See corresponding editorial on page 497.
Meta-analysis of prospective cohort studies evaluating the association
of saturated fat with cardiovascular disease
Patty W Siri-Tarino, Qi Sun, Frank B Hu, and Ronald M Krauss
A reduction in dietary saturated fat has generally
been thought to improve cardiovascular health.
The objective of this meta-analysis was to summarize
the evidence related to the association of dietary saturated fat with
risk of coronary heart disease (CHD), stroke, and cardiovascular
disease (CVD; CHD inclusive of stroke) in prospective epidemio-
Twenty-one studies identiﬁed by searching MEDLINE and
EMBASE databases and secondary referencing qualiﬁed for inclu-
sion in this study. A random-effects model was used to derive
composite relative risk estimates for CHD, stroke, and CVD.
During 5–23 y of follow-up of 347,747 subjects, 11,006
developed CHD or stroke. Intake of saturated fat was not associated
with an increased risk of CHD, stroke, or CVD. The pooled relative
risk estimates that compared extreme quantiles of saturated fat in-
take were 1.07 (95% CI: 0.96, 1.19;
= 0.22) for CHD, 0.81 (95%
CI: 0.62, 1.05;
= 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11;
= 0.95) for CVD. Consideration of age, sex, and study quality did
not change the results.
A meta-analysis of prospective epidemiologic studies
showed that there is no signiﬁcant evidence for concluding that
dietary saturated fat is associated with an increased risk of CHD
or CVD. More data are needed to elucidate whether CVD risks are
likely to be inﬂuenced by the speciﬁc nutrients used to replace
Am J Clin Nutr
Early animal studies showed that high dietary saturated fat and
cholesterol intakes led to increased plasma cholesterol concen-
trations as well as atherosclerotic lesions (1). These ﬁndings were
supported by associations in humans in which dietary saturated
fat correlated with coronary heart disease (CHD) risk (2, 3). More
recent epidemiologic studies have shown positive (4–10), inverse
(11, 12), or no (4, 13–18) associations of dietary saturated fat with
CVD morbidity and/or mortality.
A limited number of randomized clinical interventions have
been conducted that have evaluated the effects of saturated fat on
risk of CVD. Whereas some studies have shown beneﬁcial effects
of reduced dietary saturated fat (19–21), others have shown no
effects of such diets on CVD risk (22, 23). The studies that
showed beneﬁcial effects of diets reduced in saturated fat
replaced saturated fat with polyunsaturated fat, with the impli-
cation that the CVD beneﬁt observed could have been due to an
increase in polyunsaturated fat or in the ratio of polyunsaturated
fat to saturated fat (P:S), a hypothesis supported by a recent
pooling analysis conducted by Jakobsen et al (24).