Herbal medicine hepatotoxicity revisited
Authors: Kristy Appelhans, Vasilios Frankos
Journal: Journal of Hepatology (2011)

Herbal medicine hepatotoxicity: A new step with development of specific biomarkersJournal of HepatologyVol. 54Issue 4PreviewHepatic impairment resulting from the use of conventional drugs is widely acknowledged, but there is less awareness of the potential hepatotoxicity of alternative medicines such as herbal preparations [1]. The increasing attraction for herbals medicines is partly explained by the return to natural products occurring along with the ecological movement in industrialized countries [1]. It is also related to the limited efficacy or the important side effects of treatments of various chronic diseases [1–5]. Full-Text PDF Open AccessReply to: "Herbal medicine hepatotoxicity revisited"Journal of HepatologyVol. 56Issue 2PreviewThe author's letter states that the mention of some instances of herbal medicines is immaterial in the context of the article's discussion. We do not agree with this view for the following reasons. Full-Text PDF Open Access In the April 2011 issue of the Journal of Hepatology, an editorial discussed hepatotoxicity associated with the use of herbal preparations [[1]Larrey D. Faure S. Herbal medicine hepatotoxicity: a new step with development of specific biomarkers.J Hepatol. 2011; 54: 599-601Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar]. The focus of the article is primarily on the need to develop specific biomarkers for compounds or ingredients suspected to be associated with hepatotoxicity in order to establish clinical specificity when determining if a relationship exists between an adverse event and the consumption of these agents. We agree that identification methods are crucial to product safety and the industry continues to develop and validate identification methods for many commercialized ingredients. This issue is also currently being addressed by the US Food and Drug Administration (FDA) and various other regulatory agencies worldwide. In the US, beginning in 2008, the FDA has enforced the formal requirement for dietary supplement manufacturers to comply with dietary supplement-specific Current Good Manufacturing Practices (cGMP) [[2]CFR – Code of Federal Regulations Title 21 Part 111. Current good manufacturing practice in manufacturing, packaging, labeling, or holding operations for dietary supplements; April 1, 2010. Available from: <http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm>.Google Scholar]. The regulations outline the requirements that support product quality and safety including ingredient testing, manufacturing equipment and facilities, manufacturing process controls, product testing, product complaint handling, and documentation. It is important to appreciate how this higher level of scrutiny for dietary supplements allows for better assurance against potential safety issues, including issues related to contamination, adulteration, distribution, and safety monitoring. It would be equally prudent to acknowledge that since 2008, these manufacturing controls could mitigate ingredient contamination concerns that were suggested as the proposed mechanisms involved with cases of liver injury associated with these products. This article gives several examples of specific ingredients alleged to have been associated with cases of liver injury including references to Herbalife which is a brand, not a single product or ingredient. The reference to Herbalife is also somewhat immaterial in the context of the article's discussion. Herbalife has formally responded to this publication [[3]Ignarro L. Heber D. Henig Y.S. Bejar E. Herbalife nutritional products and liver injury revisited.J Hepatol. 2008; 49: 291-293Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar] to rebut articles cited by these authors [4Elinav E. Pinsker G. Sadafi R. Pappo O. Bromberg M. Anis E. et al.Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity.J Hepatol. 2007; 47: 514-520Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 5Schoepfer A.M. Engel A. Fattinger K. Marbet U.A. Criblez D. Reichen J. et al.Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products.J Hepatol. 2007; 47: 521-526Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar]. The articles were published in 2007 and present case reports with dates of onset that range from 1998 to 2004. These case reports involved a variety of food and supplement products that are not representative of currently marketed Herbalife products. Additionally, no toxic substance has been identified as responsible for the liver reactions that were alleged to have been associated with Herbalife products and none of the suspect compounds listed by these authors are found in any of Herbalife's products. Although Herbalife uses green tea extracts in its current products, all green tea extracts are water-based extracts (equivalent to a hot tea infusion) that have never been implicated in causing liver toxicity. Furthermore, since January 2005, Herbalife has met and cooperated with 25 regulatory agencies, including the Swiss BAG, to address liver-related case reports and articles in the literature. None of the 25 agencies has taken any regulatory action affecting Herbalife products. Most recently, on December 22, 2010, Evira, the food safety authority in Finland, closed its multi-year inquiry involving Herbalife case reports, with the agency stating that all requirements were satisfied, and indicating Herbalife "acted properly" and in "a thorough manner" to "demonstrate its commitments to food safety". K.A. and V.F. are paid employees of Herbalife International of America, Inc.