Exploring The Roles of Ghrelin and Nesfatin-1 As Potential Biomarkers in Human Epilepsy: A Systematic Review

Ozgun Yetkin; Anna Sojka; Yasmin Bartosik; Barbara Steinborn; Barbara Dorocka-Bobkowska; Marcin Zarowski;

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ABSTRACT

Epilepsy affects approximately 50 million people worldwide, with approximately 30% of patients exhibiting pharmacoresistance. Identifying reliable biomarkers for diagnosis, predicting treatment response, and monitoring disease progression is essential for improving epilepsy management. Neuropeptides such as ghrelin and nesfatin-1 have emerged as potential candidates owing to their roles in neuroprotection and metabolic regulation. We systematically reviewed studies on ghrelin and nesfatin-1 in human epilepsy by searching PubMed, Embase and Web of Science. Inclusion criteria comprised original research reporting neuropeptide levels in patients with epilepsy. Data extraction and study selection followed PRISMA guidelines, and the protocol was registered with PROSPERO (CRD42024567659). Thirty-two studies published between 2005 and 2025 were included (27 on ghrelin and five on nesfatin-1). Ghrelin levels showed heterogeneous patterns - 37.1% of studies reported decreases, 29.6% reported increases, and 33.3% reported no change in epilepsy patients. Higher ghrelin levels were observed in focal epilepsy and in patients responding to anti-seizure medications (ASMs). Nesfatin-1 was elevated in 80% of studies, particularly in untreated or active epilepsy, but decreased in drug-resistant temporal lobe epilepsy and after long-term treatment. Evidence suggests that nesfatin-1 correlates with seizure burden and prognosis. Both neuropeptides show potential as biomarkers of disease severity and treatment response. Ghrelin and nesfatin-1 exhibit dynamic changes in relation to the type of epilepsy, seizure activity, and treatment. These neuropeptides may serve as non-invasive biomarkers and therapeutic targets, with near-term clinical potential for monitoring adverse side effects of ASM, differentiating between seizure types, and predicting drug resistance. However, validation studies are needed to establish clinical utility before routine implementation.

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