Approaches for setting micronutrient recommendations : a case study of vitamin B12 for adults and elderly people

E.L. Doets

Research output: Thesisinternal PhD, WU


Background: Most countries in Europe provide recommendations on the micronutrient composition of diets to fulfil requirements of nearly all individuals in the general apparently healthy population. However as each country uses its own methods for deriving such recommendations, there is large variation between countries in the recommended micronutrient intakes. The objectives of this thesis are to signal key issues for harmonizing approaches for establishing micronutrient recommendations for adults and elderly across Europe and to illustrate standardized and transparent review methods that can be used to summarize and evaluate the evidence-base for setting recommendations, using vitamin B12 as a case micronutrient.
Methods: First the need for harmonization is substantiated by a descriptive study on the variation in published micronutrient recommendations across Europe. In addition methodological factors were identified that should be considered for alignment of recommended intakes across Europe. Secondly, the evidence-base for establishing recommended vitamin B12 intakes was summarized in two systematic reviews. One review focused on requirements for the compensation of daily obligatory losses (factorial approach) and the other review evaluated the relation of vitamin B12 intake and status with cognitive performance (dose-response approach). Whether interactions between folate and vitamin B12 on cognitive performance should be considered for establishing recommended vitamin B12 intakes was evaluated using data from 2203 Norwegian elderly from the Hordaland Homocysteine Study.
Results: For harmonizing approaches for establishing micronutrient recommendations, standard methods are needed to a)-select health indicators and define adequate biomarker concentrations, b)-make assumptions about inter-individual variation in requirements, c)-derive bioavailability factors, and d)-select and interpret evidence on requirements. The first systematic review showed that daily vitamin B12 losses in apparently healthy adults and elderly probably range between 2.6-3.9 µg and bioavailability from the usual diet may range between 29 and 37% rather than the generally assumed 50%.
Dose-response evidence from 2 randomized controlled trials and 19 prospective cohort studies showed no or inconsistent associations between vitamin B12 intake or status and dementia, Alzheimer’s Disease, global cognitive function or domain-specific cognitive function in adults and elderly people. Cross-sectional analyses in the Norwegian cohort study showed that low plasma vitamin B12 in combination with high folate was associated with better cognitive performance. However, these associations were not observed for sensitive markers of vitamin B12 status.
Conclusion: The main conclusion of this thesis is that evidence underlying current recommended vitamin B12 intakes is old and has large uncertainties, whereas the available evidence on the relation between vitamin B12 and cognitive performance is yet not convincing and thereby limits its use as an outcome for estimating vitamin B12 requirements.
The relation between vitamin B12 intake and markers of vitamin B12 status seems the best alternative, but sound statistical methods to define recommendations based on these dose-response data should be further developed.


Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • van 't Veer, Pieter, Promotor
  • de Groot, Lisette, Promotor
  • Cavelaars, Adrienne, Co-promotor
Award date15 Jun 2012
Place of PublicationS.l.
Print ISBNs9789461732354
Publication statusPublished - 15 Jun 2012


  • vitamin b12
  • dietary guidelines
  • recommended dietary allowances
  • adults
  • elderly
  • europe
  • harmonization


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