Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 5  |  Page : 605-608  

The level of Vitamin B12 and hemoglobin in patients with recurrent aphthous stomatitis


1 Department of Ear Nose and Throat Clinic, Bozok University School of Medicine, Yozgat, Turkey
2 Department of Internal Medine, Bozok University School of Medicine, Yozgat, Turkey
3 Department of Obstetric and Gynecology Clinic, Bozok University School of Medicine, Yozgat, Turkey

Date of Web Publication13-Oct-2016

Correspondence Address:
Kamran Sari
School of Medicine, Bozok University, Adnan Menderes Street Number 190, Yozgat
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.192164

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  Abstract 


Background: Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease of the oral cavity. Although many factors have been suggested as possible causes of RAS, its precise etiology is controversial. Vitamin B12 (vit B12) and iron deficiencies may cause RAS. Aims: We investigated the level of serum hemoglobin (Hb) and vit B12 in patients with RAS and to compare them with healthy controls.
Materials and Methods: This was a prospective, cross-sectional study. Patients who had had at least one episode of oral ulcerations per month since childhood were diagnosed as having RAS. Blood samples were drawn from the RAS group and control group for measuring blood Hb and vit B12 concentrations. Results: Exactly 195 patients (62 men and 133 women) with RAS and 217 healthy controls (62 men and 155 women) were enrolled in the study. The RAS group had significantly lower mean Hb levels than the control group (P < 0.001). No significant difference in the mean vit B12 level was demonstrated between the study group and controls. Around 58 (29.7%) patients were diagnosed as Hb deficient in the RAS group and 21 (9.7%) patients in controls. Vit B12 deficiency was diagnosed in 63 (32.3%) individuals in the RAS group and 32 (14.7%) individuals among controls. Conclusions: In our study, vit B12 and Hb deficiency were found higher in patients with RAS compared to the control group. Therefore, we suggested the investigation of the level of vit B12 and Hb in patients with RAS.

Keywords: Aphthous, deficiency, hemoglobin, stomatitis, Vitamin B12


How to cite this article:
Sari K, Yildirim T, Sari N. The level of Vitamin B12 and hemoglobin in patients with recurrent aphthous stomatitis. Med J DY Patil Univ 2016;9:605-8

How to cite this URL:
Sari K, Yildirim T, Sari N. The level of Vitamin B12 and hemoglobin in patients with recurrent aphthous stomatitis. Med J DY Patil Univ [serial online] 2016 [cited 2022 May 16];9:605-8. Available from: https://www.mjdrdypu.org/text.asp?2016/9/5/605/192164




  Introduction Top


Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease of the oral cavity. It is one of the most common mucosal diseases of the oral mucosa. Depending on the population considered, its prevalence varies from 5% to 20%.[1] Minor RAS is the most commonly seen form of RAS. It is represented as small oval ulcers with necrotic centers and red margins.[2] These ulcers are painful and generally recover in 10-14 days without scarring. Major RAS lesions are larger than 5 mm and can last for up to 6 weeks and generally leave scars.[3] Although many factors have been suggested as possible causes of RAS, its precise etiology is controversial. The factors that predispose patients to RAS are trauma, infections, toxic agents, genetic factors, dryness, irritants, hypersensitivity, and autoimmune conditions.[3] Malnutrition, iron, Vitamin C, folic acid, or Vitamin B12 (vit B12) deficiencies may also cause RAS.[4],[5],[6]

In this study, we investigated the vit B12 and hemoglobin (Hb) levels of patients with RAS and compared the results with healthy controls.


