Complementary Therapies in Medicine (2012) 20, 100106

Available online at www.sciencedirect.com

journal homepage: www.elsevierhealth.com/journals/ctim

Quality of herbal medicines: Challenges and

solutions
Junhua Zhang a,b,, Barbara Wider b, Hongcai Shang a, Xuemei Li a,
Edzard Ernst b

a
Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
b
Peninsula Medical School, University of Exeter, Exeter EX2 4NT, UK
Available online 1 November 2011

KEYWORDS Summary The popularity of herbal medicines has risen worldwide. This increase in usage ren-
ders safety issues important. Many adverse events of herbal medicines can be attributed to the
Herbal medicine;
poor quality of the raw materials or the nished products. Different types of herbal medicines
Quality control;
are associated with different problems. Quality issues of herbal medicines can be classied into
Safety;
two categories: external and internal. In this review, external issues including contamination
Contamination
(e.g. toxic metals, pesticides residues and microbes), adulteration and misidentication are
detailed. Complexity and non-uniformity of the ingredients in herbal medicines are the internal
issues affecting the quality of herbal medicines. Solutions to the raised problems are discussed.
The rigorous implementation of Good Agricultural and Collection Practices (GACP) and Good
Manufacturing Practices (GMP) would undoubtedly reduce the risk of external issues. Through
the use of modern analytical methods and pharmaceutical techniques, previously unsolved
internal issues have become solvable. Standard herbal products can be manufactured from the
standard herbal extracts.
2011 Elsevier Ltd. All rights reserved.

Contents

External challenges ...................................................................................................... 101

Contamination ...................................................................................................... 101
Heavy metals ................................................................................................. 101
Pesticides..................................................................................................... 101
Microbes and mycotoxins ..................................................................................... 103
Other foreign matter ......................................................................................... 103
Adulteration......................................................................................................... 103
Misidentication..................................................................................................... 104
Internal challenges....................................................................................................... 104

Funding: International Cooperative Project (2008DFB30070); Ministry of Science and Technology of China (2009ZX09311).

Corresponding author at: State Key laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine,
Tianjin 300193, China. Tel.::+86 22 27493265.
E-mail address: zjhtcm@gmail.com (J. Zhang).

0965-2299/$ see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ctim.2011.09.004
Quality of herbal medicines 101

Complex phytochemicals ............................................................................................ 104

Nonuniform ingredients ............................................................................................. 104
Solutions ................................................................................................................. 104
Approaches to external challenges .................................................................................. 104
Approaches to internal challenges................................................................................... 104
Conclusion ............................................................................................................... 105
Conict of interest ....................................................................................................... 105
References ............................................................................................................... 105

