Vitamin D deficiency: Is it a risk factor for recurrent aphthous stomatitis?

Researchers in this study wanted to see if people with learning disabilities had higher levels of vitamin D deficiency than the general population

Recurrent aphthous stomatitis (RAS) is the commonest from of oral ulceration with a prevalence estimated to be between 5-60%.  Studies have suggested ethnic and geographical difference in prevalence, and it can manifest in a number of different forms minor, major, and herpetiform. Its etiopathogenesis is multifactorial and a number of studies have implicated vitamin deficiencies including vitamin B1, B2, B6, B12, and folic acid and more recently some studies have suggested a role for vitamin D.

The aim of this review was to explore the possible association between vitamin D deficiency and recurrent aphthous stomatitis.


Searches were conducted in the PubMed, Scopus, and Web of Science databases. Observational studies assessing the relationship between levels of serum vitamin D (25‐hydroxycholecalciferol) and recurrent aphthous stomatitis were considered.  Two reviewers independently selected studies extracted data and assessed the quality of evidence using the Newcastle-Ottawa Scale. The main outcome was vitamin D levels expressed as nanograms per milliliter (ng/mL).  For the meta-analysis weighted mean difference (WMD) between the two groups and 95% confidence intervals (CI) was calculated.


  • 5 case control studies (208 case patients, 241 controls) were included.
  • Studies were conducted in Iran, Iraq, Poland and Turkey.
  • I study was considered to be of high quality, 4 of moderate quality.
  • All the studies reported significantly lower levels of vitamin D in RAS patients.
  • Meta-analysis (5 studies) also showed significantly lower levels of vitamin D in RAS patients, WMD = −9.67 (95%CI; −15.68 to −3.65) I2 = 90%, p < .002.


The authors concluded: –

the limited available evidence suggests that low levels of serum vitamin D might be a risk factor for RAS. However, more well‐designed studies are needed to further explore the potential association between vitamin D deficiency and RAS development.


Three databases have been searched for observational studies assessing the relationship between vitamin D and RAU. All 5 of the included studies were case controlled studies 4 of the studies using a 1:1 case to control ratio with one using close to a 1:2 ratio. Three of the included studies clearly reported vitamin D levels as ng/mL a worldwide standard unit. The other two studies reported vitamin D levels in ng/dl unit. The authors note that conversion of the ng/dl to ng/mL units provide illogical readings. Because the ng/dl readings of these 2 studies were similar to the ng/mL units of the other 3 studies the review authors have assumed the ng/dl was a typographical error after failing to get a response from the study authors which may be a concern.  As an alternative these 2 studies could have been omitted from the meta-analysis.

The included studies are small observational studies and it not clear how many potential confounders are controlled for in the studies there is all a high degree of heterogeneity in relation to the settings, assay methods, age, gender, ethnicity of the patients.  So while this review suggests a possible links between low levels of vitamin D and RAS larger well conducted and well reported studies with clear accounting of confounders are needs to better assess this potential association.


Primary Paper

Al-Maweri SA, Halboub E, Al-Sufyani G, Alqutaibi AY, Shamala A, Alsalhani A. Is vitamin D deficiency a risk factor for recurrent aphthous stomatitis? A systematic review and meta-analysis. Oral Dis. 2019 Sep 6. doi:10.1111/odi.13189. [Epub ahead of print] Review. PubMed PMID: 31493304.




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