Traditional medicine is the
earliest healthcare system known to humanity. Different plants/herbs and animal
parts have been used since ages to treat various illness 1.The use of TM has grown and evolved
over centuries 2 .Currently TM is widely used in the developing
countries as a prime health care system due to its affordability, accessibility
and availability3. Meanwhile the consumption of TM has increased in
some developed countries as well, for the reason that herbal medicines are
originated from natural sources and thus they are more likely to be safe
compared to the modern medicine which are made of synthetic substances 4.
As a result, there was a global vast growth in the popularity of traditional
healing modalities, mainly herbal remedies during the later part of the
twentieth century 5.
The rapid growing worldwide is
evident by the estimated value of the global TM market which was about US$ 60
billion annually in 20082.The global wide diffusion of TM had
highlighted the issues of safety, efficacy and quality control of such products
to be an important concern from certain global health authorities such as the
WHO and Food and Drug Administration (FDA)6. Herbal/TM must be used cautiously;
some TM products may cause negative health impact and even toxicity due to many
reasons such as the adulteration with conventional medicine and contamination
with heavy metals and other toxic substances 7.
Heavy metals contamination in TM products
In general heavy metals can be
defined as elements with metallic properties and an atomic number higher than
20, they are natural components of the earth’s crust and ubiquitous
in trace concentrations 8. It has been reported that some herbal
products contain heavy metals 9. The presence of heavy metals in
herbal/TM products is attributed to several possibilities. The environmental
factors are probably contributed in the contamination of such products. It
includes the contamination of the agricultural soils and irrigation water as a
result of the industrial waste disposal, mining activities and the usage of
certain types fertilizes 10 .
Heavy metals may also introduce
during the preparation of the raw materials for TM products which covers many
steps such as cultivation, harvesting, collecting, cleaning and drying of the
medicinal plants 11. The other
possibility is the accidental contamination during the manufacturing process
such as grinding, mixing and the exposure to heavy metals from metal-releasing equipment
which might be used in different steps of the processing part 12. The intentional addition of
heavy metals during the preparation as part of the ingredients for a curative
purpose constitutes another source of TM contamination with heavy metals 13
. Figur1 shows a diagram of different
sources of heavy metals contamination in TM
Figure 1. Diagram of different sources of heavy
metals contamination in TM products
Arsenic (As), cadmium (Cd), lead
(Pb), nickel (Ni), zinc (Zn) and iron (Fe) are often reported to be found in
TM. Prolong exposure to heavy metals
may cause adverse health effect and toxicity due to the capability of heavy
metals to bioaccumulate and disrupt the functions of vital organs in the human
body such as brain, kidneys and liver 14 . Some heavy metals are
essential as trace amounts such as zinc and iron however, they are dangerous if
present in a higher concentration 15. This article aims to provide a
summary of the obtained information regarding the toxicity and other negative
health impacts due to the exposure to some heavy metals. In addition of
reveling various clinical cases of heavy metal toxicity associated with the
consumption of some TM products and to consider some of the reported studies on
the subject of heavy metals detection in TM products which have been published
in different parts of the world.
Arsenic is a toxic heavy metal
which may be present in some herbal products. It can penetrate in to the plant
through the contaminated soil and water using the same mechanism to gain the
essential micronutrients 16 .
Exposure to As causes acute and
chronic adverse health effects, including cancer. Acute toxic effects include
abdominal cramping, chronic arsenic toxicity is mostly manifested in weight
loss and a capricious appetite 17. The most significant consequence of
chronic exposure to arsenic is the occurrence of cancers in various organs
especially in the skin and lungs 18.
The detection of arsenic in herbal
products has been reported in different parts of the world. A study in India
reported the results of arsenic concentration in 10 batches of herbal
preparation “Septiloc”. Arsenic was found in five samples, with a concentration
range of 0.28 - 0.05 mg/kg 19. In Nigeria,
a study was carried out to investigate the concentration of toxic metals
including arsenic in twenty brands of herbal products. The concentration of As
was found in the range of 0.301-1.108 µg/g 20. In California, a
screening study of 251 Chinese medicines collected from herbal retail stores
was conducted. It was found that 14% of the samples contained an average
concentration of 14.6 ppm of As 13. Another study in Boston USA, for
a total of seventy TM samples were collected from different shops .Six samples
had a high concentration range of As 37–8130 µg/g 21.
