The process of setting micronutrient recommendations: a cross-European comparison of nutrition-related scientific advisory bodies

Copyright @ The Authors 2010Objective: To examine the workings of the nutrition-related scientific advisory bodies in Europe, paying particular attention to the internal and external contexts within which they operate. Design: Desk research based on two data collection strategies: a questionnaire completed by key informants in the field of micronutrient recommendations and a case study that focused on mandatory folic acid (FA) fortification. Setting: Questionnaire-based data were collected across thirty-five European countries. The FA fortification case study was conducted in the UK, Norway, Denmark, Germany, Spain, Czech Republic and Hungary. Results: Varied bodies are responsible for setting micronutrient recommendations, each with different statutory and legal models of operation. Transparency is highest where there are standing scientific advisory committees (SAC). Where the standing SAC is created, the range of expertise and the terms of reference for the SAC are determined by the government. Where there is no dedicated SAC, the impetus for the development of micronutrient recommendations and the associated policies comes from interested specialists in the area. This is typically linked with an ad hoc selection of a problem area to consider, lack of openness and transparency in the decisions and over-reliance on international recommendations. Conclusions: Even when there is consensus about the science behind micronutrient recommendations, there is a range of other influences that will affect decisions about the policy approaches to nutrition-related public health. This indicates the need to document the evidence that is drawn upon in the decisions about nutrition policy related to micronutrient intake.This work has been carried out within the EURRECA Network of Excellence (www.eurreca.org) which is financially supported by the Commission of the European Communities, specific Research, Technology and Development (RTD) Programme Quality of Life and Management of Living Resources, within the Sixth Framework Programme, contract no. 036196

EURRECA's General Framework to make the process of setting up micronutrient recommendations explicit and transparent

EURRECA is a Network of Excellence with the objective of addressing the problem of national variations in micronutrient recommendations and working towards a framework of advice to better inform policy-makers. It became apparent that the network needed a framework that puts the process of recommendation setting in the context of science, policy and society. Although variability in recommendations originates from the scientific evidence-base used and its interpretation (e.g. health outcomes, types and methods of evaluation of evidence, quantification of risk/benefit), the background information provided in the recommendation reports does not easily facilitate the disentangling of the relative contribution of these different aspects because of lack of transparency. The present report portrays the general framework (see Figure) that has been developed by and for EURRECA in order to make the process of setting up micronutrient recommendations explicit and transparent. In explaining the link from science to policy applications, the framework distinguishes four principal components or stages (see Figure). These stages are: a) Defining the nutrient requirements: A judgement about the (best) distribution(s) of the population requirement is necessary for estimating nutrient requirements. Many assumptions need to be made about the attributes of the population group. Furthermore, several factors (consumer behaviour as well as physiology) are to be included to characterize optimal health. b) Setting the nutrient recommendations: All available evidence is needed to formulate recommendations. Incorporating different endpoints provide the basis to formulate an optimal diet in terms of (non-)nutrients and food(group)s. c) Policy options: Policy options should be formulated on how the optimal diet can be achieved. They concern the advice of scientist and/or expert committees to the policy makers. Current policy options are setting up a task force, food based dietary guidelines, general health education, educational programme for specific group(s), voluntary or mandatory fortification, labelling, supplementation (general or for specific groups), inducing voluntary action in industry, legislation on micronutrient composition in food products, fiscal change, monitoring and evaluation of intake (via food consumption surveys) and/or nutritional status. d) Policy applications: Policies and planning, usually done by government, that lead to nutritional interventions or programmes. They usually require consideration of scientific, legal, regulatory, ethical and cultural issues, economic implications, and political and social priorities. This framework illustrates three dimensions of the process of setting (micro)nutrient requirements: 1) The logical sequence of scientific thinking from setting physiological requirements for nutritional health leading to evidence-based derivation of Nutrient Intake Values. 2) In the early stages nutritional and epidemiological science is the dominant source and in the later stages evidence from consumer and social sciences as well as stakeholder influences is used in deriving the options for changing the distribution of nutrient intakes. 3) The wider socio-political context: a feedback loop between health perception, actual health and food intake exists and is directly affected by the food industry and many other stakeholders. Moreover, from the viewpoint of policymakers, there are concerns for health promotion and disease prevention because of population health indices, costs of health care, and economic interests in the agro-food sector. In conclusion: A systematic approach for development and regular review of micronutrient requirements in Europe, transparently based on scientific evidence and best practices, enables national and international authorities/bodies to use the best available information obtained through evidence-based nutrition and accomplish well-considered food policy. Funded by an EU FP6 Network of Excellence (EURRECA, grant no. FP 6–036196-2). G. T. performed part of the work under a short-term contract for WHO Europe

