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Antiepileptiklerin D vitamini ve kalsiyum düzeylerine etkisi

Year 2022, , 167 - 172, 20.08.2022
https://doi.org/10.30565/medalanya.1116431

Abstract

Amaç: Çalışmamızın amacı, farklı antiepileptik ajan kullanan epilepsi hastalarında D vitamini ve kalsiyum düzeylerini araştırmak ve D vitamini düzeyleri ile antiepileptik ajanın türü, hastanın yaşı ve cinsiyeti gibi çeşitli faktörler arasındaki ilişkiyi araştırmaktır.

Gereç ve Yöntem: Bu geriye dönük vaka-kontrol çalışmasına Alanya Alaaddin Keykubat Üniversitesi nöroloji polikliniğinde takip edilen ve 21 tanesi ilaç kullanmayan (ilaç kontrol) olmak üzere total 141 epilepsi hastası ve Ocak 2018-Ocak 2021 tarihleri arasında nöroloji polikliniğine farklı nedenlerle başvuran 160 sağlıklı birey (sağlıklı kontrol) olmak üzere toplam 301 katılımcı alındı. Demografi, Tüm katılımcıların ayrıntılı öyküsü, ilaç kullanımı, anti-epileptik kullanım süresi, plazma 25-hidroksi D vitamini ve kalsiyum düzeyleri saptandı.

Bulgular: Ortalama D vitamini düzeyi epilepsi grubunda 15.46, kontrol grubunda 16.95 idi. Gruplara arasında D vitamini düzeyi açısından anlamlı farklılık göstermedi (p>0.05). Her iki grupta da yaş ve D vitamini düzeyleri arasında anlamlı bir ilişki bulunmadı ve epilepsi grubundaki kadınlarda D vitamini düzeyleri istatistiksel olarak anlamlı derecede düşüktü. Sağlıklı kontrol grubunun %69,6'sında, karbamazepin kullanıcılarının %78,9'unun, lakozamid kullanıcılarının %62,5'inin, tüm lamotrijin kullanıcılarının %66,7'sinin ve sodyum valproat kullanıcılarının %72,4'ünün D vitamini düzeyi 20'nin altındaydı. D vitamini düzeyi ile kullanılan ilaç arasında belirgin fark yoktu (p>0.05). Sadece kalsiyum düzeyi ile karbamazepin arasında anlamlı bağlantı vardı (p<0.05).

Sonuç: Antiepileptik kullananlarda D vitamini ve kalsiyum düzeyleri düşük bulunabilir; ancak karbamazepin grubundaki kalsiyum düzeyleri dışında bu düşüş anlamlı bir fark oluşturmamaktadır.

