Search

Growing evidence has linked gut microbiota with regulation of adiposity. We aimed to examine whether the genetically determined relative abundance of gut microbial taxa was associated with long-term changes in adiposity and body composition among individuals who were overweight or obese in weight-loss diet interventions.The study included 692 participants with overweight or obese from the POUNDS Lost trial. We created a genetic risk score (GRS) for the relevant abundance of gut microbial taxa using 20 single nucleotide polymorphisms identified from a recent genome-wide association study. Body composition was assessed using dual-energy X-ray absorptiometry.Higher GRS for the relative abundance of gut microbial taxa was significantly associated with greater reductions in waist circumference, total fat mass (FM), whole-body total percentage of fat mass (FM%), and percentage of trunk fat (TF%) at 2 years (p = 0.022, 0.034, 0.023, 0.023, respectively). In addition, dietary protein significantly modified the association between GRS for gut microbial abundance and changes in total FM, FM%, and TF% (p-interactions = 0.04, 0.013, and 0.006, respectively) at 6-month, when the maximum weight loss was achieved, even though such interactions were attenuated at 2 years. In the average-protein diet group, a higher microbial abundance GRS was associated with greater reductions in total FM (p = 0.007), FM% (p = 0.002), and TF% (p 0.001) at 6 months, while no associations were found in the high-protein diet group (p 0.05).Our results suggest that the higher genetically determined relative abundance of gut microbial taxa may be related to long-term improvement of whole-body and central fatness and body composition in response to low-calorie diet interventions.

BACKGROUND: Due to the increasing disease burden, strategies to predict and prevent heart failure (HF) are urgently needed. OBJECTIVE: We aimed to investigate whether the Alternative Healthy Eating Index (AHEI) and the clinically abbreviated Prime Diet Quality Score (PDQS) are associated with the risk of overall HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). METHODS: Our study included 44,525 men from the Health Professionals Follow-up Study (HPFS) who were free from cardiovascular disease and cancer at baseline. The AHEI and PDQS were computed based on dietary data repeatedly measured using semiquantitative FFQs. HF, HFpEF, and HFrEF were adjudicated based on review of medical records through 2008. Associations of diet quality with incident HF were estimated with multivariate-adjusted Cox proportional hazards models. RESULTS: During 929,911 person-years of follow-up, 803 HF cases were documented, including 184 with HFpEF and 181 with HFrEF among those with ejection fraction (EF) data. Adjusting for potential confounders, we did not observe a significant association between the AHEI and overall HF (HR (per SD): 0.96; 95% CI: 0.89, 1.04; P-trend = 0.57) or between the PDQS and overall HF (HR (per SD): 0.98; 95% CI: 0.91, 1.06; P-trend = 0.82). Both dietary indices were not significantly associated with HFpEF. However, a higher AHEI was associated with lower risk of HFrEF upon comparison of the extreme quintiles (HR (per SD): 0.81; 95% CI: 0.69, 0.96; P-trend = 0.02). Every SD increment in the PDQS was associated with 20% lower risk of HFrEF (HR (per SD): 0.80; 95% CI: 0.68, 0.95; P-quadratic = 0.03). CONCLUSIONS: A healthy overall diet was associated with lower risk of HFrEF, and associations were similar with the AHEI and PDQS. We did not observe a significant association between dietary indices and either overall HF or HFpEF.

Background: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life. Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. We defined the regional DNAm levels as the average methylation level of 5’-cytosine-phosphate-guanine-3’ within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793), respectively. Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes. Results: The regional DNAm at LINC00319 , showed significantly different associations with 2-year changes in systolic blood pressure and diastolic blood pressure among participants assigned to low- or high-fat diets ( P for interactionLINC00319 was associated with greater reductions in both 2-year changes in systolic blood pressure (β, −1.481; P =0.020) and diastolic blood pressure (β, −1.096; P =0.009). Three trajectories of changes in systolic blood pressure or diastolic blood pressure were identified, and participants with higher regional DNAm at LINC00319 were more likely to experience and maintain decreased systolic blood pressure and diastolic blood pressure (odds ratio of being in decrease-stable versus stable [95% CI], 1.542 [1.146–2.076] and 1.463 [1.125–1.902]). Conclusions: Our findings suggest that DNAm could be a metabolic memory bridging early and later life, and an indicator of more benefits from eating a low-fat weight-loss diet.

