 mo of age. At 12 mo, MUAC remained greater in the intervention group, and we observed significant increases in skinfold thicknesses (P ≤ 0.022 for all). No other significant differences between treatment groups were detected for growth or LMRs at 9 mo or for secondary outcomes.

Conclusions: Fish-oil supplementation successfully increased plasma n−3 fatty acid status. However, in young, breastfed Gambian infants, the intervention failed to improve linear growth, intestinal integrity, morbidity, or selected measures of cognitive development. The trial was registered at www.isrctn.org as ISRCTN66645725.

Background: The effectiveness of commercial weight-loss programs consisting of very-low-calorie diets (VLCDs) and low-calorie diets (LCDs) is unclear.

Objective: The aim of the study was to quantify weight loss and dropout during a commercial weight-loss program in Sweden (Itrim; cost: $1300/€1000; all participants paid their own fee).

Design: This observational cohort study linked commercial weight-loss data with National Health Care Registers. Weight loss was induced with a 500-kcal liquid-formula VLCD [n = 3773; BMI (in kg/m2): 34 ± 5 (mean ± SD); 80% women; 45 ± 12 y of age (mean ± SD)], a 1200–1500-kcal formula and food-combination LCD (n = 4588; BMI: 30 ± 4; 86% women; 50 ± 11 y of age), and a 1500–1800-kcal/d restricted normal-food diet (n = 676; BMI: 29 ± 5; 81% women; 51 ± 12 y of age). Maintenance strategies included exercise and a calorie-restricted diet. Weight loss was analyzed by using an intention-to-treat analysis (baseline substitution).

Results: After 1 y, mean (±SD) weight changes were −11.4 ± 9.1 kg with the VLCD (18% dropout), −6.8 ± 6.4 kg with the LCD (23% dropout), and −5.1 ± 5.9 kg with the restricted normal-food diet (26% dropout). In an adjusted analysis, the VLCD group lost 2.8 kg (95% CI: 2.5, 3.2) and 3.8 kg (95% CI: 3.2, 4.5) more than did the LCD and restricted normal-food groups, respectively. A high baseline BMI and rapid initial weight loss were both independently associated with greater 1-y weight loss (P < 0.001). Younger age and low initial weight loss predicted an increased dropout rate (P < 0.001). Treatment of depression (OR: 1.4; 95% CI: 1.1, 1.9) and psychosis (OR: 2.6; 95% CI: 1.1, 6.3) were associated with an increased dropout rate in the VLCD group.

Conclusion: A commercial weight-loss program, particularly one using a VLCD, was effective at reducing body weight in self-selected, self-paying adults.

Background: Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake.

Objective: We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage.

Design: This was a double-blind, randomized, controlled intervention trial in 204 men and women that lasted 12 mo. EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHA were assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids).

Results: A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue).

Conclusions: Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN48398526.

Background: Obesity is emerging as the most significant health concern of the 21st century. Although this is attributable in part to changes in our environment—including the increased prevalence of energy-dense food—it also appears that several lifestyle factors may increase our vulnerability to this calorie-rich landscape. Epidemiologic studies have begun to show links between adiposity and behaviors such as television watching, alcohol intake, and sleep deprivation. However, these studies leave unclear the direction of this association. In addition, studies that investigated the acute impact of these factors on food intake have reported a wide variety of effect sizes, from highly positive to slightly negative.

Objective: The purpose of this article was to provide a meta-analysis of the relation between lifestyle choices and increases in acute food intake.

Design: An initial search was performed on PubMed to collect articles relating television watching, sleep deprivation, and alcohol consumption to food intake. Only articles published before February 2012 were considered. Studies that took place in a controlled, laboratory setting with healthy individuals were included. Studies were analyzed by using 3 meta-analyses with random-effects models. In addition, a 1-factor ANOVA was run to discover any main effect of lifestyle.

Results: The 3 most prominent lifestyle factors—television watching, alcohol intake, and sleep deprivation—had significant short-term effects on food intake, with alcohol being more significant (Cohen's d = 1.03) than sleep deprivation (Cohen's d = 0.49) and television watching (Cohen's d = 0.2).

Conclusions: Our results suggest that television watching, alcohol intake, and sleep deprivation are not merely correlated with obesity but likely contribute to it by encouraging excessive eating. Because these behaviors are all known to affect cognitive functions involved in reward saliency and inhibitory control, it may be that they represent common mechanisms through which this eating is facilitated.

Background: The energy content of foods is primarily determined by the Atwater factors, which may not be accurate for certain food groups. Nuts are a food group for which substantial evidence suggests that the Atwater factors may be poorly predictive.

