The authors have declared that no competing interests exist.
Conceived and designed the experiments: SG GS. Performed the experiments: SG GS IR. Analyzed the data: SG GS. Contributed reagents/materials/analysis tools: SG GS AS. Wrote the paper: SG GS AS IR.
Concern has recently emerged regarding the safety of natural health products (NHPs)–therapies that are increasingly recommended by various health providers, including conventional physicians. Recognizing that most individuals in the Western world now consume vitamins and many take herbal agents, this study endeavored to determine levels of toxic element contamination within a range of NHPs.
Toxic element testing was performed on 121 NHPs (including Ayurvedic, traditional Chinese, and various marine-source products) as well as 49 routinely prescribed pharmaceutical preparations. Testing was also performed on several batches of one prenatal supplement, with multiple samples tested within each batch. Results were compared to existing toxicant regulatory limits.
Toxic element contamination was found in many supplements and pharmaceuticals; levels exceeding established limits were only found in a small percentage of the NHPs tested and none of the drugs tested. Some NHPs demonstrated contamination levels above preferred daily endpoints for mercury, cadmium, lead, arsenic or aluminum. NHPs manufactured in China generally had higher levels of mercury and aluminum.
Exposure to toxic elements is occurring regularly as a result of some contaminated NHPs. Best practices for quality control–developed and implemented by the NHP industry with government oversight–is recommended to guard the safety of unsuspecting consumers.
The issue of harm related to healthcare provision has become a persistent problem that has been shrouded in silence.
Accordingly, this study was designed to determine if toxic element contamination of NHPs is a routine occurrence or a sporadic event. A variety of common pharmaceutical preparations were tested for comparison purposes.
Various items including foods, toys, cosmetics and other personal care products have recently been found to contain toxic compounds
Many health providers now recommend NHPs including prenatal vitamins, iron supplementation, calcium, and vitamin D for a range of recognized indications including deficiency states such as rickets and anemia, as well as illnesses such as multiple sclerosis.
With increases in globalization, cultural remedies from Chinese, Ayurvedic, and other traditions have become more available to international consumers, offering unfamiliar products with unfamiliar adverse effects. Thus, beyond questions of efficacy and drug interactions, the inherent safety of NHPs has come under increasing scrutiny in the public health community.
Ayurvedic practices stem from the Vedic culture of southern Asia, and date back over 5000 years. Rather than a purely structural, organ-based approach to health, Ayurveda focuses on the functions of organ systems and the body as a whole.
Some Ayurvedic preparations have been found to contain significant amounts of lead, mercury and arsenic.
Ayurvedic supplements containing toxic elements are widely available in the United States.
Other toxicant related problems have resulted from consumption of Ayurvedic preparations. Mercury from Ayurvedic NHPs has been associated with weight loss, diarrhea, sweating, tremors, paresthesias and peripheral neuropathy,
Dating back thousands of years, traditional Chinese Medicine (TCM), like Ayurveda, arises from a philosophy of balance as well as pattern-based diagnosis and treatment. Herbs may be classified according to taste (sour, bitter, sweet, pungent, and salty), ‘temperature’ (cold, warm, hot, cool) or direction (ascending, descending, floating, and sinking). Symptoms of illness are categorized, then treated with opposing herbs.
Lead,
Toxic Element | U.S. California Proposition 65, |
EuropeanUnion |
Australia |
World HealthOrganization |
Gestational Limits |
Mercury (Hg) | 2 | 4.2 | 2.4 Inorganic Hg0.96 Methyl Hg | 1.37 (Methyl Hg inchildren) | O.6 for Methyl Hg |
Lead | 15 | 21 | NE | 21 | Concern at low levels. No level yet established as acceptable |
Cadmium | 4.1 | 6 | 15 | 6 | NE |
Arsenic | 10 | 13.0 | NE | 12.85 | NE |
Aluminum | 7,000 | 4,286 | 12,000 | NE | NE |
Barium | 1,200 | NE | NE | NE | NE |
Antimony | 2.8 | 36 | NE | NE | NE |
Thallium | 70 | NE | NE | NE | NE |
Tin | 200 | NE | NE | NE | NE |
Cesium | NE | NE | NE | NE | NE |
NE – Not established.
European/WHO/Australian levels were established by convention as representing 10% of the daily total toxicant intake after conversion of values expressed in mg/kg/week for an average adult weight of 60 kg.
