Where do herbal medicines belong? Part 2 — herbal medicines reappraised
In this second part of a two part-article, the authors look at current use of herbal medicines, and how they are registered, and point pharmacists to sources of useful advice
In part 1 of this article we provided an overview of complementary and alternative medicine (CAM), including homoeopathy and food supplements, and discussed the development of pharmaceutical drugs from natural sources. In part 2 we continue our discussion with an overview of herbal medicinal products, and a reappraisal of them in terms of conventional medicine.
Herbal medicinal products
Although the clinical evidence available may differ from that for conventional medicines, for many herbal medicines there is now a sound basis of evidence. Most importantly, the main difference between herbal medicines and conventional medicines is that herbal medicines each contain a combination of chemicals, as opposed to a single pharmacologically active substance. Herbal medicines may also be used in a diversity of ways: they are prescribed by herbalists, often as part of a treatment (which makes claims for being holistic); and they are commonly available as OTC products for self medication, or after consultation with a pharmacist.1
It is one of the principal tenets of modern herbal medicine that within a plant several compounds act on each other, either moderating or opposing, or enhancing in an additive or a synergistic action, whereby the combination of constituents is greater than would have been expected from the sum of individual contributions.2,3 Numerous scientific studies have demonstrated that there may be a number of molecules of varying activity in a plant (which may or may not act synergistically), but when the compounds are isolated, overall activity may be lost.4,5 Polyvalence is the term used to describe the range of biological activities that a plant extract may exhibit that contribute to the overall observed clinical effects, whereas synergism applies to only one pharmacological function.4
Interestingly, the concepts of synergism and polyvalence are also found in other ancient traditional medical systems including traditional Chinese medicine (TCM) and Ayurvedic medicine, whereby combinations of herbal medicines are often employed.3
However, this difference between herbal medicines and modern drugs is perhaps not so great, since the so-called “silver bullet” concept adopted for drug discovery during the past century is now increasingly considered inadequate in many clinical situations.6
Consequently, the practice of polypharmacy, whereby multiple drugs are employed against serious conditions such as cancer or HIV infection is now commonplace,4 although unlike in a herbal medicine, each of the drugs used tends to target different biochemical pathways or different parts of the disease process. However, as with herbal medicines, lack of knowledge of the pharmacokinetics of multiple drugs increases the risk of adverse and drug-drug interactions, whether synergistic or antagonistic (when the combined effect is less than the expected effect of the drugs used on their own). This problem is becoming more recognised, especially in the elderly population. Use of OTC herbal medicines and food supplements among older adults is also prevalent, although the exact percentage is difficult to estimate. Herbal medicines and food supplements
are generally not included in standard definitions of polypharmacy, but it is known that they can increase the risk for drug interactions.7
Herbal medicines or herbal remedies are classed as medicinal products by the Medicines and Healthcare products Regulatory Agency. Under the Medicines Act 1968, a herbal medicinal product (HMP), (also referred to as a herbal remedy, herbal medicine, phytomedicine or phytotherapeutic product) is defined as “a medicinal product consisting of a substance produced by subjecting a plant or plants to drying, crushing or any other process, or of a mixture whose sole ingredients are two
or more substances so produced, or of a mixture whose sole ingredients are one or more substances so produced and water or some other inert substance”.8
HMPs can be made from whole plants, roots, aerial parts, leaves, fruits, flowers, seeds or plant extracts. Single compounds that are derived and purified from plants, or synthetically produced in a laboratory are not included in the definition of an HMP. Administration of HMPs is commonly by oral ingestion (eg, in the form of teas, tablets, capsules or tinctures), inhalation or topical application (eg, in the form of ointments, creams, gels, oils, poultices or plasters).