EURRECA-Evidence-Based Methodology for Deriving Micronutrient Recommendations

The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence explored the process of setting micronutrient recommendations to address the variance in recommendations across Europe. Work centered upon the transparent assessment of nutritional requirements via a series of systematic literature reviews and meta-analyses. In addition, the necessity of assessing nutritional requirements and the policy context of setting micronutrient recommendations was investigated. Findings have been presented in a framework that covers nine activities clustered into four stages: stage one Defining the problem describes Activities 1 and 2: Identifying the nutrition-related health problem and Defining the process; stage two Monitoring and evaluating describes Activities 3 and 7: Establishing appropriate methods, and Nutrient intake and status of population groups; stage three Deriving dietary reference values describes Activities 4, 5, and 6: Collating sources of evidence, Appraisal of the evidence, and Integrating the evidence; stage four Using dietary reference values in policy making describes Activities 8 and 9: Identifying policy options, and Evaluating policy implementation. These activities provide guidance on how to resolve various issues when deriving micronutrient requirements and address the methodological and policy decisions, which may explain the current variation in recommendations across Europe. [Supplementary materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.]This is the peer-reviewed version of the article: Dhonukshe-Rutten Rosalie, Bouwman Jildau, Brown Kerry A., Cavelaars Adrienne E., Collings Rachel, Grammatikaki Evangelia, de Groot Lisette, Gurinović Mirjana A., Harvey Linda, Hermoso Maria, Hurst Rachel, Kremer Bas, Ngo Joy, Novaković Romana, Raats Monique M., Rollin Fanny, Serra-Majem Lluis, Souverein Olga W., Timotijević Lada, van't Veer Pieter, "EURRECA-Evidence-Based Methodology for Deriving Micronutrient Recommendations" 53, no. 10 (2013):999-1040, [https://doi.org/10.1080/10408398.2012.749209

Vitamin B-12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid

The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B(12) deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B(12), Hcy, and MMA on differentiation and activity of bone cells. B(12) deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B(12) deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B(12), Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B(12) did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B(12) deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels

The Proper Motion of the Globular Cluster NGC 6553 and of Bulge Stars with HST

WFPC2 images obtained with the Hubble Space telescope 4.16 years apart have allowed us to measure the proper motion of the metal rich globular cluster NGC 6553 with respect to the background bulge stars. With a space velocity of (${\Pi}, {\Theta}, W$) = (-3.5, 230, -3) km s$^{-1}$, NGC 6553 follows the mean rotation of both disk and bulge stars at a Galactocentric distance of 2.7 kpc. While the kinematics of the cluster is consistent with either a bulge or a disk membership, the virtual identity of its stellar population with that of the bulge cluster NGC6528 makes its bulge membership more likely. The astrometric accuracy is high enough for providing a measure of the bulge proper motion dispersion and confirming its rotation. A selection of stars based on the proper motions produced an extremely well defined cluster color-magnitude diagram (CMD), essencially free of bulge stars. The improved turnoff definition in the decontaminated CMD confirms an old age for the cluster (~13 Gyr) indicating that the bulge underwent a rapid chemical enrichment while being built up at in the early Universe. An additional interesting feature of the cluster color-magnitude diagram is a significant number of blue stragglers stars, whose membership in the cluster is firmly established from their proper motions.Comment: version with full-page figure

Advancing food, nutrition, and health research in Europe by connecting and building research infrastructures in a DISH-RI: Results of the EuroDISH project

Background: Research infrastructures (RIs) are essential to advance research on the relationship between food, nutrition, and health. RIs will facilitate innovation and allow insights at the systems level which are required to design (public health) strategies that will address societal challenges more effectively. Approach: In the EuroDISH project we mapped existing RIs in the food and health area in Europe, identified outstanding needs, and synthesised this into a conceptual design of a pan-European DISH-RI. The DISH model was used to describe and structure the research area: Determinants of food choice, Intake of foods and nutrients, Status and functional markers of nutritional health, and Health and disease risk. Key findings: The need to develop RIs in the food and health domain clearly emerged from the EuroDISH project. It showed the necessity for a unique interdisciplinary and multi-stakeholder RI that overarches the research domains. A DISH-RI should bring services to the research community that facilitate network and community building and provide access to standardised, interoperable, and innovative data and tools. It should fulfil the scientific needs to connect within and between research domains and make use of current initiatives. Added value can also be created by providing services to policy makers and industry, unlocking data and enabling valorisation of research insights in practice through public-private partnerships. The governance of these services (e.g. ownership) and the centralised and distributed activities of the RI itself (e.g. flexibility, innovation) needs to be organised and aligned with the different interests of public and private partners

Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence

Background: Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12and folate status are associated with an increased fracture risk. As vitamin B12and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration. Methods/Design. The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration ( 12 mol/L). One group receives daily a tablet with 500 g vitamin B12and 400 g folic acid and the other group receives a placebo tablet. In both tablets 15 g (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology