Postępy Psychiatrii i Neurologii

Exploring the roles of ghrelin and nesfatin-1 as potential biomarkers in human epilepsy: a systematic review

  1. Department of Developmental Neurology, Poznan University of Medical Sciences, Poznan, Poland

  2. Doctoral School, Poznan University of Medical Sciences, Poznan, Poland

  3. Chair and Clinic of Prosthodontics and Gerostomatology, Poznan University of Medical Sciences, Poznan, Poland

Adv Psychiatry Neurol 2026; 35 (3)

Data publikacji online: 2026/08/31
Article file
PPiN-00549_Exploring.pdf
Confronting perimenopausal women’s knowledge of coronary heart disease with their health behaviours. Controversial role of hormone replacement therapy in the protection of coronary heart disease
  1. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology 2017; 88: 296-303.
  2. Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia 2018; 59: 2179-2193.
  3. Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev 2020; 72: 606-638.
  4. Clynen E, Swijsen A, Raijmakers M, Hoogland G, Rigo JM. Neuropeptides as targets for the development of anticonvulsant drugs. Mol Neurobiol 2014; 50: 626-646.
  5. Arabacı Tamer S, Koyuncuoğlu T, Karagöz Köroğlu A, Akakın D, Yüksel M, Yeğen B. Nesfatin-1 ameliorates oxidative brain damage and memory impairment in rats induced with a single acute epileptic seizure. Life Sci 2022; 294: 120376. DOI: 10.1016/j.lfs.2022.120376.
  6. Engel J Jr, Pitkänen A, Loeb JA, Edward Dudek F, Bertram EH III, Cole AJ, et al. Epilepsy biomarkers. Epilepsia 2013; 54 Suppl 4: 61-69. DOI: 10.1111/epi.12299.
  7. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656-660.
  8. Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 2008; 34: 2-11.
  9. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin – a hormone with multiple functions. Front Neuroendocrinol 2004; 25: 27-68.
  10. Nass R, Farhy LS, Liu J, Pezzoli SS, Johnson ML, Gaylinn BD, et al. Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults. J Clin Endocrinol Metab 2014; 99: 602-608.
  11. Whatmore A, Hall C, Jones J, Westwood M, Clayton P. Ghrelin concentrations in healthy children and adolescents. Clin Endocrinol 2003; 59: 649-654.
  12. Buckinx A, De Bundel D, Kooijman R, Smolders I. Targeting the ghrelin receptor as a novel therapeutic option for epilepsy. Biomedicines 2022; 10: 53. DOI: 10.3390/biomedicines10010053.
  13. Zigman JM, Jones JE, Lee CE, Saper CB, Elmquist JK. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J Comp Neurol 2006; 494: 528-548.
  14. Portelli J, Michotte Y, Smolders I. Ghrelin: an emerging new anticonvulsant neuropeptide. Epilepsia Rev 2012; 53: 585-595.
  15. Banks WA, Tschöp M, Robinson SM, Heiman ML. Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 2002; 302: 822-827.
  16. Oh IS, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 2006; 443: 709-712.
  17. Li C, Zhang F, Shi L, Zhang H, Tian Z, Xie J, Jiang H. Nesfatin-1 decreases excitability of dopaminergic neurons in the substantia nigra. J Mol Neurosci 2013; 52: 419-424.
  18. Dore R, Levata L, Lehnert H, Schulz C. Nesfatin-1: functions and physiology of a novel regulatory peptide. J Endocrinol Rev 2017; 232: R45-R65. DOI: 10.1530/JOE-16-0361.
  19. Price TO, Samson WK, Niehoff ML, Banks WA. Permeability of the blood-brain barrier to a novel satiety molecule nesfatin-1. Peptides 2007; 28: 2372-2381.
  20. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71. DOI: 10.1136/bmj.n71.
  21. Aydin S, Dag E, Ozkan Y, Erman F, Dagli AF, Kilic N, et al. Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders. Mol Cell Biochem 2009; 328: 49-56.
  22. Dag E, Aydin S, Ozkan Y, Erman F, Dagli AF, Gurger M. Alteration in chromogranin A, obestatin and total ghrelin levels of saliva and serum in epilepsy cases. Peptides 2010; 31: 932-937.
  23. Mohamed WS, Nageeb RS, Elsaid HH. Serum and urine ghrelin in adult epileptic patients. Egypt J Neurol Psychiatry Neurosurg 2019; 55. DOI: 10.1186/s41983-019-0127-2.
