https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822

Original Investigation | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
Alisa Likhitsup, MD, MPH; Vincent L. Chen, MD, MS; Robert J. Fontana, MD
Abstract
IMPORTANCE Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion
of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black
cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but
their prevalence and reasons for use in the general population are unknown.
OBJECTIVE To assess the prevalence and clinical characteristics of adult consumers of 6 potentially
hepatoxic botanicals.
DESIGN, SETTING, AND PARTICIPANTS This survey study analyzed nationally representative data
from the National Health and Nutrition Examination Survey (NHANES), a nationally representative,
cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the
past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data
were analyzed July 1, 2023, to February 1, 2024.
EXPOSURES Adult NHANES participants enrolled between January 2017 and March 2020.
MAINOUTCOMES ANDMEASURES Baseline weighted characteristics of HDS users and users of 6
potentially hepatotoxic botanical products were compared with non–HDS users. Multivariable
analysis was undertaken to identify factors associated with HDS use or at-risk botanical use.
RESULTS Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5)
years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use
was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was
4.7% (95% CI, 3.9%-5.7%). 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). Consumers of these 6 botanicals were
significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of
age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for 60 years of age), had a higher educational level
(AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI,
1.62-3.29]; P < .001) compared with non–HDS users. An estimated 15 584 599 (95% CI,
13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days,
which was 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]). The most common reason for
consuming turmeric and green tea was to improve or maintain health.
CONCLUSIONS ANDRELEVANCE In this survey study, an estimated 15.6 million US adults
consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the
number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed
hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of
(continued)
Key Points
Question What percentage of US adults
consume at least 1 of 6 potentially
hepatotoxic botanical products?
Findings In this survey study analyzing
nationally representative data from
9685 adults, 4.7% of US adults reported
exposure to 6 potentially hepatotoxic
botanicals: turmeric was most
frequently reported, followed in order
by green tea, ashwagandha, Garcinia
cambogia, red yeast rice, and black
cohosh products. Botanical product
users were significantly older, more
educated, and more likely to have
arthritis compared with nonusers.
Meaning The results of this study
suggest that clinicians should be aware
of possible adverse events from
consumption of these largely
unregulated products.
+ Supplemental content
Author affiliations and article information are
listed at the end of this article.
Open Access. This is an open access article distributed under the terms of the CC-BY License.
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
1/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822

Abstract (continued)
botanical products, clinicians should be aware of possible adverse events from consumption of these
largely unregulated products.
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822
Introduction
Herbal and dietary supplements (HDSs) 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 HDS
products can be purchased without a prescription at various unregulated retail outlets or via the
internet.1 The largest group of HDS products used include multivitamins, minerals, vitamin D,
omega-3 fatty acid, and calcium with well-defined ingredients on the label. However, an estimated
5% to 12% of HDS products are plant-derived, complex multi-ingredient botanicals.2,3 Chemical
analyses of HDS products associated with confirmed liver toxic effects show frequent discrepancies
between product labels and detected ingredients.3 The safety and efficacy of HDSs 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.4
The Drug Induced Liver Injury Network (DILIN), a multicenter US observational program that
collects and analyzes data from patients with hepatotoxic effects attributed to various drugs and
HDS products, found that the proportion of DILI cases from HDSs nearly tripled from 7% in 2004 to
2005 to 20% in 2013 to 2014.5,6 The most commonly implicated botanical products in the DILIN
include turmeric, kratom, green tea extract, and Garcinia cambogia, with potentially severe and even
fatal liver injury.7-13 Furthermore, the multicenter Acute Liver Failure Study Group has also
demonstrated that an increasing proportion of DILI-related acute liver failure cases were caused by
HDSs, increasing from 12.4% in 1998 to 2007, to 21.1% in 2007 to 2015.14
The National Health and Nutrition Examination Survey (NHANES) is a periodic, population-
based study of the general US population that includes comprehensive data regarding HDS use.15 In
the current study, the proportion of NHANES patients who reported exposure to 6 potentially
hepatotoxic botanicals—turmeric or curcumin, green tea, Garcinia cambogia, black cohosh, red yeast
rice, and ashwagandha—were identified.7-13 The clinical features and baseline demographics of these
individuals along with their self-reported reasons for taking these products are reviewed herein and
compared with non–HDS users. To determine population level estimates of exposure to these
products, US census data were used.
Methods
Study Population
This survey study used data from NHANES, a cross-sectional, nationally representative survey
designed to monitor the health and nutrition of the civilian noninstitutionalized resident US
population that has been conducted in 2-year cycles since 1999.16 NHANES was approved by the
research ethics review board of the US Centers for Disease Control and Prevention National Center
for Health Statistics, with written informed consent obtained from all adult participants. NHANES
collects data from interviews, standardized physical examinations, and analyses of obtained blood
and other biological specimens. Due to the COVID-19 pandemic, data collection for the NHANES
2019-2020 cycle was interrupted. Therefore, for the present analysis, data collected from January
2019 to March 2020 among adults older than 18 years of age were combined with data from the
NHANES 2017 to 2018 cycle to form a nationally representative sample of NHANES 2017 to March
2020 prepandemic data.17 The crude response rates during 2017 to March 2020 were 51.4% for
children and adolescents aged 2 to 19 years of age and 43.9% for adults aged 20 years or older.17 All
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
2/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://aapor.org/standards-and-ethics/standard-definitions/


