Relationship of body mass index with frailty and all-cause mortality among middle-aged and older adults.

BACKGROUND: Parallel to growth of aging and obese populations, the prevalence of metabolic diseases is rising. How body mass index (BMI) relates to frailty and mortality across frailty levels is controversial. We examined the associations of high BMI with frailty and mortality and explored the effects of percent body fat on these associations. METHODS: We included 29,937 participants aged ≥50 years from the 2001-2006 National Health and Nutrition Examination Survey (NHANES) cohorts (N=6062; 53.7% females) and from wave 1 (2004) of Survey of Health, Ageing and Retirement in Europe (SHARE) (N=23,875; 54% females). BMI levels were categorized as: normal: 18.5-24.9 kg/m2, overweight: 25.0-29.9, obese grade 1: 30.0-34.9, and obese grade 2 or 3: >35.0. A frailty index (FI) was constructed excluding nutrition-related items: 36 items for NHANES and 57 items for SHARE. We categorized the FI using 0.1-point increments: FI ≤ 0.1 (non-frail), 0.1 < FI ≤ 0.2 (very mildly frail), 0.2 < FI ≤ 0.3 (mildly frail), and FI > 0.3 (moderately/severely frail). Percent body fat was measured using DXA for NHANES participants. All-cause mortality data were obtained until 2015 for NHANES and 2017 for SHARE to estimate 10-year mortality risk. All analyses were adjusted for age, sex, educational, marital, employment, and smoking statuses. RESULTS: Mean age of participants was 63.3±10.2 years for NHANES and 65.0±10.0 years for SHARE. In both cohorts, BMI levels ≥25 kg/m2 were associated with higher frailty, compared to normal BMI. In SHARE, having a BMI level greater than 35 kg/m2 increased mortality risk in participants with FI≤0.1 (HR 1.31, 95%CI 1.02-1.69). Overweight participants with FI scores >0.3 were at lower risk for mortality compared to normal BMI [NHANES (0.79, 0.64-0.96); SHARE (0.71, 0.63-0.80)]. Higher percent body fat was associated with higher frailty. Percent body fat significantly mediated the relationship between BMI levels and frailty but did not mediate the relationship between BMI levels and mortality risk. CONCLUSIONS: Being overweight or obese is associated with higher frailty levels. In this study, we found that being overweight is a protective factor of mortality in moderately/severely frail people and obesity grade 1 may be protective for mortality for people with at least a mild level of frailty. In contrast, obesity grades 2 and 3 may be associated with higher mortality risk in non-frail people. The relationship between BMI and frailty is partially explained by body fat.

Eating Timing and Frequency as a Predictor of Hospitalization and/or Mortality From Coronary Artery Disease: The Linked CCHS-DAD-CMDB 2004-2013 Study.

Background: Coronary artery disease (CAD) is a major overlapping challenge in both clinical and public health realms due to high rates of hospitalization and mortality. Despite nutrition being a key risk factor for CAD, little is known about eating timing and frequency in Canadians or their relation to risk of hospitalization and/or mortality from CAD. Methods: Breakfast consumption, between-meal consumption, eating frequency, and established CAD risk factors were assessed at baseline in 13,328 adults free of cancer and CAD from the 2004 Canadian Community Health Survey, Cycle 2.2, Nutrition Focus and were linked to administrative health databases to determine incidence of hospitalization and/or mortality from CAD in the following 9 years. Multivariable-adjusted hazard ratios with 95% confidence intervals estimated from Cox proportional hazards models were computed to test for associations between eating timing/frequency and hospitalization and/or mortality from CAD (n = 746 cases). Results: Skipping breakfast (12.0% of participants) and engaging in between-meal consumption (90.2%) were common practices, as was eating 4-5 times per day (55.2%). Skipping breakfast, between-meal consumption, and eating more or less than 4-5 times/day were strongly and bi-directionally associated with many sociodemographic, lifestyle, and metabolic risk factors at baseline. No associations were observed between skipping breakfast, between-meal consumption, or eating frequency and risk of hospitalization and/or mortality from CAD. Conclusions: Skipping breakfast, between-meal consumption, and eating frequency were associated with numerous established risk and preventative factors for CAD at baseline but were not directly associated with the risk of hospitalization and/or mortality from CAD in this cohort of Canadian adults.

