{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:51:39Z","timestamp":1782906699691,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2013,12,12]],"date-time":"2013-12-12T00:00:00Z","timestamp":1386806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin B12 is a cofactor of methionine synthase in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAMe), which is involved in different epigenomic regulatory mechanisms and especially in brain development. A Vitamin B12 deficiency expresses itself by a wide variety of neurological manifestations such as paraesthesias, skin numbness, coordination disorders and reduced nerve conduction velocity. In elderly people, a latent Vitamin B12 deficiency can be associated with a progressive brain atrophy. Moderately elevated concentrations of homocysteine (&gt;10 \u00b5mol\/L) have been associated with an increased risk of dementia, notably Alzheimer\u2019s disease, in many cross-sectional and prospective studies. Raised plasma concentrations of homocysteine is also associated with both regional and whole brain atrophy, not only in Alzheimer\u2019s disease but also in healthy elderly people. Clinician awareness should be raised to accurately diagnose and treat early Vitamin B12 deficiency to prevent irreversible structural brain damage.<\/jats:p>","DOI":"10.3390\/nu5125031","type":"journal-article","created":{"date-parts":[[2013,12,12]],"date-time":"2013-12-12T13:35:11Z","timestamp":1386855311000},"page":"5031-5045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Neuroenhancement with Vitamin B12\u2014Underestimated Neurological Significance"],"prefix":"10.3390","volume":"5","author":[{"given":"Uwe","family":"Gr\u00f6ber","sequence":"first","affiliation":[{"name":"Academy of Micronutrient Medicine, Zweigertstr. 55, Essen 45130, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Kisters","sequence":"additional","affiliation":[{"name":"Academy of Micronutrient Medicine, Zweigertstr. 55, Essen 45130, Germany"},{"name":"St. Anna Hospital, Hospitalstr. 19, Herne 44649, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Academy of Micronutrient Medicine, Zweigertstr. 55, Essen 45130, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1515\/DMDI.2009.24.2-4.331","article-title":"Micronutrients: Metabolic Tuning\u2014Prevention\u2014Therapy","volume":"24","year":"2009","journal-title":"Drug Metab. Drug Interact."},{"key":"ref_2","first-page":"26","article-title":"Interactions between drugs and micronutrients","volume":"29","year":"2006","journal-title":"Med. Monatsschr. Pharm."},{"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","unstructured":"(1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, National Academy Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/00005792-199107000-00001","article-title":"Neurologic aspects of cobalamin deficiency","volume":"70","author":"Healton","year":"1991","journal-title":"Medicine (Baltimore)"},{"key":"ref_6","unstructured":"Neurologic Manifestations Related to Deficiency of Vitamin B12. Available online:http:\/\/yassermetwally.com\/blog\/?p=194."},{"key":"ref_7","first-page":"1","article-title":"Neurological manifestations of Vitamin B12 deficiency","volume":"2","author":"Sethi","year":"2005","journal-title":"Internet J. Nutr. Wellness"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1007\/s00415-003-1161-6","article-title":"Clinically and MRI documented funicular myelosis in a patient with metabolical Vitamin B12 deficiency but normal Vitamin B12 serum level","volume":"250","author":"Lorenzl","year":"2003","journal-title":"J. Neurol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/qjmed\/hcn138","article-title":"An update on cobalamin deficiency in adults","volume":"102","author":"Andres","year":"2009","journal-title":"QJM"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1515\/CCLM.2003.227","article-title":"Functional Vitamin B12 deficiency and determination of holotranscobalamin in populations at risk","volume":"41","author":"Herrmann","year":"2003","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"359S","DOI":"10.3945\/ajcn.111.013458","article-title":"Holotranscobalamin, a marker of vitamin B-12 status: Analytical aspects and clinical utility","volume":"94","author":"Nexo","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00415-010-5764-4","article-title":"Utility of measuring Vitamin B12 and its active fraction, holotranscobalamin, in neurological Vitamin B12 deficiency syndromes","volume":"258","author":"Schrempf","year":"2011","journal-title":"J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/ajh.2830340205","article-title":"Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations","volume":"34","author":"Lindenbaum","year":"1990","journal-title":"Am. J. Hematol."},{"key":"ref_15","first-page":"823","article-title":"Methylmalons\u00e4ure zur bestimmung des Vitamin B12-mangels","volume":"8","author":"Troxler","year":"2008","journal-title":"Schweiz. Med. Forum"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0002-9343(94)90149-X","article-title":"Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies","volume":"96","author":"Savage","year":"1994","journal-title":"Am. J. Med."},{"key":"ref_17","unstructured":"Nationale Verzehrsstudie II (National Nutrtion Survey II), 2008. Available online:http:\/\/www.nationale-verzehrsstudie.de."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/1389200052997384","article-title":"The usefulness of holotranscobalamin in predicting Vitamin B12 status in different clinical settings","volume":"6","author":"Herrmann","year":"2005","journal-title":"Curr. Drug Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1056\/NEJMoa072200","article-title":"Gene identification for the cblD defect of Vitamin B12 metabolism","volume":"358","author":"Coelhoo","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1373\/clinchem.2003.021717","article-title":"Vitamin B12 status in the elderly as judged by available biochemical markers","volume":"50","author":"Obeid","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1001\/archinte.160.9.1349","article-title":"Helicobacter pylori\u2014Is it a novel causative agent in Vitamin B12 deficiency?","volume":"160","author":"Kaptan","year":"2000","journal-title":"Arch. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1046\/j.1532-5415.2002.50020.x","article-title":"A randomized, double-blind, placebo-controlled study of oralVitamin B12 supplementation in older patients with subnormal or borderline serum Vitamin B12 concentrations","volume":"50","author":"Seal","year":"2002","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"De Jager, J., Kooy, A., and Lehert, P. (2010). Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial. BMJ, 340.","DOI":"10.1136\/bmj.c2181"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jdiacomp.2005.10.005","article-title":"Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and Vitamin B12 in patients with type 2 diabetes mellitus","volume":"21","author":"Sahin","year":"2007","journal-title":"J. Diabetes Complicat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1001\/archinte.166.18.1975","article-title":"Risk factors of vitamin B(12) deficiency in patients receiving metformin","volume":"166","author":"Ting","year":"2006","journal-title":"Arch. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.2337\/dc13-0229","article-title":"Increased risk of cognitive impairment in patients with diabetes is associated with metformin","volume":"36","author":"Moore","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_27","first-page":"462","article-title":"Cobalamin deficiency due to non-immune atrophic gastritis in elderly patients. A report of 25 cases","volume":"9","author":"Noel","year":"2005","journal-title":"J. Nutr. Health Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/ajcn\/78.1.131","article-title":"Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians","volume":"78","author":"Herrmann","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-2007-981249","article-title":"M\u00fctterlicher Vitamin-B12-Mangel: Ursache neurologischer Symptomatik im S\u00e4uglingsalter","volume":"211","author":"Korenke","year":"2007","journal-title":"Z. Geburtshilfe Neonatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.blre.2006.05.001","article-title":"Disorders of cobalamin (Vitamin B12) metabolism: Emerging concepts in pathophysiology, diagnosis and treatment","volume":"21","author":"Solomon","year":"2007","journal-title":"Blood Rev."},{"key":"ref_31","unstructured":"Pietrzik, K., Golly, I., and Loew, D. (2008). Handbuch der Vitamine. F\u00fcr Prophylaxe, Beratung und Therapie, Urban & Fischer. [1st ed.]. (in German)."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1001\/archinte.165.10.1167","article-title":"Oral cyanocobalamin supplementation in older people with Vitamin B12 deficiency: A dose-finding trial","volume":"165","author":"Eussen","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_33","first-page":"CD004655","article-title":"Oral Vitamin B12 versus intramuscular Vitamin B12 for Vitamin B12 deficiency","volume":"3","author":"Butler","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1212\/01.wnl.0000325581.26991.f2","article-title":"Vitamin B12 status and rate of brain volume loss in community-dwelling elderly","volume":"71","author":"Vogiatzoglou","year":"2008","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1093\/ajcn\/63.3.306","article-title":"Relations of Vitamin B-12, Vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study","volume":"63","author":"Riggs","year":"1996","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s12603-012-0051-y","article-title":"Conversion from mild cognitive impairment to dementia: Influence of folic acid and Vitamin B12 use in the VITA cohort","volume":"16","author":"Blasko","year":"2012","journal-title":"J. Nutr. Health Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/PSY.0b013e3182761b6c","article-title":"Cognitive function in an elderly population: Interaction between Vitamin B12 status, depression, and apolipoprotein E s4: The Hordaland Homocysteine Study","volume":"75","author":"Vogiatzoglou","year":"2013","journal-title":"Psychosom. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1749-6632.2000.tb06392.x","article-title":"Plasma total homocysteine and cognitive performance in a volunteer elderly population","volume":"903","author":"Budge","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1056\/NEJMoa011613","article-title":"Plasma homocysteine as a risk factor for dementia and Alzheimer\u2019s disease","volume":"346","author":"Seshadri","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1093\/brain\/awg006","article-title":"Homocysteine and brain atrophy on MRI of non-demented elderly","volume":"126","year":"2003","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/ageing\/31.6.440","article-title":"Minimal hippocampal width relates to plasma homocysteine in community-dwelling older people","volume":"31","author":"Williams","year":"2002","journal-title":"Age Ageing"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/00019442-200411000-00009","article-title":"Homocysteine and B vitamins relate to brain volume and white-matter changes in geriatric patients with psychiatric disorders","volume":"12","author":"Scott","year":"2004","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12244","DOI":"10.1371\/journal.pone.0012244","article-title":"Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial","volume":"5","author":"Smith","year":"2010","journal-title":"PLoS One"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9523","DOI":"10.1073\/pnas.1301816110","article-title":"Preventing Alzheimer\u2019s disease-related gray matter atrophy by B-vitamin treatment","volume":"110","author":"Douaud","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/5\/12\/5031\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:51:19Z","timestamp":1760219479000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/5\/12\/5031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,12]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2013,12]]}},"alternative-id":["nu5125031"],"URL":"https:\/\/doi.org\/10.3390\/nu5125031","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,12]]}}}