• DEWI IRAWATI SOERIA SANTOSO Department of Medical Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • ADITYA K MURTHI Department of Physiology, Faculty of Medicine, Trisakti University, Jakarta, Indonesia
  • SOPHIE YOLANDA Department of Medical Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia,
  • PATWA AMANI Graduate Student in Biomedical Sciences, Department of Physiology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • IMELDA ROSALYN SIANIPAR Department of Medical Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia,


Objective: Cobalamin deficiency may cause a lack of dietary methyl donors, which alter the heart metabolism. Cobalamin deficiency is common in patients with malnutrition, gastric ulcers, diabetes mellitus, and alcoholism. Most studies on cobalamin deficiency are focused on its relationship with oxidative stress and atherogenesis. Therefore, this study aims to find the correlation between cardiomyocyte’s energy metabolism in cobalamin deficiency and the risk of heart abnormalities through analysis of electrocardiography (ECG) patterns.

Methods: Adult male Sprague-Dawley rats (aged 24-28 w) were divided into 2 groups: the control group and cobalamin-deficient group. The control group was given standard diet while the treatment group received a modified diet, type AIN-93M (deficient in cobalamin), for a period of 16 w. ECG was performed in both groups on the last day of the 16-week period. Enzyme-linked immunosorbent assay (ELISA) test was also performed to evaluate plasma Hcy and B12 levels in each group at the end of the treatment period.

Results: At the end of the 16-week period, higher Hcy level and lower plasma B12 level were observed in the treatment group when compared to the control group. ECG patterns showed sinus rhythms in both groups, with a higher QRS amplitude and duration in the treatment group. Two of the seven rats in the treatment group developed cardiac arrhythmia.

Conclusions: Cobalamin deficiency impairs the heart’s energy metabolism with left ventricular enlargement and arrhythmia.

Keywords: Cobalamin deficiency, ECG abnormality, arrhythmia


1. Riset Kesehatan Dasar-Riskesdas. Jakarta: Data and information center of ministry of health, Republic of Indonesia; 2013.
2. Sakota Y, Shimokawa H. Epidemiology of heart failure in Asia. Circ J 2013;77:2209-17.
3. Kenchaiah S, Narula J, Vasan RS. Risk factors for heart failure. Med Clin North Am 2004;88:1145-72.
4. Glier MB, Green TJ, Devlin AM. Methyl nutrients, DNA methylation and cardiovascular disease. Mol Nutr Food Res 2014;58:172-82.
5. Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics; an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 2012;23:853-9.
6. Gueant JL, Fofou MC, Hsu SB, Alberto JM, Freund JN, Dulluc I, et al. Molecular and cellular effect of vitaminn B12 in brain, myocardium and liver through its role as co-factor of methionine synthase. Biochimie 2013;95:1033-40.
7. Garcia MM, Gueant Rodriguez RM, Pooya S, Brachet P, Alberto JM, Jeannesson E, et al. Methyl donors deficiency induce cardiomyopathy through altered methylation/acetylation of PGC-1? by PRMT1 and SIRT1. J Pathol 2011;225:324-35.
8. Solomon LR. Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders associated with increased oxidative stress. Eur J Clin Nutr 2015;69:687-92.
9. Vasan RS, Beiser A, D’Agostino RB, Levy D, Selhub J, Jacques PF, et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. J Am Med Association 2003;289:1251-7.
10. Hermann M, Muller S, Kindermann I, Gunther L, Konig J, Bohm M, et al. Plasma B vitamin and their relation to the severity of chronic heart failure. Am J Clin Nutr 2007;85:117-23.
11. Siddiqua TJ, Allen LH, Raqib R, Ahmed T. Vitamin B12 deficiency in pregnancy and lactation: is there a need for pre and post-natal supplementation? J Nutr Disorder Ther 2014;4:1-8.
12. Andres E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004;171:251-9.
13. Hirschowitz BI, Worthington J, Mohnen J. Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther 2008;27:1110-21.
14. Ko SH, Ahn YB, Song KH, Park YM, Ko SH. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci 2014;29:965-72.
15. Fragasso A, Mannarella C, Ciancio A, Sacco A. Functional vitamin B12 deficiency in alcoholics: an intriguing finding in a retrospective study of megaloblastic anemic patients. Eur J Int Med 2010;21:97-100.
16. Kelly J, Kelleher K. The electrocardiogram in heart failure. Age Ageing 2000;29:203-6.
17. Brower M, Grace M, Kotz CM, Koya V. Comparative analysis of growth characteristics of sprague dawley rats obtained from different sources. Lab Anim Res 2015;31:166-73.
18. Sengupta P. The laboratory rats: relating its age with humans. Int J Prev Med 2013;4:624-30.
19. Bender DA. Special topics: micronutrients, vitamin B12. In: Rodwel VW, Bender DA, Botham KM, Kenelly PJ, Weil PA. editors. Harper’s Illustrated Biochemistry. 30th ed. NewYork: McGraw-Hill; 2016. p. 558-9.
20. Troen AM, Shea Budgell M, Shukitt Hale B, Smith DE, Selhub J, Rosenberg IH. B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice. PNAS 2008;105:12474-9.
21. Werder SF. Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr Dis Treat 2010;6:159-95.
22. Devalia V, Hamilton MS, Malloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol 2014;166:496-513.
23. Scarpa E, Canditto L, Sartori R, Radossi P, Maschio N, Tagariello G. Undetected vitamin B12 deficiency due to false normal assay results. Blood Transfus 2013;11:627-9.
24. Giroux MC, Helie P, Patrick B, Vachon P. Anesthetic and pathological changes following high doses of ketamine and xylazine in sprague dawley rats. Exp Anim 2015;64:253-60.
25. Moshal KS, Camel CK, Kartha GK, Steed MM, Tyagi N, Sen U, et al. Cardiac dys-synchronization and arrythmia in hyperhomocysteinemia. Curr Neurovasc Res 2007;4:289-94.
26. Law P, Kharche S, Stott J, Zhang H. Effects of elevated homocysteine hormone on electrical activity in the human atrium: a simulation study. Conf Proc IEEE Eng Med Biol Soc 2009;2009:3936-9.
27. Postema PG, Wilde A. The measurement of the QT interval. Curr Cardiol Rev 2014;10:287-94.
28. Walker E, Black J, Parris C, Bryda EC, Cansino S, Hunt L, et al. Effect of experimental hyperhomocysteinemia on cardiac structure and function in the rats. Ann Clin Lab Sci 2004;34:175-80.
29. Joseph J, Joseph L, Shekhawat NS, Devi S, Wang J, Kennedy RH, et al. Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive rats. Am J Physiol Heart Circ Physiol 2003;285:679-86.
30. Smith OI, Wisten A, Nylander E, Bratt EL, deWahl GA, Oulhaj A, et al. Electrocardiographic amplitudes: a new risk factor for sudden death in hypertrophic cardiomyopathy. Eur Heart J 2010;31:439-49.
31. Oehler A, Feldman T, Henrikson CA, Tereshchenko LG. QRS-T angle: a review. Ann Noninvasive Electrocardiol 2014;19:534-42.
32. Berleffs CJW, Scherptong RWC, Man SC, Van Welseness GH, Bax JJ, Van Erven L, et al. Predicting ventricular arrhythmias in patients with ischemic heart disease: clinical application of the ECG derived QRS-T angle. Circ Arrhythm Electrophysiol 2009;2:548-54.
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