Effects of probiotic and vitamin D co-supplementation on clinical symptoms, mental health, and inflammation in adult patients with migraine headache: a randomized, triple-blinded, placebo-controlled trial.

Background: Migraine headache is a major public health problem. Routine medications for migraine treatment are not useful in treating all patients and may have some side effects. The present study aimed to investigate the effect of vitamin D and probiotic co-supplementation on clinical characteristics of migraine, daily functioning, mental health outcomes, and serum levels of high-sensitivity C-reactive protein (hs-CRP).

Methods: In this randomized, triple-blinded, placebo-controlled trial, patients aged 18 to 55 years diagnosed with migraine based on the International Classification of Headache Disorders-3 (ICHD-3) were randomized to either vitamin D (50,000 IU every 2 weeks) plus probiotic (4.5 × 10¹¹ CFU per day) or placebo for 12 weeks. The Headache Impact Test (HIT-6) and Depression, Anxiety, and Stress Scale (DASS) questionnaires were administered to patients at baseline and after 12 weeks. In addition, the frequency, duration, and severity of migraine headaches per month were assessed using a self-administered 30-day headache diary at baseline and the end of the intervention. Anthropometric indices, blood pressure, and serum levels of 25-hydroxy vitamin D and hs-CRP were also examined at first and the end of the study.

Results: Seventy-two migraine patients with a mean age of 37.46 $\pm$ 8.32 years were included in this trial. Probiotic and vitamin D co-supplementation compared to placebo resulted in a significant increase in serum levels of vitamin D (+ 12.86 $\pm$ 1.64 vs. + 1.12 $\pm$ 0.80 ng/mL, P < 0.001). The between-group analysis in the adjusted model showed a significantly greater reduction in migraine headache frequency (- 3.17 $\pm$ 0.84 vs. - 1.25 $\pm$ 0.34; P = 0.031) and severity (- 1.55 $\pm$ 0.35 vs. + 0.67 $\pm$ 0.29; P = 0.017) in the probiotic and vitamin D group than the placebo group. No significant difference was found between the two arms of the intervention regarding the change in headache duration, hs-CRP, scores of DASS, and HIT-6 questionnaires (P > 0.05).

Conclusions: This trial showed that probiotic and vitamin D co-supplementation for 12 weeks has beneficial effects on migraine headache characteristics. Further research is needed to confirm this finding.