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Role of certain nutritional supplements and biological regulators in the epilepsy

  • Received : 2013.07.21
  • Accepted : 2013.10.28
  • Published : 2013.11.30

Abstract

Certain dietary contents, biological supplements might influence the occurrence or treatment of epilepsy. Some studies have found that the supplementation with individual nutrients reduced seizure frequency or improved other aspects of health in patients with epilepsy. Potentially beneficial dietary interventions include treating blood glucose dysregulations. Identifying and avoiding allergenic foods, and avoiding suspected triggering agents such as alcohol, aspartame, and monosodium glutamate. The Atkins diet (very low in carbohydrates) is a less restrictive type diet that may be effective in some cases. Nutrients that may reduce seizure frequency include vitamin B6, magnesium, vitamin E, manganese, taurine, dimethylglycine, and omega-3 fatty acids. Administration of thiamine may improve cognitive function in patients with epilepsy. Supplementation with folic acid, vitamin B6, biotin, vitamin D, and L-carnitine may be needed to prevent or treat deficiencies resulting from the use of anticonvulsant drugs. Vitamin K1 has been recommended near the end of pregnancy for women taking anticonvulsants. Melatonin may reduce seizure frequency in some cases, and progesterone may be useful for women with cyclic exacerbations of seizures. In most cases, nutritional therapy is not a substitute for anticonvulsant medications. However, in selected cases, depending on the effectiveness of the interventions, dosage reductions or discontinuation of medications may be possible. However, nutrient supplementation may be necessary to prevent or reverse the effects of certain deficiencies that frequently result from the use of antiepileptic drugs.

Keywords

References

  1. AfZal S, Kalra G, Kazmi SH, Siddiqui MA. A study of serum and cerebrospinal fluid magnesium in convulsive disorders. J Assoc Physicians. 1985;33:161-163.
  2. Anderson GD. Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs. Neurology.2004;63:S3-S8.
  3. Asadi-Pooya AA, Ghafari A. Do patients with epilepsy believe they need specific dietary restrictions? Epilepsy Behav, 2004;5:945-948. https://doi.org/10.1016/j.yebeh.2004.08.010
  4. Asadi-Pooya AA, Ghetmiri E. Allergy and idiopathic generalized epilepsy: a case-control study. J Pediatr Neurol. 2007;5:231-232.
  5. Asadi-Pooya AA, Ghetmiri E. Folic acid supplementation reduces the development of some blood cell abnormalities in children receiving carbamazepine. Epilepsy Behav. 2006;8:228-231. https://doi.org/10.1016/j.yebeh.2005.10.002
  6. Asadi-Pooya AA, Hossein-Zade A. What do nurses and physicians think about the need for specific dietary restrictions in the patients with epilepsy? Epilepsy Behav. 2005;6:604-606. https://doi.org/10.1016/j.yebeh.2005.02.013
  7. Asadi-Pooya AA, Mintzer S, Sperling MR. Nutritional supplements, foods, and epilepsy Is there a relationship? Epilepsia. 2008;49:1819-1827. https://doi.org/10.1111/j.1528-1167.2008.01678.x
  8. Asadi-Pooya AA, Sperling MR. Do foods precipitate seizures? A cross-cultural comparison. Epilepsy Behav. 2007;11:450-453. https://doi.org/10.1016/j.yebeh.2007.07.004
  9. Asadi-Pooya AA. Risk factors for carbamazepine-induced leucopenia in children and adolescents. J Pediatr Neurol. 2005;3:233-235.
  10. Auer RN. Can eliminating monosodium glutamate from the diet affect Lennox-Gastaut syndrome? J Am Diet Assoc. 1998;98:857.
  11. Bankier A, Turner M, Hopkins IJ. Pyridoxine dependent selzures-a wider clinical spectrum. Arch Dis Child. 1983;58:415-418. https://doi.org/10.1136/adc.58.6.415
  12. Barbeau A, Donaldson J. Zinc, taurine, and epilepsy. Arch Neurol. 1974;30:52-58. https://doi.org/10.1001/archneur.1974.00490310054009
  13. Bennett CL, Huynh HM, Chance PF, Glass lA, Gospe SM Jr. Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures. Neurogenetics. 2005;6:143-149. https://doi.org/10.1007/s10048-005-0221-8
  14. Bergamini L, Mutani R, Delsedime M, Durelli L. First clinical experience on the antiepileptic action of taurine. Eur Neurol. 1974;11:261-269. https://doi.org/10.1159/000114324
  15. Berry-Kravis E, Booth G, Taylor A, Valentino LA. Bruising and the ketogenic diet: evidence for dietinduced changes in platelet function. Ann Neurol. 2001;49:98-103. https://doi.org/10.1002/1531-8249(200101)49:1<98::AID-ANA13>3.0.CO;2-2
  16. Bhagavan HN, Coursin DB, Stewart CN. Monosodium glutamate induces convulsive disorders in rats. Nature. 1971;232:275-276. https://doi.org/10.1038/232275a0
  17. Bonilha L, Li LM. Heavy coffee drinking and epilepsy. Seizure. 2004;13:284-285. https://doi.org/10.1016/S1059-1311(03)00079-7
  18. Borges LF, Gucer G. Effect of magnesium on epileptic foci. Epilepsia. 1978;19:81-91.
  19. Botez MI, Botez T, Ross-Chouinard A, Lalonde R. Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale. Epilepsy Res. 1993;16:157-163. https://doi.org/10.1016/0920-1211(93)90030-B
  20. Brown RS, Di Stanislao PT, Beaver WT, Bottomley WK. The administration of folic acid to institutionalized epileptic adults with phenytoininduced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study. Oral Surg Oral Med Oral Pathol. 1991;71:565-568. https://doi.org/10.1016/0030-4220(91)90363-H
  21. Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF. Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study. Neurology. 1992;42:1000-1003. https://doi.org/10.1212/WNL.42.5.1000
  22. Carl GF, Keen CL, Gallagher BB, Clegg MS, Littleton WH, Flannery DB, Hurley LS. Association of low blood manganese concentrations with epilepsy. Neurology. 1986;36:1584-1587. https://doi.org/10.1212/WNL.36.12.1584
  23. Castaneda GY, Heilbroner PL, Shah N, Forem S, Fish I. Asthma and epilepsy: are they related? A retrospective study. J Child Neurol. 1988;13:283-285.
  24. Ch'ien LT, Krurndieck CL, Scott CW Jr, Butterworth CE Jr. Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug-treated epileptics. Am J Clin Nutr. 1975;28:51-58.
  25. Chou DT, Forde JH, Hirsh KR. Unit activity in medial thalamus: comparative effects of caffeine an amphetamine. J Pharmacol Exp Ther. 1980;213:580-585.
  26. Christiansen C, Rodbro P, Lund M. Incidence of anticonvulsant osteomalacia and effect of vitamin D: controlled therapeutic trial. Br Med J. 1973;4:695-701. https://doi.org/10.1136/bmj.4.5894.695
  27. Christiansen C, Rodbro P, Sjo O. "Anticonvulsant action" of vitamin D in epileptic patients? A controlled pilot study. Br Med J. 1974;2:258-259. https://doi.org/10.1136/bmj.2.5913.258
  28. Clarke TA, Saunders BS, Feldman B. Pyridoxine-dependent seizures requiring high doses of pyridoxine for control. Am J Dis Child. 1979;133:963-965.
