Reducing saturated fat decreases mortality in high-risk individuals

1. In this systematic review, reducing intake of saturated fatty acids (SFAs) showed possible benefit for mortality, non-fatal myocardial infarction (MI), and stroke, but only in individuals with high baseline cardiovascular risk.

2. Reducing SFA intake was associated with decreased levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C).

Evidence Rating Level: 1 (Excellent)

Study Rundown: Modifiable risk factors critical to atherosclerotic cardiovascular disease include high LDL-C levels. Decades of research show that dietary fat composition significantly affects total and LDL-C, particularly the balance between saturated fatty acids (SFAs) and vegetable polyunsaturated fatty acids (PUFAs). Most studies on lowering and replacing SFA are based on observational analyses and do not establish independent associations with cardiovascular or mortality outcomes. This systematic review of seventeen randomized controlled trials (RCTs) aimed to determine the effect of reducing and replacing dietary SFA on cholesterol, mortality, and major cardiovascular events. Lower SFA intake was associated with significant reductions in total cholesterol and LDL-C compared with higher SFA intake. Reducing SFA may also influence all-cause and cardiovascular mortality, nonfatal myocardial infarction, and stroke in individuals at high cardiovascular risk, whereas effects in those at low cardiovascular risk were minimal. The study’s generalizability is limited by heterogeneity in follow-up duration, dietary fat reduction or replacement strategies, SFA intake levels, and outcome measures across trials, as well as a lack of trials examining replacement with protein and a limited number of SFA-replacement studies overall. Nevertheless, the findings suggest that lowering dietary SFA can reduce cholesterol levels and may provide clinically meaningful benefits in reducing mortality, nonfatal myocardial infarction, and stroke among individuals with elevated cardiovascular risk.

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Relevant Reading: Reduction in saturated fat intake for cardiovascular disease

In-Depth [systematic review and meta-analysis]: This systematic review and meta-analysis evaluated the effect of reducing and replacing dietary saturated fatty acids (SFA) on cholesterol, mortality, and major cardiovascular events in randomized controlled trials (RCTs). Trials were identified from MEDLINE, EMBASE, Cochrane Central, ClinicalTrials.gov, and the WHO International Clinical Trials Registry up to July 2025. Eligible trials included adults aged ≥18 years, with or without cardiometabolic conditions, randomized to interventions reducing SFA intake versus higher-SFA controls. Interventions included dietary advice, modified foods, or supplements. Trials with acutely ill, pregnant, breastfeeding participants, or those with >20% unrelated chronic disease were excluded. Outcomes were all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction (MI), stroke, total cholesterol, and LDL-C. Seventeen RCTs were included (60–48,853 participants; mean age 46–66 years). SFA was replaced primarily with PUFA (11 trials), carbohydrate (4), or monounsaturated fats (1); no trials replaced SFA with protein. Analysis from 14 RCTs (9,795 participants) showed lower SFA intake reduced total cholesterol (mean difference [MD], -0.34 mmol/L; 95% confidence interval [CI], -0.53 to -0.16; MD, -13.1 mg/dL; 95% CI, -20.5 to -6.2). Replacing SFA with PUFA (10 RCTs, 6,568 participants) produced larger reductions (MD -0.44 mmol/L; 95% CI -0.65 to -0.23; MD, -17.0 mg/dL; 95% CI, -25.1 to -8.9). LDL-C was reduced in 6 RCTs (3,630 participants) by MD -0.15 mmol/L (95% CI, -0.27 to -0.02); MD, -5.8 mg/dL; 95% CI, -10.4 to -0.8). For all-cause mortality (13 RCTs, 65,520 participants), lower SFA intake yielded a risk ratio of 0.96 (95% CI, 0.88 to 1.06), corresponding to 6 fewer deaths per 1,000 over 5 years in high-risk participants. Cardiovascular mortality, non-fatal MI, and stroke showed protective effects mainly in high-risk groups, with replacement by PUFA having the largest benefit. Overall, reducing dietary SFA lowers total cholesterol and LDL-C and may reduce mortality, non-fatal MI, and stroke among individuals at high cardiovascular risk, supporting guideline recommendations for SFA reduction and PUFA substitution.

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