Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

3rd Department of Internal Medicine Center of Preventive Cardiology University General Hospital Charles University Prague 110 00 Prague Czech Republic

Aging Research Center Karolinska Institute 171 65 Stockholm Sweden

Clinical Department of the National Institute of Gerontology and Geriatrics Ana Aslan University of Medicine and Pharmacy Carol Davila 011241 Bucharest Romania

Consultant in Neurology and Clinical Neurophysiology 41844 Wegberg Germany

Department of Biochemistry Molecular Biology Nutrition and Metabolism University Hospital of Nancy 54000 Vandoeuvre lès Nancy France

Department of Clinical Chemistry and Laboratory Medicine Saarland University Hospital 66421 Homburg Germany

Department of Internal Medicine Diabetes and Metabolic Diseases Hôpitaux Universitaires de Strasbourg 67091 Strasbourg France

Department of Internal Medicine University of Szeged 6720 Szeged Hungary

Department of Neurological Psychiatric Nursing Faculty of Health Sciences Medical University of Gdańsk 80 210 Gdańsk Poland

Department of Neurology and Stroke St Adalbert Hospital 80 462 Gdańsk Poland

Department of Neurology Benedictus Klinikum Tutzing 82327 Tutzing Germany

Department of Neurology University Hospital Alexandrovska Medical University 1431 Sofia Bulgaria

Department of Psychiatry and Psychotherapy Ludwig Maximillian University Hospital 80539 Munich Germany

INSERM UMR_S1256 NGERE Nutrition Genetics and Environmental Risk Exposure Faculty of Medicine of Nancy University of Lorraine 54500 Vandoeuvre lès Nancy France

Vietnam Institute of Diabetes and Metabolic Disorders Hanoi Medical University Hanoi 116001 Vietnam

See more in PubMed

Healton E.B., Savage D.G., Brust J.C., Garrett T.J., Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine. 1991;70:229–245. doi: 10.1097/00005792-199107000-00001. PubMed DOI

Miceli E., Lenti M.V., Padula D., Luinetti O., Vattiato C., Monti C.M., Di Stefano M., Corazza G.R. Common features of patients with autoimmune atrophic gastritis. Clin. Gastroenterol. Hepatol. 2012;10:812–814. doi: 10.1016/j.cgh.2012.02.018. PubMed DOI

Misra U.K., Kalita J. Comparison of clinical and electrodiagnostic features in B12 deficiency neurological syndromes with and without antiparietal cell antibodies. Postgrad. Med. J. 2007;83:124–127. doi: 10.1136/pgmj.2006.048132. PubMed DOI PMC

Divate P.G., Patanwala R. Neurological manifestations of B(12) deficiency with emphasis on its aetiology. J. Assoc. Physicians India. 2014;62:400–405. PubMed

Aaron S., Kumar S., Vijayan J., Jacob J., Alexander M., Gnanamuthu C. Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Neurol. India. 2005;53:55–58. PubMed

Lachner C., Martin C., John D., Nekkalapu S., Sasan A., Steinle N., Regenold W.T. Older adult psychiatric inpatients with non-cognitive disorders should be screened for vitamin B12 deficiency. J. Nutr. Health Aging. 2014;18:209–212. doi: 10.1007/s12603-013-0378-z. PubMed DOI PMC

Jain K.K., Malhotra H.S., Garg R.K., Gupta P.K., Roy B., Gupta R.K. Prevalence of MR imaging abnormalities in vitamin B12 deficiency patients presenting with clinical features of subacute combined degeneration of the spinal cord. J. Neurol. Sci. 2014;342:162–166. doi: 10.1016/j.jns.2014.05.020. PubMed DOI

Stabler S.P., Allen R.H., Savage D.G., Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990;76:871–881. doi: 10.1182/blood.V76.5.871.871. PubMed DOI

