Basic and clinical role of vitamins in epilepsy

Zalkhani, Raha; Moazedi, AhmadAli

Volume 6, Issue 2 (April 2020) Journal of Research in Applied and Basic Medical Sciences 2020, 6(2): 104-114 | Back to browse issues page

Mendeley

Zotero

RefWorks

Zalkhani R, Moazedi A. Basic and clinical role of vitamins in epilepsy. Journal of Research in Applied and Basic Medical Sciences 2020; 6 (2) :104-114
URL: http://ijrabms.umsu.ac.ir/article-1-106-en.html

Basic and clinical role of vitamins in epilepsy

Raha Zalkhani ^*

, AhmadAli Moazedi

Department of biology,Farhangian university.Tehran, Iran , rahazalkhani@gmail.com

Abstract: (4729 Views)

Background & Aims: Epilepsy is a brain disorder which affects about 50 million people worldwide. Good diet is an essential measure to controlling seizure attacks. Since some combination therapy can reduce epileptogenesis, therefore this review summarizes the available evidences about the application of vitamins in animal models and humans for understanding what specific combinations of antiepileptic drugs and vitamins are likely to be effective for epilepsy therapy.
Material and methods: In this review, electronic databases including PubMed and Google Scholar were searched for monotherapy and polytherapy by vitamins.
Results: Administration of vit A inhibits development of seizures and lethality in animal models. Also vitamins B1, B6 and B12 pre-treatment might lead to a protective effect against degenerative cellular in mice. In addition use of low dose of sodium valproate with vitamins C or E increase the anticonvulsant activity of the drug in mice. Moreover, Vitamin D enhances antiepileptic effects of lamotrigine, phenytoin and valproate in animal's models. Vitamin E has an anticonvulsant effect in ferrous chloride seizures, hyperbaric oxygen seizures as well as penicillin-induced seizures in contrast kindling, maximal electroshock and kainite models. Some researches demonstrated that vitamins D and B as adjunctive therapy in epileptic patient can relieve seizures. A clinical data have shown beneficial effects of vitamin E in raising total antioxidant capacity, catalase, and glutathione in patients with uncontrolled epilepsy. Only few clinical studies exist to support the efficacy of the vitamin A and K in epilepsy.
Conclusion: However vitamin therapy is not a substitute for antiepileptic drugs but add on therapy by them may relieve drugs- induced deficiencies as well as more researches are needed to evaluate the effectiveness of vitamins in epileptic humans.

Keywords: Vitamins, Antiepileptic drugs, Epilepsy

Full-Text [PDF 332 kb] (3523 Downloads)

Type of Study: review article | Subject: Special

References

1. Sirven JI. Epilepsy: a spectrum disorder. Cold Spring Harb Perspect Med 2015; 5(9):a022848. [DOI:10.1101/cshperspect.a022848] [PMID] [PMCID]

2. Alexopoulos AV. Pharmacoresistant epilepsy: Definition and explanation. Epileptology 2013; 1(1):38-42. [DOI:10.1016/j.epilep.2013.01.001]

3. Ramos-Lizana J, Rodriguez-Lucenilla MI, Aguilera-López P, Aguirre-Rodríguez J, Cassinello-García E. A study of drug-resistant childhood epilepsy testing the new ILAE criteria. Seizure 2012; 21(4):266-72. [DOI:10.1016/j.seizure.2012.01.009] [PMID]

4. Puttachary S, Sharma S, Stark S, Thippeswamy T. Seizure-induced oxidative stress in temporal lobe epilepsy. BioMed Res Int 2015; 745613. [DOI:10.1155/2015/745613] [PMID] [PMCID]

5. Singh A, Kukreti R, Saso L, & Kukreti, S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules 2019; 24(8): 1583. [DOI:10.3390/molecules24081583] [PMID] [PMCID]

6. Martinc, B, Grabnar, I, & Vovk, T. Antioxidants as a preventive treatment for epileptic process: a review of the current status. Curr. Neuropharmacol 2014; 12(6): 527-50. [DOI:10.2174/1570159X12666140923205715] [PMID] [PMCID]

7. Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromenty B. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol 2011; 54(4): 773-94. [DOI:10.1016/j.jhep.2010.11.006] [PMID]

8. Xavier SM, Barbosa CO, Barros DO, Silva RF, Oliveira AA, Freitas RM. Vitamin C antioxidant effects in hippocampus of adult Wistar rats after seizures and status epilepticus induced by pilocarpine. Neurosci Lett 2007; 420(1): 76-9. [DOI:10.1016/j.neulet.2007.04.056] [PMID]

9. St L, Erik K, Rosenfeld W. E, Bramley T. Antiepileptic drug monotherapy: the initial approach in epilepsy management. Curr Neuropharmacol 2009; 7(2):77-82. [DOI:10.2174/157015909788848866] [PMID] [PMCID]

10. Zalkhani R, Najafzadehvarzi H, Moazedi AA. The Effect of Acute and Chronic Sesame Oil Consumption on the Strychnine Induced Seizure in Adult Rats. J Ardebil Univ Med Sci 2019; 18(4):470-478. [DOI:10.29252/jarums.18.4.470]

11. Zalkhani R, Moazedi AA, Ghotbeddin Z, Pourmahdi Borujeni, M. Therapeutic Effects of Sodium Valproate Combined With Low Frequency Electrical Stimulations On Seizure Severity and Behaviors During CA1 Hippocampal Kindling in Adult Male Rat. Basic and Clinical Neuroscience (BCN) 2019 (In press). [DOI:10.32598/bcn.9.10.280] [PMID] [PMCID]

12. Zalkhani R, Moazedi1AA, Najafzadehvarzi H, Investigation the effect of sodium valproate in the presence of vitamin C and E on seizure induced by strychnine in adult rat. J Sabzevar Univ Med Sci 2018;26(2):195-201. [Address]

13. Soltani D, Pour MG, Tafakhori A, Sarraf P, Bitarafan S. Nutritional Aspects of Treatment in Epileptic Patients. Iran J Child Neurol. 2016; 10(3): 1. [Pub Med]

14. Asif M. Role of various Vitamins in the patients with epilepsy. IJPR, 2013; 3(1): 1-9. [DOI:10.5667/tang.2013.0020]

15. Sayyah M, Yousefi-Pour M, Narenjkar J. Anti-epileptogenic effect of β-carotene and vitamin A in pentylenetetrazole-kindling model of epilepsy in mice. Epilepsy Res. 2005; 63(1): 11-16. [DOI:10.1016/j.eplepsyres.2004.10.001] [PMID]

16. Trumbo P, Yates AA, Schlicker S, Poos M. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J. Acad. Nutr. Diet. 2001;101(3);294. [Pub Med]

17. Etchamendy N, Enderlin V, Marighetto A, Pallet V, Higueret P, Jaffard R. (2003). Vitamin A deficiency and relational memory deficit in adult mice: relationships with changes in brain retinoid signalling. Behav. Brain Res. 2003; 145(1-2): 37-49. [DOI:10.1016/S0166-4328(03)00099-8]

18. Malik MA, Blusztajn JK, Greenwood CE. Nutrients as trophic factors in neurons and the central nervous system: role of retinoic acid. J. Nutr. Biochem. 2000; 11(1): 2-13. [DOI:10.1016/S0955-2863(99)00066-2]

19. Etchamendy N, Enderlin V, Marighetto A, Vouimba RM, Pallet V, Jaffard R, Higueret P. Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling. J. Neurosci 2001; 21(16): 64239. [DOI:10.1523/JNEUROSCI.21-16-06423.2001] [PMID] [PMCID]

20. Divers TJ, Blackmon DM, Martin CL, Worrell DE. Blindness and convulsions associated with vitamin A deficiency in feedlot steers. J Am Vet Med 1986; 189(12): 1579-82. [Pub Med]

