Tryptophan metabolism in migraine: a review of experimental and clinical studies and a need to enhance research strategies.

Abstract

Tryptophan (TRP) metabolism produces various neuroactive substances in the gastrointestinal tract, as well as in the central and peripheral nervous systems and intestinal microbiota. Initially centered on the serotonin pathway in TRP metabolism and TRP itself, many studies are now focusing on the kynurenine pathway, with an increasing interest in the indole pathway. Several TRP metabolites have been associated with migraines, suggesting that TRP metabolism may serve as a potential therapeutic target. However, these studies have significant limitations, including a small number of participants, a lack of standardized diets prior to and/or during clinical trials, and insufficient information regarding the transformation of TRP after its intake. Furthermore, no thorough study encompasses all the essential components of TRP metabolism: products, enzymes, receptors, and transporters. Different mechanisms may explain the involvement of TRP metabolism in migraines, including glutamate signaling and neurovasodilatory, immune, oxidative, and inflammatory processes. The results of studies on the role of TRP metabolism in migraine may be helpful for making dietary recommendations for migraine prevention and clinical management; however, individual characteristics for metabolizing TRP should be considered. The aim of this narrative perspective review is to critically present the results of studies on the role of TRP metabolism in migraine and explore their implications for migraine prevention and therapy. Unlike many other reviews that focus solely on either the serotonin or kynurenine pathway, our paper addresses all three primary TRP metabolism pathways.