https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822

data used in this analysis were extracted from publicly available datasets.18 This study followed the
American Association for Public Opinion Research (AAPOR) reporting guideline for survey studies.
NHANESData Collection
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. Race and
ethnicity data were collected because of a potential difference in the prevalence of HDS use. Race
and ethnicity were based on self-report and were categorized as Mexican and non-Mexican Hispanic,
non-Hispanic Asian (persons having origins in any of the original peoples of East Asia, Southeast Asia,
or Indian subcontinent), non-Hispanic Black or African American, non-Hispanic White, and other (eg,
American Indian, Alaska Native, Native Hawaiian, Pacific Islander, >1 race, or any other race). HDS
and prescription drug use data were collected through personal interviews for the 30-day period
prior to the survey date. The use of HDSs reported in NHANES 2017 to 2018 and 2019 to 2020 is
detailed in the NHANES Dietary Supplement Database 1999-2020.19 An HDS ingredient was
classified as a botanical if it is part of plant, tree, shrub, or herb. We targeted our analysis to
investigate national levels of exposure to the 6 most frequently implicated causes of HDS-DILI cases
in the DILIN.7-13 The 6 potentially hepatotoxic botanicals of interest in our study, including turmeric
or curcumin, green tea, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha, were
identified by their ingredient and supplement identification numbers (eTable 1 in Supplement 1).
However, the daily dose of an HDS product consumed by an individual patient was not recorded or
available for analysis. Furthermore, confirmation of the ingredients listed on HDS product labels via
analytical chemistry methods was also not available.
Approximately 95% of adults 18 years or older provided blood samples at the mobile
examination centers. The blood samples were tested at central laboratories using standard protocols
to determine routine laboratory parameters (eg, complete blood count, comprehensive panel) as
well as fasting glycated hemoglobin, cholesterol, and triglyceride levels.
Echosens North America Vibration-Controlled Transient Elastography was performed at the
mobile examination centers by NHANES technicians. Controlled attenuation parameter was used to
quantify the presence and severity of hepatic steatosis. Similarly, the liver stiffness measurement
score in kilopascals was used to estimate the severity of hepatic fibrosis.20
Self-reported chronic medical conditions that were specifically captured were current or prior
history of hypertension, diabetes, coronary heart disease, stroke, arthritis, chronic obstructive pulmo-
nary disease, thyroid disorder, cancer, and liver condition. Liver conditions included viral, autoimmune,
genetic liver disease, drug- or medication-induced liver disease, alcoholic liver disease, metabolic
dysfunction–associated steatotic liver disease (formerly nonalcoholic fatty liver disease), liver cyst, liver
abscess, and cirrhosis. Smokers were defined as individuals who smoked 100 or more cigarettes. Regu-
lar alcohol consumption was defined as mean alcohol consumption in the past 12 months of 1 or more
alcoholic beverages per day for women and 2 or more alcoholic beverages per day for men.
Population Size Estimates
Data from the 2020 US Census were used to estimate the size with associated 95% CIs of the
resident population 18 years of age or older.21 The prevalence of use of the 6 at risk botanicals was
compared with the prevalence of widely prescribed potentially hepatotoxic medications with a
LiverTox likelihood score of A or B, which included nonsteroidal anti-inflammatory drugs (NSAIDs),
sertraline (antidepressant drug), and simvastatin (hypolipidemic drug).22,23 The NSAID prescriptions
included ibuprofen, naproxen, meloxicam, celecoxib, indomethacin, ketorolac, piroxicam, and
sulindac. The LiverTox likelihood score is a 5-point scale (A to E) that estimates whether a medication
is a cause of liver injury: A indicates well-known cause, with more than 50 published cases; B, highly
likely cause, with 12 to 49 published cases; C, probable cause, with 4 to 11 published cases; D, possible
cause, with 1 to 3 published cases; E, unlikely cause; Eb, suspected but unproven cause; and
X, unknown.23
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
3/15
Downloaded from jamanetwork.com by guest on 08/27/2024
Statistical Analysis
The complex survey design factors in the NHANES, including sample weights, clustering, and
stratification, were accounted for as specified in the NHANES statistical analysis guideline.17 Baseline
weighted characteristics were compared and summarized as estimated percentages or means, with
a margin of error, following the AAPOR reporting guidance for survey studies.24 Categorical variables
were compared using Fisher exact tests or χ2 tests if more than 2 categories existed, and continuous
variables were compared using the t test. Multivariable analysis of factors that had a value of P < .10
with univariate analysis was performed to evaluate for factors associated with any HDS use as well
as botanical products of interest exposure, adjusted for age group, sex, race and ethnicity, marital
status, alcohol use, smoking, poverty index, and educational level. Each chronic medical condition
was analyzed after adjusting for age, sex, race and ethnicity, marital status, alcohol use, smoking,
income, and educational level. Odds ratios (ORs) and 95% CIs are reported. Median numbers of HDS
products and prescription drugs were compared using Mann-Whitney tests. All statistical analyses
were conducted from July 1, 2023, to February 1, 2024, using STATA/SE version 16.1 (StataCorp LLC).
A 2-sided P < .05 was considered statistically significant.
Results
Overall HDSUse in theNHANES 2017-2020Cohort
Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, 4971
(51.8% [95% CI, 50.2-53.4]) were female, 4714 (48.2% [95% CI, 46.6-49.8]) were male, 2121 (16.3%
[95% CI, 13.5%-19.6%]) were Mexican or non-Mexican Hispanic, 1169 (5.9% [95% CI, 4.3%-8.2%])
were non-Hispanic Asian, 2552 (11.5% [95% CI, 8.8%-14.7%]) were non-Hispanic Black, 3369 (62.2%
[95% CI, 57.1%-67.0%]) were non-Hispanic White, and 474 (4.1% [95% CI, 3.4%-4.8%]) were other
race or ethnicity (Table 1). Overall, 5271 adults (57.6% [95% CI, 55.9%-59.4%]) reported using at
least 1 HDS product within the past 30 days. HDS users were significantly older (mean [SE] age, 51.9
[0.7] vs 41.5 [0.4] years; P < .001) and more likely to be female (57.7% [95% CI, 55.2%-60.1%] vs
43.7% [95% CI, 42.5%-45.0]; P < .001), non-Hispanic White (67.6% [95% CI, 62.5%-72.4%] vs
54.8% [95% CI, 49.1%-60.3%]; P < .001), married (63.5% [95% CI, 59.7%-67.0%] vs 59.0% [95% CI,
57.0%-60.9%]; P < .001), and have a higher level of education (68.6% [95% CI, 66.0%-72.0%] vs
52.6% [95% CI, 50.9%-59.2%]; P < .001) compared with non–HDS users. HDS users were also less
likely to smoke (39.6% [95% CI, 36.8%-42.4%] vs 44.1% [95% CI, 40.7%-47.5%]; P = .03) and less
likely to be below the poverty line (9.5% [95% CI, 7.6%-11.8%] vs 18.3% [95% CI, 16.0%-20.7%];
P < .001), indicative of a higher socioeconomic status. Body mass index (calculated as weight in
kilograms divided by height in meters squared; mean [SE], 29.7 [0.2] vs 29.9 [0.2]; P = .37) and
history of alcohol use (87.2% [95% CI, 85.0%-89.0%] vs 86.3% (95% CI, 83.4%-88.8%; P = .63)
were similar in the 2 groups.
Consistent with their increased age, HDS users were significantly more likely to have
hypertension, diabetes, coronary heart disease, stroke, arthritis, thyroid disorder, cancer, and liver
conditions compared with non–HDS users. The median (range) number of HDS products used within
30 days was 1 (1-22). HDS users were also significantly more likely than non–HDS users to be taking
a concomitant prescription medication (70.1% [95% CI, 67.7%-72.4%] vs 42.2% [95% CI,
39.5%-44.9%]; P < .001).
Consistent with their higher prevalence of diabetes, HDS users had significantly higher
hemoglobin A1C and total cholesterol levels, but they had lower triglyceride levels. Furthermore, HDS
users tended to have lower serum alanine aminotransferase and alkaline phosphatase levels
compared with non–HDS users (Table 1). However, there was no significant difference for controlled
attenuation parameter or liver stiffness measurement scores between the 2 groups.
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
4/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822

Use of 6 Potentially Hepatotoxic Botanicals in NHANES 2017 to 2020
In total, 731 of 9685 US adults assessed (7.5%) used a botanical-containing HDS product within the
last 30 days, and 350 participants (4.7% [95% CI, 3.9%-5.7%]) used at least 1 of the 6 botanical
products of interest within the past 30 days (eFigure in Supplement 1). The most commonly used
potentially hepatotoxic botanical products were turmeric or curcumin (n = 236) and green tea
Table 1. Clinical Characteristics of AdultsWith vsWithout HDSUse in NHANES 2017-2020a
Characteristic
Adults, No./% (95% CI)
P value
Overall (n = 9685)
With HDS use (n = 5271)
Without HDS use (n = 4414)
Age, mean (SE), y
47.5 (0.5)
51.9 (0.7)
41.5 (0.4)
<.001
Sex
Female
4971/51.8 (50.2–53.4)
3026/57.7 (55.2-60.1)
1945/43.7 (42.5-45.0
<.001
Male
4714/48.2 (46.6-49.8)
2245/42.3 (39.9-44.8)
2469/56.3 (55.0-57.5)
Race and ethnicity
<.001
Mexican or Other non-Mexican Hispanic
2121/16.3 (13.5-19.6)
1013/13.2 (10.6-16.3)
1108/20.5 (16.8-24.8)
Non-Hispanic Asian
1169/5.9 (4.3-8.2)
642/5.7 (4.0-8.0)
527/6.3 (4.6-8.7)
Non-Hispanic Black
2552/11.5 (8.8-14.7)
1258/9.5 (7.2-12.5)
1294/14.1 (11-18)
Non-Hispanic White
3369/62.2 (57.1-67.0)
2098/67.6 (62.5-72.4)
1271/54.8 (49.1-60.3)
Otherb
474/4.1 (3.4-4.8)
260/3.9 (3.1-5)
214/4.3 (3.5-5.2)
Married
5275/61.6 (59-64.1)
3034/63.5 (59.7-67.0)
2241/59.0 (57.0-60.9)
<.001
BMI, mean (SE)
29.8 (0.2)
29.7 (0.2)
29.9 (0.2)
.37
No. of HDS products used, median (IQR)
3 (1-5)
1 (1-3)
NA
NA
≥1 Prescribed drug used
5663/58.3 (55.8-60.7)
3725/70.1 (67.7-72.4)
1938/42.2 (39.5-44.9)
<.001
No. of prescribed drugs used, median (IQR)
3 (1-5)
3 (1-6)
2 (1-4)
.27c
Smoked >100 cigarettes
3886/41.5 (39.1-43.8)
2070/39.6 (36.8-42.4)
1816/44.1 (40.7-47.5)
.03
Regular alcohol used
4983/86.8 (85-88.3)
2664/87.2 (85.0-89.0)
2319/86.3 (83.4-88.8)
.63
Income: poverty ratio <1, No. (%)
1640/13.1 (11.4-15.1)
667/9.5 (7.6-11.8)
973/18.3 (16.0-20.7)
<.001
Some college or higher
5228/61.9 (59.8-66.4)
3269/68.6 (66.0-72.0)
1959/52.6 (50.9-59.2)
<.001
Chronic medical disorder
Hypertension
3575/31.7 (29.4-34.1)
2300/37.1 (34.4-40)
1275/24.4 (21.9-26.9)
<.001
Diabetes
1687/13.7 (13-14.6)
1109/16.8 (15.7-18)
578/9.6 (8.4-10.9)
<.001
Coronary heart disease
421/4.2 (3.2-5.5)
294/5.1 (3.8-6.7)
127/3.03 (2.2-4.2)
.001
Stroke
486/3.8 (3.3-4.4)
312/4.5 (3.7-5.4)
174/2.8 (2.2-3.7)
.006
Arthritis
2812/27.9 (25.3-30.6)
1930/33.8 (30.4-37.5)
882/19.5 (17.7-21.4)
<.001
COPD
846/8.6 (7.6-9.8)
519/9 (7.6-10.7)
327/8.1 (6.7-9.8)
.43
Thyroid disorder
1079/12.3 (11.4-13.2)
785/16.2 (15-17.5)
294/6.8 (5.6-8.1)
<.001
Cancer
1004/11.6 (10.6-12.7)
732/15 (13.7-16.4)
272/6.8 (5.6-8.3)
<.001
Liver disorder
462/4.6 (3.9-5.3)
297/5.3 (4.5-6.4)
165/3.5 (2.8-4.4)
.002
Glycated hemoglobin, mean (SE), %
5.6 (0.0)
5.7 (0.0)
5.6 (0.0)
.007
Total cholesterol, mean (SE), mg/dL
186.9 (1.2)
188.6 (1.4)
184.4 (1.4)
.009
Triglyceride, mean (SE), mg/dL
138.9 (2.5)
135.9 (2.6)
143 (2.9)
.003
ALT, mean (SE), U/L
22.6 (0.3)
22.1 (0.3)
23.4 (0.5)
.015
AST, mean (SE), U/L
21.8 (0.2)
21.8 (0.3)
21.8 (0.2)
.98
ALP, mean (SE), U/L
75.7 (0.5)
74.5 (0.6)
77.4 (0.6)
.001
CAP score, mean (SE), dB/m
263.3 (1.4)
262.9 (1.8)
263.9 (1.5)
.54
LSM, mean (SE), kPa
5.9 (0.12)
5.8 (0.15)
5.9 (0.11)
.37
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate
aminotransferase; BMI, body mass index (calculated as weight in kilograms divided by
height in meters squared); CAP, controlled attenuation parameter measured in decibels
per meter; COPD, chronic obstructive pulmonary disorder; HDS, herbal dietary
supplement; LSM, liver stiffness measurement, in kilopascal; NA, not applicable;
NHANES, National Health and Nutrition Examination Survey.
SI conversion factor: To convert HbA1c percentage to proportion of total, multiply by
0.01; total cholesterol level to millimoles per liter, by 0.0259; triglyceride level to
millimoles per liter, by 0.0113; ALT, AST, and ALP levels to microkatals per liter, by 0.0167.
a Data are weighted characteristics and are reported as means with SEs for continuous
variables and percentages with 95% CIs for categorical variables.
b Other race and ethnicity included American Indian, Alaska Native, Native Hawaiian,
Pacific Islander, more than 1 race, or any other race.
c Mann-Whitney test.
d Average alcohol consumption in the past 12 months 1 or more drinks per day for
women and 2 or more drinks per day for men.
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
5/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822