21. Chiang MY, Misner D, Kempermann G, Schikorski T, Giguère V, Sucov HM, Evans, RM. An essential role for retinoid receptors RARβ and RXRγ in long-term potentiation and depression. Neuron 1998; 21(6): 1353-61. [DOI:10.1016/S0896-6273(00)80654-6]

22. Carlen PL, Skinner F, Zhang L, Naus C, Kushnir M, Velazquez JLP.The role of gap junctions in seizures. Brain Res Rev 2000; 32(1): 235-41. [DOI:10.1016/S0165-0173(99)00084-3]

23. Velazquez JLP, Carlen PL. Gap junctions, synchrony and seizures. Trends in neurosci 2000; 23(2): 68-74. [DOI:10.1016/S0166-2236(99)01497-6]

24. Gajda, Z, Gyengési E, Hermesz E, Ali KS, Szente M. Involvement of gap junctions in the manifestation and control of the duration of seizures in rats in vivo. Epilepsia 2003; 44(12): 1596-600. [DOI:10.1111/j.0013-9580.2003.25803.x] [PMID]

25. Chawla J, Kvarnberg D. Hydrosoluble vitamins. In Handbook of clinical neurology. Elsevier. 2014. pp. 891-914. [DOI:10.1016/B978-0-7020-4087-0.00059-0] [PMID]

26. Rabie T, Mühlhofer W, Bruckner T, Schwab A, Bauer AT, Zimmermann M, et al. Transient protective effect of B-vitamins in experimental epilepsy in the mouse brain. J Mol Neurosci 2010; 41(1): 74-9. [DOI:10.1007/s12031-009-9286-4] [PMID]

27. Scalabrino G. The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central nervous system: Lessons learned from its deficiency. Prog neurobiol 2009; 88(3): 203-20. [DOI:10.1016/j.pneurobio.2009.04.004] [PMID]

28. Keyser A, De Bruijn S. Epileptic Manifestations and Vitamin B1Deficiency. Eur Neurol 1991; 31(3): 121-5. [DOI:10.1159/000116660] [PMID]

29. Trovero F, Gobbi M, Weil-Fuggaza J, Besson MJ, Brochet D, Pirot S. Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain. Neurosci Lett 2000; 292(1): 49-53. [DOI:10.1016/S0304-3940(00)01420-8]

30. Kannan K, Jain SK. Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and lipid peroxidation in H2O2-treated U937 monocytes. Free Radic Biol Med 2004; 36(4): 423-8. [DOI:10.1016/j.freeradbiomed.2003.09.012] [PMID]

31. Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M. (2006). Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6. Seizure 2006; 15(2): 79-85. [DOI:10.1016/j.seizure.2005.11.002] [PMID]

32. Tamura T, Aiso K, Johnston KE, Black L, Faught E. Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy. Epilepsy res. 2000; 40(1): 7-15. [DOI:10.1016/S0920-1211(00)00101-7]

33. Perna AF, Ingrosso D, Lombardi C, Acanfora F, Satta E, Cesare CM, et al. Possible mechanisms of homocysteine toxicity. Kidney Int 2003; 63: S137-S140. [DOI:10.1046/j.1523-1755.63.s84.33.x] [PMID]

34. Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci 1997; 94(11): 5923-8. [DOI:10.1073/pnas.94.11.5923] [PMID] [PMCID]

35. Marangos PJ, Loftus T, Wiesner J, Lowe T, Rossi E, Browne CE, et al. Adenosinergic modulation of homocysteine‐induced seizures in mice. Epilepsia 1990; 31(3): 239-46. [DOI:10.1111/j.1528-1157.1990.tb05371.x] [PMID]

36. Vezzani A. Inflammation and epilepsy. Epilepsy Curr 2005; 5(1): 1-6. [DOI:10.1111/j.1535-7597.2005.05101.x] [PMID] [PMCID]

37. Ha J, Choi J, Kwon A, Kim K, Kim SJ, Bae SH, et al. Interleukin-4 and tumor necrosis factor-alpha levels in children with febrile seizures. Seizure 2018; 58: 156-62. [DOI:10.1016/j.seizure.2018.04.004] [PMID]

