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Many studies have investigated the effects of soy isoflavones on weight control, but few have focused on the role of equol, a gut-derived metabolite of daidzein with greater bioavailability than other soy isoflavones.This study examined the association of equol production with obesity and explored the mediating roles of equol-related gut microbiota and microbial carnitine metabolites.This 6.6-y prospective study included 2958 Chinese adults (2011 females and 947 males) aged 60.6 ± 6.0 y (mean ± SD) at baseline. Urinary equol and isoflavones were measured using HPLC-tandem MS. BMI, percentage fat mass (%FM), and serum triglycerides (TGs) were assessed every 3 y. Metagenomics sequencing and assessment of carnitine metabolites in feces were performed in a subsample of 897 participants.Urinary equol, but not daidzein and genistein, was independently and inversely associated with the obesity-related indicators of BMI, %FM, and a biomarker (TGs). Equol producers (EPs) had lower odds of adiposity conditions and a reduced risk of 6.6-y obesity progression than non-EPs among total participants. Gut microbial analyses indicated that EPs had higher microbiome species richness (P = 3.42 × 10-5) and significantly different β-diversity of gut microbiota compared with the non-EP group (P = 0.001), with 20 of 162 species differing significantly. EPs (compared with non-EPs) had higher abundances of Alistipes senegalensis and Coprococcus catus but lower abundances of Ruminococcus gnavus (false discovery rate 0.05). Among the 7 determined fecal acylcarnitine metabolites, palmitoylcarnitine, oleylcarnitine 18:1, and stearylcarnitine were inversely associated with EPs but positively correlated with obesity conditions and progression. Path analyses indicated that the beneficial association between equol and obesity might be mediated by gut microbiota and decreased production of 3 acylcarnitines in feces.This study suggests a beneficial association between equol and obesity, mediated by the gut microbiome and acylcarnitines, in adults.This trial was registered at clinicaltrials.gov as NCT03179657.

BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), a federal nutrition assistance program supporting low-income families, serves half of United States–born infants, most of whom are issued infant formula by age 2 mo. Obesity prevalence is high among children of low-income households, particularly formula-fed children. OBJECTIVES: This study was conducted to determine whether glucose-based lactose-reduced infant formula made with corn syrup solids (CSSF) is associated with increased obesity risk compared with non-CSSFs that are lactose based. DESIGN: WIC administrative data on infant formula issuance and child weights and lengths were collected prospectively in Southern California between 2012 and 2020. Included children stopped breastfeeding by 3 mo, were issued cow’s milk–based formula through 12 mo, and were enrolled through the final year of WIC eligibility at age 4 y ( n = 15,246). CSSF issuance was assessed continuously (range 0–13 mo) and dichotomously (any, none). Poisson and linear risk regression with robust SE estimates generated risk ratios (RRs), risk differences, and CIs for child obesity [BMI for age (in kg/m (2)) ≥95th percentile]. RESULTS: Any CSSF was issued to 23% of children, and 25% were obese at age 4 y. Children with any CSSF issuance had 10% higher obesity risk (RR: 1.10; 95% CI: 1.02, 1.20) than children with no CSSF issuance at age 2 y. Associations remained significant through age 4 y (RR: 1.07; 95% CI: 1.01,1.14), independent of maternal weight status, total formula issued and breastfeeding duration, and were not modified by child race or sex. Obesity risk increased with additional mo of CSSF exposure, reaching 16% higher risk (RR: 1.16; 95% CI: 1.05, 1.28) at age 2 y for children with 12 mo of CSSF. CONCLUSIONS: CSSF issuance is associated with increased obesity risk in the first 5 y life in a dose dependent manner, independently of maternal weight status, breastfeeding duration, and total formula issuance.

BACKGROUND: Plant-based diets are recommended for chronic disease prevention, yet there has been little focus on plant-based diet quality among participants of South Asian ancestry who consume a predominantly plant-based diet. OBJECTIVES: We evaluated cross-sectional and prospective associations between plant-based diet quality and cardiometabolic risks among participants of South Asian ancestry who are living in the United States. METHODS: We included 891 participants of South Asian ancestry who completed the baseline visit in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. The prospective analysis included 735 participants who completed exam 2 (∼5 years after baseline). The plant-based diet quality was assessed using 3 indices: an overall plant-based diet index (PDI) that summarizes the consumption of plant foods, a healthy PDI (hPDI) that measures consumption of healthy plant foods, and an unhealthy PDI (uPDI) that reflects consumption of less healthy plant foods. RESULTS: At baseline, the PDI score was inversely associated with fasting glucose. We observed inverse associations between PDI and hPDI scores and HOMA-IR, LDL cholesterol, weight, and BMI (all P values

Postterm pregnancy has been associated with higher risk of perinatal mortality and morbidity, but its long-term health effects on offspring are poorly understood.The aim of the study was to investigate the prospective associations between maternal postterm pregnancy and adverse growth outcomes in children.The Jiaxing Birth Cohort is part of a large population-based health surveillance system in China and recruited pregnant females resident in the Jiaxing area between 1999 and 2013; newborns were followed up for a median duration of 5.8 y until they went to school. Mother-child pairs with maternal gestational information and offspring's anthropometric data at 4-7 y old were included. Postterm pregnancy was defined as maternal gestational age ≥42 and47 wk, and its associations with offspring obesity, overweight/obesity, and thinness during childhood were determined by using Poisson regression models.Of the 101,505 included mother-child pairs, 2369 (2.3%) children were born at postterm. Children born at postterm had significantly lower BMI-for-age z score, weight-for-age z score, and height-for-age z score than those born at term; the mean difference (95% CI) was -0.11 (-0.15, -0.06), -0.17 (-0.21, -0.13), and -0.16 (-0.20, -0.12), respectively. When comparing postterm with term pregnancy, the multivariable-adjusted RRs and 95% CIs among preschool-age children were 0.87 (0.68, 1.11) for obesity, 0.82 (0.72, 0.94) for overweight/obesity, and 1.18 (1.09, 1.28) for thinness, respectively. These risk estimates were robust in sensitivity analyses, but were attenuated in several subgroups stratified by age, sex, mode of delivery, and fetal distress.Postterm pregnancy was associated with a higher risk of thinness, and a lower risk of overweight/obesity, as well as lower growth parameters in preschool-age children. These findings imply that postterm pregnancy may impede the long-term growth of offspring.

BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs and important posttranscriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism. OBJECTIVES: We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity. METHODS: This study included adults with abdominal obesity from an 18-mo diet and physical activity intervention trial. Circulating miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 mo; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal adipose tissue [visceral (VAT), deep subcutaneous (DSAT), and superficial subcutaneous (SSAT) adipose tissue; cm(2)] (n = 144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n = 141) and pancreas (n = 143). RESULTS: Greater decreases in miR-100-5p were associated with more reductions of VAT (β ± SE per 1-SD decrease: −9.63 ± 3.13 cm(2); P = 0.0025), DSAT (β ± SE: −5.48 ± 2.36 cm(2); P = 0.0218), SSAT (β ± SE: −4.64 ± 1.68 cm(2); P = 0.0067), and intrahepatic fat percentage (β ± SE: −1.54% ± 0.49%; P = 0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-mo reductions of VAT (β ± SE: −10.12 ± 3.31 cm(2) per 1-SD decrease; P = 0.0027) and intrahepatic fat percentage (β ± SE: −1.28% ± 0.52%; P = 0.015). Further, decreases in circulating miR-99b-5p (β ± SE: per 1-SD decrease: −0.44% ± 0.21%; P = 0.038) and miR-100-5p (β ± SE: −0.50% ± 0.23%; P = 0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 mo. CONCLUSIONS: Decreases in circulating miR-99-5p/100-5p expression induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity. This trial was registered at clinicaltrials.gov as NCT01530724.