  29. Coker SB. Postneonatal vitamin B6-dependent epilepsy. Pediatrics. 1992;90:221-223.
  30. Cornelissen M, Steegers-Theunissen R, Kollee L, Eskes T, Motohara K, Monnens L. Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. Am J Obstet Gynecol. 1993;168:884-888. https://doi.org/10.1016/S0002-9378(12)90839-X
  31. Crayton JW, Stone T, Stein G. Epilepsy precipitated by food sensitivity: report of a case with double-blind placebo-controlled assessment. Clin Electroencephalogr. 1981 ;12: 192-198. https://doi.org/10.1177/155005948101200405
  32. Cronin CC, Jackson LM, Feighery C, Shanahan F, Abuzakouk M, Ryder DQ, Whelton M, Callaghan N. Celiac disease and epilepsy. QJM. 1998;91:303-308. https://doi.org/10.1093/qjmed/91.4.303
  33. Crowell GF, Roach ES. Pyridoxine-dependent seizures. Am Fam Physician. 1983;27:183-187.
  34. Cunningham AS. Allergy, immunodeficiency, and epilepsy. Lancet 1975;2:975.
  35. Davis RE, Reed PA, Smith BK. Serum pyridoxal, folate, and vitamin B12 levels in institutionalized epileptics. Epilepsia. 1975;16:463-468. https://doi.org/10.1111/j.1528-1157.1975.tb06074.x
  36. De Lecea A, Ribes-Koninckx C, Polanco I, Calvete JF. Serological screening for non-overt coeliac disease in children of short stature. Acta Paediatr Suppl. 1996;412:54-55.
  37. De Vivo DC, Bohan TP, Coulter DL, Dreifuss FE, Greenwood RS, Nordli DR Jr, Shields WD, Stafstrom CE, Tein I. L-canrntine supplementation in childhood epilepsy: current perspectives. Epilepsia. 1998;39:1216-1225. https://doi.org/10.1111/j.1528-1157.1998.tb01315.x
  38. Deb S, Cowie VA, Richens A. Folate metabolism and problem behaviour in mentally handicapped epileptics. J Ment Defic Res. 1987;31:163-168.
  39. Djukic A. Folate-responsive neurologic diseases. Pediatr Neurol. 2007;37:387-397. https://doi.org/10.1016/j.pediatrneurol.2007.09.001
  40. Dupont CL, Tanaka Y. Blood manganese levels in children with convulsive disorder. Biochem Med. 1985;33:246-255. https://doi.org/10.1016/0006-2944(85)90033-X
  41. Edelstein SF, Chisholm M. Management of intractable childhood seizures using the non-MCT oil ketogenic diet in 20 patients. J Am Diet Assoc. 1996;96:1181-1182. https://doi.org/10.1016/S0002-8223(96)00304-5
  42. Egger J, Carter CM, Soothill JF, Wilson J. Oligoantigenic diet treatment of children with epilepsy and migraine. J Pediatr. 1989;114:51-58. https://doi.org/10.1016/S0022-3476(89)80600-6
  43. Frediani T, Lucarelli S, Pelliccia A, Vagnucci B, Cerminara C, Barbato M, Cardi E. Allergy and childhood epilepsy: a close relationship? Acta Neurol Scand. 2001;104:349-352. https://doi.org/10.1034/j.1600-0404.2001.00347.x
  44. Freed WJ. Prevention of strychnine-induced seizures and death by the N-methylated glycine derivatives betaine, dimethylglycine and sarcosine. Pharmacol Biochem Behav. 1985;22:641-643. https://doi.org/10.1016/0091-3057(85)90288-6
  45. Furlanut M, Benetello P, Avogaro A, Dainese R. Effects of folic acid on phenytoin kinetics in healthy subjects. Clin Pharmacol Ther 1978;24:294-297. https://doi.org/10.1002/cpt1978243294
  46. Gaby AR. Natural Approaches to Epilepsy. Altern Med Rev. 2007;12:9-24.
  47. Gaby AR. Magnesium. (New Canaan, USA: Keats Publishing), 1994.
  48. Gaby AR. The Doctor's Guide to Vitamin B6. (Emmaus, USA: Rodale Press), 1984.
  49. Gallagher BB, Prichard JW, Glaser GH. Seizure threshold and excess dietary amino acids. Neurology. 1968;18:208-212. https://doi.org/10.1212/WNL.18.3.208
  50. Garg SK, Kumar N, Bhargava VK, Prabhakar SK. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther 1998;64:286-288. https://doi.org/10.1016/S0009-9236(98)90177-1
  51. Gasch AT. Use of the traditional ketogenic diet for treatment of intractable epilepsy. J Am Diet Assoc. 1990;90:1433-1434.
