Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition.

BACKGROUND: Weight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects. OBJECTIVES: This study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses' Health Study II cohort. METHODS: The examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause. RESULTS: In longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations. CONCLUSION: Yogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

Potato consumption is not associated with elevated cardiometabolic risk in adolescent girls.

We examined the association between potato consumption in two different age periods during adolescence and risk of obesity and cardiometabolic dysfunction in White and Black girls. We used data from the biracial prospective National Growth and Health Study. Average potato consumption was derived from multiple 3-d food records in two age periods, 9-11 and 9-17 years, and included white and sweet potatoes from all sources. Multivariable logistic regression models were used to estimate OR for becoming overweight, developing prehypertension, elevated TAG levels or impaired fasting glucose (IFG) at 18-20 years of age according to the category of daily potato intake. We also stratified by cooking method (fried/non-fried) and race. ANCOVA was also used to estimate adjusted mean levels of BMI, systolic blood pressure, diastolic blood pressure, log-transformed TAG, the TAG:HDL ratio and fasting glucose levels associated with potato intake category. Higher potato consumption was associated with higher fruit and non-starchy vegetable intakes and higher Healthy Eating Index scores in Black girls. There were no statistically significant associations overall between moderate or higher (v. lower) intakes of potatoes and risks of overweight, prehypertension, elevated fasting TAG, high TAG:HDL ratio or IFG. Also, no adverse associations were found between fried or non-fried potato intake and cardiometabolic outcomes. Potato consumption has been the subject of much controversy in recent years. This study adds evidence that potato consumption among healthy girls during the critical period of adolescence was not associated with cardiometabolic risk.

Salt and cardiovascular disease: insufficient evidence to recommend low sodium intake.

Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (2.3-4.6g/day; 1-2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

Anthropometric measures of body fat and obesity-related cancer risk: sex-specific differences in Framingham Offspring Study adults.

BACKGROUND/OBJECTIVE: Obesity has been associated with the risk of developing certain cancers. A limited number of studies have examined effects of various anthropometric measures of body composition on cancer risk. The aim of this study was to estimate the sex-specific effects of various anthropometric measures on risk of obesity-related cancers (ObCa). SUBJECTS/METHODS: Data on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and hip circumference (HC) among 3818 45-69-year olds in the Framingham Offspring Study were included. Cox proportional hazards models were used to estimate adjusted risks of 16 obesity-related cancers, with the most common being postmenopausal breast, endometrial, and colon cancers. RESULTS: Obesity as measured by BMI in both men and women was a predictor of ObCa; those in the highest quintile (Q5) of BMI (>30.07 in women; >30.80 kg/m2 in men) had more than twice the risk of ObCa (HR = 2.07; 95% CI: 1.06-4.07 (women) and HR = 2.25; 95% CI: 1.08-4.69 (men)). Waist-related measures (WC, WHtR) were stronger predictors of ObCa in men than in women, and HC confounded the relations between waist size and cancer risk. After adjusting for HC, men in Q5 of WC had more than a threefold increased risk of ObCa (HR: = 3.22; 95% CI: 1.39-7.45). Comparable effects in women were weak and non-statistically significant. Results were similar for WHtR. Finally, an inverse J-shaped relation was found between HC and ObCa after adjusting for WC among men but not in women. CONCLUSIONS: These results suggest that obesity as measured by BMI is a predictor of obesity-related cancer risk in men and women. They also suggest that waist and hip circumference measures are interrelated and confound the independent effects of each measure. Among men, a large waist size and a small hip size are independent predictors of cancer risk.

Dietary Patterns, Ceramide Ratios, and Risk of All-Cause and Cause-Specific Mortality: The Framingham Offspring Study.