38. Miller JW. Vitamin B (12) deficiency, tumor necrosis factor-(alpha), and epidermal growth factor: A novel function for Vitamin B (12)? Nutr Rev 2002; 60(5): 142. [DOI:10.1301/00296640260093805] [PMID]

39. Patel DC, Wallis G, Dahle EJ, McElroy PB, Thomson KE, Tesi RJ, et al. Hippocampal TNFα signaling contributes to seizure generation in an infection-induced mouse model of limbic epilepsy. Eneuro 2017; 4(2). [DOI:10.1523/ENEURO.0105-17.2017] [PMID] [PMCID]

40. Zhou T, Wang N, Xu L, Huang H, Yu C, Zhou H. Effects of carbamazepine combined with vitamin B12 on levels of plasma homocysteine, hs-CRP and TNF-α in patients with epilepsy. Exp Ther Med 2018; 15(3): 2327-32. [DOI:10.3892/etm.2018.5698]

41. Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 2012; 1826(2): 443-457. [DOI:10.1016/j.bbcan.2012.06.003] [PMID] [PMCID]

42. Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med 2011; 51(5): 1000-13. [DOI:10.1016/j.freeradbiomed.2011.05.017] [PMID] [PMCID]

43. Berger MM. Vitamin C requirements in parenteral nutrition. Gastroenterology 2009; 137(5): S70-S78. [DOI:10.1053/j.gastro.2009.08.012] [PMID]

44. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J 2011; 437(3): 357-72. [DOI:10.1042/BJ20110326] [PMID] [PMCID]

45. Hart A, Cota A, Makhdom A, Harvey E.J. The role of vitamin C in orthopedic trauma and bone health. Am J Orthop 2015; 44: 306-11. [Pub Med]

46. Waly MI, Al-Attabi Z, Guizani N. Low nourishment of vitamin C induces glutathione depletion and oxidative stress in healthy young adults. Prev Nutr Food Sci 2015; 20(3): 198. [DOI:10.3746/pnf.2015.20.3.198] [PMID] [PMCID]

47. Sawicka-Glazer E, Czuczwar SJ. Vitamin C: a new auxiliary treatment of epilepsy? Pharmacol Rep 2014; 66(4): 529-33. [DOI:10.1016/j.pharep.2014.02.016] [PMID]

48. Kocot J, Luchowska-Kocot D, Kiełczykowska M, Musik I, Kurzepa J. Does vitamin C influence neurodegenerative diseases and psychiatric disorders? Nutrients 2017; 9(7): 659. [DOI:10.3390/nu9070659] [PMID] [PMCID]

49. Martinc B, Grabnar I, Vovk T. Antioxidants as a preventive treatment for epileptic process: a review of the current status. Curr. Neuropharmacol 2014; 12(6):527-50. [DOI:10.2174/1570159X12666140923205715] [PMID] [PMCID]

50. Yamamoto N, Kabuto H, Matsumoto S, Ogawa N, Yokoi I. α-tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy. Pathophysiology 2002; 8(3): 205-14. [DOI:10.1016/S0928-4680(02)00009-3]

51. Ayyildiz M, Coskun S, Yildirim M, Agar E. The effects of ascorbic acid on penicillin‐induced epileptiform activity in rats. Epilepsia 2007; 48(7): 1388-95. [DOI:10.1111/j.1528-1167.2007.01080.x] [PMID]

52. González-Ramírez M, Razo-Juárez LI, Sauer-Ramírez JL, González-Trujano ME, Salgado-Ceballos H, Orozco-Suarez S. Anticonvulsive effect of vitamin C on pentylenetetrazol-induced seizures in immature rats. Pharmacol Biochem Behav 2010; 97(2): 267-72. [DOI:10.1016/j.pbb.2010.08.009] [PMID]