(n = 92), followed by ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and
black cohosh (n = 19). The number of unique products was 118 for turmeric, 26 for ashwagandha, 66
for green tea, 13 for Garcinia cambogia, 11 for black cohosh, 10 for red yeast rice, and 275 for other
botanicals (eTable 2 in Supplement 1). Among 350 patients, 291 had exposure to only 1 of the 6
botanicals, 51 had exposure to 2 botanicals, and 8 had exposure to 3 or more.
Characteristics of the 6 potentially hepatotoxic botanical users (n = 350) were compared with
those with no HDS use (n = 4414) (Table 2). At-risk botanical users were significantly older (mean
[SE] age, 51.7 [2.0] vs 41.5 [0.4] years; P < .001) and more likely to be female (56.9% [95% CI, 47.7%-
65.5%] vs 43.7% [95% CI, 42.5%-45.0%]; P = .005), non-Hispanic White (75.2% [95% CI, 65.4%-
82.9%] vs 54.8% [95% CI, 49.1%-60.3%]; P < .001), married (66% [95% CI, 58.5%-72.7%] vs 59.0%
[95% CI, 57.0%-60.9%]; P = .001), and have some college degree or higher (82.8% [95% CI,
76.7%-87.5%] vs 52.6% [95% CI, 50.9%-59.2%]; P < .001), and were less likely to be below the
poverty line (5.1% [95% CI, 3.0%-8.8%] vs 18.3% [95% CI, 16.0%-20.7%]; P < .001). Among at-risk
botanical users, the median number of HDS products used was 4 (range, 2-7) and was highest among
those who consumed red yeast rice and ashwagandha (median [IQR], 7 [4-11]). Individuals who used
at least 1 the 6 botanicals of interest were also more likely to be taking a prescription medication
compared with non–HDS users (66.0% [95% CI, 58.9%-71.8%] vs 42.0% [95% CI, 39.5%-44.9%];
P < .001). Furthermore, the botanical users were more likely to have arthritis (40.0% [95% CI,
32.4%-48.1%] vs 19.5% [95% CI, 17.7%-21.4%]; P < .001), thyroid disorder (15.8% [95% CI, 11.0%-
22.1%] vs 6.8% [95% CI, 5.6%-8.1%]; P = .004), and cancer (14.0% [95% CI, 9.7%-19.6%] vs 6.8%
[95% CI, 5.6%-8.3%]; P = .006) compared with non–HDS users.
Laboratory parameters were generally similar, but at-risk botanical users had significantly lower
triglyceride and alkaline phosphatase levels (Table 2). However, there was no significant difference
for glycated hemoglobin, serum aminotransferase levels or liver elastography parameters.
Multivariable Regression Analysis
Independent factors associated with HDS use included older age (adjusted OR [AOR], 1.77 [95% CI,
1.36-2.32]; P < .001 for 40-59 years; AOR, 3.97 [95% CI, 2.99-5.28]; P < .001 for 60 years,), female
sex (AOR, 1.76 [95% CI, 1.42-2.18]; P < .001), non-Hispanic White race and ethnicity (AOR, 1.25 [95%
CI, 1.04-1.49]; P = .02), poverty ratio higher than 1 (AOR, 1.41 [95% CI, 1.11-1.77]; P = .006), and some
college education (AOR, 2.02 [95% CI, 1.61-2.52]; P < .001) (Table 3). In addition, the presence of
hypertension (AOR, 1.37 [95% CI, 1.11-1.70]; P < .001), diabetes (AOR, 1.55 [95% CI, 1.21-1.97];
P < .001), arthritis (AOR, 1.31 [95% CI, 1.13-1.52]; P = .001) and thyroid disorder (AOR, 1.60 [95% CI,
1.13-2.25]; P = .01) remained significantly associated with HDS use after adjusting for age, sex, race
and ethnicity, marital status, smoking, income, and education level. Features associated with at-risk
botanical users included older age (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) after
adjusting for other covariates (Table 3).
Stated Reasons for Using the 6 Potentially Hepatotoxic Botanicals
The vast majority of at-risk botanical users were doing so of their own accord, and use of these
products was not recommended by their health care providers (87.6% [95% CI, 82.8%-91.9%] for
turmeric; 80.4% [95% CI, 63.8%-92.8%] for green tea; 100% for Garcinia cambogia; 63.2% [ 95%
CI, 23.5%-82.5%] for black cohosh; 40% [95% CI, 39.9%-92.2%] for red yeast rice; and 96.4% [95%
CI, 75.8%-99.7%] for ashwagandha). The most common reasons for using the botanical were to
improve or maintain health or to prevent health problems or boost immunity (Figure 1). In addition,
64 turmeric users (26.8%) consumed those products for joint health or arthritis, and 25 green tea
users (27.2%) were trying to improve their energy level. In total, 14 Garcinia cambogia users (70.0%)
were trying to lose weight and had the highest median body mass index and proportion with
diabetes (34.2% [95% CI, 13.7%-63.1%]) (Table 2). Similarly, 84.2% of black cohosh users were taking
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
6/15
Downloaded from jamanetwork.com by guest on 08/27/2024
Table2.ClinicalCharacteristicsofAdultsWithvsWithoutUseof6IndexedBotanicalProducts
a
Characteristic
Adults,No./%(95%CI)
Pvaluefor
6-indexed
HDSvsno
HDS
Turmeric
(n=236)
Greentea
(n=92)
Garciniacambogia
(n=20)
Blackcohosh
(n=19)
Redyeastrice
(n=20)
Ashwagandha
(n=28)
6-IndexedHDS
(n=350)
NoHDS
(n=4414)
Age,mean(SE),y52.2(2.8)
b
53.2(2.2)
b
44.3(2.4)53.2(4.2)
b
67.2(2.2)
b
51.7(4.2)
b
51.7(2.0)
b
41.5(0.4)<.001
Sex
Female132/51.2(41.6-60.7)54/68.3(54.5-79.5)
b
16/70(36.6-90.4)18/87.5(42.9-98.5)
b
12/66.8(43.2-84.2)14/61.9(33.9-83.7)202/56.9(47.7-65.5)
b
1945/43.7(42.5-45.0)
.005
Male104/48.8(39.3-58.4)37/31.7(20.5-45.5)4/29.9(9.6-63.4)1/12.5(1.5-57.1)8/33.2(15.8-56.8)14/38.1(16.3-66.1)145/43.1(34.5-52.3)2473/56.3(55.0-57.5)
Raceandethnicity
<.001
Mexican
orother
non-Mexican
Hispanic
41/9.6(5.6-16)19/14.8(7.5-27.2)6/25.3(7.9-57.3)2/3(0.6-14.4)4/14.5(4.6-37)4/7(2-21.9)65/11.2(6.7-18.1)1108/20.5(16.8-24.8)
Non-Hispanic
Asian
16/2(1.2-3.4)9/3.9(1.2-12.2)01/0.93(0.1-6.4)1/4.3(0.4-32.4)2/3.6(0.7-16.2)26/2.5(1.6-4)527/6.3(4.6-8.7)
Non-Hispanic
Black
44/5.7(3.5-9.2)25/10.5(5.9-17.8)5/11.3(18.9-45.6)3/4.4(1.3-13.8)4/6.3(2.1-17.5)3/2.4(0.6-8.3)67/6(3.8-9)1294/14.1(11-18)
Non-Hispanic
White
119/77.8(68.2-85.1)
b
36/69.8(60-80.1)6/40.7(14-74)12/90.8(82.4-95.4)
b
11/74.9(48.8-90.3)17/84.4
(67.4-93.4)
b
168/75.2(65.4-82.9)
b
1271/54.8(49.1-60.3)
Other
c
16/5(2.1-11.1)2/1.1(0.2-5.7)3/22.8(6-57.5)1/0.91(0.1-7.3)02/2.6(1.5-4.5)21/5.1(2.5-10.4)214/4.3(3.5-5.2)
Married145/68.7(60-76.3)
b
56/65.1(46.6-80)10/53.4(29.4-76)8/53.3(25.4-79.4)13/67(37.9-87.1)16/71.9(47.7-87.8)208/66(58.5-72.7)
b
2241/59(57-60.9).001
BMI,mean(SD)28.9(0.7)29(1.0)36.2(2.5
b
)27.1(2.2)27(0.7
b
)26.5(1.9)28.9(0.6)29.9(0.22).12
No.ofHDS
productsused,
median(IQR)
4(2-7)4(2-6)2(2-5)4(2-7)7(5-12)7(4-11)4(2-7)NANA
≥1Prescribed
drugused
165/66(57.2-74.2)65/76(61.2-86.8)11/48(23.7-73.6)15/69(37.3-89.5)15/86(62.8-95.4)15/73(49-88.5)234/66.0(58.9-71.8)1938/42.0(39.5-44.9)<.001
No.ofprescribed
drugsused,
median(IQR)
3(1-5)2(1-5)2(1-5)3(2-7)4(1-5)2(1-5)3(1-5)2(1-4)<.001
d
Smoked>100
cigarettes
84/36.3(27.6-46)29/32.9(23.3-44.2)10/57.9(29.9-81.6)9/45.2(19.9-73.3)6/30.1(13.5-54.4)12/39.5(20.4-64.5)123/36.4(28.6-45.2)1819/44.1(40.7-47.5).23
Alcoholuse
e
144/91.5(83.5-95.8)58/89.5(71.3-96.7)14/83.4(36.6-97.8)11/83.6(33.3-98.1)8/96.4(72.1-99.6)13/91.466.3-98.3)210/91.4(85.7-95)2319/86.3(83.4-88.8).06
Income:poverty
ratio<1
12/4.1(2-8.3)
b
6/2.5(1-6.5)
b
4/17.6(6.8-38.6)3/6.2(1.1-28.7)0
b
3/6.8(3.2-13.4)
b
25/5.1(3.0-8.8)
b
973/18.3(16.0-20.7)<.001
Somecollegeor
higher
187/85.8(78.4-91)
b
70/85.6(73.3-92.8)
b
14/62.9(31.7-86.1)15/89.5(67.5-97.2)
b
16/73.5(41.9-91.5)24/91.4
(66.5-98.3)
b
265/82.8(76.7-87.5)
b
1959/52.6(50.9-59.2)<.001
Chronicmedical
condition
Hypertension96/29.2(22-37.6)33/32.2(20.3-47)8/54.6(24.9-81.4)5/14.4(4-40.6)12/69.5
(40.8-88.3)
b
9/32.4(14.5-57.4)132/30(23.8-37.1)1275/24.4(21.9-26.9).06
Diabetes42/12.1(7.1-19.8)20/8.3(4.7-14.2)5/34.2(13.7-63.1)