Introduction: Salivary amylase, encoded by the AMY1 gene, plays a pivotal role in carbohydrate digestion, and genetic adaptation of carbohydrate digestion has been implicated in impaired glucose tolerance, type 2 diabetes, and cardiometabolic diseases. Hypothesis: We investigated whether AMY1 genetic variations are associated with β-cell function and glycemic responses during 2-h oral glucose tolerance tests (OGTTs) and tested whether AMY1 variations were related to changes in glucose tolerance in a randomized controlled trial testing effects of diets varying in glycemic index (GI) levels and carbohydrate (Carb) amount. Methods: The study included participants (n=146) from the OmniCarb trial, a randomized crossover-controlled feeding trial, in which overweight or obese adults were given 4 diets that differed in composition by GI and Carb amount. Each diet was consumed for 5 weeks, followed by a 2-week washout. Genetic risk score (GRS) was calculated using eight AMY1 SNPs, with higher GRS indicating higher activity of salivary amylase. The primary outcomes were glycemic and insulin responses during OGTTs. Results: At baseline, lower GRS was related to a larger area under the curve of glucose (AUC-glucose) and β-cell dysfunction assessed by the insulinogenic index and disposition index ( p p =0.038). The effect of increasing GI at low Carb amount for glucose levels at 60 min ( P interaction = 0.024) and AUC-glucose ( P interaction =0.016) significantly interacted with the GRS. Also, we found a significant interaction between GRS and the effect of increasing Carb amount at high GI for 60-min post-load glucose levels ( P interaction = 0.016). Conclusions: The AMY1 genetic variations were associated with β-cell function and impaired glucose tolerance. Effects of changing the amount or quality of carbohydrates on glucose tolerance may be partly determined by individual genetic adaptation of carbohydrate digestion.

Background: Both the glycemic index (GI) and amounts of carbohydrates are important determinants of postprandial glucose changes. Recent studies suggest the effects of carbohydrate intake on postprandial glucose metabolism may differ according to meal timing, showing circadian patterns. Hypothesis: We investigated whether the relations of altering both GI levels and the carbohydrate amount with postprandial response of glucose, insulin, and c-peptide differed by meal timing (breakfast, lunch, and dinner), in overweight and obese adults. Methods: The OmniCarb trial was a randomized trial with a crossover design in which participants were given 4 diets varying in GI levels and carbohydrate content. We included 61 participants attended the 12-h postprandial study and completed at least two diets. Area under the curve increment (AUCi) of glucose, insulin, and c-peptide after breakfast (180 min), lunch (240 min), and dinner (120 min), was calculated as outcome. Results: After consuming each diet for 5 weeks, we observed that the diet replacing effects on the postprandial responses in glucose, insulin and c-peptide significantly differed by meal timing. For postprandial glucose response to breakfast, the beneficial effects (lowered AUCi) of replacing high- by low-GI in high-carb diet, replacing high- by low-carb in high-GI diet, and replacing high-GI/high-carb by low-GI/low-carb diet were consistently observed. Such beneficial effects were less significant for lunch and dinner (Figure). For the response of insulin, the beneficial effects of the corresponding diet replacements were more consistently observed in dinner, followed by breakfast. For the response of C-peptide, similar beneficial effects of the corresponding diet replacements were observed for breakfast and dinner, but not lunch. Conclusion: Our results indicate that the beneficial effects of replacing high-GI and/or high-carbohydrate diets by low-GI and/or low-carbohydrate diets on postprandial metabolic changes may differ according to meal timing.

