Keywords

1 Introduction

1.1 Definition of Functional Foods, Nutraceuticals, and Related Terms

The advent of functional foods and nutraceuticals on the market has blurred the distinction between pharma and nutrition [1]. Obviously, the concept of foods promoting health is not new. In 400 b.c., Hippocrates already sentenced “Let food be thy medicine and medicine be thy food” [2], and in the countries of the far East, influenced by Chinese culture, foods such as glutinous rice, wheat, sesame, jujube, gingiber, or leek were included in Chinese medicine books for their traditional use for chronic diseases [3]. Nowadays, the development of functional foods is one of the most intensive areas of food product development worldwide, opening multiple challenges for countries with a vast biodiversity and historical use of plant extracts [4].

However, estimating the market size values for functional foods can be difficult, because of the ambiguity of the term “functional food,” the lack of an official or univocally accepted term (in many countries there is no regulatory definition) [5], and the diffused borders between concepts for commercial products also related to health-promoting functions such as “functional foods,” “nutraceuticals,” “superfoods,” “dietary supplements,” or “cosmeceutics,” many of which respond to marketing criteria. Table 80.1 compiles some of the terminologies currently associated to functional foods and nutraceuticals.

Table 80.1 Concepts related to functional foods and nutraceuticals
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Despite the ancestral knowledge of the link between diet and health, the appearance of specific terms related to foods promoting a health benefit is more recent. In 1984, the concept of functional food was first promoted in Japan by scientists who were studying the relationships between nutrition, sensory satisfaction, fortification, and modulation of physiological systems [12]. The Japanese Ministry of Health and Welfare then introduced “Foods for Other Specific Health Use” (FOSHU) in 1991, promoting its use as a strategic action to reduce healthcare costs. The success of the initiative (in 2000, the total number of approvals under the FOSHU label reached 174, with an estimated market value of around $2 billion [13], while more than 500 products were labeled as FOSHU in 2005 [5]), united to the success of products with health claims in the USA, paved the way for the development of the functional foods market. However, consensus on a definition or categorization of these foods was established by heterogeneous criteria by manufacturers or scientists, not by regulatory agencies.

In Europe, the International Life Science Institute (ILSI) established an operational definition of functional foods: “a food product can only be considered functional if, together with its basic nutritional impact, it has beneficial effects on one or more functions of the human organism, either improving the general and physical conditions and/or decreasing the risk of evolution of diseases. The amount of intake and form of the functional food should be as it is normally expected for dietary purposes. Therefore, it could not be in the form of pill or capsule but only as a normal food form.” This definition would establish a clear separation from nutraceuticals, which can be considered as diet supplements that deliver a concentrated form of a presumed bioactive from a food, presented in a nonfood matrix, and used with the purpose of enhancing health in dosages that exceed those that could be obtained from normal foods [14]. Nutraceuticals are sold in presentations similar to drugs: pills, extracts, tablets, etc. [15]. However, in many cases, the functional food market is referred as the “nutraceutics” market [16], and then, it is difficult to separate the exact values for each. A reason for this interconvertibility of terms is that much of the early development of the nutraceutical concept and products was driven from the USA, where the Dietary Supplement and Health Education Act (DSHEA) allowed considerable flexibility and blurred the boundaries between foods and medicines that can be found in other parts of the world [17]. Anyway, there is no definition for nutraceuticals in neither the UE nor the USA, although both have a definition for supplements, which could be considered equivalent to nutraceuticals.

In opposition, the federal Department of Canada has proposed, via Health Canada, differentiated definitions for nutraceuticals and functional foods. A nutraceutical is a product isolated or purified from foods that is generally sold in medicinal forms not usually associated with food. It is demonstrated to have a physiological benefit or provide protection against chronic disease. A functional food is similar in appearance to, or may be, a conventional food, is consumed as part of a usual diet, and is demonstrated to have physiological benefits and/or reduce the risk of chronic disease beyond basic nutritional functions. In this case, the difference of formulation between both kinds of products is well established [7].

Most functional foods definitions do not intend to exclude natural foods in the functional foods category. However, many manufacturers and the perception of the general public would disagree, since for many of them, the functional food should imply an inherent fortification of the food with a bioactive ingredient. And from the pragmatic point of view of manufacturers concerned about regulation accomplishments, functional foods would be those that bear or intend to bear a nutritional or a health claim.

Another conflictive concept is the one for cosmeceuticals. Neither the FDA nor the EFSA recognizes this term, which is widely used by the cosmetic industry to refer to cosmetic products that have medicinal or drug-like benefits. Like cosmetics, cosmeceuticals are applied topically but differ in that they contain potent ingredients that can influence the biological function of the skin and deliver nutrients to promote healthy skin [18]. Nearly universally around the world, this has become the catchword for the millennium change in cosmetics to retard aging [19].

Other marketing concepts have arisen like “superfoods,” which are referred to natural products that have a low glycemic index and provide key nutrients that are lacking in the typical western diets, like beans, dark green leafy vegetables, citrus, sweet potatoes, berries, tomatoes, fish high in omega-3 acids, whole grains, nuts, fat-free milk, and yogurt [20]. A derivative concept, “superfruits,” has emerged to design natural fruits (including blueberries, blackberries, cranberries, pomegranate and exotic ones such as açai or goji) that have a high antioxidant capacity. However, neither of those terms has been recognized by the Food and Drug Administration or the European Food Safety Authority.

Finally, other terminologies that used to be popular such as vitafoods, alicaments, or pharmafoods have become obsolete and fallen out of use.

