Quality, efficacy, and safety are parameters that are required for all medicines. These are particularly important to herbal preparations as they gain popularity. The past decade has witnessed significant worldwide growth in the use of medicinal herbs as teas and dietary supplements. Due to the increasing knowledge of both the traditional and scientifically documented benefits of herbs, consumers are now more likely to consider herbal remedies as a viable alternative to conventional medicines. The World Health Organization (WHO) estimates the total world market for medicinal botanicals to be about $60 billion.1 According to data cited in a report of the Secretariats of the Convention on Biological Diversity (CDB), sales of herbs in the United States increased from $1.6 billion in 1994 to $5.4 billion in 2000.2 In recent decades, the tremendous growth of the herbal sector has revealed the need for improved quality control in cultivation and collection of herbal raw material. Consistent and reproducible quality of herbal raw materials used for medicinal purposes is paramount for clinical efficacy and for the reproducibility of beneficial effects as observed in clinical studies. Furthermore, numerous safety issues depend on consistent composition of botanical ingredients.
Ideally, raw material for the production of herbal medicines will come from a traceable and reproducible source. In reality, the trading habits co-evolving with the growth of the market frequently obscure the origin of the plant material and facilitate adulterations, which, especially in the case of adverse events, have already damaged the reputation of otherwise relatively safe plants.
In February 2004, the WHO released “WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants,”1 which addresses quality issues in the production of herbal raw material. It covers recommendations that range from the selection of appropriate seed material and cultivation sites to the avoidance of contaminations in post-harvesting handling, training and working conditions of personnel, and general rules for handling and construction of tools and facilities. Some of the major issues and their practical implications are briefly discussed below.
Selection of appropriate plant/seed material
Though seemingly trivial, the selection of the correct species for cultivation is still of major concern. The replacement of species with seeds from species that are closely or less closely related is a common feature in modern plant trading, even though the required species is frequently defined in pharmacopeias, monographs, or other scientific literature. For example, large tracts of the world market of licorice (Glycyrrhiza glabra L., Fabaceae) root do not consist of batches of the species as defined in European Pharmacopoeia (Ph. Eur.) and United States Pharmacopeia (USP). Instead they come from G. uralensis, which is permitted by the Japanese pharmacopeia. The mixture of species of various origins, partly from uncontrolled and destructive wild harvesting, is frequently sold as G. glabra.
Another example is devil’s claw (Harpagophytum procumbens [Burch.] DC. ex Meisn., Pedaliaceae) secondary tuber from Namibia, where replacements of the root with material collected from H. zeyheri from Angola is increasingly observed.
In addition to the replacement of entire species, the question of chemotypes and cultivars must also be addressed. For instance, common thyme (Thymus vulgaris L., Lamiaceae) herb can be obtained that is rich in the phytochemicals thymol, geraniol, linalool, α -terpineol, trans-thujanol, and 1,8-cineol or carvacrol. Current trading practices often do not allow for a distinction between the thyme raw materials of various different origins, which very likely will have varying chemical profiles, and therefore, produce variations in the reproducibility of effects in pharmacological and clinical studies.
Finally, commercial orders for raw material of a given plant are often conducted using the local plant name or the English common names. These names are frequently not unique and in some cases are confusing or misleading. For example, the Siberian/Chinese adaptogenic plant eleuthero (Eleutherococcus senticosus [Rupr. & Maxim.] Maxim., Araliaceae) is frequently collected using the Chinese plant name, referring to physical attributes of the plant (five-fingered leaves, fleshy root), ci wu jia. This description not only may refer to completely unrelated plants, as was observed in a case report of a misplacement or substitution of eleuthero with the potentially toxic roots of Chinese silk vine (Periploca sepium Bunge, Asclepiadaceae),3 but it also obscures the fact that the genus Eleutherococcus (also referred to by its formerly accepted genus name Acanthopanax) contains dozens of botanical species, e.g., A. koreanus. While in the case of Eleutherococcus this does not appear to have a significant impact on the safety of the herb, there is nonetheless a question of reproducibility and reliability of clinical effects.