Introduction: La maladie coronarienne (MC) est un enjeu majeur chevauchant les domaines clinique et de santé publique en raison des taux élevés d'hospitalisation et de mortalité. Bien que la nutrition soit un facteur de risque fondamental de la MC, on en connaît peu sur le moment et la fréquence de la consommation d'aliments chez les Canadiens ou sur leur relation au risque d'hospitalisation et/ou de mortalité en raison de la MC. Méthodes: Nous avons initialement évalué la prise du déjeuner, la consommation entre les repas, la fréquence de la consommation d'aliments et les facteurs de risque établis de MC de 13 328 adultes indemnes de cancer et de MC de l'Enquête sur la santé dans les collectivités canadiennes de 2004, cycle 2.2, volet nutrition, et avons lié les bases de données administratives en santé pour déterminer la fréquence d'hospitalisation et/ou de mortalité en raison de la MC dans les neuf années subséquentes. Nous avons calculé les rapports de risque ajustés à plusieurs variables à intervalles de confiance à 95 % estimés à partir des modèles à risques proportionnels de Cox pour vérifier les associations entre le moment et la fréquence de la consommation d'aliments et l'hospitalisation et/ou la mortalité en raison de la MC (n = 746 cas). Résultats: L'absence du déjeuner (12,0 % des participants), la consommation d'aliments entre les repas (90,2 %) et la consommation d'aliments de 4 à 5 fois par jour (55,2 %) étaient des pratiques courantes. L'absence du déjeuner, la consommation d'aliments entre les repas et la consommation d'aliments plus ou moins 4-5 fois/jour étaient fortement et bidirectionnellement associées aux facteurs de risque sociodémographiques, liés au mode de vie et métaboliques initiaux. Nous n'avons observé aucune association entre l'absence du déjeuner, la consommation d'aliments entre les repas ou la fréquence de la consommation d'aliments, et le risque d'hospitalisation et/ou de mortalité en raison de la MC. Conclusions: L'absence du déjeuner, la consommation d'aliments entre les repas et la fréquence de la consommation d'aliments étaient associées à de nombreux risques établis et de facteurs préventifs initiaux de la MC, mais n'étaient pas directement associées au risque d'hospitalisation et/ou de mortalité en raison de la MC dans cette cohorte d'adultes canadiens.

Prospective study of breakfast frequency and timing and the risk of incident type 2 diabetes in community-dwelling older adults: the Cardiovascular Health Study.

BACKGROUND: No evidence-based recommendations regarding optimal breakfast frequency and timing and type 2 diabetes mellitus (T2DM) exist for older adults because of limited studies. OBJECTIVES: We sought to prospectively assess relations between breakfast frequency and timing and T2DM risk among older adults and determine whether these depended on sex or cardiometabolic risk factors. METHODS: Weekly breakfast frequency and usual daily breakfast time were assessed by questionnaire at baseline in 3747 older adults (aged ≥ 65 y) from the Cardiovascular Health Study (CHS) who were free of cancer and T2DM and followed for 17.6 y. Multivariable-adjusted hazard ratios (aHRs) with 95% CIs estimated from Cox proportional hazards models were used to quantify associations with T2DM. RESULTS: Most CHS participants (median age: 74 y; IQR: 71-78 y) consumed breakfast daily (85.5%), and 73% had their first daily eating occasion between 07:00 and 09:00, both of which were associated with higher socioeconomic status, factors that are indicative of a healthier lifestyle, and lower levels of cardiometabolic risk indicators at baseline. During follow-up, 547 T2DM cases were documented. No strong evidence was observed linking breakfast frequency and risk of T2DM. Compared with participants whose breakfast timing (first eating occasion of the day) was 07:00-09:00, those who broke fast after 09:00 had an aHR for T2DM of 0.71 (95% CI: 0.51, 0.99). This association was present in participants with impaired fasting glucose at baseline (aHR: 0.61; 95% CI: 0.39, 0.95) but not in those without (aHR: 0.83; 95% CI: 0.50, 1.38). No associations between eating frequency or timing and T2DM were observed within other prespecified subgroups. CONCLUSIONS: Eating breakfast daily was not associated with either higher or lower risk of T2DM in this cohort of older adults, whereas a later (after 09:00) daily first eating occasion time was associated with lower T2DM risk in participants with impaired fasting glucose at baseline.This trial was registered at clinicaltrials.gov as NCT00005133.

