{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:32:30Z","timestamp":1767598350455,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC-ADG-2012-322752"],"award-info":[{"award-number":["ERC-ADG-2012-322752"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Metformin (MET) is currently being used in several trials for cancer prevention or treatment in non-diabetics. However, long-term MET use in diabetics is associated with lower serum levels of total vitamin B12. In a pilot randomized controlled trial of the Mediterranean diet (MedDiet) and MET, whose participants were characterized by different components of metabolic syndrome, we tested the effect of MET on serum levels of B12, holo transcobalamin II (holo-TC-II), and methylmalonic acid (MMA). The study was conducted on 165 women receiving MET or placebo for three years. Results of the study indicate a significant overall reduction in both serum total B12 and holo-TC-II levels according with MET-treatment. In particular, in the MET group 26 of 81 patients and 10 of the 84 placebo-treated subjects had B12 below the normal threshold (&lt;221 pmol\/L) at the end of the study. Considering jointly all B12, Holo-TC-II, and MMA, 13 of the 165 subjects (10 MET and 3 placebo-treated) had at least two deficits in the biochemical parameters at the end of the study, without reporting clinical signs. Although our results do not affect whether women remain in the trial, B12 monitoring for MET-treated individuals should be implemented.<\/jats:p>","DOI":"10.3390\/nu11051020","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Monitoring Vitamin B12 in Women Treated with Metformin for Primary Prevention of Breast Cancer and Age-Related Chronic Diseases"],"prefix":"10.3390","volume":"11","author":[{"given":"Antonio","family":"Mastroianni","sequence":"first","affiliation":[{"name":"Laboratory Medicine-Department of Pathology and Laboratory Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara Maura","family":"Ciniselli","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Unit-Department of Applied Research and Technological Development, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Panella","sequence":"additional","affiliation":[{"name":"Laboratory Medicine-Department of Pathology and Laboratory Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Macciotta","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Unit-Department of Applied Research and Technological Development, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adalberto","family":"Cavalleri","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Venturelli","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Taverna","sequence":"additional","affiliation":[{"name":"Immunohematology and Transfusion Medicine Service-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arabella","family":"Mazzocchi","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Bruno","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Muti","sequence":"additional","affiliation":[{"name":"Chair Cancer Experimental Therapeutics, Department of Oncology Faculty of Health Science, McMaster University, Hamilton, ON L8V 1C3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Berrino","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Verderio","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Unit-Department of Applied Research and Technological Development, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Morelli","sequence":"additional","affiliation":[{"name":"Laboratory Medicine-Department of Pathology and Laboratory Medicine, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6278-3491","authenticated-orcid":false,"given":"Patrizia","family":"Pasanisi","sequence":"additional","affiliation":[{"name":"Epidemiology and Prevention Unit-Department of Research, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.diabet.2016.03.008","article-title":"Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"42","author":"Chapman","year":"2016","journal-title":"Diabetes Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arr.2017.08.003","article-title":"Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis","volume":"40","author":"Campbell","year":"2017","journal-title":"Ageing Res. 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