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Int. J. Mol. Sci. 2013, 14(2), 3078-3093; doi:10.3390/ijms14023078
Abstract: A total of 60 products of traditional herbal medicine (THM) in various dosage forms of herbal preparation were analyzed to determine selected trace elements (i.e., Zn, Mn, Cu, Cd, and Se) using ICP-MS. Thirty types of both Chinese and Malay THMs were chosen to represent each population. The closed vessel acid microwave digestion method, using CEM MARS 5, was employed for the extraction of the selected trace elements. The digestion method applied was validated by using certified reference material from the Trace Element in Spinach Leaves (SRM1570a). The recoveries of all elements were found to be in the range of 85.3%–98.9%. The results indicated that Zn, Mn, Cu, Cd and Se have their own trends of concentrations in all samples studied. The daily intake concentrations of the elements were in the following order: Mn > Zn > Cu > Se > Cd. Concentrations of all five elements were found to be dominant in Chinese THMs. The essentiality of the selected trace elements was also assessed, based on the recommended daily allowance (RDA), adequate intake (AI) and the United States Pharmacopeia (USP) for trace elements as reference. The concentrations of all elements studied were below the RDA, AI and USP values, which fall within the essential concentration range, except for cadmium.
The term “trace element” is applied to a group that is extremely small in quantity and plays a vital part in the metabolism of plants and animals . In the human body, the trace element is defined as that which makes up 0.01% of the body’s mass . There are a maximum of 25 trace elements distributed in multiple sites of a skeleton and in the iliac crest of 69 ancient human skeletons . Each element has made a different contribution in order to make the human body function. Essential trace elements are needed for optimal function of the mammalian organism, for growth, healing and the activity of many metabolic processes .
Trace elements have both a curative and a preventative role in combating diseases. Trace elements, for example the metals selenium, zinc and copper, are essential to maintain the metabolism of the human body. However, non-essential metals such as cadmium and chromium lead to adverse effects, even though they are only present in trace amounts. Elements, in one form or another play an important role in the field of medicine, including the trace elements present in traditional herbal medicines (THM). The consumption of THM contributes to the intake of both essential and non-essential trace elements by the human body .
The World Health Organization (WHO) has estimated that around 65%–80% of the world population, especially in developing countries, depends essentially on plants for their primary healthcare . THM use has been steadily rising with almost 70%–95% of citizens in major developing countries using THM for their primary health care needs . Use of THM is quite convincing, since it is affordable for all people regardless of their income . The WHO has defined herbal medicine as “herbs, herbal materials, herbal preparations and finished herbal products that contain active ingredients obtained from parts of plants, or plant materials, or combinations thereof” used to treat ailments [8–10] throughout the world .
THM has gained people’s satisfaction with its therapeutic outcomes [12,13] and there are perceptions that herbal medicines are inherently safe . Furthermore, the dissatisfaction of patients towards orthodox medicine in terms of effectiveness and safety has also induced the use of THM . According to Basgel and Erdemoglu, the therapeutic agents in herbal medicines are standardized herbal preparations consisting of complex mixtures of one or more plants, which are used in most countries for the management of various diseases .
Despite the claimed and wide belief in THM as being beneficial, there have been reports of acute and chronic intoxications resulting from its use [17–23]. Abbot et al. reported that not all products that are related to THM are free from adverse effects . According to Mazzanti et al., the adverse effects can be divided into two; intrinsic and extrinsic . The intrinsic adverse effects are due to predictable toxicity, overdose, pharmacological interactions, idiosyncratic reactions (i.e., allergy and anaphylaxis) and delayed effect (i.e., carcinogenicity and teratogenicity). The quality of THM is affected by substitution, adulteration, contamination, misidentification, lack of standardization and inappropriate labeling, which belong to the extrinsic adverse effect group.
While many investigations of the quality of THM have been reported in the current literature , there is less emphasis on the trace element content of THM products . The main reason for trace element monitoring was due to an increase in contamination of the general environment [28,29]. As a result of contamination, serious health hazards have occurred such as renal failure, symptoms of chronic toxicity and liver damage [30,31].
However, there have also been health hazard cases reported on THM i.e., Ayurvedic herbal medicine products (AHMP) that use trace elements as their constituents . Some consumers took AHMP containing lead (Pb) and were reported to demonstrate epilepticus , fatal infant encephalopathy , congenital paralysis and sensorineural deafness , and developmental delay . Moreover, at least 55 cases of trace element intoxication associated with AHMP in adults and children have been reported in the United States and worldwide since 1978 [33–45].
