In a recent study published in Frontiers in Nutrition, researchers investigate the potential protective effects of ketosis-inducing diets on migraines.

Study: Ketosis and migraine: a systematic review of the literature and meta-analysis. Image Credit: Chatham172 / Shutterstock.com

Background

Headaches are widespread and a significant source of impairment globally. Current therapies for migraine prophylaxis lack specificity, have poor tolerability and limited efficacy, and have potential adverse effects, thus leading to poor results.

According to recent studies, certain dietary treatments may provide symptomatic relief from migraine episodes. The ketogenic diet, which substitutes glucose, the brain's primary source of energy, with ketone bodies, is a promising approach that may reduce the number or intensity of headaches.

About the study

In the present meta-analysis, researchers evaluate the efficacy of ketogenic dietary treatment (KDT) in migraine prevention and attenuation.

The ketogenic therapies tested in migraine treatments included the very-low-calorie ketogenic diet (VLCKD, four studies), modified Atkins diet (MAD, three studies), classic ketogenic diet (cKDT, two studies), and β-hydroxybutyrate administration (BHB). Ketogenic diets were characterized by high-fat, moderate-protein, and low-carbohydrate intake.

Data on the tolerability and efficacy of different ketogenic diets as compared to other control diets or placebos, as well as the levels of ketosis in migraine management among children, adolescents, and adults, were searched through the Cochrane Library, PubMed/Medline, Web of Science, Scopus, Science Direct, and LILACS databases.

Additional references from recent studies or those found in previous review articles were also included. Only observational studies and clinical trials published within the previous ten years in Italian, English, Spanish, or Portuguese were included.

Studies including individuals without migraine, assessing ketoses unrelated to ketogenic diets or exogenous ketone body administration, such as ketosis in diabetes, and outcomes unrelated to migraine episodes, were excluded from the analysis. Non-human studies with unavailable full text, opinion articles, reviews, letters, guidelines, comments, editorials, news, case reports, case series, abstracts, dissertations, theses, and animal or in vitro studies were also excluded.

Two researchers independently screened the data, with a third researcher resolving any disagreements between these two researchers. The Cochrane RoB version 2.0 tool was used to assess bias risks, whereas the Mixed Methods Appraisal Tool (MMAT) system evaluated evidence quality.

Study findings

Initially, 2,582 studies were identified, from which 169 duplicates were removed, and 2,413 were screened. Thereafter, 1,042 studies were excluded due to the wrong sample population, and 725 studies were removed due to out-of-data period.

Additionally, 215 studies were excluded due to the inclusion of other outcomes, 195 studies differed in publication type, 39 studies were excluded due to study design, 100 studies were conducted in animals, and 59 studies were published in a different language.

This led to 41 remaining studies, 12 of which were assessed for eligibility. A total of ten studies were ultimately considered for the final analysis after excluding three studies due to their publication type and one study due to the outcome evaluated.

Half of the studies had low bias risks, with most issues concerning randomization. All studies included only adult individuals.

Ketosis evaluation was inconsistent between the included studies, with a few studies evaluating ketonuria, some evaluating ketonemia, and others with no ketosis level evaluation. Thus, no relationships between ketosis levels and migraine prevention or reduced migraine episodes could be inferred.

Despite high levels of heterogeneity in the included studies, all ketogenic interventions showed significant effects, irrespective of exogenous or endogenous ketosis induction. A mean dropout rate of 21% was documented in the included studies and was higher among patients undergoing the classic ketogenic diet and lower for the modified Atkins diet at 34% and 13%, respectively.

Conclusions

The study findings indicate that ketogenic treatment may improve migraine treatment and should be studied further through randomized clinical trials with appropriate and standardized methodologies. Proper measurement of ketone levels during ketogenic therapy is essential to monitor adherence and improve understanding of the relationship between ketone bodies and efficacy.

Some important considerations include the correlation between migraine improvement and weight loss in overweight subjects, a lack of a well-defined association between blood and urine ketones, and potential mechanisms of action for ketogenic therapy. Future studies should evaluate compliance rates according to migraine type and diverse ketogenic dietary interventions, as well as their optimal duration, repeatability, feasibility in normal-weight individuals, and association with conventional migraine prophylaxis.

Journal reference:

• de Cassya Lopes Neri, L., Ferraris, C., Catalano, G., et al. (2023) Ketosis and migraine: a systematic review of the literature and meta-analysis. Frontiers in Nutrition. doi:10.3389/fnut.2023.1204700