Zinc in Oral Health and Disease: A Narrative Review
Keywords:
zinc, oral health, oral diseases, oral cancer, tissue regenerationAbstract
Zinc is an essential trace element that plays a fundamental role in maintaining oral health through its structural, catalytic, and regulatory functions. It is involved in numerous biological processes, including immune modulation, antioxidant defense, collagen synthesis, mineralization, cellular signaling, and tissue repair, all of which contribute to oral tissue homeostasis. Recent evidence has highlighted the importance of zinc homeostasis, regulated by zinc transporters and metallothioneins, in preserving normal tooth development, periodontal integrity, and wound healing. Zinc also exerts antimicrobial, anti-inflammatory, and remineralizing effects, supporting its role in the prevention and management of dental caries, periodontal diseases, and oral mucosal disorders. Furthermore, advances in biomaterials and nanotechnology have expanded the therapeutic applications of zinc through zinc-containing restorative materials, zinc oxide nanoparticles, and zinc-L-carnosine, which demonstrate promising antimicrobial, regenerative, and tissue-healing properties. Emerging evidence also suggests that salivary zinc and zinc-associated proteins may serve as potential biomarkers for oral squamous cell carcinoma, although their diagnostic and therapeutic significance remains to be fully established. Despite these promising findings, the clinical application of zinc-based interventions is limited by inconsistencies in dosage, bioavailability, and treatment protocols. This narrative review summarizes the current evidence regarding the biological functions of zinc, its role in oral diseases, therapeutic applications in dentistry, and future perspectives, highlighting zinc as a promising adjunct in maintaining oral health and improving clinical outcomes.
References
Z. Abdullah, M. G. Nithin, and S. Siddiqui, "Zinc in Oral Health and Dental Diseases," in Zinc: Early Development, Applications, and Emerging Trends, 2024, pp. 68-82.
R. J. Lynch, "Zinc in the mouth, its interactions with dental enamel and possible effects on caries; a review of the literature," (in eng), Int Dent J, vol. 61 Suppl 3, no. Suppl 3, pp. 46-54, Aug 2011.
D. Seriwatanachai et al., "Effectiveness of a novel amine + zinc + fluoride toothpaste in reducing plaque and gingivitis: results of a six-month randomized controlled trial," (in eng), BMC Oral Health, vol. 25, no. 1, p. 188, Feb 5 2025.
M. M. Almoudi, A. S. Hussein, M. I. Abu Hassan, and N. Mohamad Zain, "A systematic review on antibacterial activity of zinc against Streptococcus mutans," Saudi Dental Journal, Review vol. 30, no. 4, pp. 283-291, 2018.
M. Khalil, S. Zraiki, and M. Khayat, "Evaluation of the salivary zinc assay as a potential diagnostic tool in potential malignant and malignant lesions of the oral cavity," Journal of Indian Academy of Oral Medicine and Radiology, Article vol. 31, no. 4, pp. 293-297, 2019.
A. A. Alqahtani, F. Alhalabi, and M. K. Alam, "Salivary elemental signature of dental caries: a systematic review and meta-analysis of ionomics studies," Odontology, Review vol. 112, no. 1, pp. 27-50, 2024.
M. J. Kim, J. H. Kang, and H. S. Kho, "Effects of Zinc Compounds on Lysozyme, Peroxidase, and α-Amylase from the Perspective of Oral Health: a Scoping Review," Biological Trace Element Research, Review vol. 202, no. 9, pp. 3900-3909, 2024.
M. J. Kim and H. S. Kho, "Efficacy of topical application of zinc compounds for oral mucosal diseases: A systematic review and meta-analysis," Medicina Oral Patologia Oral y Cirugia Bucal, Review vol. 31, no. 1, pp. e63-e72, 2026, Art. no. 27549.
T. Fukada, Y. Asada, K. Mishima, S. Shimoda, and I. Saito, "Slc39a13/Zip13 : A crucial zinc transporter involved in tooth development and inherited disorders," Journal of Oral Biosciences, Review vol. 53, no. 1, pp. 1-12, 2011.
