Electrophysiological profile of serum vitamin B12 levels, correlation with serum methylmalonic acid levels, and determination of subclinical peripheral nerve involvement

Electrophysiological profile and vitamin B12



Vitamin B12, Neuropathy, Cold, Biomarkers


Background/Aim: Vitamin B12 is essential for normal neural conduction in peripheral nerves. This study aimed to investigate the electrophysiological profile for varying degrees of serum B12 levels and to determine whether a correlation existed between electrophysiological profiles and serum methylmalonic acid (MMA) levels. Also, determination of subclinical peripheral nerve involvement with cold administration was planned in serum B12 levels.

Methods: A total of 101 (63 females, 38 males) subjects with known serum vitamin B12 levels were selected randomly from the neurology outpatient clinic for this study. The subjects were divided into three groups based on the serum total Vitamin B12 levels: (1) B12 deficiency (<126 pg/mL), (2) low B12 (126-250 pg/mL), and (3) normal B12 (250–500 pg/mL). Serum MMA and nerve conduction studies (NCS) were assessed and compared between the three groups. After the cooling procedure was applied to the ulnar and sural nerves, NCS was repeated.

Results: There were 13 subjects in the B12 deficiency group, 44 subjects in the low B12 group, and 44 subjects in the normal group. We found that ulnar sensory nerve action potential amplitudes were significantly decreased (P = 0.009), ulnar F latency (P = 0.003; P < 0.001)) was prolonged, and peroneal combined muscle action potential amplitudes decreased (P = 0.026) in the B12 deficiency when compared with the low and normal B12 groups. Sural nerve amplitude and conduction velocities were found to be significantly abnormal after the cold application in all groups (P < 0.001). The increase in sural nerve sensory nerve amplitude potentials (SNAP) amplitudes was higher in the B12 deficiency group than in the other groups. Mean serum MMA levels were high in all groups. A correlation of nerve conduction study (NCS) changes with serum vitamin B12 and MMA was not observed in the groups after cold application.

Conclusion: Vitamin B12 deficiency may cause subclinical sensorial and motor axonal nerve conduction changes. Nerve conduction changes may not always reach pathological values based on electrophysiological studies but may be detected after cooling administration even in the normal serum B12 levels. A correlation between serum MMA and vitamin B12 levels was found. Therefore, serum levels of vitamin B12, which is important for nerve conduction, should be carefully evaluated in clinical practice.


Download data is not yet available.


Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017:29;3:17040. doi: 10.1038/nrdp.2017.40. DOI: https://doi.org/10.1038/nrdp.2017.40

Leishear K, Boudreau RM, Studenski SA, Ferrucci L, Rosano C, de Rekeneire N, et al. Relationship between vitamin B12 and sensory and motor peripheral nerve function in older adults. J Am Geriatr Soc. 2012;60(6):1057-63. DOI: https://doi.org/10.1111/j.1532-5415.2012.03998.x

Hughes CF, McNulty H. Assessing biomarker status of vitamin B12 in the laboratory: no simple solution. Ann Clin Biochem. 2018;55(2):188-9. doi: 10.1177/0004563217747907. DOI: https://doi.org/10.1177/0004563217747907

Hammond N, Wang Y, Dimachkie MM, Barohn RJ. Nutritional neuropathies. Neurol Clin. 2013;31(2):477-89. doi: 10.1016/j.ncl.2013.02.002) DOI: https://doi.org/10.1016/j.ncl.2013.02.002

Kumar N. Neurologic aspects of cobalamin (B12) deficiency. Handb Clin Neurol. 2014;120:915-26. DOI: https://doi.org/10.1016/B978-0-7020-4087-0.00060-7

Calderón-Ospina CA, Nava-Mesa MO. B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther. 2020;26(1):5-13. DOI: https://doi.org/10.1111/cns.13207

Altun I, Kurutaş EB. Vitamin B complex and vitamin B12 levels after peripheral nerve injury. Neural Regen Res. 2016;11(5):842-5. DOI: https://doi.org/10.4103/1673-5374.177150

Puri V, Chaudhry N, Goel S, Gulat P, Nehru R, Chowdhury D. Vitamin B12 deficiency: A clinical and electrophysiological profile. Electromyogr Clin Neurophysiol. 2005;45:273–84.

Rutkove SB. Effects of temperature on neuromuscular electrophysiology. Muscle Nerve. 2001;24(7):867–82. DOI: https://doi.org/10.1002/mus.1084

Benatar M, Wuu J, Peng L. Reference data for commonly used sensory and motor nerve conduction studies. Muscle Nerve. 2009;40(5):772-94. DOI: https://doi.org/10.1002/mus.21490

Moelby L, Rasmussen K, Jensen MK, Pedersen KO. The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid. J Intern Med. 1990;228:373-8. DOI: https://doi.org/10.1111/j.1365-2796.1990.tb00248.x

Franques J, Chiche L, De Paula AM, Grapperon AM, Attarian S, Pouget J, et al. Characteristics of patients with vitamin B12-responsive neuropathy: a case series with systematic repeated electrophysiological assessment. Neurol Res. 2019;41(6):569-76. doi: 10.1080/01616412.2019.1588490. DOI: https://doi.org/10.1080/01616412.2019.1588490

