14 Functional foods category that does not include supplement. It is also a concept that belongs to nutrition and not to pha logy. Functional foods are and must be foods, not drugs, as they have no therapeutic effects. Moreover their role carding disease will, in most cases, be in reducing the risk of disease rather an preventing It 1.2.2 Functional food: a European consensus, 24,25 The unique features of functional food are being a conventional or everyday food to be consumed as part of the normal/usual diet of naturally occurring(as opposed to synthetic)components perhaps in unnatural concentration or present in foods that would not normally supply them having a positive effect on target function(s) beyond nutritive value/basic nutrition may enhance well-being and health and/or reduce the risk of disease or provide health benefits so as to improve the quality of life including physical psychological and behavioural performances have authorised and scientifically based claims It is in that general context that the European Commissions Concerted Action on Functional Food Science in Europe(FUFOSE), which actively involved a large number of the most prominent European experts in nutrition and related sciences, has been coordinated by the International Life Science Institute-ILSI Europe. It developed in early 1996 to reach a European Consensus on"Scientific Concepts of Functional Foods' in 1998. To reach that final objective, three undertaken 1. Critical assessment of the science base required to provide evidence that specific nutrients and food components positively affect target functions in 2. Examination of the available science from a function-driven perspective rather than a product-driven one 3. Elaboration of a consensus on targeted modifications of food and food constituents, and options for their applications In that context, target function refers to genomic, biochemical, physiological psychological or behavioural functions that are relevant to the maintenance of a state of well-being and health or to the reduction of the risk of a disease Modulation of these functions should be quantitatively evaluated by measuring change in serum or other body fluids of the concentration of a metabolite,a specific protein or a hormone, change in the activity of enzymes, change in physiological parameters(e.g. blood pressure, gastrointestinal transit time, etc. ) hange in physical or intellectual performances, and so on The major deliverables of that Concerted Action are three publication
category that does not include dietary supplement. It is also a concept that belongs to nutrition and not to pharmacology. Functional foods are and must be foods, not drugs, as they have no therapeutic effects. Moreover their role regarding disease will, in most cases, be in reducing the risk of disease rather than preventing it. 1.2.2 Functional food: a European consensus9, 24, 25 The unique features of functional food are: • being a conventional or everyday food • to be consumed as part of the normal/usual diet • composed of naturally occurring (as opposed to synthetic) components perhaps in unnatural concentration or present in foods that would not normally supply them • having a positive effect on target function(s) beyond nutritive value/basic nutrition • may enhance well-being and health and/or reduce the risk of disease or provide health benefits so as to improve the quality of life including physical, psychological and behavioural performances • have authorised and scientifically based claims. It is in that general context that the European Commission’s Concerted Action on Functional Food Science in Europe (FUFOSE), which actively involved a large number of the most prominent European experts in nutrition and related sciences, has been coordinated by the International Life Science Institute – ILSI Europe. It developed in early 1996 to reach a European Consensus on ‘Scientific Concepts of Functional Foods’ in 1998.9 To reach that final objective, three major steps were undertaken: 1. Critical assessment of the science base required to provide evidence that specific nutrients and food components positively affect target functions in the body. 2. Examination of the available science from a function-driven perspective rather than a product-driven one. 3. Elaboration of a consensus on targeted modifications of food and food constituents, and options for their applications.24 In that context, ‘target function’ refers to genomic, biochemical, physiological, psychological or behavioural functions that are relevant to the maintenance of a state of well-being and health or to the reduction of the risk of a disease. Modulation of these functions should be quantitatively evaluated by measuring change in serum or other body fluids of the concentration of a metabolite, a specific protein or a hormone, change in the activity of enzymes, change in physiological parameters (e.g. blood pressure, gastrointestinal transit time, etc.), change in physical or intellectual performances, and so on. The major deliverables of that Concerted Action are three publications: 14 Functional foods
Defining functional foods 15 1. Functional Food Science in Europe reviews the published literature to define the state of the art with respect to specific body systems, the methodologies to characterise and quantify specific related functions, the utritional options modulating these fur related to these nutritional options, the role of food technology in nutritional and safety aspects and the science base required for providing evidence that specific nutrients positively affect function 2. Technological Aspects of Functional Food Science reviews the impact of processing, the importance of the source of materials to prepared food products, processing options to modulate functionality, safety implications of materials and processes, and process monitoring of functions. 