© 2026 Could it be vitamin B12?

A list of medical evidence

Vitamin B12 deficiency is not a hype or alternative theory, it is a well-documented, evidence-based medical condition. Below you will find a curated collection of peer-reviewed literature, clinical case studies, and expert research demonstrating the far-reaching impact of B12 on cellular health, pregnancy, and neurological function.

References, literature, case studies, research:

  1. Wolffenbuttel BHR, McCaddon A, Ahmadi KR, Green R. A Brief Overview of the Diagnosis and Treatment of Cobalamin (B12) Deficiency. Food and Nutrition Bulletin. 2024;45(1_suppl):S40-S49. doi:10.1177/03795721241229500 Wolffenbuttel BH, Owen PJ, Ward M, Green R. Vitamin B12. BMJ. 2023;383:e071725. doi:10.1136/bmj-2022-071725
  2. Honzik T, Adamovicova A, Smolka V, Magner M, Hruba E, Zeman J. Clinical presentation and metabolic consequences in 40 breastfed infants with nutritional vitamin B12 deficiency – What have we learned? Eur Jour Ped Neurol 14 (2010) 488–495Hartmann, HansLücke, Thomas et al. European Journal of Paediatric Neurology, Volume 15, Issue 4, 377
  3. *78 Mills JL, Molloy AM, Reynolds EH. Do the benefits of folic acid fortification outweigh the risk of masking vitamin B12 deficiency? BMJ. 2018 Mar 1;360:k724. doi: 10.1136/bmj.k724. Erratum in: BMJ. 2018 Mar 21;360:k1334. doi: 10.1136/bmj.k1334. PMID: 29496696; PMCID: PMC6889897.
  4. Graydon JS, Claudio K, Baker S, Kocherla M, Ferreira M, Roche-Lima A, Rodríguez-Maldonado J, Duconge J, Ruaño G. Ethnogeographic prevalence and implications of the 677C>T and 1298A>C MTHFR polymorphisms in US primary care populations. Biomark Med. 2019 Jun;13(8):649-661. doi: 10.2217/bmm-2018-0392. Epub 2019 Jun 3. PMID: 31157538; PMCID: PMC6630484.
  5. Saravanan, P., Sukumar, N., Adaikalakoteswari, A. et al. Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study). Diabetologia 64, 2170–2182 (2021). https://doi.org/10.1007/s00125-021-05510-7
  6. Eline Stoutjesdijk Brain-selective nutrients in pregnancy and lactation. RUG 2020,
  7. The vitamin B12 intakes of a substantial proportion of Australian women of reproductive age consuming a vegan diet do not meet the recommended intake, which could adversely affect their health, and, if they are pregnant or lactating, that of their infants too. https://pubmed.ncbi.nlm.nih.gov/33875034/
  8. (UMFA) 2018 study by Wiens et al. in American Journal of Clinical Nutrition found that high maternal UMFA levels during pregnancy were associated with altered DNA methylation patterns in offspring, potentially affecting neurodevelopment (Wiens, D., et al., 2018, American Journal of Clinical Nutrition, 108(6), 1289-1297).
  9. Tucker KL, Rich S, Rosenberg I, et al. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring Study. The American Journal of Clinical Nutrition. February 1, 2000 2000;71(2):514-522.
  10. Sedel F, Baumann N, Turpin JC, Lyon-Caen O, Saudubray JM, Cohen D. Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults. 10.1007/s10545-007-0661-4. J Inher Metab Dis. 2007;30:631-641.