Since 1980, obesity prevalence among US adults has soared from 14% to 42%. The commonly accepted explanation is pervasive overeating: ever-increasing energy intake as the population gains weight, year after year. However, evidence does not support this hypothesis. National data on energy intake and energy availability show increases between 1961 and 2000, during modern industrialization of food; but a plateau or declines thereafter-even as obesity continued rising-and while physical activity modestly increased. Thus, Americans appear to be eating relatively less since 2000, for ever-increasing body sizes, as time has progressed. Although both energy intake and energy availability are measured with error, such errors would have to be new since 2000 and systematically increasing over time for these 2 separate, independent measures. Given the tremendous societal consequences of obesity, and failure to date of energy balance-focused interventions to stem the tide, it is critical for the scientific community to consider and test alternative hypotheses. Growing evidence suggests complex, interrelated biological interactions between food processing (including acellular nutrients, depleted prebiotics, additives), gut microbial composition and function, host metabolic expenditure, and intergenerational transmission of risk (including epigenetics, noncoding RNAs, microbial species). In this paradigm, whereas increasing energy intake may have contributed to rising obesity in earlier years, today pervasive adiposity and its physiologic adaptations have created a biological milieu which interacts with industrialized foods to promote escalating obesity, even with stable energy intake-a self-sustaining, difficult-to-reverse cycle. These scientific hypotheses must be rigorously evaluated, because even partial confirmation would dramatically shift and expand current prevention and treatment strategies. Urgent new investment in research is required. Simultaneously, uncertain evidence on the obesity epidemic's primary drivers does not mean there is no evidence on actions that can help, and existing science must be more rapidly translated and refined into clinical, public health, and policy interventions.

Mechanisms linking a proinflammatory diet to obesity remain under investigation. The ability of diet to influence the gut microbiome (GM) in creating chronic low-grade systemic inflammation provides a plausible connection to adiposity.Assess whether any associations seen between the Energy-Adjusted Dietary Inflammatory Index (E-DII score), total fat mass, visceral adipose tissue (VAT), or liver fat (percentage volume) operated through the GM or microbial related inflammatory factors, in a multiethnic cross-sectional study.In the Multiethnic Cohort-Adiposity Phenotype Study (812 men, 843 women, aged 60-77 y) we tested whether associations between the E-DII and total adiposity, VAT, and liver fat function through the GM, LPS, and high-sensitivity C-reactive protein (hs-CRP). DXA-derived total fat mass, MRI-measured VAT, and MRI-based liver fat were measured. Participants provided stool and fasting blood samples and completed an FFQ. Stool bacterial DNA was amplified and the 16S rRNA gene was sequenced at the V1-V3 region. E-DII score was computed from FFQ data, with a higher E-DII representing a more proinflammatory diet. The associations between E-DII score, GM (10 phyla, 28 genera, α diversity), and adiposity phenotypes were examined using linear regression and mediation analyses, adjusting for confounders.There were positive total effects (c) between E-DII and total fat mass (c = 0.68; 95% CI: 0.47, 0.90), VAT (c = 4.61; 95% CI: 2.95, 6.27), and liver fat (c = 0.40; 95% CI: 0.27, 0.53). The association between E-DII score and total fat mass was mediated by LPS, Flavonifractor, [Ruminococcus] gnavus group, and Tyzzerella. The association between E-DII score and ectopic fat occurred indirectly through Fusobacteria, Christensenellaceae R-7 group, Coprococcus 2, Escherichia-Shigella, [Eubacterium] xylanophilum group, Flavonifractor, Lachnoclostridium, [Ruminococcus] gnavus group, Tyzzerella, [Ruminococcus] gnavus group (VAT only), and α diversity (liver fat only). There was no significant association between E-DII score and adiposity phenotype through hs-CRP.Associations found between E-DII and adiposity phenotypes occurred through the GM and LPS.

There is little epidemiological evidence of sex differences in the association between dynapenic abdominal obesity and the decline in physical performance in older adults.The aims of the present study were to investigate whether the decline in physical performance is worse in individuals with dynapenic abdominal obesity and whether there are sex differences in this association.Of 6183 individuals aged ≥60 y from the English Longitudinal Study of Ageing, 2308 participants with missing data were excluded. Therefore, a longitudinal analysis was conducted with 3875 older adults. Abdominal obesity was determined based on waist circumference (102 cm for males, and88 cm for females), and dynapenia was based on grip strength (26 kg for males,16 kg for female). The sample was divided into 4 groups: nondynapenic/nonabdominal obesity (ND/NAO), nondynapenic/abdominal obesity (ND/AO), dynapenic/nonabdominal obesity (D/NAO), and dynapenic/abdominal obesity (D/AO). Decline in physical performance in an 8-y follow-up period was analyzed using generalized linear mixed models.At baseline, both male (-1.11 points; 95% CI: -1.58, -0.65 points; P 0.001) and female (-1.39 points; 95% CI: -1.76, -1.02 points; P 0.001) with D/AO had worse performances on the Short Physical Performance Battery (SPPB) than their counterparts in the ND/NAO group. Over the 8-y follow-up, males with D/AO had a faster rate of decline in the SPPB performance compared with males in the ND/NAO group (-0.11 points/y; 95% CI: -0.21, -0.01 points; P = 0.03).D/AO is associated with a stronger decline in physical performance in males but not in females. The identification and management of dynapenic abdominal obesity could be essential to avoiding the first signs of functional impairment in older males.

OBJECTIVES: The aims of this study are to (1) create clusters of joint temporal patterns of diet and physical activity (PA), and (2) determine the association of these clusters with health status indicators including body mass index (BMI), waist circumference (WC), fasting plasma glucose, hemoglobin A1c, triglyceride, high-density lipoprotein cholesterol, total cholesterol, blood pressure and health outcomes including obesity, Type 2 Diabetes (T2DM) and metabolic syndrome (MS) in U.S. adults 20–65 years. METHODS: A random day of PA from accelerometry data and the first day 24 hour dietary recall collected in the National Health and Nutrition Examination Survey 2003–2006 were used to determine absolute PA intensity, absolute energy intake, and the time of these activities. Dietary and PA data from 1,627 U.S. adults were Z-normalized. Dynamic time warping (DTW) coupled with kernel-k means clustering algorithm was used to develop joint temporal dietary and PA patterns that maximally partition individuals with similar temporal behaviors into mutually exclusive clusters derived from the data rather than predefined standards. Multivariate regression models adjusted for ptential confounders, multiple comparisons and survey design factors determined associations between joint temporal patterns and health status indicators along with health outcomes (P

Background There are limited systematic reviews exploring the use of social media for recruiting participants specifically for nutrition, physical activity, and obesity related studies. Objective To conduct a systematic review on the effectiveness of using social media (Facebook, Instagram, and Twitter) for recruiting healthy participants in nutrition, physical activity, or obesity related studies. Design Studies were identified from five databases and included if they reported the number of participants recruited by social media (Facebook, Instagram, or Twitter) vs traditional (printed, email, etc.). The effectiveness of recruitment was compared between methods by study procedures (in-person vs online procedures). The cost-effectiveness of methods was also explored. The protocol was published in the Prospero database (ID# CRD42020204414). Results Twenty-six studies were included. Among studies with both types of recruitment methods, 49% of the sample was reached through traditional methods, 40% through social media, and the rest by other methods. For in-person study procedures, the median number of participants recruited using social media was 19 (range 3-278) and for online study procedures, it was 298 (range 3-17,069). Median recruitment cost using social media (n = 14 studies) was ${\$}$11.9 (range ${\$}$0-517) per participant while this varied considerably for traditional methods depending on how it was calculated (${\$}$214, ${\$}$18.9-${\$}$777). The ratio of participants reached vs recruited was 0.12%; the overall ratio of participants interactions vs recruited was 21.2%. Conclusion For in-person study procedures, traditional recruitment methods were more effective than social media but for online study procedures, about half reported that social media was more effective. While more potential participants were reached through social media, only 21.2% of those who interacted with ads were enrolled. With the increased use of social media, their use for recruitment may be more frequent; therefore, future reviews may show different results.