BACKGROUND: Prior evidence suggests that diet modifies the association of blood ceramides with the risk of incident cardiovascular disease (CVD). It remains unknown if diet quality modifies the association of very long-chain-to-long-chain ceramide ratios with mortality in the community. OBJECTIVES: Our objectives were to determine how healthy dietary patterns associate with blood ceramide concentrations and to examine if healthy dietary patterns modify associations of ceramide ratios (C22:0/C16:0 and C24:0/C16:0) with all-cause and cause-specific mortality. METHODS: We examined 2157 participants of the Framingham Offspring Study (mean age = 66 y, 55% women). Blood ceramides were quantified using a validated assay. We evaluated prospective associations of the Dietary Guidelines Adherence Index (DGAI) and Mediterranean-style Diet Score (MDS) with incidence of all-cause and cause-specific mortality using Cox proportional hazards models. Cross-sectional associations of the DGAI and MDS with ceramides were evaluated using multivariable linear regression models. RESULTS: The C22:0/C16:0 and C24:0/C16:0 ceramide ratios were inversely associated with all-cause, CVD, and cancer mortality; multivariable-adjusted HRs (95% CIs) were 0.73 (0.67, 0.80) and 0.70 (0.63, 0.77) for all-cause mortality, 0.74 (0.60, 0.90) and 0.69 (0.55, 0.86) for CVD mortality, and 0.75 (0.65, 0.87) and 0.75 (0.64, 0.88) for cancer mortality, respectively. Inverse associations of the C22:0/C16:0 and C24:0/C16:0 ceramide ratios with cancer mortality were attenuated among individuals with a higher diet quality (DGAI or MDS above the median, all P-interaction ≤0.1). The DGAI and MDS had distinct associations with ceramide ratios (DGAI: lower C22:0/C16:0 across quartiles; MDS: higher C24:0/C16:0 across quartiles; all P-trend ≤0.01). CONCLUSION: In our community-based sample, ceramide ratios (C22:0/C16:0 and C24:0/C16:0) were associated with a lower risk of all-cause and cause-specific mortality. Further, we observed that a higher overall diet quality attenuates the association between blood ceramide ratios and cancer mortality and that dietary patterns have distinct relations with ceramide ratios.

Changes to dietary and health outcomes following implementation of the 2012 updated US Department of Agriculture school nutrition standards: analysis using National Health and Nutrition Examination Survey, 2005-2016.

OBJECTIVE: In 2012, the US government overhauled school nutrition standards, but few studies have evaluated the effects of these standards at the national level. The current study examines the impact of the updated school nutrition standards on dietary and health outcomes of schoolchildren in a nationally representative data set. DESIGN: Difference-in-differences. We compared weekday fruit and vegetable intake between students with daily school lunch participation and students without school lunch participation before and after implementation of updated school nutrition standards using a multivariable linear regression model. Secondary outcomes included weekday solid fat and added sugar (SoFAS) intake and overweight and obesity prevalence. We adjusted analyses for demographic and family socio-economic factors. SETTING: USA. PARTICIPANTS: K-12 students, aged 6-20 years (n 9172), from the National Health and Nutrition Examination Survey, 2005-2016. RESULTS: Implementation of updated school nutrition standards was not associated with a change in weekday fruit and vegetable intake (ß = 0·02 cups, 95 % CI -0·23, 0·26) for students with daily school lunch participation. However, implementation of the policy was associated with a 1·5 percentage point (95 % CI -3·0, -0·1) decline in weekday SoFAS intake and a 6·1 percentage point (95 % CI -12·1, -0·1) decline in overweight and obesity prevalence. CONCLUSIONS: Changes to US school nutrition standards were associated with reductions in the consumption of SoFAS as well as a decrease in overweight and obesity in children who eat school lunch. However, we did not detect a change in weekday intake of fruits and vegetables associated with the policy change.

Egg Intake Has No Adverse Association With Blood Lipids Or Glucose In Adolescent Girls.

OBJECTIVE: Longitudinal data on cardiometabolic effects of egg intake during adolescence are lacking. The current analyses aim to evaluate the impact of usual adolescent egg consumption on lipid levels, fasting glucose, and insulin resistance during late adolescence (age 17-20 years). METHODS: Data from 1392 girls, aged 9 to 10 at baseline and followed for 10 years, in the National Heart, Lung, and Blood Institute's National Growth and Health Study were used to examine the association between usual egg intake alone and in combination with other healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and insulin resistance, measured as homeostasis model assessment of insulin resistance (HOMA-IR). Diet was assessed using 3-day food records during eight examination cycles. Girls were classified according to usual weekly egg intake, ages 9-17 years: <1 egg/wk (n = 361), 1 to <3 eggs/wk (n = 703), and ≥3 eggs/wk (n = 328). Analysis of covariance modeling was used to control for confounding by other behavioral and biological risk factors. RESULTS: Girls with low, moderate, and high egg intakes had adjusted low-density lipoprotein cholesterol levels of 99.7, 98.8, and 95.5 mg/dL, respectively (p = 0.0778). In combination with higher intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were stronger and statistically significant. There was no evidence that ≥3 eggs/wk had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who consumed ≥3 eggs/wk had the lowest levels of insulin resistance. CONCLUSION: These results suggest that eggs may be included as part of a healthy adolescent diet without adverse effects on glucose, lipid levels, or insulin resistance.

