The Oral Bioavailability of Vitamin B12 at Different Doses in Healthy Indian Adults

Abstract

Background/objectives: The bioavailability of crystalline vitamin B₁₂ (B₁₂) through active absorption is reported to have a maximum capacity of 1.5-2.5 µg per dose. A small passive bioavailability has also been suggested at high doses. The present study aimed to determine the dose-dependency of active B₁₂ absorption and to quantify its passive absorption at higher doses.

Methods: The dose-dependency of crystalline B₁₂ bioavailability was determined in nine healthy adults, using oral [¹³C]-cyanocobalamin, in a cross-over design at doses of 2.5, 5, and 10 µg. The dose order was randomised, with a washout of one month. Literature data from was added to the present study data in a meta-analysis of the relation between B₁₂ bioavailability and dose, to evaluate its pattern at different doses.

Results: Bioavailability, as a function of dose, was significantly different between 2.5, 5, and 10 µg doses of [¹³C]-cyanocobalamin at 50.9 ± 32.5%, 26.7 ± 22.3%, 15.4 ± 13.6%, respectively, (p < 0.01), while the absolute bioavailability trended upward, at 1.16 ± 0.74 µg, 1.22 ± 1.02 µg, and 1.39 ± 1.23 µg (p = 0.46). The meta-analysis showed two distinct phases of bioavailability. Up to a dose of 2.6 µg, there was a significant steep positive correlation, with a slope (bioavailability) of 43%/µg suggesting an active process with a maximum of 1.2 µg. At higher doses, the slope was 1%/µg, not significantly different from zero, possibly a passive process.

Conclusions: The active bioavailability of crystalline B₁₂ is not dose-dependent, saturating at ~1.2 µg.

Keywords: [13C]-cyanocobalamin; bioavailability; dose dependency; vitamin B12.

Figure 1

Consort flow chart with participant screening and study protocol.

Figure 2

Experiment day protocol followed for each dose day in the oral dose dependency of the B₁₂ bioavailability study.

Figure 3

High-resolution accurate mass spectrometry analysis of CN (cyano)-, Ado (adenosyl)-, CH3 (methyl)-, and OH (hydroxo)-vitamin B-12 (singly, doubly, and triply charged species). The precursor masses at m/z 678.29098 and m/z 680.29738, m/z 672.80149 and m/z 674.80149, m/z 664.78568 and m/z 666.78568, and m/z 790.33645 and m/z 792.33645 for [¹²C]- and [¹³C]-cobalamin species of cyano-, methyl-, hydroxo-, and adenosylcobalamin, respectively. Figure reproduced from Ref. [21].

Figure 4

High-resolution accurate mass spectrometry analysis of the synthesised [¹³C]-cyanocobalamin showing doubly charged ion at m/z 680.29768 [M + 2H]^2⁺ with the 4-Dalton shift as compared with standard cyanocobalamin. Figure reproduced from Ref. [21].

Figure 5

Fractional bioavailability of [¹³C]-cyanocobalamin at oral doses of 2.5 µg, 5 µg, and 10 µg (n = 9). The vertical lines that spilt each box represent the median, the whiskers represent the interquartile ranges, and the filled black circles indicate mean fractional bioavailability of each oral dose. ** p < 0.01 and * p < 0.05.

Figure 6

Absolute bioavailability of [¹³C]-cyanocobalamin at oral doses of 2.5 µg, 5 µg, and 10 µg (n = 9). The vertical lines that spilt each box represent the median, the whiskers represent the interquartile ranges, and the filled black circles indicate mean absolute bioavailability of each oral dose. ns: not significant, p > 0.05.

Figure 7

Break-point analysis of absolute bioavailability at different doses of cyanocobalamin compiled from bioavailability data of the previous and present studies.