Mirjana Pavlović

Current micronutrient recommendations in Europe: towards understanding their differences and similarities

BackgroundNowadays most countries in Europe have established their own nutrient recommendations to assess the adequacy of dietary intakes and to plan desirable dietary intakes. As yet there is no standard approach for deriving nutrient recommendations, they may vary from country to country. This results in different national recommendations causing confusion for policy-makers, health professionals, industry, and consumers within Europe. EURRECA (EURopean micronutrient RECommendations Aligned) is a network of excellence funded by the European Commission (EC), and established to identify and address the problem of differences between countries in micronutrient recommendations. The objective of this paper is to give an overview of the available micronutrient recommendations in Europe, and to provide information on their origin, concepts and definitions. Furthermore this paper aims to illustrate the diversity in European recommendations on vitamin A and vitamin D, and to explore differences and commonalities in approaches that could possibly explain variations observed.MethodsA questionnaire was developed to get information on the process of establishing micronutrient recommendations. These questionnaires were sent to key informants in the field of micronutrient recommendations to cover all European countries/regions. Also the latest reports on nutrient recommendations in Europe were collected. Standardisation procedures were defined to enable comparison of the recommendations. Recommendations for vitamin A and vitamin D were compared per sex at the ages 3, 9 months and 5, 10, 15, 25, 50 and 70 years. Information extracted from the questionnaires and reports was compared focusing on: (1) The concept of recommendation (recommended daily allowance (RDA), adequate intake (AI) or acceptable range), (2) The year of publication of the report (proxy for available evidence), (3) Population groups defined, (4) Other methodological issues such as selected criteria of adequacy, the type of evidence used, and assumptions made.ResultsTwenty-two countries, the World Health Organization (WHO)/the Food and Agriculture Organization of the United Nations (FAO) and the EC have their own reports on nutrient recommendations. Thirteen countries based their micronutrient recommendations on those from other countries or organisations. Five countries, WHO/FAO and the EC defined their own recommendations. The DACH-countries (Germany, Austria and Switzerland) as well as the Nordic countries (Norway, Sweden, Finland, Denmark and Iceland) cooperated in setting recommendations. Greece and Portugal use the EC and the WHO/FAO recommendations, respectively and Slovenia adopted the recommendations from the DACH-countries. Rather than by concepts, definitions, and defined population groups, variability appears to emerge from differences in criteria for adequacy, assumptions made and type of evidence used to establish micronutrient recommendations.DiscussionThe large variation in current micronutrient recommendations for population groups as illustrated for vitamin A and vitamin D strengthens the need for guidance on setting evidence based, up-to-date European recommendations. Differences in endpoints, type of evidence used to set recommendations, experts’ opinions and assumptions are all likely to contribute to the identified variation. So far, background information was not sufficient transparent to disentangle the relative contribution of these different aspects.ConclusionEURRECA has an excellent opportunity to develop tools to improve transparency on the approaches used in setting micronutrient recommendations, including the selection of criteria for adequacy, weighing of evidence, and interpretation of data.

How we will produce the evidence-based EURRECA toolkit to support nutrition and food policy