b
4/6.3(1.7-20.9)6/16.8(5.8-40)3/3.5(1.9-6.2)
b
67/12.7(8.6-18.3)578/9.6(8.4-10.9).23
Coronaryheart
disease
8/1.9(0.6-6.3)3/1.6(0.6-4.1)0
b
0
b
0
b
0
b
10/1.6(0.5-4.5)127,3.03(2.2-4.2).15
Stroke9/3.7(1.5-8.9)3/1.7(0.4-7.1)0
b
1/3.6(0.3-29.1)0
b
2/3.5(0.4-25.3)14/3.5(1.7-6.7)174/2.8(2.2-3.7).61
Arthritis106/40.9(31.7-50.7)
b
29/33.4(21.3-48.3)
b
9/47.1(23.7-71.8)
b
9/45.8(20.2-73.8)
b
10/62(38.7-80.8)
b
8/27.6(10-56.6)146/40.0(32.4-48.1)
b
882/19.5(17.7-21.4)<.001
COPD18/4.7(2.1-10.2)4/1.8(0.5-6.4)
b
1/0.67(0.1-5.3)
b
1/2.9(3.7-19.8)2/6(0.9-32.3)1/0.4(0.1-3)
b
22/4(2-7.8)
b
327/8.1(6.7-9.8).02
Thyroid
disorder
34/15.1(9.6-23)
b
11/20.1(10.4-35.3)
b
2/7.8(1.5-32.8)7/34.8(13.2-65.3)
b
6/30(13.4-53.5)
b
5/28(9.8-58.1)53/15.8(11.0-22.1)
b
294/6.8(5.6-8.1).004
Cancer30/13.6(8.4-21.1)
b
9/16.2(7.1-32.9)
b
2/13.6(3.4-41.3)
b
1/5.8(0.7-34.6)3/6(1.7-18.8)4/14.5(3.7-42.7)
b
44/14.0(9.7-19.6)
b
272/6.8(5.6-8.3).006
Liverdisorder11/2.7(1.3-5.7)2/4.2(0.6-23.6)01/10.4(1.3-49.8)01/1.6(0.2-11.9)12/2.8(1.3-6)165/3.5(2.8-4.4).51
(continued)
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
7/15
Downloaded from jamanetwork.com by guest on 08/27/2024
Table2.ClinicalCharacteristicsofAdultsWithvsWithoutUseof6IndexedBotanicalProducts
a
(continued)
Characteristic
Adults,No./%(95%CI)
Pvaluefor
6-indexed
HDSvsno
HDS
Turmeric
(n=236)
Greentea
(n=92)
Garciniacambogia
(n=20)
Blackcohosh
(n=19)
Redyeastrice
(n=20)
Ashwagandha
(n=28)
6-IndexedHDS
(n=350)
NoHDS
(n=4414)
Glycated
hemoglobin,
mean(SE),%
5.6(0.1)5.8(0.1)6.3(0.5)5.8(0.2)5.8(0.2)5.4(0.1)
b
5.6(0.1)5.6(0.0).89
Totalcholesterol,
mean(SE),mg/dL
188.1(5.3)205(4.9)
b
179.4(9.5)197.8(9.7)217.7(7.9)
b
196.1(4.8)
b
190.7(4.2)184.4(1.37).13
Triglyceride,
mean(SE),mg/dL
122(6.5)
b
126.9(10.5)186.9(49)130.7(12.6)111.5(12.8
b
104.3(17.7)
b
126.8(5.7)
b
143(2.9).001
ALT,mean(SE),
U/L
22.7(0.821.3(0.9)25.7(2.220.5(2)17.3(1.5)
b
25.2(3)22.3(0.7)23.4(0.5).20
AST,mean(SE),
U/L
22(0.6)21.6(0.8)23.1(1.6)21(1.8)19(0.6)
b
23.3(1.8)21.9(0.5)21.8(0.2).95
ALP,mean(SE),
U/L
71.8(1.3)
b
75(3.6)65.5(5.6)69.1(6)66.8(3.6)
b
71(4.3)70.7(1.2)
b
77.4(0.6)<.001
CAPscore,
mean(SE),dB/m
255.3(7.8)257.6(9.6)283(15.5)235(10.7)
b
249.9(11.8)262(12.9)254.6(5.9)263.9(1.5).12
LSM,mean(SE),
kPa
5.2(0.15)4.9(0.26)
b
10.5(3.8)5.2(0.7)4.7(0.2)
b
5(0.4)
b
5.5(0.25)5.9(0.11).17
Abbreviations:ALP,alkalinephosphatase;ALT,alanineaminotransferase;AST,aspartateaminotransferase;BMI,
bodymassindex(calculatedasweightinkilogramsdividedbyheightinmeterssquared);CAP,controlled
attenuationparametermeasuredindecibelspermeter;COPD,chronicobstructivepulmonarydisease;HDS,
herbaldietarysupplement;LSM,liverstiffnessmeasurement,inkilopascal;NA,notapplicable.
SIconversionfactor:ToconvertHbA
1c
percentagetoproportionoftotal,multiplyby0.01;totalcholesterol
leveltomillimolesperliter,by0.0259;triglycerideleveltomillimolesperliter,by0.0113;ALT,AST,andALP
levelstomicrokatalsperliter,by0.0167.
a
DataareweightedcharacteristicsandarereportedasmeanswithSEsforcontinuousvariablesand
percentageswith95%CIsforcategoricalvariables.
b
PvaluesignificantcomparedwithnoHDS.
c
OtherraceandethnicityincludedAmericanIndian,AlaskaNative,NativeHawaiian,PacificIslander,
morethan1race,oranyotherrace.
d
Mann-Whitneytest.
e
Meanalcoholconsumptioninthepast12months1ormoredrinksperdayforwomenand2ormoredrinks
perdayformen.
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
8/15
Downloaded from jamanetwork.com by guest on 08/27/2024
these products to treat hot flashes, and the vast majority of these patients were women (87.5% [95%
CI, 42.9%-98.5%]). The main stated reason to consume red yeast rice was for heart health (90.0%),
and these individuals tended to be older and had the second highest incidence of diabetes.
USPopulation Estimates of Exposure to Botanicals of Interest
Extrapolating from the NHANES data, we observed approximately 4.7% (95% CI, 4.0%-5.7%), or an
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. The most common products used were
turmeric or curcumin, estimated at 11 400 151 (95% CI, 906 813-14 332 559) adults, and green tea,
estimated at 3 327 790 (95% CI, 2 306 389-4 777 520) adults. An estimated 1 252 040 (95% CI,
757 813-2 075 750) adults used ashwagandha, 1 219 091 (95% CI, 724 865-32 075 750) adults used
black cohosh, 889 607 (95% CI, 494 226-1 581 524) adults used Garcinia cambogia, and 626 020
(95% CI, 362 433-1 120 246) adults used red yeast rice.
Table 3. Multivariable Analysis for Factors AssociatedWith HDSUse orWith 6 Indexed Botanical Products
vs NoHDSUsea
Variable
HDS vs no HDS, AOR
(95% CI)
P value
6 Indexed HDS vs no
HDS, AOR (95% CI)
P value
Age, y
40-59
1.77 (1.36-2.32)
<.001
2.36 (1.06-5.25)
.04
≥60
3.97 (2.99-5.28)
<.001
3.96 (1.93-8.11)
.001
Female
1.76 (1.42-2.18)
<.001
1.61 (0.99-2.61)
.06
Non-Hispanic White
1.25 (1.04-1.49)
.02
1.38 (0.80-2.35)
.23
Married
0.93 (0.77-1.12)
.45
0.94 (0.63-1.41)
.77
Alcohol useb
0.99 (0.72-1.38)
.98
1.82 (0.90-3.68)
.09
Smokerc
1.17 (0.94-1.47)
.16
0.94 (0.51-1.72)
.83
Poverty index ratio >1
1.41 (1.11-1.77)
.006
2.15 (0.90-5.16)
.08
Some college or above
2.02 (1.61-2.52)
<.001
4.78 (2.62-8.75)
<.001
Hypertension
1.37 (1.11-1.70)
<.001
1.18 (0.73-1.91)
.50
Diabetes
1.55 (1.21-1.97)
.001
1.43 (0.81-2.52)
.20
Arthritis
1.31 (1.13-1.52)
.001
2.27 (1.62-3.29)
<.001
Coronary heart disease
1.55 (0.91-2.66)
.10
0.45 (0.09-2.34)
.33
Stroke
1.22 (0.83-1.78)
.30
0.97 (0.32-2.97)
.96
COPD
0.87 (0.59-1.29)
.48
0.51 (0.20-1.30)
.15
Thyroid disorder
1.60 (1.13-2.25)
.01
1.32 (0.84-2.06)
.21
Cancer
1.18 (0.80-1.74)
.39
1.10 (0.55-2.20)
.79
Liver condition
1.58 (0.76-3.27)
.21
0.65 (0.22-1.90)
.42
Abbreviations: AOR, adjusted odds ratio; COPD,
chronic obstructive pulmonary disorder; HDS, herbal
and dietary supplements.
a Medical condition was adjusted for age, sex, race and
ethnicity, marital status, income, educational level,
and smoking for HDS vs no HDS, and adjusted for
age, sex, race and ethnicity, marital status, income,
and educational level for 6 indexed botanical
products vs no HDS.
b Mean alcohol consumption in the past 12 months 1 or
more drinks per day for women and 2 or more drinks
per day for men.
c Smoked more than 100 cigarettes.
Figure 1. Self-Reported Reasons for Consuming 6 Potentially Hepatotoxic Botanical Products
60
50
40
30
20
10
0
Stated reason for use, crude %
Potentially hepatotoxic botanicals
Turmeric
Green tea
Garcinia cambogia
Ashwagandha
Red yeast rice
Black cohosh
Joint health or arthritis
Preventive or boost immunity
Improve energy
Improve or maintain health
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
9/15
Downloaded from jamanetwork.com by guest on 08/27/2024
The prevalence of using the 6 potentially hepatotoxic botanical products was compared with
the prevalence of the use of known hepatotoxic prescription medications (LiverTox class A or B) that
are used for similar indications. Approximately 14 793 837 (95% CI, 13 014 623-16 671 897) US adults
used prescription nonsteroidal anti-inflammatory drugs, which are typically used for indications
similar to those for turmeric (ie, pain or arthritis). Simvastatin, a hypolipidemic drug used to treat and
prevent cardiovascular disease similar to the use for red yeast rice, was consumed by 14 036 024
(95% CI, 11 202 460-17 594 452) individuals. The prevalence of sertraline use was 7 676 980 (95%
CI, 6 523 786-8 994 917) individuals. The comparison of the botanical products of interest with
