Simvastatin and Vitamin D for Migraine Prevention

A small trial recently demonstrated that the combination of simvastatin and vitamin D significantly reduced the frequency of episodic migraine.1

An earlier cross-sectional study conducted by these investigators showed that individuals with higher serum vitamin D levels who used statins had a significantly lower risk of severe headache or migraine (OR 0.48; 95% CI, 0.32-0.71; p=0.001).2  These results, along with evidence that statins improve endothelial function, reduce vascular inflammation, decrease platelet aggregation, and improve autonomic regulation, were the impetus for this randomized, controlled trial.1

Study Design

The study involved 57 participants with episodic migraine, which was defined as 4 to 14 migraine days per month during the baseline period.1 After a 12-week baseline period, participants were randomly assigned to simvastatin (20 mg twice daily) plus vitamin D (1000 IU twice daily) or placebo. Participants were allowed to continue stable regimens of abortive and prophylactic migraine medications. The study included two 12-week follow-up periods, during which time participants recorded headache information in a paper diary.

During the baseline period, the median number of migraine days was 25.5 and 18.0 for the active treatment and placebo groups, respectively, which was a statistically significant difference (p=0.05).1 Body mass index and age were also significantly different between the two groups. The authors controlled for these differences using post-hoc regression analyses.


The primary outcome was the change in the number of migraine days between the baseline period and each of the 12-week follow-up periods (weeks 1-12 and weeks 13-24).1 The decrease was significantly greater in the active treatment group than in the placebo group during both follow-up periods (Table), and amounted to 30% fewer migraine days. When the results were analyzed by migraine burden at baseline (<8 versus ≥8 migraine days per month), benefits were seen for patients in both groups.

Table. Change From Baseline in Number of Migraine Days

Simvastatin + Vitamin D (d)Placebo (d)P value for change  between groups
Weeks 1-12–8.0 (p<0.001)a1.0 (p=0.23)ap<0.001
Weeks 13-24–9.0 (p<0.001)a3.0 (p=0.06)ap<0.001

Adapted from: Buettner C, et al. Ann Neurol. 2015 Sep 29.

a p value for change within groups.

At 24 weeks, 29% (8/28) of the participants in the active treatment group were 50% responders, compared with only 3% (1/29) participants in the placebo group (p=0.03). Participants in the active treatment group also used less abortive migraine medication.

Migraine disability was reduced during the first follow-up period, but not the second. Simvastatin plus vitamin D was not associated with any changes in migraine symptoms, severity, or duration.


The authors note that their result—30% fewer migraine days—is greater than the effect size of other effective migraine prevention agents.1 They suggest that this study should be repeated in a larger and more diverse population, which would address issues with imbalance between the treatment groups with respect to baseline migraine days, body mass index, and age. They indicate that future studies could be designed to distinguish the effects of simvastatin alone, vitamin D alone, and combination treatment.

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