Dietary Protein and Preservation of Physical Functioning Among Middle-Aged and Older Adults in the Framingham Offspring Study.

Dietary protein may help prevent age-related declines in strength and functional capacity. This study examines the independent relationship between dietary protein and longitudinal changes in physical functioning among adults participating in the Framingham Offspring Study from examination 5 (1991-1995) to examination 8 (2005-2008). Protein intakes were derived from 3-day diet records during examinations 3 and 5; functional status was determined over 12 years using 7 items selected from standardized questionnaires. Multivariable models adjusted for age, sex, education, physical activity, smoking, height, and energy intake. Functional tasks that benefitted most from a higher-protein diet (≥1.2 g/kg/day vs. <0.8 g/kg/day) were doing heavy work at home, walking 1/2 mile (0.8 km), going up and down stairs, stooping/kneeling/crouching, and lifting heavy items. Those with higher protein intakes were 41% less likely (95% CI: 0.43, 0.82) to become dependent in 1 or more of the functional tasks over follow-up. Higher physical activity and lower body mass index were both independently associated with less functional decline. The greatest risk reductions were found among those with higher protein intakes combined with either higher physical activity, more skeletal muscle mass, or lower body mass index. This study demonstrates that dietary protein intakes above the current US Recommended Daily Allowance may slow functional decline in older adults.

Midlife weight gain is a risk factor for obesity-related cancer.

BACKGROUND: Overweight and diabetes are known cancer risk factors. This study examines independent and combined effects of weight gain and metabolic dysfunction during middle-adult years on obesity-related cancer risk. METHODS: Subjects (n = 3850) aged 45-69 years at exams 3-5 in the Framingham Offspring Study were classified according to current and prior (~14 years earlier) weight status, interim weight change and prevalent metabolic dysfunction. Cancer risk among subjects who were overweight at baseline and remained overweight, as well as those who became overweight during follow-up, was compared with risk among normal-weight individuals. RESULTS: Gaining ≥0.45 kg (≥1.0 pound)/year (vs. maintaining stable weight) over ~14 years increased cancer risk by 38% (95% confidence interval (CI), 1.09, 1.76); combined with metabolic dysfunction, weight gain increased cancer risk by 77% (95% CI, 1.21, 2.59). Compared with non-overweight adults, men and women who became overweight during midlife had 2.18-fold and 1.60-fold increased cancer risks; those who were overweight from baseline had non-statistically significant 28 and 33% increased cancer risks, respectively, despite having a midlife body mass index that was 3.4 kg/m2 higher than those who gained weight later. CONCLUSION: Midlife weight gain was a strong cancer risk factor. This excess risk was somewhat stronger among those with concurrent metabolic dysfunction.

Vitamin D status is associated with underweight and stunting in children aged 6-36 months residing in the Ecuadorian Andes.

OBJECTIVE: There is limited knowledge on vitamin D status of children residing in the Andes and its association with undernutrition. We evaluated the vitamin D status of children residing in a low socio-economic status (SES) setting in the Ecuadorian Andes and assessed the association between vitamin D status, stunting and underweight. We hypothesized that children who were underweight would have lower serum 25-hydroxyvitamin D (25(OH)D) levels and lower 25(OH)D levels would be associated with a higher risk of stunting. DESIGN: We conducted a cross-sectional secondary analysis of a randomized controlled trial, the Vitamin A, Zinc and Pneumonia study. Children had serum 25(OH)D concentrations measured. A sensitivity analysis was undertaken to determine a vitamin D cut-off specific for our endpoints. Associations between serum 25(OH)D and underweight (defined as weight-for-age Z-score≤-1) and stunting (defined as height-for-age Z-score≤-2) were assessed using multivariate logistic regression. SETTING: Children residing in five low-SES peri-urban neighbourhoods near Quito, Ecuador. SUBJECTS: Children (n 516) aged 6-36 months. RESULTS: Mean serum 25(OH)D concentration was 58·0 (sd 17·7) nmol/l. Sensitivity analysis revealed an undernutrition-specific 25(OH)D cut-off of <42·5 nmol/l; 18·6 % of children had serum 25(OH)D<42·5 nmol/l. Children who were underweight were more likely to have serum 25(OH)D<42·5 nmol/l (adjusted OR (aOR)=2·0; 95 % CI 1·2, 3·3). Children with low serum 25(OH)D levels were more likely to be stunted (aOR=2·8; 95 % CI 1·6, 4·7). CONCLUSIONS: Low serum 25(OH)D levels were more common in underweight and stunted Ecuadorian children.