As reported by Shaw et al., there are 785 cases that have been evaluated with side effects related to THM. The cases reported were referred to as liver problems resulting from the use of Chinese THM for skin disorders and heavy metal poisoning caused by consuming Indian subcontinent remedies . Garvey et al. also reported that the level of arsenic (As), lead (Pb) and mercury (Hg) in Asian remedies ranges from toxic (49% of the total number of samples analyzed) to those exceeding the public health guidelines for illness prevention (74%) even though they followed the instructions given on the packages .
However, with THM the essential parts still have to be taken into consideration. The experimental work done by Ajasa et al. does support the fact that THMs also contains nutrients and are rich in iron (Fe), phosphorus (P), magnesium (Mg), calcium (Ca), sodium (Na) and potassium (K) . Other reports revealed that the trace elements present in THM display beneficial medicinal and therapeutic properties [46,47]. Obi et al. reported that heavy metal poisoning has decreased due to an improvement in industrial hygiene and environmental controls . The trace element content in THMs should be monitored in order to prevent the consumer from suffering undesired effects. It is crucial to make sure that the trace element content is below the required limit for illness prevention. The dietary intakes for the bio-important trace elements have to be regulated to avoid poisoning and toxicity in the body [49–51].
The aim of this study was to determine the concentration of Zn, Mn, Cu, Cd, and Se in both Chinese and Malay THM. The work is a comparison of the trace element content between Chinese and Malay THM samples. The daily intake of all elements studied in both THM samples was compared with the recommended daily allowance (RDA), adequate intake (AI) and U.S. Pharmacopoeia (USP) for trace elements. Based on the daily intake of the selected trace element, their essentiality is classified as essential, non essential or non effective concentrations.
2. Results and Discussion
2.1. Method Validation
A microwave digestion program was found to be a capable method to be used for sample preparation of traditional herbal medicines thereby, taking into account information obtained when comparing recovery, the total time taken for analysis, operational difficulties, the amount of acid used and the safety requirements during the process. Table 1 and Table 2 show the results obtained for Zn, Mn, Cu, Cd, and Se in the analysis of SRM 1570A. Seven replicates of measurement (n = 7) were performed using microwave assisted digestion. During the ICP-MS analysis, a blank and six standard solutions of all elements were prepared in the range of 0–250 μg L−1 for all calibration curves. All plotted calibration curves showed that the linearity was almost perfect with a correlation coefficient of r2 = 0.9999. The accuracy study showed that the recoveries from the microwave assisted digestion method ranged from 85.3% to 98.9% as shown in Table 1. The precision of the method was achieved with the coefficient of variation (CV) for intraday and interday precision of <5% as shown in Table 2.
A total of 10 replicates (n = 10) of blank samples were analyzed and the mean values and their standard deviations were determined. Table 3 shows that the limit of detection (LOD) and limit of quantification (LOQ) were in the range of 0.03–0.38 ng L−1 and 0.10–1.15 ng L−1; respectively. The analytical method adopted was very sensitive towards all analytes studied.
2.2. Daily Intake Estimation
The daily intakes of Zn, Mn, Cu, Cd, and Se of each THM were obtained by multiplying the daily intakes of each product by the concentration of each element determined by ICP-MS. Then, the trace element intake was compared with the tolerable daily intakes for each element obtained from RDA, AI and USP.
2.3. Essentiality of Trace Elements Based on Their Estimated Daily Intake
The present study was apparently the first comparative study of Zn, Mn, Cu, Cd, and Se contents in both Chinese and Malay THM retailed in Malaysia. In this work, the essentiality of Zn, Mn, Cu, Cd, and Se content in Chinese and Malay THM products is discussed and the estimated daily intake provided by manufacturers is also highlighted.
The trend for the distribution of Zn is shown in Figure 1a,b. The highest concentration of Zn was found in both Chinese and Malay THM samples. The results indicated that all Chinese and Malay THM samples contained Zn. The concentration of Zn was in the range of 0.61–30.90 μg g−1 and 0.29–74.03 μg g−1 in Chinese and Malay THM, respectively. Zn content was significantly higher in Malay THMs than in that of Chinese THMs. Based on the daily dosage of Zn, the percentage increment in concentration of Zn is higher in Chinese THMs by 3–9 fold while Malay THMs only show 1–3 fold. Nevertheless, the results indicate that the daily dose of Zn in Chinese and Malay THM was relatively lower compared to the recommended daily allowance (RDA) (2–12 mg per day). Previous studies proved that Zn is essential to the human body at the optimum level for reducing morbidity resulting from respiratory and diarrheal illnesses [52–55]. Furthermore, Zn deficiency can lead to growth retardation, immune dysfunctions and cognitive impairment .
