Scientific Online Resource System

Scripta Scientifica Medicinae Dentalis

The role and significance of some salivary amino acids in periodontal diseases, including plaque-induced gingivitis—a literature review

Sirma Angelova, Ayshe Salim, Yoana Kiselova-Kaneva, Diana Ivanova, Radosveta Andreeva-Borisova, Stefan Peev


Nowadays the problem of plaque-induced gingivitis, including in the different periods of childhood, is marked by a considerable long-term sociomedical impact on individual, group, population and community levels globally. The purpose of this investigation is to study, analyze and summarize various scientific sources on the role and significance of some salivary amino acids in the presence of periodontal diseases, including plaque-induced gingivitis. This manuscript is based on data obtained from research articles, randomized trials, and systemic reviews published in PubMed and Google Scholar. Different salivary markers are characterized by potential for earlier diagnosis of the progression of oral diseases. We can conclude that some salivary amino acids play a considerable role in the periodontal status, including in plaque-induced gingivitis.


saliva, amino acids, plaque-induced gingivitis, periodontal status

Full Text


Bimstein E, Huja PE, Ebersole JL. The potential lifespan impact of gingivitis and periodontitis in children. J Clin Pediatr Dent. 2013; 38(2):95–9. doi: 10.17796/jcpd.38.2.j525742137780336.

Modéer T, Wondimu B. Periodontal diseases in children and adolescents. Review Dent Clin North Am. 2000;44(3):633-58.

Murakami S, Mealey BL, Mariotti A, Chapple ILC. Dental plaque-induced gingival conditions. J Periodontol. 2018;89 Suppl 1:S17-S27. doi: 10.1002/JPER.17-0095.

Tonetti MS, Chapple ILC, Jepsen S, Sanz M. Primary and secondary prevention of periodontal and peri-implant diseases. J Clin Periodontol. 2015;42(Suppl. 16): S1- S4. doi: 10.1111/jcpe.12382.

U.S. Public Health Service NCHS. Periodontal Diseases and Oral Hygiene Among Children, United States. DHEW Publication No. (HSM) 72–1060. Vol. Series 11 No. 117. Washington, DC: Government Printing Office; 1972.

Stamm JW. Epidemiology of gingivitis. J Clin Periodontol. 1986;13(5):360–70. doi: 10.1111/j.1600-051x.1986.tb01473.x.

Bhat M. Periodontal health of 14-17-year-old US schoolchildren. J Public Health Dent. 1991;51(1):5–11. doi: 10.1111/j.1752-7325.1991.tb02168.x.

Burt B; Research, Science and Therapy Committee of the American Academy of Periodontology. Position paper: epidemiology of periodontal diseases. J Periodontol. 2005;76(8):1406-19. doi: 10.1902/jop.2005.76.8.1406.

Dye BA. Global periodontal disease epidemiology. Periodontol 2000. 2012;58(1):10-25. doi: 10.1111/j.1600-0757.2011.00413.x.

Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. Lab Invest. 1976; 34(3):235–49.

Pawlaczyk-Kamieńska T, Torlińska-Walkowiak N, Borysewicz-Lewicka M. The relationship between oral hygiene level and gingivitis in children. Adv Clin Exp Med. 2018;27(10):1397-401. doi: 10.17219/acem/70417.

Leous P, Palianskaya L, Leous L. Oral hygiene and gingival inflammation in 6–8-year-olds from a junior school in Minsk who participated in a supervised oral hygiene programme. Oral Health Dent Manag. 2009;7:27–30.

Arnlaugsson S, Magnusson TE. Prevalence of gingivitis in 6-year olds in Reykjavik, Iceland. Acta Odontol Scand. 1996;54(4):247–50. doi: 10.3109/00016359609003532.

Albandar JM. Global risk factors and risk indicators for periodontal diseases. Periodontol 2000. 2002;29:177–206. doi: 10.1034/j.1600-0757.2002.290109.x.

Hemadneh S, Ayesh D. Prevalence of gingivitis in 6-7 year old Jordanian children. Pakistan Oral Dent J. 2011;31:168–170.

Varas F, Zillmann G, Munoz A, Hassi J, Yevenes I, Echeverria S, et al. Periodontal status and treatment needs of children from 6 to 8 years old in the Santiago Metropolitan Region of Chile. J Oral Res. 2011;26(1):10–5.

Bimstein E, Matsson L. Growth and development considerations in the diagnosis of gingivitis and periodontitis in children. Review Pediatr Dent. 1999;21(3):186-91.

