Biochemical Relationship Between Vitamin B12 Status, Homocysteine, and Cognitive Performance in Healthy Adults
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Background: Suboptimal vitamin B12 status may disrupt one-carbon metabolism, increase circulating homocysteine, and adversely affect neurological and cognitive function before overt clinical deficiency becomes apparent. Objective: To compare plasma homocysteine concentrations and cognitive performance across deficient, borderline, and normal vitamin B12 categories among apparently healthy adults. Methods: This cross-sectional analytical study included 180 adults aged 18–60 years from Faisalabad, Pakistan. Demographic, dietary, anthropometric, haematological, biochemical, and cognitive data were collected. Serum vitamin B12, folate, plasma homocysteine, haemoglobin, and total cognitive scores were assessed. Group differences were examined using one-way analysis of variance with Tukey–Kramer pairwise comparisons. Results: Vitamin B12 deficiency was present in 42 participants (23.3%), borderline status in 61 (33.9%), and normal status in 77 (42.8%). Mean homocysteine decreased from 20.8 ± 5.9 µmol/L in the deficient group to 16.4 ± 4.3 µmol/L in the borderline group and 11.9 ± 3.1 µmol/L in the normal group, F(2,177) = 60.33, p < 0.001. Corresponding cognitive scores increased from 23.9 ± 2.8 to 25.4 ± 2.3 and 27.1 ± 2.1, respectively, F(2,177) = 26.48, p < 0.001. Conclusion: Lower vitamin B12 status was associated with higher homocysteine concentrations and lower cognitive scores, with borderline status demonstrating an intermediate pattern. Longitudinal evidence is required before causal or treatment-related conclusions can be made
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1. Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040. doi: 10.1038/nrdp.2017.40.
2. Stabler SP. Clinical practice: vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–160. doi: 10.1056/NEJMcp1113996.
3. Hannibal L, Lysne V, Bjørke-Monsen AL, Behringer S, Grünert SC, Spiekerkoetter U, et al. Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Front Mol Biosci. 2016;3:27. doi: 10.3389/fmolb.2016.00027.
4. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50(1):3–32. doi: 10.1373/clinchem.2003.021634.
5. Fedosov SN, Brito A, Miller JW, Green R, Allen LH. Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points. Clin Chem Lab Med. 2015;53(8):1215–1225. doi: 10.1515/cclm-2014-0818.
6. Obeid R, Heil SG, Verhoeven MMA, van den Heuvel EGHM, de Groot LCPGM, Eussen SJPM. Diagnosis, treatment and long-term management of vitamin B12 deficiency in adults: a Delphi expert consensus. J Clin Med. 2024;13(8):2176. doi: 10.3390/jcm13082176.
7. Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211–239. doi: 10.1146/annurev-nutr-071715-050947.
8. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346(7):476–483. doi: 10.1056/NEJMoa011613.
9. Tangney CC, Tang Y, Evans DA, Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009;72(4):361–367. doi: 10.1212/01.wnl.0000341272.48617.b0.
10. Tangney CC, Aggarwal NT, Li H, Wilson RS, DeCarli C, Evans DA, et al. Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination. Neurology. 2011;77(13):1276–1282. doi: 10.1212/WNL.0b013e3182315a33.
11. Zhang C, Luo J, Yuan C, Ding D. Vitamin B12, B6, or folate and cognitive function in community-dwelling older adults: a systematic review and meta-analysis. J Alzheimers Dis. 2020;77(2):781–794. doi: 10.3233/JAD-200534.
12. Baroni L, Bonetto C, Rizzo G, Bertola C, Caberlotto L, Bazzerla G. Association between cognitive impairment and vitamin B12, folate, and homocysteine status in elderly adults: a retrospective study. J Alzheimers Dis. 2019;70(2):443–453. doi: 10.3233/JAD-190249.
13. Soofi S, Khan GN, Sadiq K, Ariff S, Habib A, Kureishy S, et al. Prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age in Pakistan: analysis of national-level secondary survey data. BMJ Open. 2017;7(12):e018007. doi: 10.1136/bmjopen-2017-018007.
14. Iqbal J, Begum K, Zuberi R, Sajid M, Nausheen S, Chauhadry IA, et al. Determinants of folate and vitamin B12 deficiencies in women of reproductive age: insights from the 2018 National Nutrition Survey of Pakistan. Nutrients. 2026;18(7):1128. doi: 10.3390/nu18071128.
15. Yakub M, Iqbal MP. Association of blood lead and plasma homocysteine: a cross-sectional survey in Karachi, Pakistan. PLoS One. 2010;5(7):e11706. doi: 10.1371/journal.pone.0011706.
16. Iqbal MP, Ishaq M, Kazmi KA, Yousuf FA, Mehboobali N, Ali SA, et al. Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction. Nutr Metab Cardiovasc Dis. 2005;15(2):100–108. doi: 10.1016/j.numecd.2004.05.003.
17. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies. PLoS Med. 2007;4(10):e296. doi: 10.1371/journal.pmed.0040296.
18. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244. doi: 10.1371/journal.pone.0012244.
19. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592–600. doi: 10.1002/gps.2758.
20. Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013;110(23):9523–9528. doi: 10.1073/pnas.1301816110.