Misconceptions regarding the association between Herbalife products and liver‐related case reports in Spain

In the July 2011 issue of Pharmacoepidemiology and Drug Safety, the editorial by Manso et al discussed historical reports of consumers from Spain who had reportedly taken Herbalife products and experienced liver-related injury of varying types and severity.1 Herbalife would like to offer an alternative perspective which severely weakens the authors’ conclusions. First, the authors state that Spanish State regulatory authorities published a report2 informing consumers of the risk of hepatotoxicity associated with Herbalife products. In an egregious omission, the authors failed to state that this communicado was removed by the Spanish authorities on April 15, 2009 after an extensive review of the facts and discussion involving most of these case reports with additional information that Herbalife provided to aid in the investigation. Furthermore, most of these same cases were shared by Spanish authorities with regulatory agencies globally through the World Health Organization’s (WHO) UPSALA database and have not led to regulatory action by any governments. Another glaring omission by Manso et al was the fact that the WHO causality classifications3 were previously applied to most of these same cases, yet were not included in the authors’ paper. The failure to acknowledge these assessments and instead applying the Karch/Lasagna criteria,4 is a major deficiency in this publication, and raises questions about the authors’ scientific balance given the serious and unsubstantiated accusations about a company’s whole product line. This is especially disconcerting since applying different causality assessment criteria leads to very different causality scores for a number of the cases. In fact, since the authors could not identify a causative agent with a ‘known drug response’ in any of these cases, none of the cases in this article would have met the Karch/Lasagna criteria for a definite, probable, or possible classification since a ‘known drug response’ is required for such a classification. As an example, Case 12 which was categorized as ‘Definite’ by the Karch/Lasagna method would be categorized as [‘conditional/unclassified’] based on the WHO criteria.3 The reason for the different causality conclusions in this case can be attributed to the authors’ failure to note whether the viral serology was negative, thus precluding them from ruling out other potential causes for the reported condition. Although rechallenge was noted, it is unknown whether all products were rechallenged simultaneously or individually. Additionally, since no single agent/ingredient was identified as suspect and a ‘known drug response’ cannot be affirmed for the purpose of the Karch/Lasagna causality assessment, the actual Karch/Lasagna categorization for Case 12 would be ‘Conditional’ or ‘Possible’. 4 Herbalife has similar comments on other cases reported by the authors but this letter is not an appropriate forum for a more detailed explanation of this concern. The authors also do not note that Herbalife has published responses to some of the references5,6 cited by these authors7,8 highlighting inconsistencies that would warrant further discussion regarding the certainty of causality assessments assigned to these case reports. Herbalife also has provided comments in multiple publications5,6,9,10 regarding quality control, some of which specifically address the authors’ allegation that B. subtilis contamination was associated with two case reports of liver injury.11 We believe critical deficiencies in the scientific methodology used to isolate B. subtilis in the Herbalife samples reported to have been contaminated do not support the conclusion that Herbalife products were contaminated with B. subtilis or was associated with liver injury. For example, neither patient reported symptoms consistent with classical B. subtilis food poisoning, and the product and patients were not tested for cerulide or any of the reported heat-stable toxins associated with certain strains of B. subtilis. Even though B. subtilis is ubiquitous in the environment,12 Herbalife’s testing for B. subtilis contamination in the products consumed by the patients was negative. Finally, it should be noted that Herbalife has met and cooperated with 25 regulatory agencies to address articles in the literature and liver-related case reports