Abstract
BACKGROUND: Cardiovascular disease (CVD) is a serious public health problem worldwide. The role of citrus flavanone hesperidin consumption on cardiovascular disease risk factors (CVDRFs) has been examined in many clinical trials, but conflicting results have been found. OBJECTIVES: This study aimed to systematically evaluate the effects of hesperidin extracts or purified hesperidin on CVDRFs in humans with an updated meta-analysis of randomized controlled trials. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we systematically screened and searched electronic databases from their establishment to March 2023. Reference lists and previous reviews were also searched. Intervention trials assessing hesperidin consumption on CVD outcomes were included for pooling. To assess the quality of the included articles, the tool of Cochrane risk-of-bias tool was applied. We synthesized the effect sizes with 95% CIs and weighted mean difference (WMD). The I (2) index was used to evaluate the between-study heterogeneity. To explore the heterogeneity source, we used meta-regression and subgroup analysis. Publication bias and sensitivity analysis were also performed. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the evidence quality. RESULTS: We included 12 trials with 589 participants. We found evident effects of hesperidin on low-density lipoprotein cholesterol (WMD: -0.22 mmol/L; 95% CI: -0.33, -0.11 mmol/L), total cholesterol (WMD: -0.20 mmol/L; 95% CI: -0.31, -0.08 mmol/L), fasting blood glucose (WMD: -0.15 mg/dL; 95% CI: -0.29, -0.02 mg/dL), quantitative insulin-sensitivity check index (WMD 0.06, 95% CI 0.01 to 0.10), intercellular adhesion molecule 1 (WMD: -13.60 ng/mL; 95% CI: -23.72, -3.48 ng/mL), vascular cell adhesion molecule 1 (WMD: -15.60 ng/mL; 95% CI: -30.13, -1.06 ng/mL), and C-reactive protein (WMD: -0.56 mg/L; 95% CI: -1.11, -0.01 mg/L), whereas no effects were found for other CVDRFs. CONCLUSIONS: Our current findings demonstrate that hesperidin might be advantageous in improving numerous CVDRFs in humans, such as blood lipid concentrations, blood glucose control, and management of inflammatory indicators.