Lindenbaum J., Healton E.B., Savage D.G., Brust J.C., Garrett T.J., Podell E.R., Margell P.D., Stabler S.P., Allen R.H. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N. Engl. J. Med. 1988;318:1720–1728. doi: 10.1056/NEJM198806303182604. PubMed DOI

Herrmann W., Obeid R. Utility and limitations of biochemical markers of vitamin B12 deficiency. Eur. J. Clin. Investig. 2013;43:231–237. doi: 10.1111/eci.12034. PubMed DOI

Green R., Allen L.H., Bjørke-Monsen A.L., Brito A., Guéant J.L., Miller J.W., Molloy A.M., Nexo E., Stabler S., Toh B.H., et al. Vitamin B(12) deficiency. Nat. Rev. Dis. Primers. 2017;3:17040. doi: 10.1038/nrdp.2017.40. PubMed DOI

Andres E., Zulfiqar A.A., Vogel T. State of the art review: Oral and nasal vitamin B12 therapy in the elderly. QJM Int. J. Med. 2020;113:5–15. doi: 10.1093/qjmed/hcz046. PubMed DOI

Abdelwahab O.A., Abdelaziz A., Diab S., Khazragy A., Elboraay T., Fayad T., Diab R.A., Negida A. Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis. Ir. J. Med. Sci. :2024. doi: 10.1007/s11845-023-03602-4. PubMed DOI PMC

Butler C.C., Vidal-Alaball J., Cannings-John R., McCaddon A., Hood K., Papaioannou A., Mcdowell I., Goringe A. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: A systematic review of randomized controlled trials. Fam. Pract. 2006;23:279–285. doi: 10.1093/fampra/cml008. PubMed DOI

Wang H., Li L., Qin L.L., Song Y., Vidal-Alaball J., Liu T.H. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst. Rev. 2018;3:CD004655. doi: 10.1002/14651858.CD004655.pub3. PubMed DOI PMC

National Institute for Health Care Excellence (NICE) Vitamin B12 Deficiency in over 16s: Diagnosis and Management (NG239) [(accessed on 6 March 2024)]. Available online: www.nice.org.uk/guidance/ng239. PubMed

Beiderbeck D., Frevel N., von der Gracht H.A., Schmidt S.L., Schweitzer V.M. Preparing, conducting, and analyzing Delphi surveys: Cross-disciplinary practices, new directions, and advancements. MethodsX. 2021;8:101401. doi: 10.1016/j.mex.2021.101401. PubMed DOI PMC

Stabler S.P. Clinical practice. Vitamin B12 deficiency. N. Engl. J. Med. 2013;368:149–160. PubMed

Cao J., Su Z.Y., Xu S.B., Liu C.C. Subacute combined degeneration: A retrospective study of 68 cases with short-term follow-up. Eur. Neurol. 2018;79:247–255. doi: 10.1159/000488913. PubMed DOI

Li J., Ren M., Dong A., Wu Y., Han N., Deng B., Bi X. A retrospective study of 23 cases with subacute combined degeneration. Int. J. Neurosci. 2016;126:872–877. doi: 10.3109/00207454.2015.1077331. PubMed DOI

Linazi G., Abudureyimu S., Zhang J., Wulamu A., Maimaitiaili M., Wang B., Bakeer B., Xi Y. Clinical features of different stage subacute combined degeneration of the spinal cord. Medicine. 2022;101:e30420. doi: 10.1097/MD.0000000000030420. PubMed DOI PMC

Bi Z., Cao J., Shang K., Su Z., Xu S., Liu C. Correlation between anemia and clinical severity in subacute combined degeneration patients. J. Clin. Neurosci. 2020;80:11–15. doi: 10.1016/j.jocn.2020.08.005. PubMed DOI

Cao J., Xu S., Liu C. Is serum vitamin B12 decrease a necessity for the diagnosis of subacute combined degeneration?: A meta-analysis. Medicine. 2020;99:e19700. doi: 10.1097/MD.0000000000019700. PubMed DOI PMC