  24. Berilgen MS, Mungen B, Ustundag B, Demir C. Serum ghrelin levels are enhanced in patients with epilepsy. Seizure 2006; 15: 106-111.
  25. Erkec OE, Milanlioğlu A, Komuroglu AU, Kara M, Huyut Z, Keskin S. Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study. Rev Assoc Med Brasil 2021; 67: 207-212.
  26. Atacan Yasgüçlükal M, Ayça S, Demirbilek V, Saltık S, Yalçınkaya C, Erdoğan Döventaş Y, Çokar Ö. Serum levels of neuropeptides in epileptic encephalopathy with spike-and-wave activation in sleep. Pediatr Neurol 2023; 144: 110-114.
  27. Costa AM, Lo Barco T, Spezia E, Conti V, Roli L, Marini L, et al. Prospective evaluation of ghrelin and des-acyl ghrelin plasma levels in children with newly diagnosed epilepsy: evidence for reduced ghrelin-to-des-acyl ghrelin ratio in generalized epilepsies. J Pers Med 2022; 12. DOI: 10.3390/jpm12040527.
  28. Drokov AP, Lipatova LV, Shnayder NA, Nasyrova RF. Pharmacogenetic markers for metabolic impairments in treatment with valproic acid. Neurosci Behav Physiol 2020; 50: 13-19.
  29. Gungor S, Yücel G, Akinci A, Tabel Y, Ozerol IH, Yologlu S. The role of ghrelin in weight gain and growth in epileptic children using valproate. J Child Neurol 2007; 22: 1384-1388.
  30. Greco R, Latini G, Chiarelli F, Iannetti P, Verrotti A. Leptin, ghrelin, and adiponectin in epileptic patients treated with valproic acid. Neurology 2005; 65: 1808-1809.
  31. Güzel A, Karasalihoğlu S, Küçükuğurluoğlu Y, Sayar E, Kunduracilar H. Evaluation of serum ghrelin and neuropeptide Y levels in epileptic children under valproate treatment. Trakya Universitesi Tip Fakultesi Dergisi 2009; 26: 18-23.
  32. Cansu A, Serdaroglu A, Çamurdan O, Hırfanoğlu T, Cinaz P. Serum insulin, cortisol, leptin, neuropeptide Y, galanin and ghrelin levels in epileptic children receiving valproate. Hormone Res Paediatr 2011; 76: 65-71.
  33. Tomoum HY, El-Hadidi ES. Ghrelin and resistin levels in children with epilepsy on valproic acid. J Pediatr Neurol 2009; 7: 223-229.
  34. Cansu A, Yesilkaya E, Serdaroglu A, Camurdan O, Hirfanoglu TL, Karaoglu A, et al. The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy. Endocr Res 2012; 37: 163-174.
  35. Çiçek NP, Kamaşak T, Serin M, Okten A, Alver A, Cansu A. The effects of valproate and topiramate use on serum insulin, leptin, neuropeptide Y and ghrelin levels in epileptic children. Seizure 2018; 58: 90-95.
  36. Hasaneen B, Salem NA, El Sallab S, Elgaml D, Elhelaly R. Body weight, body composition, and serum ghrelin in epileptic children receiving levetiracetam monotherapy. Egypt Pediatr Assoc Gazette 2016; 64: 154-159.
  37. Diler Durgut B, Dilber B, Kamaşak T, Yaman H, Saz ÖF, Kolaylı CC, et al. The relationship between ghrelin, epilepsy-related inflammatory biomarkers (IL-1β, IL-1R1, HMGB1), and drug-resistant epilepsy in children. Epilepsy Res 2025; 213: 107553. DOI: 10.1016/j.eplepsyres.2025.107553.
  38. Ozcelik AA, Serdaroglu A, Bideci A, Arhan E, Soysal Ş, Demir E, Gücüyener K. The effect of topiramate on body weight and ghrelin, leptin, and neuropeptide-Y levels of prepubertal children with epilepsy. Pediatr Neurol 2014; 51: 220-224.
  39. Cansu A, Serdaroglu A, Cinaz P. Serum insulin, cortisol, leptin, neuropeptide Y, galanin and ghrelin levels in epileptic children receiving oxcarbazepine. Eur J Paediatr Neurol 2011; 15: 527-531.
  40. Marchiò M, Roli L, Giordano C, Trenti T, Guerra A, Biagini G. Decreased ghrelin and des-acyl ghrelin plasma levels in patients affected by pharmacoresistant epilepsy and maintained on the ketogenic diet. Clin Nutr 2019; 38: 954-957.
  41. Marchiò M, Roli L, Lucchi C, Costa AM, Borghi M, Iughetti L, et al. Ghrelin plasma levels after 1 year of ketogenic diet in children with refractory epilepsy. Front Nutr 2019; 6: 112. DOI: 10.3389/fnut.2019.00112.