Element in mcg | Mercury | Lead | Cadmium | Arsenic | Aluminum | Barium | Antimony | Thallium | Tin | Cesium |
Allowable limit/day |
2 | 15 | 4.1 | 10 | 7,000 | 1,400 | 2.8 | 70 | 200 | NE |
|
||||||||||
(N) tested | 121 | 121 | 121 | 100 | 121 | 121 | 72 | 65 | 65 | 65 |
Average daily exposure (mean) | 0.366 | 1.49 | 0.199 | 21.7 | 573 | 59.3 | 0.126 | 0.0384 | 0.608 | 0.167 |
Standard Deviation | 3.80 | 5.33 | 0.803 | 202 | 1,590 | 138 | 0.372 | 0.0803 | 1.88 | 0.400 |
Highest daily exposure in single sample | 41.8 | 51.4 | 6.81 | 2,020 | 12,900 | 894 | 2.32 | 0.354 | 13.2 | 2.34 |
Average annual exposure | 134 | 545 | 72.9 | 7,910 | 209,000 | 21,700 | 45.9 | 14.0 | 222 | 61.0 |
Number exceeding daily limit | 1 | 2 | 2 | 5 | 2 | 0 | 0 | 0 | 0 | N/A |
Percent with detectable contaminant |
31.4 | 51.2 | 33.1 | 57 | 82.6 | 81.8 | 37.5 | 64.6 | 67.7 | 66.1 |
|
||||||||||
Average daily exposure (mean) | 0.0007 | 0.0237 | 0.0035 | 0.0069 | 336 | 0.200 | 0.012 | 0 | 0.024 | 0.0026 |
Standard Deviation | 0.0007 | 0.033 | 0.0098 | 0.01 | 104 | 0.405 | 0.035 | 0 | 0.042 | 0.103 |
Highest daily exposure in single sample | 0.0023 | 0.147 | 0.0241 | 0.0461 | 381 | 1.93 | 0.072 | 0.00 | 0.117 | 0.0694 |
Average annual exposure | 0.256 | 8.66 | 1.28 | 2.52 | 123,000 | 73.2 | 4.38 | 0 | 8.77 | 0.950 |
Number exceeding daily limit | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N/A |
Percent with detectable contaminant |
91.8 | 89.8 | 89.8 | 93.8 | 100 | 100 | 91.8 | 0 | 100 | 89.8 |
|
||||||||||
(N) tested | 91 | 91 | 91 | 72 | 91 | 91 | 49 | 44 | 44 | 44 |
Average daily exposure (mean) | 0.0146 | 0.362 | 0.0918 | 0.782 | 160 | 41.3 | 0.0853 | 0.0094 | 0.090 | 0.0411 |
Standard Deviation | 0.0781 | 1.01 | 0.334 | 3.16 | 337 | 123 | 0.340 | 0.0122 | 0.165 | 0.112 |
Highest daily exposure in single sample | 0.714 | 6.54 | 1.86 | 23.9 | 2,000 | 894 | 2.32 | 0.039 | 0.40 | 0.683 |
Average annual exposure | 5.33 | 132 | 33.5 | 286 | 58,600 | 15,100 | 31.2 | 3.43 | 32.9 | 15.0 |
Number exceeding daily limit | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Percent with detectable contaminant |
25.3 | 39.6 | 25.3 | 51.4 | 71 | 69.2 | 32.6 | 61.4 | 54.5 | 61.4 |
Category of NHP indicates classification of product in store or company where purchased. This does not necessarily indicate where source materials for the NHPs are initially manufactured or derived.
Limits from U.S. California Proposition 65,
The limit of detection will vary between analytical laboratories and may thus influence the percent with detectable contaminants when levels are at low concentrations.
