Combination of trehalose and botulinum toxin type A in REVITOX skin treatment protocols

This article presents the REVITOX protocol, developed by the author, which includes the combination of REVI products (native hyaluronic acid + trehalose) and botulinum toxin type A (BTA) for the treatment of rosacea and correction of age-related changes. A plethora of studies has demonstrated that trehalose, an exceptional stabilizer of proteins, contributes to maintaining cellular integrity, exhibits antioxidant and angioprotective effects, and has been shown to induce autophagy. In combination with the proven effects of hyaluronic acid and BTA, these properties facilitate the optimal environment for cellular structure functioning, influencing the basic mechanisms of rosacea pathogenesis and mitigating the severity of age-related changes through the balanced elimination of dynamic and static rhytides, stimulation of neocollagenesis and improvement of the mechanical properties of the dermis. By targeting the multifactorial processes of facial aging, improving skin hydration and elasticity, the REVITOX Beauty protocol has ensured the balanced rejuvenation of the perioral and periorbital skin, resulting in a significant improvement in skin quality, as confirmed by the results of 3D diagnostics. After 3 treatment sessions of the REVITOX Derma program, the patients showed a general improvement of facial skin, a visible reduction in erythema and telangiectasia severity, regression of papulopustular elements, enhanced skin hydration and elasticity, and no recurrences at the follow-up. Further studies on the combined use of BTA and REVI will investigate the potential for using these protocols in the treatment of other dermatological conditions, including in combination with energy-based devices and beauty injections.

1. Juncan AM, Moisă DG, Santini A, Morgovan C, Rus LL, Vonica-Țincu AL, Loghin F. Advantages of Hyaluronic Acid and Its Combination with Other Bioactive Ingredients in Cosmeceuticals. Molecules. 2021;26(15):4429. https://doi.org/10.3390/molecules26154429.

2. Iaconisi GN, Lunetti P, Gallo N, Cappello AR, Fiermonte G, Dolce V, Capobianco L. Hyaluronic Acid: A Powerful Biomolecule with WideRanging Applications—A Comprehensive Review. Int J Mol Sci. 2023;24(12):10296. https://doi.org/10.3390/ijms241210296.

3. Bukhari SNA, Roswandi NL, Waqas M, Habib H, Hussain F, Khan S et al. Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol. 2018;120(Pt B):1682–1695. https://doi.org/10.1016/j.ijbiomac.2018.09.188.

4. Marinho A, Nunes C, Reis S. Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation. Biomolecules. 2021;11(10):1518. https://doi.org/10.3390/biom11101518.

5. Fanian F, Deutsch JJ, Bousquet MT, Boisnic S, Andre P, Catoni I et al. A hyaluronic acid-based micro-filler improves superficial wrinkles and skin quality: a randomized prospective controlled multicenter study. J Dermatolog Treat. 2023;34(1):2216323. https://doi.org/10.1080/09546634.2023.2216323.

6. Feofilova EP, Usov AI, Mysyakina IS, Kochkina GA. Trehalose: Chemical Structure, Biological Functions and Practical Value. Mikrobiologiya. 2014;83(3):271–283. (In Russ.) https://doi.org/10.7868/S0026365614020074.

7. Khoroshinina LP. Trehalose is a Life-Saving Sugar. Eksperimental′naya i klinicheskaya gastroenterologiya. 2022;198(2):139–147. (In Russ.) Available at: https://www.nogr.org/jour/article/view/1877.

8. Jain NK, Roy I. Effect of trehalose on protein structure. Protein Sci. 2009;18(1):24–36. https://doi.org/10.1002/pro.3.

9. Ahlgren K, Olsson C, Ermilova I, Swenson J. New insights into the protein stabilizing effects of trehalose by comparing with sucrose. Phys Chem Chem Phys. 2023;25(32):21215–21226. https://doi.org/10.1039/D3CP02639F.

10. Kuczyńska-Wiśnik D, Stojowska-Swędrzyńska K, Laskowska E. Intracellular Protective Functions and Therapeutical Potential of Trehalose. Molecules. 2024;29(9):2088. https://doi.org/10.3390/molecules29092088.