The distribution trend of Mn was similar to that of Zn. The results in Figure 2a,b showed that the concentration of Mn was slightly higher in Malay THM (0.31–542.10 μg g−1) than that of Chinese THM (10.21–241.88 μg g−1). When the daily intake of THM was taken into account, the concentration of Mn in Chinese THM was increased by up to 7.5 times but all Malay THMs only showed the increment of Mn in the range of 0.4–3.0 times, except for sample 22 (S22) with an increment of five times. Since there is no RDA value set for Mn, the adequate intake (AI) value was used as the reference. The calculated intake of both THMs revealed that the Mn content is an essential element although its concentration is within the value stated by adequate intake (AI) (0.003 to 2.6 mg per day). Aschner et al., 2005, state that Mn is required in normal amino acid, lipid, protein and carbohydrate metabolism at essential concentrations. Nevertheless, high consumption of Mn can cause manganism; one of the neurodegenerative disorders that is due to the susceptibility of the brain towards excess of Mn .
Figure 3a,b reveal that both Malay and Chinese THMs contain Cu in the range of 0.40–28.95 μg g−1 and 0.24–8.49 μg g−1; respectively. The pattern of distribution was quite similar to that of Mn and Zn. The Cu content was higher in Malay than Chinese THM whereas the daily intake of copper was higher in Chinese THM. The daily intake exhibits a trend wherein Chinese THM shows a higher Cu content. As far as both kinds of THM are concerned, there are significant increments of Cu. The concentration of Cu in Chinese THM increased from 0.24–8.49 μg g−1 to 0.80–33.95 μg day−1 while in Malay THM from 0.40–28.95 μg g−1 to 0.60–44.96 μg day−1. Cu contents were comparatively lower than the RDA (0.2 to 1.3 mg per day) value. However, the concentration of Cu present in both THMs was considerably essential. Previous studies showed that Cu plays an important role in the expression of certain human genes at the optimum concentration . However, high consumption of Cu l causes chronic damage to the liver .
As can be seen in Figure 4a,b, only 80% of Chinese THM and 60% of Malay THM contain Se. The concentration of Se in Chinese THM is in the range of 0.03–2.03 μg g−1 which exhibits a higher concentration of Se than that of Malay THM samples (i.e., 0.04–0.74 μg g−1). Only four out of thirty samples of Chinese THM contain Se greater than 2 μg L−1 (S14, S15, S16 and S17). THM contains different ingredients for different purposes. Surprisingly, none of Malay THM studied contains Se greater than 2 μg g−1. The calculated daily Se intake shows that the Se content of some of the Chinese THM samples was approaching the essential value recommended by RDA (20 to 55 μg per day) that is 0.23 to 8.85 μg day−1. The concentration of Se found in Chinese THM was found as significantly essential to the human body with the assumption that the consumer takes more than one type of THM per day. The prevalence study reported that the optimum concentration of Se in the blood would prevent oxidative damage, hence preventing people from atherosclerosis . Recently, there are several studies that show that inorganic Se can enhance insulin activity by mediating insulin-like actions [61,62].
Cd is considered a toxic element. A previous finding showed that Cd could be toxic to placenta  due to its prohibition on cell proliferations [64–66]. By referring to Figure 5a,b, the concentration of Cd ranges between 0.07 and 0.39 μg g−1 and between 0.01 and 0.30 μg g−1 in Chinese THM and Malay THM; respectively. Both THMs were considered to have a low Cd content compared to the limit stated by the U.S. Pharmacopoeia (3 mg g−1). Only 63% of Chinese THM and 43% of Malay THM studied contains Cd. When the daily intake of both THMs was considered, the concentration of Cd in Chinese and Malay THM increased up to 0.03–1.79 μg day−1 and 0.01–0.44 μg day−1, respectively. Therefore, we can conclude that the concentrations of Cd in the daily intake of Chinese THM samples are still in the acceptance range and not approaching the maximum limit of cadmium stated by the U.S. Pharmacopoeia (USP). However, continuous consumption of Chinese THM will cause a huge accumulation of Cd in the body. Cd can cause intracellular damage such as protein denaturation, lipid peroxidation, generation of reactive oxygen species and DNA strand breaks [67–69].