Associations between metabolic disorders and risk of cancer in Danish men and women--a nationwide cohort study.

BACKGROUND: The prevalence of metabolic disorders is increasing and has been suggested to increase cancer risk, but the relation between metabolic disorders and risk of cancer is unclear, especially in young adults. We investigated the associations between diabetes, hypertension, and hypercholesterolemia on risk of all-site as well as site-specific cancers. METHODS: We consecutively included men and women from nationwide Danish registries 1996-2011, if age 20-89 and without cancer prior to date of entry. We followed them throughout 2012. Metabolic disorders were defined using discharge diagnosis codes and claimed prescriptions. We used time-dependent sex-stratified Poisson regression models adjusted for age and calendar year to assess associations between metabolic disorders, and risk of all-site and site-specific cancer (no metabolic disorders as reference). RESULTS: Over a mean follow-up of 12.6 (± 5.7 standard deviations [SD]) years, 4,826,142 individuals (50.2% women) with a mean age of 41.4 (± 18.9 SD) years had 423,942 incident cancers. Incidence rate ratios (IRRs) of all-site cancer in patients with diabetes or hypertension were highest immediately following diagnosis of metabolic disorder. In women, cancer risk associated with diabetes continued to decline albeit remained significant (IRRs of 1.18-1.22 in years 1-8 following diagnosis). For diabetes in men, and hypertension, IRRs stabilized and remained significantly increased after about one year with IRRs of 1.10-1.13 in men for diabetes, and 1.07-1.14 for hypertension in both sexes. Conversely, no association was observed between hypercholesterolemia (treatment with statins) and cancer risk. The association between hypertension and cancer risk was strongest in young adults aged 20-34 and decreased with advancing age. CONCLUSIONS: Diabetes and hypertension were associated with increased risk of all-site cancer.

Adolescent dietary intakes predict cardiometabolic risk clustering.

PURPOSE: To prospectively examine the relation between adolescent dietary intake and cardiometabolic risk (CMR) clustering at the end of adolescence. METHODS: Data from the NHLBI Growth and Health Study on 1369 girls enrolled at ages 9-10 in 1987-1988 and followed for 10 years were used to estimate the relative risk of having multiple (≥2 or ≥3) risk factors in late adolescence associated with usual food intake patterns from 9 to 17 years of age. Mean food intakes were derived from multiple 3-day diet records and CMR factors included larger waist circumference, insulin resistance, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, high triglycerides, and elevated systolic or diastolic blood pressures. RESULTS: Of 1369 subjects, 18.4 % girls had 3-6 prevalent risk factors by the end of adolescence and 35.0 % had at least two. Higher intakes of fruit and non-starchy vegetables, dairy, and grains were independently associated with having fewer risk factors as were eating patterns characterized by higher combined intakes of these food groups. After adjusting for age, race, socio-economic status, height, physical activity, and television watching, girls with high intakes of dairy and fruits and non-starchy vegetables (vs. those with lower intakes of both) were nearly 50 % less likely to have three or more CMR factors in late adolescence; girls with higher intakes of grains plus fruits and non-starchy vegetables were nearly 60 % less likely. CONCLUSION: These results suggest that healthy food consumption patterns during adolescence may prevent accumulation of cardiometabolic risk.

Sugar-sweetened beverage consumption and central and total adiposity in older children: a prospective study accounting for dietary reporting errors.