Arsenic toxicity due to the
consumption of TM products had been reported, in Taiwan, 17 patients had
cutaneous lesions related to chronic arsenicism, among them 14 patients had a
history of traditional Chinese medicine (TCM) intake. Squamous cell carcinomas
were developed in 11 of the 17 22. Another case of As toxicity was
reported on a five-year-old Italian boy in August 1995, with congenital
bilateral retinoblastoma. He had been given an Indian healer prescribed ethnic
remedies. Signs of toxicity were nausea, fatigue, progressive weakness of lower
limbs, and leucopenia. It was found that arsenic
concentration in the remedy was 184 mg/ kg and in the patient’s hair was 6.6 mg
/kg 13. Which provided the evidence of As toxicity.
Cadmium is a non-essential
element, soluble in the biological systems 23. It is known for its
high toxicity and similar to other heavy metals it has a tendency to
bioaccumulate and disrupts the functions of vital organs in the human body 14.
Both acute and chronic exposure
to cadmium has a negative impact for human health. Cadmium may cause
high blood pressure and destruction of red blood cells. Cadmium metal ion in
the body’s metallo-enzyme can easily replace another metal ion due to the
chemical similarities and competition for binding stage therefore, Cd2+ can replace Zn2+
which in some dehydrogenating enzymes, causes cadmium toxicity24. Studies
have provided fundamental evidence that long-term exposure to low levels of
cadmium is associated with increasing the risk of cancer 25.
Cadmium has been detected in TM
in a number of studies conducted in various parts of the world. In Nigeria, a
detection study of Cd content in herbal drugs was reported that Cd
concentration was found in the range of 16.438 -
29.796 mg/g 26. In Pakistan Cd was detected in twenty five branded
herbal products using atomic absorption spectroscopy (AAS) and the results
showed that the tested samples contained Cd in a concentration range of
1.9-45.2 µg/g 9.
Lead is one of the heavy metals
which have been recognized for its undesirable effects on different body
organs. Prolonged exposure to Pb decreases the performance of the nervous
system and lowers renal clearance 27. Lead poisoning is considered
one of the significant environmental health threats for children even at low
levels of exposure. It is associated with impairment of childhood cognitive
function 28. A high lead level during pregnancy is directly related to
several outcomes such as spontaneous abortion, low birth weight and impaired
neurodevelopment 29. Lead poisoning occur when the concentration
reach between 100-140 µg/L 30. According to the international Agency
for Research on cancer (IARC) 31 inorganic lead is carcinogenic to
Many clinical cases had been
reported regarding lead poisoning due the consumption of different types of
traditional medicine. A lead poising case was reported in Auckland New Zealand.
A 51-year-old man with 2-weeks history of colicky abdominal pain and background
history of type two diabetes had been taking Ayurvedic Jambrulin tablets. The
whole blood lead level was 375.2 µg/L. The analysis of his Ayurvedic tablets
showed that each one contained approximately 10 mg of lead 32. Another
case of lead poisoning had been reported in Bangalore for a 45-years-old man,
he was admitted twice to the hospital due to vomiting and abdominal pain. The
patient’s history revealed that he had been consuming 12 different Ayurvedic
medicines for stress relief for the past 4 years. The patient’s blood lead
level (BLL) was 1224 µg/L, which confirmed lead poisoning. Analysis of the 12
Ayurvedic products revealed that 75% of the products contained high levels of
lead, arsenic and mercury in concentration higher than the daily permissible
Many studies were preformed
regarding the detection of lead in TM in different parts of the world. In Karachi Pakistan, herbal medicine samples were
collected from three different parts of the city (southern, eastern and
western) for the determination of eight heavy metals including lead (Pb). Lead
concentrations were found in the range of 3.26-30.46 µg/g and 71.4% of the
samples were beyond the permissible limit 34. In China different batches of four types of natural herbal
medicines manufactured by local pharmaceutical
factories, were analyzed for lead content, the results indicate that all
samples contain lead in concentration range of 0.125-4.79 µg/g 35. In
Malaysia a study was performed to determine the concentration of lead in 100
products in various pharmaceutical dosage forms of tongkat Ali hitam herbal
preparation, the results showed that 8% of the samples contained lead in a
range 10.64-20.72 µg/g
and therefore Pb concentration were more than the permissible limit 36.