Y. Idaira, T. Munemasa, T. Fukada, S. Shimoda, and Y. Asada, "Role of zinc transporter ZIP13 in degenerative changes in periodontal ligament and alveolar bone," Journal of Hard Tissue Biology, Article vol. 25, no. 1, pp. 49-56, 2016.
T. Fukada, Y. Idaira, S. Shimoda, and Y. Asada, "Zinc signaling-mediated regulation of dentin and periodontal tissues," Clinical calcium, Article vol. 25, no. 12, pp. 1862-1871, 2015.
M. Jarosz, M. Olbert, G. Wyszogrodzka, K. Młyniec, and T. Librowski, "Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling," Inflammopharmacology, Review vol. 25, no. 1, pp. 11-24, 2017.
M. Stefanidou, C. Maravelias, A. Dona, and C. Spiliopoulou, "Zinc: A multipurpose trace element," Archives of Toxicology, Review vol. 80, no. 1, pp. 1-9, 2006.
J. Aziz, M. T. Rahman, and R. D. Vaithilingam, "Dysregulation of metallothionein and zinc aggravates periodontal diseases," Journal of Trace Elements in Medicine and Biology, Review vol. 66, 2021, Art. no. 126754.
O. Mohammed, A. Tufa, and S. T. Gizaw, "Emerging Roles of Metallothioneins in Human Pathophysiology: A Review," (in eng), Health Sci Rep, vol. 8, no. 9, p. e71279, Sep 2025.
H. J. Oh et al., "Zinc balance is critical for NFI-C mediated regulation of odontoblast differentiation," Journal of Cellular Biochemistry, Article vol. 113, no. 3, pp. 877-887, 2012.
K. H. Park, Y. Choi, D. S. Yoon, K. M. Lee, D. Kim, and J. W. Lee, "Zinc Promotes Osteoblast Differentiation in Human Mesenchymal Stem Cells Via Activation of the cAMP-PKA-CREB Signaling Pathway," Stem Cells and Development, Article vol. 27, no. 16, pp. 1125-1135, 2018.
M. Huang, R. G. Hill, and S. C. F. Rawlinson, "Zinc bioglasses regulate mineralization in human dental pulp stem cells," Dental Materials, Article vol. 33, no. 5, pp. 543-552, 2017.
P. H. Lin, M. Sermersheim, H. Li, P. H. U. Lee, S. M. Steinberg, and J. Ma, "Zinc in Wound Healing Modulation," (in eng), Nutrients, vol. 10, no. 1, Dec 24 2017.
F. Arrighi, E. Berrino, and D. Secci, "Angiotensin-converting enzyme," in Metalloenzymes: From Bench to Bedside, 2023, pp. 239-253.
M. Mölders, J. Felix, D. Bingmann, A. Hirner, and M. Wiemann, "Uptake of nickel from 316L stainless steel into contacting osteoblastic cells and metal ion interference with BMP-2-induced alkaline phosphatase," Journal of Biomedical Materials Research - Part A, Article vol. 83, no. 2, pp. 303-312, 2007.
R. J. S. Galvin, W. K. Ramp, L. G. Lenz, and W. M. Pierce Jr, "Smokeless tobacco contains an inhibitor of prolyl hydroxylase activity," Toxicology Letters, Article vol. 62, no. 2-3, pp. 301-310, 1992.
S. Teerakanok, M. Zhao, R. Giordano, and Y. Fan, "Interaction of doped magnesium, zinc and fluoride ions on hydroxyapatite crystals grown on etched human enamel," Journal of Crystal Growth, Article vol. 571, 2021, Art. no. 126262.
R. J. M. Lynch et al., "Effects of zinc and fluoride on the remineralisation of artificial carious lesions under simulated plaque fluid conditions," Caries Research, Article vol. 45, no. 3, pp. 313-322, 2011.