  Materials and Methods Top


This was a prospective, cross-sectional study enrolling 195 patients (62 men and 133 women) with RAS (RAS group) and 217 healthy controls (62 men and 155 women) (control group). All patients and healthy controls were referred to the Department of Otorhinolaryngology, Head and Neck Surgery, Internal Medicine, and Obstetrics and Gynecology Clinics between December 2014 and June 2015. Informed consent from each subject and the approval of the local ethical committee were obtained. Patients who were suspected RAS were referred to ear nose and throat service. Detailed ear, nose, throat, and physical examinations were performed in both groups. Patients who had had at least one episode of oral ulcerations per month during the preceding years were diagnosed as having RAS.[7] Exclusion criteria were as follows: Autoimmune diseases (such as systemic lupus erythematosus, Sjögren's syndrome, pemphigus vulgaris, and rheumatoid arthritis), RAS patients with concomitant Behçet's syndrome, coeliac disease, gluten-sensitive enteropathy, inflammatory bowel diseases, diabetes mellitus and patient-reported cardiovascular, liver, or kidney disease. Healthy controls were selected in patients that were referred to Internal Medicine and Obstetrics and Gynecology Clinics with complaints of except RAS. Healthy controls did not have any oral mucosal or systemic disease. None of the healthy controls had taken any medication at least 3 months before the study. Biochemical analysis was done before the RAS treatment. Blood samples were drawn from the RAS group and control group for measuring blood Hb and vit B12 concentrations. The blood Hb and vit B12 concentrations were investigated by an auto analyzer in the routine laboratory that was performed in the Department of Biochemistry Laboratory.

Statistical analysis

Statistical analyses were performed using the SPSS package program version 17. Continuous variables were expressed in mean ± standard deviation, and nominal variables were shown in percentage. The normality of the variables was tested by the Kolmogorov-Smirnov test. None of the variables showed normal distribution. The Mann-Whitney U-test was used to compare the groups in respect of continuous variables while the difference between the groups was tested by Pearson Chi-square test in respect of nominal variables. The results should be regarded as being significant if the P< 0.05.


  Results Top


In our study, there was no difference in terms of age between the RAS group and the control group. In the RAS group, the age ranges of men and women were between 18 and 80, and 19 and 74, respectively (mean age 45.5 ± 14.1 years). Moreover, they were 22-76 and 18-74 in healthy controls in men and women, respectively (mean age 42.8 ± 14.1). The blood Hb and vit B12 levels of the subjects are shown in [Table 1]. The Hb and vit B12 levels were analyzed separately for men and women. Our results showed that the RAS group had significantly lower mean Hb (P< 0.001 for both men and women) levels than healthy controls. On the other hand, a significant difference in the mean vit B12 level was not demonstrated between the RAS group and the control group. With regard to the World Health Organization criteria, women with Hb <12 g/dl and men with Hb <13 g/dl were defined as having Hb deficiency or anemia.[8] Moreover, patients with serum vit B12 level <200 pg/ml were defined as vit B12 deficient for both genders.[9] In our study, 58 (29.7%) patients were diagnosed as Hb deficient in the study group, and there were 21 (9.7%) in healthy controls (P< 0.001) [Table 2]. On the other hand, vit B12 deficiency was diagnosed in 63 (32.3%) subjects in the RAS group and 32 (14.7%) healthy controls (P< 0.001) [Table 3].
Table 1: Mean blood concentrations of Hb and vitamin B12 in 195 patients with RAS and in 217 healthy controls (Mann-Whitney U Test was used for the comparison of the groups)

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Table 2: Number and percentage of individuals with Hb and vitamin B12 deficiency and normal level in study group and healty controls (Mann-Whitney U Test was used for the comparison of the groups)

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Table 3: Age and sex distribution of patients with RAS

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  Discussion Top


Many factors are blamed in the etiology of RAS. In previous studies, vit B12 and Hb deficiency were repeatedly shown to be the causes of RAS.[10],[11],[12] Our results showed that RAS patients had significantly lower mean Hb (P< 0.001 for both men and women) levels than healthy controls. Moreover, 58 (29.7%) patients in the study group had Hb deficiency. On the other hand, 21 individuals (9.7%) among healthy controls had Hb deficiency. Anemia and lower Hb levels in RAS patients cause a reduction in the capacity of the blood to carry oxygen to the oral mucosa and eventually lead to atrophy of the oral mucosa.[13] Iron is present in the structure of Hb and is essential for epithelial cell functions. Oral epithelial cells have a high turnover rate and folic acid and vit B12 play important roles in DNA synthesis and cell division.[9],[14] Vit B12 deficiency affects especially hematological and neurological systems.[15] Therefore, vit B12, folic acid, and iron deficiencies can cause oral epithelial atrophy.[13] This may explain why patients with hematinic deficiencies are prone to having RAS.