Exposure to Ni may result in a
variety of pathological effects. Oral exposure to large doses of nickel mainly
targets the cardiovascular system 37. The common adverse health
effect of nickel in humans is allergic skin reaction in those who are sensitive
to nickel 38. Most of the toxicity of nickel might be attributed to
its interference with the physiological processes of zinc and calcium 39.
According to the International Agency for Research on Cancer (IARC) and the
United States Department of Health and Human Services, nickel compounds have
been classified as human carcinogens. Carcinogenic nickel compounds have been
shown to induce different types of tumours in experimental animal systems
40. A clinical case of Ni toxicity had been reported for a 2-years old
child who accidentally ingested nickel sulfate crystals rough estimate of 570
mg/kg of Ni. After few hours of the ingestion the child had cardiac arrest and
he died 8 hours after the exposure 41.
Nickel poisoning cases were
reported for a group of workers were exposed to nickel in an estimated dose of
7.1–35.7 mg /kg. The exposure was through drinking of fountain water contained
nickel sulfate, nickel chloride, and boric acid. All workers reported symptoms
included abdominal cramps nausea, vomiting and diarrhea 40.
A number of studies had been reported
for Ni detection in TM. In Pakistan two studies had been reported for Ni
determination in TM products. The first study was aimed to detect the
concentration of different heavy metals including Ni in a group of branded
herbal products using flame atomic absorption spectroscopy (FAAS). Nickel was
found in concentration range of 0.2-56.3 µg/g 9. The second study
was conducted to determine eight heavy metals including Ni in a group of
selected herbal products available in the local market in various places of
Karachi city using AAS. The results showed that Ni was found in the range of
0.48-76.97 µg/g 34.
Zinc is an essential trace
element. It exists in all types of tissues of the body and takes part in vital
roles for cell growth and other physiological activities. Despite its
important, it can be dangerous if exist in high concentration. Excessive oral
zinc exposure could lead to Zn accumulation in different organs in the human
body and subsequently cause an adverse health effects. High dose of zinc ingestion have a direct
effect to the gastrointestinal tract before it is dispersed through the body 42.
Zinc may have effect on serum
cholesterol balance as it cause increase of the low density lipoprotein (LDL)
cholesterol and a decrease in high-density lipoprotein (HDL) cholesterol 43.
Several studies had been reported
for Zn detection in TM in different parts of the world. A study to find out the
concentrations of zinc and other heavy metals in branded herbal products in
Pakistan using FAAS. Zinc was found in concentration range 5.1-1071 µg/g 9(Saeed, 2010). Another study was conducted in
Pakistan for the detection of heavy metals including Zn in selected TM products
purchased from different places in Karachi. The results showed that Zn was found
in the range of 83.74-433.76 µg/g 34.
A clinical case of
gastrointestinal disturbances after the consumption of zinc sulfate was
reported in England. The girl was given 440 mg
zinc sulfate/day (2.6 mg zinc/kg/day) in capsules as a medically prescribed
treatment for acne. After taking each capsule, she experienced epigastric
discomfort like abdominal cramps and diarrhea. After one week she had an
indicated signs of gastrointestinal bleeding and later was treated in the
It is an essential micronutrient
as it plays a critical role in major biochemical activities, such as oxygen
transport and electron transfer 45. There
are about 3-5 grams of iron (45-55 mg/kg) in human body, about 60–70% is
utilized within hemoglobin in circulating red blood cells 46. Although
iron is very important it can be hazardous when exist in high concentration.