Franques J., Chiche L., De Paula A.M., Grapperon A.M., Attarian S., Pouget J., Mathis S. Characteristics of patients with vitamin B12-responsive neuropathy: A case series with systematic repeated electrophysiological assessment. Neurol. Res. 2019;41:569–576. doi: 10.1080/01616412.2019.1588490. PubMed DOI

Bhatia P., Kulkarni J.D., Pai S.A. Vitamin B12 deficiency in India: Mean corpuscular volume is an unreliable screening parameter. Natl. Med. J. India. 2012;25:336–338. PubMed

Sanz-Cuesta T., Escortell-Mayor E., Cura-Gonzalez I., Martin-Fernandez J., Riesgo-Fuertes R., Garrido-Elustondo S., Mariño-Suárez J.E., Álvarez-Villalba M., Gómez-Gascón T., González-García I., et al. Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: A pragmatic, randomised, non-inferiority clinical trial (OB12) BMJ Open. 2020;10:e033687. doi: 10.1136/bmjopen-2019-033687. PubMed DOI PMC

Soykan I., Yakut M., Keskin O., Bektas M. Clinical profiles, endoscopic and laboratory features and associated factors in patients with autoimmune gastritis. Digestion. 2012;86:20–26. doi: 10.1159/000338295. PubMed DOI

Kim H.I., Hyung W.J., Song K.J., Choi S.H., Kim C.B., Noh S.H. Oral vitamin B12 replacement: An effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Ann. Surg. Oncol. 2011;18:3711–3717. doi: 10.1245/s10434-011-1764-6. PubMed DOI

Saperstein D.S., Wolfe G.I., Gronseth G.S., Nations S.P., Herbelin L.L., Bryan W.W., Barohn R.J. Challenges in the identification of cobalamin-deficiency polyneuropathy. Arch. Neurol. 2003;60:1296–1301. doi: 10.1001/archneur.60.9.1296. PubMed DOI

Adali Y., Binnetoglu K. Evaluation of the response to vitamin B12 supplementation in patients with atrophy in sleeve gastrectomy materials. Cir. Cir. 2022;90:17–23. doi: 10.24875/CIRUE.M21000413. PubMed DOI

Rajabally Y.A., Martey J. Neuropathy in Parkinson disease: Prevalence and determinants. Neurology. 2011;77:1947–1950. doi: 10.1212/WNL.0b013e31823a0ee4. PubMed DOI

Siswanto O., Smeall K., Watson T., Donnelly-Vanderloo M., O’Connor C., Foley N., Madill J. Examining the association between vitamin B12 deficiency and dementia in high-risk hospitalized patients. J. Nutr. Health Aging. 2015;19:1003–1008. doi: 10.1007/s12603-015-0660-3. PubMed DOI

Tu M.C., Lo C.P., Chen C.Y., Huang C.F. Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status. BMC Neurol. 2015;15:251. doi: 10.1186/s12883-015-0500-4. PubMed DOI PMC

Gupta P.K., Gupta R.K., Garg R.K., Rai Y., Roy B., Pandey C.M., Malhotra H.S., Narayana P.A. DTI correlates of cognition in conventional MRI of normal-appearing brain in patients with clinical features of subacute combined degeneration and biochemically proven vitamin B(12) deficiency. AJNR Am. J. Neuroradiol. 2014;35:872–877. doi: 10.3174/ajnr.A3785. PubMed DOI PMC

Warendorf J.K., van Doormaal P.T., Vrancken A.F., Verhoeven-Duif N.M., van Eijk R.P., van den Berg L.H., Notermans N.C. Clinical relevance of testing for metabolic vitamin B12 deficiency in patients with polyneuropathy. Nutr. Neurosci. 2022;25:2536–2546. doi: 10.1080/1028415X.2021.1985751. PubMed DOI

