Dietary Polyunsaturated to Saturated Fatty Acid Ratio as an Indicator for LDL Cholesterol Response: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 40885400 · doi:10.1016/j.advnut.2025.100502
What was done
A systematic review and random-effects meta-analysis of randomized complete feeding trials lasting ≥3 weeks in healthy adults. Trials compared two test diets with polyunsaturated-to-saturated fatty acid (P:S) ratios differing by >0.3 that were matched for energy, dietary fiber, and total fat. Searches were conducted in PubMed, Cochrane Central, and Web of Science. The primary outcome was the mean difference (MD) in LDL cholesterol, including subgroup analysis by dietary SFA difference.
What was found
Twenty-four randomized trials (n = 1011) met inclusion criteria. Higher P:S ratio diets (median P:S 1.2; PUFA 10.6% kcal, SFA 8.0% kcal) reduced LDL cholesterol compared with lower P:S ratio diets (median P:S 0.4; PUFA 4.4% kcal, SFA 12.5% kcal) by -9.83 mg/dL (95% CI: -13.63, -6.04; I2 = 79%). The reduction was present when diets differed in SFA by ≥2% kcal (MD -15.72 mg/dL; 95% CI: -20.51, -10.92; I2 = 68%), but was not statistically significant when diets were SFA-matched (MD -3.45 mg/dL; 95% CI: -7.88, 0.98; I2 = 70%; heterogeneity between subgroups P < 0.001).
Why it matters
This review clarifies that increasing the dietary P:S ratio lowers LDL cholesterol predominantly through the displacement of saturated fatty acids rather than through the addition of polyunsaturated fatty acids alone.
Limits
Statistical heterogeneity was substantial across analyses (I2 = 68% to 79%). The trials evaluated surrogate biomarker responses in short-term feeding settings (≥3 weeks) in generally healthy adults, precluding direct assessment of long-term cardiovascular clinical endpoints.