Differences in Tissue Distribution of Cyano–B12 and Hydroxo–B12 One Week after Oral Intake: An Experimental Study in Male Wistar Rats

Eva Greibe,Ole Nymark,Ebba Nexo,Christian Heegaard,Sergey Fedosov

doi:10.3390/nu10101487

Abstract

Foods contain natural vitamin B12 forms, such as hydroxo–B12 (HO–B12), whereas vitamin pills contain the synthetic cyano–B12 (CN–B12). Recent studies in rats showed different tissue distributions of CN–B12 and HO–B12 24 h after oral administration. Here, we investigate whether these differences are sustained or leveled out with time in both B12-deplete and -replete rats, thereby assessing if the two forms are equally good at maintaining a normal B12 status. Male Wistar rats were fed diets with low (n = 16) or high (n = 12) B12 content for 17 days. At day 10, the rats received a single oral dose of [57Co]-labeled CN–B12 or HO–B12 (n = 6 and n = 8, respectively, in each diet group). The rats were sacrificed on day 17 and endogenous B12 and [57Co]–B12 were measured in liver, kidney, and plasma. We found that the low-B12 diet introduced a B12-deplete state as judged from medians of endogenous B12 compared to rats on a (high-B12 diet): Plasma (565 (1410) pmol/L), liver (28.2 (33.2) pmol/g), and kidneys (123 (1300) pmol/g). One week after oral administration, the labeled B12 was distributed as follows: HO–B12 > CN–B12 (liver) and CN–B12 > HO–B12 (kidneys, plasma). The tissue/plasma ratios showed different equilibriums for labeled CN–B12 and HO–B12 in the B12-deplete and -replete groups. The equilibrium of endogenous B12 resembled [57Co]CN–B12 in replete rats but differed from both [57Co]CN–B12 and [57Co]HO–B12 in deplete rats. The data suggest long-term differences in tissue utilization of the two B12 forms and warrant further studies concerning the possible benefits of consuming HO–B12 instead of CN–B12 in oral B12 replacement.

Highlights

Vitamin B12 (B12, cobalamin) is an essential nutrient commonly obtained as hydroxo–B12(HO–B12), 50 -deoxyadenosyl–B12 (Ado–B12), and methyl–B12 (CH3 –B12), naturally found in foods of animal origin, or alternatively as the synthetic form, cyano–B12 (CN–B12), used in fortified foods and vitamin pills [1]
We present data on the tissue distribution of radiolabeled [57 Co]CN–B12 (CN)–B12 and [57 Co]HO–B12 (HO)–B12 one week after oral administration in B12-deplete and B12-replete rats
The tissue distributions of labeled CN–B12 and HO–B12 one week after oral administration show great resemblance to the tissue distribution seen after 24 h, suggesting that the short-time pattern serves as a good predictor of the “true” long-time steady-state distribution

Summary

Introduction

Vitamin B12 (B12, cobalamin) is an essential nutrient commonly obtained as hydroxo–B12(HO–B12), 50 -deoxyadenosyl–B12 (Ado–B12), and methyl–B12 (CH3 –B12), naturally found in foods of animal origin, or alternatively as the synthetic form, cyano–B12 (CN–B12), used in fortified foods and vitamin pills [1]. B12 in plasma and tissues confirmed B12 depletion, which was mostly pronounced in the kidneys, a known storage organ of B12 in the rat [11,13,14], and to a much lesser extent in the liver These findings are in agreement with previous rat studies [8,11,13] and confirm the conjecture that kidneys accumulate pools of free B12 during sufficient B12 supply [11], but recirculate the vitamin for its utilization by the rest of the body under B12 deprivation [11,13]. Further studies are needed to clarify whether the supply of HO–B12 provides more tissue coenzymes if compared with CN–B12, and whether these observations are of any relevance in a clinical setting In this context, it would be of interest to include the two coenzyme forms, CH3 –B12 and Ado–B12, since both of them are gaining popularity as alternatives to CN–B12 for oral supplementation in humans [18]

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