Tangney C.C., Aggarwal N.T., Li H., Wilson R.S., Decarli C., Evans D.A., Morris M.C. Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination. Neurology. 2011;77:1276–1282. doi: 10.1212/WNL.0b013e3182315a33. PubMed DOI PMC

Tangney C.C., Tang Y., Evans D.A., Morris M.C. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009;72:361–367. doi: 10.1212/01.wnl.0000341272.48617.b0. PubMed DOI PMC

Leishear K., Boudreau R.M., Studenski S.A., Ferrucci L., Rosano C., De Rekeneire N., Houston D.K., Kritchevsky S.B., Schwartz A.V., Vinik A.I., et al. Relationship between vitamin B12 and sensory and motor peripheral nerve function in older adults. J. Am. Geriatr. Soc. 2012;60:1057–1063. doi: 10.1111/j.1532-5415.2012.03998.x. PubMed DOI PMC

Solomon L.R. Vitamin B12-responsive neuropathies: A case series. Nutr. Neurosci. 2016;19:162–168. doi: 10.1179/1476830515Y.0000000006. PubMed DOI

Gupta K., Jain A., Rohatgi A. An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy. Diabetes Metab. Syndr. 2018;12:51–58. doi: 10.1016/j.dsx.2017.08.014. PubMed DOI

Kancherla V., Elliott J.L., Jr., Patel B.B., Holland N.W., Johnson T.M., Khakharia A., Phillips L.S., Oakley G.P., Jr., Vaughan C.P. Long-term metformin therapy and monitoring for vitamin B12 deficiency among older veterans. J. Am. Geriatr. Soc. 2017;65:1061–1066. doi: 10.1111/jgs.14761. PubMed DOI PMC

Kos E., Liszek M.J., Emanuele M.A., Durazo-Arvizu R., Camacho P. Effect of metformin therapy on vitamin D and vitamin B(1)(2) levels in patients with type 2 diabetes mellitus. Endocr. Pract. 2012;18:179–184. doi: 10.4158/EP11009.OR. PubMed DOI

Jayashri R., Venkatesan U., Rohan M., Gokulakrishnan K., Shanthi Rani C.S., Deepa M., Anjana R.M., Mohan V., Pradeepa R. Prevalence of vitamin B(12) deficiency in South Indians with different grades of glucose tolerance. Acta Diabetol. 2018;55:1283–1293. doi: 10.1007/s00592-018-1240-x. PubMed DOI

Bherwani S., Ahirwar A.K., Saumya A.S., Sandhya A.S., Prajapat B., Patel S., Jibhkate S.B., Singh R., Ghotekar L.H. The study of association of Vitamin B(12) deficiency in type 2 diabetes mellitus with and without diabetic nephropathy in North Indian Population. Diabetes Metab. Syndr. 2017;11((Suppl. 1)):S365–S368. doi: 10.1016/j.dsx.2017.03.017. PubMed DOI

Kang D., Yun J.S., Ko S.H., Lim T.S., Ahn Y.B., Park Y.M., Ko S.H. Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: A cross-sectional study. PLoS ONE. 2014;9:e109878. doi: 10.1371/journal.pone.0109878. PubMed DOI PMC

Singh A.K., Kumar A., Karmakar D., Jha R.K. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. J. Postgrad. Med. 2013;59:253–257. doi: 10.4103/0022-3859.123143. PubMed DOI

Chapman L.E., Darling A.L., Brown J.E. Association between metformin and vitamin B(12) deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2016;42:316–327. doi: 10.1016/j.diabet.2016.03.008. PubMed DOI

De Jager J., Kooy A., Lehert P., Wulffelé M.G., Van der Kolk J., Bets D., Verburg J., Donker A.J., Stehouwer C.D. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial. BMJ. 2010;340:c2181. doi: 10.1136/bmj.c2181. PubMed DOI PMC