Background Evidence is emerging that inter-daily meal pattern variability potentially impacts on response such as thermic effect of food (TEF), macronutrient metabolism and appetite. Objectives To investigate the effect of irregular meal pattern on TEF, glucose, insulin, lipid profile and appetite regulation in females with overweight or obesity and confirmed insulin resistance. Design In a randomized crossover trial, 9 females [mean±SD BMI: 33.3±3.1 kg/m2) with confirmed insulin resistance consumed a regular (14 days; 6 meals/d) and an irregular (14 days; 3-9 meals/d) meal pattern separated by a 14-d wash-out interval. Identical foods were provided during the interventions and at the start and end of each meal pattern participants attended the laboratory after an overnight fast. Energy expenditure, glucose, insulin, lipids, adiponectin, leptin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin were measured at baseline and for three hours after consumption of a test drink, after which an ad libitum test meal was offered. Subjective appetite ratings were recorded before and after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 7 consecutive days during each intervention. Results TEF (over 3 h) was significantly lower post-irregular intervention compared with post-regular (97.7±19.2 kJ*3h in post-regular visit, and 76.7±35.2 kJ*3h in post-irregular visit (Paired T-test, P = 0.048). Differences in HOMA-IR between the two interventions (3.3±1.7 and 3.6±1.6 in post-regular and post-irregular meal pattern, respectively) were not significant. Net iAUC for GLP-1 concentrations (over 3 h) post-regular meal pattern were higher (864.9±456.1 pmol/L*3h) than post-irregular meal pattern (487.6±271.7 pmol/L*3h), (Paired T-test; P = 0.005). Conclusion Following a 14-d period of irregular meal pattern, TEF was significantly less than following regular meal pattern potentially compromising weight management if sustained long term.www.clinicaltrials.gov (ID number; NCT02582606).

Background Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. Objectives This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. Methods After 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. Results Retention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. Conclusions A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.

BACKGROUND: It is unknown whether behavioral interventions to improve diet are effective in people with a genetic predisposition to obesity. OBJECTIVES: To examine associations between BMI genetic risk and changes in weight and workplace purchases by employees participating in a randomized controlled trial of an automated behavioral workplace intervention to promote healthy food choices. METHODS: Participants were hospital employees enrolled in a 12-mo intervention followed by a 12-mo follow-up. Hospital cafeterias utilized a traffic-light labeling system (e.g., green = healthy, red = unhealthy) that was used to calculate a validated Healthy Purchasing Score (HPS; higher = healthier). A weighted genome-wide BMI genetic score was generated by summing BMI-increasing alleles. RESULTS: The study included 397 adults of European ancestry (mean age, 44.9 y; 80.9% female). Participants in the highest genetic quartile (Q4) had a lower HPS and higher purchases of red-labeled items relative to participants in the lowest quartile (Q1) at baseline [Q4–Q1 Beta HPS, –4.66 (95% CI, –8.01 to –1.32); red-labeled items, 4.26% (95% CI, 1.45%–7.07%)] and at the 12-mo [HPS, –3.96 (95% CI, –7.5 to –0.41); red-labeled items, 3.20% (95% CI, 0.31%–6.09%)] and 24-mo [HPS, –3.70 (95% CI, –7.40 to 0.00); red-labeled items, 3.48% (95% CI, 0.54%–6.41%)] follow-up periods. In the intervention group, increases in HPS were similar in Q4 and Q1 at 12 mo (Q4–Q1 Beta, 1.04; 95% CI, –2.42 to 4.50). At the 24-mo follow-up, the change in BMI from baseline was similar between Q4 and Q1 (0.17 kg/m(2); 95% CI, –0.55 to 0.89 kg/m(2)) in the intervention group, but higher in Q4 than Q1 (1.20 kg/m(2); 95% CI, 0.26–2.13 kg/m(2)) in the control group. No interaction was evident between the treatment arm and genetic score for BMI or HPS. CONCLUSIONS: Having a high BMI genetic risk was associated with greater increases in BMI and lower quality purchases over 2 y. The 12-mo behavioral intervention improved employees’ food choices, regardless of the genetic burden, and may have attenuated weight gain conferred by having the genetic risk.

BACKGROUND: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements. OBJECTIVES: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors. METHODS: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression. RESULTS: Compared with usual care, PST led to reductions in left amygdala activation (−0.75; 95% CI: −1.49, −0.01) and global scores of the negative affect circuit (−0.43; −0.81, −0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized β-coefficients were −0.67 in usual care and −0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and −2.02 in usual care and −0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized β-coefficients were −0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and −1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet. CONCLUSIONS: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

Background: Observed associations of high-protein diets with changes in insulin resistance are inconclusive.Objectives: We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied.Methods: Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst - EIRep)/EIEst] × 100% and [(PRep - PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger.Results: Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger.Conclusions: During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c.This trial was registered at clinicaltrials.gov as NCT01777893.

BACKGROUND Data from the NHANES indicate that BMI has increased in some subgroups of children and adolescents in the United States over the past 20 y; however, BMI is an indirect measure of body fatness. OBJECTIVES We assessed changes in DXA-derived measures of adiposity in a nationally representative population of US children and adolescents aged 8-19 y from 1999-2006 to 2011-2018. METHODS Using data from the NHANES, we compared the means and distributions of DXA-derived percentage body fat (%BF) and fat mass index (FMI; fat mass/height2 in kg/m2) between 1999-2006 (n = 10,231) and 2011-2018 (n = 6923) among males and females by age group, race and Hispanic origin, and BMI categories. Estimates were standardized by age and race and Hispanic origin. RESULTS From 1999-2006 to 2011-2018, mean %BF increased from 25.6% to 26.3% (change in %BF: 0.7%; 95% CI: 0.2%, 1.2%; P

BACKGROUND LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. OBJECTIVES This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. METHODS We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. RESULTS This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P

BACKGROUND Wheat bran (WB) has been associated with improved gastrointestinal health and a reduced risk of metabolic disorders. Reducing the particle size of WB might increase its fermentability and facilitate cross-feeding between the gut bacteria and in this way produce health effects. OBJECTIVES We investigated the impact of WB with reduced particle size (WB RPS) on colonic fermentation and host health in normal-weight (NW) and obese (OB) participants compared with placebo (PL). METHODS During 1 mo, 36 NW and 14 OB participants daily consumed 20 g WB RPS or PL (maltodextrin). Before and after the intervention, fasting serum and fecal SCFAs, fecal metabolite profiles, and microbiota composition were measured as fermentation parameters. Fecal output, fecal dry weight (%), fat excretion, transit, stool consistency, intestinal permeability, and serum total cholesterol, triglyceride, and C-reactive protein concentrations were measured as health parameters. The impact of WB RPS on the fermentation of other carbohydrates was assessed by quantifying postprandial cumulative serum 13C-SCFA after a challenge with 13C-inulin. RESULTS WB RPS increased fasting serum acetate (P

Background While insufficient sleep duration has emerged as a strong, independent risk factor for obesity, the mechanisms remain unclear. One possibility is greater "eating in the absence of hunger" (EAH) or energy intake beyond the point of satiety, when tired. Objective The aim was to determine whether mild sleep loss increases EAH in children. Methods A crossover study was undertaken in 105 healthy children (8-12 y) with normal sleep (∼8-11 h/night). After randomization, children went to bed 1 h earlier (sleep extension) or 1 h later (sleep restriction) than their usual bedtime, over 2 intervention weeks separated by a 1-wk washout. At the end of each intervention week, children underwent an EAH feeding experiment involving a preloading meal until satiation, followed by an ad libitum buffet (of highly palatable snacks) to measure EAH, with each food item weighed before and after consumption. Results Ninety-three children completed the EAH experiment. There was no evidence of a difference in energy intake from EAH between sleep restriction and extension conditions when analyzed as a crossover design. However, a learning effect was found, with children eating significantly less (-239 kJ; 95% CI: -437, -41 kJ; P = 0.018) during the preload phase and significantly more (181 kJ; 95% CI: 38, 322 kJ; P = 0.013) in the ad libitum phase in the second week. No significant differences were seen using an underpowered parallel analysis for energy intake during the ad libitum phase when sleep deprived (106 kJ; 95% CI: -217, 431 kJ; P = 0.514). Conclusions Our findings suggest that measuring a difference in eating behavior in relation to sleep proved unsuitable using the EAH experiment in a crossover design in children, due to a learning effect. This trial was registered at the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367587&isReview=true) as ACTRN12618001671257 .