The different formulation sizes were found to be one of the contributors towards the increment of concentration of trace elements in the THM samples. As the surface area of the formulation increases, the concentrations of trace elements present in both THMs also rises. The other likely contributor is the quantity of the formulation consumed daily. Some of the Chinese THM samples were prescribed to be taken in a very high quantity every day. At the same time, the concentrations of all elements studied increased with the increase of the daily formulation intake. The concentrations of all elements studied in Malay THM also showed a steady increment with daily intake. The types of capsules, the source of herbs and the manufacturing process play a significant role as well on the presence of trace elements in both Chinese and Malay THMs.
2.4. Statistical Analysis
Analysis of variance (one-way ANOVA) was used to test hypothesis about differences between element contents. In one-way ANOVA, no statistical difference at 95% confidence interval was observed between manganese, cadmium and selenium concentrations in Chinese and Malay THM populations except for zinc and copper. We noticed significant differences at 95% confidence interval in Mn, Zn, Cu, Se and Cd concentrations within each population.
3. Experimental Section
Thirty samples of Malay and Chinese THMs were randomly purchased from herbal medical stores, kiosks, herbal medical dealers and local supermarkets in Kuala Lumpur, regardless of their uses. The formulations of THMs were found to be in several forms such as pellets, capsules, tablets, powders and “gummy pastes”. All the samples chosen were registered with the Malaysian Health Ministry Malaysia through the National Pharmaceutical Control Bureau.
3.2. Sample Preparations
The THM samples were directly used in analysis without prior treatment to avoid alteration of the concentration of trace elements in the samples. The concentrations of selenium, copper, manganese, zinc and cadmium in both Malay and Chinese THM samples were determined using an Agilent 7500a ICP-MS series (Agilent Technologies). A microwave digestion technique was applied for wet digestion of the THM samples. The National Institute of Standards and Technology (NIST) solid standard reference material (SRM) 1570a (Trace elements in Spinach) containing a concentration of specified trace elements served as positive and negative control to ensure the quality of the measurements.
3.3. Reagents and Materials
All reagents were of analytical reagent grade unless otherwise stated. Nitric acid (65% HNO3, suprapur Merck, Darmstadt, Germany) and hydrogen peroxide (30% H2O2, MOS J. T. Baker, Centre Valley, PA, USA) were used as a mixture in a ratio of 8 to 2 (HNO3:H2O2v/v). Ultrapure water (Milli-Q water purification system, Millipore, Billerica, MA, USA) with resistivity of 18.2 Ω cm−1 was used throughout the experiments including for all dilutions and for rinsing the vessels for microwave digestion. The plastic containers and glassware were cleaned by soaking in dilute HNO3 (1 + 9) and were rinsed with ultrapure water prior to use. All standards, reagent solutions and sample were kept in plastic containers and stored in the refrigerator before the measurements. A multi-element standard solution IV for ICP-MS (Fluka, Switzerland) was used to prepare the series of standard solutions of zinc (Zn), manganese (Mn), copper (Cu), cadmium (Cd), and selenium (Se). The concentration of Zn, Mn, Cu, Cd, and Se were 100, 20, 10, 10, and 100 μg L−1, respectively.
3.4. Preparation of Standard Solution
The multistandard solution was diluted with 5% nitric acid step by step; the concentration of Se and Zn were prepared by the gradient of 0.00, 25.00, 75.00, 125.00, 187.50 and 250.00 μg L−1, the concentration of Cd and Mn were prepared by the gradient of 0.00, 2.50, 7.50, 12.50, 18.75, 25.00 μg L−1, and the concentration of Cu was prepared by the gradient of 0.00, 5.00, 15.00, 25.00, 37.50, 50.00 μg L−1. The working standard solution was freshly prepared daily prior to the analyses.
3.5. Microwave Digestion
About 0.2 g of replicate sample of SRM 1570a was weighed using a Teflon vessel, and then a mixture of 8 mL of concentrated HNO3 and 2 mL of H2O2 was added. The digestion vessel was closed and heated in the CEM MARS microwave oven based on the parameters shown in Table 4. The obtained solutions were allowed to cool at room temperature, and then were filtered by Whatman No. 1 (110 mm pores size) filter paper into a 25 mL polypropylene (PP) volumetric flask. Acidified double distilled deionized water (with 5% v/v HNO3) was prepared and used for all dilutions throughout this work.
