Efficacy of phytosterols for reduction of cardiometabolic risk factors: An umbrella review of systematic reviews and meta-analyses and updated dose-response meta-analyses of randomized trials

BACKGROUND AND AIMS: Phytosterols reduce low density lipoprotein cholesterol (LDL-C) levels, supporting regulated health claims in over 10 jurisdictions. Their efficacy across different doses, matrices, and populations and on other cardiometabolic measures beyond LDL-C is unclear. We conducted a systematic umbrella review to evaluate the effects of phytosterols (plant sterols/stanols) on LDL-C and other cardiometabolic risk factors across doses, matrices, and populations, and provided an updated dose-response meta-analyses and assessment of the certainty of evidence. METHODS: We searched MEDLINE, Embase and Cochrane Library (03 Sep 2025) for systematic reviews and meta-analyses (SRMAs) of randomized controlled trials investigating phytosterol effects on cardiometabolic risk factors, including lipid, glycemic, inflammatory, blood pressure and adiposity markers. Two independent reviewers extracted relevant data as weighted mean differences (MD) with 95% confidence intervals (CIs). The certainty of the evidence was assessed using GRADE. RESULTS: ). An increase was seen in apoA-I (0.014 [0.001, 0.028] g/L) and apoC-II (0.30 [0.08, 0.52] mg/dL). There was a trivial reduction in triglycerides reported in one SRMA and no changes in HDL-C, apoC-III, apoA-II fasting blood glucose, HbA1c, TNF-α, IL-6, oxLDL-C, body weight, waist circumference, or fat mass. There was an inverse linear dose-response between phytosterols and LDL-C with reductions ≥0.2 mmol/L observed at plant sterol/stanol doses as low as 0.5-1 g/day. The certainty of evidence was generally high for LDL-C and moderate to high for most other lipid and cardiometabolic outcomes with downgrades for inconsistency, imprecision and/or publication bias. CONCLUSIONS: The evidence indicates that phytosterols result in moderate reductions in LDL-C and total cholesterol and provides a good indication for small important improvements in apoB, hs-CRP and apoC-II and trivial improvements in triglycerides, apoA-I, apoB/A-I, apoE, Lp(a), FFA, blood pressure, and BMI, with no effects on other cardiometabolic risk factors. REGISTRATION: OSF Registries (10.17605/OSF.IO/5J6M3).