Ketosis and migraine: a systematic review of the literature and meta-analysis

Lenycia de Cassya Lopes Neri; Cinzia Ferraris; Guido Catalano; Monica Guglielmetti; Ludovica Pasca; Elena Pezzotti; Adriana Carpani; Anna Tagliabue

doi:10.3389/fnut.2023.1204700

Ketosis and migraine: a systematic review of the literature and meta-analysis

Front Nutr. 2023 Jun 12:10:1204700. doi: 10.3389/fnut.2023.1204700. eCollection 2023.

Authors

Lenycia de Cassya Lopes Neri^{1

2}, Cinzia Ferraris^{1

3}, Guido Catalano^{4

5}, Monica Guglielmetti^{1

3}, Ludovica Pasca^{4

5}, Elena Pezzotti⁴, Adriana Carpani⁴, Anna Tagliabue¹

Affiliations

¹ Ketogenic Metabolic Therapy Laboratory, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
² Faculty of Medicine, Department of Pediatrics, University of São Paulo, São Paulo, Brazil.
³ Laboratory of Food Education and Sport Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
⁴ Department of Child Neurology and Psychiatry, Istituto di Ricerca e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy.
⁵ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

Abstract

Introduction: Headaches are a prevalent disorder worldwide, and there is compelling evidence that certain dietary interventions could provide relief from attacks. One promising approach is ketogenic therapy, which replaces the brain's glucose fuel source with ketone bodies, potentially reducing the frequency or severity of headaches.

Aim: This study aims to conduct a systematic review of the scientific literature on the impact of ketosis on migraine, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.

Results: After a careful selection process and bias evaluation, 10 articles were included in the review, primarily from Italy. The bias assessment indicated that 50% of the selected articles had a low risk of bias in all domains, with the randomization process being the most problematic domain. Unfortunately, the evaluation of ketosis was inconsistent between articles, with some assessing ketonuria, some assessing ketonemia, and some not assessing ketosis levels at all. Therefore, no association could be made between the level of ketosis and the prevention or reduction of migraine attacks. The ketogenic therapies tested in migraine treatments included the very low-calorie ketogenic diet (VLCKD, n = 4), modified Atkins diet (MAD, n = 3), classic ketogenic diet (cKDT, n = 2), and the administration of an exogenous source of beta-hydroxybutyrate (BHB). The meta-analysis, despite reporting high heterogeneity, found that all interventions had an overall significant effect (Z = 9.07, p < 0.00001; subgroup differences, Chi2 = 9.19, dif = 3, p = 0.03; I², 67.4%), regardless of the type of endogenous or exogenous induction of ketosis.

Conclusion: The initial findings of this study suggest that metabolic ketogenic therapy may provide some benefit in treating migraines and encourage further studies, especially randomized clinical trials with appropriate and standardized methodologies. The review strongly recommends the use of the adequate measurement of ketone levels during ketogenic therapy to monitor adherence to the treatment and improve knowledge of the relationship between ketone bodies and efficacy.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022330626.

Keywords: ketogenic diet; ketosis; meta-analysis; migraine disorders; systematic review.

Publication types

Systematic Review