The estimated daily lead, mercury, or arsenic ingestion levels were
estimated using a single measure of lead, mercury, or arsenic concentration
in the originally purchased herbal medicine products (HMPs), the unit dose
weight, and recommended dosages stated on the label. If the manufacturer recommended
a range of suggested dosages, a range of potential daily lead, mercury, or
arsenic ingestion is displayed.
*For adults, US Pharmacopeia (USP ) maximum
allowable lead content (4.5 μg) for a daily dose of 1500 mg of calcium
carbonate25; and for children, USP maximum
allowable lead content (1 μg) allowed in a daily dose of ferrous sulfate
suspension (0.8-g elemental iron per 100 mL) administered to a 10-kg child
at 2-mg elemental iron per kg/d.25,26
†Name of manufacturer is given in parentheses.
‡Estimated intake based on an assumption of 0.1 to 0.2 g of Bal
Chamcha used per dose.
§US Environmental Protection Agency (EPA) reference dose for chronic
(>365 days) oral intake of mercuric chloride or arsenic for a 70-kg adult
∥EPA reference dose for chronic (>365 days) oral intake of mercuric
chloride or arsenic for a 10-kg child (3 μg).27
Saper RB, Kales SN, Paquin J, Burns MJ, Eisenberg DM, Davis RB, Phillips RS. Heavy Metal Content of Ayurvedic Herbal Medicine Products. JAMA. 2004;292(23):2868–2873. doi:10.1001/jama.292.23.2868
Context Lead, mercury, and arsenic intoxication have been associated with the
use of Ayurvedic herbal medicine product (HMPs).
Objectives To determine the prevalence and concentration of heavy metals in Ayurvedic
HMPs manufactured in South Asia and sold in Boston-area stores and to compare
estimated daily metal ingestion with regulatory standards.
Design and Setting Systematic search strategy to identify all stores 20 miles or less from
Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online
Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India,
Indian cities, and Indian words. An online national directory of Indian grocery
stores, a South Asian community business directory, and a newspaper were also
searched. We visited each store and purchased all unique Ayurvedic HMPs between
April 25 and October 24, 2003.
Main Outcome Measures Concentrations (μg/g) of lead, mercury, and arsenic in each HMP
as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion
for adults and children estimated using manufacturers’ dosage recommendations
with comparisons to US Pharmacopeia and US Environmental Protection
Agency regulatory standards.
Results A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained
heavy metals: lead (n = 13; median concentration, 40 μg/g; range,
5-37 000), mercury (n = 6; median concentration, 20 225
μg/g; range, 28-104 000), and/or arsenic (n = 6; median
concentration, 430 μg/g; range, 37-8130). If taken as recommended by the
manufacturers, each of these 14 could result in heavy metal intakes above
published regulatory standards.
Conclusions One of 5 Ayurvedic HMPs produced in South Asia and available in Boston
South Asian grocery stores contains potentially harmful levels of lead, mercury,
and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal
toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.
Ayurvedic medicine originated in India more than 2000 years ago and
relies heavily on herbal medicine products (HMPs).1 Approximately
80% of India’s 1 billion population uses Ayurveda through more than
one-half million Ayurvedic practitioners working in 2860 Ayurvedic hospitals
and 22 100 clinics.2 Ayurveda’s
popularity in Western countries has increased.3 In
the United States, Ayurvedic remedies are now available from South Asian markets,
Ayurvedic practitioners, health food stores, and the Internet. Because Ayurvedic
HMPs are marketed as dietary supplements, they are regulated under the Dietary
Supplement Health and Education Act (DSHEA), which does not require proof
of safety or efficacy.4
Herbs, minerals, and metals are used in Ayurvedic HMPs.2 Lead
toxicity has been associated with use of Ayurvedic HMPs, including status
epilepticus,5 fatal infant encephalopathy,6 congenital paralysis and sensorineural deafness,7 and developmental delay.8 Since
1978, at least 55 cases of heavy metal intoxication associated with Ayurvedic
HMPs in adults and children have been reported in the United States and abroad.5- 17
Although Ko18 raised concern about heavy
metals in traditional Chinese medicines (Richard Ko, PharmD, PhD, written
communication, 2004) available in California, no studies have specifically
measured heavy metals in Ayurvedic (traditional Indian) HMPs sold in the United
States. We determined the heavy metal content in a sample of Ayurvedic HMPs
sold in Boston-area retail stores. We also estimated daily heavy metal intakes
for each HMP and compared these with maximum allowable regulatory standards.