Objective: A study was conducted to determine the energy value of almonds in the human diet and to compare the measured energy value with the value calculated from the Atwater factors.

Design: Eighteen healthy adults consumed a controlled diet or an almond-containing diet for 18 d. Three treatments were administered to subjects in a crossover design, and diets contained 1 of 3 almond doses: 0, 42, or 84 g/d. During the final 9 d of the treatment period, volunteers collected all urine and feces, and samples of diets, feces, and urine were analyzed for macronutrient and energy contents. The metabolizable energy content of the almonds was determined.

Results: The energy content of almonds in the human diet was found to be 4.6 ± 0.8 kcal/g, which is equivalent to 129 kcal/28-g serving. This is significantly less than the energy density of 6.0–6.1 kcal/g as determined by the Atwater factors, which is equivalent to an energy content of 168–170 kcal/serving. The Atwater factors, when applied to almonds, resulted in a 32% overestimation of their measured energy content.

Conclusion: This study provides evidence for the inaccuracies of the Atwater factors for certain applications and provides a rigorous method for determining empirically the energy value of individual foods within the context of a mixed diet. This trial was registered at clinicaltrials.gov as NCT01007188.

Cobalamin deficiency is relatively common, but the great majority of cases in epidemiologic surveys have subclinical cobalamin deficiency (SCCD), not classical clinical deficiency. Because SCCD has no known clinical expression, its diagnosis depends solely on biochemical biomarkers, whose optimal application becomes crucial yet remains unsettled. This review critically examines the current diagnostic concepts, tools, and interpretations. Their exploration begins with understanding that SCCD differs from clinical deficiency not just in degree of deficiency but in fundamental pathophysiology, causes, likelihood and rate of progression, and known health risks (the causation of which by SCCD awaits proof by randomized clinical trials). Conclusions from SCCD data, therefore, often may not apply to clinical deficiency and vice versa. Although many investigators view cobalamin testing as unreliable, cobalamin, like all diagnostic biomarkers, performs satisfactorily in clinical deficiency but less well in SCCD. The lack of a diagnostic gold standard limits the ability to weigh the performance characteristics of metabolic biomarkers such as methylmalonic acid (MMA) and holotranscobalamin II, whose specificities remain incompletely defined outside their relations to each other. Variable cutoff selections affect diagnostic conclusions heavily and need to be much better rationalized. The maximization of reliability and specificity of diagnosis is far more important today than the identification of ever-earlier stages of SCCD. The limitations of all current biomarkers make the combination of ≥2 test result abnormalities, such as cobalamin and MMA, the most reliable approach to diagnosing deficiency in the research setting; reliance on one test alone courts frequent misdiagnosis. Much work remains to be done.

Background: Increased consumption of nuts has been advocated because of their health benefits, but the role of nuts in the treatment of obesity is unclear given their high energy density.

Objective: This study was designed to evaluate the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on body weight and cardiovascular disease risk factors in the context of an 18-mo behavioral weight-management program.

Design: Overweight and obese individuals [n = 123; age = 46.8 y, BMI (in kg/m2) = 34.0] were randomly assigned to consume an AED or NFD and instructed in traditional behavioral methods of weight control. Anthropometric and metabolic measurements were made at baseline, 6 mo, and 18 mo.

Results: Those in the AED group lost slightly but significantly less weight than did those in the NFD group at 6 mo (−5.5 compared with −7.4 kg; P = 0.04), but there were no differences at 18 mo. No significant differences in body composition were found between the groups at 6 or 18 mo. The AED, compared with the NFD, was associated with greater reductions in total cholesterol (P = 0.03), total:HDL cholesterol (P = 0.02), and triglycerides (P = 0.048) at 6 mo, and no differences were observed between the groups at 18 mo.

Conclusions: The AED and NFD groups experienced clinically significant and comparable weight loss at 18 mo. Despite smaller weight loss in the AED group at 6 mo, the AED group experienced greater improvements in lipid profiles. This trial was registered at clinicaltrials.gov as NCT00194428.

Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D].

Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans.

Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials.

Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation.

Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

Background: Longitudinal growth associations with genetic variants identified for adult BMI may provide insights into the timing of obesity susceptibility.

Objective: The objective was to explore associations of known BMI loci with measures of body size from birth to adulthood.