The WHO guidelines address this problem by stating the need for a proper botanical identification not only of the plant material, but also of the seeds used for cultivation. In GACP conform cultivation, the Latin binominal name and the definition of the subspecies/cultivar/chemotype (where applicable) must be laid down in the farmer’s documentation. The same documentation applies to plants issued from wild-harvesting, where the botanical identification should be even stricter than for plants grown under the controlled conditions associated with commercial cultivation, which would take the local phytochemical variability into account.
Selection of a suitable cultivation site and appropriate cultivation methods
As trivial as it may sound, the ecological and climatic conditions found on the cultivation site must meet the needs of the cultivated plant. Factors such as local rainfall, irrigation, water and soil quality, and local climate have an important impact on plant quality. Too often, a decision to cultivate medicinal plants on a given site is made, not based on the specific requirements of the plant, but on the availability of the agricultural surface. In recent years, cultivations of St. John’s wort (Hypericum perforatum L., Clusiaceae) in Poland were affected with phytosanitary problems (red ring-root), because the genus Hypericum naturally thrives in dryer climates. Similarly, the inappropriate plantation of kava (Piper methysticum G. Forst., Piperaceae) on former sugar cane fields on Fiji might have contributed to the spreading of the “kava dieback disease.” Kava dieback disease is most likely caused by mosaic virus,4 for which sugar cane is a host. The infection destroyed large parts of some local kava cultivars. Consequently, a poor choice of cultivation site may affect not only the local harvest, but, in extreme cases, can also have a global impact on biodiversity.
The WHO guideline provides recommendations for the choice of an appropriate cultivation site. It also points to the exclusion of sites with possible industrial contaminations with heavy metals, pesticides or herbicides, and radioactive contaminations. In practice this means that soil samples must be collected and analyzed. Wherever possible, suggests WHO, organic growing techniques should be employed, thus avoiding the use of herbicides or pesticides. In addition, the impact that growing herbs has on local biodiversity must be taken into consideration.
Harvesting and processing conditions
Harvesting time and methods are in close relation to phytochemical parameters. For example, St. John’s wort (SJW) was traditionally collected in the flowering season with fully developed flowers—a season when the content of hyperforin is relatively low. SJW harvested towards the end of the flowering season, with fruit formation more or less pronounced, leads to batches with considerably higher hyperforin content. Because this compound is now suspected to be a major contributing factor in the much publicized herb-drug interactions documented with the use of SJW,5-8 techniques that limit the hyperforin content in the SJW raw materials and preparations are currently being discussed. The simplest and most logical approach to achieve this goal is to choose an appropriate harvesting time.
Another practical example is artichoke (Cynara scolymus L., Asteraceae) where the leaves are collected in the preparation of choleretic (bile stimulating) and cholesterol-lowering herbal preparations. The harvesting time greatly affects the phytochemical composition and quality of artichoke leaves. The harvest of leaves as a by-product of vegetable production (i.e., the pre-flowering heads) leads to herbal products of lesser quality (albeit cheaper) than the production of dedicated artichoke cultivations for medicinal purposes only.
Conditions associated with processing raw materials, especially drying, frequently have a major impact on drug quality. Inadequate drying and storage leads to microbiological contaminations and changes in the phytochemical composition. Again, artichoke leaves are a practical example: the higher the drying temperature, the lower the content of caffeoyl quinic acids in the dried leaves; these acids (e.g., cynarine and derivatives) are associated with the leaves’ therapeutic effects.
