Botanical species being used for manufacturing plant food supplements (PFS) and related products in the EU member states and selected third countries

Abstract

A great wealth of plants and plant derived preparations are used in the intention to supplement the basic nutrition in order to sustain and promote health. They may be used directly or consumed as manufactured plant food supplements (PFS) in dosed form. The use of these plants may already have a long tradition as fruit, vegetable or (folk) medicinal plants. Due to globalisation, more and more plants originating from all over the world are now offered and marketed in European countries, including species from China, South Africa and the American continent. For reasons of security, EU wide lists of plants accepted or prohibited to be used in food supplements are in elaboration. A crucial point is the correct identification of the plant material. The identity can be assessed by morphological, chemical and DNA specific methods. The active substances usable in PFS are secondary plant products that are often characteristic for certain plant groups (taxa), species or plant parts. They comprise not only polyphenols, essential oils, carotenoids and phytosterols, but also glucosinolates or saponins. The quality of the plant material used for PFS depends on a variety of factors, including the natural phytochemical, intraspecific variation with the occurrence of chemotypes, the ontogenetic variation, the considered plant parts and environmental influences during plant growth. In the production of the raw materials for PFS international standards (good agricultural practice, fair trade) should be applied.

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Introduction

Plants as primary producers in ecosystems are also the basis of human nutrition. Until the 1950s, the main purpose of the use of plants and plant products was feeding the body with essential nutrients (carbohydrates, lipids, proteins), followed by the knowledge on minerals, vitamins and crude fibre. Secondary substances – so far – have mainly been perceived as flavourings and colorants or even as antinutritive or toxic, and many edible plants have been selected over centuries towards low content of secondary substances like e.g.alkaloids or tannins. Only since the 1980s has the significance of the so called phytochemicals risen and their functionality in the body become more and more evident, although not yet fully understood.^1,2 In the course of it many well known plants or substances have been ‘rediscovered’ and food supplements have been generated. In particular, traditionally used plants and ethno-botanically interesting species – also from many parts of the world – came into the centre of interest, and a number of botanicals are used both as herbal medicinal products as well as food supplements. The actual trend was remarkably influenced by the US Dietary Supplement Health and Education Act of 1994 where almost all herbal products in the US obtained the status of food supplements or related products rather than drugs. Depending on the national legislation of EU member states, however, further development was either open for uncountable plant food supplements or more restricted towards medicinal products. The number of botanical species accepted and/or used therefore varies largely.

Databases and other compendia on plants used in PFS

A wealth of plants has been used since ancient times for nutritional and paranutritional purposes. Widely used food plants and their constituents are today well documented in a number of compendia,^3–5 where many plants used as sources of food supplements are also included. More recently, internet databases have been established, such as, for instance, eBASIS (Bioactive Substances in Food Information Systems) listing the composition and biological effects of over 300 major European plant foods, or the Nettox database covering 334 major European food plants and plant parts, both installed by EuroFIR (European Food Information Resource) Network of Excellence. (http://www.eurofir.net/eurofir_aisbl/membership_benefits/eurofir_ebasis) (http://www.eurofir.net/publications/eurofir_nettox_plant_list).

As regards plant food supplements (PFS), uncountable literature appeared over the last two decades dealing with plants from all over the world, their main compounds, effects and possible uses.^6–9 Such plant products as supplements for food originate from a long tradition where the consumption of herbal infusions, digestives, juices, elixirs and extracts had the purpose to maintain and promote health. Due to the regional cultural heritage, the lists of plants suitable for nutrition and health purposes or plants that must not be used in food related products vary widely. Besides ethnobotanical surveys dealing with edible and healing plants – as compiled e.g. for several East Asian, Latin-American and African regions by the authors of “Eating and Healing”⁹ – compendia of plants to be generally used for or that are prohibited in food supplements were first published on a national level in Europe at the end of the 1990s. For instance, Belgium issued in 1997 a list with more than 300 plants that are forbidden to trade as food or a food component, as well as a list of more than 450 plants that may be used for PFS but the respective products have to be notified.¹⁰ The Italian Ministry of Health published in 2011 a list with several hundred entries of plant parts usable in food supplements and a list of almost 400 entries with plants and plant parts not to be used in food products.¹¹ On the other side, the Austrian Ministry of Public Health listed in 2005 only 63 plants prohibited for use in PFS and specified just 13 species that may be used without limitations.¹² Frequently, as well as just sporadically, listed species are exemplarily shown in Table 1, and it should be pointed out that all the respective lists are open to novelties but also for restrictions. The evaluation of certain critical plants may vary from one national list to another. For instance Galega officinalis is allowed to be used in Italy but not in Belgium, Romania and Austria. A range of plants used in Belgium and Italy should not be consumed in Austria, including Cimicifuga racemosa, Crataegus sp., Fumaria officinalis, Hypericum perforatum, Sanicula europaea, Solidago virgaurea, Tanacetum parthenium, Tribulus terrestris and Vitex agnus castus. Finally Cytisus scoparius, which should not be used in Italy, Belgium and Romania, can be present as an ornamental drug up to 1% in mixtures in Switzerland.