Worldwide consumption of herbal medicines has
markedly increased. According to the Secretariat of the
Convention on Biological Diversity, global sales of herbal
products were estimated to be US $60 billion in 2000.1 In
2008, the global market for herbal remedies was about US
$83 billion with a steady growth rate ranging between 3% and
12% per year (see: http://www.nutraceuticalsworld.com).
Risks associated with herbal medicines are still notable.2
A large proportion of the adverse events are attributable
to the poor quality of the nished products, some resulting
from the raw herbal materials that were contaminated.1
The World Health Organization (WHO) dened herbal
medicine as: a plant-derived material or preparation with
therapeutic or other human health benets which con-
tains either raw or processed ingredients from one or
more plants.3 Herbal medicines can be classied into three
groups: (1) herbal materials (raw or processed herbal mate-
rials, e.g. powder, slice), (2) traditional herbal products
(decoctions, tablets, pills or capsules containing crude
herbal materials or crude extracts), and (3) standard-
ized herbal products (formulations containing standardized
extracts or puried substances).
From the cultivation of medicinal herbs to the nal herbal
product, there are many factors which inuence the quality
of herbal medicines (Fig. 1). They can be categorized into
external issues and internal issues.
External challenges
External quality problems mainly include contamination,
adulteration, and misidentication. These problems might
cause serious harms to patients.
Contamination
contained in Asian herbal medicines, especially in Chinese
patent medicines (CPMs) and Indian Ayurvedic medicines
(IAMs).5,79 Some herbal products, from Africa,10 Europe,11
and South America12,13 have also been reported to contain
high concentrations of these toxic metals. Several recent
analytical investigations have conrmed contamination with
toxic metals of herbal medicines in various regions (Table 1).
Contamination can occur due to: (1) the accumulation of
heavy metals in the environment (e.g. from contaminated
soil or atmosphere); (2) inadvertent pollution during the
production process; (3) or deliberate addition.
Minerals, including toxic metals, are commonly used
in some traditional medicine systems for specic cura-
tive purpose (e.g. traditional Chinese medicines or Indian
Ayurveda medicines). For instance, Zhusha (Cinnabaris) and
Xionghuang (Realgar), which contain mercury and arsenic,
are used in some preparations and topical drugs. Among
the 572 Chinese medicinal prescriptions recorded in the
Chinese pharmacopoeia, 53 prescriptions include Zhusha
or Xionghuang.22 Using the term contamination for such
deliberate addition of heavy metals is strictly speaking not
correct.
The notion that heavy metals have positive health effects
is based on ancient concepts which are not sustainable in
the light of modern science. Therefore heavy metals have
no place in herbal medicines. Unless there is compelling evi-
dence that their benets outweigh the risks. For example,
the benet of Realgar for leukemia has been conrmed, and
the functional mechanism has been claried gradually.62,63
Table 1 also suggests that: (1) different herbal medicines
in different countries are contaminated with different fre-
quencies; (2) Chinese herbal materials and patent medicines
exported to other counties are less contaminated with heavy
metal than the ones for domestic use. This might be due to
the higher quality standards in developed countries.

Contaminants most likely to be found in herbal materials or Pesticides

herbal products include but are not limited to heavy met-
als, pesticides, microbes and mycotoxins.46 Although the
problems are universal, they seems to be more prevalent
in Asian countries, especially in China and India, which are
the largest producers and users of herbal medicines.5 Con-
taminations also present a serious obstacle for the trade of
herbal medicines.6
Heavy metals
Heavy metals have been found in herbal medicines with
some regularity. The three most commonly detected toxic
metals are mercury, arsenic, and lead; others include cad-
mium, copper and thallium.7,8 These heavy metals are often
Pesticides include insecticides, fungicides, and herbicides.
To some degree, residues of pesticides including their
metabolites and/or degradation products will remain in
plants, animals, or in the soil. Such residues have become a
notable source of contamination for herbal medicines. The
WHO and other organizations have established requirements
to limit pesticide residues in herbal materials.1,22,23
Organochlorine pesticides (OCPs) are frequently
detected in herbal medicines, including benzene hex-
achlorides (BHC), dichloro-diphenyl-trichloroethane (DDT)
and pentachloronitrobenzene (PCNB).6,24,25 OCPs have
been banned in many countries since about 30 years
due to adverse health effects; however, because of slow
102 J. Zhang et al.

Figure 1 Flow diagram of the traditional circulation of herbal medicines.

degradation, they can persist in the environment (soil) and
accumulate in the food chain.4 Others pesticides, such as
the organophosphorus and carbamate compounds have less
frequently been detected in herbal medicines, because
they degrade more easily. Currently pyrethroid pesticides
with high efciency and low-residue are frequently used;
residues of these modern compounds, such as fenvalerate
or deltamethrin, are also found in some herbal materials.26
Many Chinese studies have addressed the problem of pes-
ticide residues in herbal materials. These residues were

Table 1 Contamination degrees of heavy metal in herbal medicines.