BACKGROUND Trends in junk food consumption, a risk for obesity, are not well established. OBJECTIVES We examined national trends in types of junk food (excluding beverages) and their sources (grocery, restaurants, schools, etc.), overall and in population subgroups. METHODS We assessed 29,970 children (aged 2-19 y) and 44,501 adults (aged ≥20 y) with 24-h dietary recall data from 9 NHANES cycles (2001-2002 to 2017-2018). Trends in junk food were assessed over time using 1-d values for individuals with single recalls and 2-d means for others. RESULTS From 2001 to 2018, percent energy (%E) from junk food remained stable for children (from 18.1% to 17.5%, P-trend = 0.25) and decreased for adults (14.1% to 13.0%, P-trend = 0.002). Among children, increases occurred in %E from crackers (1.19% to 1.35%) and snack/meal bars (0.38% to 0.69%) and decreases in candy (2.58% to 1.96%) and other desserts (3.11% to 2.48%) (all P-trends

Background The achievement of target 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy may be altered by maternal obesity. Objective The authors examined the effects of maternal supplementation of 10 μg compared with 20 μg vitamin D3/d on maternal and umbilical cord 25(OH)D. The secondary aim was to investigate the influence of maternal BMI (in kg/m2) on the response of the primary outcomes. Methods The authors performed a 2-arm parallel double-blind randomized trial with 240 pregnant women recruited throughout the year in Northern Ireland. Women were stratified by BMI to receive 10 or 20 µg vitamin D3/d from 12 gestational wk (GW) until delivery. Maternal blood samples collected at 12, 28, and 36 GW and from the umbilical cord were analyzed for total serum 25(OH)D. A total of 166 women completed the study. Results Mean ± SD 25(OH)D at 36 GW was 80.8 ± 28.2 compared with 94.4 ± 33.2 nmol/L (P < 0.001) (10 compared with 20 µg vitamin D3/d, respectively). In those classified with 25(OH)D

Background Recent work has challenged the long-held assumption that appetite functions to maintain stable body mass and fat mass (FM), suggesting instead that appetite matches food intake to energy expenditure and its correlate, fat-free mass (FFM). Whether this scenario applies to young infants, in chronic positive energy balance, remains unknown. Objectives To test associations of components of energy expenditure and body composition with milk intake (MI) and energy intake (EI) in 12-week infants, by reanalyzing published cross-sectional data. Methods Data were available for 48 infants. In addition to anthropometric measurements, we assessed MI and EI by test-weighing, sleeping metabolic rate (SMR) by indirect calorimetry, and FFM, FM, and total energy expenditure (TEE) by doubly labeled water. Mean parental height was calculated as a marker of infant growth drive. Correlation and multiple regression analyses were applied. Results MI and EI correlated with FFM (r = 0.47 and 0.57, respectively; P 0.6). MI and EI correlated with SMR (r = 0.42 and 0.53, respectively; P 0.2). In a multiple regression analysis, MI was independently associated with TEE (partial r = 0.39) and FFM (partial r = 0.35). EI showed similar associations. Mean parental height was correlated with weight gain, MI, and EI. Conclusions As in adults, MI and EI in young infants were strongly associated with FFM and with total and sleeping components of energy expenditure, but not with fatness. The infant's growth drive contributed to these associations. This suggests that appetite is regulated by the rate of energy expenditure, the size of energy-using tissues, and tissue deposition rate, and that the high levels of body fat characteristic of infants may not constrain weight gain.

BACKGROUND Low-calorie diet (LCD)-induced weight loss demonstrates response heterogeneity. Physiologically, a decrease in energy expenditure lower than what is predicted based on body composition (metabolic adaptation) and/or an impaired capacity to increase fat oxidation may hinder weight loss. Understanding the metabolic components that characterize weight loss success is important for optimizing weight loss strategies. OBJECTIVES We tested the hypothesis that overweight/obese individuals who had lower than expected weight loss in response to a 28-d LCD would be characterized by 1) impaired fat oxidation and 2) whole-body metabolic adaptation. We also characterized the molecular mechanisms associated with weight loss success/failure. METHODS This was a retrospective comparison of participants who met their predicted weight loss targets [overweight/obese diet sensitive (ODS), n = 23, females = 21, males = 2] and those that did not [overweight/obese diet resistant (ODR), n = 14, females = 12, males = 2] after a 28-d LCD (900-1000 kcal/d). We used whole-body (energy expenditure and fat oxidation) and tissue-specific measurements (metabolic proteins in skeletal muscle, gene expression in adipose tissue, and metabolites in serum) to detect metabolic properties and biomarkers associated with weight loss success. RESULTS The ODR group had greater mean ± SD metabolic adaptation (-175 ± 149 kcal/d; +119%) than the ODS group (-80 ± 108 kcal/d) after the LCD (P = 0.030). Mean ± SD fat oxidation increased similarly for both groups from baseline (0.0701 ± 0.0206 g/min) to day 28 (0.0869 ± 0.0269 g/min; P

Background Population-based studies generally show neutral associations between dairy consumption and ischemic heart disease (IHD) mortality, whereas weak inverse associations were found for cardiovascular disease (CVD) and stroke mortality. Whether dairy consumption affects long-term survival after myocardial infarction (MI) is unknown. Objectives We studied types of dairy and long-term mortality risk in drug-treated post-MI patients. Methods We included 4365 Dutch patients from the Alpha Omega Cohort aged 60–80 y (21% women) with an MI ≤10 y before enrollment. Dietary data were collected at baseline (2002–2006) using a 203-item FFQ and patients were followed for cause-specific mortality through December 2018. HRs of CVD, IHD, stroke, and all-cause mortality for types of dairy were obtained from Cox models, adjusting for age, sex, energy intake, physical activity, smoking, alcohol intake, diabetes, obesity, and dietary factors. Results Most patients were Dutch, 24% were obese, 20% had diabetes, and 97% used cardiovascular medication. Median intakes were 39 g/d for plain yogurt, 88 g/d for total nonfermented milk, and 17 g/d for hard cheeses. Of the cohort, 10% consumed high-fat milk. During ∼12 y of follow-up (48,473 person-years) 2035 deaths occurred, including 903 from CVD, 558 from IHD, and 170 from stroke. Yogurt was linearly inversely associated with CVD mortality (HR: 0.96; 95% CI: 0.93, 0.99; per 25 g/d) and nonlinearly inversely associated with all-cause mortality. Milk was not associated with any of the outcomes (HRs: ∼1.0 per 100 g/d), except for a higher mortality risk in high-fat milk consumers (HR: 1.30; 95% CI: 1.13, 1.49). Other dairy groups were not associated with mortality risk. Conclusions In Dutch post-MI patients, yogurt consumption was inversely associated with CVD mortality and all-cause mortality. Associations for milk and other dairy products were neutral or inconsistent. This trial was registered at clinicaltrials.gov as NCT03192410.