Table 1 Examples of plants used in food supplements according to various national lists^a

Plant species	Botanical family	Presence in European national lists
		D^b	I	A^c	B	RO	CH^d
a A: Austria, B: Belgium, CH: Switzerland, D: Germany, I: Italy, RO: Romania. b Plants that are available in Germany for use in food supplements according to Noweda 2007. c The Austrian list of plants that can be used without limitations in food supplements contains only 13 species. Other accepted species are not listed officially. d From a list of the Swiss federal office for Health classifying botanicals in medical products and foodstuffs (Schweizerisches Bundesamt für Gesundheit 2005).
Carum carvi	Apiaceae	x	x	x	x	x	x
Coriandrum sativum	Apiaceae	x	x		x	x	x
Foeniculum vulgare	Apiaceae	x	x		x	x	x
Levisticum officinale	Apiaceae	x	x		x	x	x
Panax ginseng	Araliaceae	x	x		x	x	x
Serenoa serrulata	Arecaceae	x	x		x	x	x
Cynara scolymus	Asteraceae	x	x		x	x	x
Silybum marianum	Asteraceae	x	x		x	x	x
Taraxacum officinale	Asteraceae	x	x		x	x	x
Betula sp.	Betulaceae	x	x		x	x	x
Eruca sativa	Brassicaceae	x	x
Lepidium peruvianum (Maca)	Brassicaceae	x	x		x		x
Opuntia ficus indica	Cactaceae	x	x		x		x
Humulus lupulus	Cannabaceae	x	x		x	x	x
Rhodiola rosea	Crassulaceae	x	x		x		x
Dioscorea sp.	Dioscoraceae	x	x		x		x
Vaccinium macrocarpum	Ericaceae	x	x		x	x	x
Tamarindus indica	Fabaceae	x	x		x	x	x
Trifolium pratense	Fabaceae	x	x		x	x	x
Trigonella foenum graecum	Fabaceae	x	x		x	x	x
Gentiana lutea	Gentianaceae	x	x		x	x	x
Melissa officinalis	Lamiaceae	x	x		x	x	X
Rosmarinus officinalis	Lamiaceae	x	x		x	x	X
Salvia officinalis	Lamiaceae	x	x		x	x	X
Cinnamomum zeylanicum	Lauraceae	x	x		x	x	X
Olea europaea	Oleaceae	x	x		x	x	X
Pinus sp.	Pinaceae	x	x		x	x	X
Cimicifuga racemosa	Ranunculaceae	x	x		x	x	X
Aronia melanocarpa	Rosaceae	x	x		x		X
Crataegus laevigata/monogyna	Rosaceae	x	x		x	x	X
Rosa canina	Rosaceae	x	x		x	x	X
Schisandra chinensis	Schisandraceae	x	x		x	x	X
Camellia sinensis	Theaceae	x	x		x	x	X
Urtica dioica	Urticaceae	x	x		x	x	X
Vitex agnus castus	Verbenaceae	x	x		x	x	X
Alpinia galanga	Zingiberaceae	x	x		x	x	X
Curcuma longa	Zingiberaceae	x	x		x	x	X

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The first attempts to consolidate over the EU the lists of generally accepted or prohibited plant species in food supplements started in the middle of the 2000s together with the discussion on health claims. In 2009 the European Food Safety Authority (EFSA) published a compendium of plants and plant parts with adverse effects pointing out possible concerns to human health. It includes not only species of genera such as e.g. Aconitum, Colchicum or Senecio containing toxic alkaloids, but also lovage (possibly photosensitizing), mango (peel possibly allergenic), walnut fruit and basil (possibly mutagenic), and finally pomegranate containing alkaloids in the tree bark, although usually the fruit pulp is consumed. Just recently, EFSA issued a new version of the “draft compendium of botanicals and botanical preparations that have been considered for food and/or food supplement use and have been reported to have also medicinal use” (http://www.profitocoop.com.ar/xls/compendium2.pdf, 24.03.2011). This compendium lists more than 500 botanical species in alphabetical order without any judgement about safety. There is the intention to periodically update both mentioned compendia by EFSA. The European Botanical Forum¹³ reviews and consolidates a European Negative List of “Prohibited Plants in selected EU and Candidate Countries” (http://www.botanicalforum.eu/uploads/EBF.TFG4.EU%20neg.list.version.2.pdf), and a consolidated list of plant species being accepted as food supplements is in preparation.

As the use of Chinese plants becomes more and more popular, a list containing about 230 botanicals used as food supplements or functional food in China has very recently been prepared¹⁴ and many of these plant products can already be found on the European market. Altogether in Europe and other countries, such as China, South Africa, as well as Latin American states, almost 1000 plant species or plant parts are used in PFS, and a selection of typical examples (families, genera, species and constituents) is given in Tables 2 and 3. Concerning the use of a new plant, plant part or plant product not yet consumed in Europe as food, the Novel Food Regulation EC 258/97 has, however, to be taken into consideration if this species or products thereof should be marketed in the EU.

Table 2 Examples of plants used in food supplements in China

Plant species	Family	Plant part
Plants that are also found in European lists, although often not of European origin:
Foeniculum vulgare	Apiaceae	Fruits
Panax ginseng	Araliaceae	Roots, Leaves, Fruit
Arctium lappa	Asteraceae	Fruits, Roots
Cichorium intybus	Asteraceae
Brassica juncea	Brassicaceae	Seeds
Raphanus sativus	Brassicaceae	Seeds
Cassia angustifolia	Caesalpiniaceae	Leaves
Cannabis sativa	Cannabaceae	Seeds
Diosporus lotus	Ebenaceae	Fruits
Hippophae rhamnoides	Elaeagnaceae	Fruits
Vaccinium vitis-idaea	Ericaceae	Fruits
Glycyrrhiza glabra	Fabaceae	Rhizome, Roots
Tamarindus indica	Fabaceae	Fruits
Trigonella foenum-graecum	Fabaceae	Seeds
Rosa spp.	Rosaceae	Flowers, Fruits
Ginkgo biloba	Ginkgoaceae	Seeds
Morus alba	Moraceae	Bark, Leaves, Fruit
Myristica fragans	Myristicaceae	Seeds
Eugenia caryophyllea	Myrtaceae	Buds
Rheum palmatum	Polygonaceae	Roots
Prunus spp.	Rosaceae	Fruits
Citrus aurantium	Rutaceae	Fruits
Schisandra chinensis	Schisandraceae	Fruits
Alpinia officinarum	Zingiberaceae	Rhizome
Curcuma longa	Zingiberaceae	Rhizome
Zingiber officinale	Zingiberaceae	Rhizome
Other species from genera that are also present in Europe:
Allium macrostemon	Alliaceae	Bulbs
Allium chinensis	Alliaceae	Bulbs
Angelica dahurica	Apiaceae	Roots
Angelica sinensis	Apiaceae	Roots
Ligusticum chaanxiong	Apiaceae	Rhizome
Asparagus cochinchinensis	Asparagaceae	Roots
Taraxacum mongolicum	Asteraceae	Herb
Glycyrrhiza uralensis	Fabaceae	Rhizome
Glycyrrhiza inflata	Fabaceae	Rhizome
Phaseolus calcaratus	Fabaceae	Seeds
Phaseolus angulatus	Fabaceae	Seeds
Salvia miltiorrhiza	Lamiaceae	Roots
Plantago asiatica	Plantaginaceae	Seeds, Herb
Cimicifuga heracleifolia	Ranunculaceae	Rhizome
Cimicifuga dahurica	Ranunculaceae	Rhizome
Cimicifuga foetida	Ranunculaceae	Rhizome
Crataegus pinnatifida	Rosaceae	Fruits
Prunus spp.	Rosaceae	Seeds
Rubus chingii	Rosaceae	Fruits
Plants with no tradition in Europe (until recently)
Apocynum venetum	Apocynaceae	Leaves
Epimedium spp.	Berberidaceae	Stems, Leaves
Cordonopsis pilulosa	Campanulaceae	Roots
Platycodon grandiflorum	Campanulaceae	Roots
Terminalia chebula	Combretaceae	Fruits
Eucomia ulmoides	Eucomiaceae	Bark, Leaves
Astragalus complanatus	Fabaceae	Seeds
Pueraria thomsonii	Fabaceae	Roots
Pueraria lobata	Fabaceae	Roots
Psoralea cordifolia	Fabaceae	Fruits
Magnolia officinalis	Magnoliaceae	Bark, Flower buds
Nelumbo nucifera	Nymphaeaceae	Leaves, Seeds
Ligustrum lucidum	Oleaceae	Fruits
Dendrobium sp.	Orchidaceae	Stems
Paeonia lactiflora	Paeoniaceae	Roots
Polygala tenuifolia	Polygalaceae	Roots
Hovenia spp.	Rhamnaceae	Seeds, Fruits
Euvodia rutaecarpa	Rutaceae	Fruits
Amomum villosum	Zingiberaceae	Fruits
Plants with possibly toxic compounds:
Polygonatum odoratum	Asparagaceae	Rhizome
Sophora japonica	Fabaceae	Flowers, Fruits
Fritillaria spp.	Liliaceae	Bulbs
Lilium spp.	Liliaceae	Bulbs
Tribulus terrestris	Zygophyllaceae	Fruits

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Table 3 Examples of plants used in South and Central America as medicinal foods^a,b

Plant species	Botanical family	Plant part	Used in
a BO: Bolivia (Vandebroek 2006), BR: Brazil, BR-A: Brazil – Atlantic Coast (Hanazaki 2006), CU: Cuba (Volpato 2006). b These plants used by the local populations are usually not present in dosed portions but they also intend to supplement the basic nutrition.
Allium cepa	Alliaceae	Bulbs	BR
Amaranthus sp.	Amaranthaceae	Leaves	BR, BO
Schinus molle	Anacardiaceae	Leaves	BO
Anacardium occidentale	Anacardiaceae	Fruits	BR, CU
Mangifera indica	Anacardiaceae	Fruits	BR,CU
Spondias purpurea	Anacardiaceae	Fruits	CU
Foeniculum vulgare	Apiaceae	Leaves	CU
Petroselinum crispum	Apiaceae	Leaves	BR
Hipochaeris brasiliensis	Asteraceae	Leaves	BR
Sonchus oleraceus	Asteraceae	Leaves	BO
Lepidium meyenii	Brassicaceae	Roots	BO, Br
Nasturtium officinale	Brassicaceae	Leaves	BR, CU
Brassica oleracea	Brassicaceae	Leaves	BR
Brassica rapa	Brassicaceae	Leaves, Flowers	BO
Bromelia pinguin	Bromeliaceae	Fruits	CU
Opuntia ficus-indica	Cactaceae	Fruits	BO
Carica papaya	Caricaceae	Fruits	BR, CU
Cucurbita sp.	Cucurbitaceae	Fruits	BR, CU
Citrullus lanatus	Cucurbitaceae	Fruits	BR
Momordica charantia	Cucurbitaceae	Fruits	CU
Phyllantus acidus	Euphorbiaceae	Fruits	CU
Melilotus indicus	Fabaceae	Herb	BO
Tamarindus indica	Fabaceae	Seeds	CU
Erodium cicutarium	Geraniaceae	Herb	BO
Rosmarinus officinalis	Lamiaceae	Herb	BR, BR-A
Salvia haenkei	Lamiaceae	Herb	BO
Salvia orbignaei	Lamiaceae	Herb	BO
Persea americana	Lauraceae	Fruits	BR, CU
Eugenia spp.	Myrtaceae		BR-A
Psidium sp.	Myrtaceae		BR, BR-A, CU
Syzygium cumini	Myrtaceae		BR-A
Pimenta dioica	Myrtaceae	Leaves	CU
Passiflora umbilicata	Passifloraceae	Fruits, Flowers	BO
Passiflora molissima	Passifloraceae	Fruits, Flowers	BO
Gouania polygala	Rhamnaceae	Bark	CU
Prunus persica	Rosaceae	Fruits	BO
Citrus sp.	Rutaceae	Fruits	BR, BR-A, CU
Castilleja pumila	Scrophulariaceae	Herb	BO
Smilax domingensis	Smilacaceae	Rhizome	CU
Guazuma ulmifolia	Sterculiaceae	Fruits	CU

