Improvement of Cardiovascular Risk Factors by Genistein Supplementation: A Systematic Review and Meta-Analysis in Diverse Population-Based RCTs.

Abstract

Genistein[5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one] is a phytoestrogens known to positively impact various cardiovascular disease (CVD) risk factors. However, not all studies have yielded consistent results, and existing meta-analyses have not comprehensively addressed all CVD risk factors. We conducted a systematic search of the PubMed, ISI Web of Science, Embase, and Cochrane Library databases up to June 2024, following PRISMA 2020 guidelines. We included adult randomized controlled trials (RCTs) that examined pure genistein supplementation without other combined interventions and reported on at least one CVD risk factor. Data extraction and quality assessment were performed independently by two authors using a standardized form and the Cochrane Collaboration Scale. A total of 21 RCTs were included, with 941 participants in the genistein supplementation group and 918 participants in the control group. Statistical analyses were conducted using R software with the meta package. The meta-analysis revealed that, compared to the placebo group, genistein supplementation significantly improved the levels of TC ([MD 95% CI: -9.38 [-14.64, -4.12]; p < 0.001]), LDL-C ([MD 95% CI: -11.14 [-19.42, -2.86]; p < 0.001]), Lp(a) levels ([MD 95% CI: -0.69 [-0.98, -0.41]; p < 0.01), SBP ([MD 95% CI: -8.32 [-12.44, -4.20]; p < 0.01), DBP ([MD 95% CI: -3.57 [-5.25, -1.89]; P=0.04]), fasting blood glucose ([MD 95% CI: -3.98 [-6.79, -1.17]; p < 0.001]), fasting insulin ([MD 95% CI: -1.79 [-2.05, -1.54]; p < 0.01), HOMA-IR ([MD 95% CI: -0.56 [-0.64, -0.49]; p < 0.01), and homocysteine levels ([MD 95% CI: -0.74 [-1.05, -0.42]; p < 0.01). However, there were no significant improvements in TG, HDL-C, and CRP levels. The observed improvements align with clinically meaningful thresholds for cardiovascular risk reduction. Substantial heterogeneity observed for most outcomes was explored via subgroup analysis. Subgroup analyses were conducted based on treatment duration, geographic region, or participant health status, and heterogeneity was assessed using the I ² statistic. Subgroup analysis did not reveal any significant differences, indicating that heterogeneity was not influenced by factors such as treatment duration, geographic region, or participant health status. Overall, this meta-analysis provides consistent evidence that genistein intake significantly reduces several important CVD risk factors, including TC, LDL-C, Lp(a), SBP, DBP, fasting blood glucose, fasting insulin, HOMA-IR, and homocysteine levels.