Clin Nutr Res.  2019 Jan;8(1):36-45. 10.7762/cnr.2019.8.1.36.

The Effect of Vitamin B12 and Folic Acid Supplementation on Serum Homocysteine, Anemia Status and Quality of Life of Patients with Multiple Sclerosis

• Nozari E
• Ghavamzadeh S
• Razazian N

• KMID: 2444237
• DOI: http://doi.org/10.7762/cnr.2019.8.1.36

Abstract

Plasma homocysteine level and megaloblastic anemia status are two factors that can affect the quality of life of patients with multiple sclerosis (MS). We conducted this study to determine the effect of vitamin B12 and folic acid supplementation on serum homocysteine, megaloblastic anemia status and quality of life of patients with MS. A total of 50 patients with relapsing remitting multiple sclerosis (RRMS) included in this study which divided into 2 groups. The vitamin group received 5 mg folic acid tablet daily and 3 doses of vitamin B12 (1,000 mcg) injection and the other group received placebo and normal saline injection (same doses). The quality of life was measured by using Multiple Sclerosis Quality of Life-54 questionnaire (MSQOL-54). Fully automated fluorescence polarization immunoassay was used to measure serum homocysteine, vitamin B12 and folate. Complete blood count blood test was conducted to determine the anemia status. The mean homocysteine level reduced by 2.49 ± 0.39 µmol/L (p = 0.001), hemoglobin increased from 11.24 ± 1.54 to 13.12 ± 1.05 g/dL (p = 0.001), and mean corpuscular volume decreased from 95.50 ± 6.65 to 89.64 ± 4.24 in the vitamin group (p = 0.001). There was a significant improvement in the mental field of life quality in the placebo group (37.46 ± 19.01 to 50.98 ± 21.64; p = 0.001), whereas both physical and mental fields of quality of life were improved significantly in the vitamin group (40.38 ± 15.07 to 59.21 ± 12.32 and 29.58 ± 15.99 to 51.68 ± 18.22, respectively; p = 0.001). Serum homocysteine level decrease and anemia status improvement with vitamin B12 and folic acid supplementation reveal the potential role of these two vitamins in improving the life quality of MS patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials Identifier: IRCT2015100313678N7

Keyword

Multiple sclerosis; Homocysteine; Anemia; Vitamin B12; Folic acid; Quality of life

MeSH Terms

Anemia*
Anemia, Megaloblastic
Blood Cell Count
Erythrocyte Indices
Fluorescence Polarization Immunoassay
Folic Acid*
Hematologic Tests
Homocysteine*
Humans
Multiple Sclerosis*
Multiple Sclerosis, Relapsing-Remitting
Plasma
Quality of Life*
Vitamin B 12*
Vitamins*
Folic Acid
Homocysteine
Vitamin B 12
Vitamins

Figure

• 

  Figure 1 Repeated measure of homocysteine changes in 2 groups (adjusted for baseline); group code 0: placebo group and group code 1: vitamin group.

Reference

1. Winquist RJ, Kwong A, Ramachandran R, Jain J. The complex etiology of multiple sclerosis. Biochem Pharmacol. 2007; 74:1321–1329.

2. Kingwell E, Bajdik C, Phillips N, Zhu F, Oger J, Hashimoto S, Tremlett H. Cancer risk in multiple sclerosis: findings from British Columbia, Canada. Brain. 2012; 135:2973–2979.

3. Etemadifar M, Sajjadi S, Nasr Z, Firoozeei TS, Abtahi SH, Akbari M, Fereidan-Esfahani M. Epidemiology of multiple sclerosis in Iran: a systematic review. Eur Neurol. 2013; 70:356–363.

4. Sandyk R, Awerbuch GI. Vitamin B12 and its relationship to age of onset of multiple sclerosis. Int J Neurosci. 1993; 71:93–99.

5. Idiman E, Uzunel F, Ozakbas S, Yozbatiran N, Oguz M, Callioglu B, Gokce N, Bahar Z. Cross-cultural adaptation and validation of multiple sclerosis quality of life questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample. J Neurol Sci. 2006; 240:77–80.

6. Holmøy T, Torkildsen Ø, Myhr KM. An update on cladribine for relapsing-remitting multiple sclerosis. Expert Opin Pharmacother. 2017; 18:1627–1635.

7. Morgante L. Hope in multiple sclerosis: a nursing perspective. Int J MS Care. 2000; 2:9–15.

8. Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Qual Life Res. 1995; 4:187–206.

9. Miller DM, Rudick RA, Baier M, Cutter G, Doughtery DS, Weinstock-Guttman B, Mass MK, Fisher E, Simonian N. Factors that predict health-related quality of life in patients with relapsing-remitting multiple sclerosis. Mult Scler. 2003; 9:1–5.

10. Ansari R, Mahta A, Mallack E, Luo JJ. Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol. 2014; 10:281–288.

11. Ashtari F, Abari SS, ShayganNejad V. Serum homocysteine level in patients with multiple sclerosis. J Res Med Sci. 2005; 10:302–304.