1.2 Socioeconomic Context of Functional Foods and Nutraceuticals

To understand the success in the functional foods and nutraceuticals sector and the reasons behind their expansion in the market as well as the menaces that can compromise their growing, it is necessary to describe the socioeconomic context, which includes many interactions between consumers, scientists, food manufacturers, and legislative bodies.

1.2.1 Functional Foods as a Vector for Health

In the last decades, the social economic development has induced profound changes in consumer behavior, involving, in particular, food consumption dynamics. The elements that have most influenced and still influence consumer eating habits are the lengthening of life expectancy, the progressive ageing of population, the health economic and social costs rising, the widespread desire for a better quality of life, and media and advertising [21].

Major current problem areas for population health include obesity, cardiovascular health, age-related cognitive decline, metabolic syndrome, insulin resistance, and diabetes [22]. All these concerns are expected to grow because of the change of the age pyramid to older societies. People are living longer, and so incidence of specific diseases or conditions of elder people, such as cardiovascular diseases, diabetes type 2, osteoporosis, or neurodegenerative diseases, will increase. The biggest health concern nowadays is obesity and overweight, especially because of the highest increase in developing countries [23]. The WHO estimated in 2003 that over one billion people are obese and over 400 million people are clinically obese [22]. Cardiovascular diseases are also a big concern: They represent 30–50 % of cause of mortality in developed countries. High blood pressure and cholesterol levels have reached pandemic dimensions, and it is predicted that the worldwide incidence of diabetes will exceed 450 million people by 2025 [22]. The prevalence of arthritis and osteoporosis in the aging populations of developed nations is also growing: In 2010, more than 5.5 million people in the seven major markets were forecast to be suffering from rheumatoid arthritis (RA) [24].

Many of the major chronic diseases are caused substantially by poor diets. The consumption of whole grains and better lifestyle choices could represent a reduction of over 100,000 deaths per year in the UK [25]. Since a major issue for public research is targeting prevention of diet-related diseases [26], there is a growing interest about the links between food and health by public health officials [27]. Functional foods have the potential to improve population health in line with the objectives identified by national public health strategies [28], promoting the prevention and risk reduction of disease, and thus reducing mortality rates and medicinal costs associated to therapeutic treatments. For example, it was estimated that in the USA, total direct and indirect costs associated to diabetes and related disorders reached $98 billions in 1997 [22]. In 2005, $466 m were spent on pharmaceutical medication to treat obesity in the seven major markets, and these sales were set to triple to $1.5 billion by 2010. In 2005, $84 billion were spent in the USA and the 5 major European markets on the pharmaceutical treatment of CVD conditions. By 2010, sales were expected to rise to $105 billion. In 2005, it was estimated that around $22.5 billion were spent worldwide on the sale of drugs used to treat rheumatoid arthritis (antirheumatics), osteoporosis (osteoporosis agents), and inflammatory conditions, with $14 billion of this generated from sale of medicines in the top seven countries [24].

In this context, public health organizations and governments share a mutual interest in promoting health through nutrition and adequate lifestyles, thus reducing medical costs. For example, the consumption of whole grains and better lifestyle choices could represent a reduction of over 100,000 deaths per year in the UK [25]. In fact, this was the key reason why the Japanese government introduced the FOSHU system: to keep the aging population healthy through functional foods and to keep the health care costs down. Similar policies are spread all over the world. For example, agriculture, food, and health are significant themes in the European Union’s current Seventh Framework Research Programme (FP7) [26].

1.2.2 The Perspective of the Consumer

Consumer acceptance of the concept functional foods, together with a better awareness of its determinants, is widely recognized as key success factor for market orientation, consumer-led product development, and successfully negotiating market opportunities [29]. However, little research has been conducted to analyze the perspective of the consumers [30].

In fact, one of the main reasons of the success of functional foods has been the role of consumers undertaking new trends to a healthier lifestyle. Many objective data show this tendency. For example, between 2006 and 2007, vegetables and fruits were the top 2 products whose use increased in North America, Western Europe, and Nordic Europe, while processed foods, salty snacks, and sugars were some of the products with the biggest decrease in use. In the last 25 years, butter has decreased from around 70 % of the yellow fat market to 25 %, while low fat spreads have captured half this market. In the cooking fat sector, vegetable oils have taken over the animal fats. Skimmed and semi-skimmed milks have copped 2/3 of milk sales, while low calorie soft drinks have increased to 20 % of the soft drink market [31].

Apart from these examples of healthier choices taken from objective market data, several surveys are periodically conducted in developed countries to follow the public attitude toward health. In 2011, according to the International Food Information Council Foundation Food & Health Survey, 59 % of Americans declared that they were attempting to make changes to improve the healthfulness of their diets, in order to ameliorate their overall well-being (65 %), lose weight (56 %), improve their physical health (56 %), because of a specific health condition (32 %), and/or maintain weight (20 %) [32]. Similar tendencies can be found in European countries.

However, these pronouncements have to be considered carefully, because some data have reported lower frequencies of healthy food consumption in American consumers, despite their intention of eating healthily more often [33]. This distance between the consumers’ aspirations and the real consumption is a clear menace to the success of the functional foods niche and should be overcome by providing functional products that are attractive to the potential buyer, both in price, and taste and efficacy.

1.2.2.1 Acceptance of Functional Foods and Willingness to Buy New Products

In the process of developing new functional ingredients or foods, there must be a consumer need or a problem that requires solution, and there must be self-awareness of the problem from the consumer. But it is also crucial that consumers must be willing to spend money to solve the problem or satisfy the need they have identified [23].