Yang R., Yu H., Wu J., Chen H., Wang M., Wang S., Qin X., Wu T., Wu Y., Hu Y. Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing, China. Front. Endocrinol. 2023;14:1082720. doi: 10.3389/fendo.2023.1082720. PubMed DOI PMC

Aroda V.R., Edelstein S.L., Goldberg R.B., Knowler W.C., Marcovina S.M., Orchard T.J., Bray G.A., Schade D.S., Temprosa M.G., White N.H., et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J. Clin. Endocrinol. Metab. 2016;101:1754–1761. doi: 10.1210/jc.2015-3754. PubMed DOI PMC

Miyan Z., Waris N. Association of vitamin B(12) deficiency in people with type 2 diabetes on metformin and without metformin: A multicenter study, Karachi, Pakistan. BMJ Open Diabetes Res. Care. 2020;8:e001151. doi: 10.1136/bmjdrc-2019-001151. PubMed DOI PMC

Parry-Strong A., Langdana F., Haeusler S., Weatherall M., Krebs J. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: A randomised trial. N. Z. Med. J. 2016;129:67–75. PubMed

Mirkazemi C., Peterson G.M., Tenni P.C., Jackson S.L. Vitamin B12 deficiency in Australian residential aged care facilities. J. Nutr. Health Aging. 2012;16:277–280. doi: 10.1007/s12603-011-0348-2. PubMed DOI

Soh Y., Won C.W. Association between frailty and vitamin B12 in the older Korean population. Medicine. 2020;99:e22327. doi: 10.1097/MD.0000000000022327. PubMed DOI PMC

Couderc A.L., Camalet J., Schneider S., Turpin J.M., Bereder I., Boulahssass R., Gonfrier S., Bayer P., Guerin O., Brocker P. Cobalamin deficiency in the elderly: Aetiology and management: A study of 125 patients in a geriatric hospital. J. Nutr. Health Aging. 2015;19:234–239. doi: 10.1007/s12603-014-0525-1. PubMed DOI

Andrès E., Affenberger S., Vinzio S., Kurtz J.E., Noel E., Kaltenbach G., Maloisel F., Schlienger J.L., Blicklé J.F. Food-cobalamin malabsorption in elderly patients: Clinical manifestations and treatment. Am. J. Med. 2005;118:1154–1159. doi: 10.1016/j.amjmed.2005.02.026. PubMed DOI

Ates B.E., Soysal P., Aydin A.E., Dokuzlar O., Kocyigit S.E., Isik A.T. Vitamin B12 deficiency might be related to sarcopenia in older adults. Exp. Gerontol. 2017;95:136–140. doi: 10.1016/j.exger.2017.05.017. PubMed DOI

Junca J., de Soria P.L., Granada M.L., Flores A., Marquez E. Detection of early abnormalities in gastric function in first-degree relatives of patients with pernicious anemia. Eur. J. Haematol. 2006;77:518–522. doi: 10.1111/j.0902-4441.2006.t01-1-EJH2913.x. PubMed DOI

Hughes J.W., Muegge B.D., Tobin G.S., Litvin M., Sun L., Saenz J.B., Gyawali C.P., McGill J.B. High-risk gastric pathology and prevalent autoimmune diseases in patients with pernicious anemia. Endocr. Pract. 2017;23:1297–1303. doi: 10.4158/EP-2017-0056. PubMed DOI

Yang G.T., Zhao H.Y., Kong Y., Sun N.N., Dong A.Q. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis. World J. Gastroenterol. 2018;24:1343–1352. doi: 10.3748/wjg.v24.i12.1343. PubMed DOI PMC

Ao M., Tsuji H., Shide K., Kosaka Y., Noda A., Inagaki N., Nakase H., Tanaka K. High prevalence of vitamin B-12 insufficiency in patients with Crohn’s disease. Asia Pac. J. Clin. Nutr. 2017;26:1076–1081. PubMed