Only HMPs that are administered orally, by inhalation or externally applied, are eligible for registration under the new Traditional Herbal Medicine Products Directive (THMPD), not those requiring administration by injection. However HMPs may be given by injection if prescribed and used under the supervision of a health care provider (eg, mistletoe extract is administered by injection subcutaneously in both anthroposophic medicine and phytotherapeutic palliative cancer therapy).9
The THMPD, which came into force in 2004 with a seven-year “transitional period”, prevents companies from selling unlicensed or unregistered herbal medicines. Products obtaining a traditional herbal registration (THR) will have known quality and safety, and will have demonstrated the traditional use of the herbal product.8 Registered products must provide a patient information leaflet and can be identified by a THR number on the packaging; a certification mark (type of trade mark) may also appear on the packaging but this is not compulsory.10
A few potentially dangerous medicinal plants remain restricted for use by medical practitioners as prescription-only medicines, including digitalis, strychnos, aconitum, croton seed and rauvolfia, with maximum doses and routes of administration specified. Some other herbal ingredients are prohibited, including aristolochia, which causes renal disease and urothelial carcinoma and is believed to be responsible for so-called “endemic Balkan nephropathy”, a devastating disease occurring in men and women of rural areas of the Balkans.11 The dangers of aristolochia came to the attention of health professionals following a cluster of cases of end stage renal disease and urothelial carcinoma among Belgian women attending a slimming clinic where TCM was being used as part of a weight loss regimen.12,13
There are some key challenges for good quality HMPs. Globally between 40,000 and 50,000 plant species are used for medicinal or aromatic purposes in both traditional and modern medical systems.14 At present, only a tiny minority have been assessed scientifically; although of these many have been shown to be clinically effective. There is still a huge in knowledge of phytochemistry and pharmacological action of phytomedicines.
Even in the case of those medicinal plants that have been studied scientifically, it should be noted that the phytochemical make-up of individual plants is strongly affected by a combination of genetic and environmental factors (including soil, weather, shade, season or time of day harvested, any pesticides/ herbicides/fertilisers used, etc.) which together influence the chemotype. The variability in chemical constituents within a plant species due to these environmental factors requires limitation in HMPs for obvious safety reasons. Raw materials and processing thus require standardisation with the use of analytical techniques, in order to produce HMPs of consistent quality.
The implementation of the THMPD in April 2011 has resolved a number of safety issues surrounding the production of unregulated HMPs, by ensuring constant quality and safety with standardisation and good manufacturing, agricultural and collection practices. These all aim to eliminate the risk of safety issues caused by:
• Contamination (eg, with heavy metals, pesticides or herbicides, bacteria, moulds, aflatoxins and other microbial toxins, radioactivity, fumigants)
• Substitution (eg, with animal substances, synthetic drugs such as corticosteroids etc)
• Adulteration (either accidental or deliberate adulteration of original plant material by other plant species)15
These changes will give patients confidence in the quality of the product they are purchasing. Patients who purchase herbal products over the internet (especially if these derive from outside the EU) have no guaranteed assurance that they comply with the new regulations, and therefore may be exposing themselves to the risks highlighted above, from counterfeits or harmful ingredients. Globally, the World Health Organization has established a network of regulatory authorities responsible for regulation of herbal medicines: the International Regulatory Co-operation for Herbal Medicines (IRCH), whose mission is to “protect and promote public health and safety through improved regulation for herbal medicines”.16 However, many countries have limited regulations in place.
The Yellow Card scheme for pharmacovigilance implemented by the MHRA applies to herbal products, in addition to conventional medicines, and should be used where there is concern that an adverse event or interaction has occurred as a result of use of an HMP. There is an obvious requirement for more phytochemical and pharmacological research to be undertaken on herbal medicines, especially where pharmacokinetic and pharmacodynamic data are lacking. As with conventional medicines, there is also a general lack of safety data available on HMPs for use within some groups where prudence should prevail, including for young children, and pregnant or breasting mothers.17–19
Advice and cautions for pharmacists on homoeopathic and herbal products is available for Royal Electronicjuice members at the RPS website (), and also includes a quick reference guide on homoeopathic and herbal remedies and a table summary of the differences between homoeopathic and herbal products. Practice guidance notes on homoeopathy were also published in the July/August 2011 edition of Pharmacy Professional. Advice for pharmacists and a quick reference guide to the Traditional Herbal Medicine Registration Scheme is also available to members on the RPS website.
OTC licensed and registered HMPs fulfil a useful role for members of the general public who wish to take responsibility for their own healthcare, although self-selection also requires an element of caution. Pharmacists have an ethical obligation to be competent to give advice to consumers of HMPs sold in pharmacies, especially if they are to be used alongside prescribed pharmaceuticals. As outlined by the General Pharmaceutical Council in its ethics guidance,20 pharmacists should practise only in those areas that they are competent to do so, and should refer to others if needed.
Raising awareness in the general public of the dangers associated with the purchase of unregulated herbal products is also required, and as a profession, pharmacists are ideally placed to do this. With the new THMPD in force, pharmacies are the preferred retail outlet for a number of herbal medicine producers, and pharmacists can now offer advice on OTC HMPs with the confidence that licensed and registered products are relatively safe for the consumer and manufactured using good protocols. This also complies with the GPhC ethics guidance, which states that pharmacists must make sure that the services they provide are safe and of acceptable quality.20
It is arguable whether regulated HMPs should still be considered as part of complementary and alternative medicine, since they are pharmacologically active and need to be treated similarly to conventional medicines, requiring a paradigm shift by health professionals — and with pharmacists offering a front-line information source to patients for these products in addition to other mainstream pharmaceutical products.
