# Dietary Modulation of Migraine: Metabolic, Neuroinflammatory and Microbiota-Mediated Mechanisms

**Authors:** Domenico Santangelo, Concetta Lobianco, Rosalia Eugenia Burrafato, Federico Tosto, Giuseppe Magro, Angelo Pascarella

PMC · DOI: 10.3390/jcm15041476 · 2026-02-13

## TL;DR

This review explores how diet can influence migraine through metabolic, inflammatory, and gut microbiota pathways, suggesting diet may help reduce migraine frequency and severity.

## Contribution

The paper provides a comprehensive overview of how diet modulates migraine through metabolic and microbiota mechanisms, highlighting gaps in current research.

## Key findings

- Dietary interventions like ketogenic and DASH diets may reduce migraine frequency by modulating metabolic and inflammatory pathways.
- The gut microbiota influences migraine through the gut–brain axis, affecting inflammation and neuronal excitability.
- Current evidence is limited by small sample sizes and lack of standardized protocols, necessitating more robust studies.

## Abstract

Migraine is a common neurological condition characterized by recurrent headache attacks, frequently associated with prodromal, aura, and postdrome phases. Increasing evidence suggests that metabolic and mitochondrial dysfunction play a central role in migraine pathophysiology, contributing to cortical hyperexcitability and increased oxidative stress. Additionally, the gut microbiota has emerged as an important modulator of migraine susceptibility via the gut–brain axis, influencing inflammation, neurotransmitter production, and neuronal excitability. Specific dietary interventions, including ketogenic diets, low-carbohydrate diets, DASH, omega-3 supplementation, and elimination diets, may modulate these metabolic and inflammatory pathways, as well as the microbiota composition, ultimately reducing the frequency and severity of migraine attacks. This review provides an overview of current evidence on the interplay between metabolism, microbiota, and diet in migraine pathophysiology and management. Overall, the available data support a biologically plausible role for diet as an adjunctive strategy in migraine prevention; however, the current evidence remains highly heterogeneous and is often limited by small sample sizes in sample size, a lack of protocol standardization, suboptimal adherence assessment, and insufficient long-term follow-up. Future studies should focus on adequately powered trials with standardized outcome measures, objective biomarkers and precision medicine approaches.

## Linked entities

- **Diseases:** migraine (MONDO:0005277)

## Full-text entities

- **Genes:** INSR (insulin receptor) [NCBI Gene 3643] {aka CD220, HHF5}, MTHFR (methylenetetrahydrofolate reductase) [NCBI Gene 4524], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TRPV1 (transient receptor potential cation channel subfamily V member 1) [NCBI Gene 7442] {aka VR1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, TRPA1 (transient receptor potential cation channel subfamily A member 1) [NCBI Gene 8989] {aka ANKTM1, FEPS, FEPS1, p120}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** systemic (MESH:D015619), cerebral energy deficiency (MESH:D011502), neurogenic inflammation (MESH:D020078), visceral hypersensitivity (MESH:D004342), migraine aura (MESH:D020325), cortical spreading (MESH:D054220), HIT-6 (MESH:D013736), hyperhomocysteinemia (MESH:D020138), nausea (MESH:D009325), phonophobia (MESH:D012001), migraine with and without aura (MESH:D020326), obesity (MESH:D009765), CSD (MESH:D003866), irritable bowel syndrome (MESH:D043183), neuronal hyperexcitability (MESH:D009410), vomiting (MESH:D014839), hypoxia (MESH:D000860), Migraine (MESH:D008881), ketosis (MESH:D007662), instability (MESH:D043171), ischemia (MESH:D007511), neurological disorder (MESH:D009461), vascular dysregulation (MESH:D021081), impaired energy metabolism (MESH:D008659), photophobia (MESH:D020795), Impaired mitochondrial function (MESH:D028361), sleep disorders (MESH:D012893), Hypertension (MESH:D006973), Pain (MESH:D010146), visual disturbances (MESH:D014786), Hyperinsulinemia (MESH:D006946), nutritional deficiencies (MESH:D044342), endotoxemia (MESH:D019446), metabolic disturbances (MESH:D024821), reperfusion injury (MESH:D015427), neurological condition (MESH:D019636), injury to (MESH:D014947), tension-type headache (MESH:D018781), axis (MESH:C566610), Headache (MESH:D006261), gastrointestinal symptoms (MESH:D012817), Inflammation (MESH:D007249), Neuroinflammation (MESH:D000090862), Anxiety (MESH:D001007), insulin resistance (MESH:D007333), dehydration (MESH:D003681), weight loss (MESH:D015431), gastrointestinal comorbidities (MESH:D005767), neurovascular disorder (MESH:D013901), Dysbiosis (MESH:D064806), ischemic (MESH:D002545), endothelial dysfunction (MESH:D014652), bacteremia (MESH:D016470), IBS (MESH:D053560), habituation (MESH:D019966), neuropsychiatric disorders (MESH:D001523), Hypoglycemia (MESH:D007003)
- **Chemicals:** vitamin B12 (MESH:D014805), LPS (MESH:D008070), amitriptyline (MESH:D000639), docosahexaenoic acid (MESH:D004281), lipid (MESH:D008055), polyphenols (MESH:D059808), ATP (MESH:D000255), eicosapentaenoic acid (MESH:D015118), blood glucose (MESH:D001786), SCFA (MESH:D005232), DHA (MESH:C027493), calcium (MESH:D002118), ROS (MESH:D017382), Folate (MESH:D005492), glucose (MESH:D005947), serotonin (MESH:D012701), Ketone bodies (MESH:D007657), Magnesium (MESH:D008274), NO (MESH:D009569), alcohol (MESH:D000438), tryptophan (MESH:D014364), vitamin C (MESH:D001205), hydrogen (MESH:D006859), glutamate (MESH:D018698), potassium chloride (MESH:D011189), acetate (MESH:D000085), vitamin B6 (MESH:D025101), oxygen (MESH:D010100), nitrate (MESH:D009566), potassium (MESH:D011188), phosphorus (MESH:D010758), vitamin D (MESH:D014807), Atkins (-), beta-hydroxybutyrate (MESH:D020155), eicosanoid (MESH:D015777), phosphocreatine (MESH:D010725), epinephrine (MESH:D004837), CoQ10 (MESH:C024989), Carbohydrate (MESH:D002241), fatty acid (MESH:D005227), VPA (MESH:D014635), acetoacetate (MESH:C016635), starch (MESH:D013213), Riboflavin (MESH:D012256), propionate (MESH:D011422), Ketone (MESH:D007659), cortisol (MESH:D006854), nitrite (MESH:D009573), D3 (MESH:D002762), homocysteine (MESH:D006710), butyrate (MESH:D002087), lactate (MESH:D019344), Omega-3 fatty acids (MESH:D015525)
- **Species:** Neisseria (genus) [taxon 482], Sutterella (genus) [taxon 40544], Eggerthella (genus) [taxon 84111], Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mus musculus (house mouse, species) [taxon 10090], Eubacterium (genus) [taxon 1730]
- **Mutations:** C677T

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942355/full.md

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Source: https://tomesphere.com/paper/PMC12942355