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Most important species and their systematic and chemotaxonomical classification

History of use

Most of the plants used as PFS have a record as use in herbal medicine, including applications in folk medicine (see Tables 2 and 3). Many of these plants have a long tradition as herbal teas. There is no precise border in the use of a plant to cure or to prevent the disease or to simply improve the quality of life. The idea is that a plant suitable to cure a given disease may be – in smaller doses – beneficial for health, also with view of preventing the dysfunction. Indigestion or a little fatigue as a consequence of a stress situation is not considered as a disease by the consumer but can be presumably mitigated by the use of PFS.

There are also plant species used for multiple purposes as food, as ingredient like food seasoning, as plant food supplements or as medicinal products. Examples are garlic, ginger or hawthorn.¹⁵ Additionally, various species used as PFS are also used for cosmetic purposes.

Plants used for a long time in Europe are, for instance, dandelion (Taraxacum officinale), often also regarded as a weed, which had various applications for centuries and is now found in supplements for healthy maintenance of the urinary system, bilberry (Vaccinium myrtillus) in PFS for the maintenance of eye-sight, lemon balm (Melissa officinalis) used as a supplement in digestion and to support relaxation and general well being.¹³

The last few decades has brought a wide range of plants used in other continents to Europe, there are plants from Traditional Chinese Medicine (TCM) with e.g. ginseng and ginkgo as the most prominent ones, or plants from South Africa e.g. rooibos (Aspalathus linearis) and to a lesser extent honey bush tea (Cyclopia sp.) or Hoodia gordonii to regulate the appetite. Also some exotic fruits, such as acerola (Malpighia glabra) from South America, that are rich in vitamin C are on the PFS market, but in Latin America itself species of the families Anacardiaceae, Brassicaceae, Cucurbitaceae and Myrtaceae are predominantly used as health food.

The search for new ideas in developing PFS also frequently resulted in the use of plant parts rich in active substances from species having another traditional record, as e.g. red wine leaves, grape seeds, olive leaves or green tea extracts. Using other parts of edible plants than those traditionally consumed, by-products or specific extracts needs careful phytochemical characterization and safety evaluation, and sometimes such products are supposed to be novel foods.

Active compounds

The intention to use PFS is based on the fact that these plants and extracts contain beneficial compounds not supplying the body with energy but aimed at sustaining health without curing diseases. These useful functional compounds are mainly found amongst the broad diversity of plant secondary metabolites that are often specific for certain plants or plant groups. Secondary products are classified according to their structures, properties or biosynthetic origin. Compound classes frequently appearing in PFS are polyphenols, essential oils, carotenoids and phytosterols, but also glucosinolates or saponins. Plant polyphenols present a very heterogeneous substance group, including cinnamic acid derivatives, flavonoids, anthocyanins, isoflavones and others. They are of various biosynthetic origins and bear at least an aromatic ring and one or more hydroxyl groups displaying antioxidant activity, and are able to modulate several receptors. Essential oils are mixtures of low-molecular-weight volatiles consisting mainly of mono- and sesquiterpenes and phenylpropenes. Besides of their flavouring, antimicrobial and beneficial gastrointestinal effects some of the compounds are supposed to be of safety concern. Alkaloids, as nitrogen containing, mostly strongly physiologically active compounds are – with the exception of e.g.caffeine – however, rather rarely found in PFS. But they could appear as trace compounds with toxic effects, as known from pyrrolizidine alkaloids.

Plant families and their main phytochemical characteristics

As mentioned above, secondary plant products are not randomly distributed over the plant kingdom but express the individual differences between and within the taxa. It is therefore easily understandable that, according to chemotaxonomical classifications, members of plant families containing the above mentioned functional products are more frequently found among source materials for PFS, as e.g. representatives of the Rosaceae, Lamiaceae or Zingiberaceae. Nevertheless, occasionally also species of other (sometimes small) plant families are used, and in this context hops, pomegranate or ginkgo might be mentioned. To more easily understand, important plant families with a range of species used as PFS should be mentioned in brief:

Rosaceae (Rose family): The most prominent functional products are polyphenols – tannins as well as anthocyanidins – and vitamins. Important plants are hawthorn (Crataegus sp.), dropwort (Filipendula ulmaria), dog rose (Rosa canina), strawberry (Fragaria × ananassa) berries of the genus Rubus (R. chamaemorus, cloudberry; raspberry, R. idaeus; bramble, R. fruticosus) and fruit trees like apple, pears, apricots, plums or cherries.

Ericaceae (Heather family): The valuable secondary compounds are anthocyans and tannins. Most frequently used species are bilberry (Vaccinium myrtillus), American cranberry (Vaccinium macrocarpum) and blueberry (Vaccinium corymbosum).