25 3. Scientific Concepts of Functional Foods in Europe: a consensus that proposes, for the first time, a consensual framework for the development of functional foods and for the elaboration of a scientific basis for claims g As already indicated above, because functional food is a concept rather than a well-defined group of food products, that consensus document proposes a working definition A food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond dequate nutritional effects, in a way that is relevant to either improved stage of health and well-being and/or reduction of risk of disease. A functional food must remain food and it must demonstrate its effects in amounts that can normally be expected to be consumed in the diet: it is not a pill or a capsule, but part of the normal food patten The main aspects of this working definition are the food nature of functional food that is not a pill, a capsule or any form of etary supplement the demonstration of the effects to the satisfaction of the scientific community he beneficial effects on body functions, beyond adequate nutritional effects hat are relevant to improved state of health and well-being and/or reduction of risk(not prevention) of disease the consumption as part of a normal food pattern The definition encompasses all main features of functional foods identified above, it is aimed at stimulating research and development in the field of nutrition so as to contribute adequately to the scientific knowledge that will be required to define optimum(optimised)nutrition by elaborating new dietary guidelines. However, it should be emphasised that a functional food will not necessarily be functional for all members of the population, and that matching individual biochemical needs with selected food component intakes may become key task as we progress in our understanding of the interactions between genes and diet. From a practical point of view, a functional food can be
1. Functional Food Science in Europe reviews the published literature to define the state of the art with respect to specific body systems, the methodologies to characterise and quantify specific related functions, the nutritional options modulating these functions, the safety implications related to these nutritional options, the role of food technology in nutritional and safety aspects and the science base required for providing evidence that specific nutrients positively affect function.24 2. Technological Aspects of Functional Food Science reviews the impact of processing, the importance of the source of materials to prepared food products, processing options to modulate functionality, safety implications of materials and processes, and process monitoring of functions.25 3. Scientific Concepts of Functional Foods in Europe: a consensus that proposes, for the first time, a consensual framework for the development of functional foods and for the elaboration of a scientific basis for claims.9 As already indicated above, because functional food is a concept rather than a well-defined group of food products, that consensus document proposes a working definition: A food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way that is relevant to either improved stage of health and well-being and/or reduction of risk of disease. A functional food must remain food and it must demonstrate its effects in amounts that can normally be expected to be consumed in the diet: it is not a pill or a capsule, but part of the normal food pattern.9 The main aspects of this working definition are: • the food nature of functional food that is not a pill, a capsule or any form of dietary supplement • the demonstration of the effects to the satisfaction of the scientific community • the beneficial effects on body functions, beyond adequate nutritional effects, that are relevant to improved state of health and well-being and/or reduction of risk (not prevention) of disease • the consumption as part of a normal food pattern. The definition encompasses all main features of functional foods identified above; it is aimed at stimulating research and development in the field of nutrition so as to contribute adequately to the scientific knowledge that will be required to define optimum (optimised) nutrition by elaborating new dietary guidelines. However, it should be emphasised that a functional food will not necessarily be functional for all members of the population, and that matching individual biochemical needs with selected food component intakes may become a key task as we progress in our understanding of the interactions between genes and diet.8 From a practical point of view, a functional food can be: Defining functional foods 15
16 Functional foods a natural food a food to which a component has been added a food from which a component has been removed a food where the nature of one or more components has been modified a food in which the bioavailability of one or more components has been modified or any combination of these possibilities 1.3 Functional food science Being foods, functional foods need to be safe according to all criteria defined in current food regulations. But in many cases, new concepts and new procedures will need to be developed and validated to assess functional food risks. In Europe, some, but certainly not all, functional foods will be classified as'novel foods' and consequently will require the decision tree assessment regarding safety that is described in the EU Novel Food Regulation. 26 However, it must be emphasised that this reg gulation not concern nutritional properties or the physiological effects of these novel foods. It is strictly a safety regulation. The requirement for safety is a prerequisite to any functional food development. Indeed, the risk versus benefit concept, which is familiar to pharmacologists developing new drugs, does not apply to functional foods except perhaps in very specific conditions for disease risk reduction when the scientific evidence is particularly strong. As described in the European The design and development of functional foods is a key issue, as wel as a scientific challenge, which should rely on basic scientific knowl- edge relevant to target functions and their possible modulation by food components. Functional foods themselves are not universal and a food based approach would have to be influenced by local considerations contrast, a science-based approach to functional food is universal The function-driven approach has the science base as its foundation-in order to gain a broader understanding of the interactions between diet and health. Emphasis is then put on the importance of the effects of food well-identified and well-characterized tions in the body that are relevant to well-being and health issues, rather than, solely, on reduction of disease risk By reference to the new concepts in nutrition outlined above, it is the role of Functional Food Science to stimulate research and development of functional foods(see Fig. 1.1 By reference to basic knowledge in nutrition and related biological sciences, such a development requires the identification and, at least partly,an understanding of the mechanism(s)by which a potential functional food or Unctional food component can modulate the target function(s) that is/are
