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Functional food science in Europe

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Europea n Commission
Community research
Project report
Functional food science
in Europe
Volume 1
^ ^ FAIR
Agriculture and fisheries
From scientific evidence based on markers for functional foods to types
of claims relevant to them
Consumption /Marker s of / ^ Markers of
o f tar /exDosure / 9.et
functional
food
component
TYPE Β CLAIMS
(reduced risk of disease)
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Functional food science in Europe
Volume 1
FAIR
Agriculture and fisheries
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2000 EUR 18591 LEGAL NOTICE
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PRINTED ON WHITE CHLORINE-FREE PAPER SI
Preface
This concerted action 'Functional Food Science in Europe' The food area is important within this programme and is
(FUFÓSE) has been funded within the FAIR RTD covered by the theme 'Generic Science and Advanced
programme, which is part of the Commission's Fourth Technologies for Nutritious Foods'.
Framework Programme for research and technological There is growing interest in Europe in the concept of
development. 'Functional Foods' and this concerted action, bringing
This programme aims at promoting trans-European together Europe's scientists and industry, is fundamental
research in the primary production sectors of agriculture, to establishing a science-based approach to such foods.
horticulture, forestry, fisheries, and aquaculture, linking Liam Breslin
these with the input and processing industries, particularly European Commission
food processing and renewable biomaterials. DG XII - FAIR Programme S3
Foreword
also include foods in which a potentially harmful component Introduction
has (or components have) been removed by technological
We stand today at the threshold of a new frontier in means.
nutritional sciences. The concepts of food are changing
from a past emphasis on survival, hunger satisfaction,
European Commission objectives absence of adverse effect on health, and health maintenance
to an emphasis on the promising use of foods to promote An important objective is to improve the understanding of
better health and well-being, thus helping to reduce the risk the role of food in the general health and well-being of the
of chronic illnesses such as cardiovascular disease, some European consumer. Food can play a major role in main­
cancers and obesity. taining and improving human health and well-being and in
These new concepts are of particular importance in view reducing the risk of major diseases. This will also lead to the
of the benefits for health, consumer demand, the demand of design of special or tailored foodstuffs and ingredients for
the elderly population for an improved quality of their late specific population groups or for specific health benefits.
life, the continuous increase in life expectancy, the increas­ This will be an expanding area for the food industry in the
ing cost of health care, technical advances in the food future, and European industry, building on the considerable
industry, and the changing regulatory environment. European research expertise, must be at the forefront here.
There is already a recognition that European research This will involve multidisciplinary research projects com­
expertise must be at the forefront in understanding the role bining the expertise of scientific partners, such as bioche­
of food in the maintenance and improvement of human mists, nutritionists, the medical professionals and process
health and well-being, in the reduction of risk of major technologists.
diseases and in improving the competitive position of the The food and drink industry ranks as a major European
European food industry. The number of major research industry processing raw materials from agriculture, horti­
programmes designed to investigate and clarify the health- culture, fisheries and aqua-culture into the diverse range of
promoting value of foods and food components is forecast to quality foodstuffs which are produced throughout Europe.
continue to grow, particularly where serious debilitating Research in this sector has the major objective to improve
diseases are concerned, e.g. heart disease, cancers and the competitive position of the food industry which is
osteoporosis. composed of leading multinationals and a wide range of
The most recent knowledge in biochemistry, cell biology small and medium-sized enterprises specializing in food
and physiology, but also in pathology, supports the hypothesis throughout Europe.
that diet also controls and modulates various functions in
the body, and, in doing so, participates in the maintenance of ILSI Europe's role the state of good health necessary to reduce the risk of some of
the diseases. It is such an hypothesis which is at the origin In response to these critical developments, ILSI Europe has
both of the concept of 'functional food' and the development elaborated a project proposal for a European Commission
of a new scientific discipline 'functional food science'. Concerted Action aimed at establishing a science-based
approach for concepts in functional food science. The goal Functional food science aims to (1) identify beneficial
interactions between the presence or absence of a food of this concerted action is to establish a multidisciplinary
component (whether a macronutrient, micronutrient or so- European network to (1) critically assess the science base
called non-nutrient) and a specific function or functions in required to provide evidence that specific nutrients posi­
the body, and (2) understand their mechanisms, so as to tively affect functions, (2) examine the available science
support hypotheses to be tested in protocols relevant for from a function-driven point of view rather than a nutrient-
human studies. The demonstration, in human subjects, of a driven one, and (3) reach consensus on targeted modifica­
specific interaction with one or a limited number of func­ tions of food and food constituents, and options for their
tions in the body will support a specific, often well-defined, application. This approach aims to provide key actors from
claim of functional effects or disease risk reduction. Func­ Europe's food and agricultural industry, governmental and
tional food science is indeed part of nutrition science, where inter-governmental bodies and the scientific community
the objectives are to maintain health and improve well- with an opportunity to exchange ideas and interact on a
being and to create the conditions for disease risk reduction, neutral platform.
and it is, in this respect, quite distinct from the medical or
pharmaceutical sciences, where the objectives are mainly to
The project cure diseases.