Element in mcg | Mercury | Lead | Cadmium | Arsenic | Aluminum | Barium | Antimony | Thallium | Tin | Cesium |
Allowable limit/day (micrograms) |
2 | 15 | 4.1 | 10 | 7,000 | 1,400 | 2.8 | 70 | 200 | NE |
Average daily exposure (mean) | 5.37 | 4.84 | 0.160 | 254 | 3,760 | 92.9 | 0.241 | 0.102 | 1.07 | 0.681 |
Standard Deviation | 14.7 | 4.79 | 0.231 | 713,000 | 4,580 | 139 | 0.423 | 0.090 | 1.20 | 0.860 |
Highest daily exposure in single sample | 41.8 | 13.0 | 0.549 | 2,020 | 13,000 | 422 | 1.93 | 0.812 | 8.53 | 5.45 |
Average annual exposure | 1,960 | 1,770 | 58 | 92,900 | 1,370,000 | 33,900 | 88 | 37 | 389 | 249 |
Number exceeding daily limit | 1 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | N/A |
Percent with detectable contaminant |
87.5 | 100 | 62.5 | 87.5 | 87.5 | 87.5 | 50 | 87.5 | 100 | 87.5 |
Average daily exposure (mean) | 0.053 | 4.05 | 0.0972 | 0.394 | 938 | 68.3 | 0.196 | 0.0565 | 2.45 | 0.156 |
Standard Deviation | 0.111 | 6.93 | 0.114 | 0.394 | 1,420 | 93.2 | 0.546 | 0.0898 | 4.39 | 0.156 |
Highest daily exposure in single sample | 0.0332 | 22.3 | 0.3 | 1.19 | 4,290 | 279 | 1.65 | 0.269 | 13.2 | 0.0858 |
Average annual exposure | 19 | 148 | 35.5 | 144 | 342,000 | 25,000 | 71.5 | 20.6 | 896 | 57 |
Number exceeding daily limit | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | N/A |
Percent with detectable contaminant |
44.4 | 100 | 55.5 | 66.7 | 100 | 100 | 88.9 | 55.5 | 100 | 66.7 |
|
||||||||||
(N) tested | 9 | 9 | 9 | 9 | 9 | 9 | 5 | 4 | 4 | 4 |
Average daily exposure (mean) | 0.029 | 7.96 | 1.67 | 7.81 | 1,420 | 228 | 0.298 | 0.194 | 1.25 | 0.554 |
Standard Deviation | 0.0497 | 16.4 | 2.59 | 13.6 | 1,460 | 220 | 0.282 | 0.196 | 2.270 | 0.500 |
Highest daily exposure in single sample | 0.0384 | 51.37 | 0.272 | 42.4 | 1,460 | 615 | 0.66 | 0.0224 | 4.65 | 0.951 |
Average annual exposure | 10.6 | 2,910 | 611 | 2,850 | 518,000 | 83,300 | 109 | 70.9 | 455 | 202 |
Number exceeding daily limit | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | N/A |
Percent with detectable contaminant |
55.5 | 100 | 88.9 | 88.9 | 100 | 100 | 77.8 | 100 | 100 | 100 |
Category of NHP indicates classification of product in store or company where purchased. This does not necessarily indicate where source materials for the NHPs are initially manufactured or derived.
Average daily exposure represents the mean level after all supplements for each category are incorporated.
Limits from U.S. California Proposition 65,
The limit of detection will vary between analytical laboratories and may thus influence the percent with detectable contaminants when levels are at low concentrations.
Element in mcg | Mercury | Lead | Cadmium | Arsenic | Aluminum |
Prenatal Allowable limit/day (micrograms) | O.6 for methyl Hg | No level established as acceptable | NE | NE | NE |
Regular Dosing: 1 per day | |||||
|
|||||
A. one single sample | 0.002 | 0.348 | negligible | 0.444 | 444 |
B. Mean –4 samples | 0.06 | 0.44 | 0.0004 | 1.65 | 444 |
B. SD in lot B | 0.0025 | 0.018 | 0 | 0.022 | 18.3 |
C. Mean –4 samples | 0.031 | 0.37 | 0.003 | 0.76 | 227 |
C. SD in lot C | 0.0005 | 0.0038 | 0 | 0.016 | 18.5 |
D. Mean –4 samples | 0.023 | 0.462 | 0.004 | 2.16 | 485 |
D. SD in lot D | 0.023 | 0.027 | 0 | 0.067 | 48.4 |
E. Mean –4 samples | 0.077 | 0.399 | 0.004 | 1.38 | 456 |
E. SD in lot E | 0.0033 | 0.036 | 0 | 0.06 | 29.4 |
Highest level in 17 samples | 0.08 | 0.492 | negligible | 2.23 | 552 |
17 sample average (mean) | 0.038 | 0.414 | negligible | 1.43 | 380 |
SD of 17 samples | 0.03 | 0.045 | negligible | 0.56 | 144 |
Mercury | Lead | ||||
Product | Daily dose | Yearly exposure | Product | Daily dose | Yearly exposure |
Chinese Herbal | 41.9 | 15,300 | Marine | 51.4 | 18,800 |
Chinese Herbal | 0.507 | 185 | Ayurvedic | 22.3 | 8,150 |
Chinese Herbal | 0.397 | 145 | Chinese Herbal | 12.8 | 4,670 |
Ayurvedic | 0.332 | 121 | Chinese Herbal | 9.75 | 3,560 |
