Insufficiency/deficiency of vitamin B12 in patients in the endocrinological practice

On March 20, 2024, an interdisciplinary meeting of the Expert Council on the current problem of B12 insufficiency/deficiency and the prevalence of this condition among endocrine patients was held at the Endocrinology Research Centre (Moscow). The purpose of the meeting was to assess the role of B12 deficiency in reducing the quality of life of patients of different groups and to outline a strategy for the management of patients with vitamin B12 insufficiency/deficiency by endocrinologists.

The resolution of the expert council was developed by leading specialists in various specialties.

1. Ya.A. Starchina. B-Group vitamins in the treatment of nervous system diseases // Neurology, neuropsychiatry, psychosomatics. 2009;2;84-87. (In Russ.) doi: https://doi.org/10.14412/2074-2711-2009-45

2. Akhmedzhanova L.T. et al Vitamins of group B in the treatment of neurological diseases // RMJ. 2009;17(11);776-83. (In Russ.)

3. Markle H.V. Cobalamin // Crit Rev Clin Lab Sci. — 1996. — Т. 33. — С. 247–356

4. Krasnovskiy AL. Modern diagnostic and treatment of B12 deficiency // The Clinician. 2016;10(3);15-25. (In Russ.) doi: https://doi.org/10.17650/1818-8338-2016-10-3-15-25

5. Divate PG, Patanwala R. Neurological manifestations of B12 deficiency with emphasis on its aetiology. J Assoc Physicians India. 2014; 62: 400–5

6. Clarke R, et al. Low vitamin B12 status and risk of cognitive decline in older adults. Am J Clinical Nutrition. 2007;86:(5):1384–91. doi: https://doi.org/10.1093/ajcn/86.5.1384

7. Dali-Youcef N, Andres E. An update on cobalamin deficiency in adults. QJM. 2009;102:17–28. doi: https://doi.org/10.1093/qjmed/hcn138

8. Khodabandehloo N, et al. Iran Red Crescent Med J. 2015;17(8):e13138. doi: https://doi.org/10.5812/ircmj.17(6)2015.13138

9. Hannibal L, Lysne V, Monsen ALB. Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Front Mol Biosci. 2016;27:3:27. doi: https://doi.org/10.3389/fmolb.2016.00027

10. Shikh EV, Sizova ZhM, Astaeva MO. Oral administration of cyanocobalamin for functional vitamin В12 deficiency: efficacy and safety. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(4):109–115 (In Russ) doi: https://doi.org/10.14412/2074-2711-2021-4-109-115

11. Polyakova OA, Klepikova MV, Ostroumova OD. Diagnosis of B12-deficiency anemia and ways to correct it in different clinical situations. Non Nocere. Novyj terapevticheskij zhurnal. 2021;11:64–74. (In Russ.).

12. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226. doi: https://doi.org/10.1136/bmj.g5226

13. Hannibal L, Lysne V, Bjørke-Monsen AL, et al. Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency. Front Mol Biosci. 2016;3:27–42. doi: https://doi.org/10.3389/fmolb.2016.00027

14. Means R.T., Fairfield K.M. Clinical manifestations and diagnosis of vitamin B12 and folate deficiency [Internet]. UpToDate [cited 03.03.2023]. Available from: https://medilib.ir/uptodate/show/7155

15. Fedosov SN, Brito A, Miller JW, et al. Combined indicator of vitamin B12 status: modifications for missing biomarkers and folate status and recommendations for revised cut-points. Clin Chim Lab Med. 2015;53(8):1215–25. doi: https://doi.org/10.1515/cclm-2014-0818.

16. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014. doi: https://doi.org/10.1111/bjh.12959

17. Ekusheva EV, Shikh EV, Ametov AS, et al. The problem of vitamin B12 deficiency: Relevance, diagnosis and targeted therapy (based on materials of AN Interdisciplinary Expert Council with international participation). S.S. Korsakov Journal of Neurology and Psychiatry. 2021; 121(11): 17–25 (In Russ.). doi: https://dx.doi.org/10.17116/jnevro202112111117

18. Jung SB, Nagaraja V, Kapur A, Eslick GD. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: A systematic review and meta-analysis. Intern Med J. 2015. doi: https://doi.org/10.1111/imj.12697

19. Hirschowitz BI, Worthington J, Mohnen J. Vitamin B12 deficiency in hypersecretors during long‐term acid suppression with proton pump inhibitors. Alimentary pharmacology & therapeutics. 2008;27:(11):1110–21. doi: https://doi.org/10.1111/j.1365-2036.2008.03658.x

20. Andrès E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251–59. doi: https://doi.org/10.1503/cmaj.1031155

21. Dharmarajan TS, Kanagala MR, Murakonda P, et al. Do acid-lowering agents affect vitamin B12 status in older adults? J Am Med Dir Assoc. 2008;9 (3):162–7 doi: https://doi.org/10.1016/j.jamda.2007.10.004

