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

2025-11-16
Nutrients 17(22)
- Anna Koperska
- Ewa Miller-Kasprzak
- Agnieszka Seraszek-Jaros
- Katarzyna Musialik
- Paweł Bogdański
- Monika Szulińska

PubMed: 41305635
DOI: 10.3390/nu17223585

Study Design

Type: Randomized Controlled Trial (RCT)
Population: seventy individuals with MAFLD who were overweight or obese
Methods: randomized, double-blind, placebo-controlled clinical trial, 1:1 ratio, BBR (1500 mg/day) or placebo orally for 12 weeks
Blinding: Double-blind
Duration: 12 weeks
Funding: Unclear

Rigorous Journal

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

In the BBR-treated cohort, VEGF concentrations demonstrated a statistically significant increase following the intervention, rising from a baseline mean of 456.23 ± 307.61 pg/mL to 561.22 ± 389.77 pg/mL (p < 0.0001). In the BBR group, a significant reduction in PWA-SP was observed after 12 weeks of supplementation (134.85 ± 16.26 vs. 124.46 ± 13.47 mmHg, p < 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.

Research Insights

Berberine→Increased VEGF Level
In the BBR-treated cohort, VEGF concentrations demonstrated a statistically significant increase following the intervention, rising from a baseline mean of 456.23 ± 307.61 pg/mL to 561.22 ± 389.77 pg/mL (p < 0.0001).
Effect
Beneficial
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Aortic Pressure
No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Augmentation Index
No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Diastolic Blood Pressure
No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Mean Arterial Pressure
No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Pulse Pressure
No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Pulse Wave Velocity
No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Berberine→Reduced Systolic Blood Pressure
In the BBR group, a significant reduction in PWA-SP was observed after 12 weeks of supplementation (134.85 ± 16.26 vs. 124.46 ± 13.47 mmHg, p < 0.0001).
Effect
Beneficial
Effect size
Large
Dose
1500 mg/day

Adverse Events Reported

Berberine→Overall tolerability
No serious adverse events were reported, and BBR was well tolerated.
Finding
Reported