Articles Quantity of Sample Producing Type of production Research Results

product source region date

Yee14 3320 Singapore China Chinese patent 19902001 Mercury (2.1%); arsenic
market medicines (1.44%); lead (0.60%);
copper (0.03%); total 4.16%
of the samples over limits
Koh15 2080 Singapore China Chinese patent Before Mercury (1.34%); lead
market medicines 2000 (0.38%); arsenic (0.29%);
copper (0.05%); total 2.02%
of the samples over limits
Tian16 40 China China Chinese patent 2006 Arsenic (8%); mercury (22%)
medicines
Melchart17 317 Germany China Herb materials 2001 3.5% of the samples over
hospital limits
Jin18 500 China China Herb materials 20002005 24% of the samples over
limits
Obi10 25 Nigerian Nigeria Herbal products 2006 100% contaminated
market
Saper19 70 Boston India Herbal products 2003 Lead (18.6%); mercury
stores (8.6%); arsenic (8.6%); total
20% of the samples over
limits
Ang20 100 Malaysian Malaysia Products 2006 Lead, 22% of the samples
market containing Eugenia over limits
dyeriana
Ang21 100 Malaysian Malaysia Products 2006 Mercury, 26% of the samples
market containing tongkat over limits
Ali hitam
Quality of herbal medicines
Table 2 Pharmaceuticals detected in herbal products.14,41,42
Detected medicines Pharmacologic
actions
Hydrochlorothiazide Diuretics; hypotensor
Glibenclamide Insulin stimulation
Diclofenac; Indomethacin; Anti-inammatory;
Phenylbutazone analgesic
Paracetamol; Phenacetin; Antipyretic; analgesic
Aminopyrine
Chlordiazepoxide; Chlormethiazole; Sedative hypnotics
Diazepam; Promethazine
Chlorpheniramine; Diphenhydramine Antihistamine
Dexamethasone; Hydrocortisone Glucocorticoid
Sildenal Vasodilation
detected both in domestic and imported herbal materi-
als, such as Panax notoginseng root, Panax quinquefolium
root, and Panax ginseng root.27,28 Two recent studies investi-
gated the pesticide residues in 155 medicinal herbal samples
(25 species) collected from 11 cultivation bases in Guizhou
province. Five kinds of pyrethroid pesticides were detected
and 14.8% of all samples were over the legal limit. Above
ground parts were more seriously affected than roots.29 The
OCPs (including 9 types) were detected and 7.09% of the
samples were over the legal limits. Roots were more seri-
ously affected than the above ground parts.30
Soil contaminated by OCPs still affects the environment
today. Improper use of pesticides, such as PCNB used as a soil
disinfectant, spraying pesticides in high dosages or too close
to harvest time, also lead to residue contamination.7,31 Using
pesticides during storage, and fumigants (e.g. SO2 ) against
insects or mildewing are further ways in which contamina-
tion occurs.6,32
Microbes and mycotoxins
Contamination with microbes is a common problem in herbal
medicines. Pathogenic organisms including enterobacter,
enterococcus, shigella and streptococcus have been shown
to grow on herbal materials.33
Mycotoxins include fusarial toxin, aatoxins, ochra-
toxin, citreoviridin, penicillic acid etc. Aatoxins are both
relatively common and highly poisonous.6 A study of medic-
inal herbs collected from a Brazilian market showed that
more than 50% of these samples exceeded the microbial
count limits set by the US Pharmacopoeia.34 Other stud-
ies have also found contamination by fungi and mycotoxins
in herbal medicines from India,35 South Africa,36 Malaysia,
Indonesia,37 and China.18
Microbial contamination of herbal medicines can occur at
any stage during production and marketing (Fig. 1). Storage
and processing conditions crucially determine the quality
of the nal herbal products. Problems are more common in
tropical and subtropical regions, because the high tempera-
ture and moisture contents are conducive to fungal growth
and toxin production.4,38
103
Possible conditions Detected herbal
medicines (example)
Hypertension Gu Ben Wan
Type 2 diabetes Zhen Qi
Arthritis Toukuwan; Feng Shi
Huo Luo Dan
Fever Gui Pi Wan; Toukuwan
Insomnia; pain Gu Ben Wan;
Shenchin herb
Allergy; cold She Tu Chieh Tu Wan;
Nasalin
Many conditions Toukuwan
Sexual dysfunction Strong capsule; Super
E-Tonic for Men
Other foreign matter
Other foreign matter, including ash, adjuvant or organic
solvents can also lead to external contamination of herbal
medicines.6,39 To ensure good quality of the endproduct, it
is necessary to minimize this problem.
Adulteration
Adulteration is always fraudulent and means to make
impure by adding extraneous, improper, or inferior ingre-
dients. Instances of herbal medicines adulterated with
orthodox drugs and plant materials have repeatedly been
documented. Adulterations can be classied into three cate-
