title: Systematic review with dose-response meta-analyses between vitamin B-12 intake and European Micronutrient Recommendations Aligned's prioritized biomarkers of vitamin B-12 including randomized controlled trials and observational studies in adults and elderly persons.
abstract: BACKGROUND
  Many randomized controlled trials (RCTs) and observational studies have provided information on the association between vitamin B-12 intake and biomarkers. The use of these data to estimate dose-response relations provides a useful means to summarize the body of evidence.
  
  
  OBJECTIVE
  We systematically reviewed studies that investigated vitamin B-12 intake and biomarkers of vitamin B-12 status and estimated dose-response relations with the use of a meta-analysis.
  
  
  METHODS
  This systematic review included all RCTs, prospective cohort studies, nested case-control studies, and cross-sectional studies in healthy adult populations published through January 2010 that supplied or measured dietary vitamin B-12 intake and measured vitamin B-12 status as serum or plasma vitamin B-12, methylmalonic acid (MMA), or holotranscobalamin. We calculated an intake-status regression coefficient ( ) for each individual study and calculated the overall pooled   and SE ( ) by using random-effects meta-analysis on a double-log scale.
  
  
  RESULTS
  The meta-analysis of observational studies showed a weaker slope of dose-response relations than the meta-analysis of RCTs. The pooled dose-response relation of all studies between vitamin B-12 intake and status indicated that a doubling of the vitamin B-12 intake increased vitamin B-12 concentrations by 11% (95% CI: 9.4%, 12.5%). This increase was larger for studies in elderly persons (13%) than in studies in adults (8%). The dose-response relation between vitamin B-12 intake and MMA concentrations indicated a decrease in MMA of 7% (95% CI: -10%, -4%) for every doubling of the vitamin B-12 intake. The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to seriously alter these results.
  
  
  CONCLUSIONS
  The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of populations.
authors.affiliation: Division of Human Nutrition, Wageningen University and Research Centre, Wageningen, Netherlands. carla.dullemeijer@wur.nl
authors.forename: Carla
authors.initials: C
authors.lastname: Dullemeijer
authors.forename: Olga W
authors.initials: OW
authors.lastname: Souverein
authors.forename: Esmée L
authors.initials: EL
authors.lastname: Doets
authors.forename: Hilko
authors.initials: H
authors.lastname: van der Voet
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.forename: Waldo J
authors.initials: WJ
authors.lastname: de Boer
authors.forename: Maria
authors.initials: M
authors.lastname: Plada
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.forename: Paulette H
authors.initials: PH
authors.lastname: In 't Veld
authors.forename: Adrienne E J M
authors.initials: AE
authors.lastname: Cavelaars
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.forename: Pieter
authors.initials: P
authors.lastname: van 't Veer
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D015415:Biomarkers / Q000097:blood; D005062:European Union; D019317:Evidence-Based Medicine; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood; D018673:Nutrition Policy; D009751:Nutritional Requirements; D014155:Transcobalamins / Q000032:analysis; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D014155:Transcobalamins; D008764:Methylmalonic Acid; D014805:Vitamin B 12