  52. Gascon G, Patterson E, Yearwood K, Slotnick H. N,N dimethylglycine and epilepsy. Epilepsia. 1989;30:90-93. https://doi.org/10.1111/j.1528-1157.1989.tb05288.x
  53. Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol. 1981;19:57-60. https://doi.org/10.1007/BF00558385
  54. Gissel T, Poulsen CS, Vestergaard P. Adverse effects of antiepileptic drugs on bone mineral density in children. Expert Opin Drug Saf 2007;6:267-278. https://doi.org/10.1517/14740338.6.3.267
  55. Goasduff T, Dreano Y, Guillois B, Menez JF, Berthou F. Induction of liver and kidney CYP1A1/1A2 by caffeine in rat. Biochem Pharmacol. 1996;52:1915-1919. https://doi.org/10.1016/S0006-2952(96)00522-9
  56. Gobbi G, Bouquet F, Greco L, Lambertini A, Tassinari CA, Ventura A, Zaniboni MG. Celiac disease, epilepsy, and cerebral calcifications. The Italian Working Group on Coeliac Disease and Epilepsy. Lancet. 1992;340:439-443. https://doi.org/10.1016/0140-6736(92)91766-2
  57. Goodman HO, Connolly BM, McLean W, Resnick M. Taurine transport in epilepsy. Clin Chem. 1980;26:414-419.
  58. Gordon N. Medium-chain triglycerides in a ketogenic diet. Dev Med Child Neurol. 1977;19:535-538.
  59. Gospe SM Jr. Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment. Curr Opin Neurol. 2006;19: 148-153. https://doi.org/10.1097/01.wco.0000218230.81301.12
  60. Goutieres F, Aicardi J. Atypical presentations of pyridoxine-dependent seizures: a treatable cause of intractable epilepsy in infants. Ann Neurol. 1985;17:117-120. https://doi.org/10.1002/ana.410170203
  61. Grant ECG. Epilepsy and manganese. Lancet. 2004;363:572.
  62. Grant RH, Stores OP. Folic acid in folate-deficient patients with epilepsy. Br Med J. 1970;4:644-648. https://doi.org/10.1136/bmj.4.5736.644
  63. Guidolin L, Vignoli A, Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol. 1998;5:301-303. https://doi.org/10.1046/j.1468-1331.1998.530301.x
  64. Haidukewych D, Rodin EA. N,N-dimethylglycine shows no anticonvulsant potential. Ann Neurol. 1984;15:405. https://doi.org/10.1002/ana.410150421
  65. Hansson O, Sillanpaa M. Letter: Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet. 1976;1:256.
  66. Hemingway C, Freeman JM, Pillas DJ, Pyzik PL. The ketogenic diet: a 3- to 6-year follow-up of 150 children enrolled prospectively. Pediatrics. 2001;108: 898-905. https://doi.org/10.1542/peds.108.4.898
  67. Hernandez MA, Colina G, Ortigosa L. Epilepsy, cerebral calcifications and clinical or subclinical celiac disease. Course and follow up with gluten-free diet. Seizure. 1998;7:49-54. https://doi.org/10.1016/S1059-1311(98)90008-5
  68. Herzog AG. Progesterone therapy in women with complex partial and secondary generalized seizures. Neurology. 1995;45:1660-1662. https://doi.org/10.1212/WNL.45.9.1660
  69. Hewitt NJ, Lecluyse EL, Ferguson SS. Induction of hepatic cytochrome P450 enzymes: methods, mechanisms, recommendations, and in vitro-in VIVO correlations. Xenobiotica. 2007;37:1196-1224. https://doi.org/10.1080/00498250701534893
  70. Hidaka M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Okumura M, Kodama H, Arimori K. Potent inhibition by star fruit of human cytochrome P450 3A (CYP3A) activity. Drug Metab Dispos. 2004;32:581-583. https://doi.org/10.1124/dmd.32.6.581
  71. Higashi A, Tamari H, Ikeda T, Ohtani Y, Matsukura M, Miyoshino S, Matsuda I. Serum vitamin E concentration in patients with severe multiple handicaps treated with anticonvulsants. Pediatr Pharmacol (New York). 1980;1:129-134.
