A comprehensive medical research conducted from 1951 to 2009 showed 578 papers related to the treatment of aphthous lesions including 110 clinical trials. Medical interventions ranging from plant medicine to multivitamins, cohesive pastes, topical antiseptics, systemic and topical antibiotics, topical non-steroidal anti-inflammatory drugs and topical and systemic immune-modulators, immune-suppressors, and corticosteroids were among treatments prescribed for aphthous patients. Many of these treatments achieved short-term goals, such as pain relief, reduced number of ulcers, and size and duration of recovery in ulcers. A few of these studies could achieve long-term goals, such as reducing the recurrence of lesions and maintaining the suppression of disease (29). Furthermore, B vitamins are soluble in water and are not stored in the body. They can be received through eating or in the form of a diet supplement. These vitamins act as a coenzyme in the metabolism of carbohydrates, proteins, and fatty acids. This research evaluated the effect of injected vitamin B in comparison with oral treatment on aphthous stomatitis in patients admitted to skin clinic of Rasoul Akram hospital in Tehran during 2016 to 2018. As stated above, in a number of patients with recurrent aphthous stomatitis, a potential effective factor that caused lesions was a deficiency of vitamins and minerals, such as lack of iron, folate, vitamin B12, and zinc. Some studies have shown that alternative treatments with minerals and vitamins can bring satisfactory treatment (
5- 7). By reviewing studies on recurrent aphthous stomatitis, it was assumed that people, who suffer from recurrent aphthous stomatitis show deficiency in B group vitamins ( 3- 8). This research evaluated the effect of the injected form of vitamin B compared to that of the oral form of vitamin B on recurrent aphthous stomatitis.
The current research showed no significant difference between the two groups in terms of ferritin, vitamin B12, and folic acid, yet the injected form of vitamin B showed a better effect in terms of reduction of recurrence and the number of lesions and the time of recovery of lesions and mitigation of symptoms. In the research conducted by Piskin et al. only the serum level of vitamin B12 was statistically lower in patients with aphthous. It was concluded that vitamin B12 deficiency might be involved in etiology of recurrent aphthous stomatitis (
12). The results of the research conducted by Kozlak showed that patients with recurrent aphthous stomatitis had an inadequate daily intake of vitamin B12 and folate compared to the general population. The exact mechanism of the effect of vitamin deficiencies on recurrent aphthous stomatitis is not known. Studies have indicated that the response to alternative treatment in a number of people have had a direct effect on oral mucosa, confirming the hypothesis that deficiency is an underlying factor for ulcers and vitamin B12 acts as a coenzyme in the metabolism of lipids and carbohydrates, and the synthesis of protein and blood cells. Recent research has indicated that changes in the oral mucosa, including glossitis and stomatitis, might be clinical symptoms of primary deficiencies of vitamin B12 or folic acid ( 7).
In the research carried out by Khan et al. (
3), blood deficiencies were higher in patients with recurrent aphthous stomatitis. Deficiencies in serum ferritin, serum vitamin B12, and red blood cell folate were significantly higher in patients than that of healthy people. In the research conducted by Olson et al. ( 13), no significant difference was found between hematological parameters in patients with aphthous and healthy people, and these results were inconsistent with those of the current research, which examined these parameters in patients and healthy controls. Since some reports indicated that about 18% of patients with recurrent aphthous stomatitis are diagnosed with deficiencies in vitamin B12, folate, or iron, the hypothesized relationship between recurrent aphthous stomatitis and hematological disorders has been discussed ( 6, 14). This suggests the importance of blood examination in diagnosis and treatment of patients. Olson et al. found that blood deficiency is common in people with recurrent aphthous stomatitis. In their research, anemia was not found in any of the patients with aphthous stomatitis, while 11.6% of aphthous patients and 4.9% of the control group showed low levels of iron. Moreover, the mean serum ferritin level was significantly reduced in patients with recurrent aphthous stomatitis. The research revealed that while patients with recurrent aphthous stomatitis rarely had anemia and usually had normal levels of vitamin B12, iron, and folate red blood cells, they might have lower levels of vitamin B12, serum ferritin, and folate compared to other patients. This is in line with the results of the current research, which showed that while patients with recurrent aphthous stomatitis (RAS) usually have normal levels of vitamin B12, ferritin, and folic acid, they have lower levels of vitamin B12, ferritin, and folic acid compared to normal people.
