Berberine, a popular over-the-counter weight loss supplement, inhibited skeletal muscle fiber assembly in cell cultures, while semaglutide had no effects on either heart or skeletal muscle cells.
Berberine blocks muscle fiber assemblyBerberine inhibited skeletal muscle myofibril formation and suppressed myosin gene expression in cell cultures, while semaglutide showed no such effects on heart or skeletal muscle cells.
What the researchers found
Berberine inhibited myofibril assembly at the nascent myofibril stage in embryonic skeletal muscle cells, preventing the normal progression to mature muscle fibers. RT-PCR experiments showed that berberine specifically inhibited mRNA for muscle myosin II heavy chains (a key structural protein) while not affecting muscle actin mRNA in skeletal muscle cells.
Importantly, berberine had no effect on myofibril assembly in embryonic heart cells, which may explain clinical reports of berberine being safe for the heart even in cancer patients. In contrast, semaglutide showed no effects on myofibril assembly in either cardiac or skeletal muscle cell cultures, suggesting a cleaner muscle safety profile.
Why it matters
Berberine has surged in popularity as an affordable alternative to prescription GLP-1 drugs for weight loss, marketed widely on social media. However, its effects on muscle tissue have received little attention. This study is the first to directly compare berberine and semaglutide for muscle cell effects, revealing that berberine — but not semaglutide — disrupts skeletal muscle development. Given widespread concerns about muscle loss during weight loss (sarcopenic obesity), this finding is clinically relevant.
How the study worked
Researchers used cultured embryonic cardiac and skeletal muscle cells as a preclinical assay system. Cells were exposed to berberine (a UHRF1 ligase inhibitor) and assessed for myofibril assembly progression through three established stages: premyofibrils, nascent myofibrils, and mature myofibrils. Semaglutide was tested in the same culture system as a comparison. RT-PCR was used to measure effects on muscle protein gene expression. The study builds on the laboratory's established three-step model of myofibrillogenesis.
What this study cannot tell us
This is an in vitro cell culture study using embryonic muscle cells, which may not directly reflect what happens in adult human muscles. The concentrations of berberine used in culture may not match physiological levels achieved through oral supplementation. No animal or human data on berberine's effects on mature muscle tissue were presented. The study does not address whether berberine-induced muscle effects would be clinically significant at typical supplement doses or whether they would be reversible.
How to read the evidence
This is a preclinical in vitro study using embryonic muscle cell cultures. While it provides mechanistic insight into potential berberine toxicity, the evidence cannot be directly translated to clinical recommendations without animal model and human studies to confirm the findings at physiological doses.
When this study was published
Published in 2025, this is a timely study addressing the safety comparison between berberine and semaglutide during a period of intense public interest in both compounds for weight loss.
The bigger picture
The rapid adoption of berberine as a 'natural Ozempic' has outpaced safety research. While semaglutide has undergone extensive clinical testing, berberine's muscle effects are poorly characterized. This study adds to growing evidence that supplements marketed as drug alternatives may carry distinct risk profiles. It also proposes an elegant preclinical screening method — cultured embryonic muscle cells — that could help identify muscle toxicity of future cancer drugs and weight loss compounds before they reach patients.
Questions still open
- Do the muscle-disrupting effects of berberine observed in cell cultures translate to measurable muscle loss or weakness in people taking berberine supplements?
- What berberine doses and duration of use would be needed to produce clinically significant skeletal muscle effects in humans?
- Should berberine supplements carry warnings about potential muscle effects, particularly for elderly users or those with sarcopenia?
Common questions
Is berberine safe for muscles compared to semaglutide?
Should I stop taking berberine as a weight loss supplement?
Read the original research
Analyses of Off-Target Effects on Cardiac and Skeletal Muscles by Berberine, a Drug Used to Treat Cancers and Induce Weight Loss.
Cytoskeleton (Hoboken, N.J.), 82(6), 344-359
Citation
Wang, Jushuo; Fan, Yingli; Dube, Syamalima; Benz, Patricia; Dube, Dipak; Sanger, Jean M; Sanger, Joseph W. (2025). Analyses of Off-Target Effects on Cardiac and Skeletal Muscles by Berberine, a Drug Used to Treat Cancers and Induce Weight Loss.. Cytoskeleton (Hoboken, N.J.), 82(6), 344-359. https://doi.org/10.1002/cm.21950