Response: Re: Effectiveness of Vitamin B12 in Treating Recurrent Aphthous Stomatitis: A Randomized, Double-Blind, Placebo-Controlled Trial
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* Ilia Volkov

*To the Editor:* We are satisfied to see that not only our last study, but recent research (including your own),1,2 support the conclusions of our previous observations3,4 as well. I have some commentaries on your remarks.

In my opinion, your adhering discs as well as sublingual tablets, injections, swallowed tablets, and intranasal sprays could be effective for many conditions (including recurrent aphthous stomatitis [RAS]) in regard to the effect of vitamin (Vit) B12 itself. Undoubtedly, the time of response depends on the chosen form of cobalamin (cyanocobalamin, methylcobalamin, or hydroxycobalamin), the mode of use, and individual dosage. For example, according to my own 6 years experience you can receive an adequate response to injections of Vit B12 (cyanocobalmin!) in first 2 or 3 wk. Nevertheless, some patients dislike injections and prefer tablets. The largest drawback our study was the issue of participant compliance. RAS is not a life-threatening disease, and therefore some patients even refused sublingual tablets.

## The Mechanism of Successful Treatment Is Still Unclear

I disagree with the claim that the positive effect of Vit B12 on RAS is related to its local action on the buccal mucosa. How can you explain the response to parenteral treatment? I presume there is a generalized effect of Vit B12, and we hold a “working hypothesis” which, in our opinion, could explain this phenomenon. Vit B12 has unique yet obscure and unrecognized function. We assume that there are universal, interchangeable (as required) biologically active substances that regulate different systems of our body and provide homeostasis. We propose that one of these substances is Vit B12. Perhaps Vit B12 can correct defects caused by other biological substances. We call this phenomenon the “Master Key effect.”5 In summary, this fascinating and unelucidated topic definitely demands further research to disclose the underlying secrets nature set in this field.

## References

1.  Burgess JA, Haley JT. Effect of bioactive B12 in adhering discs on aphthous ulcers. Inside Dentistry 2008; 4: 60–4.
    
    

2.  Gulcan E, Toker S, Hatipoğlu H, Gulcan A, Toker. A Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sc 2008; 336: 379–82.
    
    [PubMed](http://www.jabfm.org/lookup/external-ref?access_num=19011392&link_type=MED&atom=%2Fjabfp%2F22%2F5%2F591.1.atom) 

3.  Volkov I, Rudoy I, Abu-Rabia U, Masalha T, Masalha R. Recurrent apthous stomatitis responsive to vitamin B12 treatment. Can Fam Phys 2005; 51: 844–5.
    
    [FREE Full Text](http://www.jabfm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6MzoiUERGIjtzOjExOiJqb3VybmFsQ29kZSI7czozOiJjZnAiO3M6NToicmVzaWQiO3M6ODoiNTEvNi84NDQiO3M6NDoiYXRvbSI7czoyMjoiL2phYmZwLzIyLzUvNTkxLjEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

4.  Volkov I, Rudoy I, Peleg R, Press Y. Successful treatment of recurrent aphthous stomatitis of any origin with vitamin B12 (irrespective of its blood level). Internet J Fam Pract 2007; 5.
    
    

5.  Volkov I, Yan P, Inna R. Vitamin B12 could be a “master key” in the regulation of multiple pathological processes. J Nippon Med Sch 2006; 73: 65–9.
    
    [CrossRef](http://www.jabfm.org/lookup/external-ref?access_num=10.1272/jnms.73.65&link_type=DOI) 
    
    [PubMed](http://www.jabfm.org/lookup/external-ref?access_num=16641529&link_type=MED&atom=%2Fjabfp%2F22%2F5%2F591.1.atom)