{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:40:54Z","timestamp":1770723654048,"version":"3.49.0"},"reference-count":20,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T00:00:00Z","timestamp":1539302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","award":["12-132437"],"award-info":[{"award-number":["12-132437"]}],"id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Foods contain natural vitamin B12 forms, such as hydroxo\u2013B12 (HO\u2013B12), whereas vitamin pills contain the synthetic cyano\u2013B12 (CN\u2013B12). Recent studies in rats showed different tissue distributions of CN\u2013B12 and HO\u2013B12 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\u2013B12 or HO\u2013B12 (n = 6 and n = 8, respectively, in each diet group). The rats were sacrificed on day 17 and endogenous B12 and [57Co]\u2013B12 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\u2013B12 &gt; CN\u2013B12 (liver) and CN\u2013B12 &gt; HO\u2013B12 (kidneys, plasma). The tissue\/plasma ratios showed different equilibriums for labeled CN\u2013B12 and HO\u2013B12 in the B12-deplete and -replete groups. The equilibrium of endogenous B12 resembled [57Co]CN\u2013B12 in replete rats but differed from both [57Co]CN\u2013B12 and [57Co]HO\u2013B12 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\u2013B12 instead of CN\u2013B12 in oral B12 replacement.<\/jats:p>","DOI":"10.3390\/nu10101487","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T10:54:03Z","timestamp":1539341643000},"page":"1487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differences in Tissue Distribution of Cyano\u2013B12 and Hydroxo\u2013B12 One Week after Oral Intake: An Experimental Study in Male Wistar Rats"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0417-1195","authenticated-orcid":false,"given":"Eva","family":"Greibe","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Nymark","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7016-2959","authenticated-orcid":false,"given":"Sergey N.","family":"Fedosov","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian W.","family":"Heegaard","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebba","family":"Nexo","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1079\/BJN19760063","article-title":"The forms of vitamin B12 in foods","volume":"36","author":"Farquharson","year":"1976","journal-title":"Br. J. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1039\/C5DT04286K","article-title":"Photolytic properties of cobalamins: A theoretical perspective","volume":"45","author":"Kozlowski","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3109\/00365527109180702","article-title":"Absorption of cyanocobalamin, coenzyme B12, methylcobalamin, and hydroxocobalamin at different dose levels","volume":"6","author":"Adams","year":"1971","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3181\/00379727-122-31041","article-title":"Hydroxocobalamin. VI. Comparison of intestinal absorption in man of large doses of hydroxocobalamin and cyanocobalamin","volume":"122","author":"Weisberg","year":"1966","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/j.1749-6632.1964.tb45064.x","article-title":"Metabolism of the vitamin B12 coenzyme in rats and man","volume":"112","author":"Heinrich","year":"1964","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.biochi.2015.11.024","article-title":"Absorption and retention of free and milk protein-bound cyano- and hydroxocobalamins. An experimental study in rats","volume":"126","author":"Kornerup","year":"2016","journal-title":"Biochimie"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00394-017-1424-0","article-title":"Tissue distribution of oral vitamin B12 is influenced by B12 status and B12 form: An experimental study in rats","volume":"57","author":"Kornerup","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_9","first-page":"1006","article-title":"Absorption of vitamin B12 administered in buffalo milk: An experimental study in rats","volume":"2","author":"Greibe","year":"2017","journal-title":"SciTz Nutr. Food Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0304-4165(76)90178-1","article-title":"Tissue distribution of endogenous cobalamins and other corrins in the rat, cat and guinea pig","volume":"421","author":"Quadros","year":"1976","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/ndt\/gfg089","article-title":"Diversity in rat tissue accumulation of vitamin b12 supports a distinct role for the kidney in vitamin B12 homeostasis","volume":"18","author":"Birn","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1017\/S000711451800123X","article-title":"The tissue profile of metabolically active coenzyme forms of vitamin B12 differs in B12-depleted rats treated with hydroxo-B12 and cyano-B12","volume":"120","author":"Greibe","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1042\/cs0670299","article-title":"The regulatory roles of liver and kidney in cobalamin (vitamin B12) metabolism in the rat: The uptake and intracellular binding of cobalamin and the activity of the cobalamin-dependent enzymes in response to varying cobalamin supply","volume":"67","author":"Scott","year":"1984","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0304-4165(72)90317-0","article-title":"The mechanism of vitamin B12 by the kidney of the rat in vivo","volume":"261","author":"Newmark","year":"1972","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/205176b0","article-title":"Conversion of cyano- and hydroxo-cobalamin in vivo into co-enzyme form of vitamin B12 in the rat","volume":"205","author":"Uchino","year":"1965","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Hodgson, N.W., Trivedi, M.S., Abdolmaleky, H.M., Fournier, M., Cuenod, M., Do, K.Q., and Deth, R.C. (2016). Decreased brain levels of vitamin B12 in aging, autism and schizophrenia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146797"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1373\/clinchem.2009.131524","article-title":"Assessment of vitamin B(12) absorption based on the accumulation of orally administered cyanocobalamin on transcobalamin","volume":"56","author":"Hardlei","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ejcn.2014.165","article-title":"Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion","volume":"69","author":"Thakkar","year":"2015","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1042\/cs0390107","article-title":"Estimation of the total body vitamin B12 in the live subject","volume":"39","author":"Adams","year":"1970","journal-title":"Clin. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/00000542-199009000-00022","article-title":"Disruption of folate and vitamin B12 metabolism in aged rats following exposure to nitrous oxide","volume":"73","author":"Koblin","year":"1990","journal-title":"Anesthesiology"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/10\/1487\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:14Z","timestamp":1760196314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/10\/1487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,12]]},"references-count":20,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["nu10101487"],"URL":"https:\/\/doi.org\/10.3390\/nu10101487","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,12]]}}}