Panel discussion on...
The importance of the supply chain to produce
high-quality botanicals: challenges of today and tomorrow
The overall quality of a botanical food supplement depends on the plant material used in its manufacturing process, but plant extracts, unlike other raw materials that may be present in a food supplement, such as vitamins and minerals, are extremely complex matrices, consisting of countless chemical compounds. This mixture is collectively referred to as the "phytocomplex" and contributes to the biological activity of the extract (1). While the phytochemical profile, or fingerprint, remains constant over time and, until the advent of PCR techniques, was considered sufficient for the qualitative identification of a plant drug, the quantity of each bioactive compound is largely influenced by different parameters, such as plant growth and environmental conditions, the stage of harvesting, drying and storage techniques.
Due to the difficulty of standardizing all the compounds of the phytocomplex, normally a class of bioactive compounds (or a single compound) is chosen to be quantified (markers), on which to base the acceptability limits of the plant drug, the process intermediates, and the final extract. This should guarantee a plant extract with a reliable chemical composition (standardized extract) and constant reproducibility over time.
The choice of markers is generally based on literature data and official texts, such as Pharmacopoeias; in Europe, the main reference standard is the European Pharmacopoeia. Regardless of the bibliographical references used, the chosen markers, when possible, must relate to the “known therapeutic activity” of the plant drug, meaning that they are allegedly responsible for the effectiveness of the extract (2). In vitro and in vivo tests and even clinical studies can be performed on botanical extracts to prove the claimed effects, with the same scientific accuracy as chemical drugs.
However, besides standardization, with regard to the concentration of the chosen bioactive compounds during the production process, there are, in my opinion, two different schools of thought: one closer to the pharmaceutical world (favoring the extraction of a marker until an almost purified extract is obtained), and one closer to the herbal tradition (prioritizing the preservation of the plant phytocomplex); there are of course many intermediate possibilities between these two extremes and, in any case, the extraction conditions (used solvents, temperature, pH, etc.) operate a peculiar selection of the bioactive compounds, so there are as many different extracts as the extraction conditions used. The final destination of the food supplement must be also considered.
Beyond the regulatory aspects for which purified extracts in Europe can fall into the category of "Novel Food", unless a consolidated consumption before 15 May 1997 can be proved (3), there are undoubtedly many reasons to privilege the preservation of the phytocomplex; this is not only in allegiance with the traditional use: many studies have shown that the coexistence of different classes of bioactive compounds can influence different targets/pathways, giving place to synergy, or modulate the action of the main active compound, modifying its bioaccessibility and bioavailability (4) and therefore behaving differently than the isolated and purified molecules (5).
Another interesting topic is that the different classes of bioactive compounds can counterbalance possible adverse effects (4, 6); this would explain why botanical extracts are generally well tolerated, although not totally free from adverse effects.
To ensure the safety of a plant extract, as well as the quality, the first step is the correctness of the botanical species; in fact, similar species can contain different amounts of harmful compounds, making one species safer than the other. This is the case of cinnamon: while Ceylon cinnamon (Cinnamomum verum), highly prized for its aromatic profile, contains coumarin only in traces, the so-called Chinese cinnamon (Cinnamomum cassia ) contains larger quantities; since cases of hepatotoxicity in humans due to coumarin ingestion are known, the adulteration of the most valuable species with the cheapest one, deliberate or by default, is a matter not only of quality but also of safety (7). Genomic species identification (DNA barcoding) has made this selection much easier because it allows identifying the correct botanical species with a level of confidence higher than traditional qualitative tests; however, PCR techniques are not helpful when adulteration concerns the use of the correct species, but not of the declared part of the plant: for example, expensive Ginseng roots are often adulterated with cheaper leaves (8); in this case, the use of chromatographic techniques is fundamental, because the phytochemical profile of the roots is different from that of the leaves.
Plant drugs must also comply with food law with regard to all classes of contaminants (agrochemical residues such as pesticides and fumigants, heavy metals, radioactive residues, microbiological contaminants and mycotoxins, process residues such as residual solvents, etc.); moreover, some contaminations are due to poorly executed agronomic practices, such as weeding: this is the case of pyrrolizidine alkaloids and matrine/oxymatrine. Pyrrolizidine alkaloids are present in many infesting flowering herbs, especially in those belonging to the Boraginaceae family: they grow and flower together with cultivated plants and are difficult to identify and separate once harvested. Analogous is the case of licorice contaminated by Sophora spp., a plant whose roots naturally contain quinolizidine alkaloids; licorice comes almost entirely from the collection of spontaneous plants, morphologically similar to those of Sophora, with which it can be accidentally confused. It is important to underline that genomic identification can also be useful in this case, as it can detect the presence of alien DNA sequences. Finally, contamination by PAH (Polycyclic Aromatic Hydrocarbons) can result from bad drying conditions or from environmental pollution) (9).
Careful monitoring of all stages of the supply chain, from cultivation and harvesting to drying and storage, is the primary way to guarantee the quality and safety of plant extracts, but, finally, climate change is also becoming a major challenge. Atmospheric conditions greatly influence the phytocomplex, being secondary metabolites a front "defense line” for plants. As for wines, also for medicinal plants, we can speak of "good or bad vintage", but the unpredictability of extreme weather events is exacerbating this aspect. The solution can only be in the differentiation of sourcing, favoring local crops, of which it is easier to verify the supply chain.