Fabaceae (Leguminosae family): The main active compounds are isoflavones, well known as non-steroidal ‘phytoestrogens’, coumarins, but some species also contain undesired substances, such as lectines. Commonly used species are fenugreek (Trigonella foenum-graecum), red clover (Trifolium pratense), soy (Glycine max), ribbed melilot (Melilotus officinalis) and liquorice (Glycyrrhiza glabra).

Apiaceae (Carrot family): The main active substances are essential oils. Some species contain, however, substances problematic to health like furocoumarins, alkenylphenols or polyacetylenes. The most used species are fennel (Foeniculum vulgare), caraway (Carum carvi), aniseed (Pimpinella anisum), parsley (Petroselinum crispum), lovage (Levisticum officinale) but also vegetables, such as carrots (Daucus carota).

The Araliaceae (Ivy family), also with flowers in umbels, are closely related to the Apiaceae. Ginseng (Panax ginseng) and Eleutherococcus species are prominent members of this family.

Asteraceae (Compositae family): Members of this family contain essential oils, lignans, bitter substances and flavonoids. Plants frequently used in food supplements are chamomile (Chamomilla recutita), milk thistle (Silybum marianum), artichoke (Cynara scolymus) and dandelion (Taraxacum officinale).

Lamiaceae (Deadnettle family): The main active constituents are essential oils, phenolic acids (e.g.rosmarinic acid) as antioxidative compounds and flavonoids. The family comprises many aromatic plants used as spices, condiments, and medicinal plants. Prominent examples are thyme (Thymus vulgaris), lemon balm (Melissa officinalis), mints (Mentha spp.) oregano (Origanum sp.), sage (Salvia sp.) and rosemary (Rosmarinus officinalis).

Further frequently used plants in food supplements are garlic (Allium sativum, Alliaceae), St. John's wort (Hypericum perforatum, Hypericaceae), valerian (Valeriana officinalis, Valerianaceae), common nettle (Urtica dioica, Urticaceae), wine (Vitis vinifera, Vitaceae), black cohosh (Cimicifuga racemosa, Ranunculaceae) and green tea (Camellia sinesis, Theaceae). Some novel input, in addition, can be expected from South American species (Table 3).

Useful plants with harmful compounds

Some useful plants contain, as minor compounds, substances with adverse effects that may restrict or even prohibit their uses. Prominent examples are the pyrrolizidine alkaloids. Due to the high toxicity of the 1,2-unsaturated alkaloids plants containing these molecules should not be used as food supplement. Species concerned are comfrey (Symphytum officinale and S. × uplandicum) and borage (Borago officinalis), both Boraginaceae, as well as coltsfoot (Tussilago farfara, Asteraceae).^16,17Extraction technology or plant selection allows alkaloid free products, such as seed oil from borage, to be obtained. Through selection and in vitro propagation a coltsfoot variety was established with alkaloid-free leaves.¹⁸

Identification and authentication

The most crucial points in using plants, plant parts and extracts as starting material for plant food supplements are the identity of the species, the plant part used, and the chemotype. In contrast to medicinally used plants where the basic requirements are compiled in the pharmacopoeias or similar monographs¹⁹ or to food plants described in the Codex Alimentarius, respective monographs concerning the quality requirements for PFS are lacking. But risk-benefit-assessment will only be possible if the respective data are well documented.

Identification and authentication of the plant material

The correct botanical identification is the first crucial point to avoid confusion, admixtures or adulterations in the production of PFS. Characters and traits that can be used to identify the plant material can be grouped into different categories:

1) (Macro-)morphology: in this category easily visible characters are described. This method of identification can be applied when complete plant specimens are present. All relevant characters that are present on roots, leaves, stems, flowers and fruits must be consulted. The morphological description of plants can be found in a ‘Flora’ where all occurring wild growing plants of a given region are compiled and described. For Europe the most prominent compendia are the Flora Europaea,²⁰ and the national floras.^21–25 Some Floras e.g. the Flora of North America and the Flora of China, are already present on the World Wide Web (http://www.efloras.org).

2) Microscopy: In many cases the plant material used is not available as a whole but traded as plant parts or in cut drugs. Microscopic characters comprise the structure of hairs on plant surfaces, the presence of crystals in the tissues or the occurrence of specialised cells. The characteristics can be found in the monographs of various pharmacopoeias or other compilations and monographs.^26,27,19,28

3) Phytochemical characters. A fingerprint of these compounds is usually characteristic for a given plant or plant part. The compounds analysed may be the active substances, but quite often characteristic marker substances only. In the case of medicinal plants this information is also available from the above mentioned pharmacopoeias and monographs. The chemical fingerprints obtained by thin layer chromatography of plant drugs are also documented in some laboratory manuals.^29,30

4) During the last two decades a further strategy for plant identification has emerged based on DNA sequences. The DNA sequence is unique for an individual and similar between closely related individuals. Some DNA regions are conserved within a specific taxon but differ between taxa. These parts of the DNA sequence can be used to study the relationship of taxa (phylogeny) or to identify a specific taxon, often referred to as “DNA-barcoding”.³¹ Most of the DNA based methods use a polymerase chain reaction (PCR) to amplify the DNA region of interest in vitro. Therefore they can also be applied in processed products where only very minor amounts of DNA are to be found, as is the case in plant extracts.³² Another advantage of such DNA based methods is their independence from environmental influences.

