- Email: [email protected]
European Union-funded research on probiotics, prebiotics and new foods
DIGEST LIVER DIS 2002:34~SUPP121:S98-104
European prebiotics
Union-funded research and new foods
J. Lucas
on probiotics,
At the beginning of 1999, the European Commission launched the Fifth Framework Programme for Research, Technological Development and Demonstration (1998-20021, which has been conceived to help solve problems and to respond to major socio-economic challenges facing the European Union. Within its thematic programme ‘Quality of life and management of living resources’, Key Action I covers the subject ‘Food, nutrition and health’ with a total budget of 290 million euro. The key action concentrates on consumer needs, the competitiveness of the European food industry the role of nutrition in health and well-being, and the safety and integrity of the food supply Within this framework, research on probiotics, prebiotics and new foods is an important focus of the funding activities of the European Commission at present and in future.
Digest Liver Dis 2002;34~Suppl.21:S99-104 Key words: European
Commission;
Fifth
Framework
Programme;
functional
foods
The Fifth Framework Programme for Research and Technological Developmentand Demonstration ~1998-20021
html
EuropeenCommission. Research OirecCorete-General, Food.Healthand Environment IE.21,Brossels,Belgium. Dr. J. Lutes, SDME8-32, Ruede la Loi 2UL7, Biws~&, Belgium. Fax:+32-2-2@4322. E-mail:[email protected]
2OWWetstraet
599
The Fifth Framework Programme (FP5) defines the European Union’s strategic priorities for Research, Technological Development and Demonstration Activities for the period 1998-2002 ‘. FP5 has been conceived to help solve problems and to respond to major socio-economic challenges such as increasing Europe’s industrial competitiveness, job creation and improving the quality of life for European citizens. FP5 is based on scientific and technological excellence, relevance of research to main EU policies, and on European added value. Emphasis is placed throughout on the process of innovation to ensure that the output of EU research is translated into tangible benefits for all. FP5 comprises four thematic programmes covering a series of well-defined problems and three horizontal programmes responding to common needs across all research areas. A total budget of 14,960 million euro has been allocated to implement the Fifth Framework Programme. Food research is included in the Thematic Programme Quality of Life and Management of Living Resources *. ‘Quality of life’ means the quality of EU citizens’ individual lives (especially in terms of health), quality of the environment, and quality of communal life. It also includes harnessing the economic benefits of the expected developments in life sciences and technologies. In concrete terms, the Quality of Life Thematic Programme supports research aimed at development that is truly sustainable - for individuals, society and the environment. A budget of 2,413 million euro has been earmarked to implement the research priorities identified under the programme, which is carried out by shared-cost projects, concerted actions, demonstration projects and other measures selected following calls for proposals.
J. Lucas
Duality of life and Management of Living Resources The Thematic Programme Quality of Life and Management of Living Resources is primarily built around six specific key actions that are goal-oriented and problem solving. The key actions are targeted at identifiable socio-economic and market needs, such as improving quality and safety of food; controlling infectious diseases; harnessing the power of the cell; health and environment; sustainable agriculture, forestry and fisheries, integrated rural development, sustainable development; and promoting healthy ageing. A unique feature of key actions is their response to Community policy objectives, in areas like agriculture and fisheries, industry, consumer protection, environment and health. In addition, the generic activities of the programme aim to build up the basis of knowledge in identified areas of strategic importance for the future, in relation to chronic and degenerative diseases, genomes, neurosciences, public health, persons with disabilities and ethical and socio-economic issues surrounding the life sciences. Support for research infrastructures, dissemination and exploitation of results, training and an increased role for SMEs (small and medium-sized enterprises) and entrepreneurship are also an integral part of the programme.
In Area 1.1 (Food Technology) the deliverables are: development of food raw materials better adapted to processing and consumer requirements.. . to provide edible, effective and nutritionally beneficial components; use of microorganisms for the production of foods and ingredients with new characteristics; and development of safe, efficient and sustainable processes . . . to optimise the nutritional and sensory quality of foods. Area 1.2 (Food Safety) relates to the safety of probiotics, prebiotics and new foods in all of its four sub-areas. The deliverables of Area 1.3 (Nutrition) relating to probiotics, prebiotics and new foods are: new methodologies to determine the relation between nutrition and health; databases; biomarkers; better understanding of the mechanisms in the relationship between food components, food habits and health; foods with improved nutritional value; and the scientific basis for the development of nutritionally improved products. No budget has been earmarked for an area or sub-area. The proposals submitted under Key Action 1 compete with each other for the totality of the available budget of 290 million euro. The breakdown between the years of FP5 for Key Action 1 is 96 million euro in 1999, 73 million euro in 2000, 29 million euro in 2001, and 59 million euro in 2002. The remaining 33 million euro are allocated to SME-related measures (CRAFT), training grants (Human Training and Mobility), and Accompanying Measures.
Key Action 1 “Food, Nutrition and Health” The main objectives of Key Action 1 Food, Nutrition and Health are addressing consumer needs and enhancing the competitiveness of the European food industry, assuring the safety and integrity of the food supply, and understanding the role of nutrition in health and well-being. The general objective is thus to improve the health of European citizens by providing safe, healthy and varied food products. Priorities for research and technological development include the development of new raw materials as well as safe and flexible manufacturing processes and technologies (Area 1.1); the detection and elimination of infectious and toxic agents throughout the food chain (Area 1.2); and gaining a more profound understanding of the role of food in promoting and sustaining health (Area 1.3). The budget of Key Action 1 is 290 million euro. All of the three areas mentioned have deliverables relating to probiotics, prebiotics and new foods. The work programme is modified every year as a function of the outcome of the previous calls. Therefore, the projects resulting from the last calls only refer to the work programmes 2000 for Areas 1.l and 1.2 7 and 2001 for Area 1.3 +‘.The work programme for 2002, which has been focused to quite an extent, has been decided upon and published in October 2001 s.
Projects resulting from the Calls 1999 and 2000 All areas have been open twice during the last two years. In total, 737 proposals have been submitted (including resubmissions), out of which 108 proposals have been selected, of which quite a few on probiotics, prebiotics or new foods. The first projects were started in the first two months of the year 2000 and have already shown results. At the time of editing this text, the projects of the last deadline in November 2000 are still under negotiation and cannot be described here. The same holds true for the projects resulting from the deadline in March 2001. A catalogue with the project abstracts and addresses of the coordinators and participants will be published in the beginning of 2002 in book format and will also be available on the CORDIS website under http://cordis/lu/life/.
