Person:

Mozaffarian, Dariush

Dietary and policy recommendations frequently focus on reducing saturated fatty acid consumption for improving cardiometabolic health, based largely on ecologic and animal studies. Recent advances in nutritional science now allow assessment of critical questions about health effects of saturated fatty acids (SFA). We reviewed the evidence from randomized controlled trials (RCTs) of lipid and non-lipid risk factors, prospective cohort studies of disease endpoints, and RCTs of disease endpoints for cardiometabolic effects of SFA consumption in humans, including whether effects vary depending on specific SFA chain-length; on the replacement nutrient; or on disease outcomes evaluated. Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid. However, insufficient evidence exists for different chain-length-specific effects on other risk pathways or, more importantly, disease endpoints. Based on consistent evidence from human studies, replacing SFA with polyunsaturated fat modestly lowers coronary heart disease risk, with ~10% risk reduction for a 5% energy substitution; whereas replacing SFA with carbohydrate has no benefit and replacing SFA with monounsaturated fat has uncertain effects. Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects, highlighting a need for further investigation of these endpoints. Public health emphasis on reducing SFA consumption without considering the replacement nutrient or, more importantly, the many other food-based risk factors for cardiometabolic disease is unlikely to produce substantial intended benefits.

Background: Reduced saturated fat (SFA) consumption is recommended to reduce coronary heart disease (CHD), but there is an absence of strong supporting evidence from randomized controlled trials (RCTs) of clinical CHD events and few guidelines focus on any specific replacement nutrient. Additionally, some public health groups recommend lowering or limiting polyunsaturated fat (PUFA) consumption, a major potential replacement for SFA. Methods and Findings: We systematically investigated and quantified the effects of increased PUFA consumption, as a replacement for SFA, on CHD endpoints in RCTs. RCTs were identified by systematic searches of multiple online databases through June 2009, grey literature sources, hand-searching related articles and citations, and direct contacts with experts to identify potentially unpublished trials. Studies were included if they randomized participants to increased PUFA for at least 1 year without major concomitant interventions, had an appropriate control group, and reported incidence of CHD (myocardial infarction and/or cardiac death). Inclusions/exclusions were adjudicated and data were extracted independently and in duplicate by two investigators and included population characteristics, control and intervention diets, follow-up duration, types of events, risk ratios, and SEs. Pooled effects were calculated using inverse-variance-weighted random effects meta-analysis. From 346 identified abstracts, eight trials met inclusion criteria, totaling 13,614 participants with 1,042 CHD events. Average weighted PUFA consumption was 14.9% energy (range 8.0%–20.7%) in intervention groups versus 5.0% energy (range 4.0%–6.4%) in controls. The overall pooled risk reduction was 19% (RR = 0.81, 95% confidence interval [CI] 0.70–0.95, p = 0.008), corresponding to 10% reduced CHD risk (RR = 0.90, 95% CI = 0.83–0.97) for each 5% energy of increased PUFA, without evidence for statistical heterogeneity (Q-statistic p = 0.13; I2 = 37%). Meta-regression identified study duration as an independent determinant of risk reduction (p = 0.017), with studies of longer duration showing greater benefits. Conclusions: These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD.

Background: Few studies have examined the relationship of α‐linolenic acid (ALA 18:3n‐3), an intermediate‐chain essential n‐3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF). Methods and Results: The study population included participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar. Conclusions: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.

Background: Accurate data on dietary habits are crucial for understanding impacts on disease and informing policy priorities. Nation-specific food balance sheets from the United Nations FAO provided the only available global dietary estimates but with uncertain validity. Objectives: We investigated how FAO estimates compared with nationally representative, individual-based dietary surveys from the Global Dietary Database (GDD) and developed calibration equations to improve the validity of FAO data to estimate dietary intakes. Design: FAO estimates were matched to GDD data for 113 countries across the following 9 major dietary metrics for 30 y of data (1980–2009): fruit, vegetables, beans and legumes, nuts and seeds, whole grains, red and processed meats, fish and seafood, milk, and total energy. Both absolute and percentage differences in FAO and GDD mean estimates were evaluated. Linear regression was used to evaluate whether FAO estimates predicted GDD dietary intakes and whether this prediction varied according to age, sex, region, and time. Calibration equations were developed to adjust FAO estimates to approximate national dietary surveys validated by using randomly split data sets. Results: For most food groups, FAO estimates substantially overestimated individual-based dietary intakes by 74.5% (vegetables) and 270% (whole grains) while underestimating beans and legumes (−50%) and nuts and seeds (−29%) (P < 0.05 for each). In multivariate regressions, these overestimations and underestimations for each dietary factor further varied by age, sex, region, and time (P < 0.001 for each). Split–data set calibration models, which accounted for country-level covariates and other sources of heterogeneity, effectively adjusted FAO estimates to approximate estimates from national survey data (r = 0.47–0.80) with small SEs of prediction (generally 1–5 g/d). Conclusions: For all food groups and total energy, FAO estimates substantially exceeded or underestimated individual-based national surveys of individual intakes with significant variation depending on age, sex, region, and time. Calibration models effectively adjusted the comprehensive, widely accessible FAO data to facilitate a more-accurate estimation of individual-level dietary intakes nationally and by age and sex.

Background: While self‐reported trans–fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t‐16:1n9, total t‐18:1, and cis/trans‐(c/t‐), t/c‐ and t/t‐18:2) and cardiovascular disease (CVD) or total mortality are not well established. Methods and Results: We evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non‐CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person‐years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t‐18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, P‐trend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, P‐trend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, P‐trend=0.01). t/c‐18:2 was positively related to total mortality (HR=1.19, P‐trend=0.05), total CHD (HR=1.67, P‐trend=0.002), and nonfatal CHD (HR=2.06, P‐trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t‐16:1n9 nor t‐18:1 was significantly associated with total mortality or CVD, nor was c/t‐18:2 if we excluded early cases. Conclusions: Among circulating TFAs, t/t‐18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c‐18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t‐18:2 isomers.