commonly prescribed prescription medications is shown in Figure 2 (based on the 2020 US Census
estimated total resident population 18 years of age or older of 329 484 123, July 1, 202021).
Discussion
This survey study assessed the prevalence and clinical characteristics of consumers of the 6 most
frequently reported hepatoxic botanicals, including turmeric or curcumin, green tea extract, Garcinia
cambogia, black cohosh, red yeast rice, and ashwagandha, in a representative sample of US adults.
We estimated that at least 15.6 million US adults used at least 1 of 6 potentially hepatotoxic botanical
products within the past 30 days, which was similar to estimated number of US adults prescribed an
NSAID or simvastatin.
The Dietary Supplement Health and Education Act (DSHEA) of 1994 defined an HDS as a
product that contains a “dietary ingredient,” such as vitamins, minerals, herbs or botanicals, amino
acids, and dietary substances that are intended to supplement the diet.25 HDS use has dramatically
increased over time in the United States. from 32.9% in the NHANES I cohort (1971-1974) to 52% in
the NHANES 2011-2012 cohort and 57.6% in the NHANES 2017-2018 cohort.2,26 The economic
impact of the HDS products industry in the US is profound, with over $150 billion in marketplace sales
in 2023, and rivals that of all prescription drugs combined.27 The most common HDSs used are
multivitamins or minerals, calcium, fish oil, botanical supplements, and vitamin C.28,29 In the US, a
variety of adverse events related to HDS use have been described, with an estimated 23 000 annual
emergency department visits and 2154 hospitalizations in 2014.30 The incidence of HDS-DILI is also
increasing over time and accounts for over 20% of cases of liver injury recorded in the DILIN
prospective registry.7 The HDS-DILI can be not only severe, leading to hepatocellular injury with
jaundice, but also fatal, leading to death or liver transplantation.31-37 Kesar et al35 reported the
number of liver transplants due to HDS-DILI in 2010 through 2020 increased over 70% when
compared with 1994 through 2009.
Figure 2. United States Population Estimates for Use of 6 Potentially Hepatotoxic Botanical Products
ComparedWith 3 Commonly PrescribedMedications
18
15
12
9
6
3
0
Turmeric
Estimated adult population, millions
Potentially hepatotoxic botanicals
Ashwagandha
Green
tea
Black cohosh
Garcinia
cambogia
Red yeast
rice
NSAID
Simvastatin
Sertraline
Data are based on 2020 US Census estimated total
resident population 18 years of age or older of
329 484 123 July 1, 2020.21 Whiskers represent 95%
CI. NSAIDs indicates nonsteroidal
anti-inflammatory drugs.
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
10/15
Downloaded from jamanetwork.com by guest on 08/27/2024
The prevalence of the use of potentially hepatotoxic botanical products rather than use of
benign, non-hepatotoxic HDSs, such as vitamins and minerals, has not been systematically studied
nor reported. The present study found that between January 2017 and March 2020, approximately
15 million US adults consumed at least 1 potentially hepatotoxic botanical product within the past
30 days, which was comparable to the number of people taking potentially hepatotoxic prescription
drugs, such as simvastatin, NSAIDs, and sertraline (Figure 2).
The clinical characteristics of the users of the 6 botanical products of interest were similar to
overall HDS users, with older age, more women and non-Hispanic White individuals, higher income,
and higher level of education among HDS users compared with non–HDS users.38-40 Use of HDSs has
also been shown to be more prevalent among individuals with chronic medical conditions, including
cardiovascular disorders, cancer, and obesity.26,40-47 In our study, we found diabetes, arthritis, and
thyroid disorder independently associated with HDS use, but not cardiovascular disorder or cancer.
Arthritis was independently associated with the use of the 6 potentially hepatotoxic botanical
products and with overall HDS use (Table 3).
The reasons for botanical use varied substantially by the specific products as well as the age,
gender, and demographic features of the individual product users (Table 2 and Figure 1). For example,
turmeric-containing products were most commonly used for joint health or arthritis due to the
widespread belief that turmeric may have antioxidant and anti-inflammatory properties as touted in
ayurvedic medicine.48 However, multiple randomized clinical trials have failed to demonstrate any
efficacy of turmeric-containing products in osteoarthritis.48,49 Green tea–containing products were
mostly used as energy supplements. However, multiple studies have failed to demonstrate any
objective evidence of weight loss and sustained improvement in mood or energy levels with products
that contain high levels of catechins or polyphenols found in green tea extract.50-52 Garcinia
cambogia was commonly used for weight loss (70%), as it has been touted that hydroxycitric acid
promotes weight loss.53 Black cohosh was used for hot flashes, and ashwagandha was used as
muscle builder.
In the United States, HDSs are regulated under the general umbrella of foods and are not
intended to be taken for disease treatment or prevention.54,55 Assuming that HDS products are
generally safe similar to foods, the FDA does not require manufacturers to verify the ingredients in a
given product or lot. But recent studies by DILIN have shown substantial discrepancies between
product labels and the results of mass spectroscopy of the actual products.3 In addition, human
bioavailability and safety studies are not required prior to the marketing of an HDS product unless the
formulation contains a novel chemical entity that was not known prior to 1994. The active
ingredients and components in botanical products are even more challenging to standardize due to
the impact of changes in soil, local environment, and batch to batch variation in plant or cultivar
production. The majority of the at-risk botanical users in this study consumed these products
without clinician recommendations presumably due to the touted benefits of the products being
marketed. The number of HDS products marketed in the US increased from 4000 in 1993 to 55 000
in 2012, and approximately 80 000 products were available by 2022.1,56
Limitations
Our study has several important limitations. First, the survey response rate for the January 2017 to
March 2020 prepandemic cohort was low, at 43.9% for adults aged 20 years or older. Since NHANES
is a cross-sectional study, there was no opportunity to determine associations with clinical outcomes,
such as episodes of idiosyncratic hepatotoxic effects. In addition, this survey sample size was not
adequate to detect hepatotoxic effects from botanicals or other adverse events since these arise in
less than 1% of exposed individuals. Thus, our 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. Lastly, use of HDS products and medications was obtained by self-report in NHANES and
not independently verified by source documents. The ingredients data used in this study may be
limited in accuracy due to poor governmental regulation and confirmation of the ingredients listed on
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
11/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822