An inductively coupled plasma-mass spectrometer (ICP-MS) is a widely used instrument adopted for the fast determination of multi-elements in pharmaceutical samples including traditional herbal medicines. ICP-MS can identify and quantify trace elements with higher sensitivity due to relatively low detection limits. The concentrations of zinc, manganese, copper, cadmium and selenium in 60 traditional herbal medicines studied were determined by an ICP-MS Agilent 7500A series (Agilent Technologies, Palo Alto, CA, USA). The operating parameters and the setup information for all elements and masses are shown in Table 5 and Table 6, respectively.
3.7. Validation Procedure
The analytical method employed for the screening of five selected trace elements in both Chinese and Malay THM was first validated. The study consisted of linearity, precision and accuracy, limit of detection (LOD) and limit of quantification (LOQ). The Standard Reference Material, SRM 1570A, Trace Elements in Spinach from the National Institute of Standards and Technology (NIST) was chosen as the positive and negative control due to the presence of all the elements studied at specific concentrations in the SRM.
The concentrations of five trace elements (Mn, Zn, Cu, Se and Cd) were determined in both Chinese and Malay THM products by ICP-MS. The ranges of elemental concentrations were found to vary widely. Our results indicate that Chinese THM dominated with regard to the content of all elements studied i.e., Mn, Cu, Zn, Se and Cd. The concentrations of Mn, Cu, Zn and Se present in both Chinese and Malay THMs appear to be essential, except for cadmium. Several possibilities were proposed as contributors to the presence of trace elements in both THM samples. The results show that the analytical method used in this work was applicable for the determination of Se, Cu, Mn, Zn and Cd content in the herbal medicines matrix.
The author would like to thank University of Malaya for financial support through the Grant no. PS333/2010A.
Conflict of Interest
The authors declare no conflict of interest.
- Stitch, S.R. Trace elements in human tissue. 1. A semi-quantitative spectrographic survey. Biochem. J 1957, 67, 97–103. [Google Scholar]
- Nason, A.P.; Schroeder, H.A. Trace-Element Analysis in Clinical Chemistry. Clin. Chem 1971, 17, 461–474. [Google Scholar]
- Brätter, P.; Gawlik, D.; Lausch, J.; Rösick, U. On the distribution of trace elements in human skeletons. J. Radioanal. Nucl. Chem 1977, 37, 393–403. [Google Scholar]
- Ajasa, M.A.; Bello, O.M.; Ibrahim, O.M.; Ogunwande, A.I.; Olawore, O.N. Heavy metals and macronutrients status in herbal plants of Nigeria. Food Chem 2004, 85, 67–71. [Google Scholar]
- Akerele, O. Summary of WHO guidelines for the assessment of herbal medicines. HerbalGram 1993, 28, 13–19. [Google Scholar]
- Robinson, M.M.; Zhang, X. The World Medicines Situation 2011—Traditional Medicines: Global Situation, Issues And Challenges, 3th ed; World Health Organization (WHO): Geneva, Switzland, 2011. [Google Scholar]
- Memory, E.-L. Should we be concerned about herbal remedies. J. Ethnopharmacol 2011, 75, 141–164. [Google Scholar]
- Barnes, J. Quality, efficacy and safety of complementary medicines: Fashions, facts and the future. Part 1. Regulation and quality. Br. J. Clin. Pharmacol 2003, 55, 226–233. [Google Scholar]
- Eisenberg, D.M.; Foster, K.R.C.; Norlock, F.E.; Calkins, D.R.; Delbanco, T.L. Unconventional medicine in the United States. N. Engl. J. Med 1993, 328, 246–252. [Google Scholar]
- Gardiner, P.; Graham, R.; Legedza, A.T.; Ahn, A.C.; Eisenberg, D.M.; Phillips, R.S. Factors associated with herbal therapy use by adults in the United States. Altern. Ther. Health Med 2007, 13, 22–29. [Google Scholar]
- World Health Organization (WHO), WHO Traditional Medicine Strategy 2002–2005; WHO: Geneva, Switzerland, 2002.
