{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:13:02Z","timestamp":1792062782640,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the era of evidence-based medicine, the randomized clinical trial corresponds to the top step in the qualitative scale of the evidence available in the literature, while small series of cases or the description of individual cases occupy the last place. However, the latter represent an important part of clinical practice and have significantly influenced the evolution of medicine, contributing significantly to the advancement of scientific knowledge. Vitamin B12 deficiency shares several common symptoms that affect several tissues and organs with health aliments, so its diagnosis could be unobvious for the broad array of its effects and investigation methods used. In this review, we focused our attention on some case reports related to the vitamin B12 deficiency associated to anemia, neurologic disorders, and hyperhomocysteinemia. B12 deficiency reversal is simply achieved by prompt therapy, even though it is not the same for several disorders.<\/jats:p>","DOI":"10.3390\/ijms22189694","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T10:24:25Z","timestamp":1631010265000},"page":"9694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["A Brief Review on Vitamin B12 Deficiency Looking at Some Case Study Reports in Adults"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-1668","authenticated-orcid":false,"given":"Elena","family":"Azzini","sequence":"first","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4021-6829","authenticated-orcid":false,"given":"Anna","family":"Raguzzini","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Polito","sequence":"additional","affiliation":[{"name":"CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0072-9752(08)02130-1","article-title":"Chapter 30 Historical aspects of the major neurological vitamin deficiency disorders: The water-soluble B vitamins","volume":"95","author":"Lanska","year":"2009","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Azzini, E., Ruggeri, S., and Polito, A. (2020). Homocysteine: Its Possible Emerging Role in At-Risk Population Groups. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041421"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1177\/1535370217746612","article-title":"Vitamin B12 sources and microbial interaction","volume":"243","author":"Watanabe","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000346968","article-title":"Systematic Review on Daily Vitamin B12 Losses and Bioavailability for Deriving Recommendations on Vitamin B12 Intake with the Factorial Approach","volume":"62","author":"Doets","year":"2013","journal-title":"Ann. Nutr. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1024\/0300-9831\/a000041","article-title":"Bioavailability of Vitamin B12","volume":"80","author":"Allen","year":"2010","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3945\/ajcn.2008.26598","article-title":"Dietary sources of vitamin B-12 and their association with plasma vitamin B-12 concentrations in the general population: The Hordaland Homocysteine Study","volume":"89","author":"Vogiatzoglou","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","unstructured":"U.S. Department of Agriculture, Agricultural Research Service (2020). What We Eat in America, 2017\u20132018. External Link Disclaimer."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1182\/blood-2008-03-040253","article-title":"How I treat cobalamin (vitamin B12) deficiency","volume":"112","author":"Carmel","year":"2008","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"g5226","DOI":"10.1136\/bmj.g5226","article-title":"Vitamin B12 deficiency","volume":"349","author":"Hunt","year":"2014","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1056\/NEJMcp1113996","article-title":"Vitamin B12Deficiency","volume":"368","author":"Stabler","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.mcna.2016.09.013","article-title":"Megaloblastic Anemias","volume":"101","author":"Green","year":"2017","journal-title":"Med. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sakyi, S.A., Laing, E.F., Mantey, R., Kwarteng, A., Owiredu, E.-W., Dadzie, R.E., Amoani, B., Opoku, S., Afranie, B.O., and Boakye, D. (2021). Profiling immuno-metabolic mediators of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in Ghana. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249325"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/ejcn.2014.46","article-title":"The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: A review of literature","volume":"68","author":"Pawlak","year":"2014","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Berkins, S., Schi\u00f6th, H.B., and Rukh, G. (2021). Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate In-take and Global and Subcortical Brain Volumes. Nutrients, 13.","DOI":"10.3390\/nu13061790"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110625","DOI":"10.1016\/j.mehy.2021.110625","article-title":"Vitamin B12 status is a risk factor for bone fractures among vegans","volume":"153","author":"Pawlak","year":"2021","journal-title":"Med. Hypotheses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1093\/ajcn\/nqaa445","article-title":"Growth, body composition, and cardiovascular and nutritional risk of 5- to 10-y-old children consuming vegetarian, vegan, or omnivore diets","volume":"113","author":"Desmond","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1007\/s00125-021-05510-7","article-title":"Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: A prospective UK cohort study (PRiDE study)","volume":"64","author":"Saravanan","year":"2021","journal-title":"Diabetologia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3389\/fendo.2021.619176","article-title":"Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India","volume":"12","author":"Behere","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s12603-020-1489-y","article-title":"Vitamin B12 and Folate Status in Cognitively Healthy Older Adults and Associations with Cognitive Performance","volume":"25","author":"Nalder","year":"2021","journal-title":"J. Nutr. Heal. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3121\/cmr.4.3.236","article-title":"Megaloblastic anemia and other causes of macrocytosis","volume":"4","author":"Aslinia","year":"2006","journal-title":"Clin. Med. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"l1865","DOI":"10.1136\/bmj.l1865","article-title":"Investigating vitamin B12 deficiency","volume":"365","author":"Sukumar","year":"2019","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3949\/ccjm.87a.19072","article-title":"Severe megaloblastic anemia: Vitamin deficiency and other causes","volume":"87","author":"Socha","year":"2020","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5005\/jcdp-10-2-83","article-title":"A Case Report of Pernicious Anemia and Recurrent Aph-thous Stomatitis","volume":"10","author":"Garcia","year":"2009","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_25","first-page":"533","article-title":"Oral manifestations of vitamin B12 deficiency: A case report","volume":"75","author":"Pontes","year":"2009","journal-title":"J. Can. Dent. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"485","DOI":"10.4103\/2249-4863.192343","article-title":"Reversible ecchymosis and hyperpigmented. lesions: A rare presentation of dietary Vitamin B12 deficiency","volume":"5","author":"Pahadiya","year":"2016","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_27","first-page":"e6028","article-title":"A Case of Pancytopenia Caused by an Unusual Habit of Eating Pasta","volume":"11","author":"Surani","year":"2019","journal-title":"Cureus"},{"key":"ref_28","first-page":"e6921","article-title":"Suspected Metformin-induced Cobalamin Deficiency Mimicking Thrombotic Thrombocytopenic Purpura","volume":"12","author":"Hussain","year":"2020","journal-title":"Cureus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1159\/000507981","article-title":"A Rare Case of Acquired Hemolytic Anemia and Pancytopenia Secondary to Pernicious Anemia","volume":"13","author":"Sasi","year":"2020","journal-title":"Case Rep. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1136\/jnnp.65.6.822","article-title":"Subacute combined degeneration: Clinical, electro-physiological, and magnetic resonance imaging finding","volume":"65","author":"Hemmer","year":"1998","journal-title":"J. Neurol. Neurosurg. Psychiatry."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.revmed.2006.01.012","article-title":"Neurological manifestations of vitamin B12 deficiency: A retrospective study of 26 cases","volume":"27","author":"Maamar","year":"2006","journal-title":"Rev. Med. Interne"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1182\/blood-2016-10-569186","article-title":"Vitamin B12 deficiency from the perspective of a practicing hematologist","volume":"129","author":"Green","year":"2017","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1056\/NEJM198806303182604","article-title":"Neuro-psychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis","volume":"318","author":"Lindenbaum","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1186\/s13104-015-1437-9","article-title":"B12 deficiency with neurological manifestations in the absence of anaemia","volume":"8","author":"Ralapanawa","year":"2015","journal-title":"BMC Res. Notes"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ekabe, C.J., Kehbila, J., Abanda, M.H., Kadia, B.M., Sama, C.-B., and Monekosso, G.L. (2017). Vitamin B12 deficiency neuropathy; a rare diagnosis in young adults: A case report. BMC Res. Notes, 10.","DOI":"10.1186\/s13104-017-2393-3"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejim.2007.03.017","article-title":"Contribution of spinal MRI for unsuspected cobalamin deficiency in isolated sub-acute combined degeneration","volume":"19","author":"Maamar","year":"2008","journal-title":"Eur. J. Intern. Med."},{"key":"ref_37","first-page":"e330","article-title":"Reversible myelopathy with vitamin B12 deficiency","volume":"49","author":"Senol","year":"2008","journal-title":"Singap. Med. J."},{"key":"ref_38","first-page":"310","article-title":"MRI in subacute combined degeneration of spinal cord: A case report and review of literature","volume":"50","author":"Srikanth","year":"2002","journal-title":"Neurol. India"},{"key":"ref_39","first-page":"122","article-title":"Recurrent seizures: An unusual manifestation of vitamin B12 deficiency","volume":"52","author":"Kumar","year":"2004","journal-title":"Neurol. India"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/ejcn.2013.128","article-title":"Delirium as a result of vitamin B12 deficiency in a vegetarian female patient","volume":"67","author":"Mavrommati","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s12185-011-0825-8","article-title":"Vitamin B12 deficiency, hyperhomocysteinemia and thrombosis: A case and control study","volume":"93","author":"Remacha","year":"2011","journal-title":"Int. J. Hematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1093\/aje\/kwy004","article-title":"Hyperhomocysteinemia and Risk of First Venous Thrombosis: The Influence of (Unmeasured) Confounding Factors","volume":"187","author":"Cannegieter","year":"2018","journal-title":"Am. J. Epidemiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jccase.2018.07.003","article-title":"Inferior vena cava thrombus due to hyperhomocysteinemia","volume":"18","author":"Tanaka","year":"2018","journal-title":"J. Cardiol. Cases"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13256-019-1988-9","article-title":"An uncommon presentation of hyperhomocysteinemia and vitamin B12 deficiency: A case report","volume":"13","author":"Kapur","year":"2019","journal-title":"J. Med. Case Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s13256-017-1415-z","article-title":"Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: A case series","volume":"11","author":"Ammouri","year":"2017","journal-title":"J. Med. Case Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"bcr2014208622","DOI":"10.1136\/bcr-2014-208622","article-title":"Pitfalls in the diagnostic evaluation of subacute combined degeneration","volume":"2015","author":"Ulrich","year":"2015","journal-title":"BMJ Case Rep."},{"key":"ref_47","first-page":"e7818","article-title":"Hyperhomocysteinemia and Pulmonary Embolism in a Young Male","volume":"12","author":"Kovalenko","year":"2020","journal-title":"Cureus"},{"key":"ref_48","first-page":"396","article-title":"Aortic thrombus and pulmonary embolism in a patient with hyperhomocysteinemia","volume":"3","author":"Goette","year":"2006","journal-title":"Nat. Clin. Pr. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1345\/aph.10325","article-title":"Vitamin B12 Deficiency Associated with Histamine2-Receptor Antagonists and a Proton-Pump Inhibitor","volume":"36","author":"Ruscin","year":"2002","journal-title":"Ann. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1475-2891-5-6","article-title":"Homocysteine and cognitive impairment; a case series in a General Practice setting","volume":"5","author":"McCaddon","year":"2006","journal-title":"Nutr. J."},{"key":"ref_51","unstructured":"(2021, May 01). BSH Guidance on B12 Replacement during the COVID-19 Pandemic, British Society for Haematology. Available online: https:\/\/b-s-h.org.uk\/media\/18275\/bsh-guidance-b12-replacement-covid-1901052020finalv.pdf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:58:21Z","timestamp":1760165901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":51,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189694"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189694","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]}}}