Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis

Clin Exp Dent Res. 2019 Mar 27;5(3):269-275. doi: 10.1002/cre2.181. eCollection 2019 Jun.


Over 100 million Americans experience recurrent aphthous stomatitis (RAS) at some point in life. To develop targeted drugs for RAS treatment, it is critical to identify its etiology. We determined if serum insulin-like growth factor 1 (IGF-1) and related factors are associated with RAS, because both RAS prevalence and IGF-1 are highest during puberty. We analyzed data from 1,480 Third National Health and Nutrition Examination Survey participants aged 20-40 years. Participants with a history of diabetes or lupus, cotinine levels 6 ng/ml or higher or glycemia 110 mg/dl or higher were excluded. We compared levels of IGF-1, IGFBP-3, leptin, and insulin in participants with a positive vs. negative RAS history in the prior 12 months. We used logistic regression in SAS/SUDAAN to account for the complex sampling design. The odds of a positive RAS history were 1.31 times higher for every 100 ng/ml increase in serum IGF-1. This association persisted after adjustment for age, race/ethnicity, medication intake, body mass index, insulin, leptin, glycemia, and income (adjusted OR = 1.30, 95% CI [1.06, 1.60]; p = 0.013). The odds of a positive RAS history were also higher among non-Hispanic white compared with non-Hispanic black participants (adjusted OR = 4.37, 95% CI [3.00, 6.38]). Leptin, IGFBP-3, and insulin levels did not differ by RAS status. The significantly higher IGF-1 levels in participants with a positive RAS history compared with controls suggest a possible role of the IGF-1 pathway in RAS etiology.

Keywords: IGF‐1; aphthous stomatitis; growth factors; insulin; leptin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Black or African American
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Leptin / metabolism
  • Logistic Models
  • Male
  • Mexican Americans
  • Nutrition Surveys
  • Stomatitis, Aphthous / metabolism*
  • White People
  • Young Adult


  • Blood Glucose
  • IGF1 protein, human
  • IGFBP3 protein, human
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • Leptin
  • Insulin-Like Growth Factor I

Supplementary concepts

  • Sutton disease 2