A food is said to be 'functional' if it contains 'a food The Functional Food Science in Europe (FUFÓSE) project
component (whether a nutrient or not) which affects one or was submitted in March 1995, approved in November
more targeted functions in the body in a positive way'. It can 1995 and was expected to attain its objectives over a period S4 Foreword
of 3 years. Project management and coordination was (5) Research needs.
especially provided by ILSI Europe. Overall guidance on (6) Communication of the health benefits of functional
scientific and organizational issues was ensured through a foods.
steering committee, comprising members from both industry (7) Conclusions.
and academia.
The expert group that undertook the elaboration of the
To attain the project objectives, the steering committee text was composed of two ITG chairs and four members of established individual theme groups (ITG) and organized a
the steering committee. The document is currently under series of plenary meetings.
review. The goal is to publish this consensus document also
The project started with a first plenary meeting, Functional in the British Journal of Nutrition.
Food Science in Europe: State of the Art, held 2­4 April 1996
in Nice, France. Based on the results of this meeting, six areas
Food technology in human physiology were identified to be reviewed by the
ITG responsible for producing theme papers to critically A group of experts on food technology have also been
review the science base of the concept. The final composition selected to examine the impact and feasibility of food
of the ITG included industry and non­industry scientists. A technology on functional food development. Relevant view­
draft brief was prepared by the steering committee to be points are: safety, nutrition and consumer acceptance/
addressed by each ITG while reviewing the literature data: sensory quality. This expert group has identified areas to
concentrate on and terms of reference to be followed. Once (1) characterize specific body systems, including state­of­
the report is completed, it will be reviewed by the partici­the­art;
pants in the third plenary meeting. As soon as the comments (2) critically assess methodologies to characterize and
are all taken into consideration, the paper will be published quantify specific related functions;
in a scientific journal. (3) identify and critically assess nutritional options modu­
lating these functions;
(4) evaluate potential safety implications related to these Acknowledgements
nutritional options;
We wish to thank, especially, all of the individual contri­(5) identify the role of food technology in nutritional and
butors to this FUFÓSE project for devoting their time and safety aspects;
efforts within such a tight timeframe. Their commitment (6) critically assess the science base required for providing and dedication will be remembered as exceptional and evidence that specific nutrients positively affect functions;
highly enthusiastic. Authors and contributors can be assured (7) identify areas where further research is required.
of ILSI Europe's recognition and they will be paid tribute,
The resulting documents were scrutinized in a Second as often as possible. Through their collaborative work they
Plenary Meeting held in July 1997 in Helsinki, Finland, and have participated in the making of ILSI Europe's history
revised by the ITG chairs to include the comments made. and the Institute is extremely grateful to all.
The final reports of the six ITG are published in this issue of
Coordinator: Dr Berry Danse, the British Journal of Nutrition.
ILSI Europe, The papers need to be considered in the context of the
83 Avenue E. Mounier, Box 6, entire project. They are not individual contributions and
B­1200 Brussels, Belgium. they form, all together, the reference to the FUFÓSE
project. Some repetitions, overlaps and contradictions may Scientific coordinator: Prof. Marcel Roberfroid,
still appear. Only by reviewing all six papers will the reader Catholic University of Louvain,
have a balanced overview of both primary and secondary Ecole de Pharmacie,
effects of functional foods. Tour Van Helmont,
73 Avenue E. Mounier,
Consensus document B­1200 Brussels, Belgium.
These ITG papers provided the building blocks for a EC responsible: Dr Liam Breslin,
more general consensus document Concepts in Functional Agro­industrial Research, Food,
Food Science and Options for their Application. The outline Commission of the European
of this consensus document was prepared based on the Communities,
recommendations of the ITG and the steering committee Directorate­General ΧΠ, Science,
members. This outline was also reviewed by the participants Research and Development,
in the second plenary meeting who provided comments to be 200 Rue de la Loi,
taken into consideration. The topics that will be addressed in B­1049 Brussels, Belgium.
the consensus document include the following.
Project manager; Dr Laura Contor,
(1) Introduction. ILSI Europe,
(2) Scientific basis for functional food science. 83 Avenue E. Mounier, Box 6,
(3) Target functions in relation to health outcome. B­1200 Brussels, Belgium.
(4) Food technology.
