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AbstractObjectiveTo evaluate the association between egg intake and cardiovascular disease risk among women and men in the United States, and to conduct a meta-analysis of prospective cohort studies.DesignProspective cohort study, and a systematic review and meta-analysis of prospective cohort studies.SettingNurses’ Health Study (NHS, 1980-2012), NHS II (1991-2013), Health Professionals’ Follow-Up Study (HPFS, 1986-2012).ParticipantsCohort analyses included 83 349 women from NHS, 90 214 women from NHS II, and 42 055 men from HPFS who were free of cardiovascular disease, type 2 diabetes, and cancer at baseline.Main outcome measuresIncident cardiovascular disease, which included non-fatal myocardial infarction, fatal coronary heart disease, and stroke.ResultsOver up to 32 years of follow-up (>5.54 million person years), 14 806 participants with incident cardiovascular disease were identified in the three cohorts. Participants with a higher egg intake had a higher body mass index, were less likely to be treated with statins, and consumed more red meats. Most people consumed between one and less than five eggs per week. In the pooled multivariable analysis, consumption of at least one egg per day was not associated with incident cardiovascular disease risk after adjustment for updated lifestyle and dietary factors associated with egg intake (hazard ratio for at least one egg per day v less than one egg per month 0.93, 95% confidence interval 0.82 to 1.05). In the updated meta-analysis of prospective cohort studies (33 risk estimates, 1 720 108 participants, 139 195 cardiovascular disease events), an increase of one egg per day was not associated with cardiovascular disease risk (pooled relative risk 0.98, 95% confidence interval 0.93 to 1.03, I2=62.3%). Results were similar for coronary heart disease (21 risk estimates, 1 411 261 participants, 59 713 coronary heart disease events; 0.96, 0.91 to 1.03, I2=38.2%), and stroke (22 risk estimates, 1 059 315 participants, 53 617 stroke events; 0.99, 0.91 to 1.07, I2=71.5%). In analyses stratified by geographical location (P for interaction=0.07), no association was found between egg consumption and cardiovascular disease risk among US cohorts (1.01, 0.96 to 1.06, I2=30.8%) or European cohorts (1.05, 0.92 to 1.19, I2=64.7%), but an inverse association was seen in Asian cohorts (0.92, 0.85 to 0.99, I2=44.8%).ConclusionsResults from the three cohorts and from the updated meta-analysis show that moderate egg consumption (up to one egg per day) is not associated with cardiovascular disease risk overall, and is associated with potentially lower cardiovascular disease risk in Asian populations.Systematic review registrationPROSPERO CRD42019129650.

Increased lipoprotein(a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Studies of dietary interventions on changes in Lp(a) are sparse. We aimed to compare the effects of three healthy dietary interventions differing in macronutrient content on Lp(a) concentration. Secondary analysis of a randomized, 3-period crossover feeding study including 155 (89 blacks; 66 whites) individuals. Participants were given DASH-type healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each diet. Compared to baseline, all interventional diets increased mean Lp(a) by 2 to 5 mg/dl. Unsat Fat increased Lp(a) less than Prot with a difference of 1.0 mg/dl (95% CI, -0.5, 2.5; p = 0.196) in whites and 3.7 mg/dl (95% CI, 2.4, 5.0; p < 0.001) in blacks (p-value between races = 0.008); Unsat Fat increased Lp(a) less than Carb with a difference of -0.6 mg/dl, 95% CI, -2.1, 0.9; p = 0.441) in whites and -1.5 mg/dl (95% CI, -0.2, -2.8; p = 0.021) in blacks (p-value between races = 0.354). Prot increased Lp(a) more than Carb with a difference of 0.4 mg/dl (95% CI, -1.1, 1.9; p = 0.597) in whites and 2.2 mg/dl (95%CI, 0.9, 3.5; p = 0.001) in blacks (p-value between races = 0.082). Diets high in unsaturated fat increased Lp(a) levels less than diets rich in carbohydrate or protein with greater changes in blacks than whites. Our results suggest that substitutions with dietary mono- and polyunsaturated fatty acids in healthy diets may be preferable over protein or carbohydrates with regards to Lp(a). Clinicaltrials.gov NCT00051350.

A 57-year-old woman is seen in an outpatient clinic, where her blood pressure reading is 155/95 mm Hg. Dietary therapy is recommended. Dietary changes that have been shown to reduce blood pressure include reduced sodium intake, reduced caloric intake (for weight loss), and diets high in fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, nuts, and unsaturated vegetable oils. A 57-year-old patient has a blood pressure reading of 155/95 mm Hg. Dietary therapy is recommended. Dietary changes that have been shown to reduce blood pressure include reduced sodium intake, reduced caloric intake, and diets high in fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, nuts, and unsaturated vegetable oils. Foreword This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines, if they exist, are presented. The article ends with the authors' clinical recommendations. Stage A 57-year-old woman presents to an outpatient clinic for evaluation of hypertension. She has no history or symptoms of cardiovascular disease and reports having gained 15 kg over the past 30 years. Her blood pressure is 155/95 mm Hg, her weight 86 kg, her height 165 cm, her body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) 31, and her waist circumference 98 cm. Her serum triglyceride level is 175 mg per deciliter (2.0 mmol per liter), high-density lipoprotein cholesterol 42 mg per deciliter (1.1 mmol per liter), low-density lipoprotein cholesterol 110 . . .

