Liver Injury from Herbs and “Dietary Supplements”: Highlights of a Literature Review from 2015 to 2017
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Purpose of the Review
To present highlights of recent liver injury from herbs and “dietary supplements,” based on a literature review from 2015 to 2017.
Challenging are quality issues of herb and dietary supplements (HDS) products, influenced by the circadian clock system in plants that controls many important metabolic pathways including photosynthesis and molecular processes of gene expression. Important also is plant stress, caused by pathogen attacks, heavy UV radiation, draft, soil contamination by salts or heavy metals, involving oxidative stress through generation of free radicals including reactive oxygen species (ROS), damaging the plant’s integrity. Finally, expectations are high if physicians publish case reports of HDS liver injury using the Roussel Uclaf Causality Assessment Method (RUCAM), but intentional overscoring of causality gradings must be resisted. In critical situations, reevaluation of original case data was a good approach clarifying divergencies.
Plant stress impairs the quality of herbs, requiring better understanding of plant physiology, and clinical liver injury cases need better causality assessment using RUCAM.
KeywordsHerb-induced liver injury Herbal and dietary supplement liver injury Herbal product quality Causality assessment RUCAM Roussel Uclaf Causality Assessment Method Plant physiology plant chronobiology
Compliance with Ethical Standards
Conflict of Interest
The authors received no financial support for writing this commissioned manuscript. No conflicts of interest have been declared in relation to this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
- 1.Shahbaz O, Mahajan S, Lewis JH. Highlights of drug- and herb-induced liver injury in the literature from 2016: how best to translate new information into clinical practice? Expert Opin Drug Metab Toxicol 2017; 13(9):935–951. Available at: https://doi.org/10.1080/17425255.2017.1362391
- 3.Teschke R, Andrade RJ. Editorial. Special issue “drug, herb, and dietary supplement hepatotoxicity”. Int J Mol Sci. 2016;17(9):1488. https://doi.org/10.3390/ijms17091488. Available at: http://www.mdpi.com/journal/ijms/special_issues/Hepatotoxicity. Accessed 22.10.17.CrossRefPubMedCentralGoogle Scholar
- 13.Xuan TD, Khanh TD, Khang DT, Quan NT, Elzaawely AA. Changes in chemical composition, total phenolics and antioxidant activity of Alpinia (Alpinia zerumbet) leaves exposed to UV. Int Lett Nat Sci. 2016;55:25–34. https://doi.org/10.18052/www.scipress.com/ILNS.55.25.CrossRefGoogle Scholar
- 15.Teschke R, Schwarzenboeck A, Frenzel C, Schulze J, Eickhoff A, Wolff A. The mystery of the Hawaii liver disease cluster in summer 2013: a pragmatic and clinical approach to solve the problem. Ann Hepatol. 2016;15:91–119. Available at: http://www.annalsofhepatology.com.mx/revista/numeros/2016/HP161-12-Mystery%20(web)%20(FF_041215V)_PROTEGIDO%20(1).pdf. Accessed 22.10.2017CrossRefPubMedGoogle Scholar
- 21.Wang R, Han D, Sun M, Teschke R, Yang SS, Mendez-Sanchez N, et al. Efficacy and safety of integration of traditional and Western medicine for the treatment of spontaneous bacterial peritonitis in liver cirrhosis: a systematic review. AME Med J. 2017;2:138. https://doi.org/10.21037/amj.2017.08.10.CrossRefGoogle Scholar
- 23.WHO. Essential medicines and health products. Traditional Medicine: Definitions. Available at: http://www.who.int/medicines/areas/traditional/definitions/en/. Last accessed 27.09. 2017.
- 25.Teschke R, Danan G. Causality assessment in pharmacovigilance for herbal medicines. In: Barnes J, editor. Pharmacovigilance of herbal medicines: reflections, solutions and future perspectives. Berlin: Springer (Adis Books); 2017. in press.Google Scholar
- 26.Teschke R, Schulze J, Eickhoff A, Wolff A, Frenzel C. Mysterious Hawaii liver disease case—naproxen overdose as cause rather than OxyELITE pro? J Liver Clin Res. 2015;2(2):1013. Available at: http://www.jscimedcentral.com/Liver/liver-2-1013.pdf. Accessed 20.10.17Google Scholar
- 27.Teschke R, Eickhoff A, Schulze J, Wolff A, Frenzel C, Melchart D. Petadolex®, a herbal extract for migraine prophylaxis with spontaneous case reports of disputed liver injury: robust causality evaluation by RUCAM, the Roussel Uclaf Causality Assessment Method. Eur J Pharm Med Res. 2016;3(12):154–77.Google Scholar
- 29.Zambrone FAD, Corrêa CL, Sampaio do Amaral LM. A critical analysis of the hepatotoxicity cases described in the literature related to Herbalife products. Braz J Pharm Sci. 2015;51:785–96. Available at: https://doi.org/10.1590/S1984-82502015000400004.