Relationship between diet quality scores and the risk of frailty and mortality in adults across a wide age spectrum.

BACKGROUND: Beyond intakes of total energy and individual nutrient, eating patterns may influence health, and thereby the risk of adverse outcomes. How different diet measures relate to frailty-a general measure of increased vulnerability to unfavorable health outcomes-and mortality risk, and how this might vary across the life course, is not known. We investigated the associations of five dietary indices (Nutrition Index (NI), the energy-density Dietary Inflammatory Index (E-DII™), Healthy Eating Index-2015 (HEI-2015), Mediterranean Diet Score (MDS), and Dietary Approaches to Stop Hypertension (DASH)) with frailty and mortality. METHODS: We included 15,249 participants aged ≥ 20 years from the 2007-2012 cohorts of the National Health and Nutrition Examination Survey (NHANES). The NI combined 31 nutrition-related deficits. The E-DII is a literature-derived dietary index associated with inflammation. The HEI-2015 assesses adherence to the Dietary Guidelines of Americans. The MDS represents adherence to the traditional Mediterranean diet. DASH combines macronutrients and micronutrients to prevent hypertension. Frailty was evaluated using a 36-item frailty index. Mortality status was ascertained up to December 31, 2015. RESULTS: Participants' mean age was 47.2 ± 16.7 years and 51.7% were women. After adjusting for age, sex, race, educational level, marital and employment status, smoking, BMI, and study cohort, higher NI and E-DII scores and lower HEI-2015, MDS, and DASH scores were individually significantly associated with frailty. All dietary scores were significantly associated with 8-year mortality risk after adjusting for basic covariates and frailty: NI (hazard ratio per 0.1 point, 1.15, 95%CI 1.10-1.21), E-DII (per 1 point, 1.05, 1.01-1.08), HEI-2015 (per 10 points, 0.93, 0.89-0.97), MDS (per 1 point, 0.94, 0.90-0.97), and DASH (per 1 point, 0.96, 0.93-0.99). The associations of E-DII, HEI-2015, and MDS scores with 8-year mortality risk persisted after additionally adjusting for NI. CONCLUSIONS: NI, E-DII, HEI-2015, MDS, and DASH scores are associated with frailty and 8-year mortality risk in adults across all ages. Nevertheless, their mechanisms and sensitivity to predict health outcomes may differ. Nutrition scores have the potential to include measures of both consumption and laboratory and physical measures of exposure.

Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men.

The capacity of HDLs to accept cholesterol effluxing from macrophages has been proposed as a new biomarker of HDLs' anti-atherogenic function. Whether cholesterol efflux capacity (CEC) is independent of HDL cholesterol (HDL-C) as a biomarker for coronary heart disease (CHD) risk in a generally healthy primary-prevention population remains unanswered. Therefore, in this nested case-control study, we simultaneously assessed CEC (using J774 cells) and plasma HDL-C levels as predictors of CHD in healthy middle-aged and older men not receiving treatment affecting blood lipid concentrations. We used risk-set sampling of participants free of disease at baseline from the Health Professionals Follow-Up Study, and matched cases (n = 701) to controls 1:1 for age, smoking, and blood sampling date. We applied conditional logistic regression models to calculate the multivariable relative risk and 95% CIs of CHD over 16 years of follow-up. CEC and HDL-C were correlated (r = 0.50, P < 0.0001). The risk (95% CI) of CHD per one SD higher CEC was 0.82 (0.71-0.96), but completely attenuated to 1.08 (0.85-1.37) with HDL-C in the model. The association per one SD between HDL-C and CHD (0.66; 0.58-0.76) was essentially unchanged (0.68; 0.53-0.88) after adjustment for CEC. These findings indicate that CEC's ability to predict CHD may not be independent of HDL-C in a cohort of generally healthy men.