Antionidatiue effects of food components European research on functional effects of dietaq antioxidants (QLKl -I 999-l 79) The coordinator is Sian Astley from the Institute for Food Research (IFR) in Norwich (UK). This concerted
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Elf-funded research
action will set up a European research network to exchange information on the results of research into the functional effects of antioxidants present in foods. It will identify the research that will be necessary to fill gaps in knowledge about their effects on health, and encourage proactive research collaboration between scientists working on different aspects of the functional effects of antioxidants. A series of working groups will be set up and their outputs considered at a plenary meeting. The project will produce a series of reviews that describe the current knowledge concerning the possible role that reactive oxidative species (ROS) play in the initiation of disease and the process of ageing. The potential for dietary antioxidants to reduce the damage caused by oxidative stress will be assessed, the gaps in knowledge identified and priority research goals delined. The project will culminate in the organisation of an international meeting on the functional effects of antioxidants. The results of this work will be widely disseminated to end users in the scientific community, consumer groups, legislators, and the food industry. Functional properties, bioactivities and bioavailability of phytochemicals, especially anthocyanins, from processed foods (QLKI-1999-124). The coordinator is Marina Heinonen from the University of Helsinki (Finland). The project aims at investigating the functional properties of anthocyanins and anthocyanin-rich food ingredients as well as the influence of anthocyanins on parameters related to the aetiology of cardiovascular disease in humans. Novel food processing techniques are used to produce anthocyanin-rich red berry juice for potential nutritional benefits. Anthocyanins, berry juice and berry juice processing by-products will be studied to provide the basis for the development of anthocyanin-rich functional food recipes. Molecular mechanisms underlying the biological and physiological effects of anthocyanins are investigated in animal liver microsomes and cell lines. The bioavailability and biokinetics of anthocyanins are confirmed in animal models prior to a strictly controlled human intervention measuring a wide range of biomarkers. Expected results are: improved techniques to increase the content of phenolic substances in red berry juice, new biomarkers for important food components and their biological effects, and new insight into the biological and preventive actions of dietary anthocyanins in relation to heart disease. The findings will be applied in the production of red-berry juices as a healthy alternative to red wine as a dietary protection against cardiovascular disease, for the optimisation of the use of anthocyanins as natural food ingredients and food additives (colorants), and for the development of anthocyanin-rich functional foods by utilising fruit and vegetable by-products. SIOO
Health implications of natural non-nutrient antioxidants (polyphenols): bioavailability and colon carcinogenesis (QLKI-1999-505). The coordinator is Gary Williamson from the Institute for Food Research (IFR) in Norwich (UK). The scientific objectives are to increase knowledge on the metabolism of dietary polyphenols, their effect on carcinogen metabolism, the mechanisms whereby they affect cell signalling involved in apoptosis and proliferation, and their modulatory effect on early events of colon carcinogenesis. The bioavailability of flavonoid glycosides will be determined: especially, the mechanism of uptake and transport of polyphenols, the exact nature of metabolites, the effect on the gut microflora, nature of the gut flora metabolites, validity of the rat model against human data, and human pharmacokinetits. The doses of the most active polyphenols will be determined to optimise protection against colon carcinogenesis. This will be based on thorough study of the mechanism in structure-function studies in vitro and dose-response studies in vivo. The industries (including one SME) in this project will be able to improve food by optimising polyphenol levels. This may be by the selection of varieties that are more appropriate, selective breeding, modified processing or modilied ingredients. The information gained will facilitate more appropriate and safe development of novel foods with altered contents of polyphenols.
Vitamins Folate: from food to functionality and optimal health (QLKI-1999376). The coordinator is Paul Finglas from the Institute for Food Research (IFR) in Norwich (UK). Folic acid significantly reduces the incidence and recurrence of neural tube defects (such as Spina bifida) in women. Marginal folate deficiency is also associated with elevated plasma homocysteine, an emerging risk factor for vascular diseases and stroke, and linked to certain cancers, notably colon. The project starts by an assessment of the accuracy and reliability of current food folate data and implications for intakes. The expected results of this project are the development of new and refined processing techniques for foods with enhanced folate content, bioavailability and functionality as well as the development of rapid in vitro and in vivo models for predicting folate bioavailability. A critical evaluation of the efficacy of different dietary folate strategies on lowering plasma homocysteine in the general population will be carried out, and a more effective use of dietary versus supplemental strategies for population-based prevention of chronic diseases will be developed. The project will lead to the development of
foods that will enable a diet rich in folates within the range indicated to be protective for human health. Furthermore, pre-competitive information for the development of effective, sustainable and ethically acceptable dietary strategies for folate-rich foods and folate-enriched products will be provided. Neutraceuticalsfor a healthier life: n-3polyunsaturated fatty acids and 5-methyl-tetra-hydro-folate (QLKl1999-888)
The coordinator is Loni Schweikart from BASF in Ludwigshafen (Germany). The project will, for the first time, undertake a comprehensive in-depth evaluation of the beneficial roles and interactions of longchain n-3 polyunsaturated fatty acids and %methyltetra-hydro-folate in cardiovascular health and infant development. It will investigate effects on cardiovascular disease (CVD)-related biomarkers and on the development of infants after supplementation of the mothers during pregnancy. The information obtained will allow the development of various functional foods enriched with stable forms of these nutraceuticals, thereby providing an optimum taste profile and ensuring consumer acceptability. These functional foods will help to reduce the deficit between current intakes of these nutrients and their actual requirement for optimal health in a large proportion of the European population. The products will also be of high commercial value to the European food industry. Fat soluble vitamin status and metabolism during ageing: ,functional and nutritional consequences (QLKl1999-830)
The coordinator is Edmond Rock from INRA - Unite des Maladies Metaboliques et Micronutriments in Theix (France). The expected achievements are reliable scientific information about the age-effects on the status, the metabolism and the functions of fat-soluble vitamins, which will provide the basis of specific dietary recommendation for fat-soluble vitamin intake and status of the elderly. A geographical comparison of these effects between three European countries will be made, and sufficient social and economic information about the feasibility of developing specific fat-soluble vitamin-enriched dietetic foods for the healthy elderly will be gained. Reliable data showing specific nutritional requirements and a real consumer interest in this food category will be of utmost interest in the elaboration of a specific European directive on specific dietary requirements for healthy elderly people. Towards a strategy for optimal Vitamin D forti$cation (QLKI -2000-623). The coordinator is Christine Brot of the Danish Veterinary and Food Administration in Soborg (Denmark).