Design: A total of 2537 individuals from a longitudinal British birth cohort were genotyped for 11 genetic variants robustly associated with adult BMI (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, SH2B1, and MTCH2). We derived an obesity-risk-allele score, comprising the sum of BMI-increasing alleles in each individual, and examined this for an association with birth weight and repeated measures of weight, height, and BMI SD scores (SDS) at 11 time points between ages 2 and 53 y.

Results: The obesity-risk-allele score showed borderline significant association with birth weight (0.019 SDS/allele; P = 0.05) and was more clearly associated with higher weight and BMI at all time points between ages 2 and 53 y; the strongest associations with weight occurred at ages 11 and 20 y (both 0.056 SDS/allele). In longitudinal analyses, the score was positively associated with weight gain only between birth and 11 y (0.003 SDS/allele per year; 95% CI: 0.001, 0.004; P = 0.001). The risk-allele score was associated with taller height at 7 y (0.031 SDS/allele; P = 0.002) and greater height gains between 2 and 7 y (0.007 SDS/allele per year; P < 0.001), but not with adult height (P = 0.5).

Conclusions: The combined effect of adult obesity susceptibility variants on weight gain was confined to childhood. These variants conferred a faster tempo of height growth that was evident before the pubertal years.

Background: In the United Kingdom, sodium reduction targets have been set for a large number of processed food categories. Assessment and monitoring are essential to evaluate progress.

Objectives: Our aim was to determine whether household consumer panel food-purchasing data could be used to assess the sodium content of processed foods. Our further objectives were to estimate the mean sodium content of UK foods by category and undertake analyses weighted by food-purchasing volumes.

Design: Data were obtained for 21,108 British households between October 2008 and September 2009. Purchasing data (product description, product weight, annual purchases) and sodium values (mg/100 g) were collated for all food categories known to be major contributors to sodium intake. Unweighted and weighted mean sodium values were calculated.

Results: Data were available for 44,372 food products. The largest contributors to sodium purchases were table salt (23%), processed meat (18%), bread and bakery products (13%), dairy products (12%), and sauces and spreads (11%). More than one-third of sodium purchased (37%) was accounted for by 5 food categories: bacon, bread, milk, cheese, and sauces. For some food groups (bread and bakery, cereals and cereal products, processed meat), purchase-weighted means were 18–35% higher than unweighted means, suggesting that market leaders have higher sodium contents than the category mean.

Conclusion: The targeting of sodium reduction in a small number of food categories and focusing on products sold in the highest volumes could lead to large decreases in sodium available for consumption and therefore to gains in public health.

Background: Previous studies have reported that green tea consumption is associated with a lower risk of diseases that cause functional disability, such as stroke, cognitive impairment, and osteoporosis. Although it is expected that green tea consumption would lower the risk of incident functional disability, this has never been investigated directly.

Objective: The objective was to determine the association between green tea consumption and incident functional disability in elderly individuals.

Design: We conducted a prospective cohort study in 13,988 Japanese individuals aged ≥65 y. Information on daily green tea consumption and other lifestyle factors was collected via questionnaire in 2006. Data on functional disability were retrieved from the public Long-term Care Insurance database, in which subjects were followed up for 3 y. We used Cox proportional hazards regression analysis to investigate the association between green tea consumption and functional disability.

Results: The 3-y incidence of functional disability was 9.4% (1316 cases). The multiple-adjusted HR (95% CI) of incident functional disability was 0.90 (0.77, 1.06) among respondents who consumed 1–2 cups green tea/d, 0.75 (0.64, 0.88) for those who consumed 3–4 cups/d, and 0.67 (0.57, 0.79) for those who consumed ≥5 cups/d in comparison with those who consumed <1 cup/d (P-trend < 0.001).

Conclusion: Green tea consumption is significantly associated with a lower risk of incident functional disability, even after adjustment for possible confounding factors.

Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available.

Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces.

Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody.

Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients.

Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867.

Background: The number of cesarean sections (CSs) is increasing in many countries, and there are concerns about their short- and long-term effects. A recent Brazilian study showed a 58% higher prevalence of obesity in young adults born by CS than in young adults born vaginally. Because CS-born individuals do not make contact at birth with maternal vaginal and intestinal bacteria, the authors proposed that this could lead to long-term changes in the gut microbiota that could contribute to obesity.

Objective: We assessed whether CS births lead to increased obesity during childhood, adolescence, and early adulthood in 3 birth cohorts.

Design: We analyzed data from 3 birth-cohort studies started in 1982, 1993, and 2004 in Southern Brazil. Subjects were assessed at different ages until 23 y of age. Poisson regression was used to estimate prevalence ratios with adjustment for ≤15 socioeconomic, demographic, maternal, anthropometric, and behavioral covariates.