22. Parlesak A, Klein B, Schecher K, et al. Prevalence of small bowel bacterial overgrowth and its association with nutrition intake in nonhospitalized older adults. J Am Geriatr Soc. 2003;51(6):768–73. doi: https://doi.org/10.1046/j.1365-2389.2003.51259.x

23. Khodabandehloo N, et al. Iran Red Crescent Med J. 2015;17(8) e13138. doi: https://doi.org/10.5812/ircmj.17(6)2015.13138

24. Damião ChP, Rodrigues AO, Pinheiro M, et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J. 2016;134 (6): 473–9. doi: https://doi.org/10.1590/1516-3180.2015.01382111

25. Niafar M, Hai F, Porhomayon J, Nader ND. The role of metformin on vitamin B 12 deficiency: a meta-analysis review. Intern Emerg Med. 2015;10(1):93–102. doi: https://doi.org/10.1007/s11739-014-1157-5

26. 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;11:729–43. doi: https://doi.org/10.1111/1753-0407.12900

27. Didangelos T, et al. Vitamin B12 supplementation in diabetic neuropathy: a 1-year, randomized, doubleblind, placebo-controlled trial. Nutrients. 2021;13(2):395. doi: https://doi.org/10.3390/nu13020395

28. Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2016;42:316–27. doi: https://doi.org/10.1016/j.diabet.2016.03.008

29. De Jager J, Kooy A, Lehert P, Wulffelé MG, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B12 deficiency: Randomised placebo controlled trial. BMJ. 2010;340 2181. doi: https://doi.org/10.1136/bmj.c2181

30. Yang R, Yu H, Wu J, et al. Metformin treatment and risk of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus in Beijing. China Front. Endocrinol. 2023;14:1082720. doi: https://doi.org/10.3389/fendo.2023.1082720

31. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101:1754–61. doi: https://doi.org/10.1210/jc.2015-3754

32. Miyan Z, Waris N. Association of vitamin B12 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: https://doi.org/10.1136/bmjdrc-2019-001151

33. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes–2024. Diabetes Care. 2024;47(Suppl. 1):S158–78. doi: https://doi.org/10.2337/dc24-S009

34. Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes–2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022;65(12):1925–66. doi: https://doi.org/10.1007/s00125-022-05787-2

35. De Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2022;102(5):974–89. doi: https://doi.org/10.1016/j.kint.2022.08.012

36. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int 2022; 102 (5S):S1–27. doi: https://doi.org/10.1016/j.kint.2022.06.008

37. Aaron S, Kumar S, Vijayan J, et al. Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Neurol India. 2005;53:55–8. doi: https://doi.org/10.4103/0028-3886.15057

38. Lachner C, Martin C, John D, et al. Older adult psychiatric inpatients with non-cognitive disorders should be screened for vitamin B12 deficiency. J Nutr Health Aging. 2014;18:209–12. doi: https://doi.org/10.1007/s12603-013-0378-z

39. Jain KK, Malhotra HS, Garg RK, et al. 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;342:162–6. doi: https://doi.org/10.1016/j.jns.2014.05.020

40. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood. 1990;76:871–81

41. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988;318:1720–8

42. Green R, Allen LH, Bjorke-Monsen AL, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;29;3:17040. doi: https://doi.org/10.1038/nrdp.2017.40

43. Sanz-Cuesta T, González-Escobar P, Riesgo-Fuertes R, et al. OB12 Group. Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12). BMC Public Health. 2012;12:394. doi: https://doi.org/10.1186/1471-2458-12-394

44. Wang H, Li L, Qin LL, Song Y, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018;3(3):CD004655. doi: https://doi.org/10.1002/14651858.CD004655.pub3

45. Eussen SJ, De Groot LC, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005;165(10):1167-72. doi: https://doi.org/10.1001/archinte.165.10.1167

46. Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655. doi: https://doi.org/10.1002/14651858.CD004655.pub2

47. Castelli MC, Friedman K, Sherry J, et al. Comparing the efficacy and tolerability of a new daily oral vitamin B12 formulation and intermittent intramuscular vitamin B12 in normalizing low cobalamin levels: a randomized, openlabel, parallel-group study. Clin Ther. 2011;33(3):358–371.e2. doi: https://doi.org/10.1016/j.clinthera.2011.03.003

48. Butler ChC, Vidal-Alaball J, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Family Practice. 2006;23(3):279–285. doi: https://doi.org/10.1093/fampra/cml008

49. Bolieva LZ, Bolotina LV, Galstyan GR, et al. Resolution of the expert council «Vitamin B12 deficiency in clinical practice». Therapy. 2023;9(1):116-121. (In Russ.) doi: https://doi.org/10.18565/therapy.2023.1.116–121