A recent study published in the top international journal Cell offers a new approach to this problem. The study demonstrated that berberine, taken for two years after adenoma resection, significantly reduced adenoma recurrence rates (34.7% in the berberine group vs. 52.1% in the placebo group) and overall tumor incidence (63.4% vs. 71.0%), even six years after discontinuation. This finding suggests berberine may be a potential treatment for preventing long-term recurrence of colorectal adenomas after surgery.
▍Study Overview: The protective effect persists up to six years after discontinuation of treatment.
Led by the team of Fang Jingyuan and Chen Yingxuan from Shanghai Jiao Tong University, the study, initiated in 2014, was a multicenter, randomized, double-blind, placebo-controlled clinical trial. Over 1,100 patients who had undergone complete resection of colorectal adenomas were enrolled. To exclude confounding factors, patients who regularly used medications such as aspirin or vitamin D were excluded. Participants were divided into two groups in a 1:1 ratio and received either 0.1g of berberine or a placebo orally twice daily for two years. The primary endpoint was colonoscopy results at one and two years after surgery.
Two-year follow-up showed that the adenoma recurrence rate was 36% in the berberine group and 47% in the placebo group, representing a 23% relative risk reduction. No serious adverse reactions were reported.
After the randomized trial, the research team conducted a retrospective extended follow-up with a median follow-up of six years to evaluate the long-term preventive effect of berberine on colorectal adenoma recurrence.
Key findings include:
Berberine significantly reduced the risk of colorectal adenoma recurrence. At the end of follow-up, the recurrence rate was 34.7% (109/314) in the berberine group and 52.1% (174/334) in the placebo group (hazard ratio = 0.58, p < 0.001), a relative risk reduction of 42%.
Berberine also demonstrated an inhibitory effect on colorectal tumorigenesis. The incidence of any tumor type was 63.4% (199 participants) in the berberine group and 71.0% (237 participants) in the placebo group (HR = 0.75, p = 0.004), resulting in a 25% relative risk reduction. However, this difference did not persist in sensitivity analyses.
▍Potential Advantages of Berberine
Berberine is a natural alkaloid derived from traditional Chinese medicine with a favorable safety profile and widespread global application. Its mechanisms for preventing adenoma recurrence may include:
Regulating the intestinal microbiota and precisely inhibiting cancer-promoting bacteria;
Regulating the tumor microenvironment and blocking the "inflammation-to-cancer" transformation pathway;
Enhancing intestinal mucosal barrier function and promoting metabolic health through signaling pathways such as AMPK and TGR5.
Compared with aspirin or calcium supplements, berberine demonstrated a more sustained preventive effect. This study showed that taking berberine for two years can provide sustained protection for up to six years after discontinuation, with no significant adverse effects. This study is particularly suitable for people with metabolic disorders such as diabetes or hyperlipidemia.
▍Other Recommendations for Colorectal Health Management
In addition to medication, good lifestyle habits are also crucial:
Diet: Increase intake of vegetables, fruits, and dietary fiber, supplement with probiotics, and limit high-fat and high-salt foods.
Weight Management: Obese individuals have an approximately 40% increased risk of adenoma recurrence, so weight control through exercise and diet is recommended.
High-risk individuals should undergo enhanced monitoring and intervention, including Helicobacter pylori eradication therapy, genetic screening (such as APC gene mutations), and monitoring of metabolic markers such as homocysteine (supplementing with active folic acid and vitamin B12 when levels exceed 8 μmol/L can significantly reduce the risk of recurrence).
Berberine's Mechanism of Action in Metabolic Health
Berberine can improve metabolic health through multiple pathways:
It enhances intestinal L-cell function and promotes GLP-1 secretion, thereby improving insulin sensitivity and blood sugar stability;
It optimizes the microbial flora, increasing the production of beneficial bacteria such as Akkermansia and short-chain fatty acids, strengthening the intestinal barrier, and reducing the risk of endotoxemia;
It regulates the gut-liver axis, inhibits hepatic lipogenesis, and alleviates non-alcoholic fatty liver disease (NAFLD);
It inhibits xanthine oxidase and regulates renal urate transporters, thereby lowering serum uric acid levels.
These mechanisms offer berberine broad potential for application in conditions such as metabolic syndrome, type 2 diabetes, obesity, and hyperuricemia.
References:
Tan et al., Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-Year follow-up of a randomized clinical trial, Cell Reports Medicine (2025). https://doi.org/10.1016/j.xcrm.2025.102293
Xu et al., Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021;133:110984.