H. I. Atasoy and O. I. A. Ulusoy, "The relationship between zinc deficiency and children's oral health," Pediatric Dentistry, Article vol. 34, no. 5, pp. 383-386, 2012.
R. Emram, R. V. Sionov, V. Gutkin, A. Wilensky, D. Steinberg, and R. Assad, "Mechanism of Action of Zinc Oxide Nanoparticles as an Antibacterial Agent Against Streptococcus mutans," Biomolecules, Article vol. 15, no. 12, 2025, Art. no. 1660.
J. H. Lim, Y. Jeong, S. H. Song, J. H. Ahn, J. R. Lee, and S. M. Lee, "Penetration of an antimicrobial zinc-sugar alcohol complex into Streptococcus mutans biofilms," Scientific Reports, Article vol. 8, no. 1, 2018, Art. no. 16154.
Y. Liu et al., "The changes and potential effects of zinc homeostasis in periodontitis microenvironment," Oral Diseases, Review vol. 29, no. 8, pp. 3063-3077, 2023.
A. F. Gombart, A. Pierre, and S. Maggini, "A review of micronutrients and the immune system–working in harmony to reduce the risk of infection," Nutrients, Article vol. 12, no. 1, 2020, Art. no. 236.
V. Gupta et al., "To evaluate the effect of oral zinc supplementation on salivary MMP-8 levels in periodontitis: A randomized, double-blind, placebo-controlled study," Journal of Oral Biology and Craniofacial Research, Article vol. 15, no. 3, pp. 493-499, 2025.
M. F. M. T. Alkayali, F. A. Badria, A. A. B. Elbaiomy, and J. M. Youssef, "Effect of polycaprolactone nanofibers loaded with oxytetracycline hydrochloride and zinc oxide as an adjunct to SRP on GCF lipocalin-2 levels in periodontitis patients: A clinical and laboratory study," Journal of Advanced Periodontology and Implant Dentistry, Article vol. 14, no. 2, pp. 76-83, 2022.
Z. X. Bao, X. W. Yang, J. Shi, and L. X. Liu, "Serum zinc levels in 368 patients with oral mucosal diseases: A preliminary study," Medicina Oral, Patologia Oral y Cirugia Bucal, Article vol. 21, no. 3, pp. e335-e340, 2016, Art. no. 21079.
S. Hewlings and D. Kalman, "A review of zinc-L-carnosine and its positive effects on oral mucositis, taste disorders, and gastrointestinal disorders," Nutrients, Review vol. 12, no. 3, 2020, Art. no. 665.
J. C. Alarcón-Moreno et al., "“The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study”," BMC Oral Health, Article vol. 24, no. 1, 2024, Art. no. 892.
H. Dong, W. Xu, S. Virtanen, and Y. Wang, "Enhanced bioactivity and degradation behavior of zinc via micro-arc anodization for biomedical applications," High Temperature Materials and Processes, Article vol. 44, no. 1, 2025, Art. no. 20240065.
A. Esmaeilnejad and B. Yarmand, "Improving biocompatibility and corrosion behavior of biodegradable zinc implant using a calcium zinc phosphate layer sealed by hydroxyapatite/polylactic acid," Surface and Coatings Technology, Article vol. 516, 2025, Art. no. 132760.
R. Nagasaki, K. Nagano, T. Nezu, and M. Iijima, "Synthesis and Characterization of Bioactive Glass and Zinc Oxide Nanoparticles with Enamel Remineralization and Antimicrobial Capabilities," Materials, Article vol. 16, no. 21, 2023, Art. no. 6878.
L. Cheng, K. Zhang, M. D. Weir, M. A. S. Melo, X. Zhou, and H. H. K. Xu, "Nanotechnology strategies for antibacterial and remineralizing composites and adhesives to tackle dental caries," Nanomedicine, Review vol. 10, no. 4, pp. 627-641, 2015.
