Antiepileptic drugs, hyperhomocysteinemia and B-vitamins supplementation in patients with epilepsy

Epilepsy Research

Volumn 102, Issue 1-2, 2012, Pages 1-7

  Belcastro, Vincenzo ^a   Striano, Pasquale ^b  

^a SANT ANNA HOSPITAL   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

Antiepileptic drugs; B vitamins; Epilepsy; Folic acid; Homocysteine

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ADENINE; ANTICONVULSIVE AGENT; CARBAMAZEPINE; CYANOCOBALAMIN; CYSTEINE; ETIRACETAM; FOLIC ACID; HOMOCYSTINE; LAMOTRIGINE; METHIONINE; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PRIMIDONE; PYRIDOXINE; RIBOFLAVIN; THYMINE; VALPROIC ACID; VITAMIN B GROUP;

AMINO ACID BLOOD LEVEL; AMINO ACID METABOLISM; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; DNA MODIFICATION; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG MEGADOSE; ENDOTHELIAL DYSFUNCTION; ENZYME ACTIVITY; EPILEPSY; FOLIC ACID DEFICIENCY; GENE; GENETIC POLYMORPHISM; GINGIVA OVERGROWTH; HETEROZYGOTE; HUMAN; HYPERHOMOCYSTEINEMIA; MTHFR GENE; NONHUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; REVIEW; THROMBOSIS; VASCULAR ENDOTHELIUM; VITAMIN SUPPLEMENTATION;

ANTICONVULSANTS; EPILEPSY; HOMOCYSTEINE; HUMANS; HYPERHOMOCYSTEINEMIA; VITAMIN B COMPLEX;

EID: 84868302519     PISSN: 09201211     EISSN: 18726844     Source Type: Journal    
DOI: 10.1016/j.eplepsyres.2012.07.003     Document Type: Review

References (77)

