The global market for food supplements is around 120 billion dollars with annual growth figures in recent years of around 6%. The main markets are those of Asia and North America followed by the European market. In Spain, the market for dietary products is around 1 billion euros, of which the sale of food supplements is around 350 million euros with more than 600 companies registered in this sector who market their products mainly in pharmacies, health stores, herbalists, supermarkets and large retailers .
Directive 2002/46/EC of the European Parliament defines food supplements as “foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form, namely 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 designed to be taken in measured small unit quantities”. The directive was introduced to our legal system by Royal Decree 1487/2009 of the 26th September, which has recently been modified by Royal Decree 130/2018 of the 16th March. This Royal Decree includes an annex with a list of other substances other than vitamins and minerals with nutritional or physiological effect that can be used in the manufacture of food supplements.
The annex of Royal Decree 130/2018 arrives very late and its contribution to the regulation of the sector is minimal. There are many ingredients that are used regularly in the formulation of food supplements such as, for example, the botanical ingredients that are still not considered as ingredients that can be used in the manufacture of food supplements. There have been many attempts and failures in our country to implement a national regulation on these botanical ingredients. Those of us who have been in this sector for years remember the efforts of all sector organisations back in the late 90s to agree on a list of plants that could be marketed freely, a list that became known as the “pacto del Montseny” (Montseny pact). Neither that attempt, nor later ones, could move forward because the European Union was initiating the legislative development of traditional herbal medicines and food supplements and it was convenient to wait. Fortunately, many years have passed since both directives have been approved and other countries around us, such as Portugal, France, Belgium or Italy have decreed on the different ingredients that can be used in food supplements, among them botanical, but unfortunately the same has not happened in our country.
Depending on how you look at it, the good or bad thing is that this slowness in the legislative development has not slowed down the national market. Thus, the industry has established an inadequate yet effective legal mechanism to ensure the introduction of a food supplement to the national market, which passes through the communication of the same in any of the EU countries mentioned above. In this way, the lack of a Royal Decree regulating the use of botanical ingredients does not prevent them from being marketed in Spain; although it does not seem logical that regulations of third countries and their officials are those that supervise and even regulate the labelling of the products that are manufactured to be marketed in the Spanish market. For example, the Community of Madrid on its website states that “… in Spain, since there is no national regulation, only food supplements with botanical species under the principle of mutual recognition can be marketed. It should be taken into account that: i) Belgium, Italy and France have put together a list of plants that can be included as ingredients in food supplements under their national regulations: BELFRIT list; ii) EFSA has published a compendium of botanical species that, naturally, may contain substances which pose a possible health risk”.
THE MEDICINE-FOOD SUPPLEMENT DUALITY
The final result of the European regulation and its Member States on the botanical ingredients brings us to the peculiar situation that we find ourselves in, where two apparently identical valerian products – 450 mg/tablet of valerian extract, 0.8% valerenic acids, 70% ethanol extraction – are marketed as a well-established medicinal product and as a food supplement. Two completely different regulatory processes involving very different manufacturing processes, quality control, registration/communication of market placement, labelling and dispensing/marketing for exactly the same ingredient at the same dose. Seeing the two final products, one beside the other, it is very difficult for the average consumer to appreciate the remarkable regulatory differences behind each one of them.
In this sense, it is important to point out that in recent years there has been a tendency in the industry to transfer botanical products registered as medicine towards food supplements or to position their new products directly as food supplements, a decision possibly motivated by the greater flexibility offered by a supplement compared to a medicine.
The data published by the European Medicines Agency on plant medicine records in the different EU countries will illustrate this: In 2017, there were 100 medicines registered by the traditional use procedure and 33 plant medicines by the well-established use procedure in Spain, which comes to a total of 133 registered plant medicines compared to the thousands of botanical supplements currently marketed in Spain .
HEALTH CLAIMS. NOW EVERYTHING INCLUDES VITAMINS AND MINERALS…
It has already been twelve years since the publication of the famous Regulation (EC) 1924/2006 regarding nutrition and health claims in foods in which the industry had placed so much hope. Twelve years later, the considerable progress in recognising the health properties of certain foods and ingredients is undeniable. For example, Regulation (EU) 432/2012 establishes a broad list of authorised health claims for foods, most of which are related to vitamins and minerals.
The criteria established by EFSA to evaluate the health properties of ingredients other than vitamins and minerals has meant that relatively few have solid scientific evidence to approve a certain health property. Again, we turn to botanical ingredients to show the paradox of European legislation. Traditional herbal medicines base their effectiveness and, therefore, their indication, on the traditional use that these products have had in Europe.