Nutrient additions to the human food chain include Vitamin D incorporated in a wide variety of fatty foods. The vitamin D status of individuals will be determined and adjusted upwards by supplemental intervention in: 1) a population of adolescent girls at the time of maximum growth; 2) a group of older individuals with vitamin D insufficiency; and 3) an ethnic minority. A longitudinal survey will be carried out in five European countries of vitamin D status in relation to variation in dietary supply and seasonal variation in measured solar exposure. The feasibility of addressing the vitamin D deficiencies revealed is the subject of research in a work package concerned with the development of Vitamin D fortified bread.
Phyto-oestrogens Prevention of osteoporosis by nutritional phytooestrogens (QLKl-2000-431) The coordinator is Francesco Branca of the Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (National Institute of Research in Food and Nutrition) in Rome (Italy). Isoflavones, a subgroup of phyto-oestrogens mainly contained in soy and soy products, are widely held to have beneficial properties, but the evidence, to date, is only anecdotal. This proposal addresses the potential role of natural phyto-oestrogens in osteoporosis prevention among post-menopausal women living in Europe. A one-year large-scale, multicentre, randomised, controlled, intervention trial will be conducted in three European countries using specially-designed isoflavone-enriched foods, combined with rigorous assessments of the changes in bone metabolism. Acceptability of these foods among the target population (women 45 years of age and older) and expectations created by different nutritional claims will be addressed by conducting a survey in five EC state members. Role of dietary phyto-oestrogens in the prevention of breast and prostate cancer (QLKI -2000-266) The coordinator is Ian Rowland, University of Ulster in Coleraine (Northern Ireland). Cancer in Europe imposes a great social and economic burden; in particular, the hormonal cancers, breast and prostate, are major causes of death in the EU. It is now clear that a diet high in plant-based foods may offer protection. This project will analyse the effects of two groups of phyto-oestrogens (isoflavones and lignans), plant compounds with hormonal activity found in food, on the development of breast and prostate cancer. It will study the metabolism of phyto-oestrogens, individual variation and its influence on cancer risk. This will also include the development of methods for the discov-
SIOI
E&funded research
ery of new metabolites and for the rapid measurement of bioactive metabolites. This co-ordinated approach using human patients and volunteers, animal models and in vitro techniques will result in in-depth knowledge of the role of these compounds in the development of cancer and enable informed advice to be available in Europe on the beneficial effects of phytooestrogens in the diet.
Other non-nutrients Conjugated linoleic acid (CLA) in functional food: a potential benefit for overweight middle-aged Europeans (QLKI - 1999- 76) The coordinator is Jean-Louis SCbCdio from INRA Unite de Nutrition Lipidique in Dijon (France). The main objective of this project is to develop a functional food containing conjugated linoleic acid, designed to reduce overweight and the negative impact of overweight on the health of the middle-aged population. The expected results of this project are the identification of the active CLA isomer(s) and a better understanding of the impact of CLA isomers on energy metabolism and fat partitioning. A functional food containing CLA will be developed that will reduce excess weight and that will answer to the consumers’ preference for different functional food formulations. Increase in nutritional value offood raw materials by addition, activity, or in situ production of microbial nutraceuticals (QLKl-1999-1376) The coordinator is Jeroen Hugenholtz of the Dutch Institute of Dairy Research (NIZO) at Ede (The Netherlands). The main objective is to improve the nutritional value of food raw materials and fermented food products. This will be accomplished by increasing the level of nutraceuticals in food products of dairy and soy origin. The targeted nutraceuticals are low-calorysugars, digestion-stimulating oligosaccharides and essential B-vitamins. These components will all be produced by food-grade micro-organisms. In addition, some undesirable sugars such as lactose, galactose and raffinose will be selectively removed from either dairy or soy-containing food products. Functional foods against colon cancer: development of a genomics and proteomics based screening assay (QLKI-1999-706). The coordinator is Ruud Woutersen from TN0 - Nutrition and Food Research Institute in Zeist (The Netherlands). The aim of the present project is to develop a bioassay, based on genomic and proteomic changes in colorectal cells, in order to identify food components specifically designed to prevent the devel5102
opment or progression of colorectal cancer. The genomic and proteomic changes in colorectal cells will be powerful biomarkers for prevention of colon carcinogenesis as numerous genes and proteins are tested simultaneously and the assays are easy to perform. This project will contribute in a unique way to the future developments of chronic disease prevention by functional food ingredients through functional food development. Furthermore, the identification of new powerful chemopreventive dietary components as well as combination effects of known dietary compounds will be enhanced.
Actual new foods Barley /%d-glucan and wheat arabinoxylan soluble fibre technologies for health promoting bread products (QLKI-1999-324) The coordinator is Jan Delcour of the Katholieke Universiteit Leuven (Belgium). Soluble fibre in a diet is beneficial because it lowers blood cholesterol levels, a risk factor for coronary heart disease and it produces a reduced postprandial glycaemic response, potentially beneficial in controlling the adverse effects of diabetes. The main objective is to provide and implement technologies for increased barley/wheat soluble tibre levels in staple food EU bread products. This requires optimisation of hull-less barley milling technology, research into barley proteins, endogenous endoxylanase inhibitors, their action towards endoxylanases, optimisation of different types of dough and bread making processes for increased soluble fibre levels and qualities, and assessment of their organoleptic properties and consumer acceptability. Achievements will be novel barley processing and endoxylanase technologies for bread making, scientific insights in barley protein, wheat/barley dietary fibre, and endoxylanase inhibitors. Enhancing the content of beneficial fatty acids in beef and improving meat quality for the consumer (QLKI1999-1423) The coordinator is Nigel Scollan of the Institute of Grassland and Environmental Research in Aberystwyth (UK). The aim of this project is to develop strategies for the production of beef with improved nutritional value and quality. The content of saturated fat will be decreased while increasing the content of beneficial n-3 polyunsaturated fatty acids and CLA. The project seeks to exploit more extensive beef production practices with higher forage inputs (grass and clover), which are the primary source of n-3 fatty acids (mainly a-linolenic acid; C18:3n-3). Four beef production systems, representative of those used in the EU, but
J. Lucas
varying in level of intensification, will be examined. Beef produced will be characterised for fatty acid composition and meat quality, especially flavour. The role of the rumen and post absorption processes in regulating the dietary potential to manipulate the fatty acid composition of beef will be examined. Design of foods with improved functionality and superior health eflects using cereal Pglucans (QLKl2000-535) The coordinator is Gunilla Inning of the University of Lund (Sweden). For the first time, p-glucan of high purity will be prepared from cereals on a large scale. The processing conditions will be optimised to provide different preparations with tailor-made functional properties for different uses. Several partners will characterise the preparations in detail using a modern combination of advanced chemical and physico-chemical methods, in a joint effort. These new b-glucan preparations’ physiological effects (lipid and glucose metabolism) will be studied in an animal model and also in humans. The P-glucans are, thereafter, added to food prototypes, and the developed products’ properties, with respect to health effects, taste and rheology, will be evaluated. Consumer attitudes to the food prototypes and the concept behind them will also be investigated.