Marine | 0.15 | 54.8 | N American | 6.54 | 2,390 |
N American | 0.118 | 42.9 | Chinese Herbal | 6.37 | 2,330 |
Ayurvedic | 0.112 | 41.1 | Marine | 6.11 | 2,230 |
N American | 0.108 | 39.6 | N American | 5.05 | 1,850 |
Chinese Herbal | 0.103 | 37.8 | Chinese Herbal | 4.33 | 1,580 |
Prenatal | 0.080 | 29.3 | N American | 3.73 | 1,360 |
Chinese Herbal | 0.074 | 27.1 | N American | 3.32 | 1,210 |
Marine | 0.052 | 19.2 | Chinese Herbal | 3.18 | 1,160 |
|
|
||||
|
|
|
|
|
|
Marine | 6.81 | 2,490 | Chinese Herbal | 2020 | 738,000 |
N American | 4.69 | 1,710 | Marine | 42.52 | 15500 |
N American | 2.01 | 734 | Marine | 23.91 | 8,730 |
N American | 1.86 | 679 | Marine | 12.4 | 4,530 |
N American | 1.02 | 374 | N American | 11.16 | 4,080 |
N American | 1.01 | 368 | Chinese Herbal | 6.11 | 2,230 |
N American | 0.95 | 347 | N American | 5.85 | 2,140 |
Marine | 0.615 | 225 | N American | 5.46 | 2,000 |
Chinese Herbal | 0.549 | 200 | Chinese Herbal | 3.91 | 1,430 |
Marine | 0.539 | 197 | N American | 3.62 | 1,320 |
Marine | 0.514 | 188 | Marine | 3.15 | 1,150 |
Chinese Herbal | 0.505 | 184 | Chinese Herbal | 2.9 | 1,040 |
|
|||||
|
|
|
|||
Chinese Herbal | 13.0 | 4,740 | |||
Chinese Herbal | 7.18 | 2,620 | |||
Chinese Herbal | 5.62 | 2,050 | |||
Ayurvedic | 4.29 | 1,570 | |||
Marine | 3.75 | 1,370 | |||
Marine | 3.69 | 1,350 | |||
Chinese Herbal | 2.26 | 827 | |||
N American | 2.07 | 756 | |||
N American | 1.99 | 728 | |||
Ayurvedic | 1.97 | 720 | |||
Chinese Herbal | 1.77 | 645 | |||
Marine | 1.50 | 548 |
Category of NHP indicates classification of product in store or company where purchased. This does not necessarily indicate where source materials for the NHPs are initially manufactured or derived.
Study/Year/N | Supplements tested/source | Test Method | Samples containing toxic element (%) | Median concentration (mcg/g) with range | Comments | ||||
Hg |
Cd |
Pb |
As |
Cu |
|||||
Saper et al |
Ayurvedic NHPs: In USA grocery stores | XR fluorescence spectroscopy | 8.57 | 18.6 | 8.57 | Mercury: 225 (28–104,000);Lead: 40 (5–37,000);Arsenic: 430 (37–8130) | 20% of samples contained toxic elements | ||
Saper et al |
Ayurvedic NHPs: USA and Indian manufactured | XR fluorescence spectroscopy | 4.1 | 19.2 | 27 | Mercury: 103.8 (24.5–28200);Lead: 7.5 (2.5–25950);Arsenic: 27.0 (10.5–27.5) | 20.7% of samples contained toxic elements; USA manufactured: 21.7% had toxic elements; Indian manufactured: 19.5% had toxic elements | ||
Koh and Woo |
Chinese Proprietary Medicine | Atomic absorption spectroscopy, inductively couple plasma mass spectrometry | 1.35 | 0.38 | 0.34 | 0.5 | N/A (not available) | Only describes % of samples above the legal allowable limits in ppm or mcg/g: 2.02% of all samples.; Allowable limits defined as:; Mercury 0.5; Lead 20; Arsenic 5; Copper 150 | |
Martena et al |
Ayurvedic and Traditional Chinese Medicine | Inductively Coupled Plasma Mass Spectrometry | 45 | 42 | 36 | Mercury: 50 (0.2–171,000);Lead: 13 (0.5–60,000);Arsenic: 7.6 (0.2–89,800) | 64% of preparations contained mercury, lead or arsenic; 20% were deemed likely to exceed safety limits | ||
Pakade et al |
Ayurvedic Plant source Himalayan | Atomic absorption Spectrophotometry | 0.0 | 35.71 | 28.57 | 35.71 | Mercury: all below detection limit of 0.02;Lead: (2.5–6);Arsenic: (0.11–.48) | Small study, no mean concentration given | |
Harris et al |
Chinese Herbal Medicines | Inductively Coupled Plasma Mass Spectrometry | 42.8 | 95.8 | 66.2 | Mercury: 0.02 (0.1–0.28);Lead: 0.44 (0.04–8.15);Arsenic: 0.2 (0.08–20) | 5% of samples had levels that were of concern.; At least one toxic element detectable in 100% of samples; 34% had detectable levels of all metals; Wild collected plants had higher contamination than cultivated plants | ||
Radhika Singh |