The Functional Foods/Foods for Health Consumer’s trending survey is being conducted every 2–3 years since 1998 and provides ongoing American consumers insights into their interest and perceptions about food and beverages and the roles they have in promoting health and wellness [34]. This study summarizes some of the points that can explain the reasons for the success of functional foods. A first aspect to be considered is the acceptance by consumers that functional foods can have added health and wellness benefits. Most data from other surveys in other countries show conformity with this topic. According to the 2009 IFIC Functional Foods/Foods for Health Consumer Trending survey, between 68 % and 85 % of Americans agree that foods or beverages can provide specific health benefits such as improving heart health, contributing to healthy grown and development in children, or improving bone health [34]. In Europe, even when consumers had not heard the term “functional foods,” more than 50 % agreed to fortify functional ingredients in specific food products [35]. Japanese consumers have traditionally been aware of the importance of certain foods for the promotion of health.

Obviously, general health orientation varies systematically as a function of age and gender. According to the results obtained from different questionnaires, rational food consumers are the primary potential target of functional food producers. Women tend to be substantially more health-oriented than men, which explains the females’ stronger purchase interest toward functional foods, an observation that has met consensus in different studies. In general, women have shown to be more reflective about food and health issue. Another relevant socio-demographic factor is the presence of children in the family. On the other hand, middle-aged and elderly consumers tend to be substantially more health-oriented than young consumers. In truth, middle-aged and elderly are the largest group who uses functional foods to target a specific health concern. In this case, it is hypothesized that this group is more likely to have confronted relatives’ loss of good health, and this experience with illnesses and associated economic and social consequences increase probability of functional food acceptance [29]. In overall, the hypothesized effects of socio-demographic determinants are that acceptance of functional foods increases with higher age, being female, having young children, and having an ill family member.

At the same time, there are discrepancies about the role of education in the acceptance of functional foods. In Europe, it is biased toward the higher socioeconomic groups, reflecting a higher willingness or ability to pay a premium price; while in the USA, there is a higher acceptation among the lower educated. Another difference between American and European consumers is the far more critical attitude toward new product and technologies, and therefore, it can be hypothesized that European’s acceptance of functional foods is less unconditional [5].

In conclusion, it seems to be a global acceptance of functional foods, but this must not be taken for granted and cannot reflect the perception of concrete functional foods. In this sense, another of the aspects addressed in consumers’ research is the awareness of functional foods.

Concerning the awareness of the terminology of functional foods, different surveys show that consumers are not greatly informed about this concept, although there is a steady tendency to increase these levels of awareness in all the countries. For example, in an Italian quantitative survey conducted in 400 consumers, 24 % were unable to give a definition for functional foods, 20 % confused them with light and dietary products, and 16 % incorrectly associated them with food for those who have specific health problems [36]. In Belgium, 49 % of consumers were familiar with the term “functional food,” but only 30 % in Hungary and 4 % in Poland [37].

Given the positive acceptance showed for functional foods in general, it should come to no surprise that most studies have shown a significant willingness to pay for this kind of products. For example, Mintel Oxygen 2010 reported that more than half of consumers had bought a functional food or beverage in the 3 months previous to the study. More than half of the Americans reported in 2009 the consumption of foods or beverages for overall health and wellness (56 %), heart health benefit (55 %), or to contribute to a healthy body weight [34]. In a recent survey in Europe, 15 % of consumers reported a daily consumption of functional foods, 24 % reported a high-frequency consumption, and 28 % considered themselves occasional buyers. Only 21 % of respondents stated that they had never consumed these products [36].

Again, regardless of the global willingness to pay for healthy products, the acceptance of a specific functional ingredient is linked to the consumers’ knowledge of the health effects. Functional ingredients which are in the mind of the consumers for a relatively long period of time (e.g., vitamins, minerals, fiber, low sugars, etc.) achieve considerably higher rates of acceptance than ingredients that are used for a short period of time. This can have a great impact in the context of the economic recession. Although it can be demonstrated that consumers are willing to spend for relevant functional benefits even in times of financial crisis, consumers are less likely to experiment with new functional foods and beverages: In this sense, the credibility of the health effect and the perceived effectiveness of the product, as well as a correct knowledge of the ingredient and a correct association between the ingredient and the health benefit, is crucial. For example, fiber, calcium, iron, and vitamin D are well-known ingredients and consumers are correctly aware of the kind of health benefit they can expect from them. Omega-3, probiotics, and phytosterols were less known, but thanks to the advertising policies communicating their health effects, consumers have a good knowledge of their benefits. In opposite, products like oligosaccharides, lutein, or peptides are less popular. It is of great importance to have well-informed consumers, conscious of the effects of the ingredients, in order to avoid incorrect expectancies that can further lead to deception and lack of trust in future products.

In sum, for those products with limited consumers’ knowledge, there are strong needs for specific information and communication activities. Doctors, nutritional advisers, and public entities are the sources in which the consumers have most confidence (42–45 % of trust), while a lesser degree of confidence is given to producers and product labels [13, 36]. The implementation of specific regulations restricting the use of nutrition and health claims to products with a solid scientific evidence will also offer a reinforcement of the trust of consumers in the long term. But in the short term, the withdrawal of many health claims for top products, some of them very popular among consumers, because of insufficient scientific evidence, can have the contrary effect. So, it is advisable to reinforce the transparency on the information to consumers to avoid a bad global perception of the functional foods products.

1.2.3 Association of the Industry and the Scientific Community

It must not be forgotten that because of its innovative component, functional foods have been possible, thanks to the arousal of new knowledge about the relationship between ingredients and health, which has mainly been provided by the advances in the scientific research on the subject.

