geriatrРоссийский журнал гериатрической медициныRussian Journal of Geriatric Medicine2686-86362686-8709Сайт издателя10.37586/2686-8636-2-2024-100-107geriatr-432Research ArticleОБЗОРЫREVIEWSДефицит витамина В12 в патологии нервной системы у лиц пожилого возраста: причины, диагностика, подходы к терапииVitamin B12 Deficiency in Neurological Disorders of Older Adults: Etiology, Diagnostics, Treatmenthttps://orcid.org/0000-0002-9054-0881ЧердакМ. А.CherdakM. A.

Чердак Мария Алексеевна, канд. мед. наук, доцент кафедры болезней старения

Москва

Cherdak Maria A., MD, PhD, Associate Professor, Department of Aging Diseases, Faculty of Additional Professional Education

Moscow

maria.cherdak@yandex.ruhttps://orcid.org/0000-0003-2597-981XМхитарянЭ. Л.MkhitaryanE. A.

Мхитарян Элен Араиковна, канд. мед. наук, доцент кафедры болезней старения, заведующая лабораторией нейрогериатрии

Москва

Mkhitaryan Elen A., MD, PhD, Age-Related Diseases Department

Moscow

melen99@mail.ruФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России, ОСП «Российский геронтологический научно-клинический центр»РоссияRussian Gerontology Research and Clinical Centre, Pirogov Russian National Research Medical UniversityRussian Federation20243006202402100107Copyright © Чердак М.А., Мхитарян Э.Л., 20242024Чердак М.А., Мхитарян Э.Л.Cherdak M.A., Mkhitaryan E.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.geriatr-news.com/jour/article/view/432

Одной из распространенных проблем, ассоциированных со старением, является дефицит витамина В12 (кобаламина), по некоторым данным присутствующий у каждого третьего человека в возрасте старше 60 лет. Кобаламин принимает участие в многочисленных биологически важных реакциях, поэтому его дефицит будет проявляться спектром нарушений, включая гематологические, желудочно-кишечные симптомы, а также патологию различных отделов нервной системы. В статье представлены клинические варианты неврологических расстройств, ассоциированных с дефицитом витамина В12, включая поражение как периферической, так и различных отделов центральной нервной системы. Обсуждается взаимосвязь между дефицитом кобаламина и развитием когнитивных и других нервно-психических расстройств у лиц пожилого возраста. Представлены данные по специфическим для пожилых причинам формирования данного патологического состояния, включая ятрогенные факторы. Изложены современные подходы к диагностике и коррекции дефицита кобаламина, с учетом особенностей гериатрической популяции.

One of the common problems associated with aging is vitamin B12 (cobalamin) deficiency. According to some reports, it is present in every third person over the age of 60. Cobalamin is involved in numerous biologically important reactions, and its deficiency manifests itself in a range of disorders, including hematological and gastrointestinal symptoms, as well as pathology in various parts of the nervous system. The article discusses clinical variants of neurological disorders related to vitamin B12 deficiency, such as damage to both the peripheral and the central nervous systems. The relationship between cobalamin deficiency and the development of cognitive and other neuropsychiatric disorders in older individuals is discussed. Data on specific causes of vitamin B12 deficiencies in older individuals, including iatrogenic factors, are presented. Modern approaches to the diagnosis and correction of cobalamin deficiency are outlined, taking into account the characteristics of the geriatric population.