https://jamanetwork.com/pages/cc-by-license-permissions/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822


mailto:allikhit@med.umich.edu


https://jama.jamanetwork.com/article.aspx?doi=10.1001/jamanetworkopen.2024.25822&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822


https://www.ama-assn.org/delivering-care/public-health/dietary-supplements-underregulated-unknown-and-maybe-unsafe


https://www.ama-assn.org/delivering-care/public-health/dietary-supplements-underregulated-unknown-and-maybe-unsafe


https://dx.doi.org/10.1002/hep4.1346


https://dx.doi.org/10.3390/ijms17030331

the product label, given that previous analysis has shown discrepancies between product labels and
detected ingredients.3 However, NHANES is the largest available nationally representative database
with detailed information regarding dietary supplement product usage in the United States.
Conclusions
This survey study found that in the NHANES 2017 to March 2020 study, over 7% of US adults used a
botanical-containing HDS product within the last 30 days and that the 6 products most commonly
implicated in liver injury in the US are popular among US adults and used as frequently as common
hypolipidemic drugs, NSAIDs and antidepressants. 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 HDS use history when evaluating patients with unexplained symptoms or liver test
abnormalities. Considering 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.
ARTICLE INFORMATION
Accepted for Publication: June 6, 2024.
Published: August 5, 2024. doi:10.1001/jamanetworkopen.2024.25822
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2024 Likhitsup A
et al. JAMA Network Open.
Corresponding Author: Alisa Likhitsup, MD, MPH, Department of Internal Medicine, Division of Gastroenterology
and Hepatology, University of Michigan, 3912 Taubman Center, 1500 E Medical Center Dr, SPC 5362, Ann Arbor,
MI 48109 (allikhit@med.umich.edu).
Author Affiliations: Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of
Michigan, Ann Arbor, Michigan.
Author Contributions: Prof Fontana had full access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Concept and design: Likhitsup, Fontana.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Likhitsup, Fontana.
Critical review of the manuscript for important intellectual content: All authors.
Statistical analysis: Likhitsup, Chen.
Administrative, technical, or material support: Fontana.
Supervision: Fontana.
Conflict of Interest Disclosures: Dr Chen reported receiving grants from Kowa, AstraZeneca, and Ipsen outside
the submitted work. Dr Fontana reported receiving grants from Takeda Pharmaceutical Company and Kezar Life
Sciences outside the submitted work. No other disclosures were reported.
Data Sharing Statement: See Supplement 2.
REFERENCES
1. American Medical Association. Dietary supplements: underregulated, unknown, and maybe unsafe. Accessed
January 19, 2024. https://www.ama-assn.org/delivering-care/public-health/dietary-supplements-underregulated-
unknown-and-maybe-unsafe
2. Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary Supplement Use Among Adults: United States, 2017–
2018. NCHS Data Brief, No. 399. National Center for Health Statistics; 2021.
3. Navarro V, Avula B, Khan I, et al. The contents of herbal and dietary supplements implicated in liver injury in the
United States are frequently mislabeled. Hepatol Commun. 2019;3(6):792-794. doi:10.1002/hep4.1346
4. Avigan MI, Mozersky RP, Seeff LB. Scientific and regulatory perspectives in herbal and dietary supplement
associated hepatotoxicity in the United States. Int J Mol Sci. 2016;17(3):331. doi:10.3390/ijms17030331
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
12/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://dx.doi.org/10.2165/00002018-200932010-00005