Innovative concepts in the area may thus emerge from academic researchers, although they often are not aware of how to translate these ideas into final marketable food products [38]. In consequence, most frequently it is the industry that initiates the cycle of development, but working closely with academics (for example, through the formation of scientific advisory boards) to provide a solid ground to design a new functionality/ingredient, as well as to conduct the series of safety, efficacy, and bioavailability tests to prove the applicability of the new designs. This cycle of innovation can lead to breakthrough products, which can be defined as products, which provide a company with greater profits and longer-lasting competitive advantage in the marketplace in comparison to minor product development or line extensions [39], that can be as well a good and easier way to include a health claim in food products. But while the first case would in general be early-movers, in the second case, normally, it would be companies deciding to approach the functional food market in response to its astonishing growth [40]. This difference in the degree of innovation is well recognized in the UE Regulation 1924/2006, which distinguishes innovative products (Article 13.5), while at the same time provides a list (Article 13.1) that already states more usual ingredients-activities relationships.

2 Market Prospect of Functional Foods

2.1 Global Sales: A Steady Progression

Many market studies of global sales of functional foods differ in the data, depending on the criteria used for the inclusion of products in the analysis. For example, under a strict definition, according to Leatherheadfood, the functional food and drinks market had a combined value of $19.4 billion in 2007, whereas with a broader definition, the market raised to $41.9 billion [41]. In 2011, the global market for a strict definition of functional products as those offering specific health claims was estimated at $24.2 billion [42]. BCC research established a Nutraceuticals Global Market for nutraceutical foods, nutraceutical beverages, and nutraceutical supplements of $40 billion each.

Another source of confusion for the precise definition of the market size is that many functional ingredients were initially included in foods for reasons other than their health-promoting values. For example, the use of antioxidants for food preservation purposes was prior to their commercialization as health-enhancing functional additives, and bioactive compounds such as anthocyanins from red berries or lycopene from tomato were more appreciated because of their application as natural colorants rather than because of their biological activity against free radicals. Obviously, the higher added-value obtained because of their healthy properties has meant a faster growing development of these products. In 2007, global sales of antioxidants used in the manufacture of foods amounted to $788 million, representing a constant yearly increase of 3 %. Functional antioxidants in 2007 already accounted for the majority of sales, holding a value share of almost 56 %, with antioxidants used for food preservation purposes making up the remainder [43].

Despite this lack of precision concerning the data, functional foods have undeniably been reported as one of the top trends facing the food industry. They have been especially active since the last decade, when the annual growth rate of the functional foods market ranged from 15 % to 20 % at the end of the 1990s [29]. The global functional food market in 2002 was roughly estimated to be between $10 billion and $40 billion with an annual increase of about 8 % [39]. In 2008, when using a definition of functional foods that comprised all “products bearing a health claim,” this group of products had arisen as the fastest-growing sector of the food market, with estimates forecasting an expected annual growth rate of 10 % for functional foods as compared to an average 2–3 % for the food industry as a whole [44]. Although growth rates estimates have decreased over time, the numbers remain impressive compared to growth rates for the food industry as a whole.

Even in the actual situation of economic recession, which should compromise the willingness of consumers to buy more expensive foods, recent estimates remain optimistic. Consumer interest in functional foods remains strong, and the rising costs of healthcare and the needs of an aging population should still encourage the consumers’ commitment to health and wellness pursued through the diet. Recent data from 2007 by Pricewaterhouse Coopers [45] predicted that functional foods in the USA could grow by up to 20 % or five times that of the food industry as a whole [46], which is consistent with other reports by Leatherhead [47] that products making specific health claims –not including neither energy and mood drinks, nor food supplements – are predicted to grow at 4–5 % for the next few years [48]. According to market analyst Freedonia, demand for nutraceutical ingredients like botanicals, vitamins, minerals, and omega-3 s will grow 7.2 % annually until at least 2015 to be worth €18.5 billion with newer markets like Mexico and South Korea helping drive growth in the sector [49]. And a report by Global Industrial Analysts projected the global nutraceuticals market projected to exceed US$243 billion by 2015 [50].

Figure 80.1 shows this evolution in the functional foods and beverages market size.

Fig. 80.1
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Global market size of functional foods (Sources: New Nutrition Business (1995, 2000) [53]; Euromonitor International (2004, 2006, 2009) [54]; BCC Research (2013) (http://www.bccresearch.com/report/nutraceuticals-processing-markets-fod013c.html))

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Concerning differences between countries, according to Datamonitor, some of 90 % of total sales occurs in Europe, the USA, and Japan [51]. In Japan, according to a Leatherhead report utilizing tight functional food definitions, global sales in 2010 reached $24.22 billion, which would represent the 38.4 % of the global functional market, followed by the USA with 31.1 % and Europe (28.9 %) [48].

In the USA, with between $20 billion and $30 billion in sales a year, functional foods comprise about 5 % of the entire US food market [52].

In Europe, Germany, France, United Kingdom, and the Netherlands represent the most important countries within the functional foods market, but many other European markets are experiencing high growth rates, such as the Netherlands and Spain. In addition, newly emerging markets like Hungary, Poland, and Russia are also well positionated [36].

2.2 Situation of Specific Product Launches, Ingredients, and Claims

The growth of the functional food market has been correlated with a steadying increase of the number of functional food products launches. According to Mintel analysts, the global launches of functional products between 2005 and 2009 were more than doubled, from 904 to 1859. Between 2008 and the first half of 2009, USA was the leader in healthy product launches (881 products), followed by Japan (314), Italy (325), UK (237), Germany (235), and France (150) [46].