Results: In the crude analyses, subjects born by CS had ∼50% higher prevalence of obesity at 4, 11, and 15 y of age but not at 23 y of age. After adjustment for covariates, prevalence ratios were markedly reduced and no longer significant for men or women. The only exception was an association for 4-y-old boys in the 1993 cohort, which was not observed in the other 2 cohorts or for girls.

Conclusion: In these 3 birth cohorts, CSs do not seem to lead to an important increased risk of obesity during childhood, adolescence, or early adulthood.

Background: Whereas the negative effect of consuming trans fatty acids found in partially hydrogenated vegetable oils on cardiovascular disease (CVD) risk is well established, the effect of trans fatty acids from ruminant sources (rTFAs) on CVD risk factors has not yet been established, particularly among women.

Objective: We investigated the effects of a butter naturally enriched in rTFAs, of which vaccenic acid is the predominant isomer, on plasma lipid concentrations among healthy women.

Design: In a double-blind, randomized, crossover controlled study, 61 healthy women aged 19–70 y were fed 2 isoenergetic diets lasting 4 wk each. The 2 diets were defined as moderately high in rTFAs (3.7 g/d, 1.5% of daily energy) and control (0.9 g/d, 0.3% of daily energy).

Results: No significant effect of the rTFA diet was found on total plasma cholesterol, LDL cholesterol, apolipoprotein B, apolipoprotein A-I, and triglyceride concentrations compared with the control diet. There was a small yet statistically significant reduction in plasma HDL-cholesterol concentrations with the rTFA diet (−2.8%; P = 0.004), which was significant (P for the BMI × treatment interaction = 0.006) among women with a BMI (in kg/m2) ≥25 (−5.2%; P = 0.004; n = 18) but not among women with a BMI <25 (−1.2%; P = 0.13; n = 43).

Conclusions: These results suggest that an increase in dietary rTFAs equivalent to ∼1% of daily energy has no significant effect on LDL but may be associated with a reduction in plasma HDL-cholesterol concentrations, particularly in overweight women. This trial is registered at clinicaltrials.gov as NCT00930137.

Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef.

Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD).

Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk.

Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets.

Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.

Background: Protein is an indispensable component within the human diet. It is unclear, however, whether behavioral strategies exist to avoid shortages.

Objective: The objective was to investigate the effect of a low protein status compared with a high protein status on food intake and food preferences.

Design: We used a randomized crossover design that consisted of a 14-d fully controlled dietary intervention involving 37 subjects [mean ± SD age: 21 ± 2 y; BMI (in kg/m2): 21.9 ± 1.5] who consumed individualized, isoenergetic diets that were either low in protein [0.5 g protein · kg body weight (BW)−1 · d−1] or high in protein (2.0 g protein · kg BW−1 · d−1). The diets were followed by an ad libitum phase of 2.5 d, during which a large array of food items was available, and protein and energy intakes were measured.

Results: We showed that in the ad libitum phase protein intake was 13% higher after the low-protein diet than after the high-protein diet (253 ± 70 compared with 225 ± 63 g, P < 0.001), whereas total energy intake was not different. The higher intake of protein was evident throughout the ad libitum phase of 2.5 d. In addition, after the low-protein diet, food preferences for savory high-protein foods were enhanced.

Conclusions: After a protein deficit, food intake and food preferences show adaptive changes that suggest that compensatory mechanisms are induced to restore adequate protein status. This indicates that there are human behavioral strategies present to avoid protein shortage and that these involve selection of savory high-protein foods. This trial was registered with the Dutch Trial register at http://www.trialregister.nl as NTR2491.

Background: Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities.

Objective: This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease.

Design: This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program.

Results: Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P < 0.0001 compared with placebo); least-squares mean percentage changes from baseline in body weight were –1.8%, –9.3%, and –10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR–treated subjects at each dose achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56.

Conclusion: PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367.