Introduction: A previous epigenome-wide association study has causally linked DNA methylation (DNAm) at the SREBF1 gene (cg11024682) with obesity and lipids. However, little is known about whether DNAm at SREBF1 is associated with long-term changes in body adiposity and composition. Hypothesis: We hypothesized that participants with different DNAm at SRBF1 might respond differently to dietary weight-loss interventions on changes in body adiposity and composition. Methods: The current study included 314 individuals with overweight or obese, who participated in POUNDS Lost: a 2-year randomized dietary weight-loss trial. The blood DNAm level was profiled by methylC-capture sequencing at baseline. Regional DNAm at SREBF1 was calculated as the average methylation level over CpGs within ±250 bp of cg11024682. Body composition, including total fat mass (FM), percentage of FM (FM%), total fat-free mass (FFM), percentage of FFM (FFM%), and percentage of trunk fat (TF%) were measured by dual-energy X-ray absorptiometry (DEXA) at baseline, 6 months, and 2 years. Results: Lower regional DNAm at SREBF1 was significantly associated with changes in body composition across 2 years ( Table ). At 6 months, per SD lower regional DNAm at SREBF1 was significantly associated with greater reductions in FM (β [SE] -0.23 [0.07], p=0.002), FM% (-0.30 [0.09], p Conclusions: Overweight and obese individuals with a lower regional DNAm at SREBF1 achieved greater improvement in body composition across the 2-year intervention, independent of concurrent weight loss, suggesting DNAm at SREBF1 is predictive of individuals’ response to treatment.

Introduction: The microRNA-122 (miR-122) is widely involved in the post-transcriptional regulation of glucose and lipid metabolism, and cardiovascular system. Hypothesis: We assessed the hypothesis that decrease in circulating miR-122-5p would be associated with the improvement in cardiovascular health (CVH) score and each component health metric in response to dietary weight-loss interventions. Methods: Circulating miR-122-5p levels were measured at baseline and 6 months among 509 participants with overweight or obesity from the POUNDS LOST trial. We evaluated the CVH score using the newly updated algorithm -life’s essential 8 and calculated the composite score from the available biological health factors (body mass index [BMI], blood lipids, blood glucose, and blood pressure) across the 2-year intervention period. Results: At baseline, lower levels of miR-122-5p were associated with higher CVH scores (PP time*miR-122-5p =0.001). We also found a significant interaction between change in miR-122-5p and dietary fat intake on the 6-months change in CVH ( P = 0.025); a greater decrease in miR-122-5p showed a greater improvement in CVH at 6 months among participants assigned to a low-fat diet. Conclusions: In conclusion, participants with decreased circulating miR-122-5p levels in response to dietary weight-loss interventions had significant improvement in CVH and achieved CVH benefits most strongly when consuming a low-fat diet.

Introduction: Epigenome-wide association studies identified that DNA methylation (DNAm) at the ABCG1 gene (cg06500161) was associated with obesity. However, little is known about whether DNAm at ABCG1 is associated with long-term changes in adiposity and body fat distribution in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying DNAm at ABCG1 might respond differently to dietary weight-loss interventions on long-term changes in adiposity and body fat distribution. Methods: The current study included 673 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm level was profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at ABCG1 was defined as the average methylation level over CpGs within ± 250 bp of cg06500161. Two-year changes in adiposity and Computed Tomography (CT)-measured body fat distribution were calculated. Results: We found that regional DNAm at ABCG1 significantly interacted with dietary protein intake on long-term changes in body weight and waist circumference (WC) at 6 months and 2 years (P-interactionFigure ). Among participants assigned to an average-protein (15%) diet, lower regional DNAm at ABCG1 was associated with greater reductions in body weight and WC at 6 months and 2 years, while opposite associations were found among those assigned to a high-protein (25%) diet. Similar interactions were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (P-interaction Conclusion: Our data indicate that DNAm at ABCG1 interacted with dietary protein intake on long-term changes in adiposity and body fat distribution. Participants with hypomethylation at ABCG1 benefited more in long-term improvement in adiposity and body fat distribution by consuming an average-protein diet.