Ingesting excessive doses of iron causes irritation of the gastrointestinal
mucosa which increases the gastric discomfort symptoms like nausea, vomiting
and diarrhea. It may also cause severe damage to the mucosal cells which leads
to bleeding in the stomach and perforation of the gutwall 47. Excess
of iron disrupts the redox balance of the cell resulting in generation of
chronic oxidative stress, which organized the signaling networks related to
malignant transformation 48. In humans, high concentration of iron
storage has been shown to increase the risk of cancers, including breast cancer
49. The possibility for Fe accumulation in human body is higher in
contrast with other heavy metals, because iron intake from various sources such
as dietary and supplements is very high. This could subsequently lead to many
health complications such as severe necrotizing gastritis with vomiting,
hemorrhage and diarrhea 50.
Many studies conducted to
determine heavy metal concentrations including Fe. A
concentration range 8.6-2731.8 µg/g of Fe had
been found in a selected group of branded herbal products in Pakistan in a
study to detect the concentration range of several heavy metals including Fe 9.
Another study with a similar approach had been conducted and Fe concentration
range was 65.68-1652.89 µg/g in different products of herbal medicine purchased
from various places in Karachi city of Pakistan 34.
Traditional medicines products
are consumed by a wide range of the world population. Some TM products contain
toxic materials such as heavy metals. Exposure to heavy metals can cause health
hazard and toxicity. The presence of heavy metals in these
medications could expose the consumers to different adverse health effects.
Therefore, a proper general awareness should be provided to consumers and
producers to minimize this risk.
- Saganuwan, A. S. (2010). Some medicinal plants of Arabian Peninsula. J. Med. Plants Res, 4(9), 766-788.
- WHO. (2009). Panel Discussion on the Contribution of Traditional
Medicine to the Realization of International Development Objectives
related to Global Public Health. New Yourk: Economic and Social Council
- Hussin, A. H. (2001). Adverse effects of herbs and drug-herbal
interactions. Malaysian Journal
of Pharmacy, 1(2), 39-44.
- Inamdar, N., Edalat, S., Kotwal, V., & Pawar, S. (2008). Herbal
drugs in milieu of modern drugs. International
Journal of Green Pharmacy, 2(1), 2.
- Jayaraj, P. (2010). Regulation of traditional and
complementary medicinal products in Malaysia. International Journal of
Green Pharmacy, 4(1), 10.
- WHO. (2007). Guidelines for assessing quality of
herbal medicines with reference to contaminants and residues. Geneva.
- Koh, H. L., & Woo, S. (2000). Chinese proprietary medicine in
Singapore: regulatory control of toxic heavy metals and undeclared drugs. Drug safety, 23(5), 351-362.
- Saif, M. S., SulemanMemon, K., & Sial, N. B.
(2005). Heavy Metals Accumulation in Potentially Contaminated Soils of
NWFP. Asian Journal of Plant Sciences, 4(2), 159-163.
- Saeed, M. (2010). Analysis of toxic heavy metals in branded pakistani
herbal products. Journal of the
Chemical Society of Pakistan, 32(4), 471.
- Sharma, P., & Dubey, R. S. (2005). Lead
toxicity in plants. Brazilian Journal of Plant Physiology, 17(1),
- Tong, S., von Schirnding, Y. E., &
Prapamontol, T. (2000). Environmental lead exposure: a public health
problem of global dimensions. Bulletin of the World Health Organization,
- Chan, K. (2003). Some aspects of toxic contaminants in herbal
medicines. Chemosphere, 52(9),
- Ernst, E. (2002). Toxic heavy metals and undeclared drugs in Asian
herbal medicines. Trends in
Pharmacological Sciences, 23(3), 136-139.
- Ray, S. A., & Ray, M. K. (2009). Bioremediation of heavy metal
toxicity-with special reference to chromium. Al Ameen Journal of Medical Sciences, 2(2), 57-63.