  72. Hiilesmaa VK, Teramo K, Granstrom ML, Bardy AH. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J (Clin Res ed).1983;287:577-579. https://doi.org/10.1136/bmj.287.6392.577
  73. Holman CP, Bell AF. A trial of evening primrose oil in the treatment of chronic schizophrenia. J Orthomolecular Psychiatry. 1983;12:302-304.
  74. Hom AC, Weaver RC, Alderson JJ. Efficacy of D-alpha tocopherol acetate as adjunctive antiepileptic agent in patients with refractory epilepsy and profound developmental disability: a prospective, randomized, double-blind, placebo-controlled trial. Epilepsia. 1991;32:S62.
  75. Huttenlocher PR, Wilbourn AJ, Signore JM. Mediumchain triglycerides as a therapy for intractable childhood epilepsy. Neurology. 1971;21:1097-1103. https://doi.org/10.1212/WNL.21.11.1097
  76. Johnson GM. Powdered goat's milk: pyridoxine deficiency and status epilepticus. Clin Pediatr (Phila). 1982;21:494-495. https://doi.org/10.1177/000992288202100809
  77. Jones C, Huyton M, Hindley D. Melatonin and epilepsy. Arch Dis Child. 2005;90:1203.
  78. Joshi S, al-Essa MA, Archibald A, Ozand PT. Biotinidase deficiency: a treatable genetic disorder in the Saudi population. East Mediterr Health J. 1999;5:1213-1217.
  79. Kaufman KR, Sachdeo RC. Caffeinated beverages and decreased seizure control. Seizure. 2003;12:519-521. https://doi.org/10.1016/S1059-1311(03)00048-7
  80. Kerr BM, Thummel KE, Wurden CJ, Klein SM, Kroetz DL, Gonzalez FJ, Levy RH. Human liver carbamazepine metabolism Role of CYP3A4 and CYP2C8 in 10, 11-epoxide formation. Biochem Pharmacol. 1994;47:1969-1979. https://doi.org/10.1016/0006-2952(94)90071-X
  81. Keyser A, De Bruijn SF. Epileptic manifestations and vitamin B1 deficiency. Eur Neurol. 1991;31:121-125. https://doi.org/10.1159/000116660
  82. Kim H, Yoon YJ, Shon JH, Cha IJ, Shin JG, Liu KH. Inhibitory effects of fruit juices on CYP3A activity. Drug Metab Dispos. 2006;34:521-523. https://doi.org/10.1124/dmd.105.007930
  83. Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology. 2003;61:1789-1791. https://doi.org/10.1212/01.WNL.0000098889.35155.72
  84. Krause KH, Berlit P, Bonjour JP. Impaired biotin status in anticonvulsant therapy. Ann Neurol. 1982;12:485-486. https://doi.org/10.1002/ana.410120513
  85. Kroll JS. Pyridoxine for neonatal seizures: an unexpected danger. Dev Med Child Neurol. 1985;27:377-379.
  86. Kumandas S, Koklu E, Gumus H, Koklu S, Kurtoglu S, Karakukcu M, Keskin M. Effect of carbamezapine and valproic acid on bone mineral density, IGF-I and IGFBP-3. J Pediatr Endocrinol Metab. 2006;19:529-534.