BackgroundThere is considerable variation in the recommended micronutrient intakes used by countries within Europe, partly due to different methodologies and concepts used to determine requirements and different approaches used to express the recommendations. As populations become more mobile and multi-national, and more traditional foods become available internationally, harmonised recommendations based on up to date science are needed. This was recognised by the European Commission’s (EC) Directorate-General (DG) Research in their 2005 call for proposals for a Network of Excellence (NoE) on ’nutrient status and requirements of specific vulnerable population groups’. EURopean micronutrient RECommendations Aligned (EURRECA), which has 34 partners representing 17 European countries, started on its 5-year EC-funded programme in January 2007. The programme of work was developed over 2 years prior to submitting an application to the EC. The Network’s first Integrating Meeting (IM) held in Lisbon in April 2007, and subsequent consultations, has allowed further refinement of the programme.AimThis paper presents the rationale for the EURRECA Network’s roadmap, which starts by establishing the status quo for devising micronutrient recommendations. The Network has the opportunity to identify previous barriers and then explore ’evidence-based’ solutions that have not been available before to the traditional panels of experts. The network aims to produce the EURRECA ’toolkit’ to help address and, in some cases, overcome these barriers so that it can be used by those developing recommendations.ResultsThe status quo has been largely determined by two recent initiatives; the Dietary Reference Intake (DRI) reports from the USA and Canada and suggestions for approaches to international harmonisation of nutrient-based dietary standards from the United Nations University (UNU). In Europe, the European Food Safety Authority (EFSA) has been asked by the EC’s Directorate-General for Health and Consumer Protection to produce values for micronutrient recommendations. Therefore, EURRECA will draw on the uniqueness of its consortium to produce the sustainable EURRECA toolkit, which will help make such a task more effective and efficient. Part of this uniqueness is the involvement in EURRECA of small and medium-sized enterprises (SMEs), consumer organisations, nutrition societies and other stakeholders as well as many scientific experts. The EURRECA toolkit will contain harmonised best practice guidance for a more robust science base for setting micronutrient recommendations. Hence, in the future, the evidence base for deriving nutrient recommendations will have greater breadth and depth and will be more transparent.ConclusionsThe EURRECA Network will contribute to the broader field of food and nutrition policy by encouraging and enabling the alignment of nutrient recommendations. It will do this through the development of a scientific toolkit by its partners and other stakeholders across Europe. This will facilitate and improve the formulation of micronutrient recommendations, based on transparently evaluated and quantified scientific evidence. The Network aims to be sustainable beyond its EC funding period.

Challenges in Harmonizing Energy and Nutrient Recommendations in Europe

At the present time, there is considerable diversity in the dietary reference values and recommendations used across Europe, both in terms of terminology and guideline values. Harmonization of dietary reference values would be beneficial in simplifying nutritional policy, trade, and public understanding of diet and health issues. However, this is not a simple task because of the differences in methodological approaches adopted and the assumptions made. In addition, there are genuine differences in diet, lifestyle and geography that may necessitate retaining variation in some dietary reference values between European nations. The complexities of harmonization were discussed at a recent symposium held under the auspices of the Federation of European Nutrition Societies (FENS). This provided overviews of the different terminologies currently in use, of the variations in reference values for children and adolescents, and of the disparities between different groups of countries in Europe. The symposium hosted by FENS provided a forum to exchange views and to consider the steps that will be needed if harmonization is to be realized in the future. A summary of the presentations and conclusions is presented here.

Turning dilemmas into opportunities: a UNU/SCN capacity development network in public nutrition in Central and Eastern Europe

Capacity development in nutrition is a process whereby individuals, groups, institutions, organizations and societies enhance their abilities to identify and meet challenges in a sustainable manner. To address these issues, in 2001 the UN System Standing Committee on Nutrition (SCN) established a Working Group on Capacity Development under the joint coordination of the United Nations University (UNU) and the International Union of Nutritional Sciences. Several regional professional networks have developed under this working group, the latest for the Central and Eastern Europe (CEE) countries. Ten CEE countries formed a network in 2006 and identified major nutritional challenges in the region, which included: irregular meal patterns; low consumption of fruits/vegetables, milk products and fish; low intake of some micronutrients; and high intakes of fat, sugar and salt. Public policies in nutrition were either weak or absent. Some countries had recently developed nutrition plans. Higher education in nutrition was seen as very important for public nutrition work by professionals in the region, who considered it a prerequisite for reversing the negative trend of the nutrition transition. The network will continue to work on issues that are still not covered adequately. Its activities to date and prospects for the future are assessed against ten principles for good capacity development suggested by the United Nations Development Programme.

Epitope distribution in ordered and disordered protein regions - part A. T-cell epitope frequency, affinity and hydropathy.