We identified Boston-area stores selling Ayurvedic HMPs manufactured
in South Asia by searching online Yellow Pages19 using
the categories markets, supermarkets, and convenience stores, and business names
containing the wordIndia, Indian cities, and Indian
words; and an online national directory of Indian grocery stores,20 a South Asian community business directory,21 and a newspaper.22
Between April 25 and October 24, 2003, we visited all identified stores
that were 20 miles or less from Boston City Hall as measured by Microsoft
Streets and Trips 2002 (Microsoft Corp, Redmond, Wash). In each store, we
purchased 1 package of each HMP available that met the following inclusion
criteria: Ayurvedic herbal remedy, manufactured in South Asia, and intended
for oral use. When more than 1 store carried the same HMP (ie, identical name,
manufacturer, and formulation), the HMP was purchased from 1 store only. If
2 HMPs had the same name but were made by different manufacturers or had different
formulations (eg, powder and tablets), these HMPs were considered to be different
for the purposes of our study and were therefore both purchased. The name,
manufacturer, manufacturer’s location, lot number, formulation, indications,
recommended dosages, and cost per package were recorded for all HMPs purchased.
Non-English labels were professionally translated. Because this study did
not involve human participants, the Harvard Medical School’s institutional
review board determined that its approval was not required.
All HMPs were transferred to plastic pharmacy-grade vials (Tri-State
Distribution, Sparta, Tenn) and labeled with a numerical identifier only.
Vials were sent without interruption in chain of custody to the New England
Regional Environmental Protection Agency (EPA) laboratory for analysis. Laboratory
personnel were blinded to the identity of the HMPs. Solid HMPs were weighed
and homogenized thoroughly to reduce the risk of matrix interference from
particle size differences. To determine the metal concentration of the HMP,
samples were analyzed once by x-ray fluorescence spectroscopy23 using
the Spectro X-Laboratory 2000 XRF equipped with a tungsten x-ray tube, a Si(Li)-semiconductor
detector, and software version 2.2R03 I (Spectro Analytical Instruments, Kleve,
Germany). National Institute of Standards and Technology solid standard reference
materials (SRMs) 2709, 2710, 2711,24 and liquid
certified standards (SCP Science, Champlain, NY) containing specified heavy
metal concentrations served as positive and negative controls. We reported
metal concentrations in μg/g. The instrument’s minimum detection
limits were lead 5 μg/g, mercury 20 μg/g, arsenic 10 μg/g, and
cadmium 10 μg/g.
To assess reproducibility, we returned to the grocery stores from November
17 to 26, 2003, and attempted to repurchase 1 package of each HMP found on
initial testing to contain lead, mercury, arsenic, and/or cadmium. We also
used a computerized random number generator to select 14 HMPs for repurchase
among all HMPs found on initial testing to have no detectable heavy metals.
One package of each of the 14 negative HMPs was repurchased. Positive and
negative HMPs were repurchased irrespective of their lot numbers. Each repurchased
HMP received a new numerical identifier and was similarly transferred to vials,
which were sent to the EPA. At the laboratory, each HMP was split into 2 samples
and each sample was assayed twice alongside SRM controls.
We calculated the proportion of HMPs containing heavy metals. The coefficient
of variation for the metal concentrations was calculated using data from the
split-sample duplicate assays. If an HMP contained lead, we used the lead
concentration (measured in the original set of HMPs purchased), unit dose
weight, and recommended dosages to calculate the amount of lead that would
be ingested daily. If there was a range of suggested dosages, the daily ingestion
was presented as a range. For lead, we compared the daily ingestion for an
adult with the US Pharmacopeia (USP ) specifications
for the maximum allowable lead content (4.5 μg) in a 1500-mg daily dose
of calcium carbonate.25 For children, we compared
our estimated ranges with the USP specifications for the maximum
allowable lead content (1 μg) in a 2.5-mL daily dose of ferrous sulfate
suspension (assumes 2-mg elemental iron per kg/d for a 10-kg child taking
a 0.8-g elemental iron per 100-mL suspension).25,26 For
HMPs containing mercury, arsenic, or both, we similarly calculated the amount
of mercury, arsenic, or both that would be ingested daily. We compared estimated
ranges of mercury and arsenic intakes with their respective EPA established
reference doses (RfDs) for oral chronic exposure (0.3 μg/kg per day for
both mercuric chloride and arsenic).27
Using our search strategy, we purchased 70 unique Ayurvedic HMPs, manufactured
by 27 companies (26 based in India and 1 in Pakistan) in 30 Boston-area stores.
The HMPs carried a wide variety of indications, most commonly gastrointestinal
(71%). The median cost per package was $2.99 (range, $0.50-$5.99).
