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Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial



Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs.

Methods and materials

This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 μg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method.


At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055).


Based on the results of this study, we found that 2000 IU (50 μg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

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This research has been supported by Tehran University of Medical Sciences & health Services grant 96-04-161-37647 and 96-04-54-36870.

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Correspondence to Maryam Mahmoudi.

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The study protocol was reviewed and approved by ethics committee of vice-chancellor in research affairs, Tehran University of Medical Sciences (ethics code: IR.TUMS.VCR.REC.1397.170). Before undergoing any study procedure, all patients gave written informed consent.

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Ghorbani, Z., Togha, M., Rafiee, P. et al. Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial. Neurol Sci 41, 1183–1192 (2020).

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  • Analgesics
  • Cholecalciferol
  • Frequency
  • Headache attacks
  • Inflammation
  • Severity