Effectiveness of low-dose riboflavin as a prophylactic agent in pediatric migraine

Brain Dev. 2020 Aug;42(7):523-528. doi: 10.1016/j.braindev.2020.04.002. Epub 2020 Apr 23.


Background: Riboflavin may prevent migraine episodes; however, there is limited evidence of its effectiveness in pediatric populations. This study investigated the effectiveness of riboflavin and clinical predictors of response in children with migraines.

Methods: We retrospectively reviewed data from 68 Japanese children with migraines, of whom 52 also exhibited another type of headache. Patients received 10 or 40 mg/day of riboflavin. We evaluated the average migraine frequency per month as a baseline and after 3 months of riboflavin therapy to determine the effectiveness and clinical predictors of response.

Results: The frequency of migraine episodes was significantly lower at 3 months than at baseline (median, [interquartile range], 5.2 (3-7) vs. 4.0 (2-5); p < 0.01). Twenty-five patients (36.7%) showed 50% or greater reduction in episode frequency (responders), while 18 (26.5%) showed a 25%-50% reduction. We compared responders (n = 25) and non-responders (n = 43) and found no significant differences in sex, familial history, riboflavin dose, migraine type (i.e., presence or absence of aura), age at headache onset, or age at consultation. However, non-responders were more likely to have co-morbid non-migraine headaches (odds ratio, 4.11; 95% confidence interval [CI], 1.27-13.33; p = 0.02); this variable was also significant in a multivariate analysis (adjusted odds ratio, 3.8; 95% CI, 1.16-12.6; p = 0.03). Of the co-morbid headache types, only tension headaches were significant (odds ratio, 0.176; 95% CI, 0.04-0.73; p = 0.013). No adverse effects of riboflavin were identified.

Conclusions: Low-dose riboflavin is safe and modestly effective for migraines in children. It may be especially beneficial for children without other co-morbid headache types.

Keywords: Co-morbid headache; Headache; Migraine; Prevention; Prophylactic; Riboflavin.

MeSH terms

  • Adolescent
  • Child
  • Comorbidity
  • Female
  • Headache Disorders, Secondary / epidemiology
  • Humans
  • Male
  • Migraine Disorders / epidemiology
  • Migraine Disorders / physiopathology*
  • Migraine Disorders / prevention & control*
  • Outcome Assessment, Health Care*
  • Retrospective Studies
  • Riboflavin / administration & dosage*
  • Severity of Illness Index
  • Tension-Type Headache / epidemiology
  • Vitamin B Complex / administration & dosage*


  • Vitamin B Complex
  • Riboflavin