Efficacy and safety of exogenous beta-hydroxybutyrate for preventive treatment in episodic migraine: A single-centred, randomised, placebo-controlled, double-blind crossover trial. (April 2022)

• Record Type: Journal Article
• Authors: Putananickal, Niveditha; Gross, Elena C; Orsini, Anna-Lena; Schmidt, Simone; Hafner, Patricia; Gocheva, Vanya; Nagy, Sara; Henzi, Bettina C; Rubino, Daniela; Vogt, Deborah R; Cichon, Sven; Sandor, Peter; Fischer, Dirk
• Is Part Of: Cephalalgia. Volume 42:Number 4/5(2022)
• Page Start: 302
• Page End: 311
• Publication Date: 2022-04
• Subjects: Migraine -- prophylactic therapy -- randomised clinical trial -- exogenous ketone bodies -- ketone salt; Headache -- Periodicals; 616.8491
• DOI: 10.1177/03331024211043792
• Languages: English
• ISSNs: 0333-1024

Abstract

Background: Several studies propose that brain energy deficit might be partially involved in the pathophysiology of migraine. Previously, studies demonstrated that ketogenic diet causes a substantial reduction in migraine frequency. Since the ketogenic diet is restricting and its adherence is difficult, we proposed to supplement ketone bodies exogenously to provide a prophylactic effect in migraineurs. Aim: To evaluate the prophylactic effect of exogenous DL-beta-hydroxybutyrate supplementation in episodic migraineurs. Methods: A double-blind, placebo-controlled, randomised crossover trial was conducted, involving 41 patients with episodic migraine. Patients were randomised 1:1 into placebo or beta-hydroxybutyrate group before entering the first treatment period. Each treatment period was 12 weeks long, followed by four weeks of washout phase and four weeks of run-in phase before entering into the corresponding second treatment period. The primary endpoint was the number of migraine days in the last four weeks of treatment, adjusted for baseline. Results: We observed no clinically significant amelioration of migraine frequency or intensity under DL-beta-hydroxybutyrate treatment as compared to placebo regarding number of migraine days (mean difference [95% CI]: −1.1[−5.07, 2.85]), migraine intensity (0–10 VAS: 1.5[−0.8, 3.7]). Conclusion: The selected dose of supplemented exogenous DL-beta-hydroxybutyrate did not demonstrate efficacy in episodic migraineurs. ClinicalTrials.gov Identifier: NCT03132233