Rebelo MA, Queiroz AC. Gingival Diseases - Their Aetiology, Prevention and Treatment. In: Panagakos F, Davies R, editors. Gingival Indices: State of Art. IntechOpen; 2011.p.1-16. doi: 10.5772/26236.

Wei SH, Lang KP. Periodontal epidemiological indices for children and adolescents: I. Gingival and periodontal health assessments. Pediatr Dent. 1981;3(4):353-60.

Shah S. Salivaomics: The current scenario. J Oral Maxillofac Pathol. 2018;22(3):375-81. doi: 10.4103/jomfp.JOMFP_171_18.

Helmerhorst EJ, Oppenheim FG. Saliva: a dynamic proteome. J Dent Res. 2007 Aug;86(8):680-93. doi: 10.1177/154405910708600802.

Timothy CN, Samyuktha PS, Brundha MP. Dental pulp stem cells: a promising tool for bone regeneration. Stem Cell Rev. 2008;4(1):21-6. doi: 10.1007/s12015-008-9013-5.

Wong DT. Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc. 2006;137(3):313-21. doi: 10.14219/jada.archive.2006.0180.

Agarwal R, Lakshmi T. Salivary enzymes as biomarkers for periodontitis--an update. Res J Pharm Technol. 2014;7(1):98–100.

Thirumalaisamy V, Gajendran P. Role of Salivary Interleukin 1 in Chronic Periodontitis: A Review. Res J Pharm Technol. 2018; 11(1):390.

Devi TJ. Saliva – a potential diagnostic tool. IOSR J Dent Med Sci. 2014;13(2):52–7.

Koneru S, Tanikonda R. Salivaomics - a promising future in early diagnosis of dental diseases. Dent Res J (Isfahan). 2014;11(1):11-5.

ThamaraiSelvi VT, Brundha, MP. Salivaomics - a review. Eur J Mol Clin Med. 2020;7(1):2914-31.

Syrjanen S, Piironen P, Markkanen H. Free amino-acid composition of wax-stimulated whole saliva in human subjects with healthy periodontium, severe chronic periodontitis and post-juvenile periodontitis. Arch Oral Bio. 1984; 29(9):735–8. doi: 10.1016/0003-9969(84)90181-x.

Syrjanen S, Piironen P, Markkanen H. Free amino-acid content of wax stimulated whole saliva as related to periodontal disease. Arch Oral Biol. 1987; 32(9):607–10. doi: 10.1016/0003-9969(87)90032-x.

Syrjanen S, Alakuijala L, Alakuijala P, Markkanen SO, Markkanen H. Free amino acid levels in oral fluid of normal subjects and patients with periodontal disease. Arch Oral Biol. 1990; 35(3):189–93. doi: 10.1016/0003-9969(90)90054-e.

Van Wuyckhuyse BC, Perinpanayagam HE, Bevacqua D, Raubertas RF, Billings RJ, Bowen WH, et al. Association of free arginine and lysine concentrations in human parotid saliva with caries experience. J Dent Res. 1995;74(2):686-90. doi: 10.1177/00220345950740021001.

Carpenter GH. Salivary factors that maintain the normal oral commensal microflora. J Dent Res. 2020;99(6):644-649. doi: 10.1177/0022034520915486.

Gardner A, Parkes HG, So PW, Carpenter GH. Determining bacterial and host contributions to the human salivary metabolome. J Oral Microbiol. 2019;11(1):1617014. doi: 10.1080/20002297.2019.1617014.

Cleaver LM, Moazzez R, Carpenter GH. Mixed aerobic-anaerobic incubation conditions induce proteolytic activity from in vitro salivary biofilms. J Oral Microbiol. 2019;11(1):1643206. doi:10.1080/20002297.2019.1643206

Bennick A. Salivary proline-rich proteins. Mol Cell Biochem. 1982;45(2):83-99. doi: 10.1007/BF00223503.

Koopman JE, Hoogenkamp MA, Buijs MJ, Brandt BW, Keijser BJ, Crielaard W, Ten Cate JM, Zaura E. Changes in the oral ecosystem induced by the use of 8% arginine toothpaste. Arch Oral Biol. 2017;73:79-87. doi: 10.1016/j.archoralbio.2016.09.008.

Vitorino R, Barros A, Caseiro A, Domingues P, Duarte J, Amado F. Towards defining the whole salivary peptidome. Proteomics Clin Appl. 2009;3(5):528–40.