Probiotics Synbiotics and cancer prevention in humans (QLKl1999-346). The coordinator is Jan van Loo from Tiense Suikerraffinaderij BV (Orafti) in Tienen (Belgium). The overall aim of the project is to evaluate the potential cancerpreventing activity of pro- and prebiotic (synbiotic) combinations in human volunteers. After studying different synbiotic combinations using in vitro fermentation models of the colon ecosystem, the anticarcinogenie effect of the most promising synbiotic combinations shall be confirmed in a well-established animal model for colon carcinogenesis. This optimal synbiotic will combine an increased competitive advantage in the intestinal ecosystem with synergistic ‘anticancer’ properties as already observed in experimental models and will target distal parts of the colon, which are the sites where colon cancers most frequently occur. After refining a range of biomarkers reflecting the different stages of the carcinogenic process and immunological parameters, the underlying mechanisms will be examined in the rat model. It is anticipated that this longterm rat carcinogenicity study will provide substantiation of the many short-term in vivo studies on suppression of pre-cancerous lesions in rodents by pro- and
prebiotics. For the full market value of synbiotics to be realised, it is imperative that larger-scale well-controlled human diet intervention studies confirm the first sets of experimental data. Therefore, and as a last step, the biomarkers will be used in adenoma patients to explore the potential of a synbiotic combination to prevent colorectal cancer. The data from this study will form dietary guidelines for the prevention of cancer. The five projects that form the cluster on “Food, gastrointestinal tract functionality and human health’ will be presented elsewhere in these proceedings: - Nutritional enhancement of probiotics and prebiotics: technology aspects on microbial viability, stability, functionality and on prebiotic function (QLKl-1999-42) - Functional food, gut microflora and healthy ageing (QLKl -2000-67) - Development and application of high throughput molecular methods for studying the human gut microbiota in relation to diet and health (QLKl2000- 1OS) - Probiotic strains with designed health properties (QLKl-2000-146) - Probiotics and gastrointestinal disorders: controlled trials of EU patients (QLKl-2000-563) These projects, those that are being negotiated at present and those to be submitted in future, will make an important contribution to functional food science and the development of new foods.
Next Call for Proposals within the Fifth Framework Programme There is one more deadline for proposal submission to come in 2002, when all three areas will be open with a deadline on 31 January. The research priorities and work programme have been elaborated from the work programme 2001 with the intent to focus on those issues that have not been addressed sufficiently by projects resulting from the previous calls 5. More information on the work programme, future calls and deadlines can be found on the CORDIS website. For further details, the helpdesk can be contacted by e-mail at the following address [email protected].
The New Framework Programme for Research and Technological Deueiopment and Demonstration (2002-2006) and the EuropeanResearch Area In February 2001, the Commission proposed its new Framework Programme for discussion with the Council and the European Parliament 6. The proposal is based on the preliminary conclusions of the debate in 5103
Elf-funded research
the European Parliament, the Council and the other institutions, and also takes into account the views expressed by the Member States, the scientific community and industry as part of a very wide-ranging consultation. However, the text will undergo important changes during the conciliation procedure between the European Commission, Parliament and the Council, which is why it is not presented here in detail. This proposal has been designed to contribute to the development of scientific and technical excellence in Europe, in EU countries and non-EU countries, especially candidate countries, both in universities and industries. It should also have the effect of increasing its impact on the innovation process in Europe and reinforcing its contribution to the efforts to integrate European research. The new Framework Programme will be based on the following main principles: Concentrating on a selected number of priority research areas in which EU action would exert the greatest possible effect; Defining the various activities in such a way as to enable them to exert a more structuring effect on the research activities conducted in Europe thanks to a stronger link with national, regional and other European initiatives; Simplifying and streamlining the implementation arrangements, on the basis of the intervention methods defined and the decentralised management procedures envisaged. The priority thematic areas of research proposed have been defined on the basis of the following criteria: the need to assemble a critical mass of financial and human resources; to combine the complementary areas of expertise found in the different countries or to employ the comparative studies at European level; links with EU priorities and interests; or the necessarily transnational nature of the research in question. Several thematic areas have been selected, which have, within each of them, a number of subjects linked to econom-
ic and societal issues that are especially important to the EU and where its action adds specific value. Recent and future developments of the new Framework Programme and the contributions to the discussion can be found on the website http://www.cordis.lu/rtd2002/.
List of abbreviations CLA: conjugated idative species
linoleic acid:
EU: European
Union:
ROS: reactive
oxI
References ’ Council and Parliament Decision 1999/182/EC concerning the fifth framework programme of the European Community for research, technological development and demonstration activities (1998 to 2002). Official Journal L 26/l of 1 February 1999. z Council Decision 1999/167/EC adopting a specific programme for research, technological development and demonstration on quality of life and management of living resources (1998 to 2002). Official Journal L 64/l of 12 March 1999. 3 European Commission. Call for proposals for RTD actions under the specific programme for research, technologic,al development and demonstration on ‘Quality of life and management of living resources’ (1998 to 2002). Official Journal C 361/10 of 1.5 December 1999. J European Commission. Call for proposals for RTD actions under the specific programme for research, technological development and demonstration on ‘Quality of life and management of living resources’ (1998 to 2002). Official Journal C 324/18 of 1.5 November 2000. 5 European Commission. Call for proposals for RTD actions under the specific programme for research, technological development and demonstration on ‘Quality of life and management of living resources’ (1998 to 2002). To be published in the Official Journal C of 3 1 October 2001. 6 European Commission. Proposal for a decision of the European Parliament and of the Council concerning the multiannual framework programme 2002-2006 of the European community for research, technological development and demonstration activities aimed at contributing towards the creation of the European research area. In: A new Framework Programme. EUR 19460. Luxembourg: Office for Official Publications of the European Communities; 2001.
