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Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial

Piccolo V, Marzocchi A, Maisto M, Summa V, Tenore GC, Amoresano A. Frontiers in Nutrition, 2025; 12:1560654.

Randomised controlled trialHumansWith melatonin

This study tested palmitoylethanolamide together with melatonin. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Randomised controlled trial
Subjects
60 adults with low-frequency episodic migraine randomised, 30 in each group. All completed.
Dose used in the study
1,200 mg of palmitoylethanolamide with 0.2 mg of melatonin, once a day at bedtime
Duration
3 months, after a 2-month run-in
What was measured
Migraine days per month. Intensity, duration, disability, use of pain medication and associated symptoms.

What the authors reported

The authors reported a fall in migraine days from 3.4 to 2.2 a month in the combination group, with no change in the placebo group. They also reported falls in the duration and intensity of attacks and in disability. No adverse events were reported.

Limits of this study

Participants had low-frequency migraine, so the results may not apply to frequent migraine. The sample was small and the outcomes were self-reported. The authors name these limits. They reported no financial support.

Source

doi:10.3389/fnut.2025.1560654

Entry checked against the full text at the publisher (Frontiers) on 2026-09-21. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.