{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:50:16Z","timestamp":1790787016870,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Melatonin is produced by the pineal gland and plays a role in regulating circadian rhythm. It influences the physiologic processes, such as the activation of the immune system and the antioxidant function. Melatonin has been reported in the samples of patients with periodontitis. Therefore, the role of melatonin in periodontal diseases must be appraised. Using the strategy of electronic search of various databases, we included studies, published until December 2021, measuring the expression of melatonin in patient samples and evaluating the effect of periodontal therapy on melatonin expression. This review also included studies evaluating the effect of melatonin supplementation on periodontal parameters. In total, 15 articles fulfilled the study inclusion criteria. The results revealed that melatonin is negatively correlated with the severity of periodontal diseases, and melatonin supplementation reduces the levels of periodontal inflammatory parameters. Hence, melatonin has a role in periodontal diseases, but additional studies are warranted to substantiate its use as a biomarker and host modulatory agent.<\/jats:p>","DOI":"10.4103\/abr.abr_152_23","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T04:01:36Z","timestamp":1727150496000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Role of Melatonin in Periodontal Diseases: A Structured Review"],"prefix":"10.4103","volume":"13","author":[{"given":"Waleed","family":"Khalid","sequence":"first","affiliation":[{"name":"Department of Dentistry, Specialist Periodontist, Specialized Dental Center, Ministry of Health, Alhassa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Koppolu","sequence":"additional","affiliation":[{"name":"Periodontics Discipline, UWA Dental School, The University of Western Australia, Perth, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Alhulaimi","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Specialized Dental Center, Ministry of Health, Alhassa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Alkhalaf","sequence":"additional","affiliation":[{"name":"Department of Dentistry, General Dentist, Specialized Dental Center, Ministry of Health, Alhassa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Almajid","sequence":"additional","affiliation":[{"name":"Department of Periodontics, King Faisal General Hospital, Ministry of Health, Al Ahsa Health Cluster, Al Hofuf, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,9]]},"reference":[{"key":"R1-20240924","first-page":"424","article-title":"Microbiology and management of periodontal infections","volume":"51","author":"Brook","year":"2003","journal-title":"Gen Dent"},{"key":"R2-20240924","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1600-051X.2009.01517.x","article-title":"Prevalence of periodontal disease and treatment demands based on a German dental survey (DMS IV)","volume":"37","author":"Holtfreter","year":"2010","journal-title":"J Clin Periodontol"},{"key":"R3-20240924","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1600-051X.1996.tb00502.x","article-title":"Increased release of free oxygen radicals from peripheral neutrophils in adult periodontitis after Fe\u03b3\u2010receptor stimulation","volume":"23","author":"Gustafsson","year":"1996","journal-title":"J Clin Periodontol"},{"key":"R4-20240924","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1600-0765.1993.tb01069.x","article-title":"Increased oxidative product formation by peripheral blood polymorphonuclear leukocytes in human periodontal diseases","volume":"28","author":"Kimura","year":"1993","journal-title":"J Periodontal Res"},{"key":"R5-20240924","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1600-051X.2005.00669.x","article-title":"Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls","volume":"32","author":"Akalin","year":"2005","journal-title":"J Clin Periodontol"},{"key":"R6-20240924","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1113\/expphysiol.1997.sp004024","article-title":"Oxidative stress: Oxidants and antioxidants","volume":"82","author":"Sies","year":"1997","journal-title":"Exp Physiol"},{"key":"R7-20240924","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1210\/edrv-12-2-151","article-title":"Pineal melatonin: Cell biology of its synthesis and of its physiological interactions","volume":"12","author":"Reiter","year":"1991","journal-title":"Endocr Rev"},{"key":"R8-20240924","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00418-010-0698-6","article-title":"Possible involvement of melatonin in tooth development: Expression of melatonin 1a receptor in human and mouse tooth germs","volume":"133","author":"Kumasaka","year":"2010","journal-title":"Histochem Cell Biol"},{"key":"R9-20240924","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.18388\/abp.2003_3637","article-title":"Melatonin as an antioxidant: Biochemical mechanisms and pathophysiological implications in humans","volume":"50","author":"Reiter","year":"2003","journal-title":"Acta Biochim Pol"},{"key":"R10-20240924","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1034\/j.1600-079X.2003.00075.x","article-title":"Relationship between salivary melatonin levels and periodontal status in diabetic patients","volume":"35","author":"Cutando","year":"2003","journal-title":"J Pineal Res"},{"key":"R11-20240924","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1902\/jop.2006.050287","article-title":"Relationship