Abstract
BACKGROUND: Cardiovascular disease (CVD) is a pressing public health issue worldwide. Accordingly, primary and secondary CVD prevention are essential. Many clinical trials have investigated the effects of sumac (Rhus Coriaria) supplementation on CVD risk factors (CVDRFs). However, these studies have yielded contradictory findings. This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively assess the impact of sumac supplementation on CVDRFs in human subjects. METHODS AND MATERIALS: We searched the MEDLINE/PubMed, EMBASE, CENTRAL, and Web of Science to identify the relevant studies in any language until March 2025. RCTs that investigated the impact of sumac supplementation compared no sumac consumption or placebo capsule interventions or consumed substitutions containing no sumac on CVD outcomes in adults at least 2 weeks were included for data synthesis. The primary outcomes were the mean difference in lipid profiles, blood pressure, glycemic control, and anthropometric indices. Secondary outcomes were the mean difference in inflammatory and oxidative stress markers. The quality of the included trials was assessed using the Cochrane Risk-of-Bias tool. Effect sizes were calculated using a random effect model and presented as weighted mean differences and 95% confidence intervals (CIs), while the I(2) index was utilized to assess between-study heterogeneity. To explore the potential sources of heterogeneity, subgroup and meta regression analyses were evaluated. Additionally, publication bias and sensitivity analyses were conducted. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to evaluate the quality of evidence. RESULTS: A total of 17 trials (comprising 18 treatment arms) with 1170 participants were included in our analysis. The findings revealed statistically significant effects of sumac consumption on various CVDRFs, including low-density lipoprotein cholesterol (-9.62 mg/dL; 95% CI= -14.59 to -4.65), total cholesterol (-9.47 mg/dL; 95% CI= -15.92 to -3.02), triglycerides (-8.96 mg/dL; 95% CI= -16.19 to -1.73), high-density lipoprotein cholesterol (2.95 mg/dL; 95% CI = 0.66 to 5.25), diastolic blood pressure ( -2.87 mmHg; 95% CI= -4.23 to -1.51), insulin (-1.68 µU/mL; 95% CI: -3.26 to -0.09), homeostatic model assessment of insulin resistance ( -0.87; 95% CI: -1.61 to -0.14), body weight ( -1.03 kg; 95% CI= -1.89 to -0.17), body mass index (WMD = -0.31 kg/m; 95% CI= -0.55 to -0.07), waist circumference (-0.59 cm; 95% CI= -1.06 to -0.12), malondialdehyde (0.84 µmol/L; 95% CI = 0.38 to 1.30), and total antioxidant capacity ( -0.83 µU/L; 95% CI = -1.10 to -0.56). However, no significant effects were observed for other analyzed CVDRFs, such as systolic blood pressure, fasting blood glucose, quantitative insulin sensitivity check index, hip circumference, waist-to-hip ratio and hypersensitive C-reactive protein. These results were stable in sensitivity analysis, and no significant publication bias was detected. The GRADE profile for sumac supplementation evaluated the certainty of the outcomes and indicated that the quality of evidence was was rated as very low to high across all outcomes. CONCLUSION: The findings of our present study suggest that sumac supplementation may have potential benefits in improving various CVDRFs, such as blood lipid levels, blood glucose control, weight management, and oxidative stress markers. Therefore, integrating sumac could be explored as a complementary dietary approach to improve the overall cardiometabolic health. However, these results warrant cautious interpretation, as the findings were derived predominantly from Iranian populations, and significant heterogeneity was observed across trials for different outcomes. Moreover, our pooled results were based on unadjusted estimates, the precise effect of sumac on CVDRFs could be impacted by various confounders. Further large-scale and high-quality RCTs with longer duration are required to confirm these results.