BACKGROUND: Breastfeeding has beneficial effects on numerous health outcomes. OBJECTIVES: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort. METHODS: Infants with genetic susceptibility for type 1 diabetes (n=8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8.3 y (IQR: 2.8-10.2y). Information on breastfeeding was collected at 3 mo of age and prospectively thereafter. A propensity score for longer breastfeeding was calculated from the variables that were likely to influence any or exclusive breastfeeding. The risks of developing autoimmunity or allergy were assessed using Cox proportional hazards models, and the risk of obesity at 5.5 y of age was assessed using logistic regression with adjustment by the propensity score. RESULTS: Breastfeeding duration was not associated with a lower risk of either islet or transglutaminase autoimmunity (any breastfeeding>6 mo, adjusted HR: 1.07; 95% CI: 0.96, 1.19; exclusive breastfeeding>3 mo, adjusted HR: 1.03; 95% CI: 0.92, 1.15). Exclusive breastfeeding>3 mo was associated with a decreased risk of seasonal allergic rhinitis (adjusted HR: 0.70; 95% CI: 0.53, 0.92; P6 mo and exclusive breastfeeding>3mo were associated with decreased risk of obesity (adjusted OR: 0.62; 95% CI: 0.47, 0.81; P&nbsp

Background Epidemiological studies have been inconsistent regarding the relations between diabetes risk and the consumption of eggs and nutrients in eggs, such as choline, betaine, and cholesterol. There have been few studies among elderly women. Objectives The objective of this study was to examine associations between consumption of eggs, cholesterol, choline, and betaine and the risk of diabetes among elderly US women. Methods Multivariable Cox regression was used with data from the prospective Women's Health Initiative. Population attributable risks were calculated. Consumption of eggs alone (not mixed in foods) and nutrients were assessed with an FFQ. Diabetes incidence was defined as the first incidence of self-reported diabetes treated with oral diabetes medication or insulin injections. Results There were 46,263 women at follow-up baseline. During 13.3 y and 592,984 person-years of follow-up, there were 5480 incident diabetes cases. Higher egg, cholesterol, and choline consumption were each significantly associated with increases in diabetes risk. The associations for eggs and choline were not significant after adjustment for cholesterol consumption. The association for eggs was attenuated after adjustment for non-egg cholesterol consumption, with 1 significant HR in the top consumption quintile (≥3 eggs/wk) of 1.15 (95% CI: 1.05, 1.27; P for linear trend = 0.0001). The population attributable risks for obesity, overweight, consumption of ≥3 eggs/wk, inadequate exercise, and poor diet were 25.0 (95% CI: 22.3, 27.6), 12.8 (95% CI: 11.1, 14.5), 4.2 (95% CI: 2.3, 6.1), 3.5 (95% CI: 1.2, 5.8), and 3.1 (95% CI: 0.5, 5.7), respectively. Conclusions As egg consumption increased to ≥3 eggs/wk, there was a steady increase in diabetes risk that may have been due to the cholesterol in the eggs. The population attributable risk for ≥3 eggs/wk was far lower than that for being obese or overweight.

Background There is an emerging viewpoint that change in body weight is not sufficiently sensitive to promptly identify clinically meaningful change in body composition, such as skeletal muscle depletion. Objectives We aimed to determine whether body weight stability is associated with skeletal muscle depletion and whether skeletal muscle depletion is prognostic of death independently of change in body weight. Methods This retrospective cohort included 1921 patients with stage I-III colorectal cancer. Computed tomography (CT)-based skeletal muscle characteristics and body weight were measured at diagnosis and after a mean 15.0-mo follow-up. Body weight stability was defined as weight change less than ±5% during follow-up. Sarcopenia and myosteatosis were defined using established thresholds for patients with cancer. Multivariable-adjusted logistic and flexible parametric proportional hazards survival models were used to quantify statistical associations. Results At follow-up, 1026 (53.3%) patients were weight stable. Among patients with weight stability, incident sarcopenia and myosteatosis occurred in 8.5% (95% CI: 6.3%, 10.6%) and 13.5% (95% CI: 11.1%, 15.9%), respectively. Men were more likely to be weight stable than were women (56.7% compared with 49.9%; P = 0.04). Weight-stable men were less likely to develop incident sarcopenia (5.4% compared with 15.4%; P = 0.003) and myosteatosis (9.3% compared with 20.8%; P = 0.001) than weight-stable women. Among all patients, the development of incident sarcopenia (HR: 1.40; 95% CI: 1.02, 1.91) and of myosteatosis (HR: 1.41; 95% CI: 1.05, 1.90) were associated with a higher risk of death, independently of change in body weight. Patient sex did not modify the relation between skeletal muscle depletion and death. Conclusions Body weight stability masks clinically meaningful skeletal muscle depletion. Body composition quantified using clinically acquired CT images may provide a vital sign to identify patients at increased risk of death. These data may inform the design of future cachexia trials.

BACKGROUND: A processed diet, high in fat and low in fiber, is associated with differences in the gut microbiota and adverse health outcomes in humans; however, little is known about the diet–microbiota relation and its impact on pregnancy. Spontaneous preterm birth (SPTB), a pregnancy outcome with serious short- and long-term consequences, occurs more frequently in black and in obese women in the United States. OBJECTIVES: In a prospective, case-control sample matched for race and obesity (cases = 16, controls = 32), we compared the fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. We hypothesized that a Western diet would be associated with reduced microbiota richness and a metabolic signature predicting incidence of SPTB. METHODS: The fecal microbiota was characterized by 16S-tagged sequencing and untargeted metabolomics was used to analyze both plasma and fecal metabolites. Wilcoxon's rank-sum test was used for the comparison of microbiota genera, α-diversity, fecal and plasma metabolites, and dietary variables between term and SPTB. β-Diversity was analyzed using permutational multivariate ANOVA, and metabolite associations were assessed by module analysis. RESULTS: A decrease in α-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P

Background Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the United States. Food-insecure individuals often depend on low-cost, energy-dense but nutritionally poor foods, resulting in obesity and chronic diseases related to NAFLD. Objectives To determine whether food insecurity is associated with NAFLD in a cohort of HIV and hepatitis C virus (HCV) infected and uninfected adults. Methods We conducted a cross-sectional analysis of low-income, middle-aged adults from the Miami Adult Studies on HIV (MASH) cohort without a history of excessive alcohol consumption. Food security was assessed with the USDA's Household Food Security Survey. MRIs were used to assess liver steatosis and fibrosis. Metabolic parameters were assessed from fasting blood, anthropometrics, and vitals. Results Of the total 603 participants, 32.0% reported food insecurity. The prevalences of NAFLD, fibrosis, and advanced fibrosis were 16.1%, 15.1%, and 4.6%, respectively. For every 5 kg/m2 increase in BMI, the odds of NAFLD increased by a factor of 3.83 (95% CI, 2.37-6.19) in food-insecure participants compared to 1.32 (95% CI, 1.04-1.67) in food-secure participants. Food insecurity was associated with increased odds for any liver fibrosis (OR, 1.65; 95% CI, 1.01-2.72) and advanced liver fibrosis (OR, 2.82; 95% CI, 1.22-6.54), adjusted for confounders. HIV and HCV infections were associated with increased risks for fibrosis, but the relationship between food insecurity and liver fibrosis did not differ between infected and uninfected participants. Conclusions Among low-income, middle-aged adults, food insecurity exacerbated the risk for NAFLD associated with a higher BMI and independently increased the risk for advanced liver fibrosis. People who experience food insecurity, particularly those vulnerable to chronic diseases and viral infections, may be at increased risk for liver-related morbidity and mortality. Improving access to adequate nutrition and preventing obesity among low-income groups may lessen the growing burden of NAFLD and other chronic diseases.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures. OBJECTIVES: To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes. METHODS: Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity. RESULTS: For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15–1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00–1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02–1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95–1.03). No differences were seen when examining metabolic phenotypes. CONCLUSIONS: We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks.