Guo-Tao Y, Hong-Ying Z, Yu K, Ning-Ning S, Ai-Qin D. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis World J Gastroenterol. 2018;24(12):1343-52. DOI: https://doi.org/10.3748/wjg.v24.i12.1343

Kural MA, Karlsson P, Pugdahl K, Isak B, Fuglsang-Frederiksen A, Tankisi H. Diagnostic utility of distal nerve conduction studies and sural near-nerve needle recording in polyneuropathy. Clin Neurophysiol. 2017;128 (9):1590-5. DOI: https://doi.org/10.1016/j.clinph.2017.06.031

Kalita J, Chandra S, Bhoi SK, Agarwal R, Misra UK, Shankar SK. Clinical, nerve conduction and nerve biopsy study in vitamin B12 deficiency neurological syndrome with a short-term follow-up. Nutritional Neuroscience. 2014;17(4):156-63. DOI: https://doi.org/10.1179/1476830513Y.0000000073

Fıne EJ, Sorıa E, Paroskı MW, Petryk D, Thomasula RL. The neurophysiological profile of vitamin BI2 deficiency. Muscle & Nerve. 1990;13(1):158-64. DOI: https://doi.org/10.1002/mus.880130213

Domaç FM, Karlıkaya G, Çetinkaya Y, Gencer M, Tanrıdağ T, Us Ö. Electrodiagnostic Studies in Neurologically Asymptomatic Patients with Vitamin B12 Deficiency. Journal of Neurological Sciences. 2014;31(1):1-10.

Abramson DI, Chu LS, Tuck S Jr, Lee SW, Richardson G, Levin M. Effect of tissue temperatures and blood flow on motor nerve conduction velocity. JAMA. 1996:98(10):1082–8. DOI: https://doi.org/10.1001/jama.198.10.1082

Halar EM, De Lisa JA, Soine TL. Nerve conduction studies in upper extremities: skin temperature corrections. Arch Phys Med Rehab. 1983;64(9):412–6.

Halar EM, DeLisa JA, Brozovich FV. Peroneal nerve conduction velocity: the importance of temperature correction. Arch Phys Med Rehab. 1981;62(9):439–43.

Maetzler W, Klenk J, Becker C, Zscheile J, Gabor KS, Lindemann U. Longitudinal changes of nerve conduction velocity, distal motor latency, compound motor action potential duration, and skin temperature during prolonged exposure to cold in a climate chamber. Int J Neurosci. 2012;122(9):528-31. DOI: https://doi.org/10.3109/00207454.2012.685531

Say B, Ergun U, Turgal E, Yardımcı I. Cold effect in median nerve conductions in clinical carpal tunnel syndrome with normal nerve conduction studies. Journal of Clinical Neuroscience. 2019;61:102–5. DOI: https://doi.org/10.1016/j.jocn.2018.10.133

Zhou Y, Notterpek L. Promoting peripheral myelin repair. Exp Neurol. 2016;283:573-80. DOI: https://doi.org/10.1016/j.expneurol.2016.04.007

Tredici G, Buccellato FR, Braga M, Cavaletti G, Ciscato P, Moggio M, et al. Polyneuropathy due to cobalamin deficiency in the rat. J Neurol Sci. 1998;156:18–29. DOI: https://doi.org/10.1016/S0022-510X(98)00005-7

Carvalho MA, Schwartz MS. Abnormalities in motor conduction in vitamin B12 deficiency. Electromyogr Clin Neurophysiol. 1996;36:275–8.

Harrington DJ. Laboratory assessment of vitamin B12 status. J Clin Pathol. 2017;70:168-73. DOI: https://doi.org/10.1136/jclinpath-2015-203502

Nexo E, Hoffmann-Lücke E. Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility. Am J Clin Nutr. 2011;94(1):359-65. doi: 10.3945/ajcn.111.013458. DOI: https://doi.org/10.3945/ajcn.111.013458

Herrmann W, Obeid R. Utility and limitations of biochemical markers of vitamin B12 deficiency. Eur J Clin Invest. 2013;43(3):231-7. DOI: https://doi.org/10.1111/eci.12034

Matchar DB, Feussner JR, Millington DS. Isotope-dilution assay for urinary methylmalonic acid in the diagnosis of vitamin B12 deficiency. A prospective clinical evaluation. Annals of Internal Medicine. 1987;106(5):707–10. DOI: https://doi.org/10.7326/0003-4819-106-5-707

Sun AL, Ni YH, Li XB, Zhuang XH, Liu YT, Liu XH, et al. Urinary methylmalonic acid as an indicator of early vitamin B12 deficiency and its role in polyneuropathy in type 2 diabetes. J Diabetes Res. 2014;2014:921616. DOI: https://doi.org/10.1155/2014/921616






Research Article

How to Cite

Tunç M, Ergün U, Say B, Badem ND, Yapar D, İlhan MN. Electrophysiological profile of serum vitamin B12 levels, correlation with serum methylmalonic acid levels, and determination of subclinical peripheral nerve involvement: Electrophysiological profile and vitamin B12. J Surg Med [Internet]. 2022 Dec. 6 [cited 2024 Jul. 23];6(12):951-5. Available from: https://jsurgmed.com/article/view/7568