between salivary melatonin and severity of periodontal disease","volume":"77","author":"Cutando","year":"2006","journal-title":"J Periodontol"},{"key":"R12-20240924","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/j.1600-0765.2007.00978.x","article-title":"Melatonin expression in periodontal disease","volume":"42","author":"G\u00f3mez-Moreno","year":"2007","journal-title":"J Periodontal Res"},{"key":"R13-20240924","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1902\/jop.2009.090327","article-title":"Salivary and gingival crevicular fluid melatonin in periodontal health and disease","volume":"81","author":"Srinath","year":"2010","journal-title":"J Periodontol"},{"key":"R14-20240924","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4103\/2231-0754.95283","article-title":"Evaluation of melatonin levels in saliva in periodontal health and disease: A clinico-biochemical study","volume":"2","author":"Mhaske","year":"2010","journal-title":"J Int Clin Dent Res Organ"},{"key":"R15-20240924","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s00784-012-0801-6","article-title":"Non-surgical periodontal therapy influences salivary melatonin levels","volume":"17","author":"Bertl","year":"2013","journal-title":"Clin Oral Investig"},{"key":"R16-20240924","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/jre.12010","article-title":"Melatonin levels in periodontal health and disease","volume":"48","author":"Almughrabi","year":"2013","journal-title":"J Periodontal Res"},{"key":"R17-20240924","doi-asserted-by":"crossref","first-page":"217","DOI":"10.5005\/jp-journals-10015-1235","article-title":"Evaluation of nonsurgical treatment effects on salivary melatonin level in periodontal disease: A radioimmunoassay study","volume":"4","author":"Hagh","year":"2013","journal-title":"World J Dent"},{"key":"R18-20240924","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/307402","article-title":"Salivary melatonin and the severity of attachment loss: A case-control study","volume":"2014","author":"Hagh","year":"2014","journal-title":"J Oral Dis"},{"key":"R19-20240924","first-page":"ZC23","article-title":"Gingival, plasma and salivary levels of melatonin in periodontally healthy individuals and chronic periodontitis patients: A pilot study","volume":"9","author":"Balaji","year":"2015","journal-title":"J Clin Diagn Res"},{"key":"R20-20240924","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/adj.12294","article-title":"Malondialdehyde, superoxide dismutase and melatonin levels in gingival crevicular fluid of aggressive and chronic periodontitis patients","volume":"61","author":"Ghallab","year":"2016","journal-title":"Aust Dent J"},{"key":"R21-20240924","doi-asserted-by":"crossref","first-page":"519","DOI":"10.4103\/0976-237X.194115","article-title":"Evaluation of melatonin levels in saliva in gingivitis and periodontitis cases: A pilot study","volume":"7","author":"Lodhi","year":"2016","journal-title":"Contemp Clin Dent"},{"key":"R22-20240924","article-title":"The influence of non-surgical periodontal therapy on salivary melatonin levels: A pilot study","author":"Bertl","year":"2013"},{"key":"R23-20240924","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10787-018-0539-0","article-title":"The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: A double-blind, placebo-controlled trial","volume":"27","author":"Bazyar","year":"2019","journal-title":"Inflammopharmacology"},{"key":"R24-20240924","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/jre.12619","article-title":"Is dietary melatonin supplementation a viable adjunctive therapy for chronic periodontitis?-A randomized controlled clinical trial","volume":"54","author":"El-Sharkawy","year":"2019","journal-title":"J Periodontal Res"},{"key":"R25-20240924","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/jre.12686","article-title":"Melatonin as host modulating agent supporting nonsurgical periodontal therapy in patients affected by untreated severe periodontitis: A preliminary randomized, triple-blind, placebo-controlled study","volume":"55","author":"Tinto","year":"2020","journal-title":"J Periodontal Res"},{"key":"R26-20240924","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1600-0757.2006.00178.x","article-title":"The role of reactive oxygen and antioxidant species in periodontal tissue destruction","volume":"43","author":"Chapple","year":"2007","journal-title":"Periodontol 2000"},{"key":"R27-20240924","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int J Biochem Cell Biol"},{"key":"R28-20240924","first-page":"17","article-title":"Melatonin: It\u2019s antioxidant effects on periodontal disease","volume":"3","author":"Ozdem","year":"2018","journal-title":"J Healthc Commun"},{"key":"R29-20240924","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4161\/psb.1.3.2640","article-title":"The physiological function of melatonin in plants","volume":"1","author":"Arnao","year":"2006","journal-title":"Plant Signal Behav"},{"key":"R30-20240924","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.freeradbiomed.2012.11.002","article-title":"Immune modulatory and antioxidant effects of melatonin in experimental periodontitis in rats","volume":"55","author":"Kara","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"R31-20240924","first-page":"1141","article-title":"Interactions of the pineal hormone melatonin with oxygen-centered free radicals: A brief review","volume":"26","author":"Reiter","year":"1993","journal-title":"Braz J Med Biol Res"},{"key":"R32-20240924","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1902\/jop.2007.060396","article-title":"Melatonin: Potential functions in the oral cavity","volume":"78","author":"Cutando","year":"2007","journal-title":"J Periodontol"},{"key":"R33-20240924","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1600-079X.1990.tb00692.x","article-title":"Correlation between salivary and serum melatonin: Dependence on serum melatonin levels","volume":"9","author":"Laakso","year":"1990","journal-title":"J Pineal Res"},{"key":"R34-20240924","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1600-079X.1987.tb00854.x","article-title":"Melatonin rhythm in human plasma and saliva","volume":"4","author":"McIntyre","year":"1987","journal-title":"J Pineal Res"},{"key":"R35-20240924","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.phrs.2009.11.014","article-title":"Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation","volume":"62","author":"Maldonado","year":"2010","journal-title":"Pharmacol Res"},{"key":"R36-20240924","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1600-079X.1991.tb00827.x","article-title":"Melatonin-induced enhancement of antibody-dependent cellular cytotoxicity","volume":"10","author":"Giordano","year":"1991","journal-title":"J Pineal Res"},{"key":"R37-20240924","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.4049\/jimmunol.153.6.2671","article-title":"Activation of human monocytes by the pineal hormone melatonin","volume":"153","author":"Morrey","year":"1994","journal-title":"J Immunol"},{"key":"R38-20240924","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1600-079X.2007.00516.x","article-title":"Melatonin as an antibiotic: New insights into the actions of this ubiquitous molecule","volume":"44","author":"Tekbas","year":"2008","journal-title":"J Pineal Res"},{"key":"R39-20240924","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/rmv.1714","article-title":"Beneficial actions of melatonin in the management of viral infections: A new use for this \u201cmolecular handyman\u201d?","volume":"22","author":"Boga","year":"2012","journal-title":"Rev Med Virol"},{"key":"R40-20240924","doi-asserted-by":"crossref","first-page":"e0166442.","DOI":"10.1371\/journal.pone.0166442","article-title":"Melatonin receptor agonists as the \u201cperioceutics\u201d agents for periodontal disease through modulation of porphyromonas gingivalis virulence and inflammatory response","volume":"11","author":"Zhou","year":"2016","journal-title":"PLoS One"},{"key":"R41-20240924","doi-asserted-by":"crossref","first-page":"e628","DOI":"10.4317\/medoral.19851","article-title":"Effects of local melatonin application on post-extraction sockets after third molar surgery. A pilot study","volume":"19","author":"Cobo-V\u00e1zquez","year":"2014","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"R42-20240924","doi-asserted-by":"crossref","first-page":"22041","DOI":"10.1074\/jbc.274.31.22041","article-title":"Melatonin promotes osteoblast differentiation and bone formation","volume":"274","author":"Roth","year":"1999","journal-title":"J Biol Chem"},{"key":"R43-20240924","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/jpi.12133","article-title":"Melatonin regulates mesenchymal stem cell differentiation: A review","volume":"56","author":"Luchetti","year":"2014","journal-title":"J Pineal Res"},{"key":"R44-20240924","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1600-079X.2012.00989.x","article-title":"A novel calcium aluminateemelatonin scaffold enhances bone regeneration within a calvarial defect","volume":"53","author":"Clafshenkel","year":"2012","journal-title":"J Pineal Res"},{"key":"R45-20240924","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1708-8208.2009.00242.x","article-title":"Topical application of melatonin and growth hormone accelerates bone healing around dental implants in dogs","volume":"14","author":"Mu\u00f1oz","year":"2012","journal-title":"Clin Implant Dent Relat Res"},{"key":"R46-20240924","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1007\/s10856-008-3416-3","article-title":"Effect of FGF-2 and melatonin on implant bone healing: A histomorphometric study","volume":"19","author":"Takechi","year":"2008","journal-title":"J Mater Sci Mater Med"},{"key":"R47-20240924","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1111\/clr.12472","article-title":"Zirconia with laser\u2010modified microgrooved surface vs. titanium implants covered with melatonin stimulates bone formation. Experimental study in tibia rabbits","volume":"26","author":"Calvo\u2010Guirado","year":"2015","journal-title":"Clin Oral Implants Res"},{"key":"R48-20240924","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1563\/aaid-joi-D-14-00277","article-title":"Clinical and radiographic evaluation of immediate loaded dental implants with local application of melatonin: A preliminary randomized controlled clinical trial","volume":"42","author":"El-Gammal","year":"2016","journal-title":"J Oral Implantol"}],"container-title":["Advanced Biomedical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/abr.abr_152_23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:40:31Z","timestamp":1787773231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/abr.abr_152_23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/abr.abr_152_23","relation":{},"ISSN":["2277-9175"],"issn-type":[{"value":"2277-9175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2023-05-03","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-12","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}