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Clinical Chemistry 48: 1768-1771, 2002;
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(Clinical Chemistry. 2002;48:1768-1771.)
© 2002 American Association for Clinical Chemistry, Inc.

Holo-Transcobalamin Is an Early Marker of Changes in Cobalamin Homeostasis. A Randomized Placebo-controlled Study

Ebba Nexo1a, Anne-Mette Hvas2, Øyvind Bleie3, Helga Refsum4, Sergey N. Fedosov5, Stein Emil Vollset6, Jorn Schneede6, Jan Erik Nordrehaug3, Per Magne Ueland6 and Ottar Kjell Nygard3,6

1 Department of Clinical Biochemistry, AKH, and
2 Department of Clinical Biochemistry, AAS, Aarhus University Hospital, DK 8000 Aarhus C, Denmark.

3 Institute of Medicine and
4 Department of Pharmacology, University of Bergen, N-5021 Bergen, Norway.

5 The Protein Chemistry Laboratory, Aarhus University, DK-5000 Aarhus C, Denmark.

6 Locus for Homocysteine and Related Vitamins, University of Bergen, N-5021 Bergen, Norway.

aAddress correspondence to this author at: Department of Clinical Biochemistry, AKH, Aarhus University Hospital, Norrebrogade 44, DK 8000 Aarhus C, Denmark. Fax 45-8949-3060; e-mail E.Nexo{at}dadlnet.dk.

Background: We examined the effect of oral vitamin B12 treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin (TC) and haptocorrin (HC).

Methods: Patients (n = 88; age range, 38–80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to daily oral treatment with (a) vitamin B12 (0.4 mg), folic acid (0.8 mg), and vitamin B6 (40 mg); (b) vitamin B12 and folic acid; (c) vitamin B6; or (d) placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter.

Results: The intraindividual variation for patients not treated with B12 was ~10% for plasma total cobalamin, total TC, apo-TC, and apo-HC, and <20% for holo-TC and TC saturation. In B12-treated patients, the maximum change in concentrations was observed already after 3 days for total TC (-16%), holo-TC (+54%), and TC saturation (+82%). At this time holo-HC (+20%) and plasma total cobalamin (+28%) showed an initial burst, but had increased further at 84 days. All changes were highly significant compared with the control group (P <0.0001).

Conclusions: Oral vitamin B12 treatment produces maximal effects on total TC, holo-TC, and TC saturation within 3 days, whereas maximal increases in holo-HC and plasma total cobalamin occur later. The results support the view that holo-TC is an early marker of changes in cobalamin homeostasis.




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