Gonçalves Lda R, Soares MR, Nogueira FC, Garcia CH, Camisasca DR, Domont G, et al. Analysis of the salivary proteome in gingivitis patients. J Periodontal Res. 2011;46(5):599-606. doi: 10.1111/j.1600-0765.2011.01378.x.

James P. Protein identification in the postgenome era: the rapid rise of proteomics. Q Rev Biophys. 1997; 30(4):279–331. doi: 10.1017/s0033583597003399.

Amado FM, Vitorino RM, Domingues PM, Lobo MJ, Duarte JA. Analysis of the human saliva proteome. Expert Rev Proteomics. 2005;2(4):521–39. doi: 10.1586/14789450.2.4.521.

Gonçalves Lda R, Soares MR, Nogueira FC, Garcia C, Camisasca DR, Domont G, et al. Comparative proteomic analysis of whole saliva from chronic periodontitis patients. J Proteomics. 2010;73(7):1334-41. doi: 10.1016/j.jprot.2010.02.018.

Geiger S, Harper E. Human gingival collagenase in periodontal disease: The release of collagenase and the breakdown of endogenous collagen in gingival explants. J Dent Res 1980;59(1):11-6. doi: 10.1177/00220345800590010101.

Yanagimura M, Hara K, Nohara H. Collagenase activities in healthy and inflamed gingiva of dogs. J Periodont Res. 1983; 18(1):1-10. doi: 10.1111/j.1600-0765.1983.tb00329.x.

Bienkowski RS. Intracellular degradation of newly synthesized collagen. Coll Relat Res. 1984;4(5):399-411. doi: 10.1016/s0174-173x(84)80008-4.

Berg RA, Schwartz ML, Crystal RG. Regulation of the production of secretory proteins: Intracellular degradation of newly synthesized "defective" collagen. Proc Nati Acad Sci USA. 1980;77(8):4746-50. doi: 10.1073/pnas.77.8.4746.

Page RC, Narayanan AS, Schroeder HE. Connective tissue composition and collagen synthesis in diseased and normal gingiva of adult dogs with spontaneous periodontitis. Arch Oral Biol. 1980;25(11-12):727-36. doi: 10.1016/0003-9969(80)90126-0.

Akalin FA, Sengün D, Eratalay K, Renda N, Cağlayan G. Hydroxyproline and total protein levels in gingiva and gingival crevicular fluid in patients with juvenile, rapidly progressive, and adult periodontitis. J Periodontol. 1993;64(5):323-9. doi: 10.1902/jop.1993.64.5.323.

Nigra T, Friedland M, Martin GR. Controls of connective tissue synthesis: Collagen metabolism. J Invest Dem. 1972;59(1):44-9. doi: 10.1111/1523-1747.ep12625755.

Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976; 34(3):235-49.

Pérez-Tamayo R. Pathology of collagen degradation. A review. Am J Pathol. 1978;92(2):508-66.

Schacterle GR, Zaydenberg M, Carrel R. The relationship between gingival inflammation and its protein composition. J Pedod. 1985;9(3):218-24.

Mukherjee S, Das AK, Patel MK. A longitudinal study of crevicular fluid in periodontal disease in beagles. Clinical, histopathological and biochemical observations. J Periodont Res. 1983; 8(5):501-15. doi: 10.1111/j.1600-0765.1983.tb00387.x. .

Weinstein E, Mandel ID, Saikind A, Oshrain HI, Pappas CD. Studies of gingival fluid. Periodontics. 1967;5:161-6.

Alfano MC. The origin of gingival fluid. J Theor Biol. 1974;47(1):127-36. doi: 10.1016/0022-5193(74)90103-9.

Biswas S, Duperon DF, Chebib FS. Study of crevice fluid in relation to periodontal disease in children. II. Effect of age, sex and gingival inflammation on crevice fluid protein, carbohydrates, total calcium, phosphate and nitrogen. J Periodont Res. 1977;12(4):265-78. doi: 10.1111/j.1600-0765.1977.tb00130.x.

Shapiro L, Novaes AB Jr, Fillios L, Simons G, Goldman HM. Sulcular exudate protein levels as an indicator of the clinical inflammatory response. J Periodontol. 1980;51(2):86-7. doi: 10.1902/jop.1980.51.2.86.

Hino S, Nishiyama A, Matsuta T, Horie N, Shimoyama T, Tanaka S, et al. Quest for cells responsible for age-related increase of salivary glycine and proline. In Vivo. 2016;30(2):91-7.

Schaumann T, Kraus D, Winter J, Wolf M, Deschner J, Jäger A. Potential immune modularly role of glycine in oral gingival inflammation. Clin Dev Immunol. 2013; 2013:808367. doi: 10.1155/2013/808367.