1. Apeland T., Mansoor M.A., Strandjord R.E. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res. 2001, 47:27-35.
2. Apeland T., Mansoor M.A., Pentieva K., McNulty H., Seljeflot I., Strandjord R.E. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs. Epilepsy Res. 2002, 51:237-247.
3. Arya R., Gulati S., Kabra M., Sahu J.K., Kalra V. Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children. Neurology 2011, 76:1338-1343.
4. Attilakos A., Papakonstantinou E., Schulpis K., Voudris K., Katsarou E., Mastroyianni, et al. Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res. 2006, 71:229-232.
5. Baldelli E., Leo G., Andreoli N., Kjell Fuxe K., Biagini G., Agnati L. Homocysteine potentiates seizures and cell loss induced by pilocarpine treatment. Neuromolecular Med. 2010, 12:248-259.
6. Belcastro V., Striano P. Vascular risk in epilepsy patients: is antiepileptic treatment the key?. Pharmacoepidemiol. Drug Saf. 2012, 21:231.
7. Belcastro V., Gorgone G., Italiano D., Oteri G., Caccamo D., Pisani L.R., et al. Antiepileptic drugs and MTHFR polymorphisms influence hyperhomocysteinemia recurrence in epileptic patients. Epilepsia 2007, 48:1990-1994.
8. Belcastro V., Striano P., Caccamo D., Costa C., Pisani L.R., Trombetta C.J., et al. Hyperhomocysteinemia and retinal vascular changes in patients with epilepsy. Epilepsy Res. 2008, 81:86-89.
9. Belcastro V., Striano P., Ciampa C., Pierguidi L., Napoli M., Freno M.C., et al. Is retinal assessment useful in epileptic patients with hyperhomocysteinemia?. Eye 2009, 23:1532-1534.
10. Belcastro V., Striano P., Gorgone G., Costa C., Ciampa C., Caccamo D., et al. Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs. Epilepsia 2010, 51:274-279.
11. Bochyńska A., Lipczyńska-Łojkowska W., Gugała-Iwaniuk M., Lechowicz W., Restel M., Graban A., et al. The effect of vitamin B supplementation on homocysteinemetabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid. Seizure 2012, 21:276-281.
12. Bønaa K.H., Njølstad I., Ueland P.M., Schirmer H., Tverdal A., Steigen T., et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N. Engl. J. Med. 2006, 354:1578-1588.
13. Caccamo D., Condello S., Gorgone G., Crisafulli G., Belcastro V., Gennaro S., et al. Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia. Neuromolecular Med. 2004, 6:117-126.
14. Cahill M.T., Stinnett S.S., Fekrat S. Meta-analysis of plasma homocysteine, serum folate, serum vitamin B12, and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease. Am. J. Ophthalmol. 2003, 136:1136-1150.
15. Chango A., Boisson F., Barbe F., Quilliot D., Droesch S., Pifster M., et al. The effect of 677CT and 1298AC mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br. J. Nutr. 2000, 83:593-596.
16. Chuang Y.C., Chuang H.Y., Lin T.K., Chang C.C., Lu C.H., Chang W.N., et al. Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis. Epilepsia 2012, 53:120-128.
17. Cleary P., Shorvon S., Tallis R. Late-onset seizures as a predictor of subsequent stroke. Lancet 2004, 10:1184-1186.
18. Cockerell O.C., Johnson A.L., Sander J.W., Hart Y.M., Goodridge D.M., Shorvon S.D. Mortality from epilepsy: results from a prospective population-based study. Lancet 1994, 344:918-921.
19. Coppola G., Ingrosso D., Operto F.F., Signoriello G., Lattanzio F., Barone E., et al. Role of folic acid depletion on homocysteine serum level in children and adolescents with epilepsy and different MTHFR C677T genotypes. Seizure 2012, 21:340-343.
20. Czeizel A.E. Folic acid and the prevention of neural-tube defects. N. Engl. J. Med. 2004, 350:2209-2211.
21. Durga J., van Boxtel P.J., Schouten E.G., Kok F.J., Jolles J., Katan M.B., et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomized, double blind, controlled trial. Lancet 2007, 369:208-216.
22. Elliott J.O., Jacobson M.P., Haneef Z. Cardiovascular risk factors and homocysteine in epilepsy. Epilepsy Res. 2007, 76:113-123.
23. Erdemir A., Cullu N., Yis U., Demircioĝlu F., Kir M., Cakmakçi H., et al. Evaluation of serum lipids and carotid artery intima media thickness in epileptic children treated with valproic acid. Brain Dev. 2009, 31:713-716.
24. Folbergrová J., Lisý V., Haugvicová R., Stastný F. Specific [3H]glutamate binding in the cerebral cortex and hippocampus of rats during development: effect of homocysteine-induced seizures. Neurochem. Res. 1997, 22:637-646.