Assessment of the burden of diseases and injuries attributable to risk factors in Canada from 1990 to 2016: an analysis of the Global Burden of Disease Study.

BACKGROUND: An understanding of the risk factors contributing to disease burden is critical for determining research priorities and informing national health policy. We aimed to identify the risk factor trends in Canada. METHODS: As part of the Global Burden of Disease (GBD) study (1990-2016), we conducted an analysis of country-level estimates for Canada to assess the burden of diseases and injuries attributable to risk factors. For both 1990 and 2016, metabolic, environmental and behavioural risk factors were ranked according to their contribution to disability-adjusted life years (healthy years of life lost), total deaths and years lived with disability. RESULTS: In 2016, the risk factors accounting for the largest percentage of disability-adjusted life years in Canada were (1) tobacco, (2) diet, (3) high body mass index, (4) high fasting plasma glucose, (5) high systolic blood pressure, (6) alcohol and drug use, (7) occupational risks, (8) high total cholesterol, (9) impaired kidney function and (10) air pollution. Risk factor rankings remained similar from 1990 to 2016 despite some substantial declines in burden, including a 47% (± 3%) decline in the age-standardized disability-adjusted life years rate attributable to tobacco since 1990. Risk factors with an increasing contribution to disability-adjusted life years rates from 1990 to 2016 included high body mass index, high fasting plasma glucose and alcohol and drug use. INTERPRETATION: Metabolic and behavioural risk factors, including modifiable factors such as tobacco use and diet, remain the leading risk factors contributing to the burden of diseases and injuries in Canada. This work identifies priorities and targets for reducing premature death and disability burden in Canada.

Global Burden of Disease Study trends for Canada from 1990 to 2016.

BACKGROUND: The Global Burden of Disease Study represents a large and systematic effort to describe the burden of diseases and injuries over the past 3 decades. We aimed to summarize the Canadian data on burden of diseases and injuries. METHODS: We summarized data from the 2016 iteration of the Global Burden of Disease Study to provide current (2016) and historical estimates for all-cause and cause-specific diseases and injuries using mortality, years of life lost, years lived with disability and disability-adjusted life years in Canada. We also compared changes in life expectancy and health-adjusted life expectancy between Canada and 21 countries with a high sociodemographic index. RESULTS: In 2016, leading causes of all-age disability-adjusted life years were neoplasms, cardiovascular diseases, musculoskeletal diseases, and mental and substance use disorders, which together accounted for about 56% of disability-adjusted life years. Between 2006 and 2016, the rate of all-cause age-standardized years of life lost declined by 12%, while the rate of all-cause age-standardized years lived with disability remained relatively stable (+1%), and the rate of all-cause age-standardized disability-adjusted life year declined by 5%. In 2016, Canada aligned with countries that have a similar high sociodemographic index in terms of life expectancy (82 yr) and health-adjusted life expectancy (71 yr). INTERPRETATION: The patterns of mortality and morbidity in Canada reflect an aging population and improving patterns of population health. If current trends continue, Canada will continue to face challenges of increasing population morbidity and disability alongside decreasing premature mortality.

The Impact of Exclusive Enteral Nutrition (EEN) on the Gut Microbiome in Crohn's Disease: A Review.