The main functional foods category correspond to dairy products, that account for the 38 % of the market, followed by bakery and cereals (22.7 %), beverages (12.5 %), meat, fats and oils (8.1 %), fish and eggs (7.4 %), and soy products (5.8 %). In most cases, there has been a significant growth in the market. For example, according to Euromonitor the global market for pre- and probiotic spoonable yogurt had a growth of 128 % between 2004 and 2009, from $3.3 billion to $7.6 billion, while for drinking yogurt, it grew a 44 % to $11.2 billion [55]. Sales of functional spreadable oils and fats grew 54 %.

Classified according to health claims made on the product, digestive health has been the most used claim for new products (Fig. 80.2) [56].

Fig. 80.2
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Global distribution of health claims in functional products launches between 2005 and 2009 (Source: Mintel’s Global New Products Database)

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It is relevant to state that food traditions and cultural heritage influence the interest of consumers in functional foods. For example, despite dairy is the biggest segment in the global market, in the USA, this predominance is for functional beverages, including energy and mood beverages. According to Leatherhead Food International, functional drinks account for 50 % of the US functional food market, followed by cereal products [48]. Another characteristic of the USA is that consumer expenditures on nutraceuticals are especially active, having reached a reported $20.50 billion in 2004, more than double the amount spent in 2004. Supplementation is also quite popular in Japan, whereas European consumers are less driven to these kinds of products. Another example of regional particularities is the fact that Japan is the world’s largest market for green tea sold in leaf, which accounts for nearly 65 % of total leaf tea sales in the domestic market [43].

Concerning claims, digestive health is not the top claim in the USA, this honor belonging to cardiovascular health. On the opposite side, cardiovascular health claims are quite reduced in Japan (less than 10 % of the new functional foods launches). In the UK, cardiovascular health claims have represented a 20 % of the 530 new products between 2005 and 2009 [58].

2.3 New Perspectives

Despite the continuous introduction of new functional food or beverage products to the market, in the last few years, a certain reduction in the number of launches for some of the functional ingredients has been observed. Mintel reported in 2010 a slowdown in the market for energy drinks and fortified waters in the USA [57]. Figure 80.3 shows the reduction on the number of new products with claims related to the polyphenols family, according to Datamonitor. This reduction that can be attributed to different factors such as the development of new legislations such as the recent implementation of the UE 1924/2006 Regulation, that is limiting the use of nutrition and health claims by establishing the need of a strong substantiation of the evidence of the claimed effect. This has led to the dismissal of several health claims for many products, especially in areas like natural plant extracts or probiotics. This will mean a reduction on both the number of functional foods as well as their market value, at least according to the definition of functional foods as those wearing a nutrition or health claim. For example, there was an 11 % drop in the number of health claim-bearing launches between 2009 and 2010, even if the transition period for many products was still applied in the UE.

Fig. 80.3
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Number of global launches of ingredients with polyphenols associated to different claims (Source: Datamonitor)

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Additionally, in a global economic situation of recession, food companies can find difficulties to assume the costs associated to the development and scientific substantiation of evidence for new products, especially for cases that could imply expensive research.

The difference of the economic impact between products with health claims compared to those without them is uncertain. For example, in the USA in 2000, the market for functional foods with specific health claims achieved a turnover of around $0.5 billion, while functional foods without claims had an annual turnover of at least $15 billion [13].

3 Functional Foods Under Scrutiny: Situation of Natural Products Relating to the Substantiation of Evidence

3.1 Regulation of Functional Foods and Nutraceuticals Market

To ensure that the products are not misleading consumers, governments from various countries have developed regulation systems. Normally there exist associated organizations that take care of the accuracy of the claims used for functional foods and nutraceuticals. Some of these organizations are the European Authority of Food Safety (EFSA) in Europe, the Food and Drug Administration (FDA) in the United States, or the Ministry of Health, Labour and Welfare (MHLW) in Japan. We will discuss the current situation of the USA and Europe in relation to the approval of claims.

3.1.1 USA

In the USA, claims on foods and dietary supplements can belong to three different categories: nutrient content claims, structure/function claims and health claims.

Structure/function claims can be used for dietary supplements, and describe the effect on the structure or function of the body [8, 58].

Nutrient content claims can be considered as “expressed nutrient content claims,” which is any direct statement about the level (or range) of a nutrient in the food, or as “implied nutrient content claims,” which denotes any claim describing the food or an ingredient therein in a manner that suggests that a nutrient is absent or present in a certain amount or suggests that the food, because of its nutrient content, may be useful in maintaining healthy dietary practices. Annex Table 80.3 shows the nutrient content claims of the USA.

Health claim means any claim (including statements, symbols, vignettes, etc.), made on the label or in labeling of a food or dietary supplement, that characterizes the relationship of any substance to a disease or health-related condition.

In their origin (1990), health claims had to be based on a very high standard of scientific evidence, evaluated by the FDA. However, after the result from a 1999 Court of Appeals Decision, Pearson v. Shalala, the Qualified Health Claims were introduced for substance/diseases relationships with lower standards of evidence, that is considered credible but without reaching a significant scientific agreement standard. In the case of Qualified Health Claims, the proposed claim has to include qualifying language that identifies limits to the level of scientific evidence to support the relationship [59].

Table 80.2 compiles the Health Claims and Qualified Health Claims approved by the FDA.

Table 80.2 Health claims and qualified health claims approved by the FDA
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Table 80.3 Nutrient content claims approved In the USA
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3.1.2 European Union

The EU Regulation 1924/2006 [60] distinguishes two types of claims:

Nutrition claims are claims that state, suggest, or imply that a food has particular beneficial nutritional properties due to the energy it provides or the nutrients it contains [61]. Annex Table 80.4 compiles these claims.

