Vitamin B12 deficiency and Parkinson’s disease
https://doi.org/10.14412/2074-2711-2023-3-121-127
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disease with various clinical manifestations, its origin not always can be explained only by dopamine deficiency. Long-term treatment with levodopa (especially its intraduodenal administration), as well as clinical manifestations of polyneuropathy, cognitive deficits, postural disorders with freezing of gate, REM sleep behavioral disorders, are more often associated with vitamin B12 deficiency. Several reasons for this association and mechanisms of their development are discussed. Early detection of cobalamin deficiency in PD, especially in patients from high-risk groups, makes it possible to stop this pathological condition timely and prevent irreversible changes. Modern data on the use of high-dose (1000 μ g) oral vitamin B12 are presented, it has comparable clinical efficacy and significant advantages, compared with the parenteral form, in terms of the ease of use and the ability to avoid undesirable postinjection reactions.
Keywords
About the Authors
Z. A. ZalyalovaRussian Federation
Zuleikha Abdullazyanovna Zalyalova
49, Butlerova St., Kazan 420012; 5, Isaeva St., Kazan 420039
Competing Interests:
The conflict of interest has not affected the results of the investigation
E. V. Ekusheva
Russian Federation
91, Volokolamskoe Shosse, Moscow 125371; 85, Pobedy St., Belgorod 308015
Competing Interests:
The conflict of interest has not affected the results of the investigation
References
1. Shenkin A, Roberts N. Vitamins, trace elements, and nutritional assessment. In: Burtis C, Bruns D, editors. Tietz fundamentals of clinical chemistry and molecular diagnostics, 7th ed. Amsterdam: Elsevier; 2015. P. 459-98.
2. Taher J, Naranian T, Poon YY, et al. Vitamins and Infusion of Levodopa-Carbidopa Intestinal Gel. Can J Neurol Sci. 2022 Jan;49(1):19-28. doi: 10.1017/cjn.2021.78
3. Leskova E, Kubikova J, Kovacikova E, et al. Vitamin losses: Retention during heat treatment and continual changes expressed by mathematical models. J Food Compos Anal. 2006;19(4):252-76. doi: 10.1016/j.jfca.2005.04.014
4. Ekusheva EV, Chikh 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). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2021;121(11):17-25. doi: 10.17116/jnevro202112111117 (In Russ.).
5. Sukumar N, Saravanan P. Investigating vitamin B12 deficiency. BMJ. 2019 May 10;365:l1865. doi: 10.1136/bmj.l1865
6. Tisman G, Herbert V. B12 dependence of cell uptake of serum folate: an explanation for high serum folate and cell folate depletion in B12 deficiency. Blood. 1973;41(3):465-9. doi: 10.1182/blood.V41.3.465.465
7. Stabler S. Vitamin B12 deficiency. NEJM. 2013;368:149-60. doi: 10.1056/NEJMcp1113996
8. Roberts B, Taylor A, Sodi R. Vitamins and trace elements. In: Rifai N, Horvath A, Wittwer C, editors. Tietz textbook of clinical chemistry and molecular diagnostics, 6th ed. Missouri, USA: Elsevier; 2018. P. 639-718.
9. Quinlivan EP. In vitamin B12 deficiency, higher serum folate is associated with increased homocysteine and methylmalonic acid concentrations. Proc Natl Acad Sci. 2008 Feb;105(5):E7. doi: 10.1073/pnas.0711541105
10. Healton EB, Healton EB, Savage DG, et al. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore). 1991 Jul;70(4):229-45. doi: 10.1097/00005792-199107000-00001
11. 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 Jun;318(26):1720-8. doi: 10.1056/NEJM198806303182604
12. Boliyeva LZ, Bolotina LV, Galstyan GR, et al. Resolution of the Advisory Board «Deficiency/Deficit of vitamin B12 in clinical practice». Profilakticheskaya meditsina. 2023;26(1):109-13. doi: 10.17116/profmed202326011109 (In Russ.).