Wheeler MD, Ikejema K, Enomoto N, Stacklewitz RF, Seabra V, Zhong Z, et al. Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci. 1999 Nov 30;56(9-10):843-56. doi: 10.1007/s000180050030.

Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, et al. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care. 2003;6(2):229-40. doi: 10.1097/00075197-200303000-00013.

Gundersen RY, Vaagenes P, Breivik T, Fonnum F, Opstad PK. Glycine--an important neurotransmitter and cytoprotective agent. Acta Anaesthesiol Scand. 2005;49(8):1108-16. doi: 10.1111/j.1399-6576.2005.00786.x.

Bruck R, Wardi J, Aeed H, Avni Y, Shirin H, Avinoach I, et al. Glycine modulates cytokine secretion, inhibits hepatic damage and improves survival in a model of endotoxemia in mice. Liver Int. 2003;23(4):276-82. doi: 10.1034/j.1600-0676.2003.00839.x.

Breivik T, Gundersen Y, Fonnum F, Vaagenes P, Opstad PK. Chronic glycine treatment inhibits ligature-induced periodontal disease in Wistar rats. J Periodontal Res. 2005;40(1):43-7. doi: 10.1111/j.1600-0765.2004.00767.x.

Tábi T, Lohinai Z, Pálfi M, Levine M, Szöko E. CE-LIF determination of salivary cadaverine and lysine concentration ratio as an indicator of lysine decarboxylase enzyme activity. Anal Bioanal Chem. 2008;391(2):647-51. doi: 10.1007/s00216-008-2026-8.

Levine M, Lohinai ZM. Resolving the contradictory functions of lysine decarboxylase and butyrate in periodontal and intestinal diseases. J Clin Med. 2021;10(11):2360. doi:10.3390/jcm10112360.

Lohinai Z, Keremi B, Szöko E, Tábi T, Szabo C, Tulassay Z, et al. Biofilm lysine decarboxylase, a new therapeutic target for periodontal inflammation. J Periodontol. 2015;86(10):1176-84. doi: 10.1902/jop.2015.140490.

Levine M, Lohinai Z, Teles RP. Low biofilm lysine content in refractory chronic periodontitis. J Periodontol. 2017 Feb;88(2):181-9. doi: 10.1902/jop.2016.160302.

Niederman R, Buyle-Bodin Y, Lu BY, Robinson P, Naleway C. Short-chain carboxylic acid concentration in human gingival crevicular fluid. J Dent Res. 1997;76(1):575-9. doi: 10.1177/00220345970760010801.

Diaz PI, Hoare A, Hong BY. Subgingival microbiome shifts and community dynamics in periodontal diseases. J Calif Dent Assoc. 2016;44(7):421-35.

Lohinai Z, Keremi B, Szöko E, Tábi T, Szabo C, Tulassay Z, et al. Biofilm Lysine Decarboxylase, a New Therapeutic Target for Periodontal Inflammation. J Periodontol. 2015;86(10):1176-84. doi: 10.1902/jop.2015.140490.

Burne RA, Marquis RE. Alkali production by oral bacteria and protection against dental caries. FEMS Microbiol Lett. 2000;193(1):1-6. doi: 10.1111/j.1574-6968.2000.tb09393.x.

Liu YL, Nascimento M, Burne RA. Progress toward understanding the contribution of alkali generation in dental biofilms to inhibition of dental caries. Int J Oral Sci. 2012;4(3):135-40. doi: 10.1038/ijos.2012.54.

Bernier SP, Ha DG, Khan W, Merritt JH, O'Toole GA. Modulation of Pseudomonas aeruginosa surface-associated group behaviors by individual amino acids through c-di-GMP signaling. Res Microbiol. 2011;162(7):680-8. doi: 10.1016/j.resmic.2011.04.014.

Borriello G, Richards L, Ehrlich GD, Stewart PS. Arginine or nitrate enhances antibiotic susceptibility of Pseudomonas aeruginosa in biofilms. Antimicrob Agents Chemother. 2006;50(1):382-4. doi: 10.1128/AAC.50.1.382-384.2006.

Sato T, Nakazawa F. Coaggregation between Prevotella oris and Porphyromonas gingivalis. J Microbiol Immunol Infect. 2014;47(3):182-6. doi: 10.1016/j.jmii.2012.09.005.