  11. Lai JS, Mohamad Ayob MN, Cai S, et al. Maternal plasma vitamin B12 concentrations during pregnancy and infant cognitive outcomes at 2 years of age. Br J Nutr. Apr 2 2019:1-26. doi:10.1017/S0007114519000746
  12. Malhotra S, Subodh BN, Parakh P, Lahariya S. Brief report: Childhood disintegrative disorder as a likely manifestation of vitamin b12 deficiency. Journal of Autism and Developmental Disorders. 2013;doi:10.1007/s10803-013-1762-6
  13. Monagle PT, Tauro GP. Infantile megaloblastosis secondary to maternal vitamin B12 deficiency. Clinical & Laboratory Haematology. 1997;19(1):23-25. doi:10.1046/j.1365-2257.1997.00205.x

14.   Rasmussen SA, Fernhoff PM, Scanlon KS. Vitamin B<sub>12</sub> deficiency in children and adolescents. The Journal of Pediatrics. 2001;138(1):10-17. doi:10.1067/mpd.2001.112160

  1. Refsum H. Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome. 10.1049/BJN2000302. British Journal of Nutrition. 2001;85(Supplement S2):S109-S113
  2. Sole-Navais P, Cavalle-Busquets P, Fernandez-Ballart JD, Murphy MM. Early pregnancy B vitamin status, one carbon metabolism, pregnancy outcome and child development. Biochimie. Jul 2016;126:91-6. doi:10.1016/j.biochi.2015.12.003
  3. Torsvik I, Ueland PM, Markestad T, Bjørke-Monsen A-L. Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study. The American Journal of Clinical Nutrition. November 1, 2013 2013;98(5):1233-1240. doi:10.3945/ajcn.113.061549
  4. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Primer. 06/29/online 2017;3:17040. doi:10.1038/nrdp.2017.40
  5. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency, Clinical review. Journal Article. 2014-09-04 10:56:04 2014;349doi:10.1136/bmj.g5226
  6. Hannibal L, Lederer A-K, Storz MA, Huber R, Jacobsen DW. Vitamin B12 Status and Supplementation in Plant-Based Diets. Food and Nutrition Bulletin. 2024;45(1_suppl):S58–S66. doi:10.1177/03795721241227233
  7. Osborne D, Sobczyńska-Malefora A. Autoimmune mechanisms in pernicious anaemia & thyroid disease. Autoimmunity Reviews. 9// 2015;14(9):763-768. doi:http://dx.doi.org/10.1016/j.autrev.2015.04.011
  8. Webinar Thyroid and vitamin B12, “partners in crime”. Dr. Bruce Wolffenbuttel.  https://youtu.be/JTbCahQ7YfA?si=ChTisZxaEM3Y1ffi
  9. Stabler SP. Vitamin B12 Deficiency. New England Journal of Medicine. 2013;368(2):149-160. doi:doi:10.1056/NEJMcp1113996
  10. Solomon LR. Vitamin B12-responsive neuropathies: A case series. Nutritional Neuroscience. 2016/04/20 2016;19(4):162-168. doi:10.1179/1476830515Y.0000000006
  11. Solomon LR. Disorders of cobalamin (Vitamin B12) metabolism: Emerging concepts in pathophysiology, diagnosis and treatment. Blood Reviews. 2007;21(3):113-130. doi:http://dx.doi.org/10.1016/j.blre.2006.05.001
  12. Eroglu N, Kandur Y, Kalay S, Kalay Z, Guney O. Neonatal Hyperbilirubinemia in a Turkish Cohort: Association of Vitamin B12. Journal of Clinical Medicine Research. 2015;7(7):556-559. doi:10.14740/jocmr2158w
  13. Gold R, Bogdahn U, Kappos L, et al. Hereditary defect of cobalamin metabolism (homocystinuria and methylmalonic aciduria) of juvenile onset. 10.1136/jnnp.60.1.107. J Neurol Neurosurg Psychiatry. 1996;60:107-108
  14. Huemer M, Kozich V, Rinaldo P, et al. Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines. J Inherit Metab Dis. Mar 12 2015;doi:10.1007/s10545-015-9830-z
  15. Pluvinage JV, Ngo T, Fouassier C, et al. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. Sci Transl Med. Jun 26 2024;16(753):eadl3758. doi:10.1126/scitranslmed.adl3758. Ermens AA, Vlasveld LT, van Marion-Kievit JA, Lensen CJ, Lindemans J. The significance of an elevated cobalamin concentration in the blood. Ned Tijdschr Geneeskd. 2002 Mar 9;146(10):459-64. Dutch. PMID: 11913109.
  16. Armour CM, Brebner A, Watkins D, Geraghty MT, Chan A, Rosenblatt DS. A patient with an inborn error of vitamin B12 metabolism (cblF) detected by newborn screening. Pediatrics. 2013 Jul;132(1):e257-61. doi: 10.1542/peds.2013-0105. Epub 2013 Jun 17. PMID: 23776111.