In our study, although mean vit B12 levels were not significantly lower in the RAS group than in the control group, vit B12 deficiency was significantly higher in the RAS group than in the control group (P< 0.001). In the study group, 63 (32.3%) individuals had vit B12 deficiency and 32 (14.7%) individuals among healthy controls had vit B12 deficiency. In the literature, there has been a large number of studies about the prevalence of vit B12 deficiency in RAS patients.[16] In these studies, it has been stated that 0-42% of RAS patients may have vit B12 deficiency. Geographical and temporal variations in diet and food supplementation may affect this variation. Vit B12 acts as a coenzyme in fat and carbohydrate metabolism, hematopoiesis and protein synthesis.[2] It has been reported that vit B12 deficiency can suppress cell-mediated immunity and change the cells of the tongue and buccal mucosa.[3]

In this study, when we looked at the age and sex distribution of the patients with RAS, there were 133 women and 62 men in the study group and nearly half of the patients were between 30 and 50 years (49.7%). Thirty patients were younger than 30 (15.3%) and 68 patients were older than 50 (34.8%). In contrast to a study by McCullough et al.,[17] RAS was found in men higher than women and younger patients were found predominantly.

Lopez-Jornet et al.[1] investigated iron, ferritin, folic acid, and vit B12 deficiency in RAS patients and controls. They showed iron, ferritin, folic acid, and vit B12 deficiency in 7.6%, 6.5%, 4.3%, and 5.4% of cases, respectively. Moreover, they found these markers in the control group in 2.1%, 5.3%, 1.06%, and 1.06% of cases, respectively. The overall frequency of hematinic deficiencies was 14.14% in the RAS patients and 6.39% in the controls. In another study by Sun et al.,[13] they showed that 57 (20.9%), 55 (20.1%), 13 (4.8%), and 7 (2.6%) patients with RAS had deficiencies of Hb, iron, vit B12, and folic acid, respectively. Significant higher frequencies of Hb, iron, vit B12, or folic acid deficiency were found in RAS patients than in controls in their study. Piskin et al.[4] investigated serum iron, ferritin, folic acid, and vit B12 levels in 35 RAS patients and 26 controls. They found significantly lower vit B12 levels in RAS patients than in controls. On the other hand, significant differences were not found in other markers.

Kozlak et al.[2] investigated dietary vitamin intake in RAS patients and controls. They found that RAS patients had a significantly lower daily intake of vit B12 and folate than controls. They stated that patients with RAS are more prone to having lower dietary intakes of vit B12 and folate than controls. Some case reports have indicated that RAS patients with vit B12 deficiency can be treated effectively with vit B12 supplementation.[16] Volkov et al.[18] investigated the use of once daily sublingual vit B12 for RAS in a randomized, double-blind, and placebo-controlled trial. Six months later, 20 out of 31 (74.1%) RAS patients had been treated successfully, and in the placebo group, 8 out of 27 (32%) RAS patients were free of ulceration.

In our study, 132 patients (67.7%) in the study group and 185 controls (85.3%) did not have vit B12 deficiency. Furthermore, 137 RAS patients (70.3%) and 196 controls (90.3%) had normal hemogram levels. In a preview study by Sun et al.,[13] it was found that approximately 60% of RAS patients had normal hemograms and normal blood hematinic levels. This may partially explain the genetic susceptibility of some people with normal hemograms and normal blood hematinic and homocysteine levels who still have RAS. Koybasi et al.[19] stated that 54.2% of all patients with RAS had a first-degree relative with recurrent aphthosis.

Hematological research about cost-effectiveness in patients with RAS is controversial. However, in some researches, the incidence of vit B12 and hematinic deficiencies was found to be high and obtaining a good response to replacement therapy in these patients indicates the need for hematological screening of such patients.[20],[21] Routine hematological tests to detect serum iron, folic acid, and vit B12 deficiencies may be recommended in patients with RAS to treat any underlying nutritional deficiencies.