- 32.Tong K, Li ZL, Sun X, Yan S, Jiang MJ, Deng MS, et al. Metabolomics approach reveals annual metabolic variation in roots of Cyathula officinalis Kuan based on gas chromatography-mass spectrum. Chin Med. 2017;12(1):12. https://doi.org/10.1186/s13020-017-0133-1.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Lin L, Li H, Lin H, Zhang M, Qu C, Yan L, et al. A new perspective on liver injury by traditional Chinese herbs such as Polygonum multiflorum: The geographical area of harvest as an important contributory factor. Front Pharmacol. 2017. Available at: https://doi.org/10.3389/fphar.2017.00349
- 34.Kuchta K, Schmidt M, Nahrstedt A. German Kava ban lifted by court: the alleged hepatotoxicity of Kava (Piper methysticum) as a case of ill-defined herbal drug identity, lacking quality control, and misguided regulatory politics. Planta Med. 2015;81(18):1647–53. https://doi.org/10.1055/s-0035-1558295.CrossRefPubMedGoogle Scholar
- 35.Savage K, Stough C, Byrne GJ, Scholey A, Bousman C, Murphy J, et al. Kava for the Treatment of Generalised Anxiety Disorder (K-GAD): study protocol for a randomized controlled trial. Trials. 2015;16:493. Available at: http://www.trialsjournal.com/content/16/1/493/about CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Hamre HJ, Glockmann A, Heckenbach K, Matthes H. Use and safety of anthroposophic medicinal products: an analysis of 44,662 patients from the EvaMed Pharmacovigilance Network. Drugs Real World Outcomes. 2017; https://doi.org/10.1007/s40801-017-0118-5.
- 39.Melchart D, Hager S, Dai J, Weidenhammer W. Quality control and complication screening programme of Chinese medicinal drugs at the first German hospital of Traditional Chinese Medicine—a retrospective analysis. Forsch Komplementärmed. 2016;23(2):21–8. https://doi.org/10.1159/000444983.Google Scholar
- 40.Zhang P, Ye Y, Yang X, Jiao Y. Systematic review on Chinese herbal medicine induced liver injury. Evid Based Complement Alternat Med. 2016:3560812. https://doi.org/10.1155/2016/3560812.
- 42.Cho JH, Oh DS, Hong SH, Ko H, Lee NH, Park SE, et al. A nationwide study of the incidence rate of herb-induced liver injury in Korea. Arch Toxicol. 2017; https://doi.org/10.1007/s00204-017-2007-9.
- 43.Vega M, Verma M, Beswick D, Bey S, Hossack J, Merriman N, et al. The incidence of drug- and herbal and dietary supplement-induced liver injury: preliminary findings from gastroenterologist-based surveillance in the population of the State of Delaware. Drug Saf. 2017;40(9):783–7. https://doi.org/10.1007/s40264-017-0547-9.CrossRefPubMedGoogle Scholar
- 45.Teschke R, Editorial DG. Drug-induced liver injury, mortality, and liver transplantation: is it reasonable to use a global introspection causality assessment? AME Med J. 2017; https://doi.org/10.21037/amj.2017.9.05.
- 46.Teschke R, Eickhoff A, Schwarzenboeck A, Schmidt-Taenzer W, Genthner A, Frenzel C, et al. Clinical review: Herbal hepatotoxicity and the call for systematic data documentation of individual cases. J Liver Clin Res. 2015;2:1008. Available at: http://www.jscimedcentral.com/Liver/liver-2-1008.pdf Google Scholar
- 51.Teschke R, Danan G. Causality assessment methods in drug-induced liver injury. In: Drug-induced liver toxicity. Minjun Chen and Yvonne Will. Methods in pharmacology and toxicology/Y. James Kang & David C. Casey. Springer Protocols, Springer, Berlin, 2018, in press.Google Scholar
- 52.DCH T, Ng PSL, Tan SH, Lim AT, DSL T, Chan SY, et al. Drug-induced liver injury associated with complementary and alternative medicine: a review of adverse event reports in an Asian community from 2009 to 2014. BMC Complement Altern Med. 2016;16(1):192. https://doi.org/10.1186/s12906-016-1168z.CrossRefGoogle Scholar
- 55.Wang J, Ma Z, Niu M, Zhu Y, Liang Q, Zhao Y, et al. Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum. Front Med. 2015;9(4):457–67. https://doi.org/10.1007/s11684-015-0417-8.CrossRefPubMedGoogle Scholar
- 57.Hayashi PH, Rockey D, Fontana RJ, Tillmann HL, Kaplowitz N, Barnhart H, et al. Death and liver transplantation within two years of onset of drug-induced liver injury. Hepatology. 2017, in press; https://doi.org/10.1002/hep.29283.
- 59.Wong LL, Lacar L, Roytman M, Orloff SL. Urgent liver transplantation for dietary supplements: an under-recognized problem. Transplant Proc. 2017;49(2):322–5. https://doi.org/10.1016/j.transproceed.2016.11.041.CrossRefPubMedGoogle Scholar
- 67.Centers for Disease Control and Prevention. Adult obesity causes and consequences. Available at: https://www.cdc.gov/obesity/adult/causes.html.
- 68.Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: US, 2011–2014. NCHS Data Brief. 2015;219:1–8.Google Scholar