Studies of biomarker responses to intervention with vitamin B-12: a systematic review of randomized controlled trials.
What this study found
Oral vitamin B-12 supplementation reliably improved biomarkers of vitamin B-12 status. Serum/plasma total vitamin B-12 increased across 8 RCTs (WMD 185 pmol/L; 95% CI 107, 263; n = 506; P < 0.00001), while methylmalonic acid decreased (WMD 20.28 lmol/L; 95% CI 20.35, 20.22; n = 186; P < 0.00001) and total homocysteine decreased (WMD 23.3 lmol/L; 95% CI 24.5, 22.2; n = 282; P < 0.00001). Holotranscobalamin could not be evaluated reliably because it was measured in only one study. The authors concluded that serum/plasma total vitamin B-12, methylmalonic acid, and total homocysteine are…
- Study & population
- Systematic review of randomized controlled trials in humans, totaling 506 participants across 8 studies.
- Intervention
- Oral vitamin B-12 supplementation was evaluated across 8 randomized controlled trials, using cyanocobalamin or methylcobalamin delivered as capsules, added to milk, or food-based delivery.
- Key limitation
- The evidence base was small and heterogeneous, with varying doses, formulations, and study durations across the trials.
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Open PDFOriginal abstract
BACKGROUND Mild vitamin B-12 deficiency is common among older adults, but evidence for setting dietary recommendations is limited because most studies have administered vitamin B-12 via nonoral routes or at doses several hundred times higher than current recommendations. Furthermore, different biomarkers of vitamin B-12 status have not been systematically reviewed. OBJECTIVE The aim was to assess the effectiveness of biomarkers of vitamin B-12 status through a systematic review of published randomized controlled trials of oral vitamin B-12 supplementation. DESIGN Methods included a structured search strategy on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction; validity assessment; and meta-analysis. RESULTS Eight randomized controlled trials were included, and all studies measured serum and plasma total vitamin B-12, 3 studies measured methylmalonic acid, and 6 studies measured total homocysteine response. All 3 biomarkers were found to be effective measures of altered vitamin B-12 intake in populations with low and borderline baseline vitamin B-12 status (P < 0.00001); however, in the case of total vitamin B-12, substantial heterogeneity that could not be fully explained by subgroup analysis was observed. Insufficient data were available to determine the effectiveness of plasma holotranscobalamin, which was measured in only one randomized controlled trial. CONCLUSIONS The available evidence suggests that plasma and serum concentrations of total vitamin B-12, methylmalonic acid, and total homocysteine are all effective biomarkers of a change in vitamin B-12 intake; however, because the available data were limited, it was not possible to examine fully the factors that could explain the substantial heterogeneity in total vitamin B-12. Future trials should include low-dose vitamin B-12 in adults across the entire age spectrum and measure the holotranscobalamin response to supplementation.