Bergamot (Citrus bergamia) Supplementation and Cardiovascular Disease Risk Factors: A Systematic Review and...

Cardiovascular diseases remain the leading cause of global mortality. Bergamot (Citrus bergamia), a flavonoid-rich nutraceutical, has shown potential cardiometabolic benefits, yet evidence from human trials remains inconsistent. This systematic review and dose-response meta-analysis evaluated the effects of bergamot (Citrus bergamia) on cardiovascular disease risk factors in adults. We conducted a systematic review and meta-analysis of randomized controlled trials following PRISMA guidelines (PROSPERO: CRD420251127505). PubMed, Web of Science, Scopus, Embase, and the Cochrane Library were searched for relevant studies. Trials evaluating the effects of bergamot supplementation on cardiovascular outcomes in adults were included. Weighted mean differences (WMDs) were pooled using DerSimonian-Laird random-effects models. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Nine RCTs involving 615 participants were included. Bergamot supplementation was significantly associated with reduced waist circumference (WMD = -0.96 cm; 95% CI: -1.91 to -0.01; p = 0.047), systolic blood pressure (WMD = -2.09 mmHg; 95% CI: -3.33 to -0.86; p = 0.001), glucose (WMD = -12.12 mg/dL; 95% CI: -17.05 to -7.19; p < 0.001), homeostatic model assessment of insulin resistance (WMD = -0.38 units; 95% CI: -0.65 to -0.11; p = 0.005), insulin (WMD = -2.93 IU/L; 95% CI: -5.06 to -0.79; p = 0.007), low-density lipoprotein cholesterol (WMD = -39.53 mg/dL; 95% CI: -53.46 to -25.60; p < 0.001), total cholesterol (WMD = -44.69 mg/dL; 95% CI: -62.00 to -27.39; p < 0.001), and triglycerides (WMD = -52.47 mg/dL; 95% CI: -66.09 to -38.86; p < 0.001), while being associated with an increase in high-density lipoprotein cholesterol (WMD = 5.63 mg/dL; 95% CI: 3.75 to 7.51; p < 0.001). Risk-of-bias assessment classified six trials as poor, two as fair, and one as good. According to the GRADE assessment, the certainty of evidence ranged from low to very low for all outcomes. Bergamot supplementation is associated with modest improvements in cardiometabolic risk factors, including lipid profile, glycemic control, systolic blood pressure, and waist circumference, in adults with dyslipidemia or metabolic syndrome. However, these observed effects are mainly based on very-low-certainty evidence, largely from studies at high risk of bias, and should not be interpreted as establishing the clinical efficacy of bergamot.