Metabolic Syndrome and Migraine: Current Evidence, Pathophysiological Mechanisms and Clinical Implications

Abstract

Migraine and metabolic syndrome are highly prevalent disorders that increasingly appear to intersect through shared metabolic, inflammatory, neurovascular, and neuroendocrine pathways. Migraine is now recognized as a complex neurological disorder involving trigeminovascular activation, calcitonin gene-related peptide (CGRP) signaling, cortical hyperexcitability, neuroinflammation, and central sensitization, whereas metabolic syndrome comprises central obesity, insulin resistance, dyslipidemia, hypertension, and associated cardiometabolic abnormalities. Epidemiological evidence indicates that these conditions frequently coexist and that obesity, insulin resistance, adverse lipid profiles, blood-pressure abnormalities, and sex-related factors may influence migraine frequency, severity, and chronification. Mechanistically, visceral adiposity and adipokine dysregulation promote chronic low-grade inflammation, while cytokines such as TNF-α, IL-1β, and IL-6 activate NF-κB, Toll-like receptor, and NLRP3 inflammasome pathways. These processes interact with oxidative and nitrosative stress, mitochondrial dysfunction, impaired endothelial signaling, autonomic imbalance, hypothalamic dysfunction, blood–brain barrier alterations, and gut–brain axis disturbances.  CGRP provides a particularly important neuro-metabolic interface because it contributes to trigeminovascular transmission while also participating in vascular and metabolic regulation.  Mitochondrial energy failure, reactive oxygen species generation, impaired calcium handling, and ATP depletion may further lower the threshold for cortical spreading depolarization and trigeminal activation. Pasted text Collectively, current evidence supports a bidirectional metabolic–inflammatory–mitochondrial–neurovascular model linking metabolic syndrome with migraine. Recognition of this overlap may facilitate improved cardiometabolic screening, individualized migraine management, and development of integrated therapeutic strategies targeting both neurological and metabolic dysfunction.