Introduction: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life. Hypothesis: DNAm levels of genes related to both birthweight and blood pressure were associated with changes in blood pressures in response to dietary weight-loss interventions. Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm levels as the average methylation level within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793). Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes. Results: We found that the regional DNAm at LINC00319, but not the other genes, showed different associations with 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among participants assigned low- or high-fat diets (P for interaction < 0.05 for all, Figure ). In response to low-fat diet, per standard deviation higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in SBP (β: -1.481; standard error [SE]: 0.632; P = 0.020) and DBP (β: -1.096; SE: 0.413; P = 0.009). Three trajectories of changes in SBP and DBP were identified, and participants with higher baseline regional DNAm at LINC00319 were less likely to have stable or increased blood pressure levels. Conclusions: Our findings indicate that higher regional DNAm level at LINC00319 was significantly associated with greater long-term reduction in blood pressure in response to a low-fat diet, suggesting people with higher regional DNAm levels benefited more from eating a low-fat weight-loss diet.

Introduction: MicroRNA-19 (MiR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). Hypothesis: We assessed the hypothesis that change in circulating miR-19 would be associated with changes in 10-year atherosclerotic CVD (ASCVD) risk and individual cardiovascular risk factors in a dietary weight-loss intervention. Methods: This study included 509 participants with overweight or obesity from the 2-year weight-loss diet intervention study (the POUNDS LOST trial) and with available data on circulating miR-19a/b-3p at baseline and 6 months. The primary outcome was the 6-month change in the ASCVD risk score, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the change in each ASCVD component including blood pressure, lipid profiles, insulin resistance, glucose metabolism, and adiposity measures. Change in habitual physical activity and sleep disturbance were assessed from baseline to 6 months. Results: Circulating miR-19a/b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that greater decreases in log-transformed miR-19a/b-3p were related to a greater reduction in ASCVD risk (β[SE]=0.35 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.33 [0.13], P=0.01 for miR-19b-3p) over 6 months. Similar positive associations were observed for changes in diastolic blood pressure with miR-19a/b-3p. Moreover, we found that sleep disturbance was significantly associated with reductions in miR-19a/b-3p from baseline to 6 months (P trend Conclusions: In conclusion, decreased circulating miR-19 levels induced by dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and such associations were more evident in people with no/slight amount of sleep disturbance and an increase in physical activity.

Introduction: Integrating multiple metabolomics signatures related to coronary heart disease (CHD) into a metabolomic risk score (MRS) may contribute to improving the risk prediction beyond traditional risk factors, although applications of the MRS remain underdetermined, especially in people at usual risk. Hypothesis: We analyzed associations of plasma metabolites with the risk of CHD to develop MRS for predicting risk of incident CHD by incorporating comprehensive metabolic pathways among women at usual risk from the Nurses’ Health Study (NHS). We also tested whether changes in CHD-related plasma metabolites were associated with significant reductions in atherosclerotic cardiovascular disease (ASCVD) risk scores among participants in the POUNDS Lost trial. Methods: Untargeted metabolomics profiling was performed to measure plasma metabolites at baseline in a prospective nested case-control of 762 incident cases of CHD (fatal CHD and nonfatal myocardial infarction) and 762 matched controls identified over 10-14 years of follow-up time in NHS. An MRS of CHD risk was created based on metabolites that were selected through conditional logistic regression with the elastic net procedure. The POUNDS Lost trial included adults with overweight/obesity who consumed weight-loss diets with different macronutrient intakes. We measured untargeted plasma metabolomics signatures at baseline, 6 months, and 2 years to calculate changes in response to the dietary interventions. The primary outcome in the POUNDS Lost trial was the reduction of 10-year ASCVD risk scores calculated by the validated pooled cohort equations. Results: Various plasma metabolites (such as gut-microbiota-related and others in the pathways of ceramides, phospholipids, and polyamine metabolism) were associated with the risk of incident CHD ( P FDR Conclusions: Comprehensive metabolomic scores were strongly related to the risk of incident CHD among women without prior CHD. Dietary interventions may modify the unfavorable relations between CHD-risk-related metabolites and ASCVD risk. Further studies in other populations are warranted to validate the performance of MRS in predicting ASCVD events.

