de Souza · BMJ (Clinical research ed.) 2015 · systematic review and meta-analysis of prospective cohort studies · n=up to 12 prospective cohorts (339,090 participants) for saturated fat; up to 6 prospective cohorts (230,135 participants) for trans fat

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.

Cited 1441 times in the scientific literature.

Level 3 - non-randomized controlled study

Systematic review and meta-analysis of observational cohort studies

PubMed 26268692 · doi:10.1136/bmj.h3978 · record verified 2026-08-26

What was done

Systematic review and meta-analysis searching Medline, Embase, Cochrane Central Registry of Controlled Trials, Evidence-Based Medicine Reviews, and CINAHL up to May 1, 2015. Two reviewers independently extracted multivariable relative risks from prospective cohort studies examining associations of saturated fat and trans unsaturated fat with all-cause mortality, cardiovascular disease mortality, coronary heart disease (total and mortality), ischemic stroke, and type 2 diabetes. Risk of bias and heterogeneity were evaluated, and evidence certainty was graded using the GRADE approach.

What was found

For saturated fat (3 to 12 prospective cohorts per outcome, 90,501 to 339,090 participants), intake was not associated with all-cause mortality (relative risk 0.99, 95% confidence interval 0.91 to 1.09), cardiovascular disease mortality (0.97, 0.84 to 1.12), total coronary heart disease (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), with a non-significant association for coronary heart disease mortality (1.15, 0.97 to 1.36, P=0.10). GRADE certainty for saturated fat across all outcomes was very low. For total trans fat (1 to 6 prospective cohorts, 12,942 to 230,135 participants), intake was associated with all-cause mortality (1.34, 1.16 to 1.56), coronary heart disease mortality (1.28, 1.09 to 1.50), and total coronary heart disease (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 trans fats were associated with coronary heart disease mortality (1.18, 1.04 to 1.33) and total coronary heart disease (1.42, 1.05 to 1.92), whereas ruminant trans fats were not (1.01, 0.71 to 1.43 for mortality; 0.93, 0.73 to 1.18 for total CHD). Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes (0.58, 0.46 to 0.74). GRADE certainty was moderate for trans fat and coronary heart disease outcomes, and very low to low for other associations.

Why it matters

This review shows that observational evidence does not support an association between saturated fat intake and cardiovascular outcomes or mortality, while industrial trans fat intake clearly increases coronary heart disease risk and mortality.

Limits

The evidence is restricted to observational cohort studies subject to residual confounding, exposure measurement errors, and self-report dietary bias. Saturated fat analyses demonstrated heterogeneity and methodological limitations that reduced certainty to very low, and the abstract does not report specific isocaloric nutrient substitution analyses.

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