OBJECTIVE: To determine the prospective relationship between changes in sugar-sweetened beverage (SSB) intake and central adiposity in older children. DESIGN: Dietary intakes of children were obtained by 3 d food records at ages 10 and 13 years. Waist circumference (WC) and weight and height to determine BMI were measured at 10 and 13 years and total body fat mass (TBFM) at 13 years by dual-energy X-ray absorptiometry. Analyses were conducted using multivariable linear regression. Reporting errors were measured and participants were categorized as under-, plausible and over-reporters of dietary intakes. SETTING: Community-based British cohort of children participating in the Avon Longitudinal Study of Parents and Children. RESULTS: Among 2455 older children, increased SSB consumption from ages 10 to 13 years was associated with higher WC (standardized ß=0.020, P=0.19), BMI (ß=0.028, P=0.03) and TBFM (ß=0.017, P=0.20) at 13 years. Effects were strengthened among plausible dietary reporters (n 1059): WC (ß=0.097, P<0.001), BMI (ß=0.074, P<0.001) and TBFM (ß=0.065, P=0.003). The association between change in SSB and WC was weakened, but remained statistically significant after accounting for BMI (ß=0.042, P=0.02) and TBFM (ß=0.048, P=0.01). CONCLUSIONS: Higher consumption of SSB from ages 10 to 13 years was associated with a larger WC at age 13 years independent of differences in total adiposity. Accounting for dietary reporting errors strengthened associations. Our findings further support recommendations to limit intakes of SSB to reduce excess weight gain in children and suggest that SSB have an additional deleterious effect on central adiposity.

Dairy intakes at age 10 years do not adversely affect risk of excess adiposity at 13 years.

Evidence of an association between milk intake and childhood adiposity remains inconsistent, with few data available regarding the effects of the amount of dairy fat consumed. This study examined the relation between dairy consumption (total, full, and reduced fat) at age 10 y on risk of excess adiposity at age 13 y in participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2455). Intakes were assessed by 3-d dietary records. Total body fat mass (TBFM) using dual-energy X-ray absorptiometry was examined at 13 y. Outcomes included excess TBFM (top quintile of TBFM), overweight, and change in body mass index (BMI). The highest vs. lowest quartile of total dairy consumers (g/d) at age 10 y did not have an increased risk of excess TBFM (OR: 0.73; 95% CI: 0.46, 1.16; P-trend = 0.28) or overweight (OR: 0.69; 95% CI: 0.41, 1.15; P = 0.24) at age 13 y. Children in the highest quartile of full-fat dairy intakes vs. those in the lowest quartile had a reduced risk of excess TBFM (OR: 0.64; 95% CI: 0.41, 1.00; P = 0.04) and a suggestion of a reduction in overweight (OR: 0.65; 95% CI: 0.40, 1.06; P = 0.19) at age 13 y. Furthermore, the highest vs. lowest consumers of full-fat products had smaller gains in BMI during follow-up [2.5 kg/m² (95% CI: 2.2, 2.7) vs. 2.8 kg/m² (95% CI: 2.5, 3.0); P < 0.01]. Associations with reduced-fat dairy consumption did not attain statistical significance. In this study, dairy consumption was not related to excess fat accumulation during late childhood. Estimates had wide confidence limits but generally showed inverse relations between dairy intakes and risk of excess adiposity. Additional prospective research is warranted to confirm the effects of dairy intake on obesity in children.

Eggs and a Fiber-Rich Diet Are Beneficially Associated with Lipid Levels in Framingham Offspring Study Adults.

Background: For many years, United States' dietary policy recommended limiting egg intake to no more than 3/wk in the belief that restricting dietary cholesterol would lower plasma cholesterol levels and thereby reduce the risk of cardiovascular disease. The evidence supporting these recommendations is controversial. Objectives: To examine the impact of eggs, a major contributor to dietary cholesterol intake, on lipid levels and to determine whether these egg effects are modified by other healthy dietary factors in adults. Methods: Males and females aged 30-64 y with available 3-d diet record data, without cardiovascular disease and not taking lipid- or glucose-lowering medications in the prospective Framingham Offspring cohort were included (n = 1852). Analysis of covariance models were used to compare mean follow-up lipid levels adjusting for age, sex, BMI, and dietary factors. Cox proportional hazard's models were used to estimate risk for elevated lipid levels. Results: Consuming ≥5 eggs/wk was not adversely associated with lipid outcomes. Among men, consuming ≥5 (compared with <0.5) eggs/wk was associated with an 8.6 mg/dL lower total cholesterol level and a 5.9 mg/dL lower LDL cholesterol level, as well as lower triglycerides. Overall, higher egg intake combined with higher dietary fiber (compared with lower intakes of both) was associated with the lowest total cholesterol, LDL cholesterol, and LDL cholesterol-to-HDL cholesterol ratio. Finally, diets with higher (compared with lower) egg intakes in combination with higher total fish or fiber intakes, respectively, were associated with lower risks of developing elevated (>160 mg/dL) LDL cholesterol levels (hazard ratio: 0.61; 95% confidence interval: 0.44, 0.84; and HR: 0.70; 95% confidence interval: 0.49, 0.98, respectively). Conclusions: Higher egg intakes were beneficially associated with serum lipids among healthy adults, particularly those who consumed more fish and dietary fiber.