  87. Kuo MF, Wang HS. Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine. Pediatr Neurol. 2002;26:146-147. https://doi.org/10.1016/S0887-8994(01)00357-5
  88. Labate A, Gambardella A, Messina D, Tammaro S, Le Piane E, Pirritano D, Cosco C, Doldo P, Mazzei R, Oliveri RL, Bosco D, Zappia M, Valentino P, Aguglia U, Quattrone A. Silent celiac disease in patients with childhood localization-related epilepsies. Epilepsia. 2001;42:1153-1155.
  89. Lauritzen I, Blondeau N, Heurteaux C, Widmann C, Romey G, Lazdunski M. Polyunsaturated fatty acids are potent neuroprotectors. EMBO J. 2000;19:1784-1793. https://doi.org/10.1093/emboj/19.8.1784
  90. Levy. SL, Burnharn WM, Hwang PA. An evaluation of the anticonvulsant effects of vitamin E. Epilepsy Res. 1990;6:12-17. https://doi.org/10.1016/0920-1211(90)90003-E
  91. Mantovani J, De Vivo DC. Effects of taurine on seizures and growth hormone release in epileptic patients. Arch Neurol. 1979;36:672-674. https://doi.org/10.1001/archneur.1979.00500470042006
  92. Mattson RH, Gallagher BB, Reynolds EH, Glass D. Folate therapy in epilepsy. A controlled study. Arch Neurol. 1973;29:78-81. https://doi.org/10.1001/archneur.1973.00490260022002
  93. Mikati MA, Trevathan E, Krishnamoorthy KS, Lombroso CT. Pyridoxine-dependent epilepsy: EEG investigations and longterm follow-up. Electroencephalogr Clin Neurophysiol. 1991;78:215-221. https://doi.org/10.1016/0013-4694(91)90035-3
  94. Mintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine. Epilepsia. 2006;47:510-515. https://doi.org/10.1111/j.1528-1167.2006.00460.x
  95. Miwa H, Iijima M, Tanaka S, Mizuno Y. Generalized convulsions after consuming a large amount of Gingko nuts. Epilepsia.2001;42:280-281.
  96. Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology..1997;49:1444-1447. https://doi.org/10.1212/WNL.49.5.1444
  97. Mock DM, Mock NI, Nelson RP, Lombard KA. Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr. 1998;26:245-250. https://doi.org/10.1097/00005176-199803000-00002
  98. Monaco F, Mutani R, Durelli L, Delsedime M. Free amino acids in serum of patients with epilepsy: significant increase in taurine. Epilepsia. 1975;16:245-249. https://doi.org/10.1111/j.1528-1157.1975.tb06054.x
  99. Monami M, Mannucci E, Breschi A, Marchionni N. Seizures as the only clinical manifestation of reactive hypoglycemia: a case report. J Endocrinol Invest. 2005;28:940-941. https://doi.org/10.1007/BF03345327
  100. Mutani R, Monaco F, Durelli L, Delsedime M. Levels of free amino acids in serum and cerebrospinal fluid after administration of taurine to epileptic and normal subjects. Epilepsia.1975;16:765-769. https://doi.org/10.1111/j.1528-1157.1975.tb04763.x
  101. Nabbout R, Soufflet C, Plouin P, Dulac O. Pyridoxine dependent epilepsy: a suggestive electroclinical pattern. Arch Dis Child Fetal Neonatal ed. 1999;81:F125-129. https://doi.org/10.1136/fn.81.2.F125
  102. Nicolai J, van Kranen-Mastenbroek VH, Wevers RA, Hurkx Wi\, VIes JS. Folinic acid-responsive seizures initially responsive to pyridoxine. Pediatr Neurol. 2006;34:164-167. https://doi.org/10.1016/j.pediatrneurol.2005.08.019
  103. Nuytten D, Van Hees J, Meulemans A, Carton H. Magnesium deficiency as a cause of acute intractable seizures. J Neurol. 1991;238:262-264. https://doi.org/10.1007/BF00319737
  104. Ogunmekan AO, Hwang PA. A randomized, doubleblind, placebo-controlled, clinical trial of d-alphatocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. Epilepsia. 1989;30:84-89. https://doi.org/10.1111/j.1528-1157.1989.tb05287.x
  105. Ogunmekan AO. Vitamin E deficiency and seizures in animals and man. Can J Neurol Sci. 1979;6:43-45. https://doi.org/10.1017/S0317167100119353
  106. Pack AM, Morrell MJ. Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications. CNS Drugs. 2001;15:633-642. https://doi.org/10.2165/00023210-200115080-00006