A major part of the WHO guidelines cover the various aspects of harvesting, storage, and shipping. This section of the guidelines is essentially identical for cultivation and collection (wild harvesting or wildcrafting) of medicinal plants. In regard to harvesting times and post-harvesting processing, the guidelines refer to the specifications laid down in pharmacopeias, and/or experience published in the scientific literature. Cross-contamination during storage must be avoided, and organically grown material must be stored separately from conventionally grown herbs (i.e., herbs not grown organically and not certified as organic by an appropriate third party organization, regardless of whether the conventionally grown herbs have been sprayed with pesticides or not, or grown in artificially fertilized soil or not). The documentation of the harvest must contain essential indications that allow the identification and assessment of the key steps. With the measures outlined in the GACP guidelines, the best possible harvest-to-harvest reproducibility and a full traceability of the herbal raw material should be guaranteed.
Sustainability
Many medicinal plants are as yet unavailable from controlled cultivation. TRAFFIC (a division of the World Wildlife Fund) estimates that almost 75 percent of all botanical species in trade continue to be sourced from the wild.9 One of the major goals of the WHO GACP guidelines is to outline efficient, non-destructive, environmentally sound, and sustainable procedures not only for cultivation, but also for controlled collection. In the case of wildcrafting, the guidelines aim for the avoidance of negative impacts on plant population density and the maintenance of biodiversity. A major obstacle for sustainable collection projects is the over-harvesting of medicinal plants in uncontrolled wildcrafting, as can be observed with many plants such as devil’s claw in Southern Africa. However, methods for sustainable cultivation of devil’s claw were developed by Mathias Schmidt and Georges Betti (coauthors of this article), with the results being incorporated into large-scale cultivation projects conducted by firms such as the global botanical giant Martin Bauer.
Intellectual property rights
Almost hidden within the GACP guidelines is the issue of intellectual property rights for plants endemic to a certain region. The brevity of the statement that “All intellectual property rights with regard to source materials must be respected” may seem to understate the importance of this topic for which the practical implications are still under discussion. The guidelines call for a scientific botanical survey to outline the distribution and assess the abundance of the species to be cultivated.
A practical solution for the question of intellectual property rights would be to organize GACP projects in the regions where the plant naturally occurs. With this access, several problems are solved simultaneously:
• The plant grows in its natural habitat under conditions in which it is well adapted.
• There is no problem with intellectual property rights because the region the plant originates from immediately profits from the activities.
• GACP projects have a stabilizing impact on a regional economy, which is an important factor for the long-term sustainability of the cultivation.
Projects that ensure sustainability and quality in wildcrafting are not necessarily difficult to organize if addressed in a systematic manner. The authors are currently organizing projects that conform to GACP with a number of medicinal plants, and with some success thus far.
Mathias Schmidt, PhD, is a pharmacist with experience in GACP projects, specializing in quality issues related to herbal medicine: analysis, pharmacovigilance, toxicology, and clinical studies. He is affiliated with HerbResearch Germany, an herbal medicine research and consultancy company with extensive experience in the selection, validation, and supply of herbal medicines. E-mail: schmidt@herbresearch.de.
Michael Thomsen is an herbalist, Naturopath Research Associate, and course coordinator (herbal medicine) at the Graduate School of Integrative Medicine, Swinburne University, Melbourne, Australia. He is also Technical Director of HerbResearch International, based in Australia. E-mail: Michael.Thomsen@Herbresearch.com.au.
Georges Betti is an ethnobotanist, specializing in the identification of chemotypes/cultivars and GACP-conforming sustainable cultivation and collection of herbal raw material. He works at Medicinal & Aromatic Plants R&D in Sophia Antipolis, France. E-mail: plantech@cote-dazur.com.
References
1. World Health Organization. WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants. Geneva, Switzerland: World Health Organization; 2003. Available at: http://www.who.int/medicines/library/trm/medicinalplants/agricultural.pdf.
2. World Health Organization. WHO Traditional Medicines Strategy: 2002–2005. Geneva, Switzerland: World Health Organization; 2002. Available at: http://www.who.int/medicines/library/trm/trm_strat_eng.pdf.
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4. Davis RI. Dieback disease of kava, the greatest threat to large-scale production: What do we know? International Kava Conference, Suva, Fiji, December 2, 2002.
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