Plant food supplements themed issue

This issue is dedicated to a detailed analysis of regulatory, scientific and technical issues concerning safety, quality and efficacy of plant food supplements (PFS), i.e. foodstuffs, marketed namely in dose forms such as capsules, pastilles, tablets, pills and other similar forms, sachets of powder, ampoules of liquids, drop dispensing bottles, and other similar forms of liquids and powders. Plant food supplements (PFS) consist of botanical preparations obtained by subjecting plants to a variety of treatments such as extraction, expression, distillation, fractionation or concentration. This broad category of products have often been used for a long time to supplement the normal diet with additional natural nutrients or other natural substances with desirable physiological functions.

Very rarely the action of a plant food supplement can be attributed to specific single substances, because, in general, a consumer's exposure is to a highly complex mixture of primary and secondary (i.e. in response to specific stresses) metabolites of the plant (i.e. the so-called phyto-complex). As compared to their isolated constituents, phyto-complexes exhibit quite different properties, such as lower toxicity (e.g. salicine in comparison to salicicic acid) or higher bioavailability (e.g. increased solubility of hypericin in the presence of procyanidine). Moreover, the simultaneous presence of several components makes possible in some cases the expression of different activities (e.g. garlic may express hypo-cholesterolemic, calcium antagonist and anti free-radical activity).¹

There are several health-related issues when aiming to ensure efficacy and safety of plant food supplements.² They include: (i) the correct identification of the botanical species and variety used as source material for the supplement (e.g. see the similarity between Passiflora incarnata L., used against anxiety and insomnia, and Passiflora edulis L., completely inactive); (ii) the extreme variability of phyto-complexes obtained from the same species, variety and part of the plant depending on the characteristics of the culture environment, the plant developmental phase, the storage treatment after harvesting and the manufacturing process; (iii) the possible contamination of the source plant material with other plant products or with plant protection products;³ and (iv) the natural occurrence in the source plant material of undesirable substances because of their toxicity or psychotropic or addictive activities.^4,5 Moreover, the globalization of commerce has made available at a worldwide level cultivated and wild plant species once confined within specific geographical areas thus considerably increasing the risk of misuse.

Moreover, due to the fact that most users of botanical food supplements do not inform their medical doctors, when they undergo prescription of ethnical medicinal products, experience has shown the occurrence of a significant number of negative serious interactions deriving from the association of medicinal products and preparations from Aesculus hippocastaneum, Allium sativum, Aloe vera, Angelica sinensis, Arctostaphylos uva-ursi, Areca catechu, Borago officinalis, Capsicum spp., Carica papaya, Cola nitida, Crataegus laevigata, Cyamopsis tetragonolobus, Echinacea spp., Eleutherococcus senticosus, Ephedra spp., Ginkgo biloba, Glycyrrhiza glabra, Harpagophytum procumbens, Humulus lupulus, Hypericum perforatum, Melissa officinalis, Momordica charantia, Panax spp., Pausinystalia yohimbe, Plantago ovata, Rhamnus purshiana, Salvia miltiorrhiza, Senna spp., Serenoa repens, Tamarindus indica, Tanacetum parthenium and Valeriana officinalis.⁶ Also simultaneous exposure to several herbal products may result into collateral effects, such as acute and chronic hepatotoxicity and nephrotoxicity.^1,7–9

It is not surprising, therefore, that in a number of countries highly complex regulatory, scientific and technical mechanisms have been put in place to maximize benefits of plant food supplements and related products and minimize their risks.

