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

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.

Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter

“…All in all, such mechanisms may shunt the excess of B12 out of its cells for mobilization to other tissues where it is most needed. In case of B12, the liver and kidneys are typical organs that dramatically change their intracellular levels depending on extracellular supply of B12 and the requirement of the cells [ 9 ]. It should be, however noted, that different forms of B12 (e.g., cyano- vs. hydroxo-B12) can give different ratios of intracellular/extracellular vitamin if administered at equal quantities [ 9 ].…”

“…In case of B12, the liver and kidneys are typical organs that dramatically change their intracellular levels depending on extracellular supply of B12 and the requirement of the cells [ 9 ]. It should be, however noted, that different forms of B12 (e.g., cyano- vs. hydroxo-B12) can give different ratios of intracellular/extracellular vitamin if administered at equal quantities [ 9 ]. Possible explanation may be that the different conversion rates of the inactive form of B12 to the active form, where the unprocessed inert B12 forms are expelled [ 9 ].…”

“…It should be, however noted, that different forms of B12 (e.g., cyano- vs. hydroxo-B12) can give different ratios of intracellular/extracellular vitamin if administered at equal quantities [ 9 ]. Possible explanation may be that the different conversion rates of the inactive form of B12 to the active form, where the unprocessed inert B12 forms are expelled [ 9 ].…”

“…Studies have also shown that CD320 knockout mice have B12 deficiency and have behavioural abnormalities, macrocytic anaemia, infertility and hypomethylation of DNA in the brain [ 8 ]. However, current knowledge on the absorption and tissue distribution of B12 has only been reported in few animal studies [ 9 , 10 , 11 , 12 , 13 , 14 ]. A study in Wistar rats showed that kidneys contained more B12 compared to other tissues such as lungs, spleen, brain, heart and liver [ 15 ].…”

Kinetics of Cellular Cobalamin Uptake and Conversion: Comparison of Aquo/Hydroxocobalamin to Cyanocobalamin

“…Such an approximation (being not literally true) is sufficiently fair, because no leakage of HO/Me/AdoCbls to the medium was detected in the CNCbl setup (Section 3.4). In addition, previous human and rat studies revealed that the ratios of (endogenous tissue Cbl)/(plasma Cbl) ranged from approximately 10 to 100 ( [1,40] and refs. thereof).…”