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

Randomized, triple-blinded, placebo-controlled trial in adults with migraine meeting ICHD-3 criteria and recruited from a neurology clinic in Isfahan, Iran. The study randomized 36 participants in a 1:1 ratio, corresponding to about 18 participants in the probiotic plus vitamin D arm and 18 in placebo.

In the active arm, adults with migraine received a combined oral regimen of probiotic capsules (4.5 × 10^11 CFU per day) plus vitamin D pearls (50,000 IU every 2 weeks) for 12 weeks. The comparison arm received identical placebo capsules/pearls.

Twelve weeks of probiotic plus vitamin D co-supplementation improved migraine frequency and severity compared with placebo, but did not meaningfully improve headache duration, daily functioning, mental health outcomes, or hs-CRP. Migraine attacks fell from 7.76 ± 0.81 to 4.50 ± 0.56 per month, with a between-group difference of P = 0.039 and ANCOVA P = 0.031; migraine severity also improved, from 8.31 ± 0.28 to 6.75 ± 0.39 on VAS, with ANCOVA P = 0.017. Headache duration was not significantly different from placebo (ANCOVA P = 0.171), HIT-6 was not significant (ANCOVA P = 0.726), and hs-CRP did not change significantly (P = 0.261). No side effects were reported in either group.

The trial was small, with only about 18 participants in the active arm, and lasted just 12 weeks, which limits precision and long-term interpretation. It was also a single-center study in one Iranian neurology clinic, which may limit generalizability. Because probiotic and vitamin D were tested together, the effect of each component cannot be separated.