August 31, 2022 Members and Supporters Forwarded by: American Botanical Council From: American Herbal Products Association FW: AHPA statement on purported association of white mulberry leaf with tragic death ABC is sending to its members the notice that was sent out this afternoon from the American Herbal Products Association in which AHPA provides some detail and perspective on recent media stories about the unfortunate death of a woman who ingested a white mulberry leaf. A consensus of herb experts familiar with the well-established safety of mulberry leaf do not believe that any causal association is warranted, despite the coroner’s report and the uncritical media coverage of this incident. ABC is grateful to AHPA for its public statement.AHPA statement on purported association of white mulberry leaf with tragic deathOn August 24, 2022, Kaiser Health News (KHN) released an article written by Samantha Young reporting that the Sacramento County (California) coroner’s office concluded that the cause of death of Lori McClintock, the wife of Congressman Tom McClintock (R-CA4) who died last December at the age of 61, has been identified as “dehydration as a result of gastroenteritis caused by white mulberry leaf” (Morus alba). Prior to this updated report, the coroner had classified the cause of Mrs. McClintock’s death as “pending.”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 in The 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 are Chinese Herbal Medicine by Bensky et al. (Third Edition) and Chinese Medical Herbology and Pharmacology by 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 the Pharmacopoeia of the People’s Republic of China does 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 of sang 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 the Botanical 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 medical examiner. 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 medical examiner 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 medical examiner’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:To: ABC
- 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.
As is typical of the public records FDA makes available on its website about adverse event reports submitted to the agency, it is difficult to draw credible conclusions from these limited data. “It is clear that the FDA CAERS adverse event database is not generating any safety signal for white mulberry leaf,” said Dr. Kingston. “In fact, there are no other surveillance symptoms identifying white mulberry as posing any safety issue.”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.###Founded in 1982, the American Herbal Products Association (AHPA) is the national trade association and voice of the herbal products industry. AHPA is comprised of more than 400 member companies, consisting primarily of domestic and foreign companies doing business as growers, processors, manufacturers and marketers of herbs and herbal products as foods, dietary supplements, cosmetics, and non-prescription drugs, and also including companies that provide expert services to the herbal trade.Phynova is a British life science company that develops and commercializes natural health ingredients powered by plants. Phynova identifies and researches active ingredients from plants with a rich history and track record of use in traditional medicine. Phynova develops the scientific, IP and regulatory framework around these ingredients so they can be commercialized globally for a variety of health benefits and unmet needs.SafetyCall International is a multidisciplinary health care practice that provides manufacturers with adverse event management, regulatory reporting, post-market surveillance, and consulting services. It operates the world’s largest 24/7 human and animal adverse event call center, providing clients and their customers with immediate, around-the-clock access to trusted health, safety, and medical information.