12. Moghaddasi M, Mamarabadi M, Mohebi N, Razjouyan H, Aghaei M. Homocysteine, vitamin B12 and folate levels in Iranian patients with multiple sclerosis: a case control study. Clin Neurol Neurosurg. 2013; 115:1802–1805.

13. Ramsaransing GS, Fokkema MR, Teelken A, Arutjunyan AV, Koch M, De Keyser J. Plasma homocysteine levels in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006; 77:189–192.

14. Reynolds EH. Multiple sclerosis and vitamin B12 metabolism. J Neurol Neurosurg Psychiatry. 1992; 55:339–340.

15. Kocer B, Engur S, Ak F, Yilmaz M. Serum vitamin B12, folate, and homocysteine levels and their association with clinical and electrophysiological parameters in multiple sclerosis. J Clin Neurosci. 2009; 16:399–403.

16. Gupta JK, Ingegno AP, Cook AW, Pertschuk LP. Multiple sclerosis and malabsorption. Am J Gastroenterol. 1977; 68:560–565.

17. Zhu Y, He ZY, Liu HN. Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis. J Clin Neurosci. 2011; 18:933–938.

18. Hamilton M, Blackmore S. Chapter 8. Investigation of megaloblastic anaemia-cobalamin, folate, and metabolite status. In : Lewis SM, Bain BJ, Bates I, Dacie JV, editors. Dacie and Lewis Practical Haematology. 10th ed. Philadelphia (PA): Churchill Livingstone Elsevier;2006. p. 161–185.

19. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol. 2005; 58:840–846.

20. Ghaem H, Borhani Haghighi A, Jafari P, Nikseresht AR. Validity and reliability of the Persian version of the multiple sclerosis quality of life questionnaire. Neurol India. 2007; 55:369–375.

21. Sampson EJ. Laboratory procedure manual: total homocysteine in plasma by Abbott IMX [Internet]. cited 2017 March 21. Available from: https://wwwn.cdc.gov/nchs/data/nhanes/2001-2002/labmethods/l06_b_met_homocysteine_imx.pdf.

22. Madani H, Navipoor H, Roozbayani P. Effect of self-care program on the self-esteem of multiple sclerosis patients. ZUMS J. 2002; 10:47–50.

23. Pietro KJ, Jensen AM, Schumacher JR, Anderson JW. Vitamin B12 intake correlated to physical and mental improvements in multiple sclerosis specific quality of life. Int J Adv Nutr Health Sci. 2014; 2:98–108.

24. Zhang M, Han W, Hu S, Xu H. Methylcobalamin: a potential vitamin of pain killer. Neural Plast. 2013; 2013:424651.

25. Sivakumar B, Nair KM, Sreeramulu D, Suryanarayana P, Ravinder P, Shatrugna V, Kumar PA, Raghunath M, Rao VV, Balakrishna N, Kumar PU, Raghuramulu N. Effect of micronutrient supplement on health and nutritional status of schoolchildren: biochemical status. Nutrition. 2006; 22:S15–25.

26. Kira J, Tobimatsu S, Goto I. Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Intern Med. 1994; 33:82–86.

27. Baig SM, Ali Qureshi G. Homocysteine and vitamin B12 in multiple sclerosis. Biog Amines. 1995; 11:479–485.

28. Besler HT, Comoğlu S. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr Neurosci. 2003; 6:189–196.

29. Shidfar F, Homayounfar R, Fereshtehnejad SM, Kalani A. Effect of folate supplementation on serum homocysteine and plasma total antioxidant capacity in hypercholesterolemic adults under lovastatin treatment: a double-blind randomized controlled clinical trial. Arch Med Res. 2009; 40:380–386.

30. Kargiotis O, Paschali A, Messinis L, Papathanasopoulos P. Quality of life in multiple sclerosis: effects of current treatment options. Int Rev Psychiatry. 2010; 22:67–82.

31. Reynolds EH, Bottiglieri T, Laundy M, Crellin RF, Kirker SG. Vitamin B12 metabolism in multiple sclerosis. Arch Neurol. 1992; 49:649–652.

32. Plum CM. Studies in multiple sclerosis. I. Acta Psychiatr Neurol Scand Suppl. 1959; 128:1–94.

33. Crellin RF, Bottiglieri T, Reynolds EH. Multiple sclerosis and macrocytosis. Acta Neurol Scand. 1990; 81:388–391.

34. Najim al-Din AS, Khojali M, Habbosh H, Farah S, Idris AR, al-Muhtasib F. Macrocytosis in multiple sclerosis. A study in 82 de novo Arab patients. J Neurol Neurosurg Psychiatry. 1991; 54:415–416.

35. Deleva NS. Multiple sclerosis associated with anaemic syndrome: a retrospective analysis and literature review. J IMAB. 2012; 18:203–205.

36. van Dijk RA, Rauwerda JA, Steyn M, Twisk JW, Stehouwer CD. Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial. Arterioscler Thromb Vasc Biol. 2001; 21:2072–2079.