- Abbot, N.C.; Ernst, E. Patients’ opinions about complimentary medicine. Forsch. Komplementarmed 1997, 4, 164–168. [Google Scholar]
- Huxtable, R.J. The harmful potential of herbal and other plant products. Drug Saf 1990, 5, 126–136. [Google Scholar]
- Titilayo, O.F.; Rasaq, A.; Ismail, E.M. Attitude and use of herbal medicines among pregnant women in Nigeria. BMC Complement. Altern. Med 2009, 9, 53. [Google Scholar]
- Chan, K. Some aspects of toxic contaminants in herbal medicines. Chemosphere 2003, 52, 1361–1371. [Google Scholar]
- Basgel, S.; Erdemoglu, S.B. Determination of mineral and trace elements in some medicinal herbs and their infusions consumed in Turkey. Sci. Total Environ 2006, 359, 82–89. [Google Scholar]
- Chan, T.Y.K. Monitoring the safety of herbal medicine. Drug Saf 1997, 17, 209–215. [Google Scholar]
- Ernst, E. Harmless herb? A review of the recent literature. Am. J. Med 1998, 104, 170–178. [Google Scholar]
- Garvey, J.G.; Gary, H.; Richard, V.L.; Raymond, D.H.C. Heavy metal hazard of Asian traditional remedies. Int. J. Environ. Health Res 2001, 11, 63–71. [Google Scholar]
- Heck, A.M.; DeWitt, B.A.; Lukes, A.L. Potential interactions between alternative therapies and warfarin. Am. J. Health Syst. Pharm 2006, 57, 1221–1227. [Google Scholar]
- Miller, L.G. Herbal medicine: Selected clinical considerations focusing on known or potential drug-herb interaction. Arch. Intern. Med 1998, 158, 2200–2211. [Google Scholar]
- Vaes, L.P.J.; Chyka, P.A. Interaction of warfarin with garlic, ginger, ginkgo, or gingseng: Nature of the evidence. Ann. Pharmacother 2000, 34, 1478–1482. [Google Scholar]
- Whitting, P.W.; Clouston, A.; Kerlin, P. Black cohosh and other herbal remedies associated with acute hepatitis. Med. J. Aust 2002, 177, 678–685. [Google Scholar]
- Abbot, N.C.; White, A.R.; Ernst, E. Complementary medicine. Nature 1996, 381, 361. [Google Scholar]
- Mazzanti, G.; Battineli, L.; Daniele, C.; Costantini, S.; Ciaralli, L.; Evandari, M.G. Purity control of some Chinese crude herbal drugs marketed in Itali. Food Chem. Toxicol 2008, 46, 3043–3047. [Google Scholar]
- Gomez, M.R.; Cerutti, S.; Sombra, L.L.; Silva, M.F.; Martínez, L.D. Determination of heavy metals for the quality control in argentinian herbal medicines by ETAAS and ICP-OES. Food Chem. Toxicol 2007, 45, 1060–1064. [Google Scholar]
- Branter, A.H.; Males, Z. Quality assessment of Paliurus spinachristi extracts. J. Ethnopharmacol 1999, 66, 175. [Google Scholar]
- Gosslim, R.E.; Smith, R.P.; Hodge, H.C.; Braddock, J.E. Clinical Toxicology of Commercial Products, 5th ed; Willians & Wilkins: Baltimore, MD, USA, 1984; p. 437. [Google Scholar]
- Schilcher, H. Possibilities and limitations of phytotherapy. Pharm. Weekbl 1987, 9, 215. [Google Scholar]
- Andrew, A.S.; Warren, A.J.; Barchowsky, A.; Temple, K.A.; Klei, L.; Soucy, N.V.; O’Hara, K.A.; Hamilton, J.W. Genomic and proteomic profiling of responses to toxic metals in human lung cells. Environ. Health Persp 2003, 111, 825–835. [Google Scholar]
- Shaw, D.; Leon, C.; Kolev, S.; Murray, V. Traditional remedies and food supplements. A 5-year toxicological study (1991–1995). Drug Saf 1997, 17, 342–356. [Google Scholar]
- Robert, B.S.; Stefanos, K.; Janet, P.; Michael, J.B.; David, M.E.; Roger, B.D.; Russell, S.P. Heavy metal content of Ayurvedic Herbal Medicine Products. JAMA 2004, 292, 2868–2873. [Google Scholar]
- Centre of Disease Control and Prevention. Lead poisoning: Associated death from Asian Indian folk remedies—Florida. MMWR Wkly. Rep 1984, 33, 643–645.
- Centre of Disease Control and Prevention. Lead poisoning associated with use of Ayurvedic medications—five states, 2000–2003. MMWR Wkly. Rep. 2004, 53, 582–584.
