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B12 and Canker Sores
Abstract & Commentary
By Allan J. Wilke, MD. Dr. Wilke is Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of MedicineHuntsville Regional Medical Campus, Huntsville; he reports no financial relationship to this field of study. This article originally appeared in the Feb. 29, 2009, issue of Internal Medicine Alert. For that publication, it was peer reviewed by Gerald Roberts, MD, Assistant Clinical Professor of Medicine, Albert Einstein College of Medicine, Bronx, NY; Dr. Roberts reports no financial relationship to this field of study.
Synopsis: Vitamin B12 was effective in the treatment of recurrent aphthous stomatitis.
Source: Volkov I, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: A randomized, double-blind, placebo-controlled trial. J Am Board Fam Med 2009;22:9-16.
These researchers from the department of family Medicine at Ben-Gurion University in Israel previously reported the observation that treating patients with low serum levels of vitamin B12 also cleared their recurrent aphthous stomatitis (RAS).1 In this randomized, double-blind, placebo-controlled trial, they set out to confirm their observation.
The researchers recruited 84 adult patients with RAS for at least 1 year from the practices of 20 family physicians. After excluding those with Behçet's disease, other inflammatory disorders, or HIV-AIDS; recent recipients of B12; recent treatment of RAS by other means; known B12 deficiency; and other conditions, 58 patients remain. All patients had serum vitamin B12 levels at study entry. They were instructed in a method of recording severity of pain and filling out the "Aphthous Ulcers Diary." Patients were randomized to receive 1,000 mg of sublingual vitamin B12 at bedtime or matching placebo.
The intervention and control groups were similar in all respects. The patients were evenly divided between men and women. The average age was about 30 years. On average they had suffered from RAS for about 10 years. The intervention group was divided into those with an initial B12 level less than 250 pg/mL and those with a level greater than that. The two subgroups did not differ statistically.
The trial lasted six months. During the first four months of the study both groups had reductions in the average number of days of duration for an RAS episode (from 11.0 to 5.7 for the intervention group and 8.7 to 4.5 for the control group). During the next two months the average number of days for control group remained steady, but the B12 group had a further reduction to 2.0. There was a similar pattern to the reduction in the average number of aphthous ulcers per month (from 27.6 to 14.0 for the intervention group and 21.5 to 13.0 for the control group). After that, the curves diverged dramatically, and at six months the intervention group averaged 3.9 ulcers per month vs 13.4 for the control group. The graph of average level of pain showed a nonsignificant separation at month 4, and further separation at months 5 and 6 that were significant. The results did not depend on the initial serum vitamin B12 level. No patient reported an adverse reaction.
Aphthous ulcers (commonly known as canker sores) are the most common inflammatory lesions of the mouth, occurring in up to 10% of the population with more women afflicted than men.2 Their cause is unknown. They are associated with anemia, gastrointestinal disease such as Crohn's disease and ulcerative colitis, HIV infection, and Behçet's disease. Acidic, salty, and spicy foods can trigger an attack. Treatment is symptomatic with topical anesthetics. Topical tetracycline has been effective, as have sucralfate solution and topical steroids. For severe lesions, thalidomide, antimetabolites, and immunomodulating agents have all been employed.3 The association of aphthous ulcers and vitamin B12 deficiency has been recognized for many years.4-6 What set this study apart is that the majority of patients were not B12-deficient.
As you digest the findings of this study, there are some things you should consider: 1) These patients had severe ulcerative disease (I can't think of any patients that I've treated that have had that many ulcers per month); 2) This also was a small study and, therefore, there weren't enough subjects to identify harm; and 3) The investigators' method of recruitment (advertising to local family physicians) may have biased their study to patients with more severe disease. The study also raises a question: Why did both groups show improvement in the first four months? Despite my comment about low number of subjects, you should also consider that vitamin B12 is infrequently associated with adverse side effects, and it's cheap. If you have a patient who fits the profile of patients in this study, vitamin B12 may be the answer.
1. Volkov I, et al. Case report: Recurrent aphthous stomatitis responds to vitamin B12 treatment. Can Fam Physician 2005;51:844-845.
2. Jurge S, et al. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis 2006;12:1-21.
3. Altenburg A, Zouboulis CC. Current concepts in the treatment of recurrent aphthous stomatitis. Skin Therapy Lett 2008;13:1-4.
4. Walker JE. Aphthous ulceration and vitamin B12 deficiency. Br J Oral Surg 1973;11:165-170.
5. Weusten BL, van de Wiel A. Aphthous ulcers and vitamin B12 deficiency. Neth J Med 1998;53:172-175.
6. Piskin S, et al. Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2002;16:66-67.