Berberine improves IBS symptoms

Jacob Schor, ND, FABNO

www.DenverNaturopathic.com

April 25, 2016

 

A randomized controlled trial published last November suggests that berberine is useful in treating the irritable bowel syndrome and this has some curious implications.

 

In this 14-week single-center, double blind, placebo controlled clinical study, Chen et al randomized patients into two groups, and after a 2-week run-in, the participants received either the berberine HCl, 200 mg twice a day, or placebo twice a day for 8 weeks.  Treatments were discontinued after 8 weeks and the patients followed for an additional 4 weeks.

 

Between May 2011 and January 2015, 196 patients with IBS-D, aged 18–65 years, were recruited for this study from the Tenth People’s Hospital of Shanghai, Tongji University School of Medicine, Shanghai, China. All patients fulfilled the inclusion criteria based on the Rome III classification system for irritable bowel syndrome-diarrhea predominant.  A number of these patients were either excluded or unable to complete the study.  In the end, 70 patients in the berberine group and 62 in the placebo group completed the study. Patients ranged in age from 19 to 61 years in berberine group and from 18 to 65 years in placebo group.

 

The following Outcome Measures were tracked and assessed:  diarrhea, abdominal pain, urgent need for defecation frequency and any adverse events were assessed via daily questionnaires. Prior to administration of the medication and after completing the treatment, assessment of IBS symptom scores, depression and anxiety scale scores and the IBS scale for quality of life (QOL) was carried out

 

Both the berberine and the placebo groups reported a reduction in symptoms during the 8 weeks they took medication, though the placebo group reported less benefit. At week 8, diarrhea frequency was significantly lower in the berberine group than the placebo group (P= 0.032).

 

The berberine group, but not the placebo group, reported less urgency and frequency in defecation starting in week 4 and persisting through week 8 when the berberine was discontinued (P< 0.01).

 

Both groups reported less abdominal pain during the 8 weeks of treatment.  In the berberine group significant reductions in pain frequency were seen starting in week 3 of the study and continuing through week 8.  The pain frequency scores for week 8 represented a 64.6% (1.54 ± 0.26 vs. 4.35 ± 0.58) reduction compared with initial scores.  In the placebo group the final score represented a 29.4% (2.88 ± 0.37 vs. 4.08 ± 0.23) reduction.  The pain reduction was significantly greater in the berberine group than in the placebo group on week 6 (P< 0.01) and week 8 (P< 0.01).

 

Berberine significantly decreased overall IBS symptom score, anxiety score and depression score (P< 0.01). Berberine treatment was also associated with an increased QOL score (P<0.05).  No significant changes were seen on these scores in the placebo group (P> 0.05).

 

Additionally the overall IBS symptoms score, anxiety score and depression score were significantly lower in the berberine group compared to the placebo (P< 0.05). [1]

 

 

 

 

This clinical trial tells us two things.  First, and most importantly that berberine is effective in the treatment or irritable bowel syndrome when the predominant symptom is diarrhea.  The second is that many patients may also experience some benefit from simply taking a placebo.

 

Berberine’s beneficial actions are more complex and far reaching than our older image of it acting just as an ‘antibiotic’ and narrowly employing it in treating infectious gastritis. In this trial by Chen et al, those patients taking berberine not only experienced reduced frequency, urgency, diarrhea and abdominal discomfort, they also experienced significant reductions in anxiety and depression.

In this study the berberine used was isolated from Chinese Goldthread Rhizome (Coptis chinensis), while in North America, we generally use berberine extracted from Oregon grape (Mahonia aquifolium).

 

Berberine has antimicrobial action but also enhances the action of common drug antibiotics against common oral streptococcus species. [2]    It also has an antifungal action on its own and a synergistic action when given in combination with antifungal drugs. [3]    Berberine’s effect on diarrhea is more complex.  It limits secretory diarrhea in part by enhancing absorption of Na+ and water from the intestinal lumen.[4]    Berberine significantly increases pain tolerance in rats by affecting nitric oxide pathways.[5]   It slows gastrointestinal motility apparently by activating opioid pathways [6],  an action that is perhaps also responsible for it increasing pain tolerance. In fact, it doesn’t take much imagination to see how stimulating these pathways might also reduce anxiety.