  107. Peled N, Shorer Z, Peled E, Pillar G. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia. 2001;42:1208-1210.
  108. Pennetta R, Masi G, Perniola T, Ferrannini E. Electroclinical evaluation of the anti-epileptic action of taurine. Acta Neurol (Napoli). 1977;32:316-322.
  109. Peterson P, Gray P, Tolman KG. Calcium balance in drug-induced osteomalacia: response to vitamin D. Clin Pharmacol Ther. 1976;19:63-67. https://doi.org/10.1002/cpt197619163
  110. Pfeiffer CC, LaMola S. Zinc and manganese in the schizophrenias. J Orthomolecular Psychiatry. 1983;12:215-234.
  111. Raju GB, Behari M, Prasad K, Ahuja GK. Randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopherol (vitamin E) as add-on therapy in uncontrolled epilepsy. Epilepsia. 1994;35:368-372. https://doi.org/10.1111/j.1528-1157.1994.tb02446.x
  112. Ralston AJ, Snaith RP, Hinley JB. Effects of folic acid on fit-frequency and behaviour in epileptics on anticonvulsants. Lancet. 1970;295:867-868. https://doi.org/10.1016/S0140-6736(70)91694-6
  113. Reichelt KL, Ekrem J, Scott H. Gluten, milk proteins and autism: dietary intervention effects on behavior and peptide secretion. J Appl Nutr. 1990;42:1-11.
  114. Reynolds EH, Preece J, Johnson AL. Folate metabolism in epileptic and psychiatric patients. J Neurol Neurosurg Psychiatry. 1971;34:726-732. https://doi.org/10.1136/jnnp.34.6.726
  115. Roach ES, Carlin L. N,N-dimethylglycine for epilepsy. N Engl J Med. 1982;307:1081-1082. https://doi.org/10.1056/NEJM198210213071717
  116. Roach ES, Gibson P. Failure of N,N-dimethylglycine in epilepsy. Ann Neurol. 1983;14:347.
  117. Roberts HJ. Aspartame and headache. Neurology. 1995;45:1631.
  118. Said HM, Redha R, Nylander W. Biotin transport in the human intestine: inhibition by anticonvulsant drugs. Am J Clin Nutr. 1989;49:127-131.
  119. Schlanger S, Shinitzky M, Yam D. Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia. 2002;43:103-104.
  120. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet. 1998;351:1254. https://doi.org/10.1016/S0140-6736(05)79321-1
  121. Shovic A, Bart RD, Stalcup AM. 'We think yom son has LeIlllox-Gastaut syndrome'-a case study of monosodium glutamate's possible effect on a child. J Am Diet Assoc. 1997;97:793-794. https://doi.org/10.1016/S0002-8223(97)00196-X
  122. Silver J. Letter: Vitamin D therapy for children on anticonvulsants. N Engl J Med. 1975;293:1106.
  123. Snaith RP, Mehta S, Raby AH. Serum folate and vitamin B12 in epileptics with and without mental illness. Br J Psychiatry. 1970;116:179-183. https://doi.org/10.1192/bjp.116.531.179
  124. Steidl L, Tolde I, Svomova V. Metabolism of magnesium and zinc in patients treated with antiepileptic drugs and with magnesium lactate. Magnesium. 1987;6:284-295.
