Dietary Intervention for Migraine Relief

Overview

The goal of this clinical trial is to evaluate whether a low-glutamate diet can improve migraine symptoms in adults with migraine and to explore possible biological changes associated with dietary improvement. The study focuses on whether reducing dietary glutamate intake may influence processes involved in migraine, such as brain excitation, inflammation, and oxidative stress. The main questions this study aims to answer are: Does following a low-glutamate diet reduce the number of migraine days and the severity and duration of migraine attacks, and improve quality of life? Are improvements in migraine symptoms associated with changes in blood-based biological markers related to migraine activity? Researchers will compare participants assigned to the low-glutamate diet with participants assigned to a wait-list control group to evaluate differences in migraine outcomes and related biological measures. Participants will: Complete a baseline run-in period while tracking headaches using a daily migraine diary Either follow a low-glutamate dietary intervention or continue their usual diet as part of a wait-list control Complete standardized questionnaires related to migraine symptoms and quality of life Provide blood samples for laboratory analyses Undergo neuroimaging assessments (for a subset of participants)

The purpose of this clinical trial is to evaluate whether a low-glutamate diet is an effective treatment for migraine and to explore how this dietary approach may influence biological processes related to migraine. The low-glutamate diet reduces intake of free glutamate commonly found in ultra-processed foods and food additives, while emphasizing whole foods rich in nutrients that support brain health and reduce oxidative stress. The study is based on prior research showing that this diet led to substantial improvements in migraine symptoms among individuals with chronic pain, with migraine remission often observed after one month. These improvements were also associated with measurable changes in brain structure, suggesting a potential link between dietary glutamate exposure and migraine-related brain changes. The primary goals of this study are to: Determine whether one month on a low-glutamate diet reduces migraine frequency, severity, and duration and improves quality of life Examine changes in blood markers related to migraine pain signaling Assess whether dietary changes are associated with changes in brain structure or chemistry in a subset of participants Participants will first complete a 4-week run-in period during which they will continue their usual diet and record headaches and migraines using a daily electronic diary. Eligible participants will then be randomly assigned to either begin the low-glutamate diet immediately or continue their usual diet for one additional month (wait-list control). All participants will complete questionnaires, provide blood and urine samples, and undergo in-person assessments at the end of each study phase. A subset of participants will also undergo Magnetic Resonance Imaging (MRI) scans. Participants assigned to the diet will receive structured dietary training, educational materials, and weekly follow-up support to promote adherence. After the initial dietary phase, participants will complete a double-blind, placebo-controlled crossover challenge, during which they will receive short courses of monosodium glutamate (MSG) and placebo while remaining on the low-glutamate diet. This phase is designed to determine whether migraine symptoms return specifically in response to glutamate exposure. Throughout the study, participants will continue to track migraine symptoms using daily diaries. The results of this study may help determine whether a low-glutamate diet is a safe, non-pharmacologic treatment option for migraine and may provide insight into dietary factors that contribute to migraine development and persistence.