Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies

The BMJ

Aug 2015

DOI: 10.1136/bmj.h3978

Citations:1266

Influential Citations:31

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Design: Systematic review and meta-analysis of observational data; Participants: adults from general populations across the US, UK, Japan, Sweden, Israel, Finland, Denmark, Canada, China, Greece, and Australia; baseline health: generally healthy; Study designs: primarily prospective cohort studies used for quantitative synthesis, with supplementary analyses including retrospective case-control and nested case-control studies; Exposures: intake of saturated fat and trans fats measured by self-report or biomarkers; Outcomes: all-cause mortality, cardiovascular disease (including CHD) mortality, total CHD, ischemic stroke, and type 2 diabetes.

Results

Saturated fat intake showed no significant associations with all-cause mortality (RR 0.99; 95% CI 0.91–1.09), CVD mortality (0.97; 0.84–1.12), total CHD (1.06; 0.95–1.17), ischemic stroke (1.02; 0.90–1.15), or type 2 diabetes (0.95; 0.88–1.03); CHD mortality lack of association not convincing (1.15; 0.97–1.36; P=0.10). Total trans fats were associated with higher risk of all-cause mortality (RR 1.34; 1.16–1.56), CHD mortality (1.28; 1.09–1.50), and total CHD (1.21; 1.10–1.33); ischemic stroke (1.07; 0.88–1.28) and type 2 diabetes (1.10; 0.95–1.27) not clearly linked. Industrial trans fats showed stronger associations with CHD mortality (1.18; 1.04–1.33) and CHD (1.42; 1.05–1.92); ruminant trans fats showed no clear associations; trans-palmitoleic acid (dairy-derived trans fat) inversely associated with type 2 diabetes (0.58; 0.46–0.74). Certainty: saturated fat associations very low; trans fat associations with CHD outcomes moderate, and very low to low for other outcomes. Conclusions: Saturated fats do not show robust associations with mortality or major cardiometabolic outcomes in healthy adults; trans fats—especially industrial trans fats—are associated with higher risk of mortality and CHD. Dietary guidelines should carefully consider replacement nutrients and acknowledge limitations of observational evidence; further research is needed, particularly on substitution effects and distinguishing industrial vs ruminant trans fats.

Limitations

Observational design limits causal inference; very low certainty for saturated fat associations due to imprecision and inconsistency; heterogeneity and imprecision across studies; measurement error and misclassification of fat exposures (dietary self-report and biomarkers); residual confounding and potential overadjustment for intermediates; inconsistent classification of trans fats (industrial vs ruminant) and limited data for some outcomes; substitution effects and dose–response relations could not be robustly quantified; some analyses could not be pooled due to incompatible effect measures; Seven Countries Study data not included in pooled analyses.

Abstract

Objective To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015, supplemented by bibliographies of retrieved articles and previous reviews. Eligibility criteria for selecting studies Observational studies reporting associations of saturated fat and/or trans unsaturated fat (total, industrially manufactured, or from ruminant animals) with all cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. Data extraction and synthesis Two reviewers independently extracted data and assessed study risks of bias. Multivariable relative risks were pooled. Heterogeneity was assessed and quantified. Potential publication bias was assessed and subgroup analyses were undertaken. The GRADE approach was used to evaluate quality of evidence and certainty of conclusions. Results For saturated fat, three to 12 prospective cohort studies for each association were pooled (five to 17 comparisons with 90 501-339 090 participants). Saturated fat intake was not associated with all cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97, 0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to 1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10). For trans fats, one to six prospective cohort studies for each association were pooled (two to seven comparisons with 12 942-230 135 participants). Total trans fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27). Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18 (1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73 to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated fat and all outcomes was “very low.” The certainty of associations of trans fat with CHD outcomes was “moderate” and “very low” to “low” for other associations. Conclusions Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations. Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats. Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats. show less