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

Dullemeijer et al., 2013 | Am J Clin Nutr | Meta Analysis

Citation

Dullemeijer Carla, Souverein Olga W, ... van 't Veer Pieter. 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. Am J Clin Nutr. 2013-Feb;97(2):390-402. doi:10.3945/ajcn.112.033951

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. DESIGN: 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. CONCLUSION: 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.

Key Findings

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 concentrat

Outcomes Measured

Requires manual extraction

Population

Field	Value
Population	healthy adult
Sample Size	See abstract
Age Range	See abstract
Condition	See abstract

MeSH Terms

Adult
Aged
Aging
Biomarkers
European Union
Evidence-Based Medicine
Humans
Methylmalonic Acid
Nutrition Policy
Nutritional Requirements
Transcobalamins
Vitamin B 12
Vitamin B 12 Deficiency

Evidence Classification

Level: Meta Analysis
Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review
Vertical: vitamin-b12

Provenance

PMID: 23269815
DOI: 10.3945/ajcn.112.033951
PMCID: Not in PMC
Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09