Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial

J Am Dent Assoc. 2012 Apr;143(4):370-6. doi: 10.14219/jada.archive.2012.0179.


Background: Recurrent aphthous stomatitis (RAS) is a painful condition of unknown etiology, affecting more than 2.5 billion people worldwide. Vitamin deficiencies have been implicated as a possible cause.

Methods: The authors conducted a single-center, randomized, parallel-arm, double-masked, placebo-controlled study to examine the effect of daily multivitamin supplementation on the number and duration of RAS episodes. The authors randomly assigned 160 adults who had a validated history of at least three episodes of idiopathic minor RAS within the previous 12 months to one of two groups: the first group (n = 83) received a once-daily multivitamin containing 100 percent of the U.S. reference daily intake (RDI) of essential vitamins, and the second group (n = 77) received once-daily placebo for up to 365 days.

Results: The results showed no significant difference in the mean number of new RAS episodes between the multivitamin (4.19 episodes) and placebo (4.60 episodes) arms during the study period (P = .69). The mean duration of new RAS episodes also was similar for the multivitamin (8.66 days) and placebo (8.99 days) arms (P = .60). Furthermore, the authors found no differences between the two arms with regard to mouth pain, normalcy of diet or compliance with the study medication regimen.

Conclusion: Daily multivitamin supplementation, with the RDI of essential vitamins, did not result in a reduction in the number or duration of RAS episodes.

Clinical implications: Clinicians should not recommend multi-vitamin supplementation routinely as prophylaxis for RAS.

Trial registration: NCT00527306.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antioxidants / therapeutic use
  • Ascorbic Acid / therapeutic use
  • Diet
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Folic Acid / blood
  • Folic Acid / therapeutic use
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Nutrition Policy
  • Patient Compliance
  • Placebos
  • Prospective Studies
  • Recurrence
  • Stomatitis, Aphthous / blood
  • Stomatitis, Aphthous / prevention & control*
  • Treatment Outcome
  • Vitamin A / therapeutic use
  • Vitamin B 12 / blood
  • Vitamin B 12 / therapeutic use
  • Vitamin B Complex / therapeutic use
  • Vitamin D / therapeutic use
  • Vitamin E / therapeutic use
  • Vitamins / therapeutic use*
  • Young Adult


  • Antioxidants
  • Placebos
  • Vitamins
  • Vitamin A
  • Vitamin B Complex
  • Vitamin D
  • Vitamin E
  • Folic Acid
  • Vitamin B 12
  • Ascorbic Acid

Associated data