Panax is a genus with some very important species used as PFS, like P. ginseng, P. quinquefolius and many more. The roots are sold at high prices, are difficult to distinguish and many adulterations are on the market. Therefore, a multitude of different DNA based methods for the unambiguous identification of Panax species were developed.^33–48 Further DNA based methods of medicinal plants and plants used as PFS were recently reviewed by Sucher and Carles⁴⁹ and Heubl.⁵⁰

Admixtures and adulterations

Adulterations and confusions arise often from morphological similarities of the used plant parts. They may be fatal when the confused plants are toxic. Well reknowned is the example where leaves of Digitalis lanata have been taken instead of plantain leaves (Plantago lanceolata).^26,51 Another serious confusion of Chinese herbs is the mistake of the toxic Aristolochia fangchi instead of Stephania tetandra roots.^26,52 Intended adulterations, usually for profit maximisation, are in mixing or mislabelling species, spiking marker compounds or in using low cost substitutes. Examples are the confusion of the Echinaceae species or the admixture of buckwheat (Fagopyrum esculentum) or Sophora japonica to Ginkgo biloba due to their similar flavonoid patterns.⁵³Hoodia gordonii, a South African plant used to regulate the appetite, has been reported to be substituted by morphologically similar cacti (Opuntia sp.). Ellagic acid has been added to pomegranate extracts without any declaration. Adulterations may be identified during quality control where the different analytical methods are applied, including morphological evaluation, microscopic examination or specific chemical analyses. The authenticity of specific compounds in essential oils may also be determined by chiral and stable isotope analysis.⁵⁴ Adulterations and confusions have also been reported in Chinese drugs. For instance the root drug of Angelica pubescens may be contaminated with roots from Angelica dahurica, Angelica apaensis, Heracleum moellendorfii, Heracleum candicans or Aralia cordata. A HPLC fingerprint can distinguish these adulterations.⁵⁵

Factors affecting the quality

Inter- and intra-specific phytochemical variation

As the chemical constituents are essential for use as PFS, knowledge of the chemical variability of the plants is of great importance. The chemical characteristics of a plant consist of the fingerprint of secondary compounds typically occurring in the considered plant or plant part. There are not only differences in the fitting of secondary products between different plant species but also within a given species, the latter called chemotypes.

The occurrence of chemotypes is quite common and obvious in plants bearing essential oils. A well known example is the difference between bitter and sweet fennel. Various Thymus species have been proven to be differentiated into several chemotypes. In the case of thyme (Thymus vulgaris) at least 6 different essential oil chemotypes are known. Plants of different chemotypes may even occur in the same population.^56,57 Chemotypes according the content of the sesquiterpenes bisabolol and the bisobolol oxides are well known in chamomile (Chamomilla recutita). Additionally, chemotypes differing in their apigenine derivatives⁵⁸ or their methoxylated flavonoids jaceidine and chrysosplenetin⁵⁹ have been described for this species.

Intra-individual variation between plant parts and depending on development stage

The production of secondary compounds is often restricted to specific plant parts or may vary considerably from one plant organ to another. In general, the accumulation of secondary products is also changing during plant development.

During the development from the flowers to the ripe fennel fruits, the percentages of fenchone and estragole in the essential oil are increasing while limonene, α-and β-phellandrene and fenchyl acetate are decreasing.⁶⁰Hypericin content of various Hypericum species was highest in the floral budding stage compared to the vegetative or fruiting stages.⁶¹ In Hypericum diurnal variations in the hypericin content have also been reported.⁶¹ The flower heads of chamomile contain more oil than the leaves and stems. Even within the flowerheads of chamomile, the oil from the ray florets is different compared to the oil of the disc florets.⁶² Also within a plant, leaves inserted at different heights on the stem and therefore of different age may present different essential oil compositions. For instance in oregano (Origanum vulgare ssp. hirtum) the p-cymene content was higher in the lower leaves and the carvacrol and γ-terpinene content higher in the upper leaves.⁶³

The plant secondary products assume, in general, an ecological function. The circumstance that, in many essential oil bearing plants, the highest oil yields can be recorded in the pre-blooming or blooming stage may be related to the function of essential oils as attractants of pollinators. In poisonous plants, on the other hand, the toxic secondary compounds act as antifeedant agents and accumulate preferentially in plant parts that are important for the further growth of the plant or the production of offspring. High levels of toxic pyrrolizidine alkaloids can be found in the young rosette leaves of Cynoglossum officinale⁶⁴ and the pyrrolizidine alkaloids of various Senecio species are accumulated mainly in the flower heads.⁶⁵

Environmental influences

The potential to produce a certain chemical pattern is genetically coded, but the gene expression can be induced or repressed by environmental factors.⁶⁶

The formation of secondary compounds in plants is highly dependent on climatic conditions: especially day length, irradiance, temperature and water supply. Tropical species follow the dry and rainy season in their vegetation cycle. Species of the temperate zones react more on a day length.⁶⁷ Other environmental factors, for instance soil properties, water availability or temperature, mainly influence the productivity of the respective plant species and therefore the yield of secondary plant products, but have little effect on the qualitative composition.^68,69 Environmental stress is also known to influence the production of secondary metabolites. The stress situation can be an abiotic stress or a biotic stress induced by the attack of microorganisms or herbivores. For instance it has been reported that a heavy metal stress induced the accumulation of the coumarins herniarin and umbelliferone in chamomile, while the concentration of ene-yne-dicycloethers decreased.⁷⁰

Herbivory is another important environmental factor that influences the production of secondary products by plants. There are numerous examples where the attack of herbivores induces the synthesis of defence compounds. In watermint (Mentha aquatica) undamaged plants emit the volatile pulegone, which attracts the beetle Chrysolina herbacea. Upon feeding, the plants start to built up and emit menthofuran, which is a repellent for the beetle.⁷¹

Wild collected vs. cultivated plants (including sustainability, CBD, agro-techniques)

Since prehistoric times mankind has gathered wild plants for different purposes, among them health care, prevention and well-being. With increasing demand for standardized, homogeneous raw materials in industrial societies, more and more wild species have been domesticated and systematically cultivated. Nevertheless, a high number of species is still collected from the wild due to the fact that

a) many plants and plant products are used for the subsistence of the rural population,

b) small quantities of the respective species are requested at the market only, which make a systematic cultivation not profitable, some species are difficult to cultivate (slow growth rate, requirement of a special microclimate),

c) market uncertainties or political circumstances do not allow investment in long-term cultivation, or

d) the market is in favour of “ecological” or “natural” labelled wild collected material.