11. Benaroudj N, Lee DH, Goldberg AL. Trehalose Accumulation during Cellular Stress Protects Cells and Cellular Proteins from Damage by Oxygen Radicals. J Biol Chem. 2001;276(26):24261–24267. https://doi.org/10.1074/jbc.M101487200.

12. Emanuele E, Bertona M, Sanchis-Gomar F, Pareja-Galeano H, Lucia A. Protective effect of trehalose-loaded liposomes against UVB-induced photodamage in human keratinocytes. Biomed Rep. 2014;2(5):755–759. https://doi.org/10.3892/br.2014.310.

13. Maruf A, Milewska M, Varga M, Wandzik I. Trehalose-Bearing Carriers to Target Impaired Autophagy and Protein Aggregation Diseases. J Med Chem. 2023;66(23):15613–15628. https://doi.org/10.1021/acs.jmedchem.3c01442.

14. Xiao B, Huang H, Li L, Hou L, Yao D, Mo B. Trehalose inhibits proliferation while activates apoptosis and autophagy in rat airway smooth muscle cells. Acta Histochem. 2021;123(8):151810. https://doi.org/10.1016/j.acthis.2021.151810.

15. Li L, Chen H, Chen X, Chen S, Gu H. Trehalose Protects Keratinocytes against Ultraviolet B Radiation by Activating Autophagy via Regulating TIMP3 and ATG9A. Oxid Med Cell Longev. 2022;2022:9366494. https://doi.org/10.1155/2022/9366494.

16. Kaplon RE, Hill SD, Bispham NZ, Santos-Parker JR, Nowlan MJ, Snyder LL et al. Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults. Aging (Albany NY). 2016;8(6):1167–1183. https://doi.org/10.18632/aging.100962.

17. LaRocca TJ, Henson GD, Thorburn A, Sindler AL, Pierce GL, Seals DR. Translational evidence that impaired autophagy contributes to arterial ageing. J Physiol. 2012;590(14):3305–3316. https://doi.org/10.1113/jphysiol.2012.229690.

18. Chen C, Wang P, Zhang L, Liu X, Zhang H, Cao Y, Wang X, Zeng Q. Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates. Biomedicines. 2023;11(8):2153. https://doi.org/10.3390/biomedicines11082153.

19. Drozhdina MB, Bobro VA. Mechanisms of rosacea pathogenesis. A phenotypic approach to therapeutic tactics. Vestnik Dermatologii i Venerologii. 2022;98(5):90–97. (In Russ.) https://doi.org/10.25208/vdv1310.

20. Alsaati AA, Alsaadoun D, Kinkar LI, Alkhamis RS, Ahmed WA, Almathami AH. The Efficacy and Safety of Botulinum Toxin A for the Treatment of Rosacea: A Systematic Review. Cureus. 2023;15(12):е51304. https://doi.org/10.7759/cureus.51304.

21. Кубанов АА, Аравийская ЕР, Самцов АВ, Кондрахина ИН, Махакова ЮБ, Ласеев ДИ. Розацеа: клинические рекомендации. М.; 2020. 34 с. Режим доступа: https://www.rodv.ru/klinicheskie-rekomendacii/.

22. He G, Yang Q, Wu J, Huang Y, Zheng H, Cheng H. Treating rosacea with botulism toxin: Protocol for a systematic review and meta-analysis. J Cosmet Dermatol. 2024;23(1):44–61. https://doi.org/10.1111/jocd.15962.

23. Al-Niaimi F, Glagoleva E, Araviiskaia E. Pulsed dye laser followed by intradermal botulinum toxin TYPE-A in the treatment of rosacea-associated erythema and flushing. Dermatol Ther. 2020;33(6):е13976. https://doi.org/10.1111/dth.13976.

24. Friedman O, Koren A, Niv R, Mehrabi JN, Artzi O. The toxic edge – A novel treatment for refractory erythema and flushing of rosacea. Lasers Surg Med. 2019;51(4):325–331. https://doi.org/10.1002/lsm.23023.

25. Katoch S, Barua T, Barua K. Role of botulinum toxin in the management of topical corticosteroid induced rosacea like dermatitis: A case report. Indian Dermatol Online J. 2022;13(3):395–397. https://doi.org/10.4103/idoj.idoj_495_21.