витамин В12кобаламинкогнитивные расстройствадеменцияфуникулярный миелозполинейропатияпожилыелечениепероральная терапияvitamin B12cobalamincognitive disordersdementiafunicular myelosispolyneuropathyelderlytreatmentoral therapyReferencesLivingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimäki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbæk G, TeriL, Mukadam N. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413-446. https://doi.org/10.1016/S0140-6736(20)30367-6Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimäki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbæk G, TeriL, Mukadam N. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413-446. https://doi.org/10.1016/S0140-6736(20)30367-6Павлов Ч.С., Дамулин И.В., Шульпекова Ю.О., Андреев Е.А. Неврологические расстройства при дефиците витамина В12. Терапевтический архив. 2019; 91(4):122129. https://doi.org/10.26442/00403660.2019.04.000116Pavlov C.S., Damulin I.V., Shulpekova Y.O., Andreev E.A. Neurological disorders in vitamin B12 deficiency. Terapevticheskii arkhiv. 2019; 91(4):122-129. (In Russ.)] https://doi.org/10.26442/00403660.2019.04.000116Esposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency. Nutrients. 2022 Apr 17;14(8):1672. doi: 10.3390/nu14081672Esposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency. Nutrients. 2022 Apr 17;14(8):1672. doi: 10.3390/nu14081672Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994 Jul;60(1):2-11. doi: 10.1093/ajcn/60.1.2Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994 Jul;60(1):2-11. doi: 10.1093/ajcn/60.1.2Чердак М.А., Мхитарян Э.А., Захаров В.В., Вознесенский Н.А. Витамин B12 в лечении и профилактике когнитивных расстройств у лиц пожилого возраста. Журнал неврологии и психиатрии им. С.С. Корсакова. 2022;122(1):43-49. https://doi.org/10.17116/jnevro202212201143Cherdak MA, Mkhitaryan EA, Zakharov VV, Voznesenskiy NA. Vitamin B12 in the treatment and prevention of cognitive disorders in the elderly. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(1):43-49. (In Russ.).) https://doi.org/10.17116/jnevro202212201143Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, Molloy AM, Nexo E, Stabler S, Toh BH, Ueland PM, Yajnik C. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017 Jun 29;3:17040. doi: 10.1038/nrdp.2017.40Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, Molloy AM, Nexo E, Stabler S, Toh BH, Ueland PM, Yajnik C. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017 Jun 29;3:17040. doi: 10.1038/nrdp.2017.40Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015;21(2):155-164. https://doi.org/10.12809/hkmj144383Wong CW. Vitamin B12 deficiency in the elderly: is it worth screening? Hong Kong Med J. 2015;21(2):155-164. https://doi.org/10.12809/hkmj144383Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. QJM. 2009;102(1):17-28. https://doi.org/10.1093/qjmed/hcn138Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. QJM. 2009;102(1):17-28. https://doi.org/10.1093/qjmed/hcn138Gwathmey KG, Grogan J. Nutritional neuropathies. Muscle Nerve. 2020 Jul;62(1):13-29. doi: 10.1002/mus.26783Gwathmey KG, Grogan J. Nutritional neuropathies. Muscle Nerve. 2020 Jul;62(1):13-29. doi: 10.1002/mus.26783Екушева Е.В., Ших Е.В., Аметов А.С., Остроумова О.Д., Захаров В.В., Живолупов С.А., Джукич М. Проблема дефицита витамина В12: актуальность, диагностика и таргетная терапия (по материалам междисциплинарного совета экспертов с международным участием). Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(11):17–25. https://doi.org/10.17116/jnevro202112111117 https://doi.org/10.17116/jnevro202112111117)Ekusheva EV, Shikh EV, Ametov AS, Ostroumova OD, Zaharov VV, Zhivolupov SA, Djukic M. The problem of vitamin B12 deficiency: prelevance, diagnosis and targeted therapy (based on materials of an interdisciplinary expert council with international participation). S.S. Korsakov Journal of Neurology and Psychiatry = Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2021;121(11):17–25. (In Russ.). https://doi.org/10.17116/jnevro202112111117)Камчатнов П.