A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained
lead, mercury, and/or arsenic (Table 1). Table 2 lists the 14 products containing heavy
metals, their manufacturers, and their heavy metal concentrations. Seven HMPs
specifically recommended pediatric use. Twenty-four of the 30 stores sold
at least 1 heavy metal–containing HMP.
Each estimate is based on daily ingestion of the manufacturer’s
recommended dose. The Figure displays
the estimated daily lead, mercury, and arsenic ingestion for heavy metal–containing
HMPs recommended for adults and children. All 10 HMPs containing lead and
recommended for adults could result in ingestions higher than the comparable USP standard. Six HMPs were orders of magnitude higher. The estimated
daily lead ingestion for each of the 6 lead-containing HMPs recommended for
children could result in ingestions of equal to or above the USP standard.
Similar comparisons were made for arsenic and mercury. All 4 mercury-containing
HMPs intended for adults could result in estimated daily mercury intakes of
at least 1 order of magnitude higher than the EPA reference dose for a 70-kg
adult. Two of 3 mercury-containing HMPs recommended for children have estimated
ranges of daily mercury intake of 2 to 3 orders of magnitude higher than the
EPA reference dose for a 10-kg child. Four of 5 arsenic-containing HMPs recommended
for adults would result in daily intakes of 1 to 3 orders of magnitude higher
than the EPA reference dose. Chronic ingestion of the 3 arsenic-containing
HMPs intended for children would also result in daily intakes of more than
the reference dose.
We were able to repurchase 10 of the 14 positive HMPs for split-sample
retesting. For the HMPs unavailable for repurchase, we performed split-sample
retesting using the original HMPs. All 10 repurchased HMPs had heavy metal
concentrations similar to the original samples: lead, average of 112% of original
concentrations; mercury, average of 118% of original concentrations; and arsenic,
average of 112% of original concentrations. The mean coefficients of variation
for lead, mercury, and arsenic concentrations in the split-sample retesting
were 0.05, 0.03, and 0.05, respectively. This amount of variability is not
significant enough to lower the estimated daily amounts of metal ingestions
from the HMPs below acceptable regulatory standards. The 14 negative HMPs
randomly selected for repurchase did not contain any heavy metals on retesting.
Measurements of heavy metals in solid SRMs and certified liquid standards
(data not shown, available on request) were on average less than 8% different
than their certified concentrations (lead +4.8%, mercury +7.8%, and arsenic
–7.3%), consistent with the confidence limits of the standards and our
Ayurvedic HMPs containing heavy metals are readily available in most
of the South Asian grocery stores in Boston, recommended for adults and children,
and relatively inexpensive. One of 5 available Ayurvedic HMPs contained lead,
mercury, and/or arsenic. Taken as recommended, each of the 14 heavy metal–containing
HMPs we identified may result in heavy metal intake above regulatory standards.
Our data are consistent with studies of Ayurvedic HMPs sold outside
the United States and herbal remedies from other indigenous healing traditions.
In England, 30% of Ayurvedic HMPs sampled contained lead, mercury, or arsenic.17 Of 22 Ayurvedic HMPs purchased in India, 64% contained
lead and mercury, and 41% contained arsenic.16 Traditional
medicines from China,18 Malaysia,28 Mexico,29 Africa,30 and the
Middle East31 have also been shown to contain
Two lines of evidence suggest our sample of HMPs has unacceptably high
heavy metal content. First, metal concentrations in our specimens correlate
with concentrations associated with both toxic blood concentrations and symptomatic
poisoning in previously reported cases. The lead concentrations we observed
overlapped with those associated with toxicity in a recent US case series
(range, 21-96 000 μg/g)5 and in patients
from Croatia (range, 0.90-72 990 μg/g).15 Specific
HMPs containing heavy metals in our sample (eg, Mahayograj Guggulu) have been
associated with serious toxicity in case reports.5,9 Arsenic
poisoning was described in 47 children and adults in Singapore using a Chinese
HMP with 12 000 μg/g of arsenic.32 Second,
epidemiological evidence of insidious adverse effects (eg, decreased childhood
IQ,33 increased blood pressure,34 progression
of chronic renal insufficiency35) from low
levels of lead exposure previously thought to be acceptable suggests that
even HMPs with relatively lower levels of lead (<100 μg/g) may be deleterious.
Ayurvedic theory attributes important therapeutic roles to metals such
as mercury and lead.2,36 Ayurveda
experts estimate that 35% to 40% of the approximately 6000 medicines in the
Ayurvedic formulary intentionally contain at least 1 metal.2 Metal-containing
HMPs are purportedly “detoxified” through multiple heating/cooling
cycles and the addition of specific herbs.36 Whether
the heavy metals in our sample were already present in raw plant materials37 or intentionally or incidentally added in the manufacturing
process is uncertain.
