Berberine Calms GI Upset From Radiation Therapy

Study assesses the effect of berberine on toxicities resulting from radiation treatment

By Jacob Schor, ND, FABNO

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Reference

Li GH, Wang DL, Hu YD, et al. Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy. Med Oncol. 2010;27(3):919-925.

Design

Randomized, placebo-controlled, prospective trial. Two subgroups of patients received the study medication throughout the trial along with standard radiotherapy, and 2 subgroups received placebo. A 5th subgroup received placebo for the first 2 weeks of the trial and then was given the active medication.

Participants

The results of several cohorts were reported in this single paper. Thirty-six patients with seminoma or lymphomas were treated; half received the trial medication, the remainder placebo. Forty-two patients with cervical cancer were also treated, again half with medication and half with placebo. A 5th cohort was formed from 8 patients randomly selected from both groups to begin active medication 2 weeks after starting with placebo.

Study Medication and Dosage

Berberine, 300 mg tablet 3 times a day

Outcome Measures

A radiation oncologist graded radiation-induced toxicities, such as fatigue, anorexia, and nausea, according to the common toxicity criteria (CTC) version 2.0.1

Key Findings

Taking berberine significantly decreased the incidence and severity of radiation-induced acute intestinal syndrome in these patients compared to the patients in the control group (P<0.05). Berberine postponed the symptoms so that if they occurred they did so later in the course of treatment.

Practice Implications

Approximately half of the patients diagnosed with pelvic or abdominal cancers will receive radiation treatment. Resultant damage to the noncancerous tissue, particularly the intestines, is common and can be severe.2 Abayomi et al reported in 2009 that of 117 women who had been treated with radiation therapy for cervical or endometrial cancer, 47% ended up with chronic radiation enteritis.3 Although this paper examined only acute symptoms, our assumption or hope is that decreasing acute toxicities may reduce progression to chronic inflammatory states or delayed sequelae of radiation treatments.

This is not the first report suggesting that berberine protects against radiation damage. A paper by the same authors, Li et al, published in August 2010, also reported that berberine protects against radiation-caused intestinal injury. This earlier study was on mice, not people. In it mice were given berberine and then subjected to high doses of radiation. Berberine reduced measurements of radiation damage and delayed mortality that is, it reduced the lethality of treatment.4

An earlier human clinical trial that assessed the effect of berberine on toxicities resulting from radiation treatment of non-small cell lung cancer (NSCLC) was published in 2008. Liu et al gave either berberine or placebo to 90 patients who underwent chest radiation therapy. Chest radiation causes injury in a way similar to what pelvic radiation does, though in this case it is called radiation-induced lung injury (RILI).

After 6 weeks, only 45.2% of patients taking berberine had symptoms of RILI compared to 72.1% of those taking the placebo. At 6 months the numbers were 35.7% and 65.1% respectively. Measurements of lung function were also significantly better in those taking berberine.5

Thus berberine may reduce the radiation-induced toxicity symptoms caused by pelvic, abdominal, and chest radiation treatments. Will it also reduce the cytotoxicity of the treatments?

At this point, there are hints that at least in some cancers, berberine makes the cancer cells more sensitive to radiation treatment.

At this point, there are hints that at least in some cancers, berberine makes the cancer cells more sensitive to radiation treatment. Peng et al reported in 2008 that berberine has a synergistic effect with radiation against lung cancer.6

Berberine without radiation certainly has a significant anticancer effect against a wide range of cancer types. It induces apoptosis in glioblastoma cells.7 Papers published in the last few months suggest berberine also acts against cervical,8 liver,9 and colon cancer.10 Berberine enhances the cytoxic effect of the chemotherapy drug cisplatin.11

It is possible that berberine will decrease the peripheral damage and toxic side effects of radiation therapy, as well as improve patient outcomes by enhancing radiation action.

About the Author

Jacob Schor ND, FABNO, is a graduate of National College of Naturopathic Medicine, Portland, Oregon, and recently retired from his practice in Denver, Colorado. He served as president to the Colorado Association of Naturopathic Physicians and is on the board of directors of the Oncology Association of Naturopathic Physicians. He is recognized as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the International Journal of Naturopathic Medicine, Naturopathic Doctor News and Review (NDNR), and Integrative Medicine: A Clinician's Journal. In 2008, he was awarded the Vis Award by the American Association of Naturopathic Physicians. His writing appears regularly in NDNR, the Townsend Letter, and Natural Medicine Journal, where he is the Abstracts & Commentary editor.

References

    <p>1 Cancer Therapy Evaluation Program. <em>Common Toxicity Criteria</em>, Version 2.0. Published April 30, 1999. Available at: <a href="http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcv20_4-30-992.pdf" target="_blank">http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcv20_4-30-992.pdf</a>. Accessed August 29, 2011.

    <p>2  Pal N. Radiation enteritis and proctitis.<em> Medscape Reference</em>. Updated October 24, 2010. Available at <a href="http://emedicine.medscape.com/article/197483-overview" target="_blank">http://emedicine.medscape.com/article/197483-overview</a>. Accessed August 31, 2011.

    <p>3  Abayomi J, Kirwan J, Hackett A. The prevalence of chronic radiation enteritis following radiotherapy for cervical or endometrial cancer and its impact on quality of life.<em> Eur J Oncol Nurs</em>. 2009;13(4):262-267.

    <p>4  Li GH, Zhang YP, Tang JL, Chen ZT, Hu YD, Wei H, Li DZ, Hao P, Wang DL. Effects of berberine against radiation-induced intestinal injury in mice.<em> Int J Radiat Oncol Biol Phys.</em> 2010;77(5):1536-1544.

    <p>5  Liu Y, Yu H, Zhang C, et al. Protective effects of berberine on radiation-induced lung injury via intercellular adhesion molecular-1 and transforming growth factor-beta-1 in patients with lung cancer.<em> Eur J Cancer</em>. 2008;44(16):2425-2432.

    <p>6  Peng PL, Kuo WH, Tseng HC, Chou FP. Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death.<em> Int J Radiat Oncol Biol Phys.</em> 2008;70(2):529-542.

    <p>7  Eom KS, Kim HJ, So HS, Park R, Kim TY. Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction. <em>Biol Pharm Bull.</em> 2010;33(10):1644-1649.

    <p>8  Mahata S, Bharti AC, Shukla S, Tyagi A, Husain SA, Das BC. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells. <em>Mol Cancer.</em> 2011;10(1):39.

    <p>9  Hou Q, Tang X, Liu H, et al. Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147.<em> Cancer Sci.</em> 2011 Mar 28.

    <p>10  Wu K, Yang J, Zhou Q. [Preventive effects of berberine on experimental colon cancer and relationship with cyclooxygenase-2 expression]. <em>Zhongguo Zhong Yao Za Zhi</em>. 2010;35(20):2768-2773

    <p>11  Youn MJ, So HS, Cho HJ, et al. Berberine, a natural product, combined with cisplatin enhanced apoptosis through a mitochondria/caspase-mediated pathway in HeLa cells. <em>Biol Pharm Bull</em>. 2008;31(5):789-795.