Vitamin B12 for the treatment of recurrent aphthous stomatitis

Abstract

The possible association between recurrent aphthous ulceration (RAU) and vitamin B12 deficiency was first suggested more than 55 years ago. 1 Despite being unsubstantiated because of a lack of robust evidence, it is widely recognised as a possible predisposing factor for RAU. The few available controlled studies analysing hae-matological status in RAU patients give controversial results, some supporting a link 2,3 whereas others refute a connection. 4,5 Similarly, reports on supplemental treatments are scarce and almost entirely based on studies of doubtful quality that are small in size, uncon-trolled, not randomised and unmasked. 6–8 The present study therefore represents an important advance in this field as it the first randomised, double-blind, placebo-con-trolled trial on vitamin B12 supplementation in more than half a century. There are, however, a number of subtle yet important prob-lems with it. Firstly, the diagnostic criteria did not consider recur-rent intraoral herpetic ulceration, the main differential diagnosis of RAU. Older studies suggested the use of high-dose vitamin B12 in the treatment of herpetic stomatitis, and therefore its absence from the diagnostic criteria is all the more striking. 9 In addition, the vague reporting of clinical details as a possible source of bias does not appear to have been considered. It is unclear whether aphthous ulceration included in the test and control groups was limited to minor RAU or incorporated other varieties. This may be partially explained by the lack of dentists and dermatologists involved in the study. The authors are also unclear about concealment of allocation sequences, despite assurances that blinding of both physicians and participants occurred until the end of the study. Although patient age, gender and origin were apparently well-matched, educational standard was incompatible between the two groups, with two thirds of the intervention group being highly educated but less than half of the control group fitting this category. There is evidence to suggest a relationship between low income and education, and increased duration and intensity of pain in comparison with high-er income/ educational groups. 10 Thus, these differences, although not statistically significant, may have introduced another source of bias. Moreover, no intention to treat analysis was applied, thus an over-optimistic estimate of the efficacy of this intervention is likely because of all the above remarks. Finally, there is a lack of any consistent biological explanation for the benefits observed, with the authors still suggesting an unrecog-nised function of vitamin B12. In addition, alternative hypotheses such as Helicobacter pylori involvement, a proposed putative aetio-Vitamin B12 for the treatment of recurrent aphthous stomatitis Abstracted from Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomised, double-blind, placebo-controlled trial.