gories: addition of orthodox drugs to herbal medicines,14,40,41
substitution (use of fake or inferior plant materials),42
and addition of foreign materials (non-ofcinal herb parts,
sands, metals).
Several pharmaceuticals have been found in herbal
medicines (Table 2), and the incidence of adulteration of
commercially available herbal preparation was reported
to be 7% in California,9 5.5% in New York40 and 1.23% in
Singapore.14 In recent years, sildenal (Viagra) has often
been found in some herbal products marked as tonics.14,40
Adding substitutions and foreign materials to herbal
drugs is usually aimed at maximizing prots by fraudu-
lently increasing the weight or quantity of herbal materials.
This usually occurs from the second to the fth stage in
the production process (Fig. 1). In China, many compound
medicines containing both herbal materials and synthetic
drugs are approved for sale (e.g. antipyretic analgesic in
medicines for cool, hydrochlorothiazide in medicines for
hypertension). According to the denition from WHO, these
types of drugs are not considered to be herbal medicines.1
The legal addition of synthetic drugs to herbal medicine
should not be termed adulteration.
Herbal medicines including undeclared orthodox drugs
are illegal. A lack of regulation or control can lead to
improper labeling and adulteration of herbal medicines.40
Adulteration is a potentially serious problem, which needs
to be addressed by strict regulatory measures which, in turn,
must be enforced to be effective.
104
Misidentication
Contrary to adulteration/substitutions (deliberate behav-
ior), misidentication happens inadvertently. False authen-
tication can occur when an importer or retailer mistakes
one herb for another, due to incorrect labeling and similar
appearance of the herbal materials.43 Confusing nomencla-
ture can be one of the reasons. One herb may be known by
many names: one or more common names, a Latin name,
local names, and the brand name. Some different medicinal
herbs of different plant species with different constituents
may have the similar names. For example, the herb names
Mutong, Chuan mutong and Guan mutong, can combining multi-ingredient herbal medicines with prescrip-
be used in Chinese prescriptions with the same common
name Mutong. Similarly, Fangji, Feng fangji and interactions.
Guang fangji can be used as Fangji. Hence, the names
of Mutong and Fangji refer several different plant Solutions
species from different unrelated botanical families. The
misidentication of Mutong (Caulis Akebiae replaced by
Caulis Aristolochiae Manshuriensis) and Fangji (Stepha-
nia tetrandra replaced by Aristolochia fangch) has led to the
serious problem of aristolochic acid nephropathy.44,45
Similar appearances, confusion regarding historic records
and local habits of use may also contribute to the misidenti-
cation of herbs. The problem becomes even more complex
through confusing terminologies and the use of different lan-
guages in different countries. The common names of herbs
are usually not reecting the differences in scientic tax-
onomy; and the description and microscopic identication
of an herb cannot identify its constituents. Thus, a study
of ancient documents and the use of modern analysis tech-
niques are often necessary to properly authenticate herbal
materials. The WHO and other organizations are working to
achieve harmonization and specications of the botanical
nomenclature.46,47
Internal challenges
Any health effects of herbal medicines are caused by phar-
macologically active phytochemicals contained in these
medicines. External quality issues are complex, internal
ones, however, can be even more challenging.
Complex phytochemicals
Plants can synthesize a bewildering variety of phytochem-
icals, such as fatty acids, sterols, alkaloids, avonoids,
glycosides, saponins, tannins, terpenes and phenolics.48
Even a single plant extract may contain hundreds of organic
chemicals. For instance, more than 28 ginsenosides have
been extracted from P. ginseng, and each might be asso-
ciated with different therapeutic actions.49 In mixtures of
more than one herbs, the chemical compositions is even
more complex. In many instance, it may be difcult to
determine which ingredient is responsible for any given ther-
apeutic effect.
Nonuniform ingredients
Depending on the growing conditions and geographic region,
the composition of herbal medicines varies. A host of
J. Zhang et al.
environmental factors, including soil, altitude, seasonal
variation in temperature, atmospheric humidity, length of
daylight, rainfall pattern, etc, may affect the concentration
of components in any given batch. Other factors, including