  42. De Amicis R, Leone A, Lessa C, Foppiani A, Ravella S, Ravasenghi S, et al. Long-term effects of a classic ketogenic diet on ghrelin and leptin concentration: a 12-month prospective study in a cohort of italian children and adults with GLUT1-deficiency syndrome and drug resistant epilepsy. Nutrients 2019; 11: 2019. DOI: 10.3390/nu11081716.
  43. Aydin S, Dag E, Ozkan Y, Arslan O, Koc G, Bek S, et al. Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients. Peptides 2011; 32: 1276-1280.
  44. Marchiò M, Roli L, Giordano C, Caramaschi E, Guerra A, Trenti T, Biagini G. High plasma levels of ghrelin and des-acyl ghrelin in responders to antiepileptic drugs. Neurology 2018; 91: e62-e66. DOI: 10.1212/WNL.0000000000005741.
  45. Taskin E, Atli B, Kiliç M, Sari Y, Aydin S. Serum, urine, and saliva levels of ghrelin and obestatin pre- and post-treatment in pediatric epilepsy. Pediatr Neurol 2014; 51: 365-369.
  46. Varrasi C, Strigaro G, Sola M, Falletta L, Moia S, Prodam F, Cantello R. Interictal ghrelin levels in adult patients with epilepsy. Seizure 2014; 23: 852-855.
  47. Yu AH, Liu Q, Sun CJ. The clinical value of EEG monitoring and silver nanoparticles to detect the levels of serum Nesfatin-1, S100β and neuron-specific enolase in evaluating the severity and prognosis of epilepsy. Materials Express 2021; 11: 1786-1791.
  48. Chen M, Xie M, Wan J. Dynamic variety of serum Nesfatin-1 and its clinical values in evaluation on illness condition and short-term prognosis in patients with epileptic seizure. Journal of Jilin University (Medicine Edition) 2019; 45: 105-110 [In Chinese].
  49. Meierkord H, Shorvon S, Lightman SL. Plasma concentrations of prolactin, noradrenaline, vasopressin and oxytocin during and after a prolonged epileptic seizure. Acta Neurol Scand 1994; 90: 73-77.
  50. Prodam F, Bellone S, Casara G, De Rienzo F, Grassino EC, Bonsignori I, et al. Ghrelin levels are reduced in prepubertal epileptic children under treatment with carbamazepine or valproic acid. Epilepsia 2010; 51: 312-315.
  51. Aydin S. Are ghrelin levels really elevated in epileptic patients? Seizure Letter 2007; 469. DOI: 10.1016/j.seizure.2007.03.009.
  52. Keloglan SM, Aycik FB, Kocacan SE, Yazgan B, Ayyildiz M, Agar E. Nesfatin-1 exerts anticonvulsant effect by reducing oxidative stress in experimental epilepsy model. Acta Neurobiol Exp 2023; 83. DOI: 10.55782/ane-2023-2419.
  53. Pylvänen V, Pakarinen A, Knip M, Isojärvi J. Insulin-related metabolic changes during treatment with valproate in patients with epilepsy. Epilepsy Behav 2006; 8: 643-648.
  54. Wirrell EC. Valproic acid-associated weight gain in older children and teens with epilepsy. Pediatr Neurol 2003; 28: 126-129.
  55. Verrotti A, D’Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev 2011; 12: e32-e43. DOI: 10.1111/j.1467-789X.2010.00800.x.
  56. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001; 69: 89-95.
  57. Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol 2011; 10: 446-456.
  58. Tokgoz H, Aydin K, Oran B, Kiyici A. Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate. Childs Nervous Syst 2012; 28: 1049-1053.
  59. Rifai N, Gillette MA, Carr SA. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 2006; 24: 971-983.
  60. Pepe MS, Feng Z, Janes H, Bossuyt PM, Potter JD, Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J Natl Cancer Inst 2008; 100: 1432-1438.
  61. Vickers AJ, Van Calster B, Steyerberg EW. Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. BMJ 2016; 352: i6. DOI: 10.1136/bmj.i6.
  62. Ferrante di Ruffano L, Hyde CJ, McCaffery KJ, Bossuyt PM, Deeks JJ. Assessing the value of diagnostic tests: a framework for designing and evaluating trials. BMJ 2012; 344: e686. DOI: 10.1136/bmj.e686.
  63. Pitkänen A, Ekolle Ndode-Ekane X, Lapinlampi N, Puhakka N. Epilepsy biomarkers – toward etiology and pathology specificity. Neurobiol Dis 2019; 123: 42-58.
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