Précis:In the 2-year randomized weight-loss intervention, dietary fat significantly interacted with genetic variations of circulating adiponectin on long-term changes in appetite and adiponectin levels.AbstractContext:Adiponectin plays key roles in regulating appetite and food intake.Objective:To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels.Design, Setting, and Participants:A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial.Main Outcome Measures:Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger.Results:Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. Additionally, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P for interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but it was not associated with adiponectin changes in the high-fat group (P = 0.31).Conclusions:Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake.

Aims/hypothesis Vitamin D and related genetic variants are associated with obesity and insulin resistance. We aimed to examine whether vitamin D metabolism-related variants affect changes in body weight and insulin resistance in response to weight-loss diets varying in macronutrient content. Methods Three vitamin D metabolism-related variants, DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs2282679, were genotyped in 732 overweight/obese participants from a 2 year weight-loss trial (POUNDS Lost). We assessed genotype effects on changes in body weight, fasting levels of glucose and insulin, and HOMA-IR at 6 months (up to 656 participants) and 2 years (up to 596 participants) in response to low-protein vs high-protein diets, and low-fat vs high-fat diets. Results We found significant interactions between DHCR7 rs12785878 and diets varying in protein, but not in fat, on changes in insulin and HOMA-IR at both 6 months ( p for interaction <0.001) and 2 years ( p for interaction ≤0.03). The T allele (vitamin-D-increasing allele) of DHCR7 rs12785878 was associated with greater decreases in insulin and HOMA-IR ( p  < 0.002) in response to high-protein diets, while there was no significant genotype effect on changes in these traits in the low-protein diet group. Generalised estimating equation analyses indicated significant genotype effects on trajectory of changes in insulin resistance over the 2 year intervention in response to high-protein diets ( p  < 0.001). We did not observe significant interaction between the other two variants and dietary protein or fat on changes in these traits. Conclusions/interpretation Our data suggest that individuals carrying the T allele of DHCR7 rs12785878 might benefit more in improvement of insulin resistance than noncarriers by consuming high-protein weight-loss diets. Trial registration : ClinicalTrials.gov NCT00072995

A 3-year trial involving persons with a family history of dementia showed no differences in cognitive change or brain MRI outcomes between the MIND diet, designed for neuroprotection, and a control diet.

Hypertension affects almost 50 million people in the United States and places them at higher risk for cardiovascular diseases. 1 , 2 Furthermore, this risk increases with progressive elevations in blood pressure, beginning at even normal levels of blood pressure. 3 The Dietary Approaches to Stop Hypertension (DASH) trial demonstrated that a diet that emphasizes fruits, vegetables, and low-fat dairy products, that includes whole grains, poultry, fish, and nuts, that contains only small amounts of red meat, sweets, and sugar-containing beverages, and that contains decreased amounts of total and saturated fat and cholesterol lowers blood pressure substantially both in people with hypertension and . . .

Apolipoprotein A4's (APOA4's) functions on HDL in humans are not well understood. A unique feature of APOA4 is that it is an intestinal apolipoprotein secreted on HDL and chylomicrons. The goal of this study was to gain a better understanding of the origin and function of APOA4 on HDL by studying its metabolism across 6 HDL sizes. Twelve participants completed a metabolic tracer study. HDL was isolated by APOA1 immunopurification and separated by size. Tracer enrichments for APOA4 and APOA1 were determined by targeted mass spectrometry, and metabolic rates were derived by compartmental modeling. APOA4 metabolism on small HDL (alpha3, prebeta, and very small prebeta) was distinct from that of APOA4 on large HDL (alpha0, 1, 2). APOA4 on small HDL appeared in circulation by 30 minutes and was relatively rapidly catabolized. In contrast, APOA4 on large HDL appeared in circulation later (1-2 hours) and had a much slower catabolism. The unique metabolic profiles of APOA4 on small and large HDL likely indicate that each has a distinct origin and function in humans. This evidence supports the notion that APOA4 on small HDL originates directly from the small intestine while APOA4 on large HDL originates from chylomicron transfer.

There is emerging evidence linking fruit and vegetable consumption and cognitive function. However, studies focusing on the nutrients underlying this relationship are lacking. We aim to examine the association between plasma nutrients and cognition in a population at risk for cognitive decline with a suboptimal diet. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is a randomized controlled intervention that examines the effects of the MIND diet to prevent cognitive decline. The primary outcome is global cognition. A multivariate linear model was used to investigate the association between blood nutrients and global and/or domain-specific cognition. The model was adjusted for age, sex, education, study site, smoking status, cognitive activities and physical activities. High plasma α-carotene was associated with better global cognition. Participants in the highest tertile of plasma α-carotene had a higher global cognition z score of 0⋅17 when compared with individuals in the lowest tertile (P 0⋅002). Circulating α-carotene levels were also associated with higher semantic memory scores (P for trend 0⋅007). Lutein and zeaxanthin (combined) was positively associated with higher semantic memory scores (P for trend 0⋅009). Our study demonstrated that higher α-carotene levels in blood were associated with higher global cognition scores in a US population at risk for cognitive decline. The higher α-carotene levels in blood reflected greater intakes of fruits, other types of vegetables and lesser intakes of butter and margarine and meat. The higher circulating levels of lutein plus zeaxanthin reflected a dietary pattern with high intakes of fruits, green leafy, other vegetables and cheese, and low consumption of fried foods. Objective nutrient markers in the blood can better characterize dietary intake, which may facilitate the implementation of a tailored dietary intervention for the prevention of cognitive decline.

ObjectiveAlterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention.DesignWe included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated.ResultsGreater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids.ConclusionOur findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism.Trial registration numberNCT00072995.