References

  • 1. Saket S,Varasteh N, Halimi Asl A, Saneifard H, How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy. Iran J Child Neurol. 2021;15(1):19-27. doi: 10.22037/ijcn.v15i1.25952.
  • 2. Pack AM, Morrell MJ. Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications. CNS Drugs.2001;15:633-42. doi:10.2165/00023210-200115080-00006.
  • 3. Mintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepin. Epilepsia. 2006;47:510–5. doi: 10.1111/j.1528-1167.2006.00460.x.
  • 4. Bell RD, Pak CY, Zerwekh J, Barilla DE, Vasko M. Effect of phenytoin on bone and vitamin D metabolism. Ann Neurol. 1979;5:374-8. doi: 10.1002/ana.410050411.
  • 5. Yildiz EP, Poyrazoglu Ş, Bektas G, Kardelen AD, Aydinli N. Potential risk factors for vitamin D levels in medium-and long-term use of antiepileptic drugs in childhood. Acta Neurol Belg. 2017;117:447-53. doi: 10.1007/s13760-017-0775-x.
  • 6. Fong CY, Riney CJ. Vitamin D deficiency among children with epilepsy in South Queensland. J Child Neurol. 2014;29(3):368–73. doi:10.1177/0883073812472256.
  • 7. Lee SH, Yu J. Risk factors of vitamin D deficiency in children with epilepsy taking anticonvulsants at initial and during follow-up. Ann Pediatr Endocrinol Metab. 2015;20(4):198-205. doi:10.6065/apem.2015.20.4.198.
  • 8. Yavuz D., Mete T., Yavuz, R., Altunoğlu. Vitamin D, Calcium&Mineral Metabolism, Extraskeletal Effects of Vitamin D and the Use of Nutritional Vitamin D in Chronic Kidney Disease. Ankara Med J. 2014;14(4):162-71. doi:10.17098/amj.19812
  • 9. Holló A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci.2014;124(6):387-93. doi: 10.3109/00207454.2013.847836.
  • 10. Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D interactions: a systematic review of the literature. Nutr Clin Pract. 2013;28(2):194-208. doi: 10.1177/0884533612467824.
  • 11. Junges C, Machado TD, Nunes Filho PRS, Riesgo R, Mello ED. Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis. J Pediatr (Rio J). 2020;96(5):559-68. doi: 10.1016/j.jped.2020.01.004.
  • 12. Kułak, W., Sobaniec, W., Wojtal, K., Czuczwar, S.J. Calcium modulation in epilepsy. Pol. J. Pharmacol. 2004;56(1):29–41. PMID: 15047975.
  • 13. 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.
  • 14. Kulak CA, Borba VZ, Bilezikian JP, Silvado CE, Paola Ld, Boguszewski CL. Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs. Arq Neuropsiquiatr. 2004;62(4):940-8. doi: 10.1590/s0004-282x2004000600003.
  • 15. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58(9):1348-53. doi: 10.1212/wnl.58.9.1348.
  • 16. Lee, H.S., Wang, S.Y., Salter, D.M., Wang, CC., Chen, S.J., Fan, H.C. The impact of the use of antiepileptic drugs on the growth of children. BMC Pediatr. 2013;13:211. doi: 10.1186/1471-2431-13-211.
  • 17. Meldrum, BS., Rogawski, M.A. Molecular targets for antiepileptic drug development. Neurotherapeutics. 2007;4(1):18–61. doi: 10.1016/j.nurt.2006.11.010.
  • 18. Abdel-Wahab AF, Afify MA, Mahfouz AM, Shahzad N, Bamagous GA, Al Ghamdi SS. 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.
  • 19. Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. Clin Neurol Neurosurg. 2010;112(1):1-10. doi: 10.1016/j.clineuro: 2009.10.011
  • 20. Hamed SA. Influences of bone and mineral metabolism in epilepsy. Expert Opin Drug Saf 2011;10(2):265-80. doi: 10.1517/14740338.2011.534455.
  • 21. 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.

Investigation of the Antiepileptics on Levels of Vitamin D and Calcium

Year 2022, , 167 - 172, 20.08.2022
https://doi.org/10.30565/medalanya.1116431

Abstract

Aim: We investigated the connection between D vitamin and factors such as the type of antiepileptic agent, patient age and gender.

Methods: This retrospective case-control study enrolled a total of 301 participants, including 141 epilepsy patients with (n= 120) without drug (n=21) regimens followed up in Alanya Alaaddin Keykubat University neurology outpatient clinic and 160 healthy individuals who applied to the neurology outpatient clinic for different reasons from January 2018 to January 2021. Demographics, detailed history, use of medications, duration of antiepileptic use, plasma 25-hydroxy Vitamin D and calcium levels were determined.

Results: The mean level of Vitamin D was 15.46 in the epilepsy group and 16.95 in the control group. Level of D Vitamine did not differ significantly by groups (p>0.05). There were no significant relationship regarding age and vitamin D levels in both groups while decreased Vitamin D levels were detected epileptic women. Vitamin D level was below 20 in 69.6% of healthy control group, 78.9% of carbamazepine users, 62.5% of lacosamide users, all lamotrigine users, 66.7% of levatiracetam users, and 72.4% of sodium valproate users. No significant connection were detected between levels of Vitamin D and the drug used (p>0.05) while a significant association was confirmed only between calcium levels and carbamazepine (p<0.05).

Conclusion: Vitamin D and calcium levels can be found to be low in antiepileptic users; however, except for the calcium levels in the carbamazepine group, this decrease does not constitute a significant difference. 