The use of classic nonparametric tests (cNPTs), such as the Kruskal-Wallis and Mann-Whitney U tests, in the presence of unequal variance for between-group comparisons of means and medians may lead to marked increases in the rate of falsely rejecting null hypotheses and decreases in statistical power. Yet, this practice remains prevalent in the scientific literature, including nutrition and obesity literature. Some nutrition and obesity studies use a cNPT in the presence of unequal variance (i.e., heteroscedasticity), sometimes because of the mistaken rationale that the test corrects for heteroscedasticity. Herein, we discuss misconceptions of using cNPTs in the presence of heteroscedasticity. We then discuss assumptions, purposes, and limitations of 3 common tests used to test for mean differences between multiple groups, including 2 parametric tests: Fisher's ANOVA and Welch's ANOVA; and 1 cNPT: the Kruskal-Wallis test. To document the impact of heteroscedasticity on the validity of these tests under conditions similar to those used in nutrition and obesity research, we conducted simple simulations and assessed type I error rates (i.e., false positives, defined as incorrectly rejecting the null hypothesis). We demonstrate that type I error rates for Fisher's ANOVA, which does not account for heteroscedasticity, and Kruskal-Wallis, which tests for differences in distributions rather than means, deviated from the expected significance level. Greater deviation from the expected type I error rate was observed as the heterogeneity increased, especially in the presence of an imbalanced sample size. We provide brief tutorial guidance for authors, editors, and reviewers to identify appropriate statistical tests when test assumptions are violated, with a particular focus on cNPTs.

BACKGROUND Single measurements of waist circumference (WC) predict the incident cardiovascular disease (CVD); however, long-term patterns of WC and their association with the incidence of CVD are poorly characterized. OBJECTIVE We aimed to identify WC trajectories and determine their association with incident CVD (stroke and myocardial infarction) and examine whether the association persisted among individuals without obesity. METHODS We included 75,535 participants from a community-based cohort in China who were aged >18 y and free of stroke, coronary artery disease, and cancer in 2010 (the baseline). WC and other covariates were repeatedly measured in 2006, 2008, and 2010. WC trajectories were identified by latent mixture modeling. A Cox proportional hazards model was used to examine the association between WC trajectories and incident CVD, after adjustment for age, sex, income, education, systolic blood pressure, lipid profiles, plasma concentrations of glucose, C-reactive protein, smoking, and alcohol drinking. RESULTS We identified 4 WC trajectories based on 2006 WC measurement and change patterns during 2006-2010: low stable (n = 12,072; mean WC 74.1-75.1 cm), moderate stable (n = 41,750; mean WC 85.1-86.6 cm), moderate-high stable (n = 19,914; mean WC 95.6-97.2 cm), and high stable (n = 1,799; mean WC 106.3-110.9 cm). During 2010-2016, we documented 2819 incident CVD events. Compared with the low-stable group, groups with elevated WC trajectories had a higher risk of CVD events during 6 y of follow-up (2010-2016). Adjusted HRs (95% CIs) were 1.49 (1.21, 1.83) for the moderate stable group, 1.71(1.38, 2.12) for the moderate-high stable group, and 1.45 (1.06, 2.00) for the high stable group. After further adjusting for BMI or excluding obese participants, we observed similar results. The positive association between WC and incident CVD was higher in individuals who were aged

Background Effects of dietary fat quality on liver fat remain to be elucidated. Inconsistent evidence may be influenced by fatty acid saturation, chain-length, and regio-specificity within triacylglycerol (TAG) molecules. Objectives We aimed to compare eucaloric diets enriched in palm olein (POo), cocoa butter (COB), and soybean oil (SBO) on liver fat concentration in healthy participants. Secondary outcomes included visceral (VAT) and abdominal subcutaneous (aSCAT) adipose tissue, plus other obesity and cardiometabolic health outcomes. Methods Eighty-three healthy participants (20-45 y, BMI 18.5-27.5 kg/m2) commenced and 64 completed a 16-wk randomized parallel intervention, preceded by a 2-wk run-in. Participants consumed identical eucaloric background diets differing in test fats [contributing 20% total energy intake (%E)], providing 33%E total fat with the following ratios for PUFAs/SFAs/MUFAs: POo, 4.2/13.5/15%E; SBO, 14.4/8.8/9.4%E; COB, 2.3/19.5/11%E. Liver fat and abdominal adiposity were measured at weeks 0 and 16 using 1H-magnetic resonance spectroscopy/imaging; all other outcomes were measured at 0, 4, 8, 12, and 16 wk. Results Fat quality did not affect liver fat concentration, VAT, aSCAT, obesity indexes, blood pressure, liver enzymes, leptin, or fasting glucose. Body fat mass decreased with SBO and COB compared with POo. SBO decreased serum total cholesterol (TC), LDL cholesterol, and TC:HDL cholesterol relative to POo [estimated marginal mean (95% CI) differences: -0.57 (-0.94, -0.20) mmol/L; -0.37 (-0.68, -0.07) mmol/L; and -0.42 (-0.73, -0.11) mmol/L, respectively]. No diet differences were observed on HDL cholesterol, TAG, apoA1, apoB, apoB:apoA1, or fecal free fatty acids (FFAs), except for lower FFA pentadecanoic acid (15:0) with COB than with SBO and POo. Conclusions In healthy adults, when consumed as part of eucaloric typical Australian diets, 3 different dietary fat sources did not differentially affect liver fat concentration and amounts of adipose tissue. Effects on serum lipids were inconsistent across lipid profiles. The findings must be confirmed in metabolically impaired individuals before recommendations can be made.

BACKGROUND: Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA).OBJECTIVE: To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA.METHODS: The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52.RESULTS: In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively.CONCLUSIONS: In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

Background Observational studies have suggested that intake of nuts is associated with lower risk of cardiometabolic diseases, whereas refined grain consumption has been linked to higher risk. Little is known about whether substituting white rice, a refined grain, with nuts may confer benefit among adults at high risk of cardiometabolic diseases. Objectives We aimed to evaluate isocaloric substitution of peanuts for white rice bars as snacks on changes in fasting glucose, lipid profile, body weight, as well as changes in metabolic syndrome (MetS) status among participants with MetS or at risk of MetS. Methods This parallel-arm randomized controlled trial included 224 participants either with MetS (according to the International Diabetes Federation criteria for Chinese adults, n = 163) or at risk of MetS (central obesity plus 1 additional MetS risk factor, n = 61). Participants were randomly assigned to either the peanut arm (56 g/d as snacks, n = 113) or the control arm (isocaloric white rice bars, n = 111) for 12 wk. Results A total of 209 participants (93.3%) completed the 12-wk intervention with a compliance rate > 85% among all participants. No between-group differences were found for improvements in fasting glucose, HDL cholesterol, waist circumference, and body weight. Participants in the peanut group had a significantly higher MetS reversion rate (no longer meeting MetS criteria after the 12-wk trial) than those in the control group (RR: 2.33; 95% CI: 1.10, 4.89; P = 0.026). Conclusions Including peanuts as a snack in the habitual diet in place of a refined-grain snack did not significantly change glycemic or lipid parameters, but improved overall MetS risk without promoting weight gain among Chinese adults at high risk of cardiometabolic diseases. Further larger-scale trials are needed to confirm these findings and elucidate underlying biological mechanisms.This trial was registered at clinicaltrials.gov as NCT03194152.