The research conducted by Wary et al. showed that topical treatments led to improvement until the treatment process continued (
14), however, after the end, aphthous ulcers reappeared. Also, these treatments could not reduce the intervals and recurrence of the lesion. In 23 patients with deficiency of ferritin, folic acid, and vitamin B12, alternative treatment led to a better response by patients to treatment. In the current research, as recovery was observed in both interventional groups, one can consider the important role of alternative and systemic treatments in the improvement of aphthous lesions. Many studies have reported cases of nutritional deficiencies in patients with aphthous ( 12, 15, 16).
The research conducted by Porter et al. showed low levels of ferritin in 11.6% of aphthous patients, while vitamin B 12 levels were 3.2%. In the research carried out by Challacombe, in which 193 patients with aphthous lesions in London were examined, 7.3% of the patients were anemic (
17). Piskin et al. ( 12) showed that only serum vitamin B12 levels were significantly higher in patients with recurrent aphthous stomatitis compare with those in the control group (P < 0.005). In the current research, 5% of patients with aphthous were anemic, while nutritional deficiencies were 41.6%, which indicates similarities and differences with the mentioned studies. These differences might be due to differences in race and place of residence of the patients. The research conducted by Noaln et al. showed that vitamin B1, B2, and B6 deficiencies should be considered as an exacerbating factor in recurrent aphthous stomatitis ( 4). They also believed that vitamin B levels should be measured, yet if such measurements are impossible, alternative vitamin B treatment would play a major role in the treatment of patients. This result was consistent with that of the current research, which showed better results in injected forms of vitamin B compared to the oral form. In the current study, high doses of vitamins B1, B6, and B12 were used and its positive results were seen. The results of the study conducted by Volvok showed that treatment with vitamin B12 reduces pain, the number of lesions, and the duration of recovery of aphthous lesions. These results did not depend on base levels of vitamin B12. Although deficiency of vitamin B12 in the current research was seen in 13.3% of patients, yet recovery was seen in a great number of the patients; these results are in line with those of the current research. This might be due to non-measurement of other vitamin B group, and the possibility that deficiencies of vitamin B12 have not been accurately determined, since values of methylmalonic acid (MMA), homocysteine (HCY), holotranscobalamin II (holoTC) were not checked. Furthermore, HCY, MMA, holoTC were measured to increase the sensitivity and specificity of diagnosis of vitamin B 12 disorder. HoloTC is biologically a spectrum of active vitamin B12, increasing the uptake of vitamin B12 by cells. While diagnostic algorithms using vitamin B12 (MMA and HCY measurements) have been reflected in studies of some universities and scientific centers, negative predictive values have not yet been proven. Hence, the diagnosis and measurement of deficiencies of vitamin B12 are still controversial. Another explanation for the effectiveness of vitamin B12 in the treatment of aphthous lesions is that the vitamin B12 function is unique, yet it has not been yet known ( 5, 18). In a report released by Weusten and van de Wiel on aphthous lesions and vitamin B12 deficiency, in three patients with problems of anemia, Borborygmia, and Graves’ disease, who had vitamin B12 deficiency, the lesions were recovered by prescribing this vitamin. They concluded that deficiency of vitamin B12 should be considered in patients with a history of aphthous lesions ( 19). Given the recovery results in patients of the current research in injection and even oral form, the role of vitamins B1 and B6 deficiency in increasing the sensitivity and pain of oral mucosa and inflammation of the tongue and lips is emphasized ( 20). The exact role of group B vitamins has been discussed in the pathogenesis of recurrent aphthous. Further studies are required to clarify the importance of group B vitamins in recurrent aphthous stomatitis.