{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:53:55Z","timestamp":1761562435029,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T00:00:00Z","timestamp":1540512000000},"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>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.<\/jats:p>","DOI":"10.3390\/nu10111579","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T10:51:01Z","timestamp":1540551061000},"page":"1579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nutritional 1C Imbalance, B12 Tissue Accumulation, and Pregnancy Outcomes: An Experimental Study in Rats"],"prefix":"10.3390","volume":"10","author":[{"given":"Ole","family":"Nymark","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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0417-1195","authenticated-orcid":false,"given":"Eva","family":"Greibe","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":[[2018,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1753-4887.2008.00031.x","article-title":"Effect of vitamin B12 deficiency on neurodevelopment in infants: Current knowledge and possible mechanisms","volume":"66","author":"Dror","year":"2008","journal-title":"Nutr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S126","DOI":"10.1177\/15648265080292S117","article-title":"Effects of vitamin B12 and folate deficiency on brain development in children","volume":"29","author":"Black","year":"2008","journal-title":"Food Nutr. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.soard.2017.03.017","article-title":"Risk of low birth weight and micronutrient deficiencies in neonates from mothers after gastric bypass: A case control study","volume":"13","author":"Gascoin","year":"2017","journal-title":"Surg. Obes. Relat. Dis Off. J. Am. Soc. Bariatr. Surg."},{"key":"ref_4","first-page":"337","article-title":"Association between nutritional status with spontaneous abortion","volume":"10","author":"Ahmadi","year":"2017","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_5","first-page":"703","article-title":"Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects","volume":"86","author":"Kirke","year":"1993","journal-title":"Q. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ajmg.c.30288","article-title":"Inborn errors of cobalamin absorption and metabolism","volume":"157","author":"Watkins","year":"2011","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10545-016-9991-4","article-title":"Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency","volume":"40","author":"Huemer","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_8","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_9","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_10","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_11","first-page":"431","article-title":"Placental passage and fetal accumulation of labelled vitamin B12 in the mouse","volume":"167","author":"Ullberg","year":"1967","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1172\/JCI106569","article-title":"Placental transport of vitamin B12 in the pregnant rat","volume":"50","author":"Graber","year":"1971","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0003-9861(51)80020-1","article-title":"The distribution of radioactivity in the organs of the fetus or of young rats born by mothers injected with vitamin B12 containing co60","volume":"34","author":"Chow","year":"1951","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","unstructured":"Greibe, E., Nymark, O., Fedosov, S.N., Heegaard, C.W., and Nexo, E. (2018). Dietary intake of vitamin B12 is better for restoring a low B12 status than a daily high-dose vitamin pill: An experimental study in rats. Nutrients, 10.","DOI":"10.3390\/nu10081096"},{"key":"ref_16","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"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.mpmed.2017.01.007","article-title":"Iron, vitamin B12 and folate","volume":"45","author":"Moll","year":"2017","journal-title":"Medicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1071\/RD13306","article-title":"Supplementation with omega-3 fatty acids during gestation and lactation to a vitamin B12-deficient or -supplemented diet improves pregnancy outcome and metabolic variables in wistar rats","volume":"27","author":"Khaire","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_19","first-page":"532","article-title":"Observations on transfer of vitamin B12 from mother to fetus and newborn","volume":"96","author":"Luhby","year":"1958","journal-title":"Am. J. Dis. Child."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.3945\/ajcn.116.139519","article-title":"Moderate folic acid supplementation and mthfd1-synthetase deficiency in mice, a model for the r653q variant, result in embryonic defects and abnormal placental development","volume":"104","author":"Christensen","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Henderson, A.M., Tai, D.C., Aleliunas, R.E., Aljaadi, A.M., Glier, M.B., Xu, E.E., Miller, J.W., Verchere, C.B., Green, T.J., and Devlin, A.M. (2018). Maternal folic acid supplementation with vitamin B12 deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol.","DOI":"10.1096\/fj.201701503RR"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mam.2016.11.004","article-title":"Interaction between excess folate and low vitamin B12 status","volume":"53","author":"Paul","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev.nu.04.070184.001105","article-title":"Adverse effects of excessive consumption of amino acids","volume":"4","author":"Benevenga","year":"1984","journal-title":"Annu. Rev. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1722s","DOI":"10.1093\/jn\/136.6.1722S","article-title":"Toxicity of methionine in humans","volume":"136","author":"Garlick","year":"2006","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1182\/blood.V63.2.335.335","article-title":"The availability of therapeutic hydroxocobalamin to cells","volume":"63","author":"Hall","year":"1984","journal-title":"Blood"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/11\/1579\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:26:22Z","timestamp":1760196382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/11\/1579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,26]]},"references-count":25,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["nu10111579"],"URL":"https:\/\/doi.org\/10.3390\/nu10111579","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2018,10,26]]}}}