BACKGROUND: There is a paucity of evidence regarding the role of food timing on cardiometabolic health and weight loss in adults. OBJECTIVES: To determine whether late eating is cross-sectionally associated with obesity and cardiometabolic risk factors at baseline; and whether late eating is associated with weight loss rate and success following a weight loss intervention protocol. Also, to identify obesogenic behaviors and weight loss barriers associated with late eating. METHODS: Participants were recruited from a weight-loss program in Spain. Upon recruitment, the midpoint of meal intake was determined by calculating the midway point between breakfast and dinner times, and dietary composition was determined from diet recall. Population median for the midpoint of meal intake was used to stratify participants into early (before 14:54) and late (after 14:54) eaters. Cardiometabolic and satiety hormonal profiles were determined from fasting blood samples collected prior to intervention. Weekly weight loss and barriers were evaluated during the ∼19-wk program. Linear and logistic regression models were used to assess differences between late and early eaters in cardiometabolic traits, satiety hormones, obesogenic behaviors, and weight loss, adjusted for age, sex, clinic site, year of recruitment, and baseline BMI. RESULTS: A total of 3362 adults [mean (SD): age: 41 (14) y; 79.2% women, BMI: 31.05 (5.58) kg/m(2)] were enrolled. At baseline, no differences were observed in energy intake or physical activity levels between early and late eaters (P >0.05). Late eaters had higher BMI, higher concentrations of triglycerides, and lower insulin sensitivity compared with early eaters (all P

BACKGROUND: Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown. OBJECTIVES: We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases. METHODS: We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator. RESULTS: We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with β = 58.4 ± 7.27, P = 8.98 x 10(-16) for CHO intake; β = −36.4 ± 5.95, P = 9.96 x 10(-10) for FAT intake; and β = 3.30 ± 0.49, P = 1.48 x 10(-11) for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases. CONCLUSIONS: Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A. Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)—NCT01023750; and the Framingham Heart Study (FHS)—NCT00005121.

Background Obesity susceptibility genes are highly expressed in the brain suggesting that they might exert their influence on body weight through eating-related behaviors. Objectives To examine whether the genetic susceptibility to obesity is mediated by eating behavior patterns. Methods Participants were 3977 twins (33% monozygotic, 56% females), aged 31–37 y, from wave 5 of the FinnTwin16 study. They self-reported their height and weight, eating behaviors (15 items), diet quality, and self-measured their waist circumference (WC). For 1055 twins with genome-wide data, we constructed a polygenic risk score for BMI (PRSBMI) using almost 1 million single nucleotide polymorphisms. We used principal component analyses to identify eating behavior patterns, twin modeling to decompose correlations into genetic and environmental components, and structural equation modeling to test mediation models between the PRSBMI, eating behavior patterns, and obesity measures. Results We identified 4 moderately heritable (h2 = 36–48%) eating behavior patterns labeled “snacking,” “infrequent and unhealthy eating,” “avoidant eating,” and “emotional and external eating.” The highest phenotypic correlation with obesity measures was found for the snacking behavior pattern (r = 0.35 for BMI and r = 0.32 for WC; P < 0.001 for both), largely due to genetic factors in common (bivariate h2 > 70%). The snacking behavior pattern partially mediated the association between the PRSBMI and obesity measures (βindirect = 0.06; 95% CI: 0.02, 0.09; P = 0.002 for BMI; and βindirect = 0.05; 95% CI: 0.02, 0.08; P = 0.003 for WC). Conclusions Eating behavior patterns share a common genetic liability with obesity measures and are moderately heritable. Genetic susceptibility to obesity can be partly mediated by an eating pattern characterized by frequent snacking. Obesity prevention efforts might therefore benefit from focusing on eating behavior change, particularly in genetically susceptible individuals.

BACKGROUND: The normal-weight BMI range (18.5–24.9 kg/m(2)) includes adults with body shape and cardiometabolic disease risk features of excess adiposity, although a distinct phenotype developed on a large and diverse sample is lacking. OBJECTIVE: To identify demographic, behavioral, body composition, and health-risk biomarker characteristics of people in the normal-weight BMI range who are at increased risk of developing cardiovascular and metabolic diseases based on body shape. METHODS: Six nationally representative waist circumference index (WCI, weight/height(0.5)) prediction formulas, with BMI and age as covariates, were developed using data from 17,359 non-Hispanic (NH) white, NH black, and Mexican-American NHANES 1999–2006 participants. These equations were then used to predict WCI in 5594 NHANES participants whose BMI was within the normal weight range. Men and women in each race/Hispanic-origin group were then separated into high, medium, and low tertiles based on the difference (residual) between measured and predicted WCI. Characteristics were compared across tertiles; P values for significance were adjusted for multiple comparisons. RESULTS: Men and women in the high WCI residual tertile, relative to their BMI and age-equivalent counterparts in the low tertile, had significantly lower activity levels; higher percent trunk and total body fat (e.g. NH white men, X ± SE, 25.3 ± 0.2% compared with 20.4 ± 0.2%); lower percent appendicular lean mass (skeletal muscle) and bone mineral content; and higher plasma insulin and triglycerides, higher homeostatic model assessment of insulin resistance (e.g. NH white men, 1.45 ± 0.07 compared with 1.08 ± 0.06), and lower plasma HDL cholesterol. Percent leg fat was also significantly higher in men but lower in women. Similar patterns of variable statistical significance were present within sex and race/ethnic groups. CONCLUSIONS: Cardiometabolic disease risk related to body shape in people who are normal weight according to BMI is characterized by a distinct phenotype that includes potentially modifiable behavioral health risk factors.

BACKGROUND: Obesity prevalence remains high in the United States, and there is an increased risk among women who do not lose their gestational weight gain during the postpartum period. Indicators of dietary carbohydrate quality including added sugar consumption, glycemic load, and glycemic index have been linked with weight gain, whereas fiber may protect against obesity. However, these dietary factors have not been examined during the postpartum period. OBJECTIVES: The aim of this study was to determine whether dietary sugars and fiber intake were associated with changes in postpartum weight. METHODS: We examined Hispanic women from the longitudinal Southern California Mother's Milk Study (n = 99) at 1 and 6 mo postpartum. Maternal assessments included height, weight, and dietary intake based on 24-h diet recalls. We used multivariable linear regression to examine the relation between maternal diet and change in postpartum weight after adjusting for maternal age, height, and energy intake. RESULTS: Higher intake of added sugar was associated with postpartum weight gain (β: 0.05; 95% CI: 0.004, 0.10; P = 0.05). In addition, a half 8-ounce (8 fluid ounces = 236.6 mL) serving per day increase in soft drinks was associated with a 1.52-kg increase in weight (95% CI: 0.70, 2.34 kg; P

BACKGROUND The existence of metabolic adaptation, at the level of resting metabolic rate (RMR), remains highly controversial, likely due to lack of standardization of participants' energy balance. Moreover, its role as a driver of relapse remains unproven. OBJECTIVE The main aim was to determine if metabolic adaptation at the level of RMR was present after weight loss and at 1- and 2-y follow-up, with measurements taken under condition of weight stability. A secondary aim was to investigate race differences in metabolic adaptation after weight loss and if this phenomenon was associated with weight regain. METHODS A total of 171 overweight women [BMI (kg/m2): 28.3 ± 1.3; age: 35.2 ± 6.3 y; 88 whites and 83 blacks] enrolled in a weight-loss program to achieve a BMI

