Ratna Suwita Batubara, Johannes Harlan Saing, Yazid Dimyati, Cynthea Prima Destariani


Background:Epilepsy is a common neurological disorder of childhood requiring long term of antiepileptic drugs that has been associated with low 25-hydroxyvitamin D (25(OH)D) status and high prevalence of vitamin D deficiency. However, studies on the effect of long term antiepileptic drugs use on vitamin D had inconsistent results.

The aim of this study was to analyze the association of antiepileptic drugs (AED) with vitamin D status in childhood epilepsy.

Methods: A cross sectional study was conducted from February to April 2019 at children outpatient clinic Haji Adam Malik Hospital. One hundred and two epileptic children taking antiepileptic drug were enrolled consecutively. All cases who met inclusion criteria, underwent test for serum 25(OH)D that were categorized as normal (≥30 ng/ml) and abnormal (<30 ng/ml). Antiepileptic drugs were categorized based on their enzyme inducing properties, polytherapy combination and monotherapy.

Results: From 102 patients, 77 children (75.5%) had abnormal vitamin D with average level of 25(OH)D was 24.37 ng/ml (SD 9.23). The mean of age was 9.26 years (SD 4.96), 57.8% were boy and 79.4% on monotherapy. Association between enzyme inducing vs non-inducing properties, monotherapy vs polytherapy and duration of therapy with vitamin D status were non significance with p value 0.277, 0.713 and 0.728 respectively. Sodium Valproate was the most common AED used in mono therapy (87.7%) and combination of Sodium Valproate-Topiramate in polytherapy (42.9%). The differences of an abnormal vitamin D in those on AED as monotherapy were not significant (p=0.713). Similarly in polytherapy, there were non-significant difference of vitamin D level in each combination of AED (p=1).

Conclusion: There was no significant association of antiepileptic drugs with vitamin D status in childhood epilepsy.This study was presented as poster presentation at the 15th Asian Oceanian Congress of Child Neurology, Kuala Lumpur, Malaysia, September 2019  


epilepsy, antiepileptic drugs, vitamin D

Full Text:



Cebeci AN, Ekici B. Epilepsy treatment by sacrificing vitamin D. Expert Rev Neurother. 2014;14(5):481-91.

Stafstrom CE, Rho JM. Pediatric epilepsy : an overview. Dalam: Swaiman KH, Ashwal S, Ferreiro DM, Schor NF. Pediatric Neurology “principle and practice”.5th edition. England; 2012.p.703-10.

Groves NJ, McGrath JJ, Burne THJ. Vitamin D as a neurosteroid affecting the developing and adult brain. Annual review of nutrition, 2014; 34: 117-141.

Sonmez, FM. The Role of the Vitamin D in Neurology: Interrelationships between headache, epilepsy and vitamin D deficiency. J Pediatr Neonatal Care. 2016; 4.2: 00132.

Pendo K, DeGiorgio CM. Vitamin D3 for the Treatment of Epilepsy: Basic Mechanisms, Animal Models, and Clinical Trials. Front Neurol. 2016;7:218.

Tantri N L, Nur FT, Salino H. Pengaruh pemberian obat antiepilepsi terhadap kadar vitamin D pada anak penderita epilepsi. Sari Pediatri. 2017; 19.2: 97-102.

He Xin, Jiang P, Zhu W, Xue Y, Li M, Dang R, et al. Effect of antiepileptic therapy on serum 25 (OH) D3 and 24, 25 (OH)2D3 levels in epileptic children. Ann Nutr Metab. 2016; 68.2: 119-127.

Durá-travé T, Victoriano FG, Chacon MM, Gonzalez PM, Albesa SA, Petri MEY. Vitamin d deficiency in children with epilepsy taking valproate and levetiracetam as monotherapy. Epilepsy research. 2018; 139: 80-84.

Nicolaidou P, Georgouli H, Kotsalis H, Matsinos Y, Papadopoulon A, Fretzayas A, et al. Effects of anticonvulsant therapy on vitamin D status in children: prospective monitoring study. Journal of child neurology, 2006; 21.3: 205-210.

Nettekoven S, Strὅhle A, Trunz B, Wolters M, Hoffmann, Horn R, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. European journal of pediatrics, 2008; 167.12: 1369-1377.

Pohan FZ, Hendarto A, Mangunatmadja I, Gunardi H. Vitamin D levels in epileptic children on long-term anticonvulsant therapy. Paediatrica Indonesiana, 2015; 55.3: 164-70.

Holick MF. Vitamin D deficiency. New England Journal of Medicine, 2007; 357.3: 266-81.

Lee JY, So TY, Thackray J. A review on vitamin d deficiency treatment in pediatric patients. The Journal of Pediatric Pharmacology and Therapeutics, 2013;18.4: 277-91.

Ernawati F, Budiman B. Status vitamin D terkini anak indonesia usia 2,0-12,9 tahun. Gizi Indonesia, 2015; 38.1: 73-80.

Ginige N, de Silva KSH, Wanigasinghe JK, Gunawardane NS, Munasinghe TMJ. Effect of long term anti epileptic drugs on serum vitamin D levels and bone profile in a cohort of Sri Lankan children. International journal of pediatric endocrinology, 2015;1: P66.