Madanchi M., Fagagnini S., Fournier N., Biedermann L., Zeitz J., Battegay E., Zimmerli L., Vavricka S.R., Rogler G., Scharl M. The relevance of vitamin and iron deficiency in patients with inflammatory bowel diseases in patients of the Swiss IBD Cohort. Inflamm. Bowel Dis. 2018;24:1768–1779. doi: 10.1093/ibd/izy054. PubMed DOI

Yakut M., Ustun Y., Kabacam G., Soykan I. Serum vitamin B12 and folate status in patients with inflammatory bowel diseases. Eur. J. Intern. Med. 2010;21:320–323. doi: 10.1016/j.ejim.2010.05.007. PubMed DOI

Schosler L., Christensen L.A., Hvas C.L. Symptoms and findings in adult-onset celiac disease in a historical Danish patient cohort. Scand. J. Gastroenterol. 2016;51:288–294. doi: 10.3109/00365521.2015.1092576. PubMed DOI

Nguyen T., van Oijen M.G., Janssen M.J., Laheij R.J., Jansen J.B., van A.H. Vitamin B12 deficiency in patients with upper gastrointestinal symptoms in the Mekong Delta, Vietnam. Dig. Liver Dis. 2006;38:438–439. doi: 10.1016/j.dld.2006.01.014. PubMed DOI

Schiavon C.A., Bhatt D.L., Ikeoka D., Santucci E.V., Santos R.N., Damiani L.P., Oliveira J.D., Machado R.H.V., Halpern H., Monteiro F.L., et al. Three-year outcomes of bariatric surgery in patients with obesity and hypertension: A randomized clinical trial. Ann. Intern. Med. 2020;173:685–693. doi: 10.7326/M19-3781. PubMed DOI

Schijns W., Schuurman L.T., Melse-Boonstra A., van Laarhoven C.J.H.M., Berends F.J., Aarts E.O. Do specialized bariatric multivitamins lower deficiencies after RYGB? Surg. Obes. Relat. Dis. 2018;14:1005–1012. doi: 10.1016/j.soard.2018.03.029. PubMed DOI

Vilarrasa N., Fabregat A., Toro S., Gordejuela A.G., Casajoana A., Montserrat M., Garrido P., López-Urdiales R., Virgili N., Planas-Vilaseca A., et al. Nutritional deficiencies and bone metabolism after endobarrier in obese type 2 patients with diabetes. Eur. J. Clin. Nutr. 2018;72:1447–1450. doi: 10.1038/s41430-017-0074-x. PubMed DOI

Bilici A., Sonkaya A., Ercan S., Ustaalioglu B.B.O., Seker M., Aliustaoglu M., Orcun A., Gumus M. The changing of serum vitamin B12 and homocysteine levels after gastrectomy in patients with gastric cancer: Do they associate with clinicopathological factors? Tumor Biol. 2015;36:823–828. doi: 10.1007/s13277-014-2705-3. PubMed DOI

Hu Y., Kim H.I., Hyung W.J., Song K.J., Lee J.H., Kim Y.M., Noh S.H. Vitamin B(12) deficiency after gastrectomy for gastric cancer: An analysis of clinical patterns and risk factors. Ann. Surg. 2013;258:970–975. doi: 10.1097/SLA.0000000000000214. PubMed DOI

Rozgony N.R., Fang C., Kuczmarski M.F., Bob H. Vitamin B(12) deficiency is linked with long-term use of proton pump inhibitors in institutionalized older adults: Could a cyanocobalamin nasal spray be beneficial? J. Nutr. Elder. 2010;29:87–99. doi: 10.1080/01639360903574734. PubMed DOI

Aoyama T., Hara K., Maezawa Y., Kazama K., Hashimoto I., Sawazaki S., Komori K., Tamagawa H., Tamagawa A., Kano K., et al. Clinical course of vitamin B12 deficiency and associated risk factors in patients after total gastrectomy for gastric cancer. Anticancer. Res. 2023;43:689–694. doi: 10.21873/anticanres.16207. PubMed DOI

