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Vitamin B12 Absorption in a Community is 'Continuously' Distributed and Influences Response to Long-term Oral Supplementation

Yajnik, C. S.; Rush, E. C.; Bhat, D. S.; Wagh, R. S.; Deshmukh, O. A.; Ladkat, R.; Plank, L. D.; Bandopadhyay, S.; Fall, C. H.; Refsum, H.; Deshmukh, U. S.

2025-07-18 epidemiology
10.1101/2025.07.18.25331760 medRxiv
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BackgroundInsufficient dietary intake and/or reduced gastrointestinal absorption lead to low vitamin B12 (B-12) status. In a secondary data analysis of the results of the B-12 absorption (CobaSorb) test and B-12 supplementation trial in a B-12 insufficient Indian rural community, we explored characteristics of B-12 absorption and its association with post-supplementation plasma B-12 concentration. ObjectiveTo study i) the distribution of plasma holo-transcobalamin (holoTC) response during the CobaSorb test, and ii) determinants of plasma B-12 response to long-term, oral supplementation with physiological dose B-12. MethodsThe participants (parents and children in the Pune Maternal Nutrition Study) first underwent a B-12 absorption study Subsequently, they participated in a 12-month-long, double-blind RCT of daily oral B-12 (0, 2, or 10 {micro}g) and folic acid (0 or 200 {micro}g). Circulating B-12 was measured at baseline and after 4 and 12 months of supplementation. A linear mixed-effect model was used to study the predictors of B-12 absorption and response to supplementation. ResultsThree hundred and thirteen participants included children (n=109, 57 boys, mean age 9y, weight 21.9 kg, BMI 13.6 kg/m2), mothers (n=108, 30y, 47.7 kg, 19.3 kg/m2), and fathers (n=96, 37y, 59.3 kg, 21.4 kg/m2). The plasma holoTC response during the absorption test was continuously distributed and was negatively associated with weight and positively with the dose of B-12. Response to long-term B-12 supplementation was positively predicted by absorption test response, dose of B-12, length of supplementation, and compliance. ConclusionsThe continuous distribution of plasma holoTC response during the absorption test supports a graded absorption of B-12. CobaSorb protocol could be used to unravel the intricacies of B-12 absorption. Clinical Trial Registry number and website where it was obtainedISRCTN59289820. DOI: https://doi.org/10.1186/ISRCTN59289820 https://www.isrctn.com/

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