The Neuroprotective Role of Indole-3-Propionic Acid in Migraine Pathophysiology.

: Migraine is a leading cause of disability worldwide, with complex pathophysiological mechanisms involving oxidative and nitrosative stress. Recent research suggests that Indole-3-Propionic Acid (IPA) may have a neuroprotective role in reducing nitrosative stress. This study aims to elucidate the roles of IPA and nitrosative stress biomarkers in migraine patients, focusing on their potential as therapeutic targets. : This cross-sectional, case-control study included 57 migraine patients and 30 healthy controls. Patients were categorized into episodic migraine (EM) and chronic migraine (CM) groups. Socio-demographic and clinical characteristics were documented through structured interviews. Validated scales such as the Visual Analog Score (VAS), Headache Impact Test 6 (HIT-6), Migraine Disability Assessment Test (MIDAS), Migraine 24 h Quality of Life Scale (24 h QoL), Mini-Mental State Examination (MMSE), and Migraine Attacks-Subjective Cognitive Impairments Scale (Mig-SCog) were administered. Venous blood samples were collected, and serum levels of IPA, Nitric Oxide (NO), Nitric Oxide Synthase (NOS), and Peroxynitrite (ONOO) were measured using ELISA and spectrophotometric methods. : Significant differences in serum IPA and NO levels were observed between migraine patients and controls. Specifically, higher serum IPA levels were found in the EM group, while higher serum NO levels were observed in the CM group. Elevated NO levels correlated with increased migraine attack frequency. Conversely, serum IPA levels showed a negative correlation with attack frequency, suggesting a protective role. Specifically, NO levels were positively correlated with the number of painful days, NSAID usage, VAS scores, HIT-6 scores, and MIDAS scores, while negatively correlated with 24 h QoL scores. : The study highlights the significant involvement of IPA and nitrosative stress in migraine pathophysiology. Elevated IPA levels, particularly in EM patients, suggest its potential neuroprotective role. These findings underscore the importance of targeting oxidative and nitrosative stress pathways in developing effective migraine therapies.