• a natural food • a food to which a component has been added • a food from which a component has been removed • a food where the nature of one or more components has been modified • a food in which the bioavailability of one or more components has been modified, or • any combination of these possibilities. 1.3 Functional food science Being foods, functional foods need to be safe according to all criteria defined in current food regulations. But in many cases, new concepts and new procedures will need to be developed and validated to assess functional food risks. In Europe, some, but certainly not all, functional foods will be classified as ‘novel foods’ and consequently will require the decision tree assessment regarding safety that is described in the EU Novel Food Regulation.26 However, it must be emphasised that this regulation does not concern the nutritional properties or the physiological effects of these novel foods. It is strictly a safety regulation. The requirement for safety is a prerequisite to any functional food development. Indeed, the risk versus benefit concept, which is familiar to pharmacologists developing new drugs, does not apply to functional foods except perhaps in very specific conditions for disease risk reduction when the scientific evidence is particularly strong. As described in the European consensus document:9 The design and development of functional foods is a key issue, as well as a scientific challenge, which should rely on basic scientific knowledge relevant to target functions and their possible modulation by food components. Functional foods themselves are not universal and a foodbased approach would have to be influenced by local considerations. In contrast, a science-based approach to functional food is universal . . . The function-driven approach has the science base as its foundation – in order to gain a broader understanding of the interactions between diet and health. Emphasis is then put on the importance of the effects of food components on well-identified and well-characterized target functions in the body that are relevant to well-being and health issues, rather than, solely, on reduction of disease risk. By reference to the new concepts in nutrition outlined above, it is the role of Functional Food Science to stimulate research and development of functional foods (see Fig. 1.1). By reference to basic knowledge in nutrition and related biological sciences, such a development requires the identification and, at least partly, an understanding of the mechanism(s) by which a potential functional food or functional food component can modulate the target function(s) that is/are 16 Functional foods
Defining functional foods 17 Function Functional effect ypothesis-driven human nutrition studies Enhanced function Claim Disease risk reduction Fig. 1. 1 The strategy for functional food development recognised or proven to be relevant to the state of well-being and health, and/or the reduction of a disease risk. Epidemiological data demonstrating a statistically validated and biologically relevant relationship between the intake of specific food components and a particular health benefit will, if available, be very useful. The conclusion of that first step will be the demonstration of a functional effect that should serve to formulate hypotheses to be tested in a new generation of human nutrition studies aimed to show that relevant (in terms of dose, frequency, duration, etc. intake of the specified food will be associated with improvements in one or more target functions, either directly or indirectly in terms of a valid marker of an improved state of well-being and health and/or reduced disease risk. If well supported by strong scientific evidence, the conclusion could be a recommendation for improved or new dietary guidelines The new-generation human nutrition studies should be hypothesis driven but, in many cases, they will differ quite substantially from what is classically referred to as clinical studies The main differences are that nutrition studies aim at testing the effect of a food as part of the ordinary diet; they may concern the general population or generally large, at-risk target groups, they are not diagnostic; or symptom based; and they are not planned to evaluate a risk versus benefit approach. Most of these studies will rely on change(s) in validated/ relevant markers to demonstrate a positive modulation of target functions after (long-term) consumption of the potential functional food. A(double) blind ty of design based on parallel groups rather than crossing-over will generally be appropriate. Data from these studies should be collected and handled according to good standards for data management, and data analysis should prove statistical as well as biological significance. Finally, the long-term consequences of interaction(s) between functional foods and body function(s) will have to be carefully monitored 1.3.1 Markers: key to the development of functional foods The development of functional foods will, in most cases, rely on measurements of ' markers. These markers need to be identified and validated for their