Crohn's disease (CD), a form of inflammatory bowel disease (IBD), is thought to arise from a complex interaction of genetics, the gut microbiome, and environmental factors, such as diet. There is clear evidence that dietary intervention is successful in the treatment of CD-exclusive enteral nutrition (EEN) is able to induce remission in up to 80% of CD patients. While the mechanism of action of EEN is not clear, EEN is known to cause profound changes in the gut microbiome. Understanding how EEN modifies the gut microbiome to induce remission could provide insight into CD etiopathogenesis and aid the development of microbiome-targeted interventions to guide ongoing dietary therapy to sustain remission. This review includes current literature on changes in composition and function of the gut microbiome associated with EEN treatment in CD patients.

Changes in Intake of Fruits and Vegetables and Weight Change in United States Men and Women Followed for Up to 24 Years: Analysis from Three Prospective Cohort Studies.

BACKGROUND: Current dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, some particular fruits and vegetables may be more or less beneficial for maintaining or achieving a healthy weight. We hypothesized that greater consumption of fruits and vegetables with a higher fiber content or lower glycemic load would be more strongly associated with a healthy weight. METHODS AND FINDINGS: We examined the association between change in intake of specific fruits and vegetables and change in weight in three large, prospective cohorts of 133,468 United States men and women. From 1986 to 2010, these associations were examined within multiple 4-y time intervals, adjusting for simultaneous changes in other lifestyle factors, including other aspects of diet, smoking status, and physical activity. Results were combined using a random effects meta-analysis. Increased intake of fruits was inversely associated with 4-y weight change: total fruits -0.53 lb per daily serving (95% CI -0.61, -0.44), berries -1.11 lb (95% CI -1.45, -0.78), and apples/pears -1.24 lb (95% CI -1.62, -0.86). Increased intake of several vegetables was also inversely associated with weight change: total vegetables -0.25 lb per daily serving (95% CI -0.35, -0.14), tofu/soy -2.47 lb (95% CI, -3.09 to -1.85 lb) and cauliflower -1.37 lb (95% CI -2.27, -0.47). On the other hand, increased intake of starchy vegetables, including corn, peas, and potatoes, was associated with weight gain. Vegetables having both higher fiber and lower glycemic load were more strongly inversely associated with weight change compared with lower-fiber, higher-glycemic-load vegetables (p < 0.0001). Despite the measurement of key confounders in our analyses, the potential for residual confounding cannot be ruled out, and although our food frequency questionnaire specified portion size, the assessment of diet using any method will have measurement error. CONCLUSIONS: Increased consumption of fruits and non-starchy vegetables is inversely associated with weight change, with important differences by type suggesting that other characteristics of these foods influence the magnitude of their association with weight change.

Novel metabolic biomarkers of cardiovascular disease.

Coronary heart disease (CHD) accounts for one in every six deaths in US individuals. Great advances have been made in identifying important risk factors for CHD, such as hypertension, diabetes mellitus, smoking and hypercholesterolaemia, which have led to major developments in therapy. In particular, statins represent one of the greatest successes in the prevention of CHD. While these standard risk factors are important, an obvious opportunity exists to take advantage of ongoing scientific research to better risk-stratify individuals and to identify new treatment targets. In this Review, we summarize ongoing scientific research in a number of metabolic molecules or features, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. We evaluate the current state of the research and the strength of evidence supporting each emerging biomarker. We also discuss whether the associations with CHD are strong and consistent enough to improve current risk stratification metrics, and whether these markers enhance our understanding of the underlying biology of CHD and thus point towards new treatment options.

Fried-food consumption and risk of type 2 diabetes and coronary artery disease: a prospective study in 2 cohorts of US women and men.