Vargas-Ruiz A.G., Hernandez-Rivera G., Herrera M.F. Prevalence of iron, folate, and vitamin B12 deficiency anemia after laparoscopic Roux-en-Y gastric bypass. Obes. Surg. 2008;18:288–293. doi: 10.1007/s11695-007-9310-0. PubMed DOI

Aoyama T.O., Maezawa Y.U., Cho H.A., Saigusa Y.U., Tamura J.U., Tsuchida K.A., Komori K.E., Kano K., Segami K., Hara K.E., et al. Phase II study of a multi-center randomized controlled trial to evaluate oral vitamin B12 treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Anticancer. Res. 2022;42:3963–3970. doi: 10.21873/anticanres.15891. PubMed DOI

Mahawar K.K., Reid A., Graham Y., Callejas-Diaz L., Parmar C., Carr W.R., Jennings N., Singhal R., Small P.K. Oral vitamin B(12) supplementation after Roux-en-Y gastric bypass: A systematic review. Obes. Surg. 2018;28:1916–1923. doi: 10.1007/s11695-017-3102-y. PubMed DOI

Smelt H.J., Pouwels S., Smulders J.F. Different supplementation regimes to treat perioperative vitamin B12 deficiencies in bariatric surgery: A systematic review. Obes. Surg. 2017;27:254–262. doi: 10.1007/s11695-016-2449-9. PubMed DOI

Majumder S., Soriano J., Louie C.A., Dasanu C.A. Vitamin B12 deficiency in patients undergoing bariatric surgery: Preventive strategies and key recommendations. Surg. Obes. Relat. Dis. 2013;9:1013–1019. doi: 10.1016/j.soard.2013.04.017. PubMed DOI

Engebretsen K.V., Blom-Høgestøl I.K., Hewitt S., Risstad H., Moum B., Kristinsson J.A., Mala T. Anemia following Roux-en-Y gastric bypass for morbid obesity; a 5-year follow-up study. Scand. J. Gastroenterol. 2018;53:917–922. doi: 10.1080/00365521.2018.1489892. PubMed DOI

Gueant-Rodriguez R.M., Antoine D., Li Z., Quilliot D., Sirveaux M.A., Meyre D., Mangeon A., Brunaud L., Guéant J.L. Medium term post-bariatric surgery deficit of vitamin B12 is predicted by deficit at time of surgery. Clin. Nutr. 2021;40:87–93. PubMed

Didangelos T., Karlafti E., Kotzakioulafi E., Margariti E., Giannoulaki P., Batanis G., Tesfaye S., Kantartzis K. Vitamin B12 supplementation in diabetic neuropathy: A 1-year, randomized, double-blind, placebo-controlled trial. Nutrients. 2021;13:395. doi: 10.3390/nu13020395. PubMed DOI PMC

Namikawa T., Maeda M., Yokota K., Iwabu J., Munekage M., Uemura S., Maeda H., Kitagawa H., Kobayashi M., Hanazaki K. Enteral vitamin B12 supplementation is effective for improving anemia in patients who underwent total gastrectomy. Oncology. 2021;99:225–233. doi: 10.1159/000513888. PubMed DOI

Kalita J., Agarwal R., Chandra S., Misra U.K. A study of neurobehavioral, clinical psychometric, and P3 changes in vitamin B12 deficiency neurological syndrome. Nutr. Neurosci. 2013;16:39–46. doi: 10.1179/1476830512Y.0000000028. PubMed DOI

Maghsoudlou P., Varlamova J., Pandit J. Patients with unexplained neurological symptoms and signs should be screened for vitamin B12 deficiency regardless of haemoglobin levels. Eye. 2022;36:1124–1125. doi: 10.1038/s41433-021-01589-9. PubMed DOI PMC