Y. Han, R. Zhou, Y. Tong, and L. Zhu, "Development of biodegradable in situ Zn-Mg2Sn composites for bone-implant applications," Materials Letters, Article vol. 333, 2023, Art. no. 133569.
K. Efthymakis and M. Neri, "The role of Zinc L-Carnosine in the prevention and treatment of gastrointestinal mucosal disease in humans: a review," Clinics and Research in Hepatology and Gastroenterology, Review vol. 46, no. 7, 2022, Art. no. 101954.
H. S. Choi, E. S. Kim, B. Keum, H. J. Chun, and M. K. Sung, "L-carnosine and zinc in gastric protection," in Food and Nutritional Components in Focus, vol. 2015-January, 2015, pp. 548-565.
L. Togni et al., "Zinc-L-carnosine mouthwash in oral mucositis patients: a single-blind, randomized, controlled trial," Minerva dental and oral science, Article vol. 75, no. 4, pp. 263-272, 2026.
Y. J. Park, Y. Y. Kim, J. Y. Chang, J. W. Lee, and H. S. Kho, "Combined Effects of Zinc Compounds and Xylitol on the Enzymatic and Anticandidal Activities of Salivary Antimicrobials," International Dental Journal, Article vol. 76, no. 2, 2026, Art. no. 109415.
S. E. Adams et al., "A randomised, double-blind clinical study into the effect of zinc citrate trihydrate toothpaste on oral plaque microbiome ecology and function," Scientific Reports, Article vol. 15, no. 1, 2025, Art. no. 8136.
A. Bolos, O. C. Bolos, E. Maghet, A. I. Danila, R. Briceag, and B. A. Bumbu, "Clinical and Microbiological Effects of Streptococcus salivarius K12 Lozenges and Zinc Mouthrinse on Persistent Intra-Oral Halitosis," Microorganisms, Article vol. 14, no. 5, 2026, Art. no. 990.
Y. J. Jou et al., "Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages," Clinica Chimica Acta, Article vol. 412, no. 15-16, pp. 1357-1365, 2011.
S. J. Cheng et al., "Hypermethylated ZNF582 and PAX1 genes in mouth rinse samples as biomarkers for oral dysplasia and oral cancer detection," Head and Neck, Article vol. 40, no. 2, pp. 355-368, 2018.
A. Jain et al., "Identification of potential salivary biomarker panels for oral squamous cell carcinoma," Scientific Reports, Article vol. 11, no. 1, 2021, Art. no. 3365.
X. Wang, Y. Guo, C. Wang, Q. Wang, and G. Yan, "Long noncoding rna zeb1-as1 downregulates mir-23a, promotes tumor progression, and predicts the survival of oral squamous cell carcinoma patients," OncoTargets and Therapy, Article vol. 14, pp. 2699-2710, 2021.
T. Zhou, S. Liu, L. Shi, and L. Zhang, "The FUS/COL11A1/ZEB1 Axis Contributes to the Development of Oral Squamous Cell Carcinoma," Journal of Oral Pathology and Medicine, Article vol. 54, no. 3, pp. 182-191, 2025.
G. S. Panchannavar and P. V. Angadi, "Immunohistochemical expression of epithelial mesenchymal transition proteins ZEB1 and E-cadherin in oral leukoplakia and oral squamous cell carcinoma," World Journal of Experimental Medicine, Article vol. 15, no. 4, 2025, Art. no. 110372.
M. F. Ali, M. Hosein, S. Butt, and R. Siddiqui, "Zinc-alpha 2 glycoprotein a diagnostic Biomarker for early stage oral Squamous Cell Carcinoma," Pakistan Journal of Medical Sciences, Article vol. 39, no. 2, pp. 513-517, 2023.
J. Chuerduangphui et al., "Zinc-alpha-2-glycoprotein overexpression and maintaining anti-apoptotic function in oral squamous cell carcinoma," Archives of Oral Biology, Article vol. 176, 2025, Art. no. 106298.













