Tissue distribution of oral vitamin B12 is influenced by B12 status and B12 form: an experimental study in rats

Abstract

PurposeHydroxocobalamin (HOCbl) is the dominating Cbl form in food, whereas cyanocobalamin (CNCbl) is common in vitamin pills and oral supplements. This study compares single-dose absorption and distribution of oral HO[57Co]Cbl and CN[57Co]Cbl in Cbl-deficient and normal rats.MethodsMale Wistar rats (7 weeks) were fed a 14-day diet with (n = 15) or without (n = 15) Cbl. We compared the uptakes of HO[57Co]Cbl (free or bound to bovine transcobalamin) and free CN[57Co]Cbl administered by gastric gavage (n = 5 in each diet group). Rats were sacrificed after 24 h. Blood, liver, kidney, brain, heart, spleen, intestines, skeletal muscle, 24-h urine and faeces were collected, and the content of [57Co]Cbl was measured. Endogenous Cbl in tissues and plasma was analysed by routine methods.ResultsMean endogenous plasma-Cbl was sevenfold lower in deficient vs. normal rats (190 vs. 1330 pmol/L, p < 0.0001). Cbl depletion increased endogenous Cbl ratios (tissue/plasma = k in/k out) in all organs except for the kidney, where the ratio decreased considerably. Twenty-four-hour accumulation of labelled Cbl showed that HOCbl > CNCbl (liver) and CNCbl > HOCbl (brain, muscle and plasma).ConclusionsThe Cbl status of rats and the administered Cbl form influence 24-h Cbl accumulation in tissues and plasma.Electronic supplementary materialThe online version of this article (doi:10.1007/s00394-017-1424-0) contains supplementary material, which is available to authorized users.

Effect of 8-week oral supplementation with 3-µg cyano-B12 or hydroxo-B12 in a vitamin B12-deficient population

“…The rational is that this form of the vitamin is both chemically stable and cheap. In agreement with the previous studies [11][12][13][14], we find that CN-B12 induces a higher increase in the circulating total Cbl in comparison to HO-B12. Interestingly, administration of HO-B12 is as efficient-if not slightly better-in improving other markers of an impaired B12 status, notably MMA.…”

“…Interestingly, administration of HO-B12 is as efficient-if not slightly better-in improving other markers of an impaired B12 status, notably MMA. This result is in accord with our previous studies in rats [12,13]. Thus, based on our present data, we conclude that the increase in serum Cbl upon administration of CN-B12 does not mirror a superior effect of this vitamin form, but rather shows that CN-B12 has a tendency to fall behind HO-B12 in the rates of tissue uptake.…”

“…Several studies have documented that both forms are retained alike after oral uptake [9][10][11], but the tissue distributions of the two absorbed vitamins differ. For example, in rats, considerably more B12 is internalized in the liver after ingestion of HO-B12, when compared to an equal dose of CN-B12 [12,13]. Conversely, the circulating level of B12 is much higher upon administration of CN-B12 than after intake of similar dose of HO-B12 [11][12][13][14].…”

“…For example, in rats, considerably more B12 is internalized in the liver after ingestion of HO-B12, when compared to an equal dose of CN-B12 [12,13]. Conversely, the circulating level of B12 is much higher upon administration of CN-B12 than after intake of similar dose of HO-B12 [11][12][13][14].…”

The tissue profile of metabolically active coenzyme forms of vitamin B12 differs in vitamin B12-depleted rats treated with hydroxo-B12 or cyano-B12

“…Here, ADO-B 12 acts as a cofactor for methylmalonyl-CoA mutase in the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondria. CH 3 -B 12 acts as a cofactor for methionine synthase in the folatedependent methylation of homocysteine to methionine in the cytoplasm (1,2) .Both human and animal studies have demonstrated that synthetic and natural forms of B 12 are absorbed equally (7)(8)(9)(10)(11) . However, our recent data show that HO-B 12 accumulates in the liver to a higher degree than CN-B 12 , but that the patterns are opposite in the brain and plasma.…”