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Dietary Polyunsaturated to Saturated Fatty Acid Ratio as an Indicator for LDL Cholesterol Response: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Tricia Hart, Janhavi J Damani, Zachary DiMattia, Kayla E Tate, Fatemeh Jafari, Kristina Petersen

2025Advances in Nutrition9 citationsDOIOpen Access PDF

Abstract

Background Dietary guidelines recommend limiting saturated fat (SFA) intake by replacing SFA with polyunsaturated fats (PUFA). PUFA and SFA have opposing effects on LDL-cholesterol (LDL-C) and therefore the dietary ratio of PUFA to SFA (P:S) may be a better indicator of LDL-C response than SFA alone. Objectives A systematic review and meta-analysis of randomized clinical trials was conducted to examine LDL-C responses to higher P:S ratio diets compared to isoenergetic, total fat-matched diets with lower P:S ratios in healthy adults. Methods A systematic search of PubMed, Cochrane Central, and Web of Science was conducted. Randomized complete feeding trials lasting ≥3 weeks including two test diets with P:S ratios differing by >0.3 that were matched for energy, fiber, and total fat were included. Random effects meta-analysis was used to evaluate the mean difference (MD) in LDL-C with higher P:S ratio diets compared to lower P:S ratio diets. Heterogeneity in the effect of the P:S ratio by SFA content of the test diets was also evaluated. Results In total, 1001 publications were identified, and 24 publications reporting 24 trials (n=1011) were eligible. Higher P:S ratio diets (median P:S ratio 1.2; PUFA 10.6%kcal; SFA 8.0%kcal; MUFA 12.6%kcal) lowered LDL-C (MD −9.84 mg/dL; 95%CI −13.65, −6.04; I 2 =79%) compared to lower P:S ratio diets (median P:S ratio 0.4; PUFA 4.4%kcal; SFA 12.5%kcal; MUFA 14.6%kcal). Heterogeneity in the P:S ratio effect was observed by the test diet SFA content (p<0.001). Higher versus lower P:S ratio diets lowered LDL-C (MD −15.72 mg/dL; 95%CI −20.51, −10.92; I 2 =68%) when the test diets differed in SFA (≥2%kcal), but not when diets were SFA matched (MD −3.45 mg/dL; 95%CI −7.88, 0.98; I 2 =70%). Conclusion Compared to lower P:S ratio diets, higher P:S ratio diets were associated with greater LDL-C reductions in generally healthy adults, and this effect was stronger when PUFA replaced SFA. Registry Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42023452550

Topics & Concepts

Polyunsaturated fatty acidMeta-analysisRandomized controlled trialCholesterolMedicineLdl cholesterolClinical trialInternal medicineFatty acidFood scienceBiochemistryChemistryFatty Acid Research and HealthDiet and metabolism studiesNutritional Studies and Diet