Approximately one-quarter of circulating cobalamin (vitamin B-12) binds to transcobalamin (holoTC) and is thereby available for the cells of the body. For this reason, holoTC is also referred to as active vitamin B-12. HoloTC was suggested as an optimal marker of early vitamin B-12 deficiency >20 y ago. This suggestion led to the development of suitable assays for measurement of the compound and clinical studies that aimed to show the benefit of measurement of holoTC rather than of vitamin B-12. Today holoTC can be analyzed by 3 methods: direct measurement of the complex between transcobalamin and vitamin B-12, measurement of vitamin B-12 attached to transcobalamin, or measurement of the amount of transcobalamin saturated with vitamin B-12. These 3 methods give similar results, but direct measurement of holoTC complex is preferable in the clinical setting from a practical point of view. HoloTC measurement has proven useful for the identification of the few patients who suffer from transcobalamin deficiency. In addition, holoTC is part of the CobaSorb test and therefore useful for assessment of vitamin B-12 absorption. Clinical studies that compare the ability of holoTC and vitamin B-12 to identify individuals with vitamin B-12 deficiency (elevated concentration of methylmalonic acid) suggest that holoTC performs better than total vitamin B-12. To date, holoTC has not been used for population-based assessments of vitamin B-12 status, but we suggest that holoTC is a better marker than total vitamin B-12 for such studies.

Population studies such as NHANES analyze large numbers of laboratory measurements and are often performed in different laboratories using different measurement procedures and over an extended period of time. Correct clinical and epidemiologic interpretations of the results depend on the accuracy of those measurements. Unfortunately, considerable variability has been observed among assays for folate, vitamin B-12, and related biomarkers. In the past few decades, the science of metrology has advanced considerably, with the development of improved primary reference measurement procedures and high-level reference materials, which can serve as the basis for accurate measurement. A rigorous approach has been established for making field methods traceable to the highest-level reference measurement procedures and reference materials. This article reviews some basic principles of metrology and describes their recent application to measurements of folate and vitamin B-12.

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999–2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991–1994 and NHANES 1999–2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007–2010. Roundtable experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography–tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA.

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

Background: Oxidative and inflammatory stress are elevated in obesity and are further augmented in metabolic syndrome. We showed previously that dairy components suppress the adipocyte- and macrophage-mediated generation of reactive oxygen species and inflammatory cytokines and systemic oxidative and inflammatory biomarkers in obesity.

Objective: The objective of this study was to determine the early (7 d) and sustained (4 and 12 wk) effects of adequate-dairy (AD) compared with low-dairy (LD) diets in subjects with metabolic syndrome.

Design: Forty overweight and obese adults with metabolic syndrome were randomly assigned to receive AD (3.5 daily servings) or LD (<0.5 daily servings) weight-maintenance diets for 12 wk. Oxidative and inflammatory biomarkers were assessed at 0, 1, 4, and 12 wk as primary outcomes; body weight and composition were measured at 0, 4, and 12 wk as secondary outcomes.

Results: AD decreased malondialdehyde and oxidized LDL at 7 d (35% and 11%, respectively; P < 0.01), with further decreases by 12 wk. Inflammatory markers were suppressed with intake of AD, with decreases in tumor necrosis factor-α at 7 d and further reductions through 12 wk (35%; P < 0.05); decreases in interleukin-6 (21%; P < 0.02) and monocyte chemoattractant protein 1 (14% decrease at 4 wk, 24% decrease at 12 wk; P < 0.05); and a corresponding 55% increase in adiponectin at 12 wk (P < 0.01). LD exerted no effect on oxidative or inflammatory markers. Diet had no effect on body weight; however, AD significantly reduced waist circumference and trunk fat (P < 0.01 for both), and LD exerted no effect.

Conclusion: An increase in dairy intake attenuates oxidative and inflammatory stress in metabolic syndrome. This trial was registered at clinicaltrials.gov as NCT01266330.

A roundtable dialogue to discuss “NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status” took place in July 2010. This article provides an overview of the meeting and this supplement issue. Although the focus of the roundtable dialogue was on the measurement of folate and vitamin B-12 status biomarkers in NHANES, this article also describes the relevance and importance of these issues for clinical and research laboratories. The roundtable identified the microbiological assay (MA) as the gold standard for measurement of serum and red blood cell folate concentrations. The roundtable noted that differences in results between the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA) that NHANES 1991–1994 and 1999–2006 used and the MA that NHANES 2007–2010 used will require adjustment equations to evaluate time trends. The roundtable found that the close agreement between the serum results for the MA and liquid chromatography–tandem mass spectrometry (LC-MS/MS) procedures supported the conversion to LC-MS/MS for serum folate in future NHANES. The roundtable recognized the uncertainty about whether subclinical vitamin B-12 deficiency is a public health concern but encouraged reinstatement of at least one circulating vitamin B-12 measure and one functional vitamin B-12 status measure in future NHANES. The use of serum vitamin B-12 and plasma methylmalonic acid would provide continuity with past NHANES. The roundtable supported the continued use of the National Institute of Standards and Technology (NIST) reference materials in NHANES biomarker analyses and the further development of additional reference materials by the NIST.