Based on this, and following the valerian example, the therapeutic indication according to EMEA for valerian root is “traditional herbal medicine for the relief of mental stress and to aid sleep. Based exclusively on its traditional use”, while the same valerian root with exactly the same dose can be marketed in Europe as a food supplement; notwithstanding Member States’ lack of approved health claims for this botanical ingredient to inform the consumer about the properties of the product that they wish to consume –yet there is, at the moment, a provisional list pending evaluation by EFSA-.
In short, for exactly the same ingredient at the same dose, in the case of medicine –EMEA- it has been chosen that the traditional use of a product is sufficient to have a therapeutic indication; however, if that same ingredient is marketed as a food supplement –EFSA- it has been chosen that the authorisation of a health property claim needs to be supported by at least two randomised, double-blind, placebo-controlled clinical studies.
For all these shortcomings, the market always tries to find the least-bad solution, and, in this case, many companies choose to include in their products small amounts of vitamins and minerals along with the main bioactive ingredients that lack approved health claims. The incorporation of vitamins and minerals therefore allows the inclusion of approved health properties in the labelling of the product. This is the case of vitamin B6, for example, which not only helps to reduce tiredness and fatigue, but also has eight other approved health claims that can be consulted in the database of the EU Register of nutrition and health claims made on foods and that is used to declare those properties in the labelling of products with bioactive ingredients whose health properties have not yet been evaluated by EFSA and approved by the Member States. This may be the case with Ginseng. If its traditional use to reduce tiredness and fatigue is recognised as a traditional plant-based medicine, but it is marketed as a food supplement, it should be accompanied, for example, by vitamin B6 in order to carry that health claim.
NEW TRENDS IN THE INDUSTRY
1.- Scientific Support. Clinical Studies
After the publication of the regulation of health claims, many companies started their own research projects to carry out clinical studies with which to obtain the necessary scientific evidence to request their own health claims – those regulated by Articles 13.5 and 14 of the aforementioned regulation-. During the regulation’s lifespan, we have observed the EFSA level of requirement for an ingredient to demonstrate the cause-effect relationship between the food studied and the health claim requested. The level of scientific evidence required by EFSA, both in terms of the design quality of the clinical studies and in terms of the significance of the results obtained, is very high. This has led many companies to withdraw from this venture and look for alternative ways to be able to report on the properties of their products. Nevertheless, the performance of clinical trials continues to be an important trend mainly among companies that manufacture their own ingredients, as well as among large companies that market the food supplement as such.
2.- New Formulations, New Ingredients
The second area of progress in the sector is the development of new galenic formulations or unit dosage formulations. Traditional hard and soft gelatine capsules, tablets, lozenges, powders, and liquids are joined by other types of more innovative developments such as gummies, bilayer tablets or granules. In this area of product development, the need to perform stability studies of the formulations before they are put on the market is also consolidated. Consequently, in contrast to the widespread practice of years gone by where a three-year expiry date was granted by default to any food supplement that was put on the market, whatever its composition, today the need to carry out the corresponding stability studies, as is logical, becomes generalised.
However, the greatest evolution in the R&D of food supplements is in the development of ingredients, where we work on technological advances such as micro and nanoencapsulations that solve problems of stability, solubility or improve the bioavailability of many bioactive compounds.
Another one of the main areas of research and development is the search for ingredients with greater bioactivity. In some cases, the increase in efficiency is determined by the increase in the concentration of the active ingredient, as in the case, for example, of omega 3 fatty acids, amino acids and derivatives or certain natural molecules, in which the increase in the degree of purity has important advantages when formulating food supplements. For example, reducing the number of capsules or tablets to be taken during the day by increasing the purity of the assets.
In the case of botanical ingredients, and more specifically plant extracts, the trend is just the opposite. With few exceptions, the effectiveness of a plant extract is due to the joint action of several active compounds or, more correctly, to the combination of several phytochemical families present in the plant that exert complementary mechanisms of action. In fact, it is a normal occurrence that as we purify a bioactive compound from a certain plant, we lose activity. For this reason, the current trend today is to identify the different phytochemical families, each one of them, responsible in part for the activity of the plant and extract them together, thus obtaining a phytochemical profile closer to that of the plant and radically different to that of conventional market extracts.
This entails the development of new extraction and purification technologies and processes that allow the concentration of the complete phytochemical profile of the plant, from the most polar compounds to the most apolar bioactive compounds. These products begin to appear on the market under the name Full Plant Profile or Full Spectrum.