Our study has several limitations. First, increased concentrations of
lead of more than 5000 μg/g or of mercury of more than 15 000 μg/g
could theoretically produce spectral interference and falsely increase the
results for other metals. To assess this, we tested samples of metal salts
at high concentrations and found negligible spectral interference with other
metals of interest. We also analyzed diluted HMP samples and found similar
results to the original data. In addition, the spectra of nontarget elements
present in the HMPs (eg, sulfur, calcium, iron, copper) were found not to
interfere with the spectra of lead, mercury, or arsenic. Second, we were not
able to ascertain the metals’ chemical forms, which can impact bioavailability
and toxicity, especially in the case of mercury.38 Finally,
our data were limited to 70 Ayurvedic HMPs manufactured in South Asia and
found in Boston-area stores. Whether these findings can be generalized to
those HMPs sold elsewhere in the United States requires further study.
Despite these limitations, the presence of heavy metals in Ayurvedic
HMPs and the numerous reports of associated toxicity may have important public
health, clinical, and policy implications in the United States and abroad.
Although the prevalence of heavy metal–containing Ayurvedic HMP use
is unknown, the number of individuals at potential risk is substantial. Recent
analysis of the US National Health Interview Survey 2002 Alternative Medicine
Supplement estimates 750 000 adults consulted an Ayurvedic practitioner
in the past.39 In India, an estimated 80% of
the population uses Ayurveda.2 Epidemiological
studies of Ayurvedic HMP use and heavy metal toxicity in the United States
and abroad are therefore warranted. Public health and community organizations
should consider issuing advisories to current or previous Ayurvedic HMP users,
encouraging them to consult their physicians about heavy metal screening.
Use of specific heavy metal–containing HMPs in our study should be discouraged.
Physicians should also consider Ayurvedic HMP intake in the differential diagnosis
of unexplained heavy metal toxicity. Current US law stipulates that regulations
governing dietary supplements produced and sold domestically (DSHEA) should
also be applied to dietary supplements imported into the United States.40 Our findings support calls for reform of DSHEA that
would require mandatory testing of all imported dietary supplements for toxic
Corresponding Author: Robert B. Saper, MD,
MPH, Department of Family Medicine, Boston University School of Medicine,
One Boston Medical Center Place, Dowling 5 S, Boston, MA 02118-2317 (firstname.lastname@example.org).
Financial Disclosure: Dr Eisenberg has received
honoraria for educational lectures relating to the epidemiology of complementary
therapy use, ongoing research in this area at Harvard Medical School, and
national trends in complementary medicine research but has neither spoken
on the topic of Ayurveda or the efficacy, safety, or toxicity of Ayurveda,
or received grant support (federal or private) for investigations of Ayurvedic
Author Contributions: Dr Saper 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.
Study concept and design: Saper, Kales, Burns,
Eisenberg, Davis, Phillips.
Acquisition of data: Saper, Paquin.
Analysis and interpretation of data: Saper,
Kales, Burns, Eisenberg, Davis.
Drafting of the manuscript: Saper, Kales, Burns.
Critical revision of the manuscript for important
intellectual content: Saper, Kales, Paquin, Burns, Eisenberg, Davis,
Statistical analysis: Saper, Davis.
Obtained funding: Saper, Eisenberg, Phillips.
Administrative, technical, or material support:
Saper, Kales, Paquin.
Study supervision: Saper, Burns, Eisenberg,
Funding/Support: Dr Saper was supported by
an Institutional National Research Service Award for training in Alternative
Medicine Research (T32 AT00051) from the National Center for Complementary
and Alternative Medicine (NCCAM), National Institutes of Health, Bethesda,
Md. Dr Phillips is supported by a Mid-Career Investigator Award (K24 AT00589)
from NCCAM. Herbal products were purchased with funds from the Division for
Research and Education in Complementary and Integrative Medical Therapies
of Harvard Medical School.
Role of the Sponsor: Harvard Medical School
had no role in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; or preparation, review, or approval
of the manuscript for submission.
Disclaimer: The content of this article is
solely the responsibility of the authors and does not necessarily represent
the official views of the NCCAM, the National Institutes of Health, or the
US Environmental Protection Agency.
Acknowledgment: We gratefully thank Mary Beth
Hamel, MD, MPH, and Michael Shannon, MD, for their review of an earlier version
of the manuscript; DavidSolondz, BSE, for assistance with sample collection;
Brian Ambrefe, RPh, CDE, for donation of sample vials; Naseem Hines, PhD,
for label translation; Anusha Seghal, BAMS, for helpful discussions regarding
Ayurveda; and Nadia Khouri for editing.