The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies sometimes used by patients with cancer. In this installment, Eugenie Spiguel, MSN, ANP-BS, and Jyothirmai Gubili, MS, focus on Ma Zi Ren Wan because it is widely used in traditional Chinese medicine for managing constipation.
Eugenie Spiguel, MSN, ANP-BS
Jyothirmai Gubili, MS
Overview
Constipation is a common condition characterized by decreased stool frequency, incomplete evacuation, straining, and a sense of anorectal blockage. Approximately 60% of patients with cancer report having suffered constipation. Contributing factors can be organic, functional, or drug-associated in nature.1 Standard care involves laxatives, fiber supplements, stool softeners, or enemas, which are not entirely effective and may also be associated with undesirable effects.
Ma Zi Ren Wan, a traditional Chinese medicine formula, has a long medicinal history as a treatment for constipation. Described in the traditional Chinese medicine “Treatise on Cold-Induced Disorders,” written around the 3rd century, Ma Zi Ren Wan comprises six herbs. A systematic review reported this formula to be widely used in China for managing constipation,2 and epidemiologic data have shown it to be often prescribed to patients with prostate cancer in Taiwan.3
Ma Zi Ren Wan
Common Names: Hemp Seed Pill, Hemp Seed Formula, Mashiningan, TJ-126
The Science
In an 8-week randomized trial of 291 patients with functional constipation, Ma Zi Ren Wan (7.5 g twice daily) was found to be more effective than senna (15 mg daily), an herbal laxative, or a placebo. At the end of the treatment period, the complete responses were 68% with Ma Zi Ren Wan vs 57.7% with senna vs 33.0% with placebo (P < .005). Complete response was defined as a greater than one increase in complete spontaneous bowel movement per week when compared with baseline.
In addition, patients given Ma Zi Ren Wan had a significant increase in colonic transit along with decreased straining and global constipation symptoms. Furthermore, the benefits were maintained at the 16-week follow-up (47.4% with Ma Zi Ren Wan vs 20.6% with senna vs 17.5% with placebo).4
Another study found similar benefits. Ma Zi Ren Wan (7.5 mg twice daily) produced durable improvements in complete spontaneous bowel movement compared with placebo in a randomized trial of 120 patients experiencing functional constipation. The responder rate for complete spontaneous bowel movement with Ma Zi Ren Wan was 43.3% vs 8.3% with placebo (P < .005) at 8 weeks, with benefits enduring at the 16-week follow-up (30.0% vs 15.0%, P < .005). Those given Ma Zi Ren Wan also needed less rescue therapy compared with the placebo arm.5
In addition, a systematic review and meta-analysis (17 trials, 1,681 patients) found Ma Zi Ren Wan to be safe and useful in relieving functional constipation without increasing adverse effects compared with controls.6 Of note, this analysis included studies involving pediatric patients with cancer,7,8 as well as adult patients with cancer who had opioid-associated9 and chemotherapy-related10 constipation.
Of note, all the studies to date have been conducted in Asian population. Whether Ma Zi Ren Wan can ameliorate constipation in diverse communities is not known. Studies are also needed to determine its potential in alleviating non-functional constipation.
The mechanisms underlying the physiologic effects of Ma Zi Ren Wan are not fully known. Small studies have implicated some herbs in this formula in restoring gastrointestinal homeostasis to improve colonic motility and to relieve constipation. Findings also indicate that Ma Zi Ren Wan downregulates oleamide, known to regulate intestinal motility, likely by enhancing fatty acid amide hydrolase–mediated degradation.11,12
Adverse Reactions
In clinical studies, Ma Zi Ren Wan has been reported to cause cramping and bloating, diarrhea, gas, nausea and vomiting, headache, dizziness, micturition difficulty, and to worsen rhinitis.4,5,7,13,14
Herb-Drug Interactions
No herb-drug interactions have been reported.
Summary
Constipation is a common and distressing symptom in the cancer population. Ma Zi Ren Wan has been used successfully for treatment of functional constipation in Asia. The side-effect profile is similar to more commonly used over-the-counter constipation medications. It has also been shown to be more effective then senna and placebo in a large randomized clinical trial. As well, the use of Ma
Zi Ren Wan for constipation allowed for less rescue medication. This effective herbal formula can be safely considered for patients with functional constipation. It is also important to guide patients to seek licensed traditional Chinese medicine practitioners experienced in working with cancer patients for proper use of Ma Zi Ren Wan.15
DISCLOSURE: Ms. Spiguel and Ms. Gubili reported no conflicts of interest.
REFERENCES
1. Wickham RJ: Managing constipation in adults with cancer. J Adv Pract Oncol 8:149-161, 2017.
2. Zhong LLD, et al: Chinese herbal medicine for constipation: zheng-based associations among herbs, formulae, proprietary medicines, and herb-drug interactions. Chin Med 11:28, 2016.
3. Lin YH, et al: Coprescription of Chinese herbal medicine and Western medications among prostate cancer patients: A population-based study in Taiwan. Evid Based Complement Alternat Med 2012:147015, 2012.
4. Zhong LLD, et al: Efficacy of MaZiRenWan, a Chinese herbal medicine, in patients with functional constipation in a randomized controlled trial. Clin Gastroenterol Hepatol 17:1303-1310.e18, 2019.
5. Cheng CW, et al: Efficacy of a Chinese herbal proprietary medicine (hemp seed pill) for functional constipation. Am J Gastroenterol 106:120-129, 2011.
6. Yang M, et al: Herbal formula MaZiRenWan (hemp seed pill) for constipation. Phytomedicine 82:153459, 2021.
7. Zhang GJ, et al: Clinical observation of 30 cases of children with gastrointestinal dry and hot constipation treated with hemp seed pill. Chinese Pediatrics of Integrated Traditional and Western Medicine. 6:459-461, 2014.
8. Chang YS: A clinical Study on the treatment of functional chronic constipation in children with hemp seed pill. Chinese Pediatrics of Integrated Traditional and Western Medicine 9:216-218, 2017.
9. Li XY, et al: Therapeutic effect of modified MaZiRen pill for treating constipation caused by opium alike. Chinese Journal of Experimental Traditional Medical Formula 18:312-314, 2012.
10. Lu XY: Treatment of 45 cases of constipation caused by chemotherapy with hemp seed pill. Henan Traditional Chinese Medicine. 34:810-811, 2014.
11. Huang T, et al: Uncovering the mechanisms of Chinese herbal medicine (MaZiRenWan) for functional constipation by focused network pharmacology approach. Front Pharmacol 9:270, 2018.
12. Huang T, et al: Chinese herbal medicine (MaZiRenWan) improves bowel movement in functional constipation through down-regulating oleamide. Front Pharmacol 10:1570, 2019.
13. Pan HP, Duan YS: Observation on 48 cases of drug-induced constipation treated with hemp seed pill. Journal of Practical Traditional Chinese Medicine 26:150-151, 2010.
14. Zhang Q, Gao P: Clinical observation on the treatment of constipation after chemotherapy with hemp seed pill. Journal of Liaoning University of Traditional Chinese Medicine 11:117-118, 2009.
15. National Certification Commission for Acupuncture and Oriental Medicine. Available at https://www.nccaom.org. Accessed May 31, 2022.
