Guidelines advocate changes in fatty acid consumption to promote cardiovascular health. To summarize evidence about associations between fatty acids and coronary disease. MEDLINE, Science Citation Index, and Cochrane Central Register of Controlled Trials through July 2013. Prospective, observational studies and randomized, controlled trials. Investigators extracted data about study characteristics and assessed study biases. There were 32 observational studies (512 420 participants) of fatty acids from dietary intake; 17 observational studies (25 721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (105 085 participants) of fatty acid supplementation. In observational studies, relative risks for coronary disease were 1.03 (95% CI, 0.98 to 1.07) for saturated, 1.00 (CI, 0.91 to 1.10) for monounsaturated, 0.87 (CI, 0.78 to 0.97) for long-chain ω-3 polyunsaturated, 0.98 (CI, 0.90 to 1.06) for ω-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty acids when the top and bottom thirds of baseline dietary fatty acid intake were compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86 to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to 1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the associations among individual circulating fatty acids and coronary disease. In randomized, controlled trials, relative risks for coronary disease were 0.97 (CI, 0.69 to 1.36) for α-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain ω-3 polyunsaturated, and 0.86 (CI, 0.69 to 1.07) for ω-6 polyunsaturated fatty acid supplementations. Potential biases from preferential publication and selective reporting. Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats. British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.

Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances. Design Systematic review and meta-analysis of observational studies and randomised controlled trials. Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. Study selection Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes. Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. Results In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements_. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D₃ supplementation and 1.04 (0.97 to 1.11) for vitamin D₂ supplementation_. The effects observed for vitamin D₃ supplementation remained unchanged when grouped by various characteristics. However, for vitamin D₂ supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D₃ significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D₃ and D₂ have different effects on mortality risk.

Objective To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention. Design Systematic review and meta-analysis. Data sources Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. Eligibility criteria Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible. Results 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups. Conclusions Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.

The hypothesis of ‘metabolically healthy obesity’ implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study. We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study (‘EPIC-CVD’). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction (‘unhealthy’) as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses. Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of ‘metabolically healthy obesity’, encouraging population-wide strategies to tackle obesity.

Background: Evidence for the dietary determinants of obesity in children is limited. Objective: The objective was to identify a dietary pattern that explained dietary energy density (DED), fiber density (FD), and percentage of energy intake from fat and analyze its relation to fatness in children. Design: The subjects were 521 (at ages 5 and 9 y) and 682 (at ages 7 and 9 y) children participating in the Avon Longitudinal Study of Parents and Children. Diet was assessed with the use of 3-d diet diaries at ages 5 and 7 y. Reduced rank regression derived a dietary pattern with the use of DED, fiber, and fat intake as intermediate variables. Fat mass was measured at age 9 y with the use of dual-energy X-ray absorptiometry. Fat mass index (FMI) was calculated, and excess adiposity was defined (as the top quintile of logFMI). Results: Pattern score at ages 5 and 7 y was correlated with DED (r = 0.8), FD (r = −0.7), and percentage of energy intake from fat (r = 0.5). An increase of 1 SD of pattern score at ages 5 and 7 y, respectively, was associated with a 0.15-kg (95% CI: −0.1, 0.45 kg) and a 0.28-kg (95% CI: 0.05, 0.53 kg) higher fat mass at age 9 y, after controlling for confounders. The adjusted odds of excess adiposity at age 9 y for children in quintile 5 compared with quintile 1 of dietary pattern score at ages 5 and 7 y, respectively, were 2.52 (95% CI: 1.13, 6.08) and 4.18 (95% CI: 2.07, 9.38). Conclusion: An energy-dense, low-fiber, high-fat diet is associated with higher fat mass and greater odds of excess adiposity in childhood.