Indices of Mediterranean diet adherence and breast cancer risk in a community-based cohort.

Introduction: A Mediterranean-style dietary pattern is believed to have cancer-protective effects. We compared the prospective associations between adherence to four established Mediterranean diet indices and breast cancer risk (including total, postmenopausal, and hormone receptor positive cases) in women in the Framingham Offspring Study. Methods: The four indices used two different approaches to measuring adherence to a Mediterranean diet: (a) scores based on the population-specific median intakes of Mediterranean diet-related foods in a given population (i.e., alternate Mediterranean Diet (aMED) index and Mediterranean Diet Score (MDS) index), and (b) scores based on compliance with recommended intakes of relevant foods from the Mediterranean diet pyramid [i.e., Mediterranean Diet (MeDiet) index and Mediterranean Style Dietary Pattern (MSDP) index]. Dietary data were derived from semiquantitative food frequency questionnaires collected in 1991-95. Participants included 1579 women aged ≤ 30 years who were free of prevalent cancer. Women were followed through 2014, and Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for various confounders. Results: During a median follow-up of approximately 18 years, 87 breast cancer cases were documented. Women in the highest (vs. lowest) score category of the pyramid-based scores (i.e., MeDiet or MSDP) had approximately 45% statistically significantly lower breast cancer risks. These effects were even stronger for any hormone receptor positive cases using the MeDiet index (highest vs. lowest score categories: HR = 0.45, 95% CI: 0.22-0.90). Neither of the median intake-based scores (i.e., aMED, MDS) was associated with breast cancer risk. Discussion: Our results suggest that the methodology and the composition of Mediterranean diet indices influence their ability to assess conformity to this specific diet pattern and predict breast cancer risk.

Dietary fat intakes, lipid profiles, adiposity, inflammation, and glucose in women and men in the Framingham Offspring Cohort.

Introduction: The role of dietary fat in the evolution of cardiometabolic disorders is highly controversial. As both dietary intake and the development of cardiometabolic risk differ by sex, we evaluated sex-specific differences in the associations between dietary fats (saturated and unsaturated) and four key cardiometabolic risk factors-lipid profiles, body fat, inflammation, and glucose regulation. Methods: We included 2391 women and men aged ≥30 years in the prospective Framingham Offspring Cohort. Weight-adjusted dietary fats (saturated, monounsaturated, and polyunsaturated fats, including omega-3 and omega-6) were derived from 3-day dietary records. Analysis of covariance was used to derive adjusted mean levels of all outcomes. Results: In both men and women, intakes of saturated and monounsaturated fats were inversely associated with TG:HDL ratio (p < 0.02 for both types of fat). In women, higher omega-3 and omega-6 PUFAs were also inversely associated with TG:HDL (p < 0.05 for both), but for men, only omega-3 PUFAs were associated (p = 0.026). All types of dietary fat were beneficially associated with larger HDL particle sizes in both men and women, while only saturated and monounsaturated fats were associated with larger LDL particles in men. In addition, saturated and monounsaturated fats were associated with statistically significantly higher concentrations of HDL and lower concentrations of LDL and VLDL particles in both sexes, while polyunsaturated fat had favorable associations in women only. Saturated fat also had beneficial associations with three measures of body fat. For example, women with the highest (vs. lowest) saturated fat intake had a lower BMI (27.7 ± 0.25 vs. 26.2 ± 0.36 kg/m2, p = 0.001); findings were similar in men (28.2 ± 0.25 vs. 27.1 ± 0.20, p = 0.002). Unsaturated fats had beneficial associations with body fat primarily in women. Finally, omega-3 PUFAs among women were inversely associated with interleukin-6 levels. There was no association between dietary fat intake and fasting glucose levels in either women or men. Discussion: In sum, we found no evidence of an adverse association between dietary fats and several surrogate markers of cardiometabolic health. This study suggests that different dietary fats may have divergent associations with cardiometabolic risk in women and men, perhaps owing to differences in food sources of the same dietary fats.

Egg Intake Is Associated with Lower Risks of Impaired Fasting Glucose and High Blood Pressure in Framingham Offspring Study Adults.