https://dx.doi.org/10.2165/00002018-200932010-00005


https://dx.doi.org/10.1002/hep.28813


https://dx.doi.org/10.1097/MEG.0b013e3283155451


https://dx.doi.org/10.1097/MEG.0b013e3283155451


https://dx.doi.org/10.1007/s10620-013-2687-9


https://dx.doi.org/10.1007/s40264-016-0428-7


https://dx.doi.org/10.1007/s40264-016-0428-7


https://dx.doi.org/10.1002/hep.31538


https://dx.doi.org/10.1016/j.cgh.2021.08.015


https://dx.doi.org/10.1097/HC9.0000000000000270


https://dx.doi.org/10.1097/HC9.0000000000000270


https://dx.doi.org/10.1016/j.amjmed.2022.09.026


https://dx.doi.org/10.1016/j.amjmed.2022.09.026


https://dx.doi.org/10.1038/ajg.2016.114


https://dsld.od.nih.gov/


https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?Cycle=2017-2020


https://wwwn.cdc.gov/nchs/nhanes/1999-2000/DSII.htm#Analytic_Notes


https://dx.doi.org/10.1053/j.gastro.2008.01.034


https://www.census.gov/programs-surveys/decennial-census/decade/2020/2020-census-results.html


https://www.census.gov/programs-surveys/decennial-census/decade/2020/2020-census-results.html


https://clincalc.com/DrugStats/Top300Drugs.aspx


https://www.ncbi.nlm.nih.gov/books/NBK547852/


https://www.ncbi.nlm.nih.gov/books/NBK547852/


https://aapor.org/standards-and-ethics/best-practices


https://dx.doi.org/10.1093/jn/nxy093

5. Fontana RJ, Watkins PB, Bonkovsky HL, et al; DILIN Study Group. Drug-Induced Liver Injury Network (DILIN)
prospective study: rationale, design and conduct. Drug Saf. 2009;32(1):55-68. doi:10.2165/00002018-
200932010-00005
6. Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary
supplements. Hepatology. 2017;65(1):363-373. doi:10.1002/hep.28813
7. Pierard S, Coche JC, Lanthier P, et al. Severe hepatitis associated with the use of black cohosh: a report of two
cases and an advice for caution. Eur J Gastroenterol Hepatol. 2009;21(8):941-945. doi:10.1097/MEG.
0b013e3283155451
8. Navarro VJ, Bonkovsky HL, Hwang SI, Vega M, Barnhart H, Serrano J. Catechins in dietary supplements and
hepatotoxicity. Dig Dis Sci. 2013;58(9):2682-2690. doi:10.1007/s10620-013-2687-9
9. Zheng EX, Rossi S, Fontana RJ, et al. Risk of liver injury associated with green tea extract in SLIMQUICK weight
loss products: results from the DILIN prospective study. Drug Saf. 2016;39(8):749-754. doi:10.1007/s40264-016-
0428-7
10. Hoofnagle JH, Bonkovsky HL, Phillips EJ, et al; Drug-Induced Liver Injury Network. HLA-Bb35:01 and green
tea-induced liver injury. Hepatology. 2021;73(6):2484-2493. doi:10.1002/hep.31538
11. Vuppalanchi R, Bonkovsky HL, Ahmad J, et al; Drug-Induced Liver Injury Network. Garcinia cambogia, either
alone or in combination with green tea, causes moderate to severe liver injury. Clin Gastroenterol Hepatol. 2022;
20(6):e1416-e1425. doi:10.1016/j.cgh.2021.08.015
12. Philips CA, Valsan A, Theruvath AH, et al; Liver Research Club India. Ashwagandha-induced liver injury: a case
series from India and literature review. Hepatol Commun. 2023;7(10):e0270. doi:10.1097/HC9.
0000000000000270
13. Halegoua-DeMarzio D, Navarro V, Ahmad J, et al. Liver injury associated with turmeric-a growing problem: ten
cases from the Drug-Induced Liver Injury Network [DILIN]. Am JMed. 2023;136(2):200-206. doi:10.1016/j.
amjmed.2022.09.026
14. Hillman L, Gottfried M, Whitsett M, et al. Clinical features and outcomes of complementary and alternative
medicine induced acute liver failure and injury. Am J Gastroenterol. 2016;111(7):958-965. doi:10.1038/ajg.2016.114
15. National Institutes of Health Office of Dietary Supplements. Dietary Supplement Label Database (DSLD).
Accessed July 1, 2023. https://dsld.od.nih.gov/
16. Zipf G, Chiappa M, Porter KS, Ostchega Y, Lewis BG, Dostal J. National Health and Nutrition Examination
Survey: plan and operations, 1999-2010. Vital Health Stat 1. 2013;(56):1-37.
17. Stierman B, Afful J, Carroll MD, et al. National Health and Nutrition Examination Survey 2017–March 2020
Prepandemic Data Files—Development of Files and Prevalence Estimates for Selected Health Outcomes. National
Health Statistics Reports; No. 158. National Center for Health Statistics; 2021.
18. Centers for Disease Control and Prevention. NHANES 2017-March 2020 pre-pandemic. Accessed July 1, 2023.
https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?Cycle=2017-2020
19. Centers for Disease Control and Prevention. NHANES 1999-2020 data documentation, codebook, and
frequencies. Accessed July 1, 2023. https://wwwn.cdc.gov/nchs/nhanes/1999-2000/DSII.htm#Analytic_Notes
20. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver
fibrosis: a meta-analysis. Gastroenterology. 2008;134(4):960-974. doi:10.1053/j.gastro.2008.01.034
21. United States Census Bureau. 2020 U.S. Census results. Accessed July 1, 2023. https://www.census.gov/
programs-surveys/decennial-census/decade/2020/2020-census-results.html
22. ClinCalc.com. The top 300 of 2021 provided by the ClinCalc Drugstats Database. Accessed December 1, 2023.
https://clincalc.com/DrugStats/Top300Drugs.aspx
23. National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox: clinical and research information
on drug-induced liver injury, 2012-. Updated June 20, 2024. Accessed January 19, 2024. https://www.ncbi.nlm.nih.
gov/books/NBK547852/
24. American Association for Public Opinion Research. Best practices for survey research. Accessed May 22, 2024.
https://aapor.org/standards-and-ethics/best-practices
25. US Food and Drug Administration. Dietary Supplement Health and Education Act of 1994; Public Law 103–417.
US Food and Drug Administration; 1994.
26. Gahche JJ, Bailey RL, Potischman N, et al. Federal monitoring of dietary supplement use in the resident,
civilian, noninstitutionalized US population, National Health and Nutrition Examination Survey. J Nutr. 2018;
148(suppl 2):1436S-1444S. doi:10.1093/jn/nxy093
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
13/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://www.crnusa.org/resources/economic-impact-dietary-supplement-industry#:~:text=In%20the%20United%20States%2C%20the%2cfor%20health%20and%20wellness%20products


https://www.crnusa.org/resources/economic-impact-dietary-supplement-industry#:~:text=In%20the%20United%20States%2C%20the%2cfor%20health%20and%20wellness%20products


https://www.crnusa.org/resources/economic-impact-dietary-supplement-industry#:~:text=In%20the%20United%20States%2C%20the%2cfor%20health%20and%20wellness%20products


https://dx.doi.org/10.1016/j.jand.2014.01.016


https://dx.doi.org/10.1093/jn/nxaa040


https://dx.doi.org/10.1056/NEJMsa1504267


https://jama.jamanetwork.com/article.aspx?doi=10.1001/archsurg.138.8.852&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822


https://dx.doi.org/10.1053/j.gastro.2008.09.011


https://dx.doi.org/10.4321/s1130-01082008001100004


https://dx.doi.org/10.4321/s1130-01082008001100004


https://www.ncbi.nlm.nih.gov/pubmed/24113901


https://www.ncbi.nlm.nih.gov/pubmed/24113901


https://dx.doi.org/10.1002/hep.28967


https://dx.doi.org/10.1016/j.jemermed.2021.01.004


https://dx.doi.org/10.1002/lt.26260


https://dx.doi.org/10.1016/S0749-3797(02)00571-8


https://dx.doi.org/10.3390/nu14091787


https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2021.15650&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822


https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2022.8970&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamanetworkopen.2024.25822