Especially – but not only – in developing countries, parts of the rural population depend economically on gathering high-value plant material.

To regulate the sustainable use of biodiversity by avoiding over-harvesting, genetic erosion and habitat loss, international organizations like IUCN (International Union for Conservation of Nature), WWF/TRAFFIC and WHO have launched the Convention on Biological Diversity (CBD 2001), the Global Strategy for Plant Conservation (CBD 2002) and the Guidelines for the Sustainable Use of Biodiversity (CBD 2004) together. These principles and recommendations primarily address the national and international policy level, but also provide the herbal industry and the collectors with specific guidance on sustainable sourcing practices.⁷⁵ A standard for sustainable collection and use of medicinal and aromatic plants (ISSC-MAP) was issued first in 2004.

Domestication and systematic cultivation, in contrast, offers a number of advantages over wild-harvest:

a) avoidance of admixtures and adulterations by reliable botanical identification,

b) better control of the harvested volumes,

c) selection of genotypes with desirable traits, especially quality, and finally,

d) controlled influence on the history of the plant material and on post-harvest handling.

On the other side, it needs arable land and investments in starting material, maintenance and harvest techniques. Domesticating a new species starts with studies at the natural habitat. The most important steps are the exact botanical identification and the detailed description of the growing site. Scientific herbaria are, in general, helpful at this stage. In the course of collecting seeds and plant material a first phytochemical screening will be necessary to recognize chemotypes.^72,73 The phytosanitary constitution of wild populations should also be observed in order to be informed in advance on specific pests and diseases.

The first phase of domestication is a germplasm collection. In the next step the appropriate propagation method has to be developed. The appropriate cultivation method depends on the plant type – annual or perennial, herb, vine or tree – and on the agro ecosystem into which the respective species should be introduced. In contrast to large-scale field production of herbal plants in temperate and Mediterranean zones, small-scale sustainable agro forestry and mixed cropping systems adapted to the environment have the preference in tropical regions.⁷⁴ Parallel to the cultivation trials dealing with all topics from plant nutrition and maintenance to harvesting and post-harvest handling, the evaluation of the genetic resources and the genetic improvement of the plant material must be started to avoid the development of a detailed cultivation scheme with an undesired chemotype.

Contaminations, harvesting, post-harvest handling

In plant production, contaminations with heavy metals, damages caused by pests and diseases, and residues of plant protection products are to be taken into consideration. The most important toxic heavy metals are Cd, Hg, Pb and Zn, but also Cu, Ni and Mn may influence the plant growth severely and by that way also the essential oil and secondary compounds, as they may act as co-factors in the plant enzyme system. But as contaminants they often remain in the plant residues after extraction or distillation.^76,77 Some plant species, e.g. yarrow and chamomile, also accumulate heavy metals to a greater extent. This is, however, problematic for using the crude drug or for deposition of distillation wastes. The same is valid for the microbial contamination of the plant material. In contrast to organic production, where no use of pesticides is permitted, a small number of insecticides, fungicides and herbicides are approved for conventional herb production. The number, however, is very restricted, and limits for residues can be found in national law and international regulations, such as the European Pharmacopoeia.

Harvesting and the first steps of post harvest handling are the last part of the production chain of drugs. The harvest date is determined by the development stage or maturity of the plant or plant part. Harvesting techniques should keep the quality by avoiding adulterations, admixtures with undesired plant parts or contaminations, which could cause ‘off flavour’ in the final product. There are many technical aids, from simple devices to large-scale harvesters.

Post harvest handling comprises activities like washing, conserving (mostly drying), separation, cutting and storing. When cleaning plant materials by washing, the quality of the washing water is essential regarding possible contamination of the plant material. It is recommended that at least the last washing step should be performed with drinking water quality. Separation processes, like sieving, are used to separate wanted plant parts from unwanted plant parts but also things like stones, sand and metal parts. These processes are also important for protecting the consumer. The most critical part in post-harvest processing, however, is conserving the materials, especially by drying. The drying medium is air, which is often heated before use. Direct heating of the drying air is regarded as completely inappropriate as it may lead to contamination of the plant material by polycyclic aromatic hydrocarbons (PAHs). Therefore heat exchangers should be used (indirect heating). The drying temperature is the next critical factor as it has to be a compromise between increasing the velocity of drying by using higher temperatures to limit microbial growth and not damaging or losing valuable secondary compounds (especially essential oils) by too high drying temperatures. Salmonella and fungi producing toxic secondary compounds (mycotoxins), like aflatoxins and ochratoxins are amongst the most critical microbes that may contaminate plant materials.

When storing the material, pest infestation by insects and rodents has to be monitored and continuously controlled.