BACKGROUND: Through the processes of oxidation, polymerization, and hydrogenation, the cooking method of frying modifies both foods and their frying medium. However, it remains unknown whether the frequent consumption of fried foods is related to long-term cardiometabolic health. OBJECTIVE: We examined fried-food consumption and risk of developing incident type 2 diabetes (T2D) or coronary artery disease (CAD). DESIGN: Fried-food consumption was assessed by using a questionnaire in 70,842 women from the Nurses' Health Study (1984-2010) and 40,789 men from the Health Professionals Follow-Up Study (1986-2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Time-dependent Cox proportional hazards models were used to estimate RRs and 95% CIs for T2D and CAD adjusted for demographic, diet, lifestyle, and other cardiometabolic risk factors. Results were pooled by using an inverse variance-weighted random-effects meta-analysis. RESULTS: We documented 10,323 incident T2D cases and 5778 incident CAD cases. Multivariate-adjusted RRs (95% CIs) for individuals who consumed fried foods <1, 1-3, 4-6, or ≥7 times/wk were 1.00 (reference), 1.15 (0.97, 1.35), 1.39 (1.30, 1.49), and 1.55 (1.32, 1.83), respectively, for T2D and 1.00 (reference), 1.06 (0.98, 1.15), 1.23 (1.14, 1.33), and 1.21 (1.06, 1.39), respectively, for CAD. Associations were largely attenuated when we further controlled for biennially updated hypertension, hypercholesterolemia, and body mass index. CONCLUSIONS: Frequent fried-food consumption was significantly associated with risk of incident T2D and moderately with incident CAD, and these associations were largely mediated by body weight and comorbid hypertension and hypercholesterolemia.

Prospective study of breakfast eating and incident coronary heart disease in a cohort of male US health professionals.

BACKGROUND: Among adults, skipping meals is associated with excess body weight, hypertension, insulin resistance, and elevated fasting lipid concentrations. However, it remains unknown whether specific eating habits regardless of dietary composition influence coronary heart disease (CHD) risk. The objective of this study was to prospectively examine eating habits and risk of CHD. METHODS AND RESULTS: Eating habits, including breakfast eating, were assessed in 1992 in 26 902 American men 45 to 82 years of age from the Health Professionals Follow-up Study who were free of cardiovascular disease and cancer. During 16 years of follow-up, 1527 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for CHD, adjusted for demographic, diet, lifestyle, and other CHD risk factors. Men who skipped breakfast had a 27% higher risk of CHD compared with men who did not (relative risk, 1.27; 95% confidence interval, 1.06-1.53). Compared with men who did not eat late at night, those who ate late at night had a 55% higher CHD risk (relative risk, 1.55; 95% confidence interval, 1.05-2.29). These associations were mediated by body mass index, hypertension, hypercholesterolemia, and diabetes mellitus. No association was observed between eating frequency (times per day) and risk of CHD. CONCLUSIONS: Eating breakfast was associated with significantly lower CHD risk in this cohort of male health professionals.

Eating patterns and type 2 diabetes risk in older women: breakfast consumption and eating frequency.

BACKGROUND: Little is known about the association between eating patterns and type 2 diabetes (T2D) risk in women. OBJECTIVE: The objective was to examine prospectively associations between regular breakfast consumption, eating frequency, and T2D risk in women. DESIGN: Eating pattern was assessed in 2002 in a cohort of 46,289 US women in the Nurses' Health Study who were free of T2D, cardiovascular disease, or cancer and were followed for 6 y. We used Cox proportional hazards analysis to evaluate associations with incident T2D. RESULTS: We documented 1560 T2D cases during follow-up. After adjustment for known risk factors for T2D-except for body mass index (BMI), a potential mediator-women who consumed breakfast irregularly (0-6 times/wk) were at higher risk of T2D than were women who consumed breakfast daily (RR: 1.28; 95% CI: 1.14, 1.44). This association was moderately attenuated after adjustment for BMI (RR: 1.20; 95% CI: 1.07, 1.35). In comparison with women who ate 3 times/d, the RRs were 1.09 (0.84, 1.41) for women who ate 1-2 times/d, 1.13 (1.00, 1.27) for women who ate 4-5 times/d, and 0.99 (0.81, 1.21) for women who ate ≥6 times/d. Among irregular breakfast consumers, women with a higher eating frequency (≥4 times/d) had a significantly greater T2D risk (RR: 1.47; 95% CI: 1.23, 1.75) than did women who consumed breakfast daily and ate 1-3 times/d. Adjustment for BMI attenuated this association (RR: 1.24; 95% CI: 1.04, 1.48). CONCLUSION: Irregular breakfast consumption was associated with a higher T2D risk in women, which was partially but not entirely mediated by BMI.