European prebiotics
Union-funded research and new foods
J. Lucas
on probiotics,
At the beginning of 1999, the European Commission launched the Fifth Framework Programme for Research, Technological Development and Demonstration (1998-20021, which has been conceived to help solve problems and to respond to major socio-economic challenges facing the European Union. Within its thematic programme ‘Quality of life and management of living resources’, Key Action I covers the subject ‘Food, nutrition and health’ with a total budget of 290 million euro. The key action concentrates on consumer needs, the competitiveness of the European food industry the role of nutrition in health and well-being, and the safety and integrity of the food supply Within this framework, research on probiotics, prebiotics and new foods is an important focus of the funding activities of the European Commission at present and in future.
Digest Liver Dis 2002;34~Suppl.21:S99-104 Key words: European
Commission;
Fifth
Framework
Programme;
functional
foods
The Fifth Framework Programme for Research and Technological Developmentand Demonstration ~1998-20021
html
EuropeenCommission. Research OirecCorete-General, Food.Healthand Environment IE.21,Brossels,Belgium. Dr. J. Lutes, SDME8-32, Ruede la Loi 2UL7, Biws~&, Belgium. Fax:+32-2-2@4322. E-mail:[email protected]
2OWWetstraet
599
The Fifth Framework Programme (FP5) defines the European Union’s strategic priorities for Research, Technological Development and Demonstration Activities for the period 1998-2002 ‘. FP5 has been conceived to help solve problems and to respond to major socio-economic challenges such as increasing Europe’s industrial competitiveness, job creation and improving the quality of life for European citizens. FP5 is based on scientific and technological excellence, relevance of research to main EU policies, and on European added value. Emphasis is placed throughout on the process of innovation to ensure that the output of EU research is translated into tangible benefits for all. FP5 comprises four thematic programmes covering a series of well-defined problems and three horizontal programmes responding to common needs across all research areas. A total budget of 14,960 million euro has been allocated to implement the Fifth Framework Programme. Food research is included in the Thematic Programme Quality of Life and Management of Living Resources *. ‘Quality of life’ means the quality of EU citizens’ individual lives (especially in terms of health), quality of the environment, and quality of communal life. It also includes harnessing the economic benefits of the expected developments in life sciences and technologies. In concrete terms, the Quality of Life Thematic Programme supports research aimed at development that is truly sustainable - for individuals, society and the environment. A budget of 2,413 million euro has been earmarked to implement the research priorities identified under the programme, which is carried out by shared-cost projects, concerted actions, demonstration projects and other measures selected following calls for proposals.
J. Lucas
Duality of life and Management of Living Resources The Thematic Programme Quality of Life and Management of Living Resources is primarily built around six specific key actions that are goal-oriented and problem solving. The key actions are targeted at identifiable socio-economic and market needs, such as improving quality and safety of food; controlling infectious diseases; harnessing the power of the cell; health and environment; sustainable agriculture, forestry and fisheries, integrated rural development, sustainable development; and promoting healthy ageing. A unique feature of key actions is their response to Community policy objectives, in areas like agriculture and fisheries, industry, consumer protection, environment and health. In addition, the generic activities of the programme aim to build up the basis of knowledge in identified areas of strategic importance for the future, in relation to chronic and degenerative diseases, genomes, neurosciences, public health, persons with disabilities and ethical and socio-economic issues surrounding the life sciences. Support for research infrastructures, dissemination and exploitation of results, training and an increased role for SMEs (small and medium-sized enterprises) and entrepreneurship are also an integral part of the programme.
In Area 1.1 (Food Technology) the deliverables are: development of food raw materials better adapted to processing and consumer requirements.. . to provide edible, effective and nutritionally beneficial components; use of microorganisms for the production of foods and ingredients with new characteristics; and development of safe, efficient and sustainable processes . . . to optimise the nutritional and sensory quality of foods. Area 1.2 (Food Safety) relates to the safety of probiotics, prebiotics and new foods in all of its four sub-areas. The deliverables of Area 1.3 (Nutrition) relating to probiotics, prebiotics and new foods are: new methodologies to determine the relation between nutrition and health; databases; biomarkers; better understanding of the mechanisms in the relationship between food components, food habits and health; foods with improved nutritional value; and the scientific basis for the development of nutritionally improved products. No budget has been earmarked for an area or sub-area. The proposals submitted under Key Action 1 compete with each other for the totality of the available budget of 290 million euro. The breakdown between the years of FP5 for Key Action 1 is 96 million euro in 1999, 73 million euro in 2000, 29 million euro in 2001, and 59 million euro in 2002. The remaining 33 million euro are allocated to SME-related measures (CRAFT), training grants (Human Training and Mobility), and Accompanying Measures.
Key Action 1 “Food, Nutrition and Health” The main objectives of Key Action 1 Food, Nutrition and Health are addressing consumer needs and enhancing the competitiveness of the European food industry, assuring the safety and integrity of the food supply, and understanding the role of nutrition in health and well-being. The general objective is thus to improve the health of European citizens by providing safe, healthy and varied food products. Priorities for research and technological development include the development of new raw materials as well as safe and flexible manufacturing processes and technologies (Area 1.1); the detection and elimination of infectious and toxic agents throughout the food chain (Area 1.2); and gaining a more profound understanding of the role of food in promoting and sustaining health (Area 1.3). The budget of Key Action 1 is 290 million euro. All of the three areas mentioned have deliverables relating to probiotics, prebiotics and new foods. The work programme is modified every year as a function of the outcome of the previous calls. Therefore, the projects resulting from the last calls only refer to the work programmes 2000 for Areas 1.l and 1.2 7 and 2001 for Area 1.3 +‘.The work programme for 2002, which has been focused to quite an extent, has been decided upon and published in October 2001 s.
Projects resulting from the Calls 1999 and 2000 All areas have been open twice during the last two years. In total, 737 proposals have been submitted (including resubmissions), out of which 108 proposals have been selected, of which quite a few on probiotics, prebiotics or new foods. The first projects were started in the first two months of the year 2000 and have already shown results. At the time of editing this text, the projects of the last deadline in November 2000 are still under negotiation and cannot be described here. The same holds true for the projects resulting from the deadline in March 2001. A catalogue with the project abstracts and addresses of the coordinators and participants will be published in the beginning of 2002 in book format and will also be available on the CORDIS website under http://cordis/lu/life/.