53. Alhassan AW, Mohammed DK, Saleh MA, Mshelia PP, Yarube IU, Lawan I. Combined effect of sodium valproate and ascorbic acid on pentylenetetrazole-induced seizures in mice. Bayero J Pure and Appl Sci 2017; 10(1): 47-50. [DOI:10.4314/bajopas.v10i1.6]

54. Covarrubias-Pinto A, Acuña A, Beltrán F, Torres-Díaz L, Castro M. Old things new view: ascorbic acid protects the brain in neurodegenerative disorders. Int J Mol Sci 2015; 16(12): 28194-217. [DOI:10.3390/ijms161226095] [PMID] [PMCID]

55. Santos I.S, Tome AR, Saldanha GB, Ferreira PP, Militão GG, De Freitas RM. Oxidative stress in the hippocampus during experimental seizures can be ameliorated with the antioxidant ascorbic acid. Oxidative med. Cell longev 2009; 2(4): 214-21. [DOI:10.4161/oxim.2.4.8876] [PMID] [PMCID]

56. Sawicka-Glazer E, Czuczwar SJ.Vitamin C: a new auxiliary treatment of epilepsy? Pharmacol Rep 2014; 66(4): 529-533. [DOI:10.1016/j.pharep.2014.02.016] [PMID]

57. Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach Jhet al. Role of oxidative stress in epileptic seizures. Neurochem Int 2011;59(2): 122-37. [DOI:10.1016/j.neuint.2011.03.025] [PMID] [PMCID]

58. Ullah I, Badshah H, Naseer MI, Lee HY, Kim MO. Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABA B1 receptor in adult rats cortex and hippocampus. Neuromolecular Med 2015; 17(1): 35-46. [DOI:10.1007/s12017-014-8337-3] [PMID]

59. Domith I, Socodato R, Portugal CC, Munis AF, Duarte‐Silva AT, Paes‐de‐Carvalho R.Vitamin C modulates glutamate transport and NMDA receptor function in the retina. J Neurochem 2018; 144(4): 408-20. [DOI:10.1111/jnc.14260] [PMID]

60. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Kovacs CS. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011; 96(1): 53-8. [DOI:10.1210/jc.2010-2704] [PMID] [PMCID]

61. Hii C, Ferrante A. The non-genomic actions of vitamin D. Nutrients2016; 8(3): 135. [DOI:10.3390/nu8030135] [PMID] [PMCID]

62. Wrzosek M, Lukaszkiewicz J, Wrzosek M, Jakubczyk A, Matsumoto H, Piątkiewicz P, et al. Vitamin D and the central nervous system. Pharmacological reports 2013; 65(2): 271-278. [DOI:10.1016/S1734-1140(13)71003-X]

63. Wacker M, Holick M. Vitamin D effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 2013; 5(1): 111-48. [DOI:10.3390/nu5010111] [PMID] [PMCID]

64. Koduah P, Paul F, Doerr JM. Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases. EPMA J 2017; 8(4): 313-25. [DOI:10.1007/s13167-017-0120-8] [PMID] [PMCID]

65. Hollo A, Clemens Z, Kamondi A, Lakatos P, Szucs A. Correction of vitamin D deficiency improves seizure control in epilepsy: a pilot study. Epilepsy & Behavior 2012; 24(1): 131-3. [DOI:10.1016/j.yebeh.2012.03.011] [PMID]

66. Siegel A, Malkowitz L, Moskovits MJ, Christakos S. Administration of 1, 25-dihydroxyvitamin D3 results in the elevation of hippocampal seizure threshold levels in rats. Brain Res 1984; 298(1): 125-9. [DOI:10.1016/0006-8993(84)91153-3]

67. Kalueff AV, Minasyan A, Keisala T, Kuuslahti M, Miettinen S, Tuohimaa P. Increased severity of chemically induced seizures in mice with partially deleted Vitamin D receptor gene. Neuroscience letters 2006; 394(1): 69-73. [DOI:10.1016/j.neulet.2005.10.007] [PMID]