- Pearce, D. A., & Sherman, F. (1999). Toxicity of Copper, Cobalt,
and Nickel Salts Is Dependent on Histidine Metabolism in the
YeastSaccharomyces cerevisiae. Journal
of bacteriology, 181(16), 4774-4779.
- Tangahu, B. V., Abdullah, S., Rozaimah, S., Basri, H., Idris, M.,
Anuar, N., et al. (2011). A Review on Heavy Metals (As, Pb, and Hg) Uptake
by Plants through Phytoremediation. International
Journal of Chemical Engineering.
- Lilis, R. (1989). Acute arsenic intoxication from environmental
arsenic exposure. Archives of Environmental Health: An International
Journal, 44(6), 385-390.
- Ng, J. C., Wang, J., & Shraim, A. (2003). A global health problem
caused by arsenic from natural sources. Chemosphere, 52(9), 1353-1359.
- Naithani, V., Pathak, N., & Chaudhary, M. (2010a). Estimation of
Arsenic and Mercury in a Polyherbal Formulation -Septiloc. International
Journal of Pharmaceutical Sciences and Drug Research 2(1), 78-79.
- Adepoju-Bello, A., Issa, O., Oguntibeju, O., Ayoola, G., &
Adejumo, O. (2012). Analysis of some selected toxic metals in registered
herbal products manufactured in Nigeria. African Journal of Biotechnology, 11(26), 6918-6922.
- Saper, R. B., Kales, S. N., Paquin, J., Burns, M. J., Eisenberg, D.
M., Davis, R. B. (2004). Heavy metal content of ayurvedic herbal medicine
products. JAMA: Journal of American Medical Association, 292(23),
- Wong, S. T., Chan, H. L., & Teo, S. K. (1998). The spectrum of
cutaneous and internal malignancies in chronic arsenic toxicity. Singapore Med J, 39(4), 171-173.
- Arifin, A., Parisa, A., Hazandy, A., Mahmud, T., Junejo, N., Fatemeh,
A., et al. (2012). Evaluation of
cadmium bioaccumulation and translocation by Hopea odorata grown in a
contaminated soil. African
Journal of Biotechnology, 11(29), 7472-7482.
- Duruibe, J., Ogwuegbu, M., & Egwurugwu, J. (2007). Heavy metal
pollution and human biotoxic effects. International Journal of Physical Sciences, 2(5), 112-118.
- Afkhami, A., Madrakian, T., & Siampour, H. (2006). Flame atomic
determination of trace quantities of cadmium in water samples after
cloud point extraction in Triton X-114 without added chelating agents. Journal of Hazardous materials, 138(2),
- Musa, A., & Hamza, J. (2009). Comparison of cadmium (Cd) content
of herbal drugs used as antimalarials and chloroquine phosphate syrups in
Zaria, Naigeria. Nagerian. Nigerian
Journal of Pharmaceutical Sciences, 8(1), 95-101.
- Salawu Emmanuel, O., Adeleke Adeolu, A., Oyewo Oyebowale, O., Ashamu
Ebenezer, A., Ishola Olufunto, O., Afolabi Ayobami, O. & Adesanya Taiwo A. (2009). Prevention of renal toxicity from
lead exposure by oral administration of Lycopersicon esculentum. Journal of Toxicology and Environmental
Health Sciences, 1(2), 022-027.
- Canfield, R. L., Henderson Jr, C. R., Cory-Slechta, D. A., Cox, C.,
Jusko, T. A., & Lanphear, B. P. (2003). Intellectual impairment in
children with blood lead concentrations below 10 µg per deciliter. New England Journal of Medicine,
- Rabinowitz, M., Bellinger, D., Leviton, A., Needleman, H., &
Schoenbaum, S. (1987). Pregnancy hypertension, blood pressure during
labor, and blood lead levels. Hypertension,
- Goldfrank L.R., Flomenbaum N.E., Lewin N.A., Wiesman R.S., Howland A,
& R.S., H. (Eds.). (1998). Goldfrank's
Toxicologic Emergencies. Stamford, Connecticut: (8 ed.). New Yourk:
Appleton & Lange.