genetic make-up, seeding time, use of pesticides and fer-
tilizers, planting density, etc, also play important roles.50
The processing of raw materials may involve heating or
boiling, which can further alter the pharmacological activ-
ity of the organic constituents. A recent analysis of 25
ginseng products found a 15200-fold variation in the con-
centration of the two ingredients believed to have biological
activity: ginsenosides and eleutherosides.51 In addition,
tion medicines can lead to herbherb and/or herbdrug
International organizations, governments, and researchers
are working towards addressing this plethora of issues and
potential problems.
Approaches to external challenges
External quality issues can be classied into three main
aspects: cultivation, manufacturing, and circulation. The
rigorous implementation of Good Agricultural and Collec-
tion Practices (GACP) is a crucial step towards improving
the quality of herbal medicines. The WHO issued guidelines
on Good Agricultural and Collection Practices (GACP) for
medicinal plants in 2003; other countries or regions have also
developed regional and national GACP, such as the European
Union, China and Japan. The processing of herbal materi-
als and the production of herbal products must follow Good
Manufacturing Practices (GMP).52 Finally, the marketing of
herbal medicines should also comply with the Good Supply
Practices (GSP).
In China, 63 national GACP bases (special elds for cul-
tivating herbal medicines adherent to GACP) have been
certied from 2004 to 2009 (see: http://www.sfda.gov.cn).
There are also 430 local GACP bases with a planting area of
about 11,000 km2 .53 After the implementation of GACP, the
quality of Chinese herbal materials has improved.16 How-
ever, this achievement is incomprehensive. Lack of scientic
standard operating procedures (SOPs), normalized man-
agement, well-trained farmers and other relevant experts
continue to cause problems.5355
To be effective, the implementation of guidelines (GACP,
GMP) need to be legally enforced. Herbal companies are in
a key position to promote the quality of herbal medicines.
According to the requirements of national regulations,
herbal companies should guarantee the quality of their
products.
Approaches to internal challenges
Because of the multiple factors that affect the concen-
tration of active ingredients in the herbal materials and
products, controlling the quality and ensuring the stabil-
ity of herbal medicines are big challenges for the herbal
Quality of herbal medicines
industry. Currently, there are two possible approaches to
these problems.
The rst is to balance the concentrations by blending sev-
eral batches of the same herbs containing different amounts
of the desired ingredients.50 In this way, variations can be
partly reduced. However, this approach alone is unlikely to
sufce.
The second approach is to produce preparation from stan-
dardized herbal constituents. This is a hot topic, which has
been considered as the bridge between traditional herbal
medicines and modern pharmaceuticals.56 To establish the
standards or markers for mixed constituents would be the
key point. With the fast development of modern analyti-
cal methods and production technology, uniform medicinal
herbal products can be manufactured.57 For instance: a stan-
dardized St. Johns Wort (Hypericum perforatum) extract
(WS-5570) containing 36% hyperforin and 0.120.28%
hypericin has been used as a herbal antidepressant58 ; Stan-
dard herbal product including several herbal materials
has also been manufactured, such as IB-20 is a 20-herbs
preparation.59 In China, some research teams have worked
extensively in this area,60 and about 13,000 standard herbal
constituents have been developed.61
Conclusion
Our ambition and responsibility of assuring high quality of
herbal medicines presents us with unique challenges. This
article mainly identied quality issues about eastern herbal
medicines. The rigorous implementation of GACP and GMP
can minimize the risk of contamination, adulteration and
other problems. Standard herbal products with controllable
quality can be manufactured by using modern analytical
methods and pharmaceutical techniques. However, cur-
rently achievement in quality control of herbal medicine is
regional and partial. To achieve the overall improvement
of quality, efforts should be made to deepen methodologi-
cal researches and enhance regulatory in herbal medicines.
Government organizations should assume responsibility to
provide active guidance and effective regulation.
Conict of interest
None.
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