Effects of phytoestrogen supplementation on intermediate cardiovascular disease risk factors among postmenopausal women: a meta-analysis of randomized controlled trials

Importance: Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women. Objective: Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women. Evidence review: Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form. Findings: In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (-0.27 mmol/L [-0.41 to -0.13]), low-density lipoprotein (-0.25 mmol/L [-0.37 to -0.13]), triglycerides (-0.20 mmol/L [-0.28 to -0.11]), and apolipoprotein B (-0.13 g/L [-0.23 to -0.03]) and with an increase in serum apolipoprotein A-1 (0.04 g/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (-18.86 ng/mL [-30.06 to -7.65]) and E-selectin (-2.32 ng/mL [-4.05 to -0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34 mu m [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled. Conclusions and Relevance: Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health.