Ayurvedic NHPs | Double beam atomic absorption spectrophotometry | 100 | 100 | 100 | 100 | N/A (not available) | All samples had levels of lead that were 8–80 times the permissible levels; All samples had higher than permissible levels of cadmium; Copper levels were 50–100 times the permissible limit in the samples tested; Arsenic was within permissible levels; Mercury was below detection limit in all samples. |
Hg = Mercury, Cd = Cadmium, Pb = Lead, As = Arsenic, Cu = Copper.
As in Ayurveda, however, heavy metals and metalloids may be intentional components of TCMs. Mercurial compounds by the name of cinnabar (
Various accounts related to TCM contaminated supplement consumption are reported in the literature including arsenic poisoning in a 13 year old girl after ingestion of such supplementation, resulting in pulmonary edema, pericarditis, and eventually renal and liver failure as well as cerebral edema.
NHPs pass through multiple stages before landing on store shelves, all of which involve possible routes for toxicant contamination. Raw materials for NHPs often come from international sources, including nations with less stringent controls over water, air and soil pollution
Transport of products creates possible routes for toxicant exposure. Open-bed trucks, for example, may permit transfer of exhaust pollutants into NHP ingredients.
Raw materials and bulk ingredients for NHPs may originate from sources located around the world including Asia, Europe, and the Americas. Raw materials are advertised on the internet or displayed at conventions and trade shows in major jurisdictions where they are evaluated and purchased by manufacturing companies. A small number of raw material suppliers feed the many manufacturing establishments. These companies then assemble and package a proprietary formulation of specific products, which are shipped to distributors and retail suppliers for sale. The location of assembly and packaging varies depending on the company.
No testing for safety or contamination is generally required for the sale and distribution of NHPs in many jurisdictions throughout the world. Testing may take place internally by companies wishing to verify identity, strength, composition, quality, and purity; regulatory requirements for such testing, however, are usually nonexistent. In addition, lack of standardization between origin and processing of raw materials results in variation between NHP batches, complicating analysis of efficacy or safety between batches. The sourcing of raw materials for pharmaceuticals may also take place in nations where labor costs are minimal and quality-control less stringent.
In response to pressure from consumers and health professionals, regulatory measures have been established in a few countries, including Canada’s Natural Health Products Regulations (NHPR), established in 2004 by the Natural Health Product Directorate (NHPD). With this initiative, all NHPs require approval by Health Canada for safety, efficacy and quality, and a product license is required for sale within Canada. Receiving such approval can be a very expensive and arduous process for manufacturers. It is unclear what measures are taken by regulators in this country to continually assure the safety, efficacy, purity and quality of each batch of product. In Canada, exemption has been provided to products currently on the market in order to ensure NHP availability while products are being assessed and regulation processes are being put in place.
In America, ‘Guidelines for Good Manufacturing Practices’ (GMP) have been established to promote a system of processes, procedures, and documentation to ensure that NHPs have the composition, quality, and purity they purport to possess. New regulations from the Department of Health and Human Services have been proposed to enable the American Food and Drug Administration to evaluate whether a NHP is reasonably expected to be safe and accurately represented through all phases of preparation for consumer use including manufacturing, packaging and labeling.
