Abstract

Dr. Kalpesh Ladhawala*, Dr. Nidhi Tanmay Shah, Dr. Khushal R. Shah, Amit Patel, Avinash Valu Ahire, Aadit Shah

ABSTRACT

Migraine is a debilitating neurological disorder of profound global impact, fundamentally characterized by a state of neuronal hyperexcitability and a lowered threshold for cortical spreading depression (CSD).[4] Magnesium, an essential intracellular cation, functions as a critical physiological neuromodulator, and a substantial body of evidence links magnesium deficiency to migraine pathogenesis.[4] While the neuroprotective mechanisms of magnesium—primarily through voltage-dependent antagonism of the N-methyl-D-aspartate (NMDA) receptor, attenuation of CSD, and anti-inflammatory actions—are well-established, its clinical efficacy as a prophylactic agent is often constrained by two principal physiological barriers: systemic bioavailability following oral administration and, more critically, transport across the blood–brain barrier (BBB) to exert its effects within the central nervous system.[5] The "Triple Magnesium Complex" has emerged as a modern nutraceutical strategy, formulating multiple magnesium salts to theoretically optimize absorption and tolerability.[16] This comprehensive review synthesizes the current understanding of migraine pathophysiology, the pharmacology of various magnesium forms, and the intricate molecular mechanisms governing magnesium transport across the BBB. A critical analysis of the clinical evidence reveals that while oral magnesium is a probably effective prophylactic therapy, a significant gap exists between the compelling theoretical rationale for multi-component and novel chelated magnesium supplements and the direct clinical trial data supporting their superiority in migraine management.[19] Ultimately, enhancing and validating efficient BBB transport represents the next frontier in developing magnesium-based therapies capable of realizing their full neuroprotective potential in migraine.