Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status
Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status
Eva Greibe 0 1 2 4
Namita Mahalle 0 1 2 4
Vijayshri Bhide 0 1 2 4
Christian W. Heegaard 0 1 2 4
Sadanand Naik 0 1 2 4
Ebba Nexo 0 1 2 4
0 Department of Molecular Biology and Genetics, Aarhus University , Aarhus , Denmark
1 Department of Pathology, Deenanath Mangeshkar Hospital and Research Center , Pune , India
2 Department of Clinical Biochemistry and Institute of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark
3 Sadanand Naik
4 Clinical Biochemistry, Deenanath Mangeshkar Hospital and Research Center , Pune , India
Purpose To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. Methods We 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). Results In 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]. Conclusions Administration 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 number NCT02832726 at https:// clinicaltrials.gov and 2016/09/012147 at Clinical Trials Registry India.
Vitamin B12; Cyanocobalamin; Hydroxocobalamin; Holotranscobalamin; CobaSorb test; Cobalamin absorption
Introduction
Cobalamin (vitamin B12) is an essential micronutrient.
Inadequate intake or impaired intestinal absorption leads
to cobalamin deficiency and clinical signs of neurological
impairment and/or anemia [
1
].
Cyanocobalamin (CN-Cbl) is the synthetic form of the
vitamin, most often used in vitamin pills. In food items,
cobalamin is present as hydroxocobalamin (HO-Cbl), or the
coenzymes methylcobalamin or 5′-deoxyadenosylcobalamin
[
2
]. Upon light exposure, the coenzymes are converted to
HO-Cbl.
A number of studies have investigated the absorption
of CN-Cbl, while only a few over 40-year-old studies have
compared the uptake of various other forms of the vitamin.
Employing radioactive-labeled cobalamin and whole-body
monitoring, Weisberg and Glass [
3
] found that CN-Cbl and
HO-Cbl were equally absorbed at large pharmacological
dosages (100–1000 µg), and Heinrich and Gabbe [
4
] and
Adams et al. [
5
] confirmed these findings for low doses of
cobalamin (< 5 µg). In more recent time, usage of
radioactive-labeled cobalamin has not been considered suitable for
human studies. To circumvent this problem, we designed a
test that we named CobaSorb [
6–8
]. In its original design,
serum holotranscobalamin (holoTC, active cobalamin) was
measured before and after oral intake of three doses of 9 µg
CN-Cbl for 2 days [
6–8
]. Further studies have shown that
the test is suitable for judging cobalamin absorption even in
a population with a low cobalamin status and that doses as
low as 2 µg can be used [
9
].
The studies performed so far leave three questions
unanswered. Does intake of cobalamin present in a vitamin pill
(CN-Cbl) and present in food (HO-Cbl) result in similar
increase in plasma holoTC? Which physiological dose
of cobalamin should be administered to give the highest
increase in holoTC? Moreover, is there any difference in the
cobalamin-induced increase in holoTC between individuals
with a low and a normal cobalamin status? In the present
study, we address these questions.
Subjects and methods
Participants with low cobalamin status (group A)
Participants were recruited from Pune, India, and the study
was carried out at Deenanath Mangeshkar Hospital and
Research Center, Pune, India, in the fall of 2015. In total, 62
healthy lacto-vegetarian Indian individuals aged ≥ 18 years
were included. Mo (...truncated)