Antionidatiue effects of food components European research on functional effects of dietaq antioxidants (QLKl -I 999-l 79) The coordinator is Sian Astley from the Institute for Food Research (IFR) in Norwich (UK). This concerted
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action will set up a European research network to exchange information on the results of research into the functional effects of antioxidants present in foods. It will identify the research that will be necessary to fill gaps in knowledge about their effects on health, and encourage proactive research collaboration between scientists working on different aspects of the functional effects of antioxidants. A series of working groups will be set up and their outputs considered at a plenary meeting. The project will produce a series of reviews that describe the current knowledge concerning the possible role that reactive oxidative species (ROS) play in the initiation of disease and the process of ageing. The potential for dietary antioxidants to reduce the damage caused by oxidative stress will be assessed, the gaps in knowledge identified and priority research goals delined. The project will culminate in the organisation of an international meeting on the functional effects of antioxidants. The results of this work will be widely disseminated to end users in the scientific community, consumer groups, legislators, and the food industry. Functional properties, bioactivities and bioavailability of phytochemicals, especially anthocyanins, from processed foods (QLKI-1999-124). The coordinator is Marina Heinonen from the University of Helsinki (Finland). The project aims at investigating the functional properties of anthocyanins and anthocyanin-rich food ingredients as well as the influence of anthocyanins on parameters related to the aetiology of cardiovascular disease in humans. Novel food processing techniques are used to produce anthocyanin-rich red berry juice for potential nutritional benefits. Anthocyanins, berry juice and berry juice processing by-products will be studied to provide the basis for the development of anthocyanin-rich functional food recipes. Molecular mechanisms underlying the biological and physiological effects of anthocyanins are investigated in animal liver microsomes and cell lines. The bioavailability and biokinetics of anthocyanins are confirmed in animal models prior to a strictly controlled human intervention measuring a wide range of biomarkers. Expected results are: improved techniques to increase the content of phenolic substances in red berry juice, new biomarkers for important food components and their biological effects, and new insight into the biological and preventive actions of dietary anthocyanins in relation to heart disease. The findings will be applied in the production of red-berry juices as a healthy alternative to red wine as a dietary protection against cardiovascular disease, for the optimisation of the use of anthocyanins as natural food ingredients and food additives (colorants), and for the development of anthocyanin-rich functional foods by utilising fruit and vegetable by-products. SIOO
Health implications of natural non-nutrient antioxidants (polyphenols): bioavailability and colon carcinogenesis (QLKI-1999-505). The coordinator is Gary Williamson from the Institute for Food Research (IFR) in Norwich (UK). The scientific objectives are to increase knowledge on the metabolism of dietary polyphenols, their effect on carcinogen metabolism, the mechanisms whereby they affect cell signalling involved in apoptosis and proliferation, and their modulatory effect on early events of colon carcinogenesis. The bioavailability of flavonoid glycosides will be determined: especially, the mechanism of uptake and transport of polyphenols, the exact nature of metabolites, the effect on the gut microflora, nature of the gut flora metabolites, validity of the rat model against human data, and human pharmacokinetits. The doses of the most active polyphenols will be determined to optimise protection against colon carcinogenesis. This will be based on thorough study of the mechanism in structure-function studies in vitro and dose-response studies in vivo. The industries (including one SME) in this project will be able to improve food by optimising polyphenol levels. This may be by the selection of varieties that are more appropriate, selective breeding, modified processing or modilied ingredients. The information gained will facilitate more appropriate and safe development of novel foods with altered contents of polyphenols.
Vitamins Folate: from food to functionality and optimal health (QLKI-1999376). The coordinator is Paul Finglas from the Institute for Food Research (IFR) in Norwich (UK). Folic acid significantly reduces the incidence and recurrence of neural tube defects (such as Spina bifida) in women. Marginal folate deficiency is also associated with elevated plasma homocysteine, an emerging risk factor for vascular diseases and stroke, and linked to certain cancers, notably colon. The project starts by an assessment of the accuracy and reliability of current food folate data and implications for intakes. The expected results of this project are the development of new and refined processing techniques for foods with enhanced folate content, bioavailability and functionality as well as the development of rapid in vitro and in vivo models for predicting folate bioavailability. A critical evaluation of the efficacy of different dietary folate strategies on lowering plasma homocysteine in the general population will be carried out, and a more effective use of dietary versus supplemental strategies for population-based prevention of chronic diseases will be developed. The project will lead to the development of
foods that will enable a diet rich in folates within the range indicated to be protective for human health. Furthermore, pre-competitive information for the development of effective, sustainable and ethically acceptable dietary strategies for folate-rich foods and folate-enriched products will be provided. Neutraceuticalsfor a healthier life: n-3polyunsaturated fatty acids and 5-methyl-tetra-hydro-folate (QLKl1999-888)
The coordinator is Loni Schweikart from BASF in Ludwigshafen (Germany). The project will, for the first time, undertake a comprehensive in-depth evaluation of the beneficial roles and interactions of longchain n-3 polyunsaturated fatty acids and %methyltetra-hydro-folate in cardiovascular health and infant development. It will investigate effects on cardiovascular disease (CVD)-related biomarkers and on the development of infants after supplementation of the mothers during pregnancy. The information obtained will allow the development of various functional foods enriched with stable forms of these nutraceuticals, thereby providing an optimum taste profile and ensuring consumer acceptability. These functional foods will help to reduce the deficit between current intakes of these nutrients and their actual requirement for optimal health in a large proportion of the European population. The products will also be of high commercial value to the European food industry. Fat soluble vitamin status and metabolism during ageing: ,functional and nutritional consequences (QLKl1999-830)
The coordinator is Edmond Rock from INRA - Unite des Maladies Metaboliques et Micronutriments in Theix (France). The expected achievements are reliable scientific information about the age-effects on the status, the metabolism and the functions of fat-soluble vitamins, which will provide the basis of specific dietary recommendation for fat-soluble vitamin intake and status of the elderly. A geographical comparison of these effects between three European countries will be made, and sufficient social and economic information about the feasibility of developing specific fat-soluble vitamin-enriched dietetic foods for the healthy elderly will be gained. Reliable data showing specific nutritional requirements and a real consumer interest in this food category will be of utmost interest in the elaboration of a specific European directive on specific dietary requirements for healthy elderly people. Towards a strategy for optimal Vitamin D forti$cation (QLKI -2000-623). The coordinator is Christine Brot of the Danish Veterinary and Food Administration in Soborg (Denmark).
