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

BACKGROUND: Debates about optimal saturated fat advice continue. PURPOSE: To systematically summarize randomized trial data on reducing or modifying saturated fat intake on cholesterol, mortality, and major cardiovascular events. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to July 2025. STUDY SELECTION: Eligible trials enrolled adults with or without cardiovascular disease and studied the effect of reducing or modifying saturated fat intake. DATA EXTRACTION: Standard Cochrane methods. DATA SYNTHESIS: for interaction = 0.05; moderate credibility of subgroup effect based on Instrument to assess the Credibility of Effect Modification Analyses assessments). LIMITATIONS: 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. CONCLUSION: 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. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42023387377).