In our study, although the level of vit B12 and Hb is normal in many of our patients, vit B12 and Hb deficiencies were found higher in patients with RAS compared to the control group. Therefore, we suggested the investigation of the level of vit B12 and Hb in patients with RAS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Lopez-Jornet P, Camacho-Alonso F, Martos N. Hematological study of patients with aphthous stomatitis. Int J Dermatol 2014;53:159-63.  Back to cited text no. 1
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Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of Vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med 2010;39:420-3.  Back to cited text no. 2
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Volkov I, Rudoy I, Abu-Rabia U, Masalha T, Masalha R. Case report: Recurrent aphthous stomatitis responds to Vitamin B12 treatment. Can Fam Physician 2005;51:844-5.  Back to cited text no. 3
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Piskin S, Sayan C, Durukan N, Senol M. Serum iron, ferritin, folic acid, and Vitamin B12 levels in recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2002;16:66-7.  Back to cited text no. 4
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Wray D, Ferguson MM, Mason DK, Hutcheon AW, Dagg JH. Recurrent aphthae: Treatment with Vitamin B12, folic acid, and iron. Br Med J 1975;2:490-3.  Back to cited text no. 5
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Sun A, Chang YF, Chia JS, Chiang CP. Serum interleukin-8 level is a more sensitive marker than serum interleukin-6 level in monitoring the disease activity of recurrent aphthous ulcerations. J Oral Pathol Med 2004;33:133-9.  Back to cited text no. 7
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WHO/UNICEF/UNU. Iron deficiency anaemia assessment, prevention, and control: A guide for programme managers. Geneva, Switzerland: World Health Organization; 2001.  Back to cited text no. 8
    
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Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and Vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 2007;85:193-200.  Back to cited text no. 9
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Aynali G, Ozkan M, Aynali A, Ceyhan B, Armagan H, Yariktas M, et al. The evaluation of serum Vitamin B12, folic acid and hemoglobin levels in patients with recurrent minor aphthous stomatitis. Kulak Burun Bogaz Ihtis Derg 2013;23: 148-52.  Back to cited text no. 10
    
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Gulcan E, Toker S, Hatipoglu 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 Sci 2008;336:379-82.  Back to cited text no. 11
    
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Sun A, Chen HM, Cheng SJ, Wang YP, Chang JY, Wu YC, et al. Significant association of deficiencies of hemoglobin, iron, Vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis. J Oral Pathol Med 2015;44:300-5.  Back to cited text no. 13
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Lahner E, Annibale B. Pernicious anemia: New insights from a gastroenterological point of view. World J Gastroenterol 2009;15:5121-8.  Back to cited text no. 14
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Incecik F, Herguner MO, Altunbassak S. Deficiency of Vitamin B12 in Children and Epilepsy. Balkan Med J 2010;27:351-3.  Back to cited text no. 15
    
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Baccaglini L, Lalla RV, Bruce AJ, Sartori-Valinotti JC, Latortue MC, Carrozzo M, et al. Urban legends: Recurrent aphthous stomatitis. Oral Dis 2011;17:755-70.  Back to cited text no. 16
    
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McCullough MJ, Abdel-Hafeth S, Scully C. Recurrent aphthous stomatitis revisited; clinical features, associations, and new association with infant feeding practices? J Oral Pathol Med 2007;36:615-20.  Back to cited text no. 17
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Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R, 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.  Back to cited text no. 18
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Koybasi S, Parlak AH, Serin E, Yilmaz F, Serin D. Recurrent aphthous stomatitis: Investigation of possible etiologic factors. Am J Otolaryngol 2006;27:229-32.  Back to cited text no. 19
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Porter SR, Scully C, Flint S. Hematologic status in recurrent aphthous stomatitis compared with other oral disease. Oral Surg Oral Med Oral Pathol 1988;66:41-4.  Back to cited text no. 20
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Compilato D, Carroccio A, Calvino F, Di Fede G, Campisi G. Haematological deficiencies in patients with recurrent aphthosis. J Eur Acad Dermatol Venereol 2010;24:667-73.  Back to cited text no. 21
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    Tables

  [Table 1], [Table 2], [Table 3]


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