The association between egg consumption and cardiometabolic risk factors such as high blood pressure (HBP) and impaired fasting glucose (IFG) or type 2 diabetes (T2D) is still under debate. This study examines the association between egg consumption and these outcomes among 2349 30-64 year-old adults in the prospective Framingham Offspring Study. Diet was assessed using three-day dietary records. Potential confounders retained in the final models included age, sex, body mass index, and other dietary factors. The analysis of covariance and Cox proportional hazard's models were used to assess the relevant continuous (i.e., FG, SBP, DBP) and categorical (i.e., T2D, HBP) outcomes. Consuming ≥5 eggs per week was associated with lower mean FG (p = 0.0004) and SBP (p = 0.0284) after four years of follow-up. Higher egg intakes led to lower risks of developing IFG or T2D (HR: 0.72; 95% CI: 0.51-1.03) and high blood pressure (HBP) (HR: 0.68; 0.50-0.93). The beneficial effects of egg consumption were stronger in combination with other healthy dietary patterns. This study found that regular egg consumption as part of a healthy diet had long-term beneficial effects on blood pressure and glucose metabolism and lowered the long-term risks of high blood pressure and diabetes.

Types of dairy foods and risk of fragility fracture in the prospective Nurses' Health Study cohort.

BACKGROUND: Fragility fractures present enormous health challenges for women. Dairy products provide many bone-beneficial nutrients, such as calcium and vitamin D. Individual dairy foods may exert different effects on bone health. OBJECTIVES: The aim of this study was to investigate the associations between total dairy, yogurt, milk, and cheese and fragility fracture risk among females in the prospective Nurses' Health Study (NHS) conducted in the United States. METHODS: In the current analysis, 103,003 females with mean age of 48 y were followed from 1980-2004. Proportional hazards models were used to estimate risk of first fracture (of the wrist, hip, or vertebrae) by intakes of dairy foods (total dairy, milk, yogurt, or cheese) obtained from a food frequency questionnaire. Fractures that were caused by high-trauma events were not included. We relied on self-reported data for wrist and hip fractures whereas for vertebral fractures, medical records were used to confirm cases. RESULTS: A total of 5495 incident fracture cases were documented during follow-up. After controlling for relevant confounding variables, consumption of ≥2 servings/d of total dairy (compared with <1 serving/d) was associated with lower fracture risk (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.61, 0.89). More than 2 servings of milk per day (compared with <1 serving/d) were associated with a lower fracture risk (HR: 0.85; 95% CI: 0.77, 0.94). Intakes of calcium, vitamin D, and protein from nondairy sources did not modify the effects of total dairy or milk on fracture risk. There was no association between yogurt intake and fracture risk. Intake of cheese (≥1 servings/d compared with <1 serving/wk) was weakly associated with lower fracture risk (HR: 0.89; 95% CI: 0.79, 0.99). CONCLUSIONS: Higher total dairy, milk, and cheese intakes are associated with lower risks of fracture in females in the NHS.

Integrative Mendelian randomization reveals the soluble receptor for advanced glycation end products as protective in relation to rheumatoid arthritis.

Rheumatoid arthritis (RA) is a risk factor for atherosclerotic cardiovascular diseases (CVD). Given the critical roles of the immune system and inflammatory signals in the pathogenesis of CVD, we hypothesized that interrogation of CVD-related proteins using integrative genomics might provide new insights into the pathophysiology of RA. We utilized two-sample Mendelian randomization (MR) for causal inference between circulating protein levels and RA by incorporating genetic variants, followed by colocalization to characterize the causal associations. Genetic variants from three sources were obtained: those associated with 71 CVD-related proteins measured in nearly 7000 Framingham Heart Study participants, a published genome-wide association study (GWAS) of RA (19 234 cases, 61 565 controls), and GWAS of rheumatoid factor (RF) levels from the UK Biobank (n = 30 565). We identified the soluble receptor for advanced glycation end products (sRAGE), a critical inflammatory pathway protein, as putatively causal and protective for both RA (odds ratio per 1-standard deviation increment in inverse-rank normalized sRAGE level = 0.364; 95% confidence interval 0.342-0.385; P = 6.40 × 10-241) and RF levels (ß [change in RF level per sRAGE increment] = - 1.318; SE = 0.434; P = 0.002). Using an integrative genomic approach, we highlight the AGER/RAGE axis as a putatively causal and promising therapeutic target for RA.