  17. Huemer M, Kozich V, Rinaldo P, et al. Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines. J Inherit Metab Dis. Mar 12 2015;doi:10.1007/s10545-015-9830-z
  18. MacFarlane AJ, Greene- Finestone LS, Shi Y. Vitamin B- 12 and homocysteine status in a folate- replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr 2011;94:1079–87
  19. The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants https://pubmed.ncbi.nlm.nih.gov/34717141/
  20. Helga Refsum et al, Screening for Serum Total Homocysteine in Newborn Children Clinical Chemistry, Volume 50, Issue 10, 1 October 2004, Pages 1769–1784
  21. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. https://pubmed.ncbi.nlm.nih.gov/10648266/
  22. Molloy AM, Kirke PN, Troendle JF, Burke H, Sutton M, Brody LC, Scott JM, Mills JL. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification. Pediatrics. 2009 Mar;123(3):917-23. doi: 10.1542/peds.2008-1173. PMID: 19255021; PMCID: PMC4161975
  23. Wang, J.; Lv, S.; Chen, G.; Gao, C.; He, J.; Zhong, H.; Xu, Y. Meta-Analysis of the Association between Vitamin D and Autoimmune Thyroid Disease. Nutrients 2015, 7, 2485-2498. https://doi.org/10.3390/nu7042485
  24. Latitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta-analysis https://jnnp.bmj.com/content/90/11/1193.long
  25. The latitude gradient for multiple sclerosis prevalence is established in the early life course. Clive E Sabel , John F Pearson , Deborah F Mason , Ernest Willoughby , David A Abernethy , Bruce V Taylor Author NotesBrain, Volume 144, Issue 7, July 2021, Pages 2038–2046, https://doi.org/10.1093/brain/awab104
  26. Lukina P, Andersen IL, Klaasen RA, Warren DJ, Bolstad N, Mjønes P, Rønne E, Iversen R, Sollid LM, Lundin KEA, Ness-Jensen E. The Prevalence and Rate of Undiagnosed Celiac Disease in an Adult General Population, the Trøndelag Health Study, Norway. Clin Gastroenterol Hepatol. 2024 Jul 8:S1542-3565(24)00602-5. doi: 10.1016/j.cgh.2024.06.027. Epub ahead of print. PMID: 38987013.
  27. Mathey C, Di Marco JN, Poujol A, Cournelle MA, Brevaut V, Livet MO, Chabrol B, Michel G [Failure to thrive and psychomotor regression revealing vitamin B12 deficiency in 3 infants]. Arch Pediatr. 2007 May;14(5):467-71. French. doi: 10.1016/j.arcped.2007.01.014. Epub 2007 Apr 6. PMID: 17412572.
  28. McLeod DSA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine 2012;42:252–65.
  29. Ness- Abramof R, Nabriski DA, Braverman LE, etal. Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease. Am J Med Sci 2006;332:119–22
  30. MacFarlane AJ, Greene- Finestone LS, Shi Y. Vitamin B- 12 and homocysteine status in a folate- replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr 2011;94:1079–87.
  31. Mathey C, Di Marco JN, Poujol A, Cournelle MA, Brevaut V, Livet MO, Chabrol B, Michel G [Failure to thrive and psychomotor regression revealing vitamin B12 deficiency in 3 infants]. Arch Pediatr. 2007 May;14(5):467-71. French. doi: 10.1016/j.arcped.2007.01.014. Epub 2007 Apr 6. PMID: 17412572
  32. https://www.ntvg.nl/system/files/publications/2006104650001a.pdf
  33. Smolka V, Bekárek V, Hlídková E, Bucil J, Mayerová D, Skopková Z, Adam T, Hrubá E, Kozich V, Buriánková L, Saligová J, Buncová M, Zeman J. Metabolické komplikace a neurologické projevy pri deficitu vitaminu B12 u dĕtí vegetariánských matek [Metabolic complications and neurologic manifestations of vitamin B12 deficiency in children of vegetarian mothers]. Cas Lek Cesk. 2001 Nov 22;140(23):732-5. Czech. PMID: 11787236.
  34. Azad C, Jat KR, Kaur J, et al. Vitamin B12 status and neurodevelopmental delay in  Indian infants: a hospital- based cross- sectional study. Paediatr Int Child Health  2020;40:78–84
  35. Goraya JS, Kaur S. Infantile tremor syndrome: A review and critical appraisal of its etiology. J Pediatr Neurosci. 2016 Oct-Dec;11(4):298-304. doi: 10.4103/1817-1745.199475. PMID: 28217150; PMCID: PMC5314841.
  36. Goraya JS, Kaur S, Mehra B. Neurology of Nutritional Vitamin B12 Deficiency in Infants: Case Series From India and Literature Review. J Child Neurol. 2015 Nov;30(13):1831-7. doi: 10.1177/0883073815583688. Epub 2015 May 7. PMID: 25953825
  37. Retardation of myelination due to dietary vitamin B12 deficiency, cranial MRI findings K.-O. Lovblad ( L. Remonda C. Ozdoba • G. Schroth Department of Neuroradiology, University of Bern Pediatr Radio! (1997) 27: 155-158
  38. Refusal_to_eat_solids_growth_failure_and_developmental_regression_in_a_breastfed_infant November 2024 BMJ Case Reports 17(11):e262339 DOI:10.1136/bcr-2024-262339
  39. An Implicit Cause of Prolonged Neonatal Jaundice: Vitamin B12 Deficiency, Erhan Aygun et al.  https://d-nb.info/1283587440/34
  40. Severe vitamin B12 deficiency presenting with hemolytic anemia case study. https://bmjpaedsopen.bmj.com/content/8/Suppl_5/A89.3
  41. Eroglu N, Kandur Y, Kalay S, Kalay Z, Guney O. Neonatal hyperbilirubinemia in a Turkish cohort: association of vitamin B12. J Clin Med Res. 2015 Jul;7(7):556-9. doi: 10.14740/jocmr2158w. Epub 2015 May 8. PMID: 26015822; PMCID: PMC4432899.
