The Influence of Berberine on Vascular Function Parameters, Among Them VEGF, in Individuals with MAFLD: A Double-Blind, Randomized, Placebo-Controlled Trial

BACKGROUND: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology-supporting vascular repair in early stages, but potentially contributing to fibrosis in later stages. In this study, berberine (BBR), a plant-derived isoquinoline alkaloid, exhibits multiple beneficial properties, including anti-inflammatory, antioxidant, and endothelial-protective effects, on the study group, perhaps by influencing VEGF concentration. OBJECTIVE: This study aimed to investigate the effectiveness of BBR in addressing vascular function parameters linked to MAFLD, particularly its impact on serum VEGF levels and arterial stiffness. METHODS: This randomized, double-blind, placebo-controlled clinical trial enrolled seventy individuals with MAFLD who were overweight or obese. Participants were randomly assigned in a 1:1 ratio to receive either BBR (1500 mg/day) or a placebo orally for 12 weeks. The following parameters were assessed pre- and post-intervention: VEGF, brachial SBP (Systolic Blood Pressure)/DBP (Diastolic Blood Pressure), MAP (Mean Arterial Pressure), AIx (Augmentation Index), AP (Aortic Pressure), number of waveforms, Pulse Pressure (PP), PWV (Pulse Wave Velocity), and PWA-SP/PWA-DP (Pulse Wave Analysis Systolic/Diastolic Pressure). The results for the metabolic parameters-FLI (Fatty Liver Index)-and anthropometric parameters-BMI (Body Mass Index), fat mass corp-and laboratory parameters, among them, hsCRP (high-sensitivity C-reactive protein), were published by us earlier. RESULTS: < 0.0001). No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups. In the BBR group, delta VEGF correlated negatively with delta FLI; no such associations were observed in the placebo group. Changes in PWV were consistent and significantly correlated with changes in brachial SBP/DBP, PWA-SP, PWA-DP, and MAP. No serious adverse events were reported, and BBR was well tolerated. CONCLUSIONS: BBR appears to be a safe and promising adjunct in MAFLD therapy, potentially exerting reparative effects through VEGF modulation and vascular support. Further research is warranted to confirm its long-term impact and elucidate underlying protective mechanisms.