The untimely and sudden death of a family member is always heartbreaking, and AHPA's deepest sympathies go out to the McClintock family. AHPA further regrets that Rep. McClintock and members of his family suddenly find themselves back in the limelight following last week's reporting.
Unfortunately, the KHN article has used this tragic event to challenge the robust regulation of dietary supplements by the federal government, despite the fact that there is no information in the report showing that Mrs. McClintock's assumed consumption of white mulberry leaf was in the form of a dietary supplement.
White mulberry leaf has been safely consumed for millenniaThe use of the white mulberry leaf is first mentioned inThe Divine Farmer's Classic of Materia Medica, a compendium of traditional Chinese medicine practices published sometime before 220 AD. The leaf is normally administered for therapeutic use in the form of a tea or powdered extract, and the leaf is also used as a food ingredient.
The two most comprehensive English language compendia of traditional Chinese medicine areChinese Herbal Medicineby Bensky et al. (Third Edition) andChinese Medical Herbology and Pharmacologyby Chen & Chen. Neither of these authoritative texts lists any significant cautions or contraindications associated with mulberry leaf use. In addition, the 2015 English language edition of thePharmacopoeia of the People's Republic of Chinadoes not indicate any precautions or warnings for white mulberry leaf, as it does when such information is relevant to safe use.
“The 1800-year history ofsang ye[white mulberry leaf] use is one of general safety,” said Bill Schoenbart, LAc, DAOM, a practitioner of traditional Chinese medicine based in Santa Cruz, Calif. “There is nothing in the historical or contemporary records to indicate that use at normal consumption levels could possibly result in gastroenteritis leading to death.”
Recent clinical research supports the safety of white mulberry leafThe majority of clinical trials studying white mulberry leaf report no adverse events, but some studies did report minor gastrointestinal issues – such as upset stomach – in both mulberry leaf and placebo control groups. A pooled analysis of these studies found that there was no statistically significant difference in adverse events between the two groups.
The Phynova Group has conducted extensive clinical studies on white mulberry leaf as used in its Reducose® white mulberry leaf extract product.
“Reducose has been the subject of multiple animal model studies and eight clinical trials, and it is considered non-genotoxic and non-toxic,” said Andrew Gallagher, MSc, MBA, Phynova's Global Head of Science. “In addition to studies conducted on Reducose, numerous published toxicological examinations of mulberry leaf have similarly reported mulberry leaf to be safe and non-toxic.”
The scientific consensus on the safety of white mulberry leaf is also reflected in theBotanical Safety Handbook,Second Edition (2013), a reference on the safety of botanicals maintained by AHPA and subject to strict standards of expert review. The contributing experts placed white mulberry leaf in the reference's safest classification based on an extensive review of the scientific literature. This classification process included a systematic literature review covering acute, short-term, and sub-chronic toxicity studies as well as in vitro, human, and animal research. The reviewers also searched for, and did not identify, any case reports in which white mulberry leaf produced a suspected drug or dietary supplement interaction.
No causality can be inferred from the facts reported in the coroner's reportThe death certificate and accompanying coroner's report identify the cause of death to be dehydration due to gastroenteritis due to adverse effects of white mulberry leaf ingestion. In addition, the coroner's report states that “a partial plant leaf” was present in the stomach at autopsy and also that “portions of tablets and capsules [were not] discerned in the stomach.” Absent from these records is any information on what tests or examinations were performed to verify the identity of the “partial plant leaf” as white mulberry leaf.
More importantly, there are well-established toxicological criteria for conducting a causality assessment to determine the degree to which any suspected cause-and-effect relationship can be established with certainty or with some degree of probability or possibility.
Rick Kingston, PharmD, senior clinical toxicologist and adverse event expert at SafetyCall International and Clinical Professor in the Department of Experimental and Clinical Pharmacology at the University of Minnesota College of Pharmacy, has expressed concern over the findings of the coroner. Dr. Kingston and his practice group routinely work with pathologists investigating death cases involving drug, alcohol, or other potential toxins. In his view, the stated autopsy findings and conclusions raise more questions than answers.
While the death certificate declares, “An autopsy with toxicology testing confirmed the cause of death,” there is no toxicology test for white mulberry, and none of the toxicology testing that was performed for other unrelated drugs or common toxins revealed anything linking death to white mulberry.
“Simply finding a leaf in stomach contents that is suspected to be white mulberry provides no confirmation that white mulberry was somehow implicated or caused the effects leading up to death,” said Dr. Kingston. “There is no weight of evidence with multiple streams of data implicating white mulberry in this tragic case.”
The coroner's report did not explain how the leaf was identified as white mulberry, whether or not there was evidence of any specific product(s) the deceased might have been taking, and ultimately how a conclusion was drawn to implicate white mulberry. Without this additional information, it is not possible to corroborate the coroner's findings and conclusions. For the sake of transparency, answers to these questions must be provided.
KHN article is inappropriately speculativeAs noted above, the coroner's report states that no tablet or capsule material was found in the stomach on autopsy, and Ms. Young's KHN article acknowledges that “[i]t's unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea.” However, nearly half of the article is presented as a criticism of the robust federal regulation of dietary supplements, claiming that “McClintock's death underscores the risks of the vast, booming market of dietary supplements and herbal remedies.”
Ms. Young's article reports that two cases of people “sickened by mulberry supplements” have been reported to FDA since 2004 and that “[a]t least one of those cases led to hospitalization.” AHPA has reviewed the publicly available records of these two cases and notes the following significant details omitted from the article:
- A 77-year-old woman was hospitalized in July 2008 with conditions described as including diabetes mellitus, gallbladder disorder, hypotension, myocardial infarction, renal disorder, and thrombosis; whether these conditions were pre-existing is not clear in the currently available public record. This record identifies 31 different dietary supplements (including a mulberry leaf product) associated with this case.
- In the other case, a 63-year-old woman was reported as taking 4 separate products – goji berry; a combination of cinnamon extract, Gymnema sylvestre leaf, and mulberry leaf; a multivitamin; and fish oil. She was diagnosed with hypoesthesia (numbness) and was hospitalized in December 2009.
Using the Freedom of Information Act, AHPA has requested the full records associated with these two cases, and AHPA will revise this statement if documents received in response contain any meaningful additional information. But the conclusion drawn by the KHN article that either of these reports represents an individual who was “sickened by mulberry supplements” is simply not substantiated by the FDA CAERS adverse event database entries.
ConclusionGiven that consumption of white mulberry leaf was unlikely to have been a direct or indirect cause of Mrs. McClintock's death, the Sacramento County Coroner's Office should seriously consider conducting additional investigations and, as appropriate, revising the death certificate.
Norman Farnsworth, former Professor of Pharmacy at the University of Illinois at Chicago, stated in 1993 that, “based on published reports, side effects or toxic reactions associated with herbal medicines in any form are rare … of all the classes of substances reported to cause toxicities of sufficient magnitude to be reported in the United States, plants are the least problematic.” Nothing has occurred in the intervening 30 years to change this accurate appraisal of the general safety of herbs and herbal products.