Phytosterol Supplementation Could Improve Atherogenic and Anti-Atherogenic Apolipoproteins: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials

Phytosterol and phytostanol (PS) supplementation is reported to improve atherogenic and anti-atherogenic apolipoproteins (Apo). The purpose of the present study is to critically investigate the effectiveness of PS supplementation on Apo in adults. A comprehensive search was conducted of all randomized controlled trials (RCTs) conducted up to September 2018 in the following databases: PubMed, Web of Science, Cochrane Library, and Scopus. Mean difference with 95% confidence intervals (CIs) were pooled using a random-effects model (DerSimonian-Laird method). Fifty-one arms from 37 RCTs were included in the present meta-analysis. Findings showed that PS supplementation and fortification increased Apo-AI (weighted mean difference [WMD]: 0.014 mg/dl, 95% CI: 0.001, 0.028, p = 0.042) and Apo-CII (WMD: 0.303 mg/dl, 95% CI: 0.084, 0.523, p = 0.007) and lowered Apo-B (WMD: -0.063 mg/dl, 95% CI: -0.075, -0.051, p < 0.001), Apo-B/Apo-A-I ratio (WMD: -0.044 mg/dl, 95% CI: -0.062, -0.025, p < 0.001), and Apo-E (WMD: -0.255 mg/dl, 95% CI: -0.474, -0.036, p = 0.023). However, PS supplementation did not have significant effects on Apo-AII and Apo-CIII. PS supplementation or fortification significantly changes Apo-E (r = -0.137, p nonlinearity = 0.006) and Apo-CIII (r = 1.26, p nonlinearity = 0.028) based on PS dosage (mg/d) and Apo-CIII (r = 3.34, p nonlinearity = 0.013) and Apo-CII (r = 1.09, p nonlinearity = 0.017) based on trial duration (weeks) in a nonlinear fashion. Based on our findings, supplements or fortified foods containing PS might have a considerable favorite effect in achieving Apo profile target; however, due to high heterogeneity among included studies, results must be interpreted with caution.KEY TEACHING POINTS Cardiovascular diseases (CVDs) recognized as main public health concern worldwide with considerable mortality of all global deaths. Apo-lipoproteins are amphipathic molecules involved in the lipoprotein metabolism which introduced as biomarkers in the evaluation of CVD risk. Phytosterols bioactive components of plants have important biological functions in cholesterol metabolism in humans. Here we showed that phytosterols and phytostanols improve apo-lipoproteins profile of humans; finding from meta-analysis of randomized controlled trials. Phytosterols supplementation lowered atherogenic apo-lipoproteins (Apo-B and Apo-E) and increased anti-atherogenic apo-lipoproteins (Apo-AI, Apo-CII).