68. Janjoppi L, Katayama MH, Scorza FA, Folgueira M.K, Brentani M, Pansani AP, et al. Expression of vitamin D receptor mRNA in the hippocampal formation of rats submitted to a model of temporal lobe epilepsy induced by pilocarpine. Brain Res Bulletin 2008; 76(5): 480-4. [DOI:10.1016/j.brainresbull.2008.01.002] [PMID]

69. Abdel-Wahab AF, Afify MA, Mahfouz AM, Shahzad N, Bamagous GA, Al Ghamdi S. Vitamin D enhances antiepileptic and cognitive effects of lamotrigine in pentylenetetrazole-kindled rats. Brain Res 2017; 1673: 78-85. [DOI:10.1016/j.brainres.2017.08.011] [PMID]

70. Borowicz K, Morawska M, Furmanek-Karwowska K, Luszczki J, Czuczwar SJ. Cholecalciferol enhances the anticonvulsant effect of conventional antiepileptic drugs in the mouse model of maximal electroshock. Eur J Pharmacol 2007; 573(1-3): 111-5. [DOI:10.1016/j.ejphar.2007.07.002] [PMID]

71. Mardones P, Rigotti A. Cellular mechanisms of vitamin E uptake: relevance in α-tocopherol metabolism and potential implications for disease. J Nutr Biochem 2004; 15(5): 252-60. [DOI:10.1016/j.jnutbio.2004.02.006] [PMID]

72. Mehvari J, Motlagh FG, Najafi M, Ghazvini M.A, Naeini AA, Zare M. Effects of Vitamin E on seizure frequency, electroencephalogram findings, and oxidative stress status of refractory epileptic patients. Adv Biomed Res 2016; 5. [DOI:10.4103/2277-9175.178780] [PMID] [PMCID]

73. Ogunmekan AO, Hwang PA. A Randomized, Double‐Blind, Placebo‐Controlled, Clinical Trial of D‐α‐Tocopheryl Acetate (Vitamin E), as Add‐On Therapy, for Epilepsy in Children. Epilepsia 1989; 30(1): 84-9. [DOI:10.1111/j.1528-1157.1989.tb05287.x] [PMID]

74. Barros DO, Xavier SL, Barbosa CO, Silva RF, Freitas RM, Maia FD, Takahashi RN. Effects of the vitamin E in catalase activities in hippocampus after status epilepticus induced by pilocarpine in wistar rats. Neuroscience letters 2007; 416(3): 227-30. [DOI:10.1016/j.neulet.2007.01.057] [PMID]

75. Kaya M, Cimen V, Kalayci R, Kucuk M, Gurses C, Arican N, Elmas, I. Catalase andα-tocopherol attenuate blood-brain barrier breakdown in pentylenetetrazole-induced epileptic seizures in acute hyperglycaemic rats. Pharmacol Res 2002; 45(2): 129-33. [DOI:10.1006/phrs.2001.0915] [PMID]

76. Levy SL, Burnham WM, Hwang PA. An evaluation of the anticonvulsant effects of vitamin E. Epilepsy Res 1990; 6(1): 12-7. [DOI:10.1016/0920-1211(90)90003-E]

77. Jerrett SA, Jefferson D, Mengel CE. Seizures, H 2 O 2 formation and lipid peroxides in brain during exposure to oxygen under high pressure. Aerospace Med 1973; 44(1): 40-4. [Pub Med]

78. Kryzhanovskii GN, Nikushkin EV, Braslavskii VE, Glebov RN. Lipid peroxidation in a focus of hyperactivity in the rat cerebral cortex. Bulletin of Experimental Biology and Medicine 1980; 89(1): 16-9. [DOI:10.1007/BF00835488]

79. Jain SK, McVie R, Jaramillo J, Palmer M, Smith T. Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients. J American College Nutr 1996; 15(5): 458-61. [DOI:10.1080/07315724.1996.10718624] [PMID]

80. Khosroshahi HT, Asl BH, Habibzadeh A, Chaichi P, Ghanbarpour A, Badie AH. Comparison of vitamin e and L-carnitine, separately or in combination in patients with intradialytic complications. Nephro-urology monthly 2013; 5(4): 862. [DOI:10.5812/numonthly.10670] [PMID] [PMCID]