25. Gidal B.E., Tamura T., Hammer A., Vuong A. Blood homocysteine, folate and vitamin B-12 concentrations in patients with epilepsy receiving lamotrigine or sodium valproate for initial monotherapy. Epilepsy Res. 2005, 64:161-166.
26. Gorgone G., Caccamo D., Pisani L.R., Currò M., Parisi G., Oteri G., et al. Hyperhomocysteinemia in patients with epilepsy: does it play a role in the pathogenesis of brain atrophy? A preliminary report. Epilepsia 2009, 50:33-36.
27. Guéant-Rodriguez R.M., Spada R., Moreno-Garcia M., Anello G., Bosco P., Lagrost L., et al. Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an ambulatory elderly population. Atherosclerosis 2011, 214:480-485.
28. Guttormsen A.B., Ueland P.M., Kruger W.D., Kim C.E., Ose L., Følling I., et al. Disposition of homocysteine in subjects heterozygous for homocystinuria due to cystathionine beta-synthase deficiency: relationship between genotype and phenotype. Am. J. Med. Genet. 2001, 100:204-213.
29. Hamed S.A., Nabeshima T. The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins. J. Pharm. Sci. 2005, 98:340-353.
30. Hamed S.A., Hamed E.A., Hamdy R., Nabeshima T. Vascular risk factors and oxidative stress as independent predictors of asymptomatic atherosclerosis in adult patients with epilepsy. Epilepsy Res. 2007, 74:183-192.
31. Hankey G.J., Eikelboom J.W. Homocysteine and vascular disease. Lancet 1999, 354:407-413.
32. Hankey G.J., Eikelboom J.W. Homocysteine and stroke. Curr. Opin. Neurol. 2001, 14:95-102.
33. Harden C.L., Pennell P.B., Koppel B.S., Hovinga C.A., Gidal B., Meador K.J., et al. Management issues for women with epilepsy - focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2009, 50:1247-1255.
34. Hirsch A.T., Haskal Z.J., Hertzer N.R., Bakal C.W., Creager M.A., Halperin J.L., et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation 2006, 113:463-654.
35. Holmes M.V., Newcombe P., Hubacek J.A., Sofat R., Ricketts S.L., Cooper J., et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 2011, 378:584-594.
36. Huemer M., Ausserer B., Graninger G., Hubmann M., Huemer C., Schlachter K., et al. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Epilepsia 2005, 46:1677-1683.
37. Ientile R., Curro' M., Ferlazzo N., Condello S., Caccamo D., Pisani F. Front Biosci. (Schol Ed) 2010, 2:359-372.
38. Institute of Medicine Folate. Dietary Reference Intakes for Thiamine, Riboflavin Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline 1998, Institute of Medicine, Food and Nutrition Board; National Academic Press, Washington, DC.
39. Kaneko S., Otani K., Fukushima Y., Ogawa Y., Nomura Y., Ono T., et al. Teratogenicity of antiepileptic drugs: analysis of possible risk factors. Epilepsia 1988, 29:459-467.
40. Karabiber H., Sonmezgoz E., Ozerol E., Yakinci C., Otlu B., Yologlu S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev. 2003, 25:113-115.
41. Kelly G.S. Folates: supplemental forms and therapeutic applications. Altern. Med. Rev. 1998, 3:208-220.
42. Khandanpour N., Loke Y.K., Meyer F.J., et al. Homocysteine and peripheral arterial disease: systematic review and meta-analysis. Eur. J. Vasc. Endovasc. Surg. 2009, 38:316-322.
43. Kishi T., Fujita N., Eguchi T., Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J. Neurol. Sci. 1997, 145:109-112.
44. Kwan P., Brodie M.J. Early identification of refractory epilepsy. N. Engl. J. Med. 2000, 342:314-319.
45. Linnebank M., Moskau S., Semmler A., et al. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann. Neurol. 2011, 69:352-359.
46. Linnebank M., Moskau S., Semmler A, et al. Antiepileptic drugs and vitamin B6 plasma levels in adult patients. Epilepsy Res. 2012, (March).
47. Lonn E., Yusuf S., Arnold M.J., Sheridan P., Pogue J., Micks M., et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N. Engl. J. Med. 2006, 354:1567-1577.
48. Mansoor M.A., Kristensen O., Hervig T., Bates C.J., Pentieva K., Vefring H., et al. Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate. Scand. J. Clin. Lab. Invest. 1999, 59:139-146.
49. Mattson M.P., Shea T.B. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003, 26:137-146.
50. Mintzer S., Skidmore C.T., Abidin C.J., Morales M.C., Chervoneva I., Capuzzi D.M., et al. Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein. Ann. Neurol. 2009, 65:448-456.