3.- Food Supplement Safety
The third area of progress is the safety of food supplements. The placement of safe products in the market for the consumer must be the priority of all the agents involved in the market. The work area in the field of food safety is twofold. On the one hand, we must address the safety problems that are intrinsic to each ingredient and, on the other hand, the safety problems stemming from the possible contaminants and adulterants that they may contain.
Regarding the first aspect, the safety of the ingredient itself, we must progress in avoiding the overdose of certain ingredients brought about by the simultaneous consumption of the normal diet + fortified foods + food supplements, as in knowing the adverse effects of certain ingredients through a nutrivigilance system, similar to the successful pharmacovigilance model that we have implemented in all European countries.
In terms of the second, we must proceed with the control of contaminants, adulterations, and falsifications which may be present in certain ingredients and which, in fact, are the greatest safety threat to the consumer. There are three pressing issues in this matter:
Villani et al., in the analysis of 21 food supplements that supposedly contained grape seed extract, describe the adulteration by peanut skin extract in nine of these products (42%)  . In 2013, an internal study carried out by our company on 12 products with American cranberry extract revealed that more than 70% of the analysed products did not contain this extract but an extract of a red fruit of Chinese origin. The American Botanical Council describes the adulteration of cranberry extract (bilberry, Vaccinium myrtillus L.) with dyes, other species of Vaccinum or other botanical species rich in anthocyanins. Saffron extract is adulterated with different types of dyes, some of which are not food grade. In recent years, our laboratory has identified botanical adulterations in Siberian or Eleutherococcus ginseng with extract of Periploca sepium, as well as other adulterations in plants as diverse as echinacea, ginkgo, pomegranate, black cohosh, passionflower, horsetail, guarana or grapevine.
All these observations show the importance of being aware at all times of the quality issues related to food supplements due to the importance these aspects hold in consumer safety.
4.- Personalised Nutrition
Nutrigenomics studies how the components of the diet affect the gene expression of the individual so that they modulate a certain response to the organism, modifying, for example, the risk of getting sick. On the contrary, nutrigenetics studies how, depending on the genetic variants of each individual, certain responses will be generated for the different components of the diet. Personalised nutrition is based exactly on knowing the individual characteristics of each person, not only the physiological characteristics, but also the molecular alterations that may occur throughout their life, and relate them to those components of the diet that are specifically beneficial for those individual characteristics.
So that, depending on the genetic profile of each person, we can make a personalised recommendation for one food supplement or another.
The precision nutritional advice is based on the use of a genetic chip consisting of a set of polymorphisms of a single nucleotide or SNP (“Single Nucleotide Polymorphism”) associated with certain phenotypes (characteristics), which give us the knowledge necessary to give personalised nutritional advice for the achievement of specific health objectives. This chip, consisting of a set of SNPs designed specifically to obtain this information, is marketed as a genetic test. The companies specialising in precision nutrition develop genetic tests in order to deliver personalised nutritional advice (recommendation report) aimed at meeting specific nutritional and health objectives such as increasing sports performance, maintaining health in the aging process, enhancing school performance, fertility, etc. The lines of research are nearing towards being able to offer scientifically validated tests, incorporating recommendations of different lifestyle aspects (nutrition, activity, chronobiology…), and specific products where their effect on the objectives sought by the client has previously been demonstrated.
5.- Organic/Ecological Product
Finally, another one of the trends emerging in the food supplement market is the need to use organic/ecological or sustainable ingredients. This trend is marked by two fundamental aspects, the need to consume “healthier” ingredients and the consumers’ increasing concern for “sustainability”.
Although there are differences between the “Eco”, “Bio”, “Organic” and “Sustainable” concepts, they are similar in broader terms and the European Community legislation equates them in Regulation (EC) No. 834/2007, on production and labelling of organic products to designate as organic/ecological the products that have not been treated with any type of fertilizer, pesticide or chemical product, have been grown without genetic manipulation (no GMOs) and respecting the environment making responsible use of energy and natural resources such as water, soil, organic matter and air.
Although the greatest demand for organic products comes from the US market, in Europe it was growing at a rate of 12% in 2015 according to the latest FIBL study in 2017 , with Germany, France, the United Kingdom, Switzerland, and Italy being the five countries leading the market for organic products in Europe.
This boom in the demand for organic products shows a great market opportunity, especially in the field of botanical-based food supplements where the concepts of ‘natural’ and ‘sustainable’ are very much in demand by the consumer.