Effect of fish oil on circulating adiponectin: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Seafood long-chain polyunsaturated omega-3 fatty acids (n-3 PUFAs) improve insulin sensitivity in animal experiments, but findings remain inconsistent in humans. Adiponectin is a robust marker for insulin sensitivity and adipocyte function. Whether n-3 PUFAs affect adiponectin in humans is unknown. OBJECTIVE: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the objective of the study was to perform a systematic review and meta-analysis of randomized, placebo-controlled clinical trials (RCTs) to determine the effect of n-3 PUFA consumption on circulating adiponectin in humans. DATA SOURCES: MEDLINE, EMBASE, CABI (CAB abstracts), Cochrane Central Registry of Controlled Trials, ClinicalTrials.gov, SIGLE, and Faculty of 1000 were searched through to June 2012, supplemented with author contact and reference list searches. STUDY SELECTION: RCTs of either fish oil supplementation or isocaloric fish meal feeding that evaluated adiponectin as an outcome were selected for the study. DATA EXTRACTION: Two investigators independently extracted the data. Effect estimates were pooled using inverse-variance weighted, random-effects meta-analysis. Heterogeneity was assessed by the I(2) and Q statistic. Prespecified sources of heterogeneity were investigated by meta-regression. Publication bias was assessed using funnel plots and Egger's test. DATA SYNTHESIS: Of 110 studies, 14 RCTs met inclusion criteria. Fourteen trial arms evaluated fish oil (fish oil, n = 682; placebo, n = 641). Fish oil increased adiponectin by 0.37 µg/mL [95% confidence interval (CI) 0.07; 0.67, P = .02]. Although effects in 11 of 14 trials were 0 or greater, statistical heterogeneity was evident (I(2) = 72.9%), unexplained by n-3 PUFA dose or duration, study quality score, study location, or baseline body mass index (meta-regression P > .05 each). The funnel plot was asymmetric in favor of smaller trials with greater effects (Egger's P = .11); the fill-and-trim method suggested a theoretical pooled effect of 0.18 µg/mL (95% CI -0.15; +0.52, P = .28). Only 2 trial arms evaluated fish feeding (n = 136 intervention and 68 control subjects), for which the pooled effect on adiponectin was not statistically significant (-0.01 µg/mL, 95% CI -0.65; 0.64, P = 0.99), although CIs were broad due to the small number of subjects. CONCLUSIONS: In placebo-controlled RCTs, fish oil moderately increases circulating adiponectin, although with unexplained heterogeneity as well as potential publication bias. These findings provide no evidence for harm and support possible benefits of n-3 PUFA consumption on insulin sensitivity and adipocyte function.

Hemoglobin a1c is associated with increased risk of incident coronary heart disease among apparently healthy, nondiabetic men and women.

BACKGROUND: Hemoglobin A1c (HbA1c), a time-integrated marker of glycemic control, predicts risk of coronary heart disease (CHD) among diabetics. Few studies have examined HbA1c and risk of CHD among women and men without clinically elevated levels or previously diagnosed diabetes. METHODS AND RESULTS: We conducted parallel nested case-control studies among women (Nurses' Health Study) and men (Health Professionals Follow-up Study). During 14 and 10 years of follow-up, 468 women and 454 men developed incident nonfatal myocardial infarction (MI) and fatal CHD. Controls were matched 2:1 based on age, smoking, and date of blood draw. For these analyses, participants with a history of diabetes or HbA1c levels ≥6.5% at baseline were excluded. Compared with HbA1c of 5.0% to <5.5%, those with an HbA1c of 6.0% to <6.5% had a multivariable-adjusted relative risk (RR) of CHD of 1.90 (95% CI 1.11 to 3.25) in women and 1.81 (95% CI 1.09 to 3.03) in men. The pooled RR of CHD was 1.29 (95% CI 1.11 to 1.50) for every 0.5%-increment increase in HbA1c levels and 1.67 (95% CI 1.23 to 2.25) for every 1%-increment increase, with the risk plateauing around 5.0%. Furthermore, participants with HbA1c levels between 6.0% and <6.5% and C-reactive protein levels >3.0 mg/L had a 2.5-fold higher risk of CHD compared with participants in the lowest categories of both biomarkers. CONCLUSIONS: Our findings suggest that HbA1c is associated with CHD risk among apparently healthy, nondiabetic women and men and may be an important early clinical marker of disease risk.