Р., Дамулин И.В. Когнитивные нарушения при дефиците витамина В12, фолиевой кислоты и гипергомоцистеинемии. Клиницист. 2015;9(1):18-23. https://doi.org/10.17650/1818-8338-2015-1-18-23Kamchatnov P.R., Damulin I.V. Cognitive impairments in vitamin B12 and folic deficiencies and hyperhomocysteinemia. The Clinician. 2015;9(1):1823. (In Russ.)] https://doi.org/10.17650/1818-8338-2015-1-18-23Pandey S, V Holla V, Rizvi I, Qavi A, Shukla R. Can vitamin B12 deficiency manifest with acute posterolateral or posterior cord syndrome? Spinal Cord Ser Cases. 2016 Jul 7;2:16006. doi: 10.1038/scsandc.2016.6Pandey S, V Holla V, Rizvi I, Qavi A, Shukla R. Can vitamin B12 deficiency manifest with acute posterolateral or posterior cord syndrome? Spinal Cord Ser Cases. 2016 Jul 7;2:16006. doi: 10.1038/scsandc.2016.6Moore E, Mander A, Ames D, Carne R, Sanders K, Watters D. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr. 2012;24(4):541-556. https://doi.org/10.1017/S1041610211002511Moore E, Mander A, Ames D, Carne R, Sanders K, Watters D. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr. 2012;24(4):541-556. https://doi.org/10.1017/S1041610211002511Luthra NS, Marcus AH, Hills NK, Christine CW. Vitamin B12 measurements across neurodegenerative disorders. J Clin Mov Disord. 2020 Mar 12;7:3. doi: 10.1186/s40734-020-00085-8Luthra NS, Marcus AH, Hills NK, Christine CW. Vitamin B12 measurements across neurodegenerative disorders. J Clin Mov Disord. 2020 Mar 12;7:3. doi: 10.1186/s40734-020-00085-8Rafiee S, Asadollahi K, Riazi G, Ahmadian S, Saboury AA. Vitamin B12 Inhibits Tau Fibrillization via Binding to Cysteine Residues of Tau. ACS Chem Neurosci. 2017 Dec 20;8(12):2676-2682. doi: 10.1021/acschemneuro.7b00230Rafiee S, Asadollahi K, Riazi G, Ahmadian S, Saboury AA. Vitamin B12 Inhibits Tau Fibrillization via Binding to Cysteine Residues of Tau. ACS Chem Neurosci. 2017 Dec 20;8(12):2676-2682. doi: 10.1021/acschemneuro.7b00230Rai SN, Singh P, Steinbusch HWM, Vamanu E, Ashraf G, Singh MP. The Role of Vitamins in Neurodegenerative Disease: An Update. Biomedicines. 2021; 9(10):1284. https://doi.org/10.3390/biomedicines9101284Rai SN, Singh P, Steinbusch HWM, Vamanu E, Ashraf G, Singh MP. The Role of Vitamins in Neurodegenerative Disease: An Update. Biomedicines. 2021; 9(10):1284. https://doi.org/10.3390/biomedicines9101284Andrès E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, Noblet-Dick M, Maloisel F, Schlienger JL, Blicklé JF. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-259. https://doi.org/10.1503/cmaj.1031155Andrès E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, Noblet-Dick M, Maloisel F, Schlienger JL, Blicklé JF. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-259. https://doi.org/10.1503/cmaj.1031155Керкешко Г.О., Дорофейков В.В., Патрухина Н.А., Мозговая Е.В. Роль активного витамина В12 (холотранскобаламина) в формировании анемии беременных. Журнал акушерства и женских болезней. 2015;64(5):96-105. https://doi.org/10.17816/JOWD64596-105Kerkeshko G.O., Dorofeykov V.V., Patrukhina N.A., Mozgovaya E.V. The role of active vitamin B12 (holotranscobalamin) in the development of anemia of pregnancy. Journal of obstetrics and women's diseases. 2015;64(5):96-105. (In Russ.)] https://doi.org/10.17816/JOWD64596-105IDF Diabetes Atlas, 10th edn. Brussels, Belgium: International Diabetes Federation, 2021.(URL: https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf)IDF Diabetes Atlas, 10th edn. Brussels, Belgium: International Diabetes Federation, 2021.