OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Chi R Yun – Generic

DRUG CLASS

Herbal and Dietary Supplements

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 24 May 2022

• Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4.

  (Expert review of hepatotoxicity published in 1999; hepatotoxicity of Asian herbal products and teas are discussed generally without focus on any specific product or herb).
• Seeff L, Stickel F, Navarro VJ. Hepatotoxicity of herbs and dietary supplements. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 631-58.

  (Review of hepatotoxicity of herbal and dietary supplements [HDS]; Chinese and other Asian herbal medicines and teas are discussed, including Breynia).
• Stedman C. Herbal hepatotoxicity. Semin Liver Dis. 2002;22:195–206. [PubMed: 12016550]

  (Review and description of patterns of herbal-induced liver injury, including discussion of potential risk factors, and herb-drug interactions).
• Ernst E. Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review. J Intern Med. 2002;252:107–13. [PubMed: 12190885]

  (Systematic review of literature on adulteration of herbals with conventional medications, in 15 case reports and 2 cases series of 21 patients; included NSAIDs, corticosteroids, benzodiazepines, diuretics and antidiabetic medications, in up to 24% of products).
• Lin TJ, Tsai MS, Chiou NM, Deng JF, Chiu NY. Hepatotoxicity caused by Breynia officinalis. Vet Hum Toxicol. 2002;44:87–8. [PubMed: 11931510]

  (Two women ages 43 and 51 years took large amounts of Breynia [one in suicide attempt] and rapidly developed vertigo, vomiting, headache and numbness [peak bilirubin 2.2 and 1.0 mg/dL, ALT 2443 and 2730 U/L, Alk P 103 and 107 U/L], resolving over the next 4 to 6 weeks).
• Lin TJ, Su CC, Lan CK, Jiang DD, Tsai JL, Tsai MS. Acute poisonings with Breynia officinalis—an outbreak of hepatotoxicity. J Toxicol Clin Toxicol. 2003;41:591–4. [PubMed: 14514003]

  (Breynia officinalis is used in many Chinese medicines, but it also contains a poison and the plant can be mistaken for other herbs; 19 Chinese villagers drank a soup made from Breynia and developed diarrhea, nausea and liver test abnormalities [peak bilirubin 1.5-2.6, ALT 65-7398 U/L, Alk P 269 U/L], returning to normal in 1-2 months).
• Wai CT, Tan BH, Chan CL, Sutedja DS, Lee YM, Khor C, Lim SG. Drug-induced liver injury at an Asian center: a prospective study. Liver Int. 2007;27:465–74. [PubMed: 17403186]

  (Prospective survey of drug induced liver injury presenting over 26 months at a single hospital in Singapore identified 31 cases, ages 18-90 years, 55% male, Chinese traditional medicines being implicated in 17 [55%] and Malay agents in 5 cases [16%], adulterants were found in 9 of 31 tested traditional agents [codeine, corticosteroids, metformin, mercury, nonsteroidal antiinflammatory agents]).
• García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry. Rev Esp Enferm Dig. 2008;100:688–95. [PubMed: 19159172]

  (Among 521 cases of drug induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals, none attributed to Breynia).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications; Breynia not listed).
• Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis. 2009;29:373–82. [PubMed: 19826971]

  (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS including traditional Chinese herbal medicines; breynia not discussed).
• Wang YP, Shi B, Chen YX, Xu J, Jiang CF, Xie WF. Drug-induced liver disease: an 8-year study of patients from one gastroenterological department. J Dig Dis. 2009;10:195–200. [PubMed: 19659787]

  (30 patients with drug induced liver disease seen at a single medical university in Shanghai between 2000 and 2008, of which 12 were attributed to Chinese herbs, but specific agents not discussed, 9 were jaundiced, 6 hepatocellular, 3 cholestatic and 2 mixed).
• Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int. 2012;32:1543–56. [PubMed: 22928722]

  (Systematic tabulation of the literature on hepatotoxicity of herbals does not list or discuss Chi R Yun or Breynia).
• Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37:3–17. [PubMed: 23121117]

  (Review of HDS associated hepatotoxicity does not discuss Chi R Yun or Breynia officinalis).
• Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60:1399–408. [PMC free article: PMC4293199] [PubMed: 25043597]

  (Among 85 cases of HDS associated liver injury enrolled in a US prospective study between 2004 and 2013, neither Chi R Yun nor Breynia officinalis were implicated in any).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a U.S. prospective database between 2004 and 2012, HDS were implicated in 145 [16%] cases, but none were attributed to Chi R Yun or Breynia officinalis).
• Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology. 2015;148:517–532.e3. [PubMed: 25500423]

  (Extensive review of herbal associated liver injury does not discuss Chi R Yun or Breynia officinalis).
• Brown AC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. Food Chem Toxicol. 2017;107:472–501. [PubMed: 27402097]

  (Description of an online compendium of cases of liver toxicity attributed to HDS products, does not mention Chi R Yun or Breynia officinalis).
• Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, Sanjuan-Jimenez R, et al. Spanish DILI Registry. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16:1495–1502. [PubMed: 29307848]

  (Among 856 cases of hepatotoxicity enrolled in the Spanish DILI Registry between 1994 and 2016, 32 were attributed to herbal products, the most frequent cause being green tea [n=8] and Herbalife products [n=6], while none were attributed to Chi R Yun or Breynia officinalis).
• Bessone F, García-Cortés M, Medina-Caliz I, Hernandez N, Parana R, Mendizabal M, Schinoni MI, et al. Herbal and dietary supplements-induced liver injury in Latin America: experience from the LATINDILI Network. Clin Gastroenterol Hepatol. 2021:S1542-3565(21)00013-6. [PubMed: 33434654]

  (Among 367 cases of hepatotoxicity enrolled in the Latin American DILI Network between 2011 and 2019, 29 [8%] were attributed to herbal products, the most frequent being green tea [n=7], Herbalife products [n=5] and garcinia [n=3], while none were attributed to Chi R Yun or Breynia officinalis).
• Ballotin VR, Bigarella LG, Brandão ABM, Balbinot RA, Balbinot SS, Soldera J. Herb-induced liver injury: Systematic review and meta-analysis. World J Clin Cases. 2021;9:5490–5513. [PMC free article: PMC8281430] [PubMed: 34307603]

  (Systematic review of the literature on herb induced liver injury identified 446 references describing 936 cases due to 79 different herbal products, the most common being He Shou Wu [91], green tea [90] Herbalife products [64], kava [62 and greater celandine [48]; but none were attributed to Chi R Yun or Breynia officinalis).