Gupta P.K., Garg R.K., Gupta R.K., Malhotra H.S., Paliwal V.K., Rathore R.K.S., Verma R., Singh M.K., Rai Y., Pandey C.M. Diffusion tensor tractography and neuropsychological assessment in patients with vitamin B12 deficiency. Neuroradiology. 2014;56:97–106. doi: 10.1007/s00234-013-1306-y. PubMed DOI

Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5:949–960. doi: 10.1016/S1474-4422(06)70598-1. PubMed DOI

Puri V., Chaudhry N., Goel S., Gulati P., Nehru R., Chowdhury D. Vitamin B12 deficiency: A clinical and electrophysiological profile. Electromyogr. Clin. Neurophysiol. 2005;45:273–284. PubMed

Misra U.K., Kalita J., Das A. Vitamin B12 deficiency neurological syndromes: A clinical, MRI and electrodiagnostic study. Electromyogr. Clin. Neurophysiol. 2003;43:57–64. PubMed

Bolaman Z., Kadikoylu G., Yukselen V., Yavasoglu I., Barutca S., Senturk T. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: A single-center, prospective, randomized, open-label study. Clin. Ther. 2003;25:3124–3134. doi: 10.1016/S0149-2918(03)90096-8. PubMed DOI

Xiao C.P., Ren C.P., Cheng J.L., Zhang Y., Li Y., Li B.B., Fan Y.Z. Conventional MRI for diagnosis of subacute combined degeneration (SCD) of the spinal cord due to vitamin B-12 deficiency. Asia Pac. J. Clin. Nutr. 2016;25:34–38. PubMed

Roy B., Trivedi R., Garg R.K., Gupta P.K., Tyagi R., Gupta R.K. Assessment of functional and structural damage in brain parenchyma in patients with vitamin B12 deficiency: A longitudinal perfusion and diffusion tensor imaging study. Magn. Reson. Imaging. 2015;33:537–543. doi: 10.1016/j.mri.2015.02.012. PubMed DOI

Urbanski G., Hamel J.F., Prouveur B., Annweiler C., Ghali A., Cassereau J., Lozac’h P., Lavigne C., Lacombe V. Strength of the association of elevated vitamin B12 and solid cancers: An adjusted case-control study. J. Clin. Med. 2020;9:474. doi: 10.3390/jcm9020474. PubMed DOI PMC

Obeid R. High plasma vitamin B12 and cancer in human studies: A scoping review to judge causality and alternative explanations. Nutrients. 2022;14:4476. doi: 10.3390/nu14214476. PubMed DOI PMC

Yang W., Cai X., Wu H., Ji L. Associations between metformin use and vitamin B(12) levels, anemia, and neuropathy in patients with diabetes: A meta-analysis. J. Diabetes. 2019;11:729–743. doi: 10.1111/1753-0407.12900. PubMed DOI

Ceravolo R., Cossu G., Bandettini di Poggio M., Santoro L., Barone P., Zibetti M., Frosini D., Nicoletti V., Manganelli F., Iodice R., et al. Neuropathy and levodopa in Parkinson’s disease: Evidence from a multicenter study. Mov. Disord. 2013;28:1391–1397. doi: 10.1002/mds.25585. PubMed DOI

Park J.S., Park D., Ko P.W., Kang K., Lee H.W. Serum methylmalonic acid correlates with neuropathic pain in idiopathic Parkinson’s disease. Neurol. Sci. 2017;38:1799–1804. doi: 10.1007/s10072-017-3056-9. PubMed DOI

Jhunjhnuwala D., Tanglay O., Briggs N.E., Yuen M.T.Y., Huynh W. Prognostic indicators of subacute combined degeneration from B12 deficiency: A systematic review. PM R. 2022;14:504–514. doi: 10.1002/pmrj.12600. PubMed DOI