51. Mintzer S., Skidmore C.T., Sperling M.R. B-Vitamin deficiency in patients treated with antiepileptic drugs. Epilepsy & Behav. 2012, 24:341-344.
52. Mitchell P., Wang J.J., Wong T.Y., Smith W., Klein R., Leeder S.R. Retinal microvascular signs and risk of stroke and stroke mortality. Neurology 2005, 65:1005-1009.
53. Morrell M.J. Folic acid and epilepsy. Epilepsy Curr. 2002, 2:31-34.
54. Morrow J.I., Hunt S.J., Russell A.J., Smithson W.H., Parsons L., Robertson I., et al. Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register. J. Neurol. Neurosurg. Psychiatry 2009, 80:506-511.
55. Nilsson K., Gustafson L., Hulteberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int. J. Geriatr. Psychiatry 2001, 16:609-614.
56. Ogawa Y., Kaneko S., Otani K., Fukushima Y. Serum folic acid levels in epileptic mothers and their relationship to congenital malformations. Epilepsy Res. 1991, 8:75-78.
57. Osganian S., Stampfer M.J., Spiegelman D., Rimm E., Cutler J.A., Feldman H.A., et al. Distribution of and factors associated with serum homocysteine levels in children: child and adolescent trial for cardiovascular health. JAMA 1999, 281:1189-1196.
58. Oz O., Gökçil Z., Bek S., Cakir E., Odabasi Z. Is asymmetric dimethylarginine responsible for the vascular events in patients under antiepileptic drug treatment?. Epilepsy Res. 2009, 87:54-58.
59. Ozdemir O., Yakut A., Dinleyici E.C., Aydogdu S.D., Yarar C., Colak O. Serum asymmetric dimethylarginine (ADMA), homocysteine, vitamin B(12), folate levels, and lipid profiles in epileptic children treated with valproic acid. Eur. J. Pediatr. 2011, 170:873-877.
60. Perla-Kajàn J., Twardowski T., Jakubowski H. Mechanisms of homocysteine toxicity in humans. Amino Acids 2007, 32:561-572.
61. Polak J.F., Pencina M.J., Pencina K.M., O'Donnell C.J., Wolf P.A., D'Agostino R.B. Carotid-wall intima-media thickness and cardiovascular events. N. Engl. J. Med. 2011, 365:213-221.
62. Reynolds E.H. Mental effects of anticonvulsants, and folic acid metabolism. Brain 1968, 91:197-214.
63. Reynolds E.H. Anticonvulsants, folic acid and epilepsy. Lancet 1973, 1:1376-1378.
64. Reynolds E.H. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006, 5:949-960.
65. Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb. Haemost. 1997, 78:523-526.
66. Sauer J., Mason J.B., Choi S.W. Too much folate: a risk factor for cancer and cardiovascular disease?. Curr. Opin. Clin. Nutr. Metab. Care 2009, 12:30-36.
67. Schwaninger M., Ringleb P., Winter R., Kohl B., Fiehn W., Rieser P.A., et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999, 40:345-350.
68. SEARCH Collaborative Group, 2010. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 303, 2486-2494.
69. Sniezawska A., Dorszewska J., Rozycka A., et al. MTHFR, MTR, and MTHFD1 gene polymorphisms compared to homocysteine and asymmetric dimethylarginine concentrations and their metabolites in epileptic patients treated with antiepileptic drugs. Seizure 2011, 20:533-540.
70. Soleimani A., Usefzadeh M., Mianehsaz E., et al. Comparison of oral folic acid and folinic acid on blood homocysteine level of patients on hemodialysis. Iran J. Kidney Dis. 2011, 5:45-49.
71. Spence J.D. Homocysteine-lowering therapy: a role in stroke prevention?. Lancet Neurol. 2007, 6:830-838.
72. Tsai M.Y., Garg U., Key N.S., Hanson N.Q., Suh A., Schwichtenberg K. Molecular and biochemical approaches in the identification of heterozygotes for homocystinuria. Atherosclerosis 1996, 132:69-77.
73. Vallance P. Importance of asymmetric dimethylarginine in cardiovascular risk. Lancet 2001, 358:2096-2097.
74. Verrotti A., Pascarella R., Trotta D., Giuva T., Morgese G., Chiarelli F. Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Epilepsy Res. 2000, 41:253-257.
75. Weisberg I., Tran P., Christensen B., Sibani S., Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol. Genet. Metab. 1998, 64:169-172.
76. Weisberg I.S., Jacques P.F., Selhub J., Bostom A.G., Chen Z., Curtis Ellison R., et al. The 1298A3C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine. Atherosclerosis 2001, 156:409-415.
77. Wolff T., Witkop C.T., Miller T., Syed S.B. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann. Intern. Med. 2009, 150:632-639.