International standards (GACP, ISSC-MAP, fair trade, organic)

The quality and safety of medicinal plants as raw materials for pharmaceutical products, flavours and fragrances are of the highest priority from the consumer point of view. To meet the respective demands, standards as well as safety and quality assurance measures are needed to ensure that the plants are produced with care, so that negative impacts during wild collection, cultivation, processing and storage can be limited. To overcome these problems and to guarantee a steady, affordable and sustainable supply of PFS plants of good quality, in recent years guidelines for Good Agricultural and Wild Collection Practices (GACP) and standards for Sustainable Wild Collection (ISSC) have been established on national and international levels.

a) GA(C)P, guidelines for good agricultural (and collection) practice of medicinal and aromatic plants

First initiatives for the elaboration of such guidelines trace back to a round-table discussion in Angers, France in 1983, and intensified at an International Symposium in Novi Sad 1988.⁷⁸ A first comprehensive paper was published by Pank et al.⁷⁹ and in 1998 the European Herb Growers Association (EUROPAM) released a first version (Máthé and Franz 1999). The actual version can be downloaded from http://www.europam.net.

It was adopted and slightly modified by the European Agency for the Evaluation of Medicinal Products (EMA), and finally as Guidelines on good agricultural and collection practices (GACP) by the World Health Organization (WHO) in 2003.

All these guidelines follow almost the same concept dealing with the following topics: identification and authentication of the plant material, especially botanical identity and deposition of specimens; seeds and other propagation material, respecting the specific standards and certifications; cultivation, including site selection, climate, soil, fertilization, irrigation, crop maintenance and plant protection with special regard to contaminations and residues; harvest, with specific attention to harvest time and conditions, equipment, damage, contaminations with (toxic) weeds and soil, transport, possible contact with any animals, and cleaning of all equipment and containers; primary processing, i.e. washing, drying, distilling; cleanness of the buildings; according to the actual legal situation these processing steps including distillation – if performed by the farmer – is still part of GA(C)P; in all other cases it is subjected to GMP; packaging and labelling, including suitability of the material; storage and transportation, especially storage conditions, protection against pests and animals, fumigation, transport facilities; equipment: material, design, construction, easy to clean; personnel and facilities, with special regard to education, hygiene, protection against allergens and other toxic compounds, welfare.

A very important topic is finally the documentation of all steps and measurements to be able to trace back the starting material, the exact location of the field, any treatment with agrochemicals, and the special circumstances during the cultivation period. Quality assurance is only possible if the traceability is given and the personnel are educated appropriately.

b) ISSC-MAP

The international standard on sustainable wild collection of medicinal and aromatic plants (ISSC-MAP) is a joint initiative of the German Bundesamt für Naturschutz (BfN), WWF/TRAFFIC Germany, IUCN Canada and IUCN Medicinal Plant Specialist Group (MPSG). ISSC-MAP intends to ensure the long-term survival of MAP populations in their habitats by setting principles and criteria for the management of MAP wild collection.^75,80 ISSC-MAP includes legal and ethical requirements (legitimacy, customary rights and transparency), resource assessment, management planning and monitoring, responsible collection and collection area practices and responsible business practices. One of the strengths of this standard is that resource management not only includes target MAP resources and their habitats but also social, cultural and economic issues.

c) FairWild

The FairWild standard (http://www.fairwild.org) was initiated by the Swiss Import Promotion Organisation (SIPPO) and combines the principles of FairTrade (Fairtrade Labelling Organizations International, FLO), international labour standards (International Labour Organisation, ILO) and sustainability (ISSC-MAP).

d) Organic standards

Organic standards are a set of production standards for growing, storage, processing, packaging and shipping intending to produce plants with an absolute minimum of synthetic chemical inputs (fertilizers, pesticides, etc.) on soils free from synthetic chemicals. Furthermore, strict physical separation of organic products from non-organic products must be guaranteed. Many service marks are on the market promoted by individual certification bodies.

Conclusions

Some 500–1000 plants and/or plant parts are used in PFS in Europe and third countries as China and South Africa. EU wide lists of plants accepted or prohibited for being ingredients of food supplements are in elaboration; there are, however, guidelines for quality control and standard monographs for plants and extracts to be used in PFS still missing, due to that fact one can find substitutes of related species or similar looking or named botanicals, other plant parts of the same species, or at least another chemotype.

As regards quality assurance, plant identification is crucial to guarantee that the right plant raw material has been used, and on the other hand to detect possible admixtures, adulterations and confusions. Identification should be carried out combining various methods, including macroscopic and microscopic examination, chemical fingerprinting and DNA based characterisation. The useful active compounds in plants for food supplements are amongst the huge diversity of secondary plant products that are often specific for certain plants or plant groups. Quality control of plants that are manufactured for food supplements has to consider the plant identification, natural biological variability, the use of the correct plant part, quality influencing factors during plant production and finally the influence of harvest and post harvest technology. Only under these circumstances and with complete documentation of all relevant data, can high quality PFS be assured. Following this direction, a promising development in this expanding field can be expected, contributing beneficially to health and well being.

Acknowledgements

This report has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement n°245199. It has been carried out within the PlantLIBRA project (website: http://www.plantlibra.eu). This report does not necessarily reflect the Commission’s views or its future policy in this area. The authors are deeply grateful to Elizabeth de Souza Nascimento, University of Sao Paolo, Maija Salmenhaara, Finnish Food Safety Authority Evira, Mihaela Badea, Universitatea Transilvania din Brasov and Ivonne M. C. M. Rietjens, Wageningen University for supporting us with information on national PFS lists.

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Footnote

† This paper forms part of the themed issue on Plant Food Supplements: regulatory, scientific and technical issues concerning safety, quality and efficacy.

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