What is berberine?

Berberine is an isoquinolone alkaloid with a distinctive yellow colour.¹

Where does berberine come from?

Berberine is an important constituent of several medicinal plants, including various species of Berberis spp. (including Barberry), Hydrastis canadensis (Golden Seal), Coptis chinensis (Chinese Goldthread), and Phellodendron amurense (Phellodendron).¹

When might berberine be prescribed?

- Berberine has a broad spectrum of therapeutic activity and has shown benefit in
   a wide range of health conditions, including the following:

- Metabolic syndrome, encompassing obesity, dyslipidaemia, hypertension, and
   diabetes²

- Non-alcoholic fatty liver disease²

- Improving insulin sensitivity, dyslipidaemia and ovulation in polycystic ovarian
   syndrome (PCOS)^2,3

- Atherosclerosis²

- Diarrhoeal disease²

- Bacterial infections, including Helicobacter pylori infection (with triple therapy).⁴
   Berberine also appears to exert synergistic effects with some antibiotics, which
   may prove to be an effective therapeutic tool for antibiotic-resistant bacterial
   infections.²

- Correcting intestinal microbiome imbalances in other conditions such as Graves’
   disease⁵ and Parkinson’s disease⁶

- Preventing antipsychotic-induced weight gain in schizophrenia via a regulatory
   effect on leptin levels.⁷ Berberine may also improve negative symptoms of
   schizophrenia.⁸

- Reducing the risk of recurrence of colorectal adenomas⁹

- Reducing the risk of postoperative atrial fibrillation via effects on the intestinal
   microbiota¹⁰

How does berberine exert its effect?

Microbiome modulation is key to berberine’s mechanism of action in metabolic conditions such as diabetes. Berberine has been shown to suppress several bacterial strains that produce single sugars from fermenting polysaccharides or oligosaccharides, including Ruminococcus bromii. R. bromii produces the secondary bile acid deoxycholic acid (DCA),¹¹ which negatively impacts glycaemic control by altering insulin signalling.^12,13 The antidiabetic drug, metformin, works via a similar mechanism to improve glucose tolerance. Metformin modulates Bacteroides fragilis levels, resulting in a change of bile acid composition and bile acid signalling in the gut.¹⁴

Despite berberine’s broad spectrum of antimicrobial activity, tests have shown that it is less active against healthy bowel flora than pathogenic bacteria.¹⁵ In fact, in vivo studies have shown that berberine is able to enrich healthy bowel flora (short-chain fatty acid [SCFA] producers).¹⁶

Is berberine safe long term?

Due to its poor oral bioavailability and the chronic nature of many of its indications, berberine is usually used at relatively high doses for longer periods of time.^1,2

Appropriate oral use of berberine has been safely used in doses up to 1500 mg per day for six months.¹⁷ In a longer-term study in 1108 colorectal cancer patients, taking 600 mg of berberine daily for 24 months was found to be safe, as no major adverse effects were reported.⁹

What side effects may arise while taking berberine?

Oral berberine treatment is generally well tolerated. The most common adverse effects appear to be gastrointestinal, i.e., abdominal pain and distension, constipation, diarrhoea, flatulence, nausea, and vomiting.¹⁷ The occurrence of gastrointestinal adverse effects does not appear to influence the efficacy or safety of treatment.¹¹

The risk of side effects can be reduced by prescribing according to personalised medicine principles. This is a developing area of research known as precision medicine, assessing the individual’s genes, age, diet, body systems, microbiota, environment, and lifestyle, and adjusting treatment accordingly.¹⁸ Rather than prescribing berberine as an isolated constituent, naturopaths and herbalists typically prescribe berberine-containing herbs such as Phellodendron, which has a long history of safe traditional use.¹⁹

References

1. Habtemariam S. Berberine pharmacology and the gut microbiota: a hidden therapeutic link. Pharmacol Res. 2020 May;155:104722. DOI: 10.1016/j.phrs.2020.104722

