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, Yen Nien (Jason) Hou, PharmD, DiplOM, LAc, and Jyothirmai Gubili, MS, focus on Shen Ling Bai Zhu San because it is widely used in traditional Chinese medicine for the treatment of chronic diarrhea.
Yen Nien (Jason) Hou, PharmD, DiplOM, LAc
Jyothirmai Gubili, MS
Scientific Name: Shen Ling Bai Zhu San
Common Names: Ginseng and Atractylodes formula, Samryungbaekchul-san, Jinryobyakujutsu-san
Overview
Diarrhea has a significant impact on the social functioning and quality of life of patients with cancer. Contributing factors include several types of malignant tumors, chemotherapy, radiotherapy, overuse of laxatives and antibiotics, malabsorption syndromes, colectomy, and enteral feeding.1 Long-term cancer survivors also experience diarrhea.2 Opiate agonists and adsorbents offer relief but are associated with side effects.
Shen Ling Bai Zhu San (SLBZS) is a botanical formula consisting of 10 herbs. It has a long medicinal history as a treatment for chronic diarrhea in traditional Chinese medicine. Today, practitioners in the Asia-Pacific region continue to prescribe it: A survey found SLBZS to be the second-most prescribed formula for managing symptoms in patients with colon cancer after surgery.3
The Science
Diarrhea-Predominant Irritable Bowel Syndrome: In an 8-week trial, 80 patients with diarrhea-predominant irritable bowel syndrome were randomly assigned to receive SLBZS (5 g, three times daily) plus the antispasmodic agent otilonium bromide (40 mg, three times daily); SLBZS plus placebo otilonium bromide; placebo SLBZS plus otilonium bromide; or placebo SLBZS plus placebo otilonium bromide. At the end of the study period, the authors found significant improvements in abdominal discomfort (P = .005) with SLBZS plus otilonium bromide and SLBZS plus placebo otilonium bromide compared with the other treatments. After 12 weeks, significant differences were also reported in both abdominal pain (P = .030), frequency of abdominal pain (P = .005), and stool consistency (P = .003). Differences in stool frequency and adverse effects, however, were statistically insignificant (P > .05).4
Ulcerative Colitis: In a 12-week clinical trial, 48 patients were randomly assigned to receive SLBZS (6 g, three times daily) or the standard medication for ulcerative colitis, mesalamine (1 g, four times daily). Data revealed that SLBZS was superior to mesalamine in controlling diarrhea, abdominal pain, and fever, and the improvements were statistically significant (P > .05).5
Similar findings were reported in another study of 100 patients. Compared with those who received mesalamine (1 g, four times daily), patients given -SLBZS (250 mL daily in divided doses) had significant improvements in their symptoms after 24 weeks (P > .05). Although adverse effects that included nausea, vomiting, heartburn, and constipation were less frequent with SLBZS, the difference was statistically insignificant.6
Additionally, SLBZS has been reported to be useful in patients experiencing chronic diarrhea of an unknown etiology. In a study of 150 patients, SLBZS (300 mL daily in divided doses) was found to be more effective for symptom control than the quinolone antibiotic norfloxacin (0.1 g, three times daily).7
A large systematic review and meta-analysis (14 trials, 1,158 patients with diarrhea) also concluded that SLBZS, used alone or combined with conventional antidiarrheal agents, was associated with greater patient-reported satisfaction compared with conventional medicine (P < .00001 and P = .0004, respectively). Of note, the use of SLBZS was not correlated with a higher risk of adverse reactions (eg, constipation, nausea, vomiting, or abdominal distention) compared with conventional treatments or placebo (P = .009).8
Guest Editor
Jun J. Mao, MD, MSCE
Dr. Mao is the Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.
Although available data suggest that SLBZS is safe and beneficial in patients with chronic diarrhea, most of the studies have been conducted in Asian populations, and many are limited by poor methodology, small sample sizes, variable dosing regimens, and moderate risk of bias in reporting outcomes. Larger, well-designed clinical trials are needed to further the evidence base. Studies are also needed to determine the effectiveness of SLBZS in non-Asian populations.
Mechanistic studies have revealed that the components of SLBZS may help to promote the integrity of the intestinal barrier; modulate gut microbiota by reducing levels of potential pathogens while increasing the numbers of beneficial species; and regulate inflammatory factors.9-12
Adverse Reactions
In clinical studies, SLBZS has been reported to cause constipation, nausea, vomiting, abdominal distension, rash, and allergy.6,13,14
Summary
SLBZS is used in patients with diarrhea especially with accompanying fatigue, and therefore it contains Ren Shen (Asian ginseng). Because this herb may increase the risk of bleeding, use of SLBZS should be discontinued at least 1 week prior to surgery. SLBZS also contains Gan Cao (licorice) and Shan Yao (Chinese yam related to wild yam), which have estrogenic properties. However, data are lacking to determine whether SLBZS acts as a phytoestrogen.
