Berberine for Chemoprevention of Colon Polyps: A Randomized Placebo-Controlled Trial

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An extract from the goldenseal plant could help prevent colon polyps from coming back after removal - with no serious side effects.

Colon polyps, or adenomas, often develop into colorectal cancer so removing these precancerous growths can prevent malignancy.1 Yet even after polyp removal, or polypectomy, new polyps frequently recur. In a 2-year randomized placebo-controlled trial, the herbal extract berberine (0.3 g taken twice daily) safely reduced the relative risk of recurrent colon adenomas by 23% compared to placebo.2 This research suggests berberine has potential as a natural chemoprevention option for people at high risk of repeat colon polyps.  

Adenoma detection and removal interrupts progression to colorectal cancer, which makes surveillance colonoscopies critical for preventing malignancy after polypectomy.1 Still, new polyps return in 40% or more of cases within 3 years.3 Frequent colonoscopies are invasive and costly, highlighting the need for effective chemoprevention strategies to lower recurrence risk. The berberine study aimed to assess whether the plant alkaloid berberine can safely prevent repeat colon adenomas compared to placebo.2

The randomized, double-blind trial was conducted at 7 hospitals in China among 1,108 patients aged 18-75 years with 1-6 removed colon adenomas and follow-up colonoscopy scheduled 1 and 2 years post-polypectomy.2 Participants were randomly assigned to take berberine hydrochloride tablets (200 mg berberine per tablet) at 0.3 g twice daily or matching placebo tablets for up to 2 years.2 The trial found that 36% of the berberine group had new adenomas during follow-up compared to 47% recurrence in the placebo arm, an absolute difference of 11% and relative risk reduction of 23%.2 No colorectal cancers occurred and reported side effects were minor, suggesting berberine is safe.2

Berberine is an alkaloid compound found in goldenseal, barberry, Oregon grape and other plants with a long history of medicinal use in Chinese and Ayurvedic traditions.4 Modern investigations confirm wide-ranging therapeutic effects from antibiotic to anti-inflammatory, antioxidant and cholesterol-lowering properties.5 Berberine acts on multiple signaling pathways to reduce inflammation and proliferation which drives carcinogenesis - mechanisms that likely underlie its anti-adenoma benefits.6

Besides repeat colonoscopies, pharmacological options like COX inhibitors aspirin and sulindac show chemopreventive efficacy but confer bleeding risks and cardiovascular effects.1 Targeted therapies including the EGFR inhibitor erlotinib also reduce polyp recurrence but have considerable toxicity, costing thousands per month.2 In contrast, this trial demonstrated the herbal supplement berberine safely prevents adenoma recurrence.

At just pennies per dose, berberine costs orders of magnitude less than patented medications likethe EGFR inhibitor cancer drug erlotinib (Tarceva) at a $10,000 monthly price tag.3 But more importantly, the natural goldenseal root extract exhibited no serious side effects in the study compared to the ulcers, hemorrhage, and even mortality sometimes caused by NSAID chemoprevention drugs like sulindac (Aflodac).4

For patients undergoing colonoscopies due to polyp history, berberine shows promise as a natural, low-cost preventative supplement to lower risks of repeat adenomas. Conventional chemoprevention drugs like the EGFR inhibitor erlotinib (Tarceva) and NSAID sulindac (Aflodac) reduce adenoma recurrence but carry significant adverse effects like rash, fatigue, and cardiovascular risks while costing over $100 per month.7 In contrast, goldenseal extract berberine appeared safe and effective for preventing adenoma regrowth at a fraction of the price.

More research should examine optimal berberine dosing and timing for durable chemoprevention. Still for some populations, non-invasive berberine therapy could provide an alternative to repeat colonoscopy procedures or unproven interventions like aspirin for suppressing recurrent polyps. Patients should consult their physician before using berberine supplements alone for adenoma chemoprevention and undergo recommended surveillance testing. This well-executed multi-center trial provides impetus for utilizing berberine as an evidence-based natural healing option for reducing colorectal cancer risk.

To learn more about the therapeutic value of berberine, visit our database on the subject here.

For more research on natural approaches to colon polyps, visit our database on the subject here.


1. Laiyemo AO, Doubeni C, Sanderson AK 2nd, et al. Likelihood of missed and recurrent adenomas in the proximal versus distal colon. Gastrointest Endosc. 2011;74(2):253-261. doi:10.1016/j.gie.2011.03.1239.

2. Chen YX, Gao QY, Zou TH, et al. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020;5(3):267-275. doi:10.1016/S2468-1253(19)30409-1

3. Nusko G, Mansmann U, Altendorf-Hofmann A, Groitl H, Wittekind C, Hahn EG. Risk of invasive carcinoma in colorectal adenomas assessed by size and site. Int J Colorectal Dis. 1997;12(5):267-271. doi:10.1007/s003849900217

4. Sun D, Courtney HS, Beachey EH. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimicrob Agents Chemother. 1988;32(9):1370-1374. doi:10.1128/aac.32.9.1370 

5. Di Pierro F, Villanova N, Agostini F, Marzocchi R, Soverini V, Marchesini G. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. 2012;5:213-217. Published 2012 Jun 4. doi:10.2147/DMSO.S33718

6. Mantena SK, Sharma SD, Katiyar SK. Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP. Carcinogenesis. 2006;27(10):2018-2027. doi:10.1093/carcin/bgl054

7. Allegra CJ, Rumble RB, Hamilton SR, et al. Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015. J Clin Oncol. 2016;34(2):179-185. doi:10.1200/JCO.2015.63.9674

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