© Nutrition Society 1998 S5
Growth, development and differentiation: a functional food science approach
1 2 3 4 5 6 7 8 B. Koletzko *, P. J. Aggett , J. G. Bindels , P. Bung , P. Ferré , A. Gil , M. J. Lentze , M. Roberfroid
9 and S. Strobel
1 Kinderpoliklinik, Klinikum Innenstadt der Ludwig­Maximilians­Universität, Pettenkoferstr. 8a, D­80336 München, Germany
2Institute of Food Research, Norwich Laboratory, Norwich Research Park, Colney, Norwich NR4 7UA, UK
3Nutricia Research, Verenigde Bedrijven Nutricia NV, PO Box 1, NL­2700 MA Zoetermeer, The Netherlands
4 University of Bonn, Women's Hospital, Sigmund­Freud­Strasse 25, D­53105 Bonn, Germany
SINSERM, Unité 465, Centre Biomédical des Cordeliers, 15, rue de l'Ecole de Médecine, F­75270 Paris, France
6 University of Granada, School of Pharmacy, Department of Biochemistry and Molecular Biology, Campus of Cartuja,
E­18071 Granada, Spain
1 University of Bonn, Children's Hospital, Adenauerallee 119, D­53113 Bonn, Germany
SUCL, Ecole de Pharmacie, Tour Van Helmont, Avenue E. Mounier, B­1200 Brussels, Belgium
9 Clinical Sub­Dean's Office, Institute of Child Health, 30 Guilford Street, London WC IN 1EH, UK
Contents
1. Introduction S7 5.5. Human milk oligosaccharides and growth S16
2. Nutrient-gene interaction, genetic regulation S7 5.6. Free amino acids and tissue growth S16
2.1. Introduction S7 5.7. Polyamines and tissue growth S17
S17 2.2. Modulation of gene expression participates in the 5.8. Dietary nucleotides and tissue growth
S17 adaptations of energy metabolism S8 5.8.1. Nucleotides and small intestine growth
S17 2.3. Examples of gene regulation by nutrients S8 5.8.2. and liver growth
2.3.1. Carbohydrates S8 5.9. Long­chain polyunsaturated fatty acids and cell
2.3.2. Fatty acids S9 growth S18
2.3.3. Cholesterol S9 5.10. Early growth and later obesity S18
2.3.4. Amino acids S9 Maturation of the gastrointestinal tract S18
Nutrients and cell differentiation S10 6.1. Introduction S18 2.4.
2.4.1. Fatty acids S10 6.2. Development of sugar hydrolases and transporters S18
6.3. Biosynthesis of intestinal brush­border membrane 2.4.2. Retinole acid S10
hydrolases 2.5. Concluding remarks S10 S19
6.4. Intestinal absorption of glucose and fructose 3. An overview of programmed cell death (apoptosis) S10 S20
4. Supply of food ingredients before and during 6.5. Oligosaccharides and mucins S20
pregnancy S12 6.6 Probiotic substances in milk or milk substitutes S21
4.1. Physiological aspects of nutritional requirements 6.7. Dietary regulation of xenobiotic metabolism S21
in pregnancy SI2 Development of the immune system S21
4.1.1. Energy SI2 7.1. Introduction S21
4.1.2. Protein S13 7.1.1. Which constituents of the immune system to
4.1.3. Carbohydrates SI3 investigate? S22
4.1.4. Lipids S13 7.1.2. Special considerations for the immune
S22 4.1.5. Vitamins, minerals and trace elements S14 system of the developing child
S22 5. Modulation of growth SIS 7.2. Antioxidants and vitamins
5.1. Introduction S15 7.2.1. In general S22
5.2. Methods for the determination of growth SI 5 7.2.2. Vitamin A S22
Growth factors in human milk and their influence 7.2.3. C S22 5.3.
S22 on infant growth S16 7.2.4. Vitamin B complex
S22 5.4. Potential roles of non­protein nitrogen compounds 7.2.5. E
S22 as growth modulators S16 7.2.6. Vitamin D
Abbreviations: APRT, adenosine phosphoribosyltransferase; cDNA, complementary DNA; DEXA dual­energy X­ray absorptiometry; DHA,
docosahexaenoic acid; EFA, essential fatty acids; EGF, epidermal growth factor; GLUT, glucose transporter; hGH, human growth hormone; HGPRT,
hypoxanthine phosphoribosyltransferase; ΗΡΑ, hyperphenylalaninaemia; IDDM, insulin­dependent diabetes mellitus; Ig, immunoglobulin; IGF, insulin­
like growth factor; LPH, lactase­phlorizin­hydrolase; MUC1, high­molecular mass glycoprotein; NPN, non­protein nitrogen; PAH, phenylalanine
hydroxylase; PCD, programmed cell death; PKU, phenylketonuria; PPAR, peroxisome proliferator activated receptors; PUFA, polyunsaturated fatty acids;
SGLT1, sodium­dependent glucose transporter 1; SI, sucrase­isomaltase; SPA, single­photon absorptiometry; SREBP, sterol regulatory element binding
protein; XME, xenobiotic­metabolizing enzymes.