(URL: https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf)Flory JH, Keating SJ, Siscovick D, Mushlin AI. Identifying prevalence and risk factors for metformin non-persistence: a retrospective cohort study using an electronic health record. BMJ Open. 2018 Jul 23;8(7):e021505. doi: 10.1136/bmjopen-2018-021505Flory JH, Keating SJ, Siscovick D, Mushlin AI. Identifying prevalence and risk factors for metformin non-persistence: a retrospective cohort study using an electronic health record. BMJ Open. 2018 Jul 23;8(7):e021505. doi: 10.1136/bmjopen-2018-021505Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schade DS, Temprosa MG, White NH, Crandall JP; Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr;101(4):1754-61. doi: 10.1210/jc.2015-3754Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schade DS, Temprosa MG, White NH, Crandall JP; Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016 Apr;101(4):1754-61. doi: 10.1210/jc.2015-3754AlMutairi H, O'Dwyer M, McCarron M, McCallion P, Henman MC. The use of proton pump inhibitors among older adults with intellectual disability: A cross sectional observational study. Saudi Pharm J. 2018 Nov;26(7):1012-1021. doi: 10.1016/j.jsps.2018.05.009AlMutairi H, O'Dwyer M, McCarron M, McCallion P, Henman MC. The use of proton pump inhibitors among older adults with intellectual disability: A cross sectional observational study. Saudi Pharm J. 2018 Nov;26(7):1012-1021. doi: 10.1016/j.jsps.2018.05.009Mumtaz H, Ghafoor B, Saghir H, Tariq M, Dahar K, Ali SH, Waheed ST, Syed AA. Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study. Ann Med Surg (Lond). 2022 Sep 26;82:104762. doi: 10.1016/j.amsu.2022.104762Mumtaz H, Ghafoor B, Saghir H, Tariq M, Dahar K, Ali SH, Waheed ST, Syed AA. Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study. Ann Med Surg (Lond). 2022 Sep 26;82:104762. doi: 10.1016/j.amsu.2022.104762Gröber U, Kisters К, Schmidt J. Neuroenhancement with Vitamin B12 — Underestimated Neurological Significance. Nutrients. 2013 Dec 12;5(12):5031-45. doi: 10.3390/nu5125031Gröber U, Kisters К, Schmidt J. Neuroenhancement with Vitamin B12 — Underestimated Neurological Significance. Nutrients. 2013 Dec 12;5(12):5031-45. doi: 10.3390/nu5125031Langan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6):384389. Ссылка активна на 29.05.2021. https://www.aafp.org/afp/2017/0915/p384.htmlLangan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6):384389. Ссылка активна на 29.05.2021. https://www.aafp.org/afp/2017/0915/p384.htmlValente E, Scott J.M, Ueland P.M, Cunningham C, Casey M, Molloy A.M. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly. Clin Chem. 2011;57(6):856-863. https://doi.org/10.1373/clinchem.2010.158154Valente E, Scott J.M, Ueland P.M, Cunningham C, Casey M, Molloy A.M. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly. Clin Chem. 2011;57(6):856-863. https://doi.org/10.1373/clinchem.2010.158154Ших ЕВ, Сизова ЖМ, Астаева МО. Пероральное применение цианокобаламина при функциональном дефиците витамина В12: эффективность и безопасность. Неврология, нейропсихиатрия, психосоматика. 2021;13(4). DOI: 10.14412/2074-2711-2021-4Shikh EV, Sizova ZhM, Astaeva MO. Oral administration of cyanocobalamin for functional vitamin В12 deficiency: efficacy and safety. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2021;13(4). DOI: 10.14412/2074-2711-2021-4)Ding X, Wang Y, Liu J, Wang G. Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Homocysteine Levels in the Euthyroid Population. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3731-e3737. doi: 10.1210/clinem/dgac371Ding X, Wang Y, Liu J, Wang G. Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Homocysteine Levels in the Euthyroid Population. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3731-e3737. doi: 10.1210/clinem/dgac371Jarquin Campos A, Risch L, Nydegger U, Wiesner J, Vazquez Van Dyck M, Renz H, Stanga Z, Risch M. Diagnostic Accuracy of Holotranscobalamin, Vitamin B12, Methylmalonic Acid, and Homocysteine in Detecting B12 Deficiency in a Large, Mixed Patient Population. Dis Markers. 