Highly disordered protein regions are prevalently hydrophilic, extremely sensitive to proteolysis in vitro, and are expected to be under-represented as T-cell epitopes. The aim of this research was to find out whether disorder and hydropathy prediction methods could help in understanding epitope processing and presentation. According to the pan-specific T-cell epitope predictors NetMHCpan and NetMHCIIpan and 9 publicly available disorder predictors, frequency of epitopes presented by human leukocyte antigens (HLA) class-I or -II was found to be more than 2.5 times higher in ordered than in disordered protein regions (depending on the disorder predictor). Both HLA class-I and HLA class-II binding epitopes are prevalently hydrophilic in disordered and prevalently hydrophobic in ordered protein regions, whereas epitopes recognized by HLA class-II alleles are more hydrophobic than those recognized by HLA class-I. As regards both classes of HLA molecules, high-affinity binding epitopes display more hydrophobicity than low affinity-binding epitopes (in both ordered and disordered regions). Epitopes belonging to disordered protein regions were not predicted to have poor affinity to HLA class-II molecules, as expected from disorder intrinsic proteolytic instability. The relation of epitope hydrophobicity and order/disorder location was also valid if alleles were grouped according to the HLA class-I and HLA class-II supertypes, except for the class-I supertype A3 in which the main part of recognized epitopes was prevalently hydrophilic. Regarding specific supertypes, the affinity of epitopes belonging to ordered regions varies only slightly (depending on the disorder predictor) compared to the affinity of epitopes in corresponding disordered regions. The distribution of epitopes in ordered and disordered protein regions has revealed that the curves of order-epitope distribution were convex-like while the curves of disorder-epitope distribution were concave-like. The percentage of prevalently hydrophobic epitopes increases with the enhancement of epitope promiscuity level and moving from disordered to ordered regions. These data suggests that reverse vaccinology, oriented towards promiscuous and high-affinity epitopes, is also oriented towards prevalently hydrophobic, ordered regions. The analysis of predicted and experimentally evaluated epitopes of cancer-testis antigen MAGE-A3 has confirmed that the majority of T-cell epitopes, particularly those that are promiscuous or naturally processed, was located in ordered and disorder/order boundary protein regions overlapping hydrophobic regions.

G cells and gastrin in chronic alcohol-treated rats.

Numerous reports have described gastric mucosal injury in rats treated with high ethanol concentrations. However, to the best of our knowledge, ultrastructural characteristics of G cells and antral gastrin levels have not been previously reported, either in rats that chronically consumed alcohol or in human alcoholics. The goal of this study was to examine the effect of ethanol consumption (8.5 g/kg) over a 4-month period, under controlled nutritional conditions, on antral and plasma levels of gastrin, ultrastructure of G cells, morphometric characteristics of G cells by stereological methods, and analysis of endocrine cells in the gastric mucosa by immunohistochemistry. The chronic alcohol consumption resulted in a nonsignificant decrease in gastrin plasma levels and unchanged antral gastrin concentrations. A slightly damaged glandular portion of the gastric mucosa and dilatation of small blood vessels detected by histological analysis, suggests that ethanol has a toxic effect on the mucosal surface. Chronic alcohol treatment significantly decreased the number of antral G cells per unit area, and increased their cellular, nuclear, and cytoplasmatic profile areas. In addition, the volume density and diameter of G-cell granules, predominantly the pale and lucent types, were increased, indicating inhibition of gastrin release. Ethanol treatment also decreased the number of gastric somatostatin-, serotonin-, and histamine-immunoreactive cells, except the somatostatin cells in the pyloric mucosa, as well as both G: D: enterochromaffin cells (EC) cell ratios in the antrum and D: ECL cell ratios in the fundus. These results indicate that the change of morphometric parameters in G cells may be related to cellular dysfunction. Our findings also suggest that regulation of G-cell secretion was not mediated by locally produced somatostatin in ethanol-consuming rats, but may involve gastric luminal content and/or neurotransmitters of gastric nerve fibers.

Software tools for simultaneous data visualization and T cell epitopes and disorder prediction in proteins

We have developed EpDis and MassPred, extendable open source software tools that support bioinformatic research and enable parallel use of different methods for the prediction of T cell epitopes, disorder and disordered binding regions and hydropathy calculation. These tools offer a semi-automated installation of chosen sets of external predictors and an interface allowing for easy application of the prediction methods, which can be applied either to individual proteins or to datasets of a large number of proteins. In addition to access to prediction methods, the tools also provide visualization of the obtained results, calculation of consensus from results of different methods, as well as import of experimental data and their comparison with results obtained with different predictors. The tools also offer a graphical user interface and the possibility to store data and the results obtained using all of the integrated methods in the relational database or flat file for further analysis. The MassPred part enables a massive parallel application of all integrated predictors to the set of proteins. Both tools can be downloaded from http://bioinfo.matf.bg.ac.rs/home/downloads.wafl?cat=Software. Appendix A includes the technical description of the created tools and a list of supported predictors.