Table 80.4 Nutrition claims approved in UE
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Health claims are any claim that state, suggest, or imply that a relationship exists between a food category, a food, or one of its constituents and health. Reduction disease risk claims are health claims that state, suggest, or imply that the consumption of a food category, a food, or one of its constituents significantly reduces a risk factor in the development of a human disease.

The regulation classifies health claims into three main types. Article 13.1 claims pertain to “general function” claims relating to growth, development, and functions of the body. They should be based on generally accepted evidence and could be used by any manufacturers as long as the conditions of use are kept. Article 13.5 claims pertain to general function claims based on new and/or proprietary data. This type of claim is particularly relevant for manufacturers who have invested in innovation and wish to protect their claim and/or underpinning scientific data [62]. Article 14 claims refer to risk reduction claims or claims related to children’s health and development.

According to the Regulation, the European Food and Safety Authority (EFSA) is the consulting organization for the analysis of the scientific substantiation of evidence of Health Claims. Its evaluating process, which started after the implementation of the Regulation, will imply a change in the allowed health claims for functional foods in Europe. The Fig. 80.4 compares, for some of the most popular ingredients, the successes and failures on obtaining a positive opinion about the scientific substantiation of evidence for the ingredient’s intake and health relationship.

Fig. 80.4
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Percentage of positive and negative opinion for different families of ingredients published by EFSA (Source: EFSA Journal, 2008–July 2012)

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As it can be inferred from EFSA opinions, while there are some ingredients with well-established relationships of cause and effect between their intake and the claimed effects, for many other compounds, this association is much less proven.

On the positive side, with a high percentage of success, the cholesterol-lowering effect of phytosterols, the role of carbohydrate-electrolyte solutions for the enhancement of water absorption during physical exercise, or the importance of vitamins and minerals toward different processes is well accepted.

In opposition, the cause-effect relationship of probiotics, prebiotic fiber, and phytochemicals (including plant extracts), among other ingredients, has commonly been considered as insufficiently substantiated. For probiotics, an inadequate identification of the probiotic strains, as well as the difficulty to correlate the changes in microflora with a beneficial physiological outcome, can be stated as the main reasons for most of the negative opinions emitted. In the case of phytochemicals, the characterization is also a main reason of rejection, together with the quality of the studies presented and the relevance of biomarkers used to sustain the effect.

Other ingredients show a more equilibrated balance between positive and negative opinions. With reference to fatty acids, positive opinions, for example, in the case of some omega-3 fatty acids like docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), or linolenic acid and their role in maintenance of triglycerides levels, and for long-chain omega-3 fatty acids maintenance and development of vision and brain function have been published. In contrast, the evidence for conjugated linolenic acids or gamma-linolenic acids has been considered unsatisfactory. Concerning fibers, the importance of distinguishing the effects depending on the concrete fiber has been established. For example, the maintenance of normal blood cholesterol levels is well accepted for beta-glucans, glucomannans, or guar gum, but not for acacia gum or isomalto-oligosaccharides. The role of soluble and insoluble fibers is well known to be different, and in consequence, concrete claims related to non-well characterized fibers usually lack enough scientific evidence. For example, reduction on many claims for various foods related to glycaemic index control has been dismissed because of an inadequate definition of the type or carbohydrates.

It is out of the scope of this chapter to make an exhaustive analysis of the scientific gaps that have been found by the EFSA panel. However, they provide valuable lessons for the future development of future functional foods, and will undeniably have an impact on the market as well as on the approach to scientific evidence substantiation studies. In consequence, we will analyze some of the key aspects, focused on the families of plant extracts and phytochemicals, that scientists must take into account in order to assist in these developments.

3.2 EFSA Opinions on Phytochemicals and Plant Extracts

In the case of plant extracts and bioactive compounds deriving from them, the levels of success throughout the process of evaluation of health claims by EFSA have been modest at the best. Concerning phytochemicals, between 2008 and July 2012, very few compounds have obtained a positive opinion:

  • Caffeine (from guarana, tea, chocolate, coffee, or as a pure form) and increased attention/alertness, reduction in the perceived effort, and increase in endurance capacity and physical performance during short-term high-intensity exercise.

  • Polyphenols in olive and protection of LDL particles from oxidative damage.

  • Monacolin K from red yeast rice and maintenance of normal LDL-cholesterol concentrations.

  • Beta-carotene and maintenance of the normal function of the immune system.

  • Cocoa flavanols and maintenance of normal endothelium-dependent vasodilation.

Other popular compounds such as lycopene, lutein, resveratrol, quercetin, catechins from tea, grapes, or cranberries, or soy isoflavones have not obtained a favorable opinion, except in cases where they were actually associated with other compounds that had already proven to have an effect like vitamin E or C.

Concerning plant extracts, many of them have been kept on hold by the European legislation. Prior to this reschedule, all those evaluated by the provisions of Article 13.1 obtained a negative opinion. But at the same time, stories of success have also arisen. It is an illustrative example the case of the tomato WSC extract, whose effect over platelets aggregation was well established by pertinent and company-proprietary clinical studies and was worth of being the first accepted ingredient via the Article 13.5.

This example illustrates how, although there have been more deceptions than triumphs in the evaluation of scientific evidence provided by plant extracts and phytochemicals, these results, rather than being seen as a disappointment, can be considered an excellent opportunity for manufacturers to invest in scientific research in order to complete standardized quality studies that clearly establish a cause-relation effect between the ingredient intake and the claimed effect, and thus obtaining specific claims according to the article 13.5 of the 1924/2006 Regulation.

3.3 Lessons Learned: Key Scientific Aspects to be Controlled for Obtaining a Health Claim

Following the lessons learned by the EFSA evaluation of health claims, 3 different aspects have to be assessed for obtaining a health claim:

  1. 1.