Nutrient additions to the human food chain include Vitamin D incorporated in a wide variety of fatty foods. The vitamin D status of individuals will be determined and adjusted upwards by supplemental intervention in: 1) a population of adolescent girls at the time of maximum growth; 2) a group of older individuals with vitamin D insufficiency; and 3) an ethnic minority. A longitudinal survey will be carried out in five European countries of vitamin D status in relation to variation in dietary supply and seasonal variation in measured solar exposure. The feasibility of addressing the vitamin D deficiencies revealed is the subject of research in a work package concerned with the development of Vitamin D fortified bread.
Phyto-oestrogens Prevention of osteoporosis by nutritional phytooestrogens (QLKl-2000-431) The coordinator is Francesco Branca of the Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (National Institute of Research in Food and Nutrition) in Rome (Italy). Isoflavones, a subgroup of phyto-oestrogens mainly contained in soy and soy products, are widely held to have beneficial properties, but the evidence, to date, is only anecdotal. This proposal addresses the potential role of natural phyto-oestrogens in osteoporosis prevention among post-menopausal women living in Europe. A one-year large-scale, multicentre, randomised, controlled, intervention trial will be conducted in three European countries using specially-designed isoflavone-enriched foods, combined with rigorous assessments of the changes in bone metabolism. Acceptability of these foods among the target population (women 45 years of age and older) and expectations created by different nutritional claims will be addressed by conducting a survey in five EC state members. Role of dietary phyto-oestrogens in the prevention of breast and prostate cancer (QLKI -2000-266) The coordinator is Ian Rowland, University of Ulster in Coleraine (Northern Ireland). Cancer in Europe imposes a great social and economic burden; in particular, the hormonal cancers, breast and prostate, are major causes of death in the EU. It is now clear that a diet high in plant-based foods may offer protection. This project will analyse the effects of two groups of phyto-oestrogens (isoflavones and lignans), plant compounds with hormonal activity found in food, on the development of breast and prostate cancer. It will study the metabolism of phyto-oestrogens, individual variation and its influence on cancer risk. This will also include the development of methods for the discov-
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ery of new metabolites and for the rapid measurement of bioactive metabolites. This co-ordinated approach using human patients and volunteers, animal models and in vitro techniques will result in in-depth knowledge of the role of these compounds in the development of cancer and enable informed advice to be available in Europe on the beneficial effects of phytooestrogens in the diet.
Other non-nutrients Conjugated linoleic acid (CLA) in functional food: a potential benefit for overweight middle-aged Europeans (QLKI - 1999- 76) The coordinator is Jean-Louis SCbCdio from INRA Unite de Nutrition Lipidique in Dijon (France). The main objective of this project is to develop a functional food containing conjugated linoleic acid, designed to reduce overweight and the negative impact of overweight on the health of the middle-aged population. The expected results of this project are the identification of the active CLA isomer(s) and a better understanding of the impact of CLA isomers on energy metabolism and fat partitioning. A functional food containing CLA will be developed that will reduce excess weight and that will answer to the consumers’ preference for different functional food formulations. Increase in nutritional value offood raw materials by addition, activity, or in situ production of microbial nutraceuticals (QLKl-1999-1376) The coordinator is Jeroen Hugenholtz of the Dutch Institute of Dairy Research (NIZO) at Ede (The Netherlands). The main objective is to improve the nutritional value of food raw materials and fermented food products. This will be accomplished by increasing the level of nutraceuticals in food products of dairy and soy origin. The targeted nutraceuticals are low-calorysugars, digestion-stimulating oligosaccharides and essential B-vitamins. These components will all be produced by food-grade micro-organisms. In addition, some undesirable sugars such as lactose, galactose and raffinose will be selectively removed from either dairy or soy-containing food products. Functional foods against colon cancer: development of a genomics and proteomics based screening assay (QLKI-1999-706). The coordinator is Ruud Woutersen from TN0 - Nutrition and Food Research Institute in Zeist (The Netherlands). The aim of the present project is to develop a bioassay, based on genomic and proteomic changes in colorectal cells, in order to identify food components specifically designed to prevent the devel5102
opment or progression of colorectal cancer. The genomic and proteomic changes in colorectal cells will be powerful biomarkers for prevention of colon carcinogenesis as numerous genes and proteins are tested simultaneously and the assays are easy to perform. This project will contribute in a unique way to the future developments of chronic disease prevention by functional food ingredients through functional food development. Furthermore, the identification of new powerful chemopreventive dietary components as well as combination effects of known dietary compounds will be enhanced.
Actual new foods Barley /%d-glucan and wheat arabinoxylan soluble fibre technologies for health promoting bread products (QLKI-1999-324) The coordinator is Jan Delcour of the Katholieke Universiteit Leuven (Belgium). Soluble fibre in a diet is beneficial because it lowers blood cholesterol levels, a risk factor for coronary heart disease and it produces a reduced postprandial glycaemic response, potentially beneficial in controlling the adverse effects of diabetes. The main objective is to provide and implement technologies for increased barley/wheat soluble tibre levels in staple food EU bread products. This requires optimisation of hull-less barley milling technology, research into barley proteins, endogenous endoxylanase inhibitors, their action towards endoxylanases, optimisation of different types of dough and bread making processes for increased soluble fibre levels and qualities, and assessment of their organoleptic properties and consumer acceptability. Achievements will be novel barley processing and endoxylanase technologies for bread making, scientific insights in barley protein, wheat/barley dietary fibre, and endoxylanase inhibitors. Enhancing the content of beneficial fatty acids in beef and improving meat quality for the consumer (QLKI1999-1423) The coordinator is Nigel Scollan of the Institute of Grassland and Environmental Research in Aberystwyth (UK). The aim of this project is to develop strategies for the production of beef with improved nutritional value and quality. The content of saturated fat will be decreased while increasing the content of beneficial n-3 polyunsaturated fatty acids and CLA. The project seeks to exploit more extensive beef production practices with higher forage inputs (grass and clover), which are the primary source of n-3 fatty acids (mainly a-linolenic acid; C18:3n-3). Four beef production systems, representative of those used in the EU, but
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varying in level of intensification, will be examined. Beef produced will be characterised for fatty acid composition and meat quality, especially flavour. The role of the rumen and post absorption processes in regulating the dietary potential to manipulate the fatty acid composition of beef will be examined. Design of foods with improved functionality and superior health eflects using cereal Pglucans (QLKl2000-535) The coordinator is Gunilla Inning of the University of Lund (Sweden). For the first time, p-glucan of high purity will be prepared from cereals on a large scale. The processing conditions will be optimised to provide different preparations with tailor-made functional properties for different uses. Several partners will characterise the preparations in detail using a modern combination of advanced chemical and physico-chemical methods, in a joint effort. These new b-glucan preparations’ physiological effects (lipid and glucose metabolism) will be studied in an animal model and also in humans. The P-glucans are, thereafter, added to food prototypes, and the developed products’ properties, with respect to health effects, taste and rheology, will be evaluated. Consumer attitudes to the food prototypes and the concept behind them will also be investigated.
