A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D₃ supplementation in adult patients with migraine

Abstract

Background: Vitamin D levels have been linked to certain pain states, including migraine. This study investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460).

Methods: A randomized, double-blinded, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18–65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin (n = 24, 18 women and 6 men, 100 μg/day D3-Vitamin) or placebo (n = 24, 18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e. experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6^TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)₂D were assessed from baseline to week 24.

Results: The number of headache days changed from 6.14 ± 3.60 in the treatment group and 5.72 ± 4.52 in the placebo group at baseline to 3.28 ± 3.24 and 4.93 ± 3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin demonstrated a significant decrease (p < .001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds, or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)₂D. No side-effects were reported or noted.

Conclusions: D3-Vitamin was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D₃ might be one of the prophylactic options for adult patients with migraine.

Trial registration: ClinicalTrials.gov identifier: NCT01695460.

Keywords:

• Vitamin D
• Migraine
• 25(OH)D
• 1,25(OH)₂D
• Pain
• Headache

Transparency

Declaration of funding

This study was financially supported by FSS grants (grant numbers 031301 and 831302) from the Danish Research Council to PG. Eir (Empowering Industry and Research) at SMI also partially supported the student’s work in this project based on a co-financing time-plan. The supporting organizations did not have any role in study design, data collection, data analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication. No funded writing assistance was used in the creation of this manuscript.

Declaration of financial/other relationships

The authors have no financial/other relationships to disclose. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We warmly thank all staff, study nurses, and laboratory assistants at CCBR Aalborg for their assistance in practical aspects of the study at the clinic, sampling, and laboratory procedures. We especially thank Morten R. Sørensen, Michael W. Boserup, Lone Kristiansen, Susanne Henriksen, and Maria E. Jensen for their excellent support. Furthermore, we would like to thank Anne Bülow-Olsen and Migraenikerforbundet for their assistance in advertising for recruitment. Gratitude also goes to Hans Ch. Hoeck, Flemming W. Bach, Ali Karshenas, Søren Due Andersen, and Meike Heskamp for their professional input and kind assistance. Brian Edwin Cairns, Lars Arendt-Nielsen, and Lone Schødt Andersen are also acknowledged for their input at the initial phases of the study protocol development. This study was not possible without excellent engagement and cooperation of our participants; we would like to extend our special appreciation to all of them.