13. National Institute for Health and Care Excellence. Active B12 assay for diagnosing vitamin B12 deficiency. 2015. Report No.: Med-tech innovation briefing MIB40. Available from: https://www.jstor.org/stable/26963076
14. Brokner M, Hager HB, Lindberg M. Biological variation of holotranscobalamin and cobalamin in healthy individuals. Scand J Clin Lab Invest. 2017;77:433-6. doi: 10.1080/00365513.2017.1335881
15. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med. 1999 Jun;159(12):1289-98. doi: 10.1001/archinte.159.12.1289
16. Bain BJ, Wickramasinghe SN, Broom GN, et al. Assessment of the value of a competitive protein binding radioassay of folic acid in the detection of folic acid deficiency. J Clin Pathol. 1984 Aug;37(8):888-94. doi: 10.1136/jcp.37.8.888
17. Gazewood JD, Richards DR, Clebak K. Parkinson disease: an update. Am Fam Physician. 2013 Feb;87(4):267-73.
18. Dong B, Wu R. Plasma homocysteine, folate and vitamin B12 levels in Parkinson’s disease in China: A meta-analysis. Clin Neurol Neurosurg. 2020 Jan;188:105587. doi: 10.1016/j.clineuro.2019.105587. Epub 2019 Nov 4.
19. Bostantjopoulou S, Katsarou Z, Frangia T, et al. Endothelial function markers in parkinsonian patients with hyperhomocysteinemia. J Clin Neurosci. 2005 Aug;12(6):669-72. doi: 10.1016/j.jocn.2004.09.012
20. Hu XW, Qin SM, Li D, et al. Elevated homocysteine levels in levodopa-treated idiopathic Parkinson’s disease: a meta-analysis. Acta Neurol Scand. 2013 Aug;128(2):73-82. doi: 10.1111/ane.12106. Epub 2013 Feb 21.
21. Fan X, Zhang L, Li H, et al. Role of homocysteine in the development and progression of Parkinson’s disease. Ann Clin Transl Neurol. 2020 Nov;7(11):2332-8. doi: 10.1002/acn3.51227. Epub 2020 Oct 21.
22. Anamnart C, Kitjarak R. Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson’s disease patients: A randomized controlled study. J Clin Neurosci. 2021 Jun;88:226-31. doi: 10.1016/j.jocn.2021.03.047. Epub 2021 Apr 20.
23. Kim JH, Jin S, Eo H, et al. Two Faces of Catechol-O-Methyltransferase Inhibitor on One-Carbon Metabolism in Parkinson’s Disease: A Meta-Analysis. Nutrients. 2023 Feb 10;15(4):901. doi: 10.3390/nu15040901
24. Lahner E, Persechino S, Annibale B. Micronutrients (other than iron) and Helicobacter pyloriinfection: A systematic review. Helicobacter. 2012 Feb;17(1):1-15. doi: 10.1111/j.1523-5378.2011.00892.x
25. Gravina AG, Priadko K, Ciamarra P, et al. Extra-Gastric Manifestations of Helicobacter pylori Infection. J Clin Med. 2020 Nov;9(12):3887. doi: 10.3390/jcm9123887
26. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pyloriinfection-the Maastricht V/Florence Consensus Report. European Helicobacter and Microbiota Study Group and Consensus panel. Gut. 2017 Jun;66(1):6-30. doi: 10.1136/gutjnl-2016312288
27. Valdes-Socin H, Leclercq P, Polus M, et al. La gastrite chronique auto-immune: une prise en charge multidisciplinaire [Chronic autoimmune gastritis: a multidisciplinary management]. Rev Med Liege. 2019 Nov;74(11):598605 (In French).
28. Fasano A, Bove F, Gabrielli M, et al. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord. 2013 Aug;28(9):1241-9. doi: 10.1002/mds.25522
29. Dardiotis E, Tsouris Z, Mentis AFA, et al. H. pylori and Parkinson’s disease: Metanalyses including clinical severity. Clin Neurol Neurosurg. 2018 Dec;175:16-24. doi: 10.1016/j.clineuro.2018.09.039
30. Miliukhina IV, Ermolenko EI, Ivanova АS, Suvorov АN. Role of gut microbiota in pathogenesis of Parkinson’s disease. Nevrologicheskiy zhurnal = The Neurological Journal. 2017;22(6):280-6. doi: 10.18821/15609545-2017-22-6-280-286 (In Russ.).