(1987). Monographs on the Evaluation of the Carcinogenic Risk to Humans:
Arsenic and arsenic compounds (Group 1). Supplement 7, International
Agency for Research on Cancer, Lyon, pp. 100–103.
- 32.Van Schalkwyk, J., Davidson, J., Palmer, B., & Hope, V.
(2006). Ayurvedic medicine: patients in peril from plumbism. Journal of New Zealand Medical
Association, 119 (1233).
- Raviraja, A., Vishal Babu, G., Sehgal, A., Saper, R. B., Jayawardene,
I., Amarasiriwardena, C. J., & Venkatesh, T. (2010). Three cases of
lead toxicity associated with consumption of ayurvedic medicines. Indian Journal of Clinical
Biochemistry, 25(3), 326-329.
- Hina, B., Rizwani, G. H., & Naseem, S. (2011). Determination of
toxic metals in some herbal drugs through atomic absorption spectroscopy. Pakistan journal of pharmaceutical
sciences, 24(3), 353.
- Qi, L., & Huirong, L. (1998). Determination of lead in natural
herbal medicines by flame atomic absorption spectrometry with a slotted,
sputtered quartz tube. J. Anal.
At. Spectrom., 13(10), 1203-1205.
- Ang, H. (2008). Lead contamination in
Eugenia dyeriana herbal
preparations from different commercial sources in Malaysia. Food and
Chemical Toxicology, 46(6), 1969-1975.
- Das, K. K. (2009). A Comprehensive Review on Nickel (II) And Chromium
VI Toxicities-Possible Antioxidant (Allium Sativum Linn) Defenses. Am. J. Med. Sci, 2, 43-50.
- Duda-Chodak, A., & Baszczyk, U. (2008). The impact of nickel on
human health. J. Elementol, 13(4),
- Das, K. K., Das, S. N., & Dhundasi, S. A. (2008). Nickel, its
adverse health effects & oxidative stress. Indian Journal of Medical Research, 128(4), 412.
- Sunderman, F. W., Jr., Dingle, B., Hopfer, S. M., & Swift, T.
(1988). Acute nickel toxicity in electroplating workers who accidently
ingested a solution of nickel sulfate and nickel chloride. Am J Ind Med, 14(3), 257-266.
- Daldrup T, Haarhoff K, & Szathmary SC. (1983). Toedliche nickel
zur Serichtlichen Medizin 41, 141-144.
- Plum, L. M., Rink, L., & Haase, H. (2010). The essential toxin:
impact of zinc on human health. International
Journal of Environmental Research and Public Health, 7(4), 1342-1365.
- 43.Nriagu, J. (2010). Zinc toxicity in humans. Encyclopedia of Environmental Health,
- Samman, S., & Roberts, D.
C. K. (1988). The effect of zinc supplements on lipoproteins and copper
status. Atherosclerosis, 70(3),
- 45.Aisen, P., Enns, C., & Wessling-Resnick, M. (2001). Chemistry
and biology of eukaryotic iron metabolism. The international journal of biochemistry & cell biology,
- Papanikolaou, G., & Pantopoulos, K. (2005). Iron metabolism and
toxicity. Toxicology and applied
pharmacology, 202(2), 199-211.
- Anim, A., Laar, C., Osei, J., Odonkor, S., & Enti-Brown, S.
(2012). Trace metals quality of some herbal medicines
sold in Accra, Ghana. Proceedings
of the International Academy of Ecology and Environmental Sciences, 2(2),
- Benhar, M., Engelberg, D., &
Levitzki, A. (2002). ROS, stress-activated kinases and stress signaling in cancer. EMBO reports, 3(5), 420-425.
- 49.Gurzau, E. S., Neagu, C., & Gurzau, A.
E. (2003). Essential metals—case study on iron. Ecotoxicology and environmental safety, 56(1), 190-200.
- Vaikosen, E. N., & Alade, G. O. (2011). Evaluation of
pharmacognostical parameters and heavy metals in some locally manufactured
herbal drugs. Journal of Chemical
and Pharmaceutical Research, 3(2),