2020 Feb 7;2020:7468506. doi: 10.1155/2020/7468506Jarquin Campos A, Risch L, Nydegger U, Wiesner J, Vazquez Van Dyck M, Renz H, Stanga Z, Risch M. Diagnostic Accuracy of Holotranscobalamin, Vitamin B12, Methylmalonic Acid, and Homocysteine in Detecting B12 Deficiency in a Large, Mixed Patient Population. Dis Markers. 2020 Feb 7;2020:7468506. doi: 10.1155/2020/7468506Alam MS, Kamrul-Hasan A, Kalam ST. Serum vitamin B12 status of patients with type 2 diabetes mellitus on metformin: A single-center cross-sectional study from Bangladesh. J Family Med Prim Care. 2021 Jun;10(6):2225-2229. doi: 10.4103/jfmpc.jfmpc_2388_20Alam MS, Kamrul-Hasan A, Kalam ST. Serum vitamin B12 status of patients with type 2 diabetes mellitus on metformin: A single-center cross-sectional study from Bangladesh. J Family Med Prim Care. 2021 Jun;10(6):2225-2229. doi: 10.4103/jfmpc.jfmpc_2388_20Боголепова А.Н., Васенина Е.Е., Гомзякова Н.А. и др. Клинические рекомендации «Когнитивные расстройства у пациентов пожилого и старческого возраста». Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(10-3):6-137.Bogolepova AN, Vasenina EE, Gomzyakova NA, et al. Clinical Guidelines for Cognitive Disorders in Elderly and Older Patients. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2021;121(103):6-137. https://doi.org/10.17116/jnevro20211211036)Zugravu CA, Macri A, Belc N, Bohiltea R. Efficacy of supplementation with methylcobalamin and cyancobalamin in maintaining the level of serum holotranscobalamin in a group of plant-based diet (vegan) adults. Exp Ther Med. 2021 Sep;22(3):993. doi: 10.3892/etm.2021.10425Zugravu CA, Macri A, Belc N, Bohiltea R. Efficacy of supplementation with methylcobalamin and cyancobalamin in maintaining the level of serum holotranscobalamin in a group of plant-based diet (vegan) adults. Exp Ther Med. 2021 Sep;22(3):993. doi: 10.3892/etm.2021.10425Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022 Mar 10;80(4):931-949. doi: 10.1093/nutrit/nuab057Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev. 2022 Mar 10;80(4):931-949. doi: 10.1093/nutrit/nuab057Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. https://doi.org/10.1111/bjh.12959Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. https://doi.org/10.1111/bjh.12959Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655. https://doi.org/10.1002/14651858.CD004655.pub3Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655. https://doi.org/10.1002/14651858.CD004655.pub3Eussen SJ, de Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, van Staveren WA. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005;165(10):1167-1172. https://doi.org/10.1001/archinte.165.10.1167Eussen SJ, de Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, van Staveren WA. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005;165(10):1167-1172. https://doi.org/10.1001/archinte.165.10.1167Rajan S, Wallace JI, Brodkin KI, et al. Responseof elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc. 2002 Nov;50(11):1789-95. doi: 10.1046/j.1532-5415.2002.50506.xRajan S, Wallace JI, Brodkin KI, et al. Responseof elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc. 2002 Nov;50(11):1789-95. doi: 10.1046/j.1532-5415.2002.50506.xMoleiro J, Mao de Ferro S, Ferreira S, et al. Efficacy of long- term oral vitamin B12 supplementation after total gastrectomy: results from a prospective study. GE Port J Gastroenterol. 2018 Apr;25(3):117-22. doi: 10.1159/000481860Moleiro J, Mao de Ferro S, Ferreira S, et al. Efficacy of long- term oral vitamin B12 supplementation after total gastrectomy: results from a prospective study. GE Port J Gastroenterol. 2018 Apr;25(3):117-22. doi: 10.1159/000481860Sanz-Cuesta T, Escortell-Mayor E, Cura-Gonzalez 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 Aug 20;10(8):e033687. doi: 10.1136/bmjopen-2019-033687Sanz-Cuesta T, Escortell-Mayor E, Cura-Gonzalez 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 Aug 20;10(8):e033687. doi: 10.1136/bmjopen-2019-033687

The authors declare that there are no conflicts of interest present.