Zhu Y, Weiss EC, Otto M, Fey PD, Smeltzer MS, Somerville GA. Staphylococcus aureus biofilm metabolism and the influence of arginine on polysaccharide intercellular adhesin synthesis, biofilm formation, and pathogenesis. Infect Immun. 2007;75(9):4219-26. doi: 10.1128/IAI.00509-07.

Huang X, Zhang K, Deng M, Exterkate RAM, Liu C, Zhou X, et al. Effect of arginine on the growth and biofilm formation of oral bacteria. Arch Oral Biol. 2017;82:256-62. doi: 10.1016/j.archoralbio.2017.06.026.

Ledder RG, Mistry H, Sreenivasan PK, Humphreys G, McBain AJ. Arginine exposure decreases acidogenesis in long-term oral biofilm microcosms. mSphere. 2017;2(4):e00295-17. doi: 10.1128/mSphere.00295-17.

Koning TJ. Amino acid synthesis deficiencies. J Inherit Metab Dis. 2017;40(4):609-20. doi:10.1007/s10545-017-0063-1.

Stachowicz-Stencel T, Synakiewicz A. Glutamine as a supplemental treatment in pediatric and adult oncology patients. Expert Opin Investig Drugs. 2012;21(12):1861-71. doi:10.1517/13543784.2012.717929.

Ren W, Wang K, Yin J, Chen S, Liu G, Tan B, Wu G, Bazer FW, Peng Y, Yin Y. Glutamine-Induced Secretion of Intestinal Secretory Immunoglobulin A: A Mechanistic Perspective. Front Immunol. 2016;7:503. doi: 10.3389/fimmu.2016.00503.

Socransky SS, HaffajeeAD. Dental biofilms: difficult therapeutic targets. Periodontol 2000. 2002;28(1):12-55. doi:10.1034/j.1600-0757.2002.280102.x.

Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809-20. doi:10.1016/S0140-6736(05)67728-8.

Ahmadi-Motamayel F, Goodarzi MT, Jamshidi Z, Kebriaei R. Evaluation of salivary and serum antioxidant and oxidative stress statuses in patients with chronic periodontitis: a case-control study. Front Physiol. 2017;8:189. doi:10.3389/fphys.2017.00189.

Listyarifah D, Al-Samadi A, Salem A, Syaify A, Salo T, Tervahartiala T, et al. Infection and apoptosis associated with inflammation in periodontitis: An immunohistologic study. Oral Dis. 2017;23(8):1144-54. doi: 10.1111/odi.12711.

Junior AR, Segundo AS, Semenoff TD, Silva NF, Caporossi C. Effect of glutamine ingestion on the progression of induced periodontitis: experimental study in rats. Rev Odontol UNESP. 2018;47(2):119-23.

Chojnowska S, Baran T, Wilińska I, Sienicka P, Cabaj-Wiater I, Knaś M. Human saliva as a diagnostic material. Adv Med Sci. 2018;63(1):185-91. doi: 10.1016/j.advms.2017.11.002.

Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57(5):675-87. doi: 10.1373/clinchem.2010.153767.

Zhang CZ, Cheng XQ, Li JY, Zhang P, Yi P, Xu X, et al. Saliva in the diagnosis of diseases. Int J Oral Sci. 2016;8(3):133-7. doi: 10.1038/ijos.2016.38.

Liu J, Duan Y. Saliva: a potential media for disease diagnostics and monitoring. Oral Oncol. 2012;48(7):569-77. doi: 10.1016/j.oraloncology.2012.01.021.

Kaczor-Urbanowicz KE, Martin Carreras-Presas C, Aro K, Tu M, Garcia-Godoy F, Wong DT. Saliva diagnostics - Current views and directions. Exp Biol Med (Maywood). 2017;242(5):459-72. doi: 10.1177/1535370216681550.

PB, Patil BR. Saliva: A diagnostic biomarker of periodontal diseases. J Indian Soc Periodontol. 2011;15(4):310-7. doi: 10.4103/0972-124X.92560.

Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: current state and future directions. Periodontol 2000. 2009;50:52-64. doi: 10.1111/j.1600-0757.2008.00288.x.



About The Authors

Sirma Angelova
Medical University of Varna

Department of Pediatric Dentistry, Faculty of Dental Medicine

Ayshe Salim
Medical University of Varna

Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy

Yoana Kiselova-Kaneva
Medical University of Varna

Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy

Diana Ivanova
Medical University of Varna

Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy

Radosveta Andreeva-Borisova
Medical University of Varna

Department of Pediatric Dentistry, Faculty of Dental Medicine

Stefan Peev
Medical University of Varna

Department of Periodontology and Dental Implantology, Faculty of Dental Medicine

Font Size