  42. Chalouhi C, Faesch S, Anthoine-Milhomme MC, Fulla Y, Dulac O, Chéron G. Neurological consequences of vitamin B12 deficiency and its treatment. Pediatr Emerg Care. 2008 Aug;24(8):538-41. doi: 10.1097/PEC.0b013e318180ff32. PMID: 18708898
  43. Calcaterra V, Montalbano C, Miceli E, Luinetti O, Albertini R, Vinci F, Regalbuto C, Larizza D. Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease. J Endocrinol Invest. 2020 Jan;43(1):81-86. doi: 10.1007/s40618-019-01081-y. Epub 2019 Jul 1. PMID: 31264142.
  44. Muller, A., Drexhage, H., & Berghout, A. (2001). Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocrine Reviews. Retrieved from http://hdl.handle.net/1765/9769
  45. B12 NICE guidelines, maart 2024 https://www.nice.org.uk/guidance/ng239/chapter/recommendations
  46. https://rarediseases.info.nih.gov/diseases/3024/hereditary-intrinsic-factor-deficiency
  47. https://www.discovermagazine.com/the-human-brain-has-been-getting-smaller-since-the-stone-age-11139 Since starting agriculture
  48. Lindenbaum, J., Healton, E. B., Savage, D. G., Brust, J. C. M., Garrett, T. J., Podell, E. R., . . . Allen, R. H. (1988). Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis. New England Journal of Medicine, 318(26), 1720-1728. doi: doi:10.1056/NEJM198806303182604
  49. https://abcd.amsterdamumc.nl/en/results/ More crying babies in mothers with low B12.
  50. https://www.researchgate.net/publication/340020959_Maternal_vitamin_B12_deficiency_in_rats_alters_DNA_methylation_in_metabolically_important_genes_in_their_offspring
  51. Vitamin B12 Deficiency: A Treatable Cause of Developmental Delay In Infancy https://onlinelibrary.wiley.com/doi/10.1111/jpc.12158
  52. Isik et al, 2017 Epileptic Spasms and Partial Seizures Associated with Vitamin B12 Deficiency: Case Report and Literature Review DOI: 10.14744/epilepsi.2016.08760
  53. https://www.theguardian.com/society/2025/jan/01/hospital-admissions-lack-of-vitamins-iron-nhs-
  54. McNeil K, Chowdhury D, Penney L, Rashid M. Vitamin B12 deficiency with intrinsic factor antibodies in an infant with poor growth and developmental delay. Paediatr Child Health. 2014 Feb;19(2):84-6. doi: 10.1093/pch/19.2.84. PMID: 24596481; PMCID: PMC3941681.
  55. Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: Current knowledge and possible mechanisms. Nutr Rev. 2008;66:250–5. doi: 10.1111/j.1753-4887.2008.00031.x.
  56. Korenke GC, Hunneman DH, Eber S, Hanefeld F. Severe encephalopathy with epilepsy in an infant caused by subclinical maternal pernicious anemia: Case report and review of the literature. Eur J Pediatr. 2004;163:196–201. doi: 10.1007/s00431-004-1402-4.
  57. Wagner CL, Hollis BW. The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child. Front Endocrinol (Lausanne). 2018 Aug 31;9:500. https://pmc.ncbi.nlm.nih.gov/articles/PMC6127214/
  58. Hollis BW, Wagner CL, Howard CR, Ebeling M, Shary JR, Smith PG, Taylor SN, Morella K, Lawrence RA, Hulsey TC. Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial. Pediatrics. 2015 Oct;136(4):625-34. doi: 10.1542/peds.2015-1669. Erratum in: Pediatrics. 2019 Jul;144(1):e20191063. doi: 10.1542/peds.2019-1063. PMID: 26416936; PMCID: PMC4586731. https://pubmed.ncbi.nlm.nih.gov/26416936/
  59. Bruce W Hollis, Carol L Wagner, Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant23,The American Journal of Clinical Nutrition,Volume 80, Issue 6,2004,Pages 1752S-1758S,ISSN 0002-9165, https://doi.org/10.1093/ajcn/80.6.1752S.
  60. Mulligan ML, Felton SK, Riek AE, Bernal-Mizrachi C. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol. 2010 May;202(5):429.e1-9. doi: 10.1016/j.ajog.2009.09.002. Epub 2009 Oct 20. PMID: 19846050; PMCID: PMC3540805.
  61. https://myemail.constantcontact.com/Approximately-68–of-Pregnant-Black-Women-have-Vitamin-D-Levels-Below-20-ng-ml.html?soid=1102722411090&aid=gQRe_WqRaIM
September 28, 2026
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