More than purely physical health
When we look at the science of sports and active nutrition, it has shifted fro m a purely physical health focus to overall health, highlighting mental well-being. As emphasized by Nutrition insight referring to the Olympics, “mental health is a topic that is now being more and more communicated by athletes and is no longer hidden as it was before.” The key success factors to win any competition are not only the strength, but also a clear-mind with sharp focus, and less anxiety. For companies working on the active lifestyle space, key elements for new product launch are a holistic approach focusing on prevention as well as recovery and strong and scientific claims according to individual market regulations. Brands have the opportunity to accompany consumers in a long-term process of forming healthier habits. They can do that by offering products that are not only functional but also tasty and affordable and thus help people adopt a proactive approach and avoid ephemeral diets and nutrition traps.
Latest ingredient innovation for active nutrition
Before deciding which trend and which innovation to apply to your brand, there is a simple checklist one can follow:
- For each of the trends and ingredients or new science, what is the awareness in your market? It can vary from high, something everyone knows, to something very niche that only people with specific lifestyles/ specific concerns know and would be interested in.
- Do you know what type of consumer you want to address? You can target the mass market consumer or the early adopter consumer, but you need to be conscious about it and select the right innovation and the right message that will be attractive to each target group. Many of the trends and innovations still have low awareness in the mass market and are more relevant for the early adopter consumer. This is something to be aware of when building your strategy and choosing a trend and therefore make a conscious choice.
- Choose the right consumer narrative and connect it to your brand. Think about the story you want to tell and choose the right consumer narrative. For example, do you want to appeal to a consumer’s emotions? Or connect them with their roots and traditions? Or maybe sell a ritual and an experience and not just a product? All valid options but you need to be clear about it to choose the one that best resonates in your market.
R&D Manager - Bionap
Scientific and Marketing Director - EPO
Head of Scientific Communications & Marketing - Euromed
CEO - Fermedix
R&D Coordinator - FLANAT Research Italia
Data Analyst - FMCG Gurus
CSO - Flytexia
Scientific Manager - Flytexia
Product Innovation and Development Manager - INDENA
Senior Research Manager - INDENA
Junior Product Scientist - INDENA
Medicine Hunter - KSM-66 Ashwagandha
Alessandro Giuseppe Tricomi
Food Supplement Manufacturing - Natural Ingredients Solution
Quality Control - Natural Ingredients Solution
Market Manager, Nutraceutical – ROELMI HPC
General Secretary – S.I.Fit. (Italian Society of Phytotherapy)
Associate Professor in Organic Chemistry - University of Milano-Bicocca
Associate Professor in Organic Chemistry - University of Milano-Bicocca
References and notes
- Mazzanti G., Dell’Agli M., Izzo AA. Farmacognosia e Fitoterapia. 2020. Piccin ed.
- Draft Reflection paper on markers used for quantitative and qualitative analysis of herbal medicinal products and traditional herbal medicinal products. London, 10 January 2008.Doc. Ref. EMEA/HMPC/253629/2007
- Yang Y, Zhang Z, Li S, Ye X, Li X, He K. Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis. Fitoterapia. 2014 Jan;92:133-47. doi: 10.1016/j.fitote.2013.10.010. Epub 2013 Oct 28. PMID: 24177191.
- Gertsch J. Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures. Planta Med. 2011 Jul;77(11):1086-98. doi: 10.1055/s-0030-1270904. Epub 2011 Mar 16. PMID: 21412698.
- Gori L, Gallo E, Mascherini V, Mugelli A, Vannacci A, Firenzuoli F. Can estragole in fennel seed decoctions really be considered a danger for human health? A fennel safety update. Evid Based Complement Alternat Med. 2012;2012:860542. doi: 10.1155/2012/860542. Epub 2012 Jul 29. PMID: 22899959; PMCID: PMC3414240.
- V. P. Swetha, V. A. Parvathy, T. E. Sheeja & B. Sasikumar (2014) DNA Barcoding for Discriminating the Economically Important Cinnamomum verum from Its Adulterants, Food Biotechnology, 28:3, 183-194, DOI: 10.1080/08905436.2014.931239
- Ichim MC, de Boer HJ. A Review of Authenticity and Authentication of Commercial Ginseng Herbal Medicines and Food Supplements. Front Pharmacol. 2021 Jan 11;11:612071. doi: 10.3389/fphar.2020.612071. PMID: 33505315; PMCID: PMC7832030.
- Sampaio, G.R.; Guizellini, G.M.; da Silva, S.A.; de Almeida, A.P.; Pinaffi-Langley, A.C.C.; Rogero, M.M.; de Camargo, A.C.; Torres, E.A.F.S. Polycyclic Aromatic Hydrocarbons in Foods: Biological Effects, Legislation, Occurrence, Analytical Methods, and Strategies to Reduce Their Formation. Int. J. Mol. Sci. 2021, 22, 6010. https://doi.org/10.3390/ijms22116010