The mainstream media headlines are alarming:
- Over 15M Americans take these 6 supplements — even though they may cause liver damage
- Six popular 'health' supplements that could damage your liver beyond repair
- Millions of Americans May Risk Liver Damage Via Unregulated Herbal Products
Those articles were written in response to an investigation published in JAMA Open Network titled Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults. The study looked at the impacts of:
- turmeric
- green tea extract
- Garcinia cambogia
- black cohosh
- red yeast rice
- ashwagandha
The American Botanical Council (ABC) reported that much of the dietary supplement usage information in the paper is based on the U.S. government-sponsored National Health and Nutrition Examination Survey (NHANES) data from 2017-2020.
Natural products industry trade associations were quick to respond, issuing statements and press releases to the media in an attempt to clarify the science.
ABC stressed that the concern over safety of botanical ingredients is a very important topic, and the study authors’ efforts to raise awareness of the liver-toxic potential of botanicals is reasonable.
The Council for Responsible Nutrition (CRN) described the article as further confirmation of the wide range of safety of six herbal supplement ingredients, and noted that, contrary to misleading headlines about potential “hepatotoxicity” of these products, there is nothing in the actual study findings that exposes any new risk of liver injury or that should alarm consumers who take any of these six herbals supplements.
“This analysis of existing NHANES survey data doesn’t appreciate that the overall risk these ingredients pose is exceedingly low," Steve Mister, President & CEO of CRN. "Revealing that more than 15 million Americans use at least one of these herbal supplements, when compared to their actual reported risks, only strengthens the case for their safety.”
ABC also stressed this point, noting that the number of case reports for each of the six botanicals included are very small compared to the estimated number of people using these supplements. "For example, there were 23 global case reports of liver injury associated with ashwagandha based on a review published in 2023—only eight of which were from people in the United States—and an estimated 1.25 million U.S. users of ashwagandha in 2020, according to data that was cited in the JAMA Network Open paper. Additionally, these case reports not only include dietary supplements, but also—in the case of ashwagandha—herbal jams, syrups, and powders of unclear composition from unbranded producers selling at local markets in India."
CRN explained that "news coverage that sounds the alarm based on this publication reflects that the reporters have either not read the study or do not fully appreciate its limitations. Liver injury from botanicals may occur in rare cases, especially in individuals with specific genetic predispositions or pre-existing conditions. But the vast majority of the population taking these botanical supplements uses them as directed without issue."
Taking a closer look at the numbers, ABC reported: "The article also mentions that the percentage of liver injury associated with herbal dietary supplements (HDS) relative to liver injury caused by all medications (except the over-the-counter (OTC) drug acetaminophen*) increased from 7% in 2004/2005 to 20% in 2013 according to data from the Drug Induced Liver Injury Network (DILIN). However, the authors do not report that the overall number of HDS-induced liver injury cases over the 10-year period was only 136, including 45 cases linked to bodybuilding products, many of which were found to contain illegal anabolic steroids masquerading as HDS."
Offering more perspective, ABC shared the take of Richard Kingston, PharmD, President of Regulatory and Scientific Affairs at SafetyCall International (a leading consumer reporting service on adverse events for dietary supplements, OTC drugs, and household products) and Clinical Professor in the Department of Experimental and Clinical Pharmacology at the College of Pharmacy, University of Minnesota. Dr. Kingston said: “It’s disappointing that the authors provided only the percentage of DILIN-enrolled patients that experienced liver damage due to HDS as compared to all other medications...Although the percentage of cases looks ominous, the actual numbers add context to any potential concerns. Consider that the actual total number of patients that experienced liver damage from HDS was 136 over the 10-year period, amounting to about 14 patients a year. If you exclude the 45 body-building products, that would leave about 9 patients per year with potential liver damage secondary to mainstream HDS.” Read ABC's full report, which outlines more of the issues, here.
There are several aspects of the study that experts say need clarifying.
"This study contains significant inaccuracies and methodological limitations that its authors are using as a platform for their opinions about dietary supplement regulation," said Consumer Healthcare Products Association (CHPA) Senior Vice President of Dietary Supplements Duffy MacKay. "For example, the authors misrepresent and overinflate the size of the dietary supplement industry, repeat misconceptions about regulatory oversight, and overlook the fact that Red Yeast Rice is not actually a botanical. The study is a self-reported survey concluding that an estimated 15.5 million people consume one of six ingredients (five are botanicals) in dietary supplements. There is no data in the study on clinical outcomes, adverse effects, or hepatotoxic effects.
“The six ingredients included in the survey have been studied extensively and have a long history of safe use. CHPA will continue to reiterate the importance of ensuring accurate, responsible, and rigorous approaches to such research. This is especially critical considering the impact and far-reaching consequences misleading studies can have, both in terms of threatening consumer trust and also discounting the decades of research reinforcing the beneficial role supplementation plays in optimizing health."
Another issue with this study and some of the subsequent media coverage: The authors incorrectly contend that the dietary supplement industry is largely “unregulated,” ABC pointed out. "Unfortunately, this notion of an unregulated industry is too often repeated in medical journals and mainstream media. Dietary supplement products are subject to various federal regulations including the requirement to be made according to current good manufacturing practices (cGMPs) and to be tested for identity, purity, strength, composition, and absence of contaminants by appropriate analytical methods. The FDA is carrying out hundreds of inspections of manufacturers each year in its attempt to ensure that the regulations are followed, although admittedly, the agency is inadequately resourced to inspect all facilities as often as might be optimal."
CRN stressed that while it is important to be aware of potential risks, it also is crucial to recognize the long history of safe use of these herbs. As always, consumers are encouraged to use these products as directed and to consult their healthcare providers, especially when combining supplements with prescription medications. And CRN encourages healthcare practitioners to understand the benefits and proper use of these popular supplements in order to provide their patients with accurate information about their safe use.
“What consumers and healthcare practitioners should take away from this study is that there is great—and growing—interest in using herbal supplements to promote health and wellness. Practitioners should encourage candid and open-minded conversations with their patients about supplement usage,” Mister said. “Alarmist headlines that mislead doctors and panic consumers shut down those conversations and do a disservice to the millions of people who trust and use these products safely every day.”
The bottom line: ABC Chief Science Officer Stefan Gafner, Ph.D., commented: “In my opinion, the main issue is that the paper implies that 15 million U.S. adults are exposed to potentially hepatotoxic botanicals. This sounds like a huge problem, even if the actual risk of liver injury from the six botanicals in question is low. The authors provide some information to support the hepatotoxic potential of botanicals, but these data are provided without proper context and suggest that the risk of liver injury is much greater than it actually is.”