81. Singh U, Otvos J, Dasgupta A, De Lemos JA, Devaraj S, Jialal I. High-dose α-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy. Clinical Chem 2007; 53(3): 525-8. [DOI:10.1373/clinchem.2006.078865] [PMID]

82. Li J, Lin J, Wang H, Peterson JW, Furie BC, Furie B, et al. Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. J Neuroscience 2003; 23(13): 5816-26. [DOI:10.1523/JNEUROSCI.23-13-05816.2003] [PMCID]

83. Sundaram KS, Fan JH, Engelke JA, Foley AL, Suttie JW, Lev M. Vitamin K status influences brain sulfatide metabolism in young mice and rats. J Nutr 1996; 126(11): 2746-51. [Pub Med]

84. Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. AM Medi 1980; 68(1): 122-40. [DOI:10.1016/0002-9343(80)90181-3]

85. Rahn J, Bestman JE, Josey BJ, Inks ES, Stackley KD, Rogers CE, et al. Novel vitamin K analogs suppress seizures in zebrafish and mouse models of epilepsy. Neuroscience 2014; 259: 142-54. [DOI:10.1016/j.neuroscience.2013.11.040] [PMID] [PMCID]

86. Sudha K, Rao A, Rao A. Oxidative stress and antioxidants in epilepsy. Clinica Chimica Acta 2001; 303(1-2): 19-24. [DOI:10.1016/S0009-8981(00)00337-5]

87. Veinbergs I, Mallory M, Sagara Y, Masliah E. Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoproteinE‐deficient mice. Eur J Neuroscience 2000; 12(12): 4541-6. https://doi.org/10.1046/j.1460-9568.2000.01308.x [DOI:10.1111/j.1460-9568.2000.01308.x]

88. Linnebank M, Moskau S, Semmler A, Widman G, Stoffel‐Wagner B, Weller M, Elger C. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Annals Neurol 2011; 69(2): 352-9. [DOI:10.1002/ana.22229] [PMID]

89. Afshar M, Moallem SA, Baharara J, Takjo T, Golalipour MJ. Preventive effect of vitamin B6 on developmental toxicity of carbamazepine in mice. Iran J Basic Med Sci 2011; 14(2): 99-106. [ResearchGate]

90. Krause KH, Bonjour JP, Berlit P, Kochen W. Biotin status of epileptics. Annals New York Academy Sci 1985; 297-313. [DOI:10.1111/j.1749-6632.1985.tb18447.x] [PMID]

91. Schwaninger M, Ringleb P, Winter R, Kohl B, Fiehn W, Rieser PA, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999; 40(3): 345-50. [DOI:10.1111/j.1528-1157.1999.tb00716.x] [PMID]

92. Teagarden DL, Meador KJ, Loring DW. Low vitamin D levels are common in patients with epilepsy. Epilepsy Res 2014; 108(8): 1352-6. [DOI:10.1016/j.eplepsyres.2014.06.008] [PMID] [PMCID]

93. Lee RH, Lyles KW, Colón-Emeric C. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am J Geriatric Pharmacotherapy 2010; 8(1): 34-46. [DOI:10.1016/j.amjopharm.2010.02.003] [PMID] [PMCID]

94. Shellhaas RA, Barks AK, Joshi SM. Prevalence and risk factors for vitamin D insufficiency among children with epilepsy. Pediatric Neurol 2010; 42(6): 422-6. [DOI:10.1016/j.pediatrneurol.2010.03.004] [PMID] [PMCID]

95. Garg A, Dabla S, Nagenhalli S, Fotedar S. Levetiracetam monotherapy effect on serum calcium and serum vitamin D in patient of epilepsy. International Journal of Research in Medical Sciences Garg A et al. Int J Res Med Sci 2017; 5(2): 503-8. [DOI:10.18203/2320-6012.ijrms20170140]

