Effect of Interventions Aimed at Reducing or Modifying Saturated Fat Intake on Cholesterol, Mortality, and Major...

Debates about optimal saturated fat advice continue.

To systematically summarize randomized trial data on reducing or modifying saturated fat intake on cholesterol, mortality, and major cardiovascular events.

MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to July 2025.

Eligible trials enrolled adults with or without cardiovascular disease and studied the effect of reducing or modifying saturated fat intake.

Standard Cochrane methods.

There were 17 eligible trials (66 337 participants). Risk stratified evidence provides low to moderate certainty that reducing saturated fat intake may result in a reduction in all-cause mortality (risk ratio [RR], 0.96 [95% CI, 0.88 to 1.06]), cardiovascular mortality (RR, 0.93 [CI, 0.77 to 1.11]), nonfatal myocardial infarction (MI) (RR, 0.86 [CI, 0.70 to 1.06]), and fatal and nonfatal stroke (RR, 0.83 [CI, 0.58 to 1.19]). For persons at low baseline cardiovascular risk, absolute reductions were below our thresholds of importance (5 and 10 per 1000 persons followed over 5 years for fatal and nonfatal outcomes, respectively); for those at high risk, the benefits were above our thresholds, suggesting there may be important absolute reductions. The effects were more pronounced when replacing saturated fat with polyunsaturated fat for nonfatal MI (RR, 0.75 [CI, 0.58 to 0.99]; P for interaction = 0.05; moderate credibility of subgroup effect based on Instrument to assess the Credibility of Effect Modification Analyses assessments).

Data were limited on the replacement of saturated fat with monounsaturated fat or protein. Trials varied considerably in their efficacy in reducing saturated fat intake and in their replacement macronutrients and concomitant dietary interventions, and new trials are needed to clarify uncertainty.

For persons at low cardiovascular risk, reducing or modifying saturated fat intake has little or no benefit over a period of 5 years. Among persons at high cardiovascular risk, low- to moderate-certainty evidence was found for important reductions in mortality and major cardiovascular events, particularly for MI, with respect to replacing saturated fat with polyunsaturated fat.

None. (PROSPERO: CRD42023387377).