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International Journal of Medical Sciences And Clinical Research

Peer Reviewed | Open Access | E-ISSN: 2771-2265
Published Article

Scientific Rationale for the Use of Proteolytic Enzymes in Tooth Whitening: A Clinical and Methodological Analysis of Efficacy and Risks

Scientific Rationale for the Use of Proteolytic Enzymes in Tooth Whitening: A Clinical and Methodological Analysis of Efficacy and Risks

  • Khasanjon Shokirjonovich Mirzayev
    Assistant at the Department of Propedeutics of Therapeutic Dentistry Tashkent State Medical University Tashkent, Uzbekistan
Enzymatic tooth whitening proteolytic enzymes papain bromelain

In recent years, enzymatic tooth whitening has been increasingly regarded as a scientifically substantiated and biologically oriented alternative to conventional peroxide-based methods for the correction of dental discoloration. The growing relevance of this approach is associated with the need to improve the safety of aesthetic dental procedures while maintaining clinically significant efficacy. Enzymatic whitening systems are based on the use of plant-derived proteolytic enzymes (papain, bromelain, ficin, etc.) capable of selectively degrading protein components of the acquired pellicle and pigmented organic complexes without causing pronounced oxidative effects on the mineral matrix of enamel and dentinal structures. Such a mechanism is presumed to provide a more conservative interaction with hard dental tissues and reduce the likelihood of pulpal irritation.

The aim of the present systematic review was to comprehensively evaluate current evidence regarding the mechanisms of action of enzymatic whitening formulations, analyze their clinical efficacy based on objective instrumental color parameters (CIELab, ΔE*ab, ΔE00, and the Whiteness Index for Dentistry — WI_D), and assess their safety profile with respect to enamel morphological alterations, microhardness parameters, and the incidence of post-procedural hypersensitivity.

The methodological basis of the review included an analysis of recent in vitro, in situ, and clinical studies employing standardized colorimetric methods and sensitivity assessment scales (Schiff, NRS/VAS). A comparative analysis was performed between the obtained findings and the outcomes associated with conventional peroxide-based whitening protocols.

The reviewed literature demonstrated that enzymatic formulations are capable of producing statistically significant and clinically perceptible improvements in tooth color parameters corresponding to established visual perception thresholds. In addition, the frequency and severity of hypersensitivity were generally lower compared with high-concentration peroxide systems. Morphological investigations indicated minimal alterations in enamel surface structure and no significant reduction in microhardness values when recommended application protocols were followed.

However, considerable variability in enzyme concentrations, exposure regimens, and instrumental assessment methodologies was identified, limiting the comparability of available findings and reducing the overall level of evidence of individual studies. Furthermore, the absence of long-term randomized clinical trials does not allow definitive conclusions regarding the stability of the achieved whitening effect and potential delayed biological consequences.

Thus, enzymatic tooth whitening may be considered a promising direction in personalized aesthetic dentistry, combining a favorable balance between efficacy and safety. Further integration of this technology into clinical algorithms requires protocol standardization, harmonization of objective color assessment criteria, and the implementation of multicenter controlled clinical studies.

Garazha S.N., Gotlib A.O., Kodzhakova T.Sh., Grishilova E.N., Zelenskaya A.V. Hypersensitivity during vital tooth whitening and its treatment. Chief Physician of Southern Russia. 2021;(6):45–49.

Irsaliev H., Valieva F., Irsalieva F. Photodynamic tooth whitening. Stomatology. 2023;1(2–3):27–30.

Latifova M., Rikhsieva D. Study and evaluation of the in vitro tooth whitening method. Current Problems of Dentistry and Maxillofacial Surgery. 2022;1(1):235–236.

Makedonova Yu.A., Chizhikova T.V., Mosyagina A.V., Nechaev M.V. Comparative analysis of the effect of whitening toothpaste on enamel hypersensitivity. Chief Physician of Southern Russia. 2023;(6):52–56.

Nefedova I.F., Brekhov S.D., Magsumova O.A., Postnikov M.A., Chigarina S.E., Ryskina E.A. Evaluation of the effectiveness of a remineralizing agent on enamel and dentin after chemical whitening using scanning microscopy. Clinical Dentistry. 2024;27(4):34–39.

Orekhova L.Yu., Novak M.O., Petrov A.A., Ivakhnenko E.A. Investigation of the effect of clinical whitening on hard dental tissues and pulpal microcirculation. Stomatologist. 2020;(1):52–59.

Uspenskaya O.A., Trefilova O.V. Severity of dental hypersensitivity during professional and home tooth whitening. Clinical Dentistry. 2019;(3):28–30.

Uspenskaya O.A., Trefilova O.V., Shevchenko E.A. Investigation of clinical and histological parameters during professional tooth whitening. Stomatology. 2020;99(3):11–17.

Khabadze Z.S., Shevchenko E.A. Modern approaches to the assessment of tooth whitening efficacy. Russian Dental Journal. 2022;26(4):15–20.

Chernyavsky Yu.P., Klimova A.V. Clinical assessment of the safety of whitening systems in aesthetic dentistry. Institute of Dentistry. 2021;(2):64–68.

Cuc S., et al. Whitening efficiency of papain and bromelain gels in removing dental stains. Gels. 2025;11(2):100.

Donassollo S.H., Donassollo T.A., Coser S., et al. Triple-blinded randomized clinical trial comparing efficacy and tooth sensitivity of in-office and at-home bleaching techniques. Journal of Applied Oral Science. 2021;29:e20200794.

Gasmi A., Menzel A., Hrynovets I., et al. A review on natural teeth whitening. Journal of Oral Biosciences. 2022;64(1):49–58.

Gupta P., et al. A randomized clinical trial comparing post-bleaching sensitivity and whitening outcomes. SAGE Open Medicine. 2025.

Hortkoff D., Farago P.V., Gomes J.C., Reis A., Gomes G.M. In-office bleaching after a desensitizing protocol: a 4.5-year follow-up of a randomized controlled trial. Journal of Dentistry. 2025;161:105932.

Münchow E.A., Hamann H.J., Carvajal M.T., Pinal R., Bottino M.C. Stain removal effect of novel papain- and bromelain-containing gels applied to enamel. Clinical Oral Investigations. 2016;20:2315–2320.

Paravina R.D., Pérez M.M., Ghinea R., et al. Acceptability and perceptibility thresholds in dentistry: a comprehensive review. Journal of Esthetic and Restorative Dentistry. 2019;31:103–112.

Pérez M.M., Ghinea R., Herrera L.J., et al. Development of a customized whiteness index for dentistry based on the CIELAB color space. Journal of Dentistry. 2016;48:7–13.

Ribeiro J.S., Barboza A.S., Cuevas-Suárez C.E., et al. Novel in-office peroxide-free tooth-whitening gels: bleaching effectiveness, enamel surface alterations, and cell viability. Scientific Reports. 2020;10:10016.

Terra R.M.O., Favoreto M.W., Morris T., Loguercio A.D., Reis A. Effect of at-home bleaching agents and concentrations on tooth sensitivity: a systematic review and network meta-analysis. Journal of Dentistry. 2025;160:105891.