Review Systematic review of the in vitro effects of statins on oral and perioral microorganisms Ting M, Whitaker EJ, Albandar JM. Systematic review of the in vitro effects of statins on oral and perioral microorganisms. Eur J Oral Sci 2016; 124: 4–10. © 2015 Eur J Oral Sci Statins are medications administered orally and are widely used for lowering the blood cholesterol level. The aim of this study was to investigate the effects of orally adminis- tered statins on microorganisms infecting oral and perioral tissues. We performed a systematic review of published studies of the in vitro antimicrobial effects of statins on bacteria, viruses, and fungi, and searched PubMed, Web of Science, Cochrane Central, and Google scholar. Studies show that most statins exhibit antimicrobial effects against various oral microorganisms. Simvastatin is most effective against the periodontal pathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, and against most dental plaque bacteria, including Streptococcus mutans. Statins also exhi- bit antiviral properties against human cytomegalovirus, hepatitis B virus, and hepatitis C virus, and have antifungal properties against Candida albicans, Aspergillus fumigatus, and Zygomycetes spp. There were notable differences in the minimum inhibitory con- centrations (MICs) between different studies, which may be attributed to differences in study design. Further studies are warranted to ascertain if statins can be solubilized so that patients, who have been prescribed statins for cardiovascular diseases, can use the medication as a swish and swallow, giving patients the added benefit of the antimicro- bial action topically in the mouth against infectious oral diseases. Miriam Ting 1 , Eugene J. Whitaker 2 , Jasim M. Albandar 3 1 Predoctoral Program; 2 Department of Restorative Dentistry; 3 Department of Periodontology and Oral Implantology, Temple University School of Dentistry, Philadelphia, PA, USA Jasim M. Albandar, Department of Periodontology and Oral Implantology, Temple University School of Dentistry, 3223 North Broad Street, Philadelphia, PA 19140, USA E-mail: Jasim.Albandar@temple.edu Key words: antimicrobial; microorganisms; oral; periodontal; statins Accepted for publication November 2015 Statins are specific competitive inhibitors of 3-hydroxy- 3-methylglutaryl coenzyme A (HMG-CoA) reductase. They are orally administered medications widely used to lower the blood cholesterol level (1), and have been shown to be effective in reducing the risk of cardiovas- cular diseases (2) and the rate of mortality in adults (3, 4). Statins can rapidly delipidate atheromas and strip plaques off potentially unstable lipid cores (5). There is evidence suggesting that statins also have other properties that may influence systemic and oral health. For instance, it has been reported that statins possess antibacterial effects against certain microorgan- isms (6), including periodontal pathogens (7). In addi- tion, other properties have been described, including immune modulation, anti-inflammatory effects, and bone-inductive properties (8). Statins modulate the immune response and attenuate the pathophysiological responses of sepsis (9, 10). For example, statin users admitted to hospital for acute infections show reduced morbidity and mortality com- pared with non-statin users (9, 11). Statins have biolog- ically significant antioxidant and anti-inflammatory effects and reduce plasma inflammatory markers, such as C-reactive protein (CRP) (12). The statin-mediated decrease in CRP concentrations in vascular tissues could be a result of the inhibition of interleukin-6 (13). Statins modulate bone formation by increasing the expression of bone morphogenetic protein-2, inflamma- tion, and angiogenesis (13). Animal studies (14, 15) have shown that simvastatin assists in bone regenera- tion as well as having an anti-inflammatory effect when applied systemically or locally. Simvastatin, at low con- centrations, exerts a positive dose-dependent effect on the proliferation and osteoblastic differentiation of human periodontal ligament cells, and may be related to inhibition of the mevalonate pathway (8). Simvas- tatin also stimulates vascular endothelial growth factor (VEGF) release in a dose-dependent manner, and sim- vastatin may promote bone formation and osteoblast differentiation via VEGF expression in bone tissue (14). The addition of statins, including simvastatin, induces a two- to threefold increase of new-bone formation in organ-cultured neonatal murine calvarial bone (13). Statins may have a potential role in periodontal regenerative therapy. PRADEEP &THORAT (16) recently reported a greater decrease in gingival index and prob- ing depth at chronic periodontitis sites treated non-sur- gically with scaling and root planing and locally delivered simvastatin, compared with scaling and root planing plus placebo, in humans. In addition, simvas- tatin-treated individuals exhibit more clinical attach- ment level gain as well as significant intrabony defect Eur J Oral Sci 2016; 124: 4–10 DOI: 10.1111/eos.12239 Printed in Singapore. All rights reserved Ó 2015 Eur J Oral Sci European Journal of Oral Sciences