The Effectiveness of Vitamin B12 for Relieving Pain in Aphthous Ulcers: A Randomized, Double-blind, Placebo-controlled Trial

Pain Manag Nurs. 2015 Jun;16(3):182-7. doi: 10.1016/j.pmn.2014.06.008.


Aphthous ulcers, the most common oral mucosal lesions seen in primary care, occur in up to ∼2%-50% of the general population. Our objective was to confirm the analgesic benefit of treatment of mouth ulcers with vitamin B12 as adjunctive therapy. A randomized, double-blind, placebo-controlled trial was performed with primary care patients. The intervention group received vitamin B12 ointment for 2 days. In total, 42 patients suffering from aphthous ulcers participated in the study: 22 were included in the intervention group and 20 in the control group. All parameters of aphthous ulcers of patients in the intervention group were recorded and compared with those in the control group. We assessed the patients' pain levels before and after treatment using a visual analog scale. The statistical analyses were performed using a nonparametric Mann-Whitney test. Statistically significant differences in pain levels were found between the intervention group and the control group after 2 days of treatment (mean visual analog scale, 0.36 [95% CI, 0.01-0.71] vs. 1.80 [1.16-2.44]; p < .001). In conclusion, the results of this research study provide evidence that vitamin B12 is an effective analgesic treatment for aphthous ulcers. This study indicates that healthcare providers could use vitamin B12 as an adjunctive therapy for mouth ulcers, providing more effective pain management and improving the quality of life for patients with mouth ulcers.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain / prevention & control*
  • Stomatitis, Aphthous / drug therapy*
  • Treatment Outcome
  • Vitamin B 12 / therapeutic use*
  • Vitamin B Complex / therapeutic use*
  • Young Adult


  • Analgesics
  • Vitamin B Complex
  • Vitamin B 12