    Characterization of the ingredients

  2. 2.

    Relevance of the sustained claimed effect

  3. 3.

    Scientific evidence provided by efficacy studies

3.3.1 Characterization

Although many of the functional ingredients (vitamins, minerals, omega-3 fatty acids, etc.) possess reliable methodologies of quantification, this aspect is sometimes incomplete for plant extracts. In some cases, there was no reference to the content of bioactive compounds, the part of the plant used for the preparation, no indication of diary doses, or the extracts were used as multibotanical combinations without specification of the other components.

One of the main reasons for this lack of concretion is the complexity of plant matrices, whose diversified secondary metabolism includes a vast number of different compounds with close structures that can be hard to identify. Some of these families with a well-documented bibliography related to health effects comprise alkaloids, phenolic compounds (including phenolic acids, stilbenes like resveratrol, or flavonoids such as anthocyanins, procyanidins, or isoflavones), terpenoids, carotenoids, sulfur compounds (such as glucosinolates and isothiocyanates), etc. Their presence and amount in the plant source depend on multiple factors including variety, organ of the plant, soil, sun exposure, climate, or even ways of cultivation.

There are several fast tests that estimate the content of these compounds as a whole by spectrophotometric methodologies. However, it is well stated that many of these compounds interact with the metabolic pathways and exert their effect on a structure-dependent manner. So, for understanding the mechanism of action of an extract, and more important, to obtain standardized extracts on the bioactive principles, the development of validated methodologies of identification, analysis, and quantification of individual components should be mandatory.

3.3.2 Relevance of the Claimed Effect

Another aspect that must not be overlooked is the nature of the intended claim. The use of clinical claims should be avoided (these could fall under the scope of the Directive 2004/24/EC for traditional herbal medicinal products, but not for health claims on foods). Claims too vague and unspecific also fall out of the consideration of the Regulation. It would be the case of “energy and vitality,” “tonic,” or “detoxification,” often used in plant extracts submissions.

Finally, it has to be assessed that the claimed effect has significance to human health. In this aspect, it is worthy to make a detailed analysis of the claims related to antioxidants.

3.3.2.1 “Antioxidant” Claims

More than half of the claimed effects for phytochemicals and plant extracts are related to their protective effect as antioxidants, and many products include this term on their presentations for marketing purposes.

In fact, a first discussion should contemplate the adequateness of the use of the term “antioxidants” as a nutrition claim. There are main differences between UE and US legislations.

In the USA, it has been finally included in the US Food Labeling Part of the Code of Regulations, § 101.54 (f), which states that “a nutrient content claim that characterizes the level of antioxidant nutrients present in a food may be used on the label or in the labeling of that food when: An RDI has been established for each of the nutrients; The nutrients that are the subject of the claim have recognized antioxidant activity; that is, when there exists scientific evidence that, following absorption from the gastrointestinal tract, the substance participates in physiological, biochemical, or cellular processes that inactivate free radicals or prevent free radical-initiated chemical reactions; The level of each nutrient that is the subject of the claim is sufficient to qualify for the claim The names of the nutrients that are the subject of the claim are included as part of the claim (e.g., – high in antioxidant vitamins C and E‖).”

In contraposition, the term “antioxidants” as a nutrition claim has not been included in the corresponding Annex for Nutrition Claims of the UE 1924/2006 Regulation or its amendments. In consequence, for submitting an antioxidant claim, it should be submitted as a health claim, and thus, the significance of the effect for human health has to be considered. And, in this case, the terminology used is of importance.

  • “Antioxidant activity, antioxidant capacity, antioxidant properties”: These claims would refer to the capacity of food/constituents to scavenge free radicals and/or to their reducing capacity, normally in in vitro models. Since there is no evidence that having antioxidant activity/content and/or antioxidant properties is a beneficial physiological effect on human health (factors such as bioavailability would affect the effects in human), it cannot be considered an acceptable claim [63].

  • “Protection of DNA, proteins, and lipids from oxidative damage.” This wording reflects correctly and effect that is significant for human health, and so it is acceptable.

3.3.3 Providing the Evidence from Science

The important objective for the development of health claims is to ensure that claims for food components and nutraceuticals are properly justified and they are scientifically substantiated [64]. The evidence provided has to be sufficient to establish a cause and effect relationship between the consumption of the ingredient and the claimed effect. For phytochemicals and plant extracts, it is often not the case. One of the main problems is that in many cases, only in vitro or animal studies have been conducted to sustain the evidence of the claim, or the human data consist of epidemiological studies. Information related to the pharmacopeia alone, often used for the plant extracts submissions, is also insufficient.

Substantiation of a claim should be based on human data, primarily from well-designed intervention studies considering target population, appropriate controls, adequate duration of exposure, and follow-up to demonstrate the intended effect [17]. Randomized clinical trials are the standard trials for providing evidence.

The design and quality of the human studies conducted is a key point to obtain a positive opinion about the scientific substantiation of the effect. Common mistakes include an inadequate choice of outcomes measured to assess the effect or the use of nonvalidated biomarkers, recruiting individuals not representative of the target population, or conducting studies with products that differ from the ingredient object of the claim.

The major factors involved in the design, conduct, and reporting of human studies can be adapted from the Consolidated Standards of Reporting Trials (CONSORT) checklist for medical trials [65]. Recently, the ILSI has published their own guidelines for the design, conduct, and reporting of human intervention studies to evaluate the health benefits of foods [66].

