EURRECA: determining dose-response relationships between micronutrient intake, biomarkers for micronutrient status and health outcomes

We systematically assembled scientific literature on the relationships between micronutrient intake, micronutrient status (biomarkers) and health outcomes for folate, iodine, zinc, vitamin B12 and iron for several population groups. This evidence will be reviewed and, where possible quantitatively summarized with meta-analyses, to support the process of deriving micronutrient recommendations. We will illustrate this process for vitamin B12 in adults and elderly. Methods We searched for all randomized controlled trials, prospective cohort studies, nested case-control studies and cross-sectional studies in human adult (>18 yrs) and elderly populations that measured vitamin B12 intake with either a validated food frequency questionnaire or a dietary history method, or a 24hour recall, food record or food diary for at least 3 days; measured vitamin B12 status as serum or plasma vitamin B12, serum or plasma MMA or holoTC; and/or included a health outcome related to osteoporosis, cognitive function, neurological function or anemia. Searches were performed in duplicate by two investigators using the Cochrane Library, MEDLINE, and Embase databases. We will perform separate systematic reviews on the relationship between vitamin B12 intake and vitamin B12 status, vitamin B12 intake and health outcomes, and vitamin B12 status and health outcomes. We will select studies that are comparable with regard to study design, measurement of vitamin B12 intake, vitamin B12 status and health outcomes to calculate the overall pooled association or effect using random effects meta-analysis. The studies that are not included in a meta-analysis will be reviewed according to a narrative approach. Results The results of three meta-analyses will be presented: 1) a meta-analysis investigating the relationship between vitamin B12 intake and vitamin B12 status (plasma or serum vitamin B12); 2) a meta-analysis investigating the relationship between vitamin B12 status and osteoporosis (measured as fracture risk); and 3) a meta-analysis investigating the relationship between vitamin B12 status and cognitive function (measured as incident dementia). Discussion We will discuss how the evidence from both the narrative approach and the meta-analytic approach can be integrated to contribute to the process of deriving micronutrient recommendations. This research was undertaken as an activity of the European Micronutrient Recommendations Aligned (EURRECA) Network of Excellence (www.eurreca.org), funded by the European Commission Contract Number FP6 036196-2 (FOOD). The original conception of the systematic review was undertaken by the EURRECA Network and coordinated by partners based at Wageningen University (WU), the Netherlands and the University of East Anglia (UEA), United Kingdom.