Effects of phytosterols on cardiovascular risk factors: A systematic review and meta‐analysis of randomized controlled trials

Cardiovascular diseases are the major cause of death globally. The primary risk factors are high blood lipid levels, hypertension, diabetes, and obesity. Phytosterols are naturally occurring plant bioactive substances. Short-term clinical trials have demonstrated phytosterols' cholesterol-lowering potential, but their effects on cardiovascular risk factors remain controversial, and relevant meta-analyses are limited and incomplete. We conducted a systematic and comprehensive search of PubMed, Web of Science, Embase and Cochrane Library up to December 22, 2023. A total of 109 randomized controlled trials (RCTS) of phytosterols (PS) intervention on cardiovascular risk factor outcomes were included in a preliminary screening of the retrieved literature by Endnote 20. We assessed the quality of all included randomized controlled trials using the Cochrane Collaboration's Risk of Bias tool. Cochrane data conversion tool was used for data conversion, and finally Stata was used for meta-analysis, egger test and sensitivity analysis of the included studies. The results indicated that dietary phytosterols intake could significantly decrease total cholesterol (TC) level (mean difference = -13.41; 95% confidence interval [CI]: -15.19, -11.63, p < 0.001), low density lipoprotein cholesterol (LDL-C) level (mean difference = -12.57; 95% CI: -13.87, -11.26, p < 0.001), triglycerides (TG) level (mean difference = -6.34; 95% CI: -9.43, -3.25, p < 0.001), C-reactive protein (CRP) level (mean difference = -0.05; 95% CI: -0.08, -0.01, p = 0.671), systolic blood pressure (SBP) level (mean difference = -2.10; 95% CI: -3.27, -0.9, p < 0.001), diastolic blood pressure (DBP) level (mean difference = -0.83; 95% CI: -0.58, -0.07, p = 0.032), increased high-density lipoprotein cholesterol (HDL-C) level (mean difference = 0.46; 95% CI: 0.13, 0.78, p = 0.005), but did not alter the levels of blood glucose (GLU) (mean difference = -0.44; 95% CI: -1.64, 0.76, p = 0.471), glycosylated hemoglobin, Type A1C (HbA1c) (mean difference = -0.28; 95% CI: -0.75, 0.20, p = 0.251), interleukin-6 (IL-6) (mean difference = 0.00; 95% CI: -0.02, 0.02, p = 0.980), tumor necrosis factor (TNF-α) (mean difference = 0.08; 95% CI: -0.08, 0.24, p = 0.335), oxidized low-density lipoprotein cholesterol (OXLDL-C) (standard mean difference = 0.16; 95% CI: -0.38, 0.06, p = 0.154), body mass index (BMI) (mean difference = 0.01; 95% CI: -0.07, 0.09, p = 0.886), waist circumference (WC) (mean difference = -0.10; 95% CI: -0.50, 0.30, p = 0.625) and body weight (mean difference = 0.03; 95% CI: -0.18, 0.24, p = 0.787). Our results suggest that phytosterols may be beneficial in reducing the levels of TC, LDL-C, TG, CRP, SBP, and DBP, but have no significant effect on GLU, HbA1c, TNF-α, IL-6, OXLDL-C, BMI, WC, and Weight. However, there were a small number of RCTS included in this study and their small population size may have reduced the quality of the study. And most of the included studies were short-term intervention trials. Therefore, higher quality studies need to be designed in future studies to establish more accurate conclusions.