 

While the benefits of berberine exceeded those reported in the placebo group, we must recognize that the placebo did have significant benefit at least during some weeks of this trial.  Placebo benefit is common in IBS studies. A 2010 meta-analysis by Ford and Moayyedi identified 73 randomized controlled studies that included 8,364 patients with IBS allocated to placebo. The pooled placebo response rate was 37.5% (95% CI 34.4-40.6%). Response rates were higher in European RCTs, RCTs that used physician-reported outcomes and RCTs using shorter duration of therapy. [7]   While this study was conducted in China, the 29.4% placebo response reported by Chen et al is remarkably close to Ford’s result. We must keep this placebo effect is mind in treating patients with IBS; about a third will respond even to a placebo for some period of time.  Don’t congratulate yourself too quickly in being a successful prescriber.

 

 

Berberine has many parallel uses as the drug metformin. Both increase insulin sensitivity, and are used to treat DM-2 and PCOS. [clinical uses for berberine are reviewed in an article in the Natural Medicine Journal published about four years ago: http://www.naturalmedicinejournal.com/journal/2012-12/clinical-applications-berberine ]  Both have similar actions on the gut microbiome, decreasing bacterial diversity and increasing production of short chain fatty acids. [8]  

Yet they seem to have different effects on gastric motility.  For many patients, metformin causes diarrhea and even vomiting through still unknown mechanisms. [9] 

 

These current results on IBS raise the question as to whether berberine could be useful at reducing some of the gut related side effects of metformin?  At this point there are no reports in the medical literature to inform us but it certainly is tempting to prescribe berberine to patients taking metformin, in particular those with digestive upset that they attribute to the drug.

 

There is a cautionary bit of information related to berberine that is newly reported in the literature.  In August 2015, a paper by Zhi et al reported that berberine act in combination with two macrolide antibiotics, azithromycin (Zithromax) and clarithromycin (Biaxin), by blocking hERG channels that regulate cardiac repolarization leading to Long QT Syndrome (LQTS).  Berberine combined with clarithromycin also significantly inhibits CYP3a. [10]  While this was a preliminary study, it should caution us against the use of berberine in combination with either of these antibiotics or with drugs that are dependent on CYP3a action

 

 

References:

 

1.  Chen C, Tao C, Liu Z, Lu M, Pan Q, Zheng L, Li Q, Song Z, Fichna J. A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. Phytother Res. 2015 Nov;29(11):1822-7.

 

2.  Dziedzic A, Wojtyczka RD, Kubina R. Inhibition of Oral Streptococci Growth Induced by the Complementary Action of Berberine Chloride and Antibacterial Compounds. Molecules. 2015 Jul 28;20(8):13705-24

 

3.  Liu H, Wang L, Li Y, Liu J, An M, Zhu S, Cao Y, et al. Structural optimization of berberine as a synergist to restore antifungal activity of fluconazole against drug-resistant Candida albicans. ChemMedChem. 2014 Jan;9(1):207-16.

 

4.  Zhang Y, Wang X, Sha S, et al. 2012. Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model. Fitoterapia 83: 1014–1022.

 

5.  Tang QL, Lai NL, Zhong YF, et al. 2013. Antinociceptive effect of berberine on visceral hypersensitivity in rats. World J Gastroenterol 19: 4582–4589.

 

6.  Feng Y, Li Y, Chen C, et al. 2013. Inhibiting roles of berberine in gut movement of rodents are related to activation of the endogenous opioid system. Phytother Res 27: 1564–1571

 

7.  Ford AC, Moayyedi P. Meta-analysis: factors affecting placebo response rate in the irritable bowel syndrome. Aliment Pharmacol Ther. 2010 Jul;32(2):144-58.

 

8.  Zhang X, Zhao Y, Xu J, Xue Z, Zhang M, Pang X, Zhang X, Zhao L1. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci Rep. 2015 Sep 23;5:14405. doi: 10.1038/srep14405.

 

9.  Bouchoucha M, Uzzan B, Cohen R. Metformin and digestive disorders. Diabetes Metab. 2011 Apr;37(2):90-6. doi: 10.1016/j.diabet.2010.11.002. Epub 2011 Jan 13.

 

10.  Zhi D, Feng PF, Sun JL, Guo F, Zhang R, Zhao X, Li BX. The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides. Eur J Pharm Sci. 2015 Aug 30;76:149-55.