»Corresponding author: Professor B. Koletzko, fax +49 89 5160 3336, email: berthold.koletzko@kk­i.med.uni­muenchen.de S6 Β. Koletzko et al.
7.3. Multiple micronutrient supplementation studies S23 8.4. Bone growth and mineralization in infants and
7.4. Fatty acids S2young children S26
7.5. Arginine3 8.5. Calcium supplementation in children and
7.6. Nucleotidesadolescents and bone health7
7.7. Maturation of the immune system in formula-fed v. 8.6. Nutrients other than calcium and environmental
breast-fed infantsfactors involved in bone growth S2
7.7.1. Effects of antigen transfer via breast milk 9. Nutrient effects on development of neural functions
on the infant's immunity S24 and behaviour8
9.1. Introduction7.7.2. Maternal diet during pregnancy and effects
9.2. Physiology of neural developmenton the infant's immunity
Nutrition and S29 7.7.3. Maternal diet during pregnancy and 9.3.
lactation S29.3.1. Protein S2
7.8. Role of the gut flora and probiotic bacteria in the 9.3.2. Iodine
infant's immunity and gut defence4 9.3.3. Iron
7.8.1. Immune exclusion and elimination S29.3.4. Zinc9
7.9. Effects of formulas with protein hydrolysates on 9.3.5. Polyunsaturated fatty acids S2
the infant's immune responses S29.4. Early nutrition and development of taste
7.10. Insulin-dependent type 1 diabetes mellitus and preferences S30
cow's milk exposure in infancy5 9.5. Methodological aspects S30
Bone growth and mineralization10. Production of bioactive factors for inclusion into
8.1. Cell biology of bone growthfood products
8.2. Methodological aspects in bone-mass-related studies S211. Commentary on biomarkers1
8.3. Peak bone mass and relative risk of osteoporosis S26 12. Conclusions3
Abstract
Few other aspects of food supply and metabolism are of greater biological importance than the
feeding of mothers during pregnancy and lactation, and of their infants and young children.
Nutritional factorsg early development not only have short-term effects on growth, body
composition and body functions but also exert long-term effects on health, disease and mortality
risks in adulthood, as well ast of neural functions and behaviour, a phenomenon
called 'metabolic programming'. The interaction of nutrients and gene expression may form the
basis of many of these programming effects and needs to be investigated in more detail. The
relation between availability of food ingredients and cell and tissue differentiation and its
possible uses for promoting health and development requires further exploration. The course of
pregnancy, childbirth and lactation as well as human milk composition and the short- and long-
term outcome of the child are influenced by the intake of foods and particularly micronutrients,
e.g. polyunsaturated fatty acids, Fe, Zn and I. Folic acid supplementation from before conception
through the first weeks of pregnancy can markedly reduce the occurrence of severe embryonic
malformations; other potential benefits of modulating nutrient supply on maternal and child
health should be further evaluated. The evaluation of dietary effects on child growth requires
epidemiological and field studies as well asn of specific cell and tissue growth. Novel
substrates, growth factors and conditionally essential nutrients (e.g. growth factors, amino acids,
polyunsaturated fatty acids) may be potentially useful as ingredients in functional foods and need
to be assessed carefully. Intestinal growth, maturation, and adaptation as well as long-term
function may be influenced by food ingredients such as oligosaccharides, gangliosides, high-
molecular-mass glycoproteins, bile salt-activated lipase, pre- and probiotics. There are indica­
tions for some beneficial effects of functional foods on the developing immune response, for
example induced by antioxidant vitamins, trace elements, fatty acids, arginine, nucleotides, and
altered antigen contents in infant foods. Peak bone mass at the end of adolescence can be
increased by dietary means, which is expected to be of long-term importance for the prevention of
osteoporosis at older ages. Future studies should be directed to the combined effects of Ca and
other constituents of growing bone, such as P, Mg and Zn, as well as vitamins D and K, and the
trace elements F and B. Pregnancy and the first postnatal months are critical time periods for the
growth and development of the human nervous system, processes for which adequate substrate
supplies are essential. Early diet seems to have long-term effects on sensory and cognitive
abilities as well as behaviour. The potential beneficial effects of a balanced supply of nutrients
such as I, Fe, Zn and polyunsaturated fatty acids should be further evaluated. Possible long-term
effects of early exposure to tastes and flavours on later food choice preferences may have a major
impact on public health and need to be further elucidated. The use of biotechnology and
recombinant techniques may offer the opportunity to include various bioactive substances in
special dietary products, such as human milk proteins, peptides, growth factors, which may have
beneficial physiological effects, particularly in infancy and early childhood.
Growth: Development: Differentiation

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