Effect of nicotine on human gingival, periodontal ligament and oral epithelial cells. A systematic review of the literature

J Dent. 2019 Jul:86:81-88. doi: 10.1016/j.jdent.2019.05.030. Epub 2019 May 25.


Objectives: A systematic review was conducted to evaluate the in vitro effects of nicotine on human gingival, periodontal ligament and oral epithelial cells, specifically: cell viability, cell attachment, cell proliferation and inflammatory mediator production.

Materials and methods: This report followed the PRISMA statement. Two reviewers performed a literature search up to October 2018 in 3 databases: MEDLINE, EMBASE and Web of Science, supplemented by manual searching. Inclusion criteria comprised: in vitro studies evaluating human gingival fibroblasts, human periodontal ligament cells or human gingival/oral epithelial cells; nicotine exposure as a variable; including an appropriate control (no nicotine); published in English. Quality assessment was based on a 15-item checklist.

Results: Of 356 potentially eligible studies, 42 were included. The median quality assessment score was 8/15. Study designs were highly heterogeneous. IC50 values for nicotine (exposure concentration causing 50% cell death or inhibition of cell growth or other utilised toxicity metric) derived from ten studies ranged from 6 μM to 25 mM. Studies investigating cell attachment, proliferation and inflammatory mediator production suggested that effects can be seen at a wide range of nicotine concentrations, but results were often contradictory.

Conclusions: According to findings from in vitro studies, nicotine, at levels found in tobacco smokers, nicotine replacement therapy users and e-cigarette users, is unlikely to be cytotoxic to human gingival and periodontal cells, though saliva levels in smokeless tobacco users may be high enough to achieve cytotoxicity. There was limited and contradictory evidence for nicotine effects on cell attachment, proliferation and inflammatory mediator production.

Clinical significance: It is well established that whole tobacco smoke is highly damaging to oral tissues. The specific effects of nicotine are not well understood but are of increasing importance given the recent popularity of novel nicotine products. Increased knowledge on this topic will help to better inform dental professionals and patients.

Keywords: Cell viability; Electronic cigarettes; Nicotine; Periodontal diseases; Tobacco.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Electronic Nicotine Delivery Systems
  • Epithelial Cells
  • Humans
  • Nicotine / toxicity*
  • Periodontal Ligament*
  • Smoking
  • Smoking Cessation
  • Tobacco Use Cessation Devices


  • Nicotine