More Than 15 Million US Adults Use Herbal, Dietary Supplements with Hepatotoxic Botanicals

Alisa Likhitsup, MD, MPH

Credit: University of Michigan Health

An estimated 15.6 million US adults used at least 1 potentially hepatotoxic botanical herbal and dietary supplement product within the past 30 days, according to findings from a recent analysis of National Health and Nutrition Examination Survey (NHANES) data.¹

Results showed 4.7% of US adults reported exposure to at least 1 of 6 potentially hepatotoxic botanicals commonly implicated in liver injury, including turmeric, green tea, ashwagandha, Garcinia cambogia, red yeast rice, and black cohosh products. Given the growing popularity of such products despite their lack of regulation and their frequent use without recommendation from a health care provider, findings suggest the importance of monitoring patients’ history of herbal and dietary supplement use.¹

“Herbal and dietary supplements include a multitude of products consumed by millions of people every day to improve their general health and to treat minor ailments. Over 80,000 herbal and dietary supplement products can be purchased without a prescription at various unregulated retail outlets or via the internet,” Alisa Likhitsup, MD, MPH, a clinical assistant professor at the University of Michigan, and colleagues wrote.¹ “The safety and efficacy of herbal and dietary supplements are not well established due to the lack of regulatory requirements by the US Food and Drug Administration for human pharmacokinetic or prospective clinical trials prior to marketing.”

Herbal and dietary supplements are considered foods and are defined as products taken by mouth that contain a dietary ingredient intended to supplement the diet. Since they are not drugs, herbal and dietary supplements are regulated differently than conventional pharmaceuticals and do not require FDA approval before marketing. The hepatotoxic potential of these supplements has been recognized for many years, with many of the most prominent instances of hepatotoxicity resulting from multi‐ingredient products.^2,3

To assess the prevalence and clinical characteristics of adult consumers of potentially hepatoxic botanicals in the US, investigators analyzed nationally representative data from the NHANES. Acknowledging disruptions to NHANES 2019-2020 data collection due to the COVID-19 pandemic, investigators combined data collected from January 2019 to March 2020 with data from the NHANES 2017 to 2018 cycle to form a nationally representative sample of NHANES 2017 to March 2020 prepandemic data.¹

Information on participant age, sex, race and ethnicity, marital status, educational level, family income to poverty level index, and medical history were collected through questionnaires. Herbal and dietary supplement and prescription drug use data were collected through personal interviews for the 30-day period prior to the survey date. Investigators classified a herbal and dietary supplement ingredient as a botanical if it is part of a plant, tree, shrub, or herb, focusing specifically on 6 potentially hepatotoxic botanicals of interest: turmeric or curcumin, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha.¹

Among 9685 adults enrolled in this NHANES cohort, the mean age was 47.5 years, 51.8% were female, and 62.2% were non-Hispanic White. The overall prevalence of herbal and dietary supplement product use was 57.6% (95% CI, 55.9%-59.4%), with investigators acknowledging these participants were significantly older (51.9 vs 41.5 years; P <.001) and more likely to be female (57.7% vs 43.7%; P <.001) and non-Hispanic White (67.6%vs 54.8%; P <.001).¹

In total, 7.5% of participants reported using a botanical-containing herbal and dietary supplement product within the last 30 days, 4.7% of whom used at least 1 of the 6 botanical products of interest in this study. Investigators noted turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19).¹

Features associated with at-risk botanical use included older age (adjusted odds ratio [aOR], 2.36; 95% CI, 1.06-5.25; P = .04 for 40-59 years of age; aOR, 3.96; 95% CI, 1.93-8.11; P = .001 for age ≥60 years), some college education (aOR, 4.78; 95% CI, 2.62-8.75; P <.001), and the presence of arthritis (aOR, 2.27; 95% CI, 1.62-3.29; P <.001). Investigators pointed out the majority of at-risk botanical users were doing so of their own accord, and the use of these products was not recommended by their health care providers. The most common reasons for using botanicals were to improve or maintain health and to prevent health problems or boost immunity.¹

Using 2020 US Census data, investigators estimated 15,584,599 (95% CI, 13,047,571-18,648,801) of US adults used at least 1 of the 6 potentially hepatotoxic botanical products within the past 30 days, similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14,036,024; 95% CI, 11,202,460-17,594,452]) and nonsteroidal anti-inflammatory drugs (14,793,837; 95% CI, 13,014,623-16,671,897).¹

Investigators mentioned several potential limitations to these findings, including the low NHANES survey response rate for the January 2017 to March 2020 prepandemic cohort; the inadequate survey sample size for detecting hepatotoxic effects from botanicals or other adverse events; the fact that the study was not designed to identify any causal relationship between consumption of the 6 botanicals of interest and the development of liver injury over time; and the reliance on self-reported NHANES data for use of herbal and dietary supplements without independent verification by source documents.¹

“In light of the lack of regulatory oversight on the manufacturing and testing of botanical products, it is recommended that clinicians obtain a full medication and herbal and dietary supplement use history when evaluating patients with unexplained symptoms or liver test abnormalities,” investigators concluded.¹ “Considering the widespread and growing popularity of botanical products, we urge government authorities to consider increasing the regulatory oversight on how botanicals are produced, marketed, tested, and monitored in the general population.”

References

1. ^{Likhitsup A, Chen VL, Fontana RJ. Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults. JAMA Netw Open. doi:10.1001/jamanetworkopen.2024.25822}
2. ^{National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. July 22, 2024. Accessed August 20, 2024. https://www.ncbi.nlm.nih.gov/books/NBK548441/}
3. ^{Fontana RJ, Liou I, Reuben A, et al. AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury. Hepatology. doi:10.1002/hep.32689}