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Chinese Herbal May Be Chemoprotective Against Colorectal Cancer

— Polypectomy patients given the supplement developed fewer colorectal adenomas

MedpageToday

The herbal-based supplement berberine reduced the recurrence risk of colorectal adenomas and polypoid lesions after polypectomy versus placebo, a Chinese randomized trial found.

With median follow-up of 2 years, 36% of berberine recipients and 47% of placebo recipients had recurrent adenomas, for an unadjusted relative risk ratio for recurrence of 0.77 (95% CI 0·66-0.91, P=0·001), reported Jing-Yuan Fang, MD, of Shanghai Jiao-Tong University School of Medicine in Shanghai, and colleagues in .

Advanced adenomas were detected in 3% of the berberine group vs 6% in the placebo group, while non-advanced adenomas were detected in 33% vs 41% in these two arms.

No serious adverse events occurred, and no colorectal cancers were detected during colonoscopic follow-up, the researchers said.

"The results of this double-blind, placebo-controlled, randomized trial indicate that berberine could significantly decrease the risk of recurrence of colorectal adenoma," the investigators wrote, calling for further study of berberine's mechanism of action. "The low cost and safety profile of berberine suggest its potential in the chemoprevention of colorectal cancer."

The compound, whose chemical name is benzyltetrahydroxyquinoline, is now synthesized but was initially extracted from the herb coptis chinensis. A common ingredient in traditional Chinese medicines, this alkaloid has been used for centuries to cure diarrhea and enteritis, and is thought to have a positive effect on the microbiota of the gut.

Animal research has suggested an antitumor effect, with a reporting that berberine reduced colonic tumorigenesis in mice by modulating the tumor microenvironment. Berberine has also demonstrated boosting energy expenditure by increasing brown fat activity in rodents.

Study Details

From November 2014 to December 2016, a total of 553 participants were randomly assigned to receive berberine at 0.3 grams twice daily and 555 were assigned to placebo. The participants' mean age was about 57 in both arms, and a total of 65% were male. Slightly more (41%) in the placebo group had baseline advanced adenomas than in the berberine group (35%).

The full analysis set consisted of 429 patients in the treatment group and 462 in the placebo group. The final analysis, done in 2018 after the last-enrolled patient had completed 2 years of follow-up, found that 155 in the berberine arm and 216 in the placebo arm had recurrent adenomas.

The most common adverse event in both groups was constipation: six (1%) of 446 patients in the berberine group versus one (less than 0.5%) of 478 patients in the placebo group.

"Further randomized trials should be performed to replicate our findings and explore dose responses," Fang's group wrote, noting that an open-label follow-up study is underway to investigate the relationship between berberine and advanced colorectal adenoma or cancer.

Writing in an Sohee Kwon, MD, and Andrew T. Chan, MD, MPH, both of Massachusetts General Hospital in Boston, called the results exciting, writing, "This well-designed trial is the first evidence of a causal relationship for berberine and colorectal neoplasia in human beings, validating the significant body of experimental data and offering compelling proof-of-principle of the potential value of repurposing a natural product for chemoprevention."

Despite these promising results, however, the commentators cautioned that it is too soon to recommend berberine in the post-polypectomy setting and called for further trials to evaluate the compound, especially in combination with other chemopreventives such as aspirin.

"Taken together, such studies may open a new frontier for chemoprevention by charting an exciting new future for an agent with an ancient past," Kwon and Chan wrote.

Study limitations, the researchers noted, included the inability to assess plasma concentrations of berberine and the relationship to recurrent adenomas owing to the poor oral bioavailability of berberine and its low blood absorption from the intestines. Additionally, the number and time intervals of colonoscopies were not specifically defined in the study protocol, and the detection rate of colorectal adenoma might have increased with greater frequency and prolonged intervals. Also, because colonoscopy with a confirmed clean colon was not performed after initial polypectomy, some lesions may have been missed at baseline.

Finally, the team said, some participants withdrew and were lost to follow-up, and the study did not stratify randomization by age, sex, and site of enrollment nor analyze the location of adenoma recurrence.

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    Diana Swift is a freelance medical journalist based in Toronto.

Disclosures

This study was funded by the National Natural Science Foundation of China.

The authors reported having no competing interests.

Kwon reported having no competing interests; Chan disclosed ties to Bayer Pharma AG, Pfizer, and Janssen outside of the commentary.

Primary Source

The Lancet Gastroenterology & Hepatology

Chen Y-X, et al "Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study" Lancet Gastroenterol Hepatol 2020; DOI: 10.1016/S2468-1253(19)30409-1.

Additional Source

The Lancet Gastroenterology & Hepatology

Kwon S, Chan AT "Extracting the benefits of berberine for colorectal cancer" Lancet Gastroenterol Hepatol 2020; DOI: 10.1016/S2468-1253(19)30430-3.