https://dx.doi.org/10.1093/aje/kwh207


https://dx.doi.org/10.1093/ajcn/85.1.277S


https://www.ncbi.nlm.nih.gov/pubmed/12616253


https://dx.doi.org/10.1016/j.jada.2007.12.005


https://dx.doi.org/10.1080/01635581.2020.1820050


https://dx.doi.org/10.1371/journal.pone.0269241


https://dx.doi.org/10.1371/journal.pone.0269241

27. Council for Responsible Nutrition. The science behind the supplements: economic impact of the dietary
supplement industry. Accessed January 31, 2024. https://www.crnusa.org/resources/economic-impact-dietary-
supplement-industry#:~:text=In%20the%20United%20States%2C%20the,for%20health%20and%20wellness
%20products
28. Farina EK, Austin KG, Lieberman HR. Concomitant dietary supplement and prescription medication use is
prevalent among US adults with doctor-informed medical conditions. J Acad Nutr Diet. 2014;114(11):1784-90.e2.
doi:10.1016/j.jand.2014.01.016
29. Du M, Luo H, Blumberg JB, et al. Dietary supplement use among adult cancer survivors in the United States.
J Nutr. 2020;150(6):1499-1508. doi:10.1093/jn/nxaa040
30. Geller AI, Shehab N, Weidle NJ, et al. Emergency department visits for adverse events related to dietary
supplements. N Engl J Med. 2015;373(16):1531-1540. doi:10.1056/NEJMsa1504267
31. Estes JD, Stolpman D, Olyaei A, et al. High prevalence of potentially hepatotoxic herbal supplement use in
patients with fulminant hepatic failure. Arch Surg. 2003;138(8):852-858. doi:10.1001/archsurg.138.8.852
32. Chalasani N, Fontana RJ, Bonkovsky HL, et al; Drug Induced Liver Injury Network (DILIN). Causes, clinical
features, and outcomes from a prospective study of drug-induced liver injury in the United States.
Gastroenterology. 2008;135(6):1924-1934, 1934.e1-1934.e4. doi:10.1053/j.gastro.2008.09.011
33. García-Cortés M, Borraz Y, Lucena MI, et al. Liver injury induced by “natural remedies”: an analysis of cases
submitted to the Spanish Liver Toxicity Registry [in Spanish]. Rev Esp Enferm Dig. 2008;100(11):688-695. doi:10.
4321/s1130-01082008001100004
34. Centers for Disease Control and Prevention (CDC). Notes from the field: acute hepatitis and liver failure
following the use of a dietary supplement intended for weight loss or muscle building—May-October 2013. MMWR
Morb Mortal Wkly Rep. 2013;62(40):817-819.
35. Bonkovsky HL, Kleiner DE, Gu J, et al; U.S. Drug Induced Liver Injury Network Investigators. Clinical
presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology.
2017;65(4):1267-1277. doi:10.1002/hep.28967
36. Koenig G, Callipari C, Smereck JA. Acute liver injury after long-term herbal “liver cleansing” and “sleep aid”
supplement use. J Emerg Med. 2021;60(5):610-614. doi:10.1016/j.jemermed.2021.01.004
37. Kesar V, Channen L, Masood U, et al. Liver transplantation for acute liver injury in Asians is more likely due to
herbal and dietary supplements. Liver Transpl. 2022;28(2):188-199. doi:10.1002/lt.26260
38. Satia-Abouta J, Kristal AR, Patterson RE, Littman AJ, Stratton KL, White E. Dietary supplement use and
medical conditions: the VITAL study. Am J Prev Med. 2003;24(1):43-51. doi:10.1016/S0749-3797(02)00571-8
39. Mah E, Chen O, Liska DJ, Blumberg JB. Dietary supplements for weight management: a narrative review of
safety and metabolic health benefits. Nutrients. 2022;14(9):1787. doi:10.3390/nu14091787
40. O’Connor EA, Evans CV, Ivlev I, et al. Vitamin and mineral supplements for the primary prevention of
cardiovascular disease and cancer: updated evidence report and systematic review for the US Preventive Services
Task Force. JAMA. 2022;327(23):2334-2347. doi:10.1001/jama.2021.15650
41. Mangione CM, Barry MJ, Nicholson WK, et al; US Preventive Services Task Force. Vitamin, mineral, and
multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force
recommendation statement. JAMA. 2022;327(23):2326-2333. doi:10.1001/jama.2022.8970
42. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults:
data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol. 2004;160(4):
339-349. doi:10.1093/aje/kwh207
43. Rock CL. Multivitamin-multimineral supplements: who uses them? Am J Clin Nutr. 2007;85(1):277S-279S. doi:
10.1093/ajcn/85.1.277S
44. Patterson RE, Neuhouser ML, Hedderson MM, Schwartz SM, Standish LJ, Bowen DJ. Changes in diet, physical
activity, and supplement use among adults diagnosed with cancer. J Am Diet Assoc. 2003;103(3):323-328.
45. Miller MF, Bellizzi KM, Sufian M, Ambs AH, Goldstein MS, Ballard-Barbash R. Dietary supplement use in
individuals living with cancer and other chronic conditions: a population-based study. J Am Diet Assoc. 2008;108
(3):483-494. doi:10.1016/j.jada.2007.12.005
46. Abdel-Rahman O. Dietary supplements use among adults with cancer in the United States: a population-
based study. Nutr Cancer. 2021;73(10):1856-1863. doi:10.1080/01635581.2020.1820050
47. Barrett LA, Xing A, Sheffler J, et al. Assessing the use of prescription drugs and dietary supplements in obese
respondents in the National Health and Nutrition Examination Survey. PLoS One. 2022;17(6):e0269241. doi:10.
1371/journal.pone.0269241
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
14/15
Downloaded from jamanetwork.com by guest on 08/27/2024

https://dx.doi.org/10.3390/foods6100092


https://dx.doi.org/10.3390/foods6100092


https://dx.doi.org/10.3389/fimmu.2022.891822


https://dx.doi.org/10.1111/j.1467-789X.2011.00862.x


https://dx.doi.org/10.3390/nu13020644


https://dx.doi.org/10.2174/1570159X18666200529152625


https://dx.doi.org/10.2174/1570159X18666200529152625


https://dx.doi.org/10.3390/nu14153077


https://www.fda.gov/food/dietary-supplements


https://www.fda.gov/food/dietary-supplements


https://www.fda.gov/drugs/news-events-human-drugs/fdas-regulation-dietary-supplements-dr-cara-welch


https://www.fda.gov/drugs/news-events-human-drugs/fdas-regulation-dietary-supplements-dr-cara-welch


https://dx.doi.org/10.1111/j.1532-5415.2009.02329.x

48. Hewlings SJ, Kalman DS. Curcumin: a review of its effects on human health. Foods. 2017;6(10):92. doi:10.
3390/foods6100092
49. Zeng L, Yang T, Yang K, et al. Efficacy and safety of curcumin and Curcuma longa extract in the treatment of
arthritis: a systematic review and meta-analysis of randomized controlled trial. Front Immunol. 2022;13:891822.
doi:10.3389/fimmu.2022.891822
50. Hursel R, Viechtbauer W, Dulloo AG, et al. The effects of catechin rich teas and caffeine on energy expenditure
and fat oxidation: a meta-analysis. Obes Rev. 2011;12(7):e573-e581. doi:10.1111/j.1467-789X.2011.00862.x
51. Rondanelli M, Riva A, Petrangolini G, et al. Effect of acute and chronic dietary supplementation with green tea
catechins on resting metabolic rate, energy expenditure and respiratory quotient: a systematic review. Nutrients.
2021;13(2):644. doi:10.3390/nu13020644
52. Akbarialiabad H, Dahroud MD, Khazaei MM, Razmeh S, Zarshenas MM. Green tea, a medicinal food with
promising neurological benefits. Curr Neuropharmacol. 2021;19(3):349-359. doi:10.2174/
1570159X18666200529152625
53. Mena-García A, Bellaizac-Riascos AJ, Rada-Mendoza M, Chito-Trujillo DM, Ruiz-Matute AI, Sanz ML. Quality
Evaluation of dietary supplements for weight loss based on Garcinia cambogia. Nutrients. 2022;14(15):3077. doi:
10.3390/nu14153077
54. US Food and Drug Administration. Dietary supplements. Accessed January 1, 2024. https://www.fda.gov/food/
dietary-supplements
55. US Food and Drug Administration. FDA’s regulation of dietary supplements with Dr. Cara Welch: Q&A with FDA
podcast/transcript. Accessed January 1, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fdas-
regulation-dietary-supplements-dr-cara-welch
56. Nahin RL, Pecha M, Welmerink DB, Sink K, DeKosky ST, Fitzpatrick AL; Ginkgo Evaluation of Memory Study
Investigators. Concomitant use of prescription drugs and dietary supplements in ambulatory elderly people. J Am
Geriatr Soc. 2009;57(7):1197-1205. doi:10.1111/j.1532-5415.2009.02329.x
SUPPLEMENT 1.
eTable 1. Ingredient Identification Number and Supplement Identification Number Identified the 6 Potential
Hepatotoxic Botanical Products
eTable 2. Botanical Products by Name (Alphabetical)
eFigure. Herbal and Dietary Supplement Use Among U.S. Adults Enrolled in NHANES 2017-2020
SUPPLEMENT 2.
Data Sharing Statement
JAMANetworkOpen | Complementary andAlternativeMedicine
Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
JAMA Network Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822 (Reprinted)
August 5, 2024
15/15
Downloaded from jamanetwork.com by guest on 08/27/2024