Nutrigenetics and nutrigenomics: viewpoints on the current status and applications in nutrition research and practice.

Nutrigenetics and nutrigenomics hold much promise for providing better nutritional advice to the public generally, genetic subgroups and individuals. Because nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and ever new 'omic' technologies, it is often difficult, even for educated professionals, to appreciate their relevance to the practice of preventive approaches for optimising health, delaying onset of disease and diminishing its severity. This review discusses (i) the basic concepts, technical terms and technology involved in nutrigenetics and nutrigenomics; (ii) how this emerging knowledge can be applied to optimise health, prevent and treat diseases; (iii) how to read, understand and interpret nutrigenetic and nutrigenomic research results, and (iv) how this knowledge may potentially transform nutrition and dietetic practice, and the implications of such a transformation. This is in effect an up-to-date overview of the various aspects of nutrigenetics and nutrigenomics relevant to health practitioners who are seeking a better understanding of this new frontier in nutrition research and its potential application to dietetic practice.

Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid.

BACKGROUND/AIMS: Vitamin C transporter proteins SVCT1 and SVCT2 are required for the absorption and transport of vitamin C in humans. This study aims to determine whether common SVCT genotypes modify the association between dietary vitamin C and serum ascorbic acid. METHODS: Non-smoking men and women (n=1,046) aged 20-29 were participants of the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for two SVCT1 (rs4257763 and rs6596473) and two SVCT2 (rs6139591 and rs2681116) polymorphisms. RESULTS: No diet-gene interactions were observed for the vitamin C transporter polymorphisms, however, the average (mean+/-SE) serum ascorbic acid concentrations differed between rs4257763 genotypes (GG: 24.4+/-1.3, GA: 26.8+/-1.1, AA: 29.7+/-1.4 micromol/l; p=0.002). For this polymorphism, the correlation between dietary vitamin C and serum ascorbic acid was only significant in subjects with a G allele. The SVCT2 polymorphisms also appeared to modify the strength of the diet-serum correlation. CONCLUSIONS: Our findings demonstrate that genetic variation in SVCT1 can influence serum ascorbic acid concentrations and that SVCT1 and SVCT2 genotypes modify the strength of the correlation between dietary vitamin C and serum ascorbic acid.

Late dietary intervention limits benefits of soy protein or flax oil in experimental polycystic kidney disease.

BACKGROUND/AIMS: Dietary soy protein and flax oil retard kidney disease progression when initiated in the early stages of disease in several experimental models, including the Han:SPRD-cy rat. However, individuals with kidney disease often do not become aware of their condition until injury to the kidney is extensive. The objective of this study was to determine whether initiating these interventions in established disease would alter further progression of renal injury. METHODS: Two-month-old adult male Han:SPRD-cy rats were given either a flax oil diet (7% flax oil), a soy protein diet (20% soy protein) or a control diet (7% corn oil, 20% casein) for 4 months. Renal disease progression was assessed by examining morphological, immunohistochemical and biochemical parameters. RESULTS: Compared to controls, there was 21-24% less staining of proliferating cells, 21-24% less oxidative damage and 13-15% less renal inflammation in kidneys from rats given dietary soy protein and flax oil. Renal cystic growth and fibrosis and serum creatinine levels were not altered by these dietary treatments. CONCLUSIONS: Late intervention with dietary soy protein and flax oil reduces some disease-associated pathologies in established renal disease in Han:SPRD-cy rats. The potential benefits of the antioxidant and anti-inflammatory effects on ultimate renal disease outcome in the long term remains to be determined.