- Tait, P.A.; Amish, V.; James, S.; Fitzgerald, D.J.; Pester, B.A. Severe congenital lead poisoning in a preterm infant due to a herbal remedy. Med. J. Aust 2002, 177, 193–195. [Google Scholar]
- Moore, C.; Adler, R. Herbal vitamins: Lead toxicity and developmental delay. Pediatrics 2000, 177, 193–195. [Google Scholar]
- Aslam, M.; Davis, S.; Healy, M.A. Heavy metals in some Asian medicines and cosmetics. Public Health 1979, 93, 274–284. [Google Scholar]
- Ernst, E. Risk Associated with Complementary Therapies. Meyler’s Side Effects of Drugs; Elsevier: Amsterdam, The Netherlands, 2000. [Google Scholar]
- Ibrahim, A.S.; Latif, A.H. Adult lead poisoning from a herbal medicine. Saudi Med. J 2002, 23, 591–593. [Google Scholar]
- Lecours, S.; Osterman, J.; Lacasse, Y.; Melnychuck, D.; Gellinas, J. Environmental lead poisoning in three Montreal women of Asian Indian origin. Can. Dis. Wkly. Rep 1989, 15, 177–179. [Google Scholar]
- McElvaine, M.D.; Harder, E.M.; Johnson, L.; Baer, R.D.; Satzger, R.D. Lead poisoning from the use of Indian folk medicines. JAMA 1990, 264, 2212–2213. [Google Scholar]
- Prpic-Majic, D.; Pizent, A.; Jurasovic, J.; Pongracic, J.; Restek-Samarzija, N. Lead poisoning associated with the use of Ayurvedic metal-mineral tonics. J. Toxicol. Clin. Toxicol 1996, 34, 417–423. [Google Scholar]
- Spriewald, B.M.; Rascu, A.; Schaller, K.H.; Angerer, J.; Kalden, J.R.; Harrer, T. Lead induced anaemia due to traditional Indian medicine: a case report. Occup. Environ. Med 1999, 56, 282–283. [Google Scholar]
- Traub, S.J.; Hoffman, R.S.; Nelson, L.S. Lead toxicity due to use of an Ayurvedic compound. J. Toxicol. Clin. Toxicol 2002, 40, 322. [Google Scholar]
- Weide, R.; Klings, E.S.; Faber, H.; Kaufmann, F.; Heymanns, J.; Koopler, H. Severe lead poisoning due to Ayurvedic Indian plant medicine. Dtsch. Med. Wochenschr 2003, 128, 2418–2420. [Google Scholar]
- Fahey, J.W.; Zhang, Y.; Talalay, P. Broccoii sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. USA 1997, 94, 10367–10372. [Google Scholar]
- Elless, M.P.; Blaylock, M.J.; Huang, J.W.; Gussman, C.D. Plants as a natural source of concentrated mineral nutritional supplements. Food Chem 2000, 77, 181–188. [Google Scholar]
- Obi, E.; Akunyili, D.N.; Ekpo, B.; Orisakwe, O.E. Heavy metal hazards of Nigerian herbal remedies. Sci. Total Environ 2006, 369, 35–41. [Google Scholar]
- Fosmire, G.J. Zinc Toxicity. Am. J. Clin. Nutr 1990, 51, 225–227. [Google Scholar]
- Nolan, K. Copper Toxicity Syndrome. J. Orthomol. Psychiatry 2003, 12, 270–282. [Google Scholar]
- Young, R.A. Toxicity Profiles: Toxicity Summary for Cadmium, Risk Assessment Information System, RAIS; University of Tennessee: Nashville, TN, USA, 2005. [Google Scholar]
- George, K.S.; Andrea, J.R.; Robert, B. Zinc and human immunodeficiency virus infection. Nutr. Res. 2002, 22, 527–538. [Google Scholar]
- Nita, B.; Rajiv, B.; Sunita, T.; Tor, S.; Kåre, M.; Rune, J.U.; Halvor, S.; Maharaj, K.B. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: Randomised controlled trial in an urban slum. BMJ 2002, 324, 1358. [Google Scholar]
- Bahl, R.N.B.; Hambidge, K.M.; Bhan, M.K. Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting. Am. J. Clin. Nutr 1998, 68, 414s–417s. [Google Scholar]
- Sazawal, S.R.B.; Bhan, M.K.; Jalla, S.; Sinha, A.; Bhandari, N. Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea—a community-based, double-blind, controlled trial. Am. J. Clin. Nutr 1997, 66, 413–418. [Google Scholar]
- Prasad, A.S.; Bao, B.; Beck, F.W.J.; Kucuk, O.; Sarkar, F.H. Antioxidant effect of zinc in humans. Free Radic. Bio. Med 2004, 37, 1182–1190. [Google Scholar]
