Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status

Abstract

PurposeTo investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status.MethodsWe included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotranscobalamin (ΔholoTC) before and after 2 day administration of different doses of cyanocobalamin and hydroxocobalamin (CobaSorb test). In the low status group, the test was performed using a cross-over design with identical doses of both cobalamin forms (1.5, 3, and 6 µg, respectively). In the normal status group, the test was performed with either 3, 6, and 9 µg cyanocobalamin (n = 28), or with 9 µg cyanocobalamin and 9 µg hydroxocobalamin (n = 14).ResultsIn both groups, median ΔholoTC (pmol/L) was higher after intake of cyanocobalamin compared to (hydroxocobalamin) [low status: 1.5 µg: 19 (6); 3 µg: 23 (7); 6 µg: 30 (14); normal status: 9 µg: 30 (13) pmol/L]. Independent of B12 form, no difference was observed in ΔholoTC between those receiving 1.5 and 3 µg in the low status group or 6 and 9 µg cyanocobalamin in the normal status group. However, in both groups, administration of 6 µg cobalamin resulted in a significant higher ΔholoTC than did 3 µg [low status: p = 0.02 (0.009) for cyanocobalamin (hydroxocobalamin); normal status: p = 0.03 for cyanocobalamin].ConclusionsAdministration of cyanocobalamin resulted in a more than twofold increase in holoTC in comparison with hydroxocobalamin. The absorptive capacity was reached only by doses above 3 µg cobalamin. Our results underscore the importance of using the same form of cobalamin when comparing uptake under different conditions.Clinical trial registry numberNCT02832726 at https://clinicaltrials.gov and 2016/09/012147 at Clinical Trials Registry India.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-017-1553-5) contains supplementary material, which is available to authorized users.

Effect of 8-week oral supplementation with 3-µg cyano-B12 or hydroxo-B12 in a vitamin B12-deficient population

“…The rational is that this form of the vitamin is both chemically stable and cheap. In agreement with the previous studies [11][12][13][14], we find that CN-B12 induces a higher increase in the circulating total Cbl in comparison to HO-B12. Interestingly, administration of HO-B12 is as efficient-if not slightly better-in improving other markers of an impaired B12 status, notably MMA.…”

“…All capsules, with or without B12, were stored in light-protected containers at 4 °C together with a desiccant. The maximal storage time of 6 weeks did not cause any changes in the B12 content, as previously demonstrated [14].…”

“…The baseline concentration of totalHC (Table 1) is above reference intervals (determined for a Scandinavian population [17]); but at the same level of a comparable Indian population with low B12 status [14].…”

“…The two forms are interchangeable, and their presence depends on the pH of the solution. CN-B12 and HO-B12 were given as aqueous solutions absorbed in 30-mg sugar and packed in two-piece hard-shell gelatin capsules (Natur-Drogeriet, Horning, Denmark) as described in Greibe et al [14]. In brief, CN-B12 (Betolvex, A ctavis, Gentofte, Denmark) and HO-B12 (Vibeden, Sandox, Copenhagen, Denmark) were dissolved in sterile demineralized water and centrifuged at 12,000×g for 5 min at room temperature.…”

“…For example, in rats, considerably more B12 is internalized in the liver after ingestion of HO-B12, when compared to an equal dose of CN-B12 [12,13]. Conversely, the circulating level of B12 is much higher upon administration of CN-B12 than after intake of similar dose of HO-B12 [11][12][13][14].…”