{"doi":"10.1016/j.advnut.2025.100502","title":"Dietary Polyunsaturated to Saturated Fatty Acid Ratio as an Indicator for LDL Cholesterol Response: A Systematic Review and Meta-Analysis of Randomized Clinical Trials","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","journal":"Advances in Nutrition","year":2025,"id":513555,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1030586,"name":"Janhavi J Damani","orcid":"0000-0003-3523-5160","position":1,"is_corresponding":false},{"id":1030585,"name":"Zachary DiMattia","orcid":"0000-0002-6275-9405","position":2,"is_corresponding":false},{"id":1375324,"name":"Kayla E Tate","orcid":"0000-0002-0833-0069","position":3,"is_corresponding":false},{"id":1374730,"name":"Fatemeh Jafari","orcid":"0000-0002-5958-7278","position":4,"is_corresponding":false},{"id":233816,"name":"Kristina Petersen","orcid":"0000-0003-3914-0353","position":5,"is_corresponding":false},{"id":1037967,"name":"Tricia Hart","orcid":"0000-0002-7999-3994","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:48:17.908238Z","pmid":"40885400","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}