Probiotics Synbiotics and cancer prevention in humans (QLKl1999-346). The coordinator is Jan van Loo from Tiense Suikerraffinaderij BV (Orafti) in Tienen (Belgium). The overall aim of the project is to evaluate the potential cancerpreventing activity of pro- and prebiotic (synbiotic) combinations in human volunteers. After studying different synbiotic combinations using in vitro fermentation models of the colon ecosystem, the anticarcinogenie effect of the most promising synbiotic combinations shall be confirmed in a well-established animal model for colon carcinogenesis. This optimal synbiotic will combine an increased competitive advantage in the intestinal ecosystem with synergistic ‘anticancer’ properties as already observed in experimental models and will target distal parts of the colon, which are the sites where colon cancers most frequently occur. After refining a range of biomarkers reflecting the different stages of the carcinogenic process and immunological parameters, the underlying mechanisms will be examined in the rat model. It is anticipated that this longterm rat carcinogenicity study will provide substantiation of the many short-term in vivo studies on suppression of pre-cancerous lesions in rodents by pro- and
prebiotics. For the full market value of synbiotics to be realised, it is imperative that larger-scale well-controlled human diet intervention studies confirm the first sets of experimental data. Therefore, and as a last step, the biomarkers will be used in adenoma patients to explore the potential of a synbiotic combination to prevent colorectal cancer. The data from this study will form dietary guidelines for the prevention of cancer. The five projects that form the cluster on “Food, gastrointestinal tract functionality and human health’ will be presented elsewhere in these proceedings: - Nutritional enhancement of probiotics and prebiotics: technology aspects on microbial viability, stability, functionality and on prebiotic function (QLKl-1999-42) - Functional food, gut microflora and healthy ageing (QLKl -2000-67) - Development and application of high throughput molecular methods for studying the human gut microbiota in relation to diet and health (QLKl2000- 1OS) - Probiotic strains with designed health properties (QLKl-2000-146) - Probiotics and gastrointestinal disorders: controlled trials of EU patients (QLKl-2000-563) These projects, those that are being negotiated at present and those to be submitted in future, will make an important contribution to functional food science and the development of new foods.
Next Call for Proposals within the Fifth Framework Programme There is one more deadline for proposal submission to come in 2002, when all three areas will be open with a deadline on 31 January. The research priorities and work programme have been elaborated from the work programme 2001 with the intent to focus on those issues that have not been addressed sufficiently by projects resulting from the previous calls 5. More information on the work programme, future calls and deadlines can be found on the CORDIS website. For further details, the helpdesk can be contacted by e-mail at the following address [email protected].
The New Framework Programme for Research and Technological Deueiopment and Demonstration (2002-2006) and the EuropeanResearch Area In February 2001, the Commission proposed its new Framework Programme for discussion with the Council and the European Parliament 6. The proposal is based on the preliminary conclusions of the debate in 5103
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the European Parliament, the Council and the other institutions, and also takes into account the views expressed by the Member States, the scientific community and industry as part of a very wide-ranging consultation. However, the text will undergo important changes during the conciliation procedure between the European Commission, Parliament and the Council, which is why it is not presented here in detail. This proposal has been designed to contribute to the development of scientific and technical excellence in Europe, in EU countries and non-EU countries, especially candidate countries, both in universities and industries. It should also have the effect of increasing its impact on the innovation process in Europe and reinforcing its contribution to the efforts to integrate European research. The new Framework Programme will be based on the following main principles: Concentrating on a selected number of priority research areas in which EU action would exert the greatest possible effect; Defining the various activities in such a way as to enable them to exert a more structuring effect on the research activities conducted in Europe thanks to a stronger link with national, regional and other European initiatives; Simplifying and streamlining the implementation arrangements, on the basis of the intervention methods defined and the decentralised management procedures envisaged. The priority thematic areas of research proposed have been defined on the basis of the following criteria: the need to assemble a critical mass of financial and human resources; to combine the complementary areas of expertise found in the different countries or to employ the comparative studies at European level; links with EU priorities and interests; or the necessarily transnational nature of the research in question. Several thematic areas have been selected, which have, within each of them, a number of subjects linked to econom-
ic and societal issues that are especially important to the EU and where its action adds specific value. Recent and future developments of the new Framework Programme and the contributions to the discussion can be found on the website http://www.cordis.lu/rtd2002/.
List of abbreviations CLA: conjugated idative species
linoleic acid:
EU: European
Union:
ROS: reactive
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References ’ Council and Parliament Decision 1999/182/EC concerning the fifth framework programme of the European Community for research, technological development and demonstration activities (1998 to 2002). Official Journal L 26/l of 1 February 1999. z Council Decision 1999/167/EC adopting a specific programme for research, technological development and demonstration on quality of life and management of living resources (1998 to 2002). Official Journal L 64/l of 12 March 1999. 3 European Commission. Call for proposals for RTD actions under the specific programme for research, technologic,al development and demonstration on ‘Quality of life and management of living resources’ (1998 to 2002). Official Journal C 361/10 of 1.5 December 1999. J European Commission. Call for proposals for RTD actions under the specific programme for research, technological development and demonstration on ‘Quality of life and management of living resources’ (1998 to 2002). Official Journal C 324/18 of 1.5 November 2000. 5 European Commission. Call for proposals for RTD actions under the specific programme for research, technological development and demonstration on ‘Quality of life and management of living resources’ (1998 to 2002). To be published in the Official Journal C of 3 1 October 2001. 6 European Commission. Proposal for a decision of the European Parliament and of the Council concerning the multiannual framework programme 2002-2006 of the European community for research, technological development and demonstration activities aimed at contributing towards the creation of the European research area. In: A new Framework Programme. EUR 19460. Luxembourg: Office for Official Publications of the European Communities; 2001.