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

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. 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. 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. 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; I2=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; 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%). 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. Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42023452550.