96. Baek JH, Seo YH, Kim GH, Kim MK, Eun BL. Vitamin D levels in children and adolescents with antiepileptic drug treatment. Yonsei Med J 2014; 55(2): 417-21. [DOI:10.3349/ymj.2014.55.2.417] [PMID] [PMCID]

97. Zhou H, Wang N, Xu L, Huang HL, Yu C. Clinical study on anti-epileptic drug with B vitamins for the treatment of epilepsy after stroke. Eur Rev Med Pharmacol Sci 2017; 21(14): 3327-31. [Pub Med]

98. Shaikh AS, Guo X, Li Y, Cao L, Liu X, Li P, et al.The Impact of Antiepileptic Drugs on Vitamin Levels in Epileptic Patients. Curr Pharm Biotechnol 2018; 19(8): 674-81. [DOI:10.2174/1389201019666180816104716] [PMID]

99. Nabzdyk CS, Bittner EA.Vitamin C in the critically ill-indications and controversies. World J Critical Care Med 2018; 7(5): 52. [DOI:10.5492/wjccm.v7.i5.52] [PMID] [PMCID]

100. Harijan P, Khan A, Hussain N.Vitamin D deficiency in children with epilepsy: Do we need to detect and treat it? J Pediatric Neurosciences 2013; 8(1): 5. [DOI:10.4103/1817-1745.111413] [PMID] [PMCID]

101. Mintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia 2006; 47(3): 510-5. [DOI:10.1111/j.1528-1167.2006.00460.x] [PMID]

102. Xiao F, Chen D, Lu Y, Xiao Z, Guan LF, Yuan J, et al. Proteomic analysis of cerebrospinal fluid from patients with idiopathic temporal lobe epilepsy. Brain Res 2009; 1255: 180-9. [DOI:10.1016/j.brainres.2008.12.008] [PMID]

103. Christiansen C, Rodbro P, Sjo O. Anticonvulsant action of vitamin D in epileptic patients? A controlled pilot study. Br Med J 1974; 2(5913): 258-9. [DOI:10.1136/bmj.2.5913.258] [PMID] [PMCID]

104. Aycicek A, Iscan A.The effects of carbamazepine, valproic acid and phenobarbital on the oxidative and antioxidative balance in epileptic children. Eur Neurol 2007; 57(2): 65-9. [DOI:10.1159/000098053] [PMID]

105. Rezvani M, Koren G. Does vitamin K prophylaxis prevent bleeding in neonates exposed to enzyme-inducing antiepileptic drugs in utero? Can Fam Physician 2006; 52(6): 721-2. [Pub Med]

106. Clarkson PM, James AG. Parenteral vitamin K1: the effective prophylaxis against haemorrhagic disease for all newborn infants. N Z Med J 1990; 103(885): 95. [Pub Med]

107. Kazmin A, Wong RC, Sermer M, Koren G. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: an update. Can Fam Physician 2010; 56(12): 1291-2. [Pub Med]

108. Steinweg DL, Bentley ML. Seizures following reduction in phenytoin level after orally administered folic acid. Neurology 2005; 64(11): 1982. [DOI:10.1212/01.WNL.0000163997.67472.C5] [PMID]

109. Gaby AR. Natural approaches to epilepsy. Alternative medicine review 2007; 12(1): 9. [Pub Med]

110. Mattson RH, Gallagher BB, Reynolds EH, Glass D. Folate therapy in epilepsy: a controlled study. Arch Neurol 1973; 29(2): 78-81. [DOI:10.1001/archneur.1973.00490260022002] [PMID]

111. Ohare J, Odriscoll D, Duggan B, Callaghan N. (1979). Increase in seizure frequency following folic-acid. Irish Med J 1979; 72(6): 241-2.

112. Hansson O, Hagberg B. Effect of pyridoxine treatment in children with epilepsy. Acta Societatis Botanicorum Poloniae 1968; 73: 35-43. [Google Scholar]

113. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. The Lancet 1976; 307(7953): 256. [DOI:10.1016/S0140-6736(76)91385-4]