  125. Sullivan C, Capaldi N, Mack G, Buchanan N. Seizures and natural vitamin E. Med J Aust. 1990;152:613-614.
  126. Tallian KB, Nahata MC, Tsao CY. Role of the ketogenic diet in children with intractable seizures. Ann Pharmacother. 1998;32:349-361. https://doi.org/10.1345/aph.16245
  127. Tamai H, Wakamiya E, Mino M, Iwakoshi M. Alphatocopherol and fatty acid levels in red blood cells in patients treated with antiepileptic diugs. J Nutr Sci Vitaminol (Tokyo). 1988;34:627-631. https://doi.org/10.3177/jnsv.34.627
  128. Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid-responsive neonatal seizures. J Child Neurol. 1999;14:529-532. https://doi.org/10.1177/088307389901400809
  129. Trauner DA. Medium-chain triglyceride (MCT) diet in intractable seizure disorders. Neurology. 1985;35:237-238. https://doi.org/10.1212/WNL.35.2.237
  130. Trimble MR, Corbett JA, Donaldson D. Folic acid and mental symptoms in children with epilepsy. J Neurol Neurosurg Psychiatry. 1980;43:1030-1034. https://doi.org/10.1136/jnnp.43.11.1030
  131. Turner TL, Cockburn F, Forfar JO. Magnesium therapy in neonatal tetany. Lancet. 1977;1:283-284.
  132. Tyagi A, Delanty N. Herbal remedies, dietary supplements and seizures. Epilepsia. 2003;44:228-235. https://doi.org/10.1046/j.1528-1157.2003.19902.x
  133. Vaddadi KS, Gilleard CJ, Mindham RH, Butler R. A controlled trial of prostaglandin E1 precursor in chronic neuroleptic resistant schizophrenic patients. Psychopharmacology (Berl). 1986;88:362-367.
  134. Vaddadi KS. The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. Prostaglandins Med. 1981;6:375-379. https://doi.org/10.1016/0161-4630(81)90069-0
  135. Van Gelder NM, Sherwin AL, Sacks C, Anderman F. Biochemical observations following administration of taurine to patients with epilepsy. Brain Res. 1975;94:297-306. https://doi.org/10.1016/0006-8993(75)90063-3
  136. Verrotti A, Greco R, Morgese G, Chiarelli F. Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs. Int J Clin Lab Res. 1999;29:36-40. https://doi.org/10.1007/s005990050060
  137. Vining EP. Clinical efficacy of the ketogenic diet. Epilepsy Res. 1999;37:181-190. https://doi.org/10.1016/S0920-1211(99)00070-4
  138. Volpe SL, Schall Jl, Gallagher PR, Stallings VA, Bergqvist AG. Nutrient intake of children with intractable epilepsy compared with healthy children. J Am Diet Assoc. 2007;107:1014-1018. https://doi.org/10.1016/j.jada.2007.03.011
  139. Walton RG. Seizure and mania after high intake of aspartame. Psychosomatics. 1986;27:218-220. https://doi.org/10.1016/S0033-3182(86)72715-1
  140. Wolf P, Okujava N. Possibilities of non-pharmacological conservative treatment of epilepsy. Seizure. 1999;8:45-52. https://doi.org/10.1053/seiz.1998.0243
  141. Wurtman RJ. Aspartame: possible effect on seizure susceptibility. Lancet. 1985;2:1060.
  142. Yuen AW, Sander JW, Fluegel D, Patsalos PN, Bell GS, Johnson T, Koepp MJ. Omega-3 fatty acid supplementation in patients with chronic epilepsy: a randomized trial. Epilepsy Behav. 2005;7:253-258. https://doi.org/10.1016/j.yebeh.2005.04.014