31. Dobbs RJ, Charlett A, Purkiss AG, et al. Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism. Acta Neurol Scand. 1999 Jul;100(1):34-41. doi: 10.1111/j.1600-0404.1999.tb00721.x
32. Müller T, Laar Tv, Cornblath DR, et al. Peripheral neuropathy in Parkinson’s disease: Levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord. 2013 May;19(5):501-7. doi: 10.1016/j.parkreldis.2013.02.006
33. Rispoli V, Simioni V, Capone JG, et al. Peripheral neuropathy in 30 duodopa patients with vitamins B supplementation. Acta Neurol Scand. 2017 Dec;136(6):660-7. doi: 10.1111/ane.12783
34. Toth C, Brown MS, Furtado S, et al. Neuropathy as a potential complication of levodopa use in Parkinson’s disease. Mov Disord. 2008 Oct;23(13):1850-9. doi: 10.1002/mds.22137
35. Litvinenko IV, Bobkov AV. Peripheral neuropathy and pain in Parkinson’s disease. Vestnik Rossiyskoy voyenno-meditsinskoy akademii. 2012;1(37):162-6 (In Russ.).
36. Manca D, Cossu G, Murgia D, et al. Reversible encephalopathy and axonal neuropathy in Parkinson’s disease during duodopatherapy. Mov Disord. 2009 Nov;24(15):2293-4. doi: 10.1002/mds.22807
37. Oppo V, Melis M, Melis M, Cossu G. Acute stereotypic behavior: expanding the spectrum of movement disorders attributed to vitamin B12 deficiency. Mov Disord Clin Pract. 2020 Sep;7(Suppl 3):S63-S64. doi: 10.1002/mdc3.13060
38. Merola A, Rosso M, Romagnolo A, et al. Peripheral neuropathy as marker of severe Parkinson’s disease phenotype. Mov Disord. 2017 Aug;32(8):1256-8. doi: 10.1002/mds.27025
39. Loens S, Chorbadzhieva E, Kleimann A, et al. Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy. Brain Behav. 2017 Apr;7(5):e00698. doi: 10.1002/brb3.698
40. Zalyalova ZA. The role of continuous dopaminergic stimulation by the method of intestinal infusion of levodopa/carbidopa (duodopa) gel in the treatment of Parkinson’s disease: from theory to practice. Nevrologicheskiy zhurnal. 2010;(5):52-7 (In Russ.).
41. Jugel C, Ehlen F, Taskin B, et al. Neuropathy in Parkinson’s disease patients with intestinal levodopa infusion versus oral drugs. PLoS One. 2013 Jun;8:e66639. doi: 10.1371/journal.pone.0066639
42. Romagnolo A, Merola A, Artusi CA, et al. Levodopa-induced neuropathy: a systematic review. Mov Disord Clin Pract. 2018 Nov;6(2):96-103. doi: 10.1002/mdc3.12688
43. Toth C, Breithaupt K, Ge S, et al. Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease. Ann Neurol. 2010 Jul;68(1):28-36. doi: 10.1002/ana.22021
44. Blusztajn JK, Wurtman RJ. Choline and cholinergic neurons. Science. 1983 Aug;221(4611):614-20. doi: 10.1126/science.6867732
45. Murray LK, Jadavji NM. The role of onecarbon metabolism and homocysteine in Parkinson’s disease onset, pathology and mechanisms. Nutr Res Rev. 2019 Dec;32(2):218-30. doi: 10.1017/S0954422419000106. Epub 2019 Jul 15.
46. Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. 2013 Sep;5(9):3481-95. doi: 10.3390/nu5093481
47. Compher CW, Kinosian BP, Stoner NE, et al. Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients. JPEN J Parenter Enteral Nutr. 2002 JanFeb;26(1):57-62. doi: 10.1177/014860710202600157
48. Chan A, Tchantchou F, Graves V, et al. Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: critical role of S-adenosyl methionine. J Nutr Health Aging. 2008 Apr;12(4):252-61. doi: 10.1007/BF02982630
49. Bohnen NI, Frey KA, Studenski S, et al. Gait speed in Parkinson disease correlates with cholinergic degeneration. Neurology. 2013 Oct;81(18):1611-6. doi: 10.1212/WNL.0b013e3182a9f558
50. 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, open-label, parallel-group study. Clin Ther. 2011 Mar;33(3):358-71.e2. doi: 10.1016/j.clinthera.2011.03.003
51. 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 Jul;(3):CD004655. doi: 10.1002/14651858.CD004655.pub2
52. Wang H, Li L, Qin LL, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2018 Mar;3(3):CD004655. doi: 10.1002/14651858
Review
For citations:
Zalyalova ZA, Ekusheva EV. Vitamin B12 deficiency and Parkinson’s disease. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2023;15(3):121-127. (In Russ.) https://doi.org/10.14412/2074-2711-2023-3-121-127