Berberine Shows Lasting Protection Against Colorectal Adenoma Recurrence

Berberine may offer lasting benefits in colorectal cancer (CRC) prevention. In a 6-year posttreatment follow-up of nearly 800 patients across China, researchers found that berberine significantly lowered adenoma recurrence and reduced colorectal neoplasm occurrence after polypectomy.1

This retrospective cohort study is published in Cell Reports Medicine.

A 6-year follow-up study finds berberine reduces adenoma and neoplasm rates after polypectomy, highlighting its potential for long-term chemoprevention. | Image credit: Oleksandr - stock.adobe.com

“In this post-treatment follow-up study of the CBAR [NCT02226185] trial, we found that a 2-year berberine treatment had prolonged chemoprevention effects against colorectal adenoma recurrence and neoplasm occurrence in polypectomy patients over a median observation time of 78.0 months (6 years),” wrote the researchers of the study. “Compared with that during the CBAR trial, the chemopreventive effects of berberine were more evident in the post-treatment period, whereby the recurrence rate of colorectal adenoma decreased further.”

Berberine is a plant-derived bioactive alkaloid used in traditional medicine for its antimicrobial and digestive health benefits.2 It acts at the cellular level by activating an enzyme that regulates energy metabolism, potentially improving glucose control, fat utilization, and insulin sensitivity. Berberine may help lower blood sugar, improve cholesterol profiles, support modest weight loss, and promote gut health through antimicrobial and anti-inflammatory effects.

The researchers recruited 781 patients who had completed the prior trial of berberine for adenoma prevention from 7 clinical centers across 6 provinces in China and followed them during the posttreatment observational phase between December 29, 2018, and October 10, 2024.1 Colonoscopic surveillance was conducted, with 648 patients undergoing at least 1 colonoscopy during the follow-up period.

The primary outcome was the recurrence of colorectal adenomas. Secondary outcomes included the occurrence of colorectal neoplasms and nonadvanced adenomas. Data were analyzed to compare long-term outcomes between participants who had previously received berberine and those who had received a placebo, assessing the persistence of protective effects beyond the treatment period.

After a median (IQR) follow-up of 78.0 (73-85) months, in patients who underwent at least 1 colonoscopy, the adenoma recurrence rate was significantly lower in the prior berberine (34.7%) group compared with the placebo (52.1%) group (HR, 0.58; 95% CI, 0.45-0.74; P < .001). Berberine recipients also showed a reduced occurrence of colorectal neoplasms (63.4% vs 71.0%) and a lower incidence of nonadvanced adenomas (29.5% vs 45.2%) compared with the placebo group (adjusted HR, 0.75; 95% CI, 0.62-0.91; P = .004).

Furthermore, year-by-year analysis revealed that the protective effect reached statistical significance by the third year post treatment (OR, 0.63; 95% CI, 0.41-0.97; P = .04) and stabilized from the fifth year onward (OR, 0.50; 95% CI, 0.35-0.70; P < .001), indicating durable long-term prevention of adenoma recurrence after endoscopic resection.

However, the researchers acknowledged some limitations, including variable colonoscopy frequency, loss to follow-up, and low event rates that may have limited statistical power. Additionally, unmeasured factors such as genetics, diet, and lifestyle could have also influenced outcomes, and potential mechanisms like gut microbiota changes were not assessed. Lastly, incomplete data on adenoma size, number, and location warrant further study.

Despite these limitations, the researchers believe these findings position berberine as a promising candidate for long-term chemoprevention.

“In conclusion, at 6 to 8 years after treatment, berberine can prevent colorectal adenoma recurrence and colorectal neoplasm occurrence without continual supplementation,” wrote the researchers. “Thus, it might be a crucial secondary chemopreventive agent for colorectal adenoma and a potential candidate for colorectal cancer.”

References

1. Tan YJ, Zou TH, Yu K, et al. Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-year follow-up of a randomized clinical trial. Cell Rep Med. 2025;102293. doi:10.1016/j.xcrm.2025.102293

2. What is berberine? Mayo Clinic. April 22, 2025. Accessed August 13, 2025. https://store.mayoclinic.com/education/what-is-berberine/