OF NOTE
Shen Ling Bai Zhu San, an herbal formula used in Traditional Chinese Medicine, may benefit patients with chronic diarrhea. Methodologically robust studies are needed to strengthen the current evidence.
It is advisable for patients with hormone-sensitive breast cancer to discuss with their physicians the risks and benefits of starting or continuing SLBZS. It is also important to guide patients to seek licensed traditional Chinese medicine practitioners experienced in working with patients who have cancer for proper use of this formula.15
DISCLOSURE: Dr. Hou and Ms. Gubili reported no conflicts of interest.
REFERENCES
1. Solomon R, Cherny NI: Constipation and diarrhea in patients with cancer. Cancer J 12:355-364, 2006.
2. Verhaar S, Vissers PAJ, Maas H, et al: Treatment-related differences in health related quality of life and disease specific symptoms among colon cancer survivors: Results from the population-based PROFILES registry. Eur J Cancer 51:1263-1273, 2015.
3. Chao TH, Fu PK, Chang CH, et al: Prescription patterns of Chinese herbal products for post-surgery colon cancer patients in Taiwan. J Ethnopharmacol 155:702-708, 2014.
4. Lee JH, Kim JI, Baeg MK, et al: Effect of Samryungbaekchul-san combined with otilonium bromide on diarrhea-predominant irritable bowel syndrome: A pilot randomized controlled trial. J Clin Med 8:1558, 2019.
5. He KS: Ulcerative colitis spleen qi deficiency parallel randomized controlled study Shenlingbaizhu casual treatment. J Pract Trad Chin Int Med 28:58-59, 2014.
6. Quan L, Tan J: Clinical study of Shenling Baizhu San for ulcerative colitis. J New Chin Med 49:42-44, 2017.
7. Ma Z: Clinical observation of Shen Ling Bai Zhu San in treatment of chronic diarrhea. Contemp Med 18:148, 2012.
8. Wang H, Hou YN, Yang M, et al: Herbal formula Shenling Baizhu San for chronic diarrhea in adults: A systematic review and meta-analysis. Integr Cancer Ther 21:15347354221081, 2022.
9. Lv WJ, Liu C, Li YF, et al: Systems pharmacology and microbiome dissection of Shen Ling Bai Zhu San reveal multiscale treatment strategy for IBD. Oxid Med Cell Longev 2019:8194804, 2019.
10. An X, Bao Q, Di S, et al: The interaction between the gut Microbiota and herbal medicines. Biomed Pharmacother 118:109252, 2019.
11. Shi K, Qu L, Lin X, et al: Deep-fried Atractylodis Rhizoma protects against spleen deficiency-induced diarrhea through regulating intestinal inflammatory response and gut microbiota. Int J Mol Sci 21:124, 2019.
12. Ma Q, Ouyang Y, Meng F, et al: A review of pharmacological and clinical studies on the application of Shenling Baizhu San in treatment of ulcerative colitis. J Ethnopharmacol 244:112105, 2019.
13. Li Q, Jiang J: Clinical observation on 80 cases of diarrhea predominant irritable bowel syndrome treated with Shen ling Bai Zhu granule. Guid J Trad Chin Med Pharm 19:41-42, 2013.
14. Wang MH, Wang H: Clinical effect of Shenling Baizhu San in treating diarrhea with spleen deficiency. Shenzhen J Integr Trad Chin West Med 29:59-60, 2019.
15. National Certification Commission for Acupuncture and Oriental Medicine: NCCAOM Find a Practitioner Directory. Available at https://www.nccaom.org/find-a-practitioner-directory/. Accessed October 14, 2022.
Dr. Hou is the Manager of the “About Herbs” website, maintained by Memorial Sloan Kettering Cancer Center’s Integrative Medicine Service, and Ms. Gubili is Editor, both at the Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York.
About Herbs App
Dietary supplement use by patients with cancer has increased significantly over the past 3 decades despite insufficient evidence of safety and effectiveness. Yet, finding reliable sources of information about dietary supplements continues to be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information.
The Integrative Medicine Service at Memorial Sloan Kettering developed and maintains a free website About Herbs (www.mskcc.org/aboutherbs) that provides reliable and evidence-based information about herbs, vitamins, minerals and other dietary supplements, as well as unproven anticancer treatments. Each of the 290 and growing number of entries has health-care professional and patient versions that are regularly updated with the latest research findings.
The free About Herbs app is now available on both Android and iOS devices! Download at Google Play for Android devices and App Store for iOS.