Chaudhuri, Jaydip Ray, et al. Association of 25-hydroxyvitamin D deficiency in pediatric epileptic patients. Iranian journal of child neurology, 2017;11.2: 48-56.

Baek JH, Seo YH, Kim GH, Kim MY, Eun BL. Vitamin D levels in children and adolescents with antiepileptic drug treatment. Yonsei medical journal, 2014; 55.2: 417-21.

Fong CY, Kong AN, Pooh BK, Mohamed AR, Khoo TB, Ng LR, et al. Vitamin D deficiency and its risk factors in Malaysian children with epilepsy. Epilepsia, 2016; 57.8: 1271-79.

Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. The Journal of Clinical Endocrinology & Metabolism, 2011; 96.1: 53-58.

Holick MF, Binkley NC, Ferrari HAB, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism.2011 96.7: 1911-30.

Gröber U, Spitz J, Reichrath J, Kister K, Holick MF. Vitamin D: update 2013: from rickets prophylaxis to general preventive healthcare. Dermato Endocrinology,2013; 5.3: 331-347.

DeLuca HF. Overview of general physiologic features and functions of vitamin D. The American journal of clinical nutrition, 2004;80.6 : 1689S-1696S

Misra M, Pacaud D, Petryk A, Solberg PFC, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics, 2008; 122.2: 398-417.

Munns C, Zacharin MR, Rodda CP, Jennifer AB, Morley R, Cranswick NE, et al. Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement. Medical Journal of Australia, 2006;185.5: 268-272.

Li XH, Hou XY, Chen R. The roles of vitamin B12 and vitamin D in children with intractable epilepsy. Int J Clin Exp Med. 2015;8(1):764-9.

Robert H, Haslam H. The Nervous system. Dalam: Klegman R, Behrman R, Jenson H, Stanton B. Nelson Textbook of Pediatrics.18 th edition. Philadelphia: Saunders; 2008.p.2457-530.

Louis EKS, Rosenfeld WE, Barmley T. Antiepileptic drug monotherapy: the initial approach in epilepsy management. Current Neuropharmacology, 2009;7: 77-82.

Louis EK, Gidal BE, Henry TR, Kaydanova V, Krumholz A, McCabe PH, et al. Conversions between monotherapies in epilepsy: expert consensus. Epilepsy & Behavior, 2007;11.2: 222-34.

Sreedharan M, Devadathan K, Kunju PM, Sasidharan B, Pillat JP, Amma MAV, et al. Vitamin D deficiency in ambulant children on carbamazepine or sodium valproate monotherapy. Indian pediatrics, 2018; 55.4: 307-10.

Nagarjunakond S, Amalakanti S, Uppala V, Rajanala L, Athina S. Vitamin d in epilepsy: vitamin d levels in epilepsy patients, patients on antiepileptic drug polytherapy and drug-resistant epilepsy sufferers. European journal of clinical nutrition. 2016; 70.1: 140.

Ramya S, Anita C, Ravi MD. A study of vitamin-D status in epileptic children in age group 2-15 years. International Journal of Advances, 2016;3(2): 319-23.

Valsamis HA, Arora SK, Labban B, McFarlane S. Antiepileptic drugs and bone metabolism. Nutrition & metabolism, 2006; 3.36:1-11

Zhou C, Assem M, Tay JC, Watkons PB, Blumberg B, Schuetz EG, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. The Journal of clinical investigation, 2006;116.6: 1703-12.

Pascussi JM, Robert A, Nguyen M, Walrant-Debray O, Garabedian M, Martin P, et al. Possible involvement of pregnane X receptor–enhanced CYP24 expression in drug-induced osteomalacia. The Journal of clinical investigation, 2005; 115.1: 177-86.

Holick MF. Stay tuned to PXR: an orphan actor that may not be D-structive only to bone. The Journal of clinical investigation, 2005; 115.1: 32-34.

Teagarden DL, Meador JK, Loring DW. Low vitamin D levels are common in patients with epilepsy. Epilepsy research. 2014; 108.8: 1352-1356.

Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug–vitamin D interactions: a systematic review of the literature. Nutrition in Clinical Practice, 2013; 28.2: 194-208.

Misra A, Aggarwal A, Singh O, Sharma S. Effect of carbamazepine therapy on vitamin D and parathormone in epileptic children. Pediatric neurology, 2010;43.5: 320-24

Menon B, Harinarayan CV. The effect of anti epileptic drug therapy on serum 25-hydroxyvytamin D and parameters of calcium and bone metabolism- A longitudinal study. Seizure, 2010;19.3:153-58

Feldkamp J, Becker A, Witte OW, Scharff D, Scherbaum WA. Long-term anticonvulsant therapy leads to low bone mineral density-evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Experimental and clinical endocrinology & diabetes, 2000;108.01: 37-43.

Lee RH, Kenneth WL, Cathleen CE. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. The American journal of geriatric pharmacotherapy, 2010;8.1: 34-46.


  • There are currently no refbacks.