The association of PFASs with blood lipids, lipoproteins and apolipoproteins, and coronary heart disease (CHD) risk are inconsistent in previous studies. The aim of current study is to examine the potential association between plasma PFASs, blood lipoproteins and their subspecies defined by apolipoproteins, and whether PFASs are associated with CHD risk.A case-control study was conducted in 100 men and 102 women aged 45-70 years. We leveraged 101 participants from HPFS and NHS who were initially free of cardiovascular disease and developed a fatal or non-fatal myocardial infarction during follow-up, and randomly matched controls in a 1:1 ratio for age, smoking status, and date of blood draw. Seven plasma PFASs measurements were examined at baseline, including perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), linear PFOS (nPFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), with all mean CVs

To examine associations between sleep disturbance and changes in weight and body composition and the mediating role of changes of appetite and food cravings in the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) 2-year weight-loss diet intervention trial, this study included 810 overweight or obese individuals with baseline sleep disturbance assessment who were randomly assigned one of four diets varying in macronutrient composition. Changes in body weight and fat distribution were assessed by DEXA and computed tomography during the 2-year intervention. Participants were asked to provide sleep disturbance levels (no, slight, moderate, or great) at baseline and to recall their sleep disturbances since last visit at 6, 12, 18, and 24 months. Weight loss during the first 6 months was followed by 1.5 years of steady weight regain. Participants with greater sleep disturbance from baseline to 6 months showed significant losses of body weight (Ptrend

AIMS: To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight-loss diet interventions. METHODS: This study included 535 participants with overweight/ obesity randomly assigned to 4 weight-loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual-energy X-ray absorptiometry (DEXA) scans and computed tomography (CT) scans at baseline, 6 months, and 24 months. RESULTS: From baseline to 6 months, when the maximum weight loss was achieved, each 1000 daily steps increment in PA was associated with a greater reduction in body weight (β[SE]=−0.48[0.11]) and waist circumference (β[SE]=−0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P

Background Thioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5’-cytosine-phosphate-guanine-3’ (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions. Methods We included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses. Results We found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P 0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention. Conclusions Our data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

Supplemental Digital Content is available in the text., Objective: Plasma total HDL (high-density lipoprotein) is a heterogeneous mix of many protein-based subspecies whose functions and associations with coronary heart disease vary. We hypothesize that increasing HDL by CETP (cholesteryl ester transfer protein) inhibition failed to reduce cardiovascular disease risk, in part, because it increased dysfunctional subspecies associated with higher risk such as HDL that contains apoC3. Approach and Results: We studied participants in 2 randomized, double-blind, placebo-controlled trials of a CETP inhibitor on a background of atorvastatin treatment: ACCENTUATE (The Addition of Evacetrapib to Atorvastatin Compared to Placebo, High Intensity Atorvastatin, and Atorvastatin With Ezetimibe to Evaluate LDL-C Lowering in Patients With Primary Hyperlipidemia; 130 mg evacetrapib; n=126) and ILLUMINATE (Phase 3 Multi Center, Double Blind, Randomized, Parallel Group Evaluation of the Fixed Combination Torcetrapib/Atorvastatin, Administered Orally, Once Daily [Qd], Compared With Atorvastatin Alone, on the Occurrence of Major Cardiovascular Events in Subjects With Coronary Heart Disease or Risk Equivalents; 60 mg torcetrapib; n=80). We measured the concentration of apoA1 in total plasma and 17 protein-based HDL subspecies at baseline and 3 months. Both CETP inhibitors increased apoA1 in HDL that contains apoC3 the most of all HDL subspecies (median placebo-adjusted percent increase: evacetrapib 99% and torcetrapib 50%). They also increased apoA1 in other HDL subspecies associated with higher coronary heart disease risk such as those involved in inflammation (α-2-macroglobulin and complement C3) or hemostasis (plasminogen), and in HDL that contains both apoE and apoC3, a complex subspecies associated with higher coronary heart disease risk. ApoA1 in HDL that contains apoC1, associated with lower risk, increased 71% and 40%, respectively. Only HDL that contains apoL1 showed no response to either drug. Conclusions: CETP inhibitors evacetrapib and torcetrapib increase apoA1 in HDL subspecies that contain apoC3 and other HDL subspecies associated with higher risk of coronary heart disease. Subspecies-specific effects shift HDL subspecies concentrations toward a profile associated with higher risk, which may contribute to lack of clinical benefit from raising HDL by pharmaceutical CETP inhibition.

