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

Background: Dietary guidelines recommend limiting saturated fatty acid (SFA) intake by replacing SFA with polyunsaturated fatty acid (PUFA). PUFA and SFA have opposing effects on low density lipoprotein (LDL) cholesterol, and therefore, the dietary ratio of PUFA to SFA (P:S) may be a better indicator of LDL cholesterol response than SFA alone. Objectives: A systematic review and meta-analysis of randomized clinical trials was conducted to examine LDL cholesterol responses to higher P:S ratio diets compared with 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 wk, including 2 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 cholesterol 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; and MUFA 12.6% kcal) lowered LDL cholesterol [MD −9.83 mg/dL; 95% confidence interval (CI): −13.63, −6.04; I² = 79%] compared with lower P:S ratio diets (median P:S ratio 0.4; PUFA 4.4% kcal; SFA 12.5% kcal; and MUFA 14.6% kcal). Heterogeneity in the P:S ratio effect was observed by the test diet SFA content (P < 0.001). Higher compared to lower P:S ratio diets lowered LDL cholesterol (MD −15.72 mg/dL; 95% CI: −20.51, −10.92; I² = 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; I² = 70%). Conclusions: Compared with lower P:S ratio diets, higher P:S ratio diets were associated with greater LDL cholesterol reductions in generally healthy adults, and this effect was stronger when PUFA replaced SFA. This trial was registered at Prospective Register of Systematic Reviews (PROSPERO) as CRD42023452550.