{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:41:16Z","timestamp":1775932876646,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,6]],"date-time":"2019-10-06T00:00:00Z","timestamp":1570320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology , Ministry of Science and Technology","award":["BT\/IN\/Denmark\/06\/SSN\/2015"],"award-info":[{"award-number":["BT\/IN\/Denmark\/06\/SSN\/2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Lactovegetarians (n = 35) with low vitamin B12 (B12) status were intervened for eight weeks capsules containing cyano-B12 (CN-B12), (2 \u00d7 2.8 \u00b5g\/day), or equivalent doses of endogenous B12 (mainly hydroxo-B12 (HO-B12)) in whey powder. Blood samples were examined at baseline, every second week during the intervention, and two weeks post-intervention. The groups did not differ at baseline in [global median (min\/max)] plasma B12 [112(61\/185)] pmol\/L, holotranscobalamin [20(4\/99)] pmol\/L, folate [13(11\/16)], the metabolites total homocysteine [18(9\/52)] \u00b5mol\/L and methylmalonic acid [0.90(0.28\/2.5)] \u00b5mol\/L, and the combined indicator of B12 status (4cB12) [\u22121.7(\u22123.0\/\u22120.33)]. Both supplements caused significant effects, though none of the biomarkers returned to normal values. Total plasma B12 showed a higher increase in the capsule group compared to the whey powder group (p = 0.02). However, the increase of plasma holotranscobalamin (p = 0.06) and the lowering of the metabolites (p &gt; 0.07) were alike in both groups. Thereby, the high total plasma B12 in the capsule group was not mirrored in enhanced B12 metabolism, possibly because the B12 surplus was mainly accumulated on an \u201cinert\u201d carrier haptocorrin, considered to be of marginal importance for tissue delivery of B12. In conclusion, we demonstrate that administration of whey powder (HO-B12) or capsules (CN-B12) equivalent to 5.6 \u00b5g of B12 daily for eight weeks similarly improves B12 status but does not normalize it. We document that the results for plasma B12 should be interpreted with caution following administration of CN-B12, since the change is disproportionately high compared to the responses of complementary biomarkers.<\/jats:p>","DOI":"10.3390\/nu11102382","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T03:34:01Z","timestamp":1570419241000},"page":"2382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cyano-B12 or Whey Powder with Endogenous Hydroxo-B12 for Supplementation in B12 Deficient Lactovegetarians"],"prefix":"10.3390","volume":"11","author":[{"given":"Sadanand","family":"Naik","sequence":"first","affiliation":[{"name":"Department of Pathology, Deenanath Mangeshkar Hospital and Research Center, Pune 411004, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namita","family":"Mahalle","sequence":"additional","affiliation":[{"name":"Department of Pathology, Deenanath Mangeshkar Hospital and Research Center, Pune 411004, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Greibe","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Institute of Clinical Medicine, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie S.","family":"Ostenfeld","sequence":"additional","affiliation":[{"name":"Arla Foods Ingredients Group P\/S, DK-8260 Viby, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-2624","authenticated-orcid":false,"given":"Christian W.","family":"Heegaard","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9406-9081","authenticated-orcid":false,"given":"Ebba","family":"Nexo","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Institute of Clinical Medicine, Aarhus University Hospital, DK-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, DK-8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,6]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1995S","DOI":"10.1093\/jn\/nxy201","article-title":"Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review","volume":"148","author":"Allen","year":"2018","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"693S","DOI":"10.3945\/ajcn.2008.26947A","article-title":"How common is vitamin B-12 deficiency","volume":"89","author":"Allen","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1079\/PHN2002430","article-title":"EPIC-Oxford: Lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK","volume":"6","author":"Davey","year":"2003","journal-title":"Public Health Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/ajcn\/53.2.524","article-title":"Vitamin B12 status in a macrobiotic community","volume":"53","author":"Miller","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ralapanawa, D.M., Jayawickreme, K.P., Ekanayake, E.M., and Jayalath, W.A. (2015). B12 deficiency with neurological manifestations in the absence of anaemia. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1437-9"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/1475-2891-12-136","article-title":"Daily milk intake improves vitamin B-12 status in young vegetarian Indians: An intervention trial","volume":"12","author":"Naik","year":"2013","journal-title":"Nutr. J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mahalle, N., Bhide, V., Greibe, E., Heegaard, C.W., Nexo, E., Fedosov, S.N., and Naik, S. (2019). Comparative Bioavailability of Synthetic B12 and Dietary Vitamin B12 Present in Cow and Buffalo Milk: A Prospective Study in Lactovegetarian Indians. Nutrients, 11.","DOI":"10.3390\/nu11020304"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3945\/ajcn.2008.26598","article-title":"Dietary sources of vitamin B12 and their association with plasma vitamin B12 concentrations in the general population: The Hordaland Homocysteine Study","volume":"89","author":"Vogiatzoglou","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7781","DOI":"10.3390\/nu7095364","article-title":"Dietary sources of vitamin B-12 and their association with vitamin B-12 status markers in healthy older adults in the B-PROOF study","volume":"7","author":"Zwaluw","year":"2015","journal-title":"Nutrients"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1017\/S0007114511002364","article-title":"Bioavailability of vitamin B12 in cow\u2019s milk","volume":"107","author":"Matte","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.idairyj.2017.08.005","article-title":"Binding aquacobalamin to bovine casein and its peptides via coordination to histidine residues","volume":"76","author":"Fedosov","year":"2017","journal-title":"Int. Dairy J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.3168\/jds.2018-15016","article-title":"Vitamin B12 and its binding proteins in milk from cow and buffalo in relation to bioavailability of B12","volume":"102","author":"Fedosov","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00394-017-1424-0","article-title":"Tissue distribution of oral vitamin B12 influenced by vitamin B12 status and B12 form. An experimental study in rats","volume":"57","author":"Kornerup","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"1600915","DOI":"10.1002\/mnfr.201600915","article-title":"Whey protein isolate improves vitamin B(12) and folate status in elderly Australians with subclinical deficiency of vitamin B(12)","volume":"61","author":"Dhillon","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1007\/s00394-017-1553-5","article-title":"Increase in circulating holotranscobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin satus","volume":"57","author":"Greibe","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_19","unstructured":"WHO (2011). Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. Vitamin and Mineral Nutrition Information System, World Health Organization."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1373\/clinchem.2008.114132","article-title":"A new principle for measurement of cobalamin and corrinoids, used for studies of cobalamin analogs on serum haptocorrin","volume":"55","author":"Hardlei","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1515\/cclm-2014-0818","article-title":"Combined indicator of vitamin B12 status: Modification for missing biomarkers and folate status and recommendations for revised cut\u2013points","volume":"53","author":"Fedosov","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/0003-2697(83)90552-3","article-title":"Determination of cobalamins in biological material: I. Improvement in the unequal recovery of cobalamins by preincubation with cadmium acetate","volume":"129","author":"Gimsing","year":"1983","journal-title":"Anal. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/0003-2697(83)90553-5","article-title":"Determination of cobalamins in biological material: II. The cobalamins in human plasma and erythrocytes after desalting on nonpolar adsorbent material, and separation by one-dimensional thin-layer chromatography","volume":"129","author":"Gimsing","year":"1983","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00394-017-1590-0","article-title":"Effect of 8-week oral supplementation with 3-\u00b5g cyano-B12 or hydroxo-B12 in a vitamin B12-deficient population","volume":"58","author":"Greibe","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1515\/CCLM.2007.343","article-title":"Haptocorrin in humans","volume":"45","author":"Morkbak","year":"2007","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fedosov, S.N. (2012). Physiological and molecular aspects of cobalamin transport. Water Soluble Vitamins, Springer.","DOI":"10.1007\/978-94-007-2199-9_18"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mutti, E., Ruetz, M., Birn, H., Kr\u00e4utler, B., and Nexo, E. (2013). 4-ethylphenyl-cobalamin impairs tissue uptake of vitamin B12 and causes vitamin B12 deficiency in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075312"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/10\/2382\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:27:54Z","timestamp":1760189274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/10\/2382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,6]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["nu11102382"],"URL":"https:\/\/doi.org\/10.3390\/nu11102382","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,6]]}}}