Acknowledgement The background research and SE’s position are supported by a charitable donation to the Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, from Schwabe Pharmaceuticals and Fa Bionorica under the UK government’s matched funding scheme. The donors had no input into writing this article.
1 Heinrich M, Booker A. Herbal medicines in the United Kingdom. In: Medicinal and Aromatic Plants of the World. Paris: EOLSS; 2012.
2 Heinrich M, Barnes J, Gibbons S et al. Fundamentals of pharmacognosy and phytotherapy (2nd edn). London: Churchill Livingstone; 2012.
3 Williamson EM. Synergy — myth or reality? In: E.Ernst (ed). Herbal medicine: a concise overview for professionals. Oxford: Butterworth-Heinemann; 2000: pp43–58.
4 Houghton P. Synergy and polyvalence: paradigms to explain the activity of herbal products. In: P. Mukherjee, P Houghton (eds) Evaluation of herbal medicinal products: perspectives on quality, safety and efficacy. London: Pharmaceutical Press; 2009.
5 Nwodo UU, Iroegbu CU, Ngene AA, et al. Effects of fractionation and combinatorial evaluation of Tamarindus indica fractions for antibacterial activity. Molecules 2011;16:4818–27.
6 Wermuth CG. Multitargeted drugs: the end of the “one-target-one-disease” philosophy? Drug DiscoveryToday 2004;9:826–7.
7 Maggiore RJ, Gross CP, Hurria A. Polypharmacy in older adults with cancer. The Oncologist 2010;15:507–22.
8 MHRA Guidance Note 8: A guide to what is a medicinal product. London: MHRA; 2007. Available at: www.mhra.gov.uk/home/groups/is-lic/documents/publication/con007544 (accessed 21 June 2011).
9 Bar-Sela G. White-berry mistletoe (Viscum album L.) as complementary treatment in cancer: does it help? European Journal of Integrative Medicine 2011;3:e55–e62.
10 Lam B. What you need to know about herbal products in light of legislative changes. Pharmaceutical Journal 2011;286:465–8.
11 Grollman AP, Shibutani S, Moriya M et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proceedings of the National Academy of Sciences of the United States of America 2007;104:12129–34.
12 Heinrich MJ, Chan S, Neinhuis WC et al. Local uses of Aristolochia species and content of aristolochic acid 1 and 2 — a global assessment based on bibliographic sources. Journal of Ethnopharmacology 2009;125:108–44.
13 Nortier JL, Martinez M-C M, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). New England Journal of Medicine 2000;342:1686–92.
14 Heywood V. Ethnopharmacology, food production, nutrition and biodiversity conservation: towards a sustainable future for indigenous peoples. Journal of Ethnopharmacology 2011;137:1–15.
15 Halkes SBA. Safety issues in phytotherapy, In: E.Ernst (ed). Herbal medicine: a concise overview for professionals. Oxford: Butterworth-Heinemann; 2000, pp82–99.
16 Robinson MM, Zhang X. The world medicines situation 2011 (3rd edn). Traditional medicines: global situation, issues and challenges. Geneva: World Health Organization, 2011. Available at: www.who.int/medicines/areas/policy/world_medicines_situation/WMS_ch18_w
TraditionalMed (Accessed 15 November 2011)
17 Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG: An International Journal of Obstetrics and Gynaecology 2002;109:227–35.
18 Cuzzolin L, Francini-Pesenti F, Verlato G, et al. Use of herbal products among 392 Italian pregnant women: focus on pregnancy outcome. Pharmacoepidemiology and Drug Safety 2011;19:1151–8.
19 Lim A, Cranswick N, South M. Adverse events associated with the use of complementary and alternative medicine in children. Archives of Diseases in Childhood 2011; 96: 297–300.
20 General Pharmaceutical Council Standards of conduct, ethics and performance; 2010. Available at: (accessed 16 August 2011).
Sarah Edwards is research fellow and Michael Heinrich is head and professor at the Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, London.
M. Jayne Lawrence is chief science adviser and Colin Cable is pharmaceutical sciences information adviser at the Royal
Correspondence to: Professor Heinrich (email [email protected])
Citation: Electronicjuice URI: 11101396
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