Objective:To evaluate the properties of the cognitive battery used in the MIND Diet Intervention to Prevent Alzheimer’s Disease. The MIND Diet Intervention is a randomized control trial to determine the relative effectiveness of the MIND diet in slowing cognitive decline and reducing brain atrophy in older adults at risk for Alzheimer’s dementia.Methods:The MIND cognitive function battery was administered at baseline to 604 participants of an average age of 70 years, who agreed to participate in the diet intervention study, and was designed to measure change over time. The battery included 12 cognitive tests, measuring the 4 cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and the statistical performance of participants in each domain. To further establish the validity of each domain, we regressed the domain scores against a late-life cognitive activity score, controlling for age, race, sex, and years of education.Results:Four factors emerged in the principal component analyses that were similar to the theoretical domains. In regression equations, we found the expected associations with age, education, and late-life cognitive activity with each of the four cognitive domains.Conclusions:These results indicate that the MIND cognitive battery is a comprehensive and valid battery of four separate domains of cognitive function that can be used in diet intervention trials for older adults.

Background Vitamin D is critical to brain health and a promising candidate to prevent cognitive decline and onset of Alzheimer disease (AD), although the underlying brain mechanisms are unclear. Objectives This study aimed to determine the association between vitamin D intake and brain cortical thickness in older adults. Methods This was a cross-sectional investigation of 263 cognitively unimpaired participants, aged 65 y and older, participating in the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) trial (an ongoing study testing the effects of a 3-y diet intervention on cognitive decline). Vitamin D intake, from diet and supplements, was ascertained from an FFQ. Linear regression analysis, adjusted for age, sex, race, education, income, cognitive and physical activities, and cardiovascular disease risk factors, was used to determine the association between vitamin D intake and cortical thickness of the whole brain, lobes, and AD signature. Results Total vitamin D intake was associated with cortical thickness of the temporal lobe and AD signature. Compared with individuals in the lowest quartile of total vitamin D intake [median: 140 international units (IU)/d], those in the highest quartile (median: 1439 IU/d) had a 0.038-mm (95% CI: 0.006, 0.069 mm) thicker temporal lobe and 0.041-mm (95% CI: 0.012, 0.070 mm) thicker AD signature. Most vitamin D intake was from supplements, and supplemental intake was also associated with cortical thickness. Compared with those who used no supplement, individuals taking 800-1000 IU/d and >1000 IU/d of supplemental vitamin D had a 0.039-mm (95% CI: 0.013, 0.066 mm) and 0.047-mm (95% CI: 0.013, 0.081 mm) thicker temporal lobe and a 0.037-mm (95% CI: 0.013, 0.061 mm) and 0.046-mm (95% CI: 0.015, 0.077 mm) thicker AD signature, respectively. Dietary vitamin D was not related to brain cortical thickness in our sample. Conclusions In cognitively unimpaired older adults, total and supplemental vitamin D intakes were associated with cortical thickness in regions vulnerable to AD.This trial was registered at clinicaltrials.gov as NCT02817074.

