Vitamin B12 (B12) is present in foods of animal origin, and vegans are encouraged to take supplements with synthetic B12 in order to ensure a sufficient uptake. Recent rat studies suggest that natural (hydroxo-B12, HO-B12) and synthetic (cyano-B12, CN-B12) B12 behave differently in the body. Here, we test if a daily vitamin pill matches dietary B12 in ability to restore a low B12 status in rats. B12-depleted male Wistar rats (n = 60) were divided into five groups (n = 12 in each) and subjected to two weeks intervention with various schemes of B12 supplementation. Two “dietary” groups received a low-B12 chow that was fortified with either HO-B12 or CN-B12 providing a continuous supply. Two “pill” groups received a single daily dose of CN-B12, where the vitamin content either matched or exceeded by factor four the provisions for the “dietary” groups. A control group received the low-B12 chow without B12 fortification. B12 was measured in plasma and tissues. Dietary B12 provides 35% more B12 to the tissues than an equivalent single daily dose (p < 0.0001). Natural B12 delivers 25% more B12 to the liver than synthetic B12 (p = 0.0007). A fourfold increase in B12, supplemented as a single daily dose, does not provide any extra B12 to the tissues (p = 0.45). We conclude that dietary B12 is better at rescuing a low B12 status than a daily vitamin pill.

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.

Vitamin B12 deficiency during pregnancy has been associated with poor fetal outcome. Here we investigate the influence of a one-carbon (1C) imbalanced diet (low B12, high folate, high methionine) on maternal B12 status, fetal outcome, B12 distribution, and on the 24-h distribution of synthetic cyano-B12 (CN-B12) and natural hydroxo-B12 (HO-B12). Female Wistar rats were mated while on a 1C balanced (n = 12) or imbalanced diet starting two weeks (n = 10) or four weeks (n = 9) prior to pregnancy and continuing throughout pregnancy. At gestation day 18 (out of 21), all rats received an oral dose of labeled CN-B12 or HO-B12. After 24 h, the rats were sacrificed. Fetuses were inspected, and maternal tissues and fetuses were measured for endogenous and labeled B12. Pregnancy caused a redistribution of B12 from the kidneys to the liver and fetal compartment (uterus, placenta, fetuses). The 1C imbalanced diet reduced maternal kidney B12 and gave rise to lower-weight fetuses with visual malformations. In contrast, fetal B12 did not reflect fetal outcome. This suggests that maternal B12 is more important for fetal outcome than fetal B12. The 24-h distribution of labeled B12 in the rats on the 1C imbalanced diet showed a higher fetal accumulation of CN-B12 than HO-B12, while the opposite was seen in the maternal tissues.