BACKGROUND: Plant-based dietary patterns may be related to better cardiovascular profiles. Whether a healthy plant-based dietary index is predictive of future cardiovascular disease (CVD) across people with different genetic susceptibility remains uncertain. OBJECTIVE: We investigated associations of adherence to healthy plant-based diets with the incidence of CVD considering the genetic susceptibility. METHODS: This prospective cohort study included a total of 156,148 adults initially free of CVD and cancer. We calculated a healthful plant-based diet index (healthful-PDI) in which healthy plant foods received positive scores, and less healthy plant foods and animal foods received reverse scores. Genetic risk scores (GRSs) for myocardial infarction (MI) and stroke were calculated to assess interactions between healthful-PDI and GRSs. RESULTS: During 5 y of follow-up, we observed 1812 incident cases of CVD. Higher healthful-PDI was associated with a lower CVD risk [HR per 10-unit increment: 0.87 (95% CI: 0.81, 0.93) after adjusting for demographic, lifestyle, and other dietary factors (model 1); HR 0.90 (0.84, 0.97) after further adjusting for obesity and metabolic factors (model 2)]. The risk of CVD was gradually decreased in association with higher adherence to healthful-PDI, regardless of genetic susceptibility. The inverse associations of healthful-PDI with CVD were consistently observed in people with low GRS-MI [HR 0.85 (95% CI: 0.76, 0.94) in model 1; HR 0.88 (0.79, 0.97) in model 2] and those with high GRS-MI [HR 0.91 (0.82, 0.99) in model 1; HR 0.94 (0.86, 1.04) in model 2], without significant interactions (P(interaction) = 0.59 in model 1; P(interaction) = 0.66 in model 2). Similarly, higher healthful-PDI was related to a lower risk of CVD, regardless of low/high GRS-stroke. CONCLUSION: Adherence to healthy plant-based diets may be associated with a decreased incidence of CVD in the entire population, suggesting that plant-based dietary patterns may modify the risk of CVD, regardless of genetic susceptibility.

BACKGROUND With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood. OBJECTIVES Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota. METHODS We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet. RESULTS While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study. CONCLUSIONS These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591.

Many food items included in the Mediterranean diet (MedDiet) are rich in polyamines, small aliphatic amines with potential cardioprotective effects. The consumption of a MedDiet could increase polyamine concentrations. Based on experimental models, polyamine concentrations may be also influenced by physical activity (PA).We aimed to evaluate whether an intervention based on an energy-restricted MedDiet (er-MedDiet) and PA promotion, in comparison with an energy-unrestricted MedDiet and traditional health care, influences the serum pattern of polyamines and related metabolites in subjects at high risk of cardiovascular disease (CVD).This was a substudy from the PREDIMED-Plus trial, an ongoing randomized clinical trial including 6874 participants allocated either to an intensive weight-loss lifestyle intervention based on er-MedDiet, PA promotion, and behavioral support (er-MedDiet + PA group), or to an energy-unrestricted MedDiet and traditional health care group (MedDiet group). A total of 75 patients (n = 38, er-MedDiet + PA group; n = 37, MedDiet group) were included in this study. Serum concentrations of arginine, ornithine, polyamines, and acetyl polyamines at baseline and 26 wk of intervention were measured by an ultra-high-performance LC-tandem MS platform.At week 26, study groups had similar adherence to the MedDiet but patients randomly assigned to the er-MedDiet + PA group showed significantly lower mean energy intake (-340.3 kcal/d; 95% CI: -567.3, -113.4 kcal/d; P = 0.004), higher mean PA (1290.6; 95% CI: 39.9, 2541.3 metabolic equivalent tasks · min/d; P = 0.043), and higher mean decrease in BMI (in kg/m2) (-1.3; 95% CI: -1.8, -0.6; P 0.001) than the MedDiet group. However, no significant differences in serum polyamines or related metabolites were found between study groups after 26 wk of intervention and no significant between-group differences were found in glycated hemoglobin, HDL-cholesterol, or triglyceride concentrations.In individuals at high CVD risk, an er-MedDiet with increased PA did not result in significant changes of serum concentrations of polyamines or related metabolites in comparison with an energy-unrestricted MedDiet and no increase in PA. This trial was registered at isrctn.com as ISRCTN89898870.

BACKGROUND: Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. OBJECTIVES: The aims were to determine, in vitamin D–deficient overweight and obese children, whether supplementation with vitamin D(3) 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. METHODS: We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. RESULTS: Dose–response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [−2.66 (95% CI: −5.27, −0.046), −3.57 (−5.97, −1.17), and −3.28 (−5.55, −1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (−2.67; 95% CI: −4.88, −0.46 mg/dL) in the 2000-IU group. CONCLUSIONS: Correction of vitamin D deficiency in overweight and obese children by vitamin D(3) supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.

BACKGROUND: Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown. OBJECTIVE: Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed. METHODS: Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations. RESULTS: Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2′-fucosyllactose (2′FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition. CONCLUSIONS: The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2′FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.

Background Food advertising is a major contributor to obesity, and fast food (FF) restaurants are top advertisers. Research on the impact of food advertising in adolescents is lacking and no prior research has investigated neural predictors of food intake in adolescents. Neural systems implicated in reward could be key to understanding how food advertising drives food intake. Objectives To investigate how neural responses to both unhealthy and healthier FF commercials predict food intake in adolescents. Methods A cross-sectional sample of 171 adolescents (aged 13-16 y) who ranged from normal weight to obese completed an fMRI paradigm where they viewed unhealthy and healthier FF and nonfood commercials. Adolescents then consumed a meal in a simulated FF restaurant where foods of varying nutritional profiles (unhealthy compared with healthier) were available. Results Greater neural activation in reward-related regions (nucleus accumbens, r = 0.29; caudate nucleus, r = 0.27) to unhealthy FF commercials predicted greater total food intake. Greater responses to healthier FF relative to nonfood commercials in regions associated with reward (i.e., nucleus accumbens, r = 0.24), memory (i.e., hippocampus, r = 0.32), and sensorimotor processes (i.e., anterior cerebellum, r = 0.33) predicted greater total food and unhealthier food intake, but not healthier food intake. Lower activation in neural regions associated with visual attention and salience (e.g., precuneus, r = -0.35) to unhealthy relative to healthier FF commercials predicted healthier food intake. Conclusions These findings suggest that FF commercials contribute to overeating in adolescents through reward mechanisms. The addition of healthier commercials from FF restaurants is unlikely to encourage healthier food intake, but interventions that reduce the ability of unhealthy FF commercials to capture attention could be beneficial. However, an overall reduction in the amount of FF commercials exposure for adolescents is likely to be the most effective approach.

Background: The role of dietary fiber in obesity management remains debatable. Evidence suggests that intake of viscous fiber may have the potential to facilitate weight loss. Objective: We aimed to summarize and quantify the effects of viscous fiber on body weight, BMI, waist circumference, and body fat, independent of calorie restriction, through a systematic review and meta-analysis of randomized controlled trials. Methods: Trials ≥4 wk in duration that assessed the effect of viscous fiber supplemented to an ad libitum diet along with comparator diets were included. MEDLINE, EMBASE, and the Cochrane library were searched through 24 July, 2019. Two independent reviewers extracted relevant data. Data were pooled using the generic inverse variance method and random-effects models and expressed as mean differences with 95% CIs. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of evidence was explored using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Findings from 62 trials (n = 3877) showed that viscous fiber reduced mean body weight (-0.33 kg ; 95% CI: -0.51, -0.14 kg ; P = 0.004), BMI (in kg/m2) (-0.28 ; 95% CI: -0.42, -0.14 ; P = 0.0001), and waist circumference (-0.63 cm ; 95% CI: -1.11, -0.16 cm ; P = 0.008), with no change in body fat (-0.78% ; 95% CI: -1.56%, 0.00% ; P = 0.05) when consumed with an ad libitum diet. Greater reductions in body weight were observed in overweight individuals and those with diabetes and metabolic syndrome. The certainty of evidence was graded moderate for body weight, high for waist circumference and body fat, and low for BMI. Conclusions: Dietary viscous fiber modestly yet significantly improved body weight and other parameters of adiposity independently of calorie restriction. Future trials are warranted to address the inconsistency and imprecision identified through GRADE and to determine long- term weight-loss sustainability.This systematic review and meta-analysis was registered at clinicaltrials.gov as NCT03257449.