Body weight and insulin resistance (IR) are closely correlated, and their temporal sequences in affecting blood pressure (BP) remain poorly defined. We examined the temporal sequences of weight loss and IR change, and their relations with BP in the Pounds Lost trial, a randomized weight-loss diet intervention study. The present study included overweight/obese adults, who were randomized in a 2 × 2 factorial design to low-calorie diets containing 20 or 40% fat and 15 or 25% protein (diets with 65, 55, 45 and 35% carbohydrate). Weight, IR, systolic and diastolic BP levels were measured at baseline, 6 and 24 months. After excluding the subjects who took antihypertensive drugs, cross-lagged path and mediation analyses were performed among 540 participants. After adjusting for age, race, sex, and diet groups, the cross-lagged path coefficient from baseline weight to 24-month IR (β1 = 0.135, P = 0.04) was significantly greater than the path coefficient (β2 = 0.022, P > 0.05) from baseline IR to 24-month weight (P

Background SCFAs are involved in regulation of body weight and bone health. Objectives We aimed to examine whether genetic variations related to butyrate modified the relation between dietary fiber intake and changes in bone mineral density (BMD) in response to weight-loss dietary interventions. Methods In the 2-y Preventing Overweight Using Novel Dietary Strategies trial, 424 participants with BMD measured by DXA scan were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A polygenic score (PGS) was calculated based on 7 genetic variants related to the production of butyrate for 370 of the 424 participants. Results SCFA PGS significantly modified the association between baseline dietary fiber intake and sex on 2-y changes in whole-body BMD (P-interaction = 0.049 and 0.008). In participants with the highest tertile of SCFA PGS, higher dietary fiber intake was related to a greater increase in BMD (β: 0.0022; 95% CI: 0.0009, 0.0035; P = 0.002), whereas no such association was found for participants in the lower tertiles. In the lowest tertiles of SCFA PGS, men showed a significant increase in whole-body BMD (β: 0.0280; 95% CI: 0.0112, 0.0447; P = 0.002) compared with women. In the highest tertile, no significant difference was found for the change in BMD between men and women. Conclusions Our data indicate that genetic variants related to butyrate modify the relations of dietary fiber intake and sex with long-term changes in BMD in response to weight-loss diet interventions.

Background The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown. Objectives The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation. Methods DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro–B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period. Results Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: −27% to −7%) and hs-CRP by 13% (95% CI: −24% to −1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: −24% to −14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: −31% to −7%) and NT-proBNP by 23% (95% CI: −32% to −12%), whereas hs-CRP was not significantly changed (−7%; 95% CI: −22% to 9%) compared with the high sodium-control diet. Conclusions Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH – Sodium]; NCT00000608 )

Background Dietary recommendations to prevent gout emphasize a low-purine diet. Recent evidence suggests that the Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate while also improving blood pressure and lipids. Objective To compare the effects of DASH-style diets emphasizing different macronutrient proportions on serum urate reduction. Methods We conducted a secondary analysis of the Optimal Macronutrient Intake Trial to Prevent Heart Disease feeding study, a 3-period, crossover design, randomized trial of adults with prehypertension or hypertension. Participants were provided with 3 DASH-style diets in random order, each for 6 wk. Each DASH-style diet emphasized different macronutrient proportions: a carbohydrate-rich (CARB) diet, a protein-rich (PROT) diet, and an unsaturated fat-rich (UNSAT) diet. In the PROT diet, approximately half of the protein came from plant sources. We compared the effects of these diets on serum urate at weeks 4 and 6 of each feeding period. Results Of the 163 individuals included in the final analysis, the mean serum urate at baseline was 5.1 mg/dL. Only the PROT diet reduced serum urate from baseline at the end of the 6-wk feeding period (-0.16 mg/dL; 95% CI: -0.28, -0.04; P = 0.007). Neither the CARB diet (-0.03 mg/dL; 95% CI: -0.14, 0.09; P = 0.66) nor the UNSAT diet (-0.01 mg/dL; 95% CI: -0.12, 0.09; P = 0.78) reduced serum urate from baseline. The PROT diet lowered serum urate by 0.12 mg/dL (95% CI: -0.20, -0.03; P = 0.006) compared with CARB and by 0.12 mg/dL (95% CI: -0.20, -0.05; P = 0.002) compared with UNSAT. Conclusions A DASH-style diet emphasizing plant-based protein lowered serum urate compared with those emphasizing carbohydrates or unsaturated fat. Future trials should test the ability of a DASH-style diet emphasizing plant-based protein to lower serum urate and prevent gout flares in patients with gout. This trial was registered at clinicaltrials.gov as NCT00051350.