2. Imenshahidi M, Hosseinzadeh H. Berberine and barberry (Berberis vulgaris): a clinical review. Phytother Res. 2019 Mar;33(3):504-523. DOI: 10.1002/ptr.6252

3. Xie L, Zhang D, Ma H, He H, Xia Q, Shen W, et al. The effect of berberine on reproduction and metabolism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized control trials. Evid Based Complement Alternat Med. 2019;2019:7918631. DOI: 10.1155/2019/7918631

4. Hu Q, Peng Z, Li L, Zou X, Xu L, Gong J, et al. The efficacy of berberine-containing quadruple therapy on helicobacter pylori eradication in China: a systematic review and meta-analysis of randomized clinical trials. Front Pharmacol. 2019;10:1694. DOI: 10.3389/fphar.2019.01694

5. Han Z, Cen C, Ou Q, Pan Y, Zhang J, Huo D, et al. The potential prebiotic berberine combined with methimazole improved the therapeutic effect of Graves' disease patients through regulating the intestinal microbiome. Front Immunol. 2021;12:826067. DOI: 10.3389/fimmu.2021.826067

6. Li J, Meng P, Zhang J, He M. Effect of berberine hydrochloride on the diversity of intestinal flora in Parkinson's disease patients. Contrast Media Mol Imaging. 2022;2022:8381870. DOI: 10.1155/2022/8381870

7. Qiu Y, Li M, Zhang Y, Liu Y, Zhao Y, Zhang J, et al. Berberine treatment for weight gain in patients with schizophrenia by regulating leptin rather than adiponectin. Asian J Psychiatr. 2022 Jan;67:102896. DOI: 10.1016/j.ajp.2021.102896

8. Li M, Qiu Y, Zhang J, Zhang Y, Liu Y, Zhao Y, et al. Improvement of adjunctive berberine treatment on negative symptoms in patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2022 Jun;272(4):633-642. DOI: 10.1007/s00406-021-01359-4

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

10. Zhang J, Wang Y, Jiang H, Tao D, Zhao K, Yin Z, et al. Preventive effect of berberine on postoperative atrial fibrillation. Circ Arrhythm Electrophysiol. 2022 Oct;15(10):e011160. DOI: 10.1161/CIRCEP.122.011160

11. Zhang Y, Gu Y, Ren H, Wang S, Zhong H, Zhao X, et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020 Oct;11(1):5015. DOI: 10.1038/s41467-020-18414-8

12. Zaborska KE, Lee SA, Garribay D, Cha E, Cummings BP. Deoxycholic acid supplementation impairs glucose homeostasis in mice. PLoS One. 2018;13(7):e0200908. DOI: 10.1371/journal.pone.0200908

13. Kuipers F, Bloks VW, Groen AK. Beyond intestinal soap--bile acids in metabolic control. Nat Rev Endocrinol. 2014 Aug;10(8):488-498. DOI: 10.1038/nrendo.2014.60

14. Sun L, Xie C, Wang G, Wu Y, Wu Q, Wang X, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018 Dec;24(12):1919-1929. DOI: 10.1038/s41591-018-0222-4

15. Yan D, Wei L, Xiao XH, Han YM. Microcalorimetric investigation of effect of berberine alkaloids from Coptis chinensis Franch on intestinal diagnostic flora growth. Chin Sci Bull. 2009;54(3):369-373. DOI: 10.1007/s11434-009-0001-1

16. Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS One. 2012;7(8):e42529. DOI: 10.1371/journal.pone.0042529

17. Natural Medicines Database [Internet]. Denver (CO): TRC Healthcare; 2023. Berberine; 2023 Sep [cited 2023 Nov 29]. Available from: https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1126

18. Cheng H, Liu J, Tan Y, Feng W, Peng C. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine. J Pharm Anal. 2022 Aug;12(4):541-555. DOI: 10.1016/j.jpha.2021.10.003

19. Sun Y, Lenon GB, Yang AWH. Phellodendri cortex: a phytochemical, pharmacological, and pharmacokinetic review. Evid. Based Complementary Altern. Med. 2019 Apr;2019. DOI: 10.1155/2019/7621929