- Dobson, A.W.; Erikson, K.M.; Aschner, M. Manganese Neurotoxicity. Ann. N. Y. Acad. Sci 2004, 1012, 115–128. [Google Scholar]
- Uauy, R.; Olivares, M.; Gonzalez, M. Essentiality of copper in humans. Am. J. Clin. Nutr 1998, 67, 952S–959S. [Google Scholar]
- De Romaña, D.L.; Olivares, M.; Uauy, R.; Araya, M. Risks and benefits of copper in light of new insights of copper homeostasis. J. Trace Elem. Med. Biol 2011, 25, 3–13. [Google Scholar]
- Blankenberg, S.; Rupprecht, H.J.; Bickel, C.; Torzewski, M.; Hafner, G.; Tiret, L.; Smieja, M.; Cambien, F.; Meyer, J.; Lackner, K.J. Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients with Coronary Artery Disease. N. Engl. J. Med 2003, 349, 1605–1613. [Google Scholar]
- Mueller, A.S.; Pallauf, J. Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice. J. Nutr. Biochem 2006, 17, 548–560. [Google Scholar]
- Stapleton, S.R. Selenium: An insulin mimetic. Cell. Mol. Life Sci 2000, 57, 1874–1879. [Google Scholar]
- Powlin, S.S.; Keng, P.C.; Miller, R.K. Toxicity of Cadmium in Human Trophoblast Cells (JAr Choriocarcinoma): Role of Calmodulin and the Calmodulin Inhibitor, Zaldaride Maleate. Toxicol. Appl. Pharmacol 1997, 144, 225–234. [Google Scholar]
- Kaji, T.; Mishima, A.; Yamamoto, C.; Sakamoto, M.; Kozuka, H. Zinc protection against cadmium-induced destruction of the monolayer of cultured vascular endothelial cells. Toxicol. Lett 1993, 66, 247–255. [Google Scholar]
- Kreis, I.A.; de Does, M.; Hoekstra, J.A.; de Lezenne Coulander, C.; Peters, P.W.J.; Wentink, G.H. Effects of cadmium on reproduction, an epizootologic study. Teratology 1993, 48, 189–196. [Google Scholar]
- Piersma, A.H.; Roelen, B.; Roest, P.; Haakamt-Hoesenie, A.S.; Van Achterberg, T.A.E.; Mummery, C.L. Cadmium-induced inhibition of proliferation and differentiation of embryonal carcinoma cells and mechanistic aspects of protection by zinc. Teratology 1993, 48, 335–341. [Google Scholar]
- Hengstler, J.G.; Bolm-Audorff, U.; Faldum, A.; Janssen, K.; Reifenrath, M.; Götte, W.; Jung, D.; Mayer-Popken, O.; Fuchs, J.; Gebhard, S.; et al. Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected. Carcinogenesis 2003, 24, 63–73. [Google Scholar]
- Youngs, H.L.; Sundaramoorthy, M.; Gold, M.H. Effects of cadmium on manganese peroxidase. Competitive inhibition of Mn(II) oxidation and thermal stabilization of the enzyme. Eur. J. Biochem 2000, 267, 1761–1769. [Google Scholar]
- López, E.; Arce, C.; Oset-Gasque, M.J.; Cañadas, S.; González, M.P. Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture. Free Radic. Biol. Med 2006, 40, 940–951. [Google Scholar]
|Trace element||Certified concentration||Measured concentration||Recovery (%)|
|Zinc||82 ± 3||71 ± 2||86.4|
|Manganese||75.9 ± 0.6||72.5 ± 0.3||95.6|
|Copper||12.2 ± 0.6||11.5 ± 0.3||86.5|
|Cadmium||2.89 ± 0.07||2.47 ± 0.02||85.3|
|Selenium||0.117 ± 0.009||0.116 ± 0.003||98.9|
|Trace element||Coefficient of variation (%)|
|Intraday precision||Interday precision|
|Step||Power (W)||% max||Time (min) to raise temperature||Temperature (°C)||Running time (min)|
|RF Power||1550 watts|
|RF Matching||1.55 V|
|Reflected Power||0 W|
|Sample Uptake Time||30 sec|
|Sample Uptake Rate||0.4 r sec−1|
|Sample Depth||5.0–5.5 mm|
|Coolant Argon Flow Rate||15 L min−1|
|Carrier Gas Flow Rate||1.2 L min−1|
|Auxiliary gas flow rate||0.9 L min−1|
|Water RF/TP Flow Rate||2.4 L min−1|
|Water RF/TP Temperature||20 °C|
|Element||Mass||Mode||Integration Time (sec per point)|
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