4 The Impact of New Methodologies for the Assessment of Functional Foods

4.1 Hyphenated Methods for the Characterization of Ingredients

The role of advances in chromatographic techniques has been a step point in the development of phytochemistry [67]. Because of the complexity of crude herbal extracts, various online hyphenated techniques have been developed for the analysis of the complex mixtures. These techniques include liquid chromatography (LC), mass spectrometry (MS), LC nuclear magnetic resonance (NMR), and LC-NMR-MS [68]. They facilitate the structure determination of unknown constituents in crude extracts. For example, they are of great applicability in the analysis of flavonoids and other phenolic compounds [69, 70].

Regarding MS instruments, time-of-flight detectors provide elevated mass resolution and accuracy over a broad mass of range, and thus help structural elucidation of nontargeted compounds based on accurate mass measurements and isotopic patterns. Triple quadrupole instruments are particularly well suited for targeted analysis and provide excellent sensitive and selectivity by performing tandem MS/MS analysis [71].

Despite the prominence attributed in scientific research to these hyphenated methodologies, other techniques are worth to be considered in the identification of bioactive vegetal compounds. High-performance thin-layer chromatography (HPTLC) is an evolution of thin layer chromatography (TLC) that remains the sole technique in which all the components of the sample are included in the chromatogram and presents the results as an image [67]. In HPLC, irreversible adsorption of some compounds can occur in the stationary phase, which in consequence cannot be eluted or detected, while TLC and HPTLC avoid this problem. Another technique avoiding this irreversible adsorption is countercurrent chromatography, which is an all-liquid separation technique which relies on the partition of a sample between two immiscible solvents [67], and can be used for the fractionation of crude plant extracts (in multigram quantities) or for final purification steps.

4.2 Bioinformatics

In several aspects, the approach toward finding a new functional ingredient is quite similar to the development of new pharmaceuticals. Bioinformatics tools have been largely employed as the first steps for drug design and recently, they are beginning to be used in connection with food or food-related components in several areas of food chemistry [72]. It is widely reported that natural compounds in the diet can improve health conditions and prevent disease by direct interaction with key proteins in metabolic pathways. For example, pure monacolin K (lovastatin) has been shown to be effective in reducing total cholesterol and LDL-cholesterol concentrations in individuals with hypercholesterolemia and is a well-known inhibitor of HMG-CoA reductase.

Studies of molecular similarity, pharmacophore modeling, molecular docking, and quantitative structure-analysis relationships (QSAR), based on in silico calculations, can be good screening methodologies for selecting those ingredients with the best predicted probability to interact with those targets and to predict their activity. At the same time, they can assist in formulating theoretical plausible mechanisms of action for the ingredients.

Molecular similarity searches are based on the hypothesis that similar molecules will have similar properties. In pharmacophore modeling, the chemical features and conformation of the modulating ligands in relation to the target proteins is extracted from 3D structures, and in consequence the response of multiple ingredients can be screened depending on their fitting with this model. Molecular docking actually calculates the best conformation of a molecule to fit into the target-binding pocket. In the case of QSAR models, a prediction of the activity of molecules according to 2D or 3D descriptors is obtained after establishing a model with experimentally measured outcomes.

4.3 Omics Data

One of the biggest challenges in nutrition is the establishment of adequate biomarkers that are able to predict health benefits, as well as early indicators for disease risk [73]. Nowadays, new -omics technologies are used in nutrition research, giving access to holistic discovery of efficacy biomarkers by transcriptomics, proteomics, and metabolomics data. They are considered by the ILSI as emerging technologies for efficacy demonstration [74].

Transcriptomic studies, which analyze gene expression, have improved the understanding of the complex interaction between genetic and environmental factors, such as lifestyle and nutrition. Transcriptomic technologies have arguably achieved the highest level of technical maturity of any of the functional genomics. Production of very high-quality, genome-wide expression profiling data by DNA microarrays is now a routine matter.

Proteomics is a central platform in elucidating the molecular events in nutrition: It can identify and quantify bioactive proteins and peptides and address questions of nutritional bioefficacy. The advances in methods of separation of peptides by microflow and nanoflows or chip detections, as well as mass spectrometry–rooted proteomic techniques like MALDI-TOF for protein identification and quantification have been pivotal in the application of these methodologies to understand nutritional effects of ingredients [75].

Metabolomics is the comprehensive analysis of metabolites and has gained a strong impact on nutritional research [76]. The great asset of these methodologies is the quantitative, noninvasive analysis of easily accessible human body fluids like urine, blood, saliva, and tears. The metabolome is complex, and thus requires multiple highly sophisticated techniques of separation and identification, such as NMR and MS. Additionally, the use of chemometrics for analyzing the complex data obtained is mandatory [73].

5 Conclusions

The functional foods and nutraceuticals market is one of the healthiest sectors in food industry, and is experiencing a continuous growth even in the context of an economic recession. However, to keep being successful, it is mandatory to assure the acceptance and awareness of consumers. The presence of many ingredients whose efficacy can be doubted can first mislead consumers and later compromise the credibility of the whole functional foods concept.

In consequence, manufacturers have to collaborate actively with academic researchers in order to provide the scientific evidence to substantiate health claims. This substantiation has to address three main points: the characterization of the ingredient, the relevance of the claimed effect, and the establishment of a cause and effect relationship between the ingredient’s intake and the claimed effect by efficacy studies on human intervention trials. These trials have to follow strict criteria of quality and design in order to be successful, especially by choosing adequate participants, outcomes, and biomarkers.

At the same time, scientific research is very important for the development of new functional foods. Discoveries provided by holistic techniques like -omics methodologies are allowing a better comprehension of the effects of nutrition and the interaction with the human metabolism. This will allow to define new biomarkers, especially early indicators of disease risk, that will contribute to designing new functional products.