Various primary and secondary bile acids (BAs) may play pivotal roles in glucose/insulin metabolism. We investigated whether changes in specific BA subtypes were associated with long-term changes in glucose and insulin sensitivity.This study included 515 adults with overweight or obesity who participated in a 2-year intervention study of weight-loss diets with different macronutrient intakes. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after the interventions. We analyzed associations of changes in BA subtypes with two-year changes in fasting glucose, insulin, and insulin resistance (HOMA-IR).Greater decreases in primary and secondary BA subtypes induced by the interventions were significantly associated with greater reductions of fasting insulin and HOMA-IR at 6 months, showing various effects across the BA subtypes. The reductions of specific BA subtypes (chenodeoxycholate [CDCA], taurocholate [TCA], taurochenodeoxycholate [TCDCA], and taurodeoxycholate [TDCA]) were significantly related to improved glucose levels at 6 months. The initial (6-month) decreases in primary and secondary BA subtypes (glycochenodeoxycholate [GCDCA], TCDCA, and glycoursodeoxycholate [GUDCA]) were also significantly associated with long-term improvements in glucose and insulin metabolism over 2 years. We found significant interactions between dietary fat intake and changes in the BA subtypes for changes in glucose metabolism (PWeight-loss diet-induced changes in distinct subtypes of circulating BAs were associated with improved glucose metabolism and insulin sensitivity in adults with overweight or obesity. Dietary fat intake may modify the associations of changes in BA metabolism with glucose metabolism.

Cholesterol efflux (CE) is a major athero-protective function of high density lipoproteins (HDL). HDL is a heterogeneous mixture of lipoproteins that contain apoA1, the prime protein of HDL, and may contain one or more of >200 other proteins. These other proteins cluster on subpopulations of HDL particles to form HDL subspecies. It is not entirely clear by simply measuring individual protein abundances what drives HDL function. We aimed to study the differential association of 7 HDL subspecies defined by presence or absence of a functional protein with extreme and persistent cholesterol efflux capacity (CEC). From ~3000 individuals in the multi-ethnic population-based DHS (Dallas Heart Study) cohort, people at the bottom 10% and top 90% of CEC were reassessed after 15 years resulting in 36 participants with extreme persistent high or low CEC for the present study. HDL with and without 7 individual proteins potentially relevant to HDL function were quantified using ELISA. Differences in association with CEC between HDL subspecies that contain or lack a defining protein were examined by heterogeneity test. In the low CEC group, HDL lacking apolipoprotein C3 (apoC3), complement C3, apoE (apolipoprotein E) and PLMG (plasminogen) were each associated positively with CEC while HDL subspecies containing these proteins were not positively associated with CEC. (Pearson correlation coefficient range 0.55369 to 0.66562 vs -0.08432 to -0.25198; p

Context Selective androgen receptor modulators (SARMs), because of their preferential muscle vs prostate selectivity, are being developed for muscle-wasting conditions. Oral SARMs suppress high-density lipoprotein cholesterol (HDL-C) but their effects on functional capacity and atherogenic potential of HDL particles are unknown. Objective To determine the effects of an oral SARM (OPK-88004) on cholesterol efflux capacity, HDL particle number and size, apolipoprotein particle number and size and HDL subspecies Methods We measured cholesterol efflux capacity (CEC); HDL particle number and size; APOB; APOA1; and protein-defined HDL subspecies associated with coronary heart disease (CHD) risk in men, who had undergone prostatectomy for low-grade prostate cancer during 12-week treatment with placebo or 1, 5, or 15 mg of an oral SARM (OPK-88004). Results SARM significantly suppressed HDL-C (P Conclusion SARM treatment suppressed HDL-C but had minimal effect on its size or cholesterol efflux function. SARM reduced APOA1 in HDL subspecies associated with increased as well as decreased CHD risk. SARM-induced increase in HTGL could contribute to HDL-C suppression. These data do not support the simplistic notion that SARM-associated suppression of HDL-C is necessarily proatherogenic; randomized trials are needed to determine SARM’s effects on cardiovascular events.