This study was designed to i) determine if toxic element contamination of NHPs and pharmaceuticals is a routine or rare event, and ii) bring attention to the issue of contamination in NHPs and drugs in order to create credible regulatory processes to ensure public safety.
Testing for toxic elements was carried out on a range of pharmaceuticals and over-the-counter NHPs. To the authors’ knowledge, some preliminary work has been done, but no toxic element contamination studies to date have focused on a broad spectrum of NHP preparations available in Canada. The scientific literature was reviewed to explore relevant information regarding NHP contamination. This was done by assessing available scientific literature from Medline, reviewing books and conference proceedings, consulting several toxicologists, and studying various government publications. Searching techniques included key word searches with terms related to NHPs and toxic element contamination.
In this study, undertaken in 2010–2011, 121 commonly used NHPs (as recommended by retailers) were gathered from 8 health-food stores, industry samples, and 3 herbal dispensaries in Ontario and Alberta, Canada. 49 commonly used pharmaceutical medications were also gathered from physician samples and pharmacies in Edmonton, Alberta. In addition, 5 separate batches of one prenatal supplement manufactured in North America and purchased from 5 independent pharmacies in Alberta (with one sample from the first batch, and 4 samples within each of the remaining 4 batches) were tested. This was done to compare toxicant levels between different batches of the same brand, and within samples of the same batch. An effort was made to include NHPs manufactured in differing areas of the world. The country of manufacture may be listed on NHPs, but labels do not provide the source of raw materials used to manufacture final products. Because of this limitation, we were unable to identify products according to the source countries of their components.
The NHPs (excluding the prenatal supplements) were sent for toxic element testing in three separate groups – each group was analyzed at one of three accredited and specialized toxicology laboratories. (ALS Laboratories, CanAlt Laboratories, or Maxxam Analytics). The pharmaceuticals and the prenatal supplements were all tested as one group at ALS laboratories. The full range of element testing was done at ALS laboratories (only toxic element testing was performed at the other labs) but only toxic elements are reported in this study. The results for each group were combined for purposes of analysis. Daily exposure levels were determined for the maximum recommended daily dose for each NHP or drug. When dosing information was based upon volume, the laboratory-determined specific weight of each NHP or drug was factored in, along with the concentration determined by analysis. All laboratories used inductively coupled plasma – mass spectrometry for detection, and the analytical methodology for testing at ALS laboratories (where the majority of products were tested) follows as an example.
Fluid samples were diluted 10-fold with 1.4 M HNO3 (SP grade). For solids, 0.1–0.7 g of sample (depending upon available sample size) were subjected to closed-vessel microwave-assisted digestion (MARS-5 oven, 600W. 1 h holding time) using 5 mL concentrated HNO3 (SP grade), 0.5 mL H2O2 (PA grade) and 0.02 ml HF (SP grade). After digestion, solutions were diluted with 1.4 M HNO3 (SP grade) providing a final dilution factor of approximately 500. A set of digestion blanks and CRMs were prepared together with each digestion batch. (All solutions were also spiked with 2 µg/L (internal standard) and analyzed by ICP-SFMS (ELEMENT2, Thermoscientific) using a combination of internal standardization and external calibration. Testing for organic pollutants including biotoxins, various synthetic compounds, and various chemical byproducts was not done.
Toxic element contamination results from the laboratories were provided for each NHP and pharmaceutical in ng/g (equivalent to parts per billion), mg/kg (parts per million) or mcg/g (parts per million). While it has been common in the literature to report NHP contamination concentrations, the actual exposure level to individuals was deemed to be of more importance from a clinical and public health perspective. In order to determine how intake levels compare to established limits, calculation of daily intake rather than simple concentration is required. Accordingly, each laboratory result was multiplied by the weight in grams for each NHP and drug tested to ascertain the total amount of contaminant contained per product. This figure was then multiplied by the maximum daily dose recommended in the product instructions for each specific NHP and pharmaceutical in order to determine a maximum daily intake of each product.
While some individuals may consume lower or higher amounts than is recommended for any given NHP or drug, it was determined through discussion with colleagues, patients, pharmacists, NHP distributors and retailers that most people tend to i) consume the maximal recommended NHP dose in order to achieve what is perceived to be the maximum benefit; and ii) take a pharmaceutical dose within the recommended range provided for the product.