In this context, the European Union has adopted a quite peculiar and particularly ambitious approach aiming at differentiating traditional food supplements expected to exert nutritional or physiological effects [Directive 2002/46/EC, article 2], and traditional herbal medicinal products expected to exert pharmacological, immunological or metabolic actions [Directive 2001/83/EC, article 1, 2b and Directive 2004/24/EC]. In fact, some plants contain substances that may be used to treat diseases. Medicinal products that are made from these substances are known as “Herbal Medicinal Products”. Even though they are natural, a number of these products may be dangerous for patients. This is why they are covered by pharmaceutical legislation, which aims to protect public health by ensuring the safety, efficacy and quality of medicinal products. Within the group of herbal medicinal products, some have a long tradition of use. European Union legislation classifies as traditional herbal medicinal products those herbal medicinal products that have been used for at least 30 years, including at least 15 years within the EU, are intended to be used without the supervision of a medical practitioner and are not administered by injection. Some examples of herbals used in traditional herbal medicinal products are: Calendula officinalis L.; Echinacea purpurea L., Moench; Eleutherococcus senticosus (Rupr. et Maxim.) Maxi; Foeniculum vulgare Miller subsp. vulgare var. vulgare; Foeniculum vulgare Miller subsp. vulgare var. dulce (Miller) Thellung; Hamamelis virginiana L; Mentha x piperita L. and Pimpinella anisum L. However, even a long tradition of use does not exclude concerns about the product's safety. Therefore competent authorities of the Member States are entitled to ask for additional data, if they deem it necessary, to assess the safety of the medicinal product. In summary, the Herbal Directive introduces a simplified procedure compared with the requirements of a full marketing authorization.

However, depending on the difference between phyto-complexes to be used as traditional food supplements or traditional medicinal products, which are quite specific in different EU Member States, the distinction of the botanical species and preparations used as traditional food supplements and medicinal products across EU Member States is highly problematic. In fact, a number of botanical species and varieties used for manufacturing food supplements in some EU Member States are also used to manufacture traditional medicinal products in other Member States. Therefore, the market of such products depends largely on the country under consideration, as a consequence of its medical and nutritional practices and on how competent National Authorities and manufacturing companies interpret and apply current EU regulations rather than on intrinsic properties of the botanical species and varieties.

Upon inception of the EU Research PlantLIBRA Project (see the last paper of this supplement for its objectives and strategies), it was considered particularly useful to undertake a review of the status of knowledge in the many above-mentioned relevant sectors in order to benchmark the level of current understanding and clearly indicate the main future knowledge needs. To this end, the present volume has been structured into 8 papers, starting from that on the “Regulations applicable to plant food supplements (PFS) and related products in the European Union”. Botanical species being more widely used for manufacturing PFS and related products are addressed in the second paper, whereas market structures in Member States and consumer attitudes and beliefs about PFS are dealt with in papers 3 and 4, respectively. Moreover, quality, efficacy and safety aspects associated with PFS are the main subjects of papers 5, 6 and 7.

References

1. F. Firenzuoli, “Fitoterapia clinica: opportunità e problematiche”, in Il ruolo delle piante officinali: Confine fra alimentazione e terapia, 2004, Istituto Superiore di Sanità, 7, maggio.
2. M. Silano and V. Silano, Prodotti di origine vegetale in medicina, alimentazione, erboristeria e cosmetica, 2006, Tecniche Nuove, Milano, p. 438.
3. E. Ernst, Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review, J. Int. Med., 2002, 252, 107–113.
4. EFSA Journal, 2009, 7(9), p. 281.
5. L. Caprino and M. C. Braganò, Gli integratori fitoterapici: uso e abuso, 2004, in Il ruolo delle piante officinali: Confine fra alimentazione e terapia, Istituto Superiore di Sanità, 7, maggio.
6. S. Garattini and M. Nobili, Interazioni fra farmaci, 2004, Selecta Medica, Milano.
7. D. M. Marcus and A. P. Grollman, Ephedra-free is not danger-free, Science, 2003, 3012, 1669–1671.
8. D. J. Smith and K. E. Olive, Chinese red rice-induced myopathy, South Med. J., 2003, 96(12), 1265–1267.
9. K. L. Willett, R. A. Roth and L. Walker, Hepatotoxicity for botanical dietary supplements, Toxicological Sciences, 2004, 79(1), 4–9.

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