Summary:
In diabetes-free individuals with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), berberine treatment at a dose of 1 g/day for 6 months did not significantly reduce visceral adipose tissue (VAT) area or liver fat content compared to placebo, though it was associated with improvements in lipid and inflammatory markers and had a similar rate of adverse events to placebo.
| PICO | Description |
|---|---|
| Population | Diabetes-free adults with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), enrolled at 11 hospitals in China. |
| Intervention | Oral berberine at a daily dose of 1 gram for 6 months. |
| Comparison | Matching placebo administered orally once daily. |
| Outcome | No significant reduction in VAT area (1.4% [97.5% CI, -2.4% to 5.2%]) or liver fat content (0.9% [97.5% CI, -0.4% to 2.1%]). Berberine was associated with modest reductions in LDL cholesterol (-7.72 mg/dL), apolipoprotein B (-3.42 mg/dL), and hs-CRP (-0.072 mg/dL). Adverse event rates were comparable between groups. |
Clinical Context
Berberine, an isoquinoline alkaloid derived from plants such as Berberis and Coptis species, has garnered substantial attention as a potential metabolic modifier based on preclinical studies and smaller clinical trials suggesting benefits for glucose metabolism and lipid profiles. The compound has been widely marketed as a natural alternative for metabolic health, with particular claims regarding its ability to reduce visceral adiposity and hepatic steatosis. Metabolic dysfunction-associated steatotic liver disease affects approximately 30% of the global population and shares pathophysiological links with visceral obesity, insulin resistance, and systemic inflammation. Given the limited pharmacological options specifically approved for MASLD and the widespread consumer interest in natural supplements, rigorous evaluation of berberine’s efficacy on clinically meaningful endpoints became essential. This multicenter randomized controlled trial provides the largest and most methodologically robust assessment to date of berberine’s effects on visceral and hepatic fat compartments in a well-characterized population with obesity and MASLD.
Clinical Pearls
- Berberine at 1 g daily for 6 months failed to demonstrate significant reductions in either visceral adipose tissue area or liver fat content compared to placebo, challenging promotional claims about its fat-reducing properties.
- Despite the null primary findings, berberine produced statistically significant improvements in LDL cholesterol (-7.72 mg/dL) and apolipoprotein B (-3.42 mg/dL), suggesting potential cardiovascular benefits independent of fat reduction.
- The reduction in high-sensitivity C-reactive protein indicates anti-inflammatory effects that may contribute to metabolic health through mechanisms unrelated to adipose tissue mass.
- Adverse event rates were comparable between berberine and placebo groups, confirming the supplement’s acceptable safety profile at this dosage over 6 months.
Practical Application
Clinicians should counsel patients that berberine cannot be recommended as an evidence-based treatment for reducing visceral fat or hepatic steatosis based on this well-designed trial. Patients using berberine specifically for weight loss or fatty liver disease should be informed of these negative findings and directed toward interventions with established efficacy, particularly structured lifestyle modification programs emphasizing caloric restriction and physical activity. However, the modest lipid-lowering effects observed may support berberine’s role as an adjunctive therapy for dyslipidemia in patients who cannot tolerate statins or who prefer natural alternatives, though this represents an off-label application requiring shared decision-making. The anti-inflammatory effects warrant further investigation but do not currently justify clinical recommendations.
Broader Evidence Context
These results temper the enthusiasm generated by earlier, smaller trials and mechanistic studies suggesting berberine could meaningfully impact body composition and hepatic fat accumulation. The findings align with a broader pattern in supplement research where promising preclinical and preliminary clinical data often fail to replicate in adequately powered, rigorously designed trials. The lipid-lowering effects observed are consistent with prior meta-analyses demonstrating berberine’s modest impact on LDL cholesterol, providing mechanistic coherence even as the primary hypotheses were not confirmed.
Study Limitations
- The study population was exclusively Chinese adults, limiting generalizability to other ethnic groups with different metabolic phenotypes and body fat distribution patterns.
- Six months of treatment may be insufficient to detect slower-developing changes in visceral or hepatic fat compartments.
- The exclusion of patients with diabetes eliminates a population potentially more responsive to berberine’s metabolic effects.
- Dietary and physical activity interventions were standardized but compliance with lifestyle recommendations was not rigorously monitored.
- The berberine dose of 1 g daily, while commonly used, may not represent the optimal therapeutic dose for fat reduction.
Bottom Line
Berberine at 1 g daily does not reduce visceral adipose tissue or liver fat content in diabetes-free individuals with obesity and MASLD. While modest improvements in lipid and inflammatory markers were observed, clinicians should not recommend berberine for fat reduction and should direct patients toward proven lifestyle interventions for these conditions.
Source: Lubi Lei, et al. “Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD: A Randomized Clinical Trial.” Read article here.