References

  • 1. Saket S,Varasteh N, Halimi Asl A, Saneifard H, How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy. Iran J Child Neurol. 2021;15(1):19-27. doi: 10.22037/ijcn.v15i1.25952.
  • 2. Pack AM, Morrell MJ. Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications. CNS Drugs.2001;15:633-42. doi:10.2165/00023210-200115080-00006.
  • 3. Mintzer S, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepin. Epilepsia. 2006;47:510–5. doi: 10.1111/j.1528-1167.2006.00460.x.
  • 4. Bell RD, Pak CY, Zerwekh J, Barilla DE, Vasko M. Effect of phenytoin on bone and vitamin D metabolism. Ann Neurol. 1979;5:374-8. doi: 10.1002/ana.410050411.
  • 5. Yildiz EP, Poyrazoglu Ş, Bektas G, Kardelen AD, Aydinli N. Potential risk factors for vitamin D levels in medium-and long-term use of antiepileptic drugs in childhood. Acta Neurol Belg. 2017;117:447-53. doi: 10.1007/s13760-017-0775-x.
  • 6. Fong CY, Riney CJ. Vitamin D deficiency among children with epilepsy in South Queensland. J Child Neurol. 2014;29(3):368–73. doi:10.1177/0883073812472256.
  • 7. Lee SH, Yu J. Risk factors of vitamin D deficiency in children with epilepsy taking anticonvulsants at initial and during follow-up. Ann Pediatr Endocrinol Metab. 2015;20(4):198-205. doi:10.6065/apem.2015.20.4.198.
  • 8. Yavuz D., Mete T., Yavuz, R., Altunoğlu. Vitamin D, Calcium&Mineral Metabolism, Extraskeletal Effects of Vitamin D and the Use of Nutritional Vitamin D in Chronic Kidney Disease. Ankara Med J. 2014;14(4):162-71. doi:10.17098/amj.19812
  • 9. Holló A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci.2014;124(6):387-93. doi: 10.3109/00207454.2013.847836.
  • 10. Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D interactions: a systematic review of the literature. Nutr Clin Pract. 2013;28(2):194-208. doi: 10.1177/0884533612467824.
  • 11. Junges C, Machado TD, Nunes Filho PRS, Riesgo R, Mello ED. Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis. J Pediatr (Rio J). 2020;96(5):559-68. doi: 10.1016/j.jped.2020.01.004.
  • 12. Kułak, W., Sobaniec, W., Wojtal, K., Czuczwar, S.J. Calcium modulation in epilepsy. Pol. J. Pharmacol. 2004;56(1):29–41. PMID: 15047975.
  • 13. 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.
  • 14. Kulak CA, Borba VZ, Bilezikian JP, Silvado CE, Paola Ld, Boguszewski CL. Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs. Arq Neuropsiquiatr. 2004;62(4):940-8. doi: 10.1590/s0004-282x2004000600003.
  • 15. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58(9):1348-53. doi: 10.1212/wnl.58.9.1348.
  • 16. Lee, H.S., Wang, S.Y., Salter, D.M., Wang, CC., Chen, S.J., Fan, H.C. The impact of the use of antiepileptic drugs on the growth of children. BMC Pediatr. 2013;13:211. doi: 10.1186/1471-2431-13-211.
  • 17. Meldrum, BS., Rogawski, M.A. Molecular targets for antiepileptic drug development. Neurotherapeutics. 2007;4(1):18–61. doi: 10.1016/j.nurt.2006.11.010.
  • 18. Abdel-Wahab AF, Afify MA, Mahfouz AM, Shahzad N, Bamagous GA, Al Ghamdi SS. 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.
  • 19. Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. Clin Neurol Neurosurg. 2010;112(1):1-10. doi: 10.1016/j.clineuro: 2009.10.011
  • 20. Hamed SA. Influences of bone and mineral metabolism in epilepsy. Expert Opin Drug Saf 2011;10(2):265-80. doi: 10.1517/14740338.2011.534455.
  • 21. 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.
There are 21 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Research Article
Authors

Burak Yuluğ 0000-0002-9704-6173

Ahmet Özşimşek 0000-0003-0696-6749

Ece Özdemir Öktem 0000-0002-1264-5696

Publication Date August 20, 2022
Submission Date May 13, 2022
Acceptance Date July 8, 2022
Published in Issue Year 2022

Cite

Vancouver Yuluğ B, Özşimşek A, Özdemir Öktem E. Investigation of the Antiepileptics on Levels of Vitamin D and Calcium. Acta Med. Alanya. 2022;6(2):167-72.

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