recognised or proven to be relevant to the state of well-being and health, and/or the reduction of a disease risk. Epidemiological data demonstrating a statistically validated and biologically relevant relationship between the intake of specific food components and a particular health benefit will, if available, be very useful. The conclusion of that first step will be the demonstration of a functional effect that should serve to formulate hypotheses to be tested in a new generation of human nutrition studies aimed to show that relevant (in terms of dose, frequency, duration, etc.) intake of the specified food will be associated with improvements in one or more target functions, either directly or indirectly in terms of a valid marker of an improved state of well-being and health and/or reduced disease risk. If well supported by strong scientific evidence, the conclusion could be a recommendation for improved or new dietary guidelines. The new-generation human nutrition studies should be hypothesis driven but, in many cases, they will differ quite substantially from what is classically referred to as clinical studies.The main differences are that nutrition studies aim at testing the effect of a food as part of the ordinary diet; they may concern the general population or generally large, at-risk target groups; they are not diagnostic; or symptom based; and they are not planned to evaluate a risk versus benefit approach. Most of these studies will rely on change(s) in validated/ relevant markers to demonstrate a positive modulation of target functions after (long-term) consumption of the potential functional food. A (double) blind type of design based on parallel groups rather than crossing-over will generally be appropriate. Data from these studies should be collected and handled according to good standards for data management, and data analysis should prove statistical as well as biological significance. Finally, the long-term consequences of interaction(s) between functional foods and body function(s) will have to be carefully monitored. 1.3.1 Markers: key to the development of functional foods The development of functional foods will, in most cases, rely on measurements of ‘markers’. These markers need to be identified and validated for their Fig. 1.1 The strategy for functional food development Defining functional foods 17
1 8 Functional foods predictive value of potential benefits to a target function or the risk of a particular disease Markers of correlated events are indicators whereas markers representing an event directly involved in the process are factors.When related to the risk of disease. indicators and even factors might. in some instances, be equivalent to surrogate markers' defined as a biologic observation, result or index that predicts the development of chronic disease The more that is known about the mechanisms leading to health outcomes the more refined will be the identification of the markers and their appreciation. The markers should be feasible, valid, reproducible, sensitive and specific. They can be biochemical, physiological, behavioural or psychological in nature. However dynamic responses might be as useful as, or more useful than, static or single point measurements. In many cases, a battery of markers might be needed in order to create a decision tree from multiple tests(see Fig. 1.2 These markers. most of which still need to be identified and validated will Exposure to the food component under study by measuring serum, faecal, urine or tissue level of the food component itself or its metabolite(s), or the oncentration of an endogenous molecule that is directly influenced by the consumption of the food Target function(s) or biological response such as change in serum or body fluids of the concentration of a metabolite, a specific protei enzyme, a hormone, etc These first two markers are either indicators or factors An appropriate endpoint of an improved state of well-being and health and/or reduction of a disease risk. Such a marker is likely to be a factor rather than an indicator Individual susceptibility or genetic polymorphism controlling the metabolism and/or the effect of the food component under study Markers of Consumption of Markers of functional food target function/ biological response of disease Markers]of endpoint Fig. 1. 2 Markers for functional food development
predictive value of potential benefits to a target function or the risk of a particular disease. Markers of correlated events are ‘indicators’ whereas markers representing an event directly involved in the process are ‘factors’. 9 When related to the risk of disease, indicators and even factors might, in some instances, be equivalent to ‘surrogate markers’ defined as a biological observation, result or index that predicts the development of chronic disease.27 The more that is known about the mechanisms leading to health outcomes, the more refined will be the identification of the markers and their appreciation. The markers should be feasible, valid, reproducible, sensitive and specific. They can be biochemical, physiological, behavioural or psychological in nature. However, dynamic responses might be as useful as, or more useful than, static or single point measurements. In many cases, a battery of markers might be needed in order to create a decision tree from multiple tests (see Fig. 1.2). These markers, most of which still need to be identified and validated, will relate to: • Exposure to the food component under study by measuring serum, faecal, urine or tissue level of the food component itself or its metabolite(s), or the concentration of an endogenous molecule that is directly influenced by the consumption of the food component. • Target function(s) or biological response such as change in serum or other body fluids of the concentration of a metabolite, a specific protein, an enzyme, a hormone, etc. These first two markers are either indicators or factors. • An appropriate endpoint of an improved state of well-being and health and/or reduction of a disease risk. Such a marker is likely to be a factor rather than an indicator. • Individual susceptibility or genetic polymorphism controlling the metabolism and/or the effect of the food component under study.8 ! " Fig. 1.2 Markers for functional food development 18 Functional foods