Whether an element is toxic or not is determined by many factors including route of exposure, dose, site of accumulation, nutritional status, detoxification biochemistry, and the particular form or species in which the element exists within the body. Different species of elements have the potential to display distinct toxicity patterns. For example, hexavalent chromium (chromium-VI) is highly toxic and carcinogenic while trivalent chromium (chromium-III) is an essential metal involved in lipid and carbohydrate metabolism.
Similarly, inorganic and organic arsenic are both naturally occurring compounds that display different toxicities. While certain inorganic arsenic species are classified as human carcinogens, some forms of organic arsenic, such as arsenobetaine (which accumulates in some aquatic organisms such as shrimp) are relatively nontoxic. Specific forms of some elements also have the potential to be converted within the body to different forms, which changes their properties and potential toxicity. Nonetheless, in this study, only the total amount of each element was determined – no speciation was undertaken to determine the oxidation state or associated organic species.
Our results indicate varying levels of toxic element contamination in the NHPs and pharmaceuticals tested. Proposed limits of acceptable contamination as determined by various agencies can be found in
Most of the existing literature on toxic element NHP contamination has reported on contaminant concentrations, with no indication of the dose that an individual would receive at the prescribed rate of intake. In this study, however, we endeavored to estimate daily exposure levels of toxic elements for many NHPs and drugs in an effort to determine if some existing NHPs may pose a health hazard to the consuming public. The results of this study demonstrate that toxic element contamination of NHPs and pharmaceuticals is common, but that none of the drugs and only a few NHPs exceeded established daily limits for contamination when taken on their own. Many people, however, consume multiple different NHPs and/or drugs each day; the total level of toxicant exposure will thus be additive.
The results of our testing on one prenatal supplement brand suggest that ascertaining the safety or purity of one NHP batch does not ensure safety of other same-brand batches. While this finding has significance to all NHPs, gestational exposures merit particular attention as ongoing research continues to link assorted prenatal toxicant exposures and pediatric toxicant levels (including toxic elements) with potentially significant health outcomes.
The findings of this study, however, likely underestimate the overall extent of supplement and pharmaceutical contamination as there are many potential synthetic (e.g. parabens, phthalates, pesticides), biological (e.g. mycotoxins), or petrochemical contaminants not assessed in this research. In the scientific literature, there is a paucity of research reported which explores the spectrum of potential contaminants in NHPs and drugs.
Endeavoring to link specific toxic element exposure levels found in this study directly with health problems is challenging. Causal links between toxic element exposure and illness have, however, been established as extensive evidence from observational studies of exposed populations and individuals, from epidemiological studies of the general population, and from animal studies investigating mechanisms of toxicity has confirmed causality.
It is also of note that the relevance of specific contamination levels found in this study is uncertain. Assigned tolerance limits for toxic element exposures (
Widespread and apparently irreconcilable controversy exists regarding the regulation of NHPs. Many within the medical community have expressed concern about the safety and efficacy of NHPs,
Some propose that NHPs be available only by physician prescription. Others consider this strategy to be ill-advised as most medical doctors have limited toxicological or nutritional training
A potential solution may involve the NHP industry developing and implementing stringent self-regulatory procedures to ensure safe and reliable NHPs – procedures that are amenable to government oversight by elected officials. ‘Country of Origin’ labeling – including the source country of each component of the product (e.g. ascorbic acid – USA; Vitamin D – New Zealand; folic acid – Japan; etc.) as well as the country where the final product was manufactured, may facilitate full transparency and provide consumers with informed choice. Routine toxicant testing for a wide range of potential contaminants is also required, with full disclosure of toxicant content. The lack of consistency of purity between same-brand batches in this study indicates that ongoing assessment for each batch of every raw material component as well as each batch of manufactured product is needed. This supervised self-regulatory approach is likely more acceptable to industry, and more cost-effective and efficient for governments. Such a process would ensure safety and public confidence.
NHP use has become commonplace in the 21st century with at least half of the North American and European populations ingesting supplements daily.
With increasing recognition of widespread iatrogenic illness and potential adverse sequelae resulting from assorted therapies, concerted action is required to secure patient safety and public health in all healthcare domains.
The authors would like to express gratitude to Dr. Shelagh K. Genuis, Dr. Meg Sears, Dr. Jon Martin, Dr. Emerson D. Genuis, Ruby Williams, Daniel Eriksson, Patricia Naylor and a peer reviewer who provided invaluable assistance with this research project and/or the preparation of this paper.