26. Kim MJ, Kim JH, Cheon HI, Hur MS, Han SH, Lee YW et al. Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Randomized, Double-Blind, Placebo-Controlled, SplitFace Pilot Study in Rosacea Patients With Facial Erythema. Dermatol Surg. 2019;45(9):1155–1162. https://doi.org/10.1097/DSS.0000000000001819.

27. Lewandowski M, Świerczewska Z, Barańska-Rybak W. Off-Label Use of Botulinum Toxin in Dermatology – Current State of the Art. Molecules. 2022;27(10):3143. https://doi.org/10.3390/molecules27103143.

28. Luque A, Rojas AP, Ortiz-Florez A, Perez-Bernal J. Botulinum Toxin: An Effective Treatment for Flushing and Persistent Erythema in Rosacea. J Clin Aesthet Dermatol. 2021;14(3):42–45. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021409/.

29. Zhang H, Tang K, Wang Y, Fang R, Sun Q. Use of Botulinum Toxin in Treating Rosacea: A Systematic Review. Clin Cosmet Investig Dermatol. 2021;14:407–417. https://doi.org/10.2147/CCID.S307013.

30. Choi JE, Werbel T, Wang Z, Wu CC, Yaksh TL, Di Nardo A. Botulinum toxin blocks mast cells and prevents rosacea like inflammation. J Dermatol Sci. 2019;93(1):58–64. https://doi.org/10.1016/j.jdermsci.2018.12.004.

31. Gart MS, Gutowski KA. Overview of Botulinum Toxins for Aesthetic Uses. Clin Plast Surg. 2016;43(3):459–471. https://doi.org/10.1016/j.cps.2016.03.003.

32. Carruthers JDA, Glogau RG, Blitzer A. Advances in facial rejuvenation: botulinum toxin type A, hyaluronic acid dermal fillers, and combination therapies – consensus recommendations: Plast Reconstr Surg. 2008;121(5 Suppl): 5S–30S. https://doi.org/10.1097/PRS.0b013e31816de8d0.

33. Tirnaksiz F, Kayiş A, Çelebi N, Adişen E, Erel A. Preparation and Evaluation of Topical Microemulsion System Containing Metronidazole for Remission in Rosacea. Chem Pharm Bull (Tokyo). 2012;60(5):583–592. https://doi.org/10.1248/cpb.60.583.

34. Berg M, Edström DW. Flashlamp pulsed dye laser (FPDL) did not cure papulopustular rosacea. Lasers Surg Med. 2004;34(3):266–268. https://doi.org/10.1002/lsm.10254.

35. Chebotareva YuYu, Tonakanyan BM, Privalova EG. Combined rosacea treatment protocol using a pulsed dye laser and a dermal bioreparant with trehalose. Russian Journal of Clinical Dermatology and Venereology. 2023;22(5): 616–624. (In Russ.) https://doi.org/10.17116/klinderma202322051616.

36. Echigo R, Shimohata N, Karatsu K, Yano F, Kayasuga-Kariya Y, Fujisawa A et al. Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage. J Transl Med. 2012;10(1):80. https://doi.org/10.1186/1479-5876-10-80.

37. Panigrahi T, Shivakumar S, Shetty R, D’souza S, Nelson EJR, Sethu S, Jeyabalan N, Ghosh A. Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells. Ocul Surf. 2019;17(4):699–713. https://doi.org/10.1016/j.jtos.2019.08.004.

38. Korolkova TN, Ambartsumyan LL, Shepilova IA. The role of trehalose in the duration of the clinical effect of biorevitalizants. Russian Journal of Clinical Dermatology and Venereology. 2020;19(2):240–248. (In Russ.) https://doi.org/10.17116/klinderma202019021240.

39. Chaikovskaya EA, Rodina YuA, Manturova NE, Stenko AG. Patient assessment of effectiveness of facial skin biorevitalization procedures: a prospective study. Plastic Surgery and Aesthetic Medicine. 2023;(4):93–100. (In Russ.) https://doi.org/10.17116/plast.hirurgia202304193.

40. Kislitsyna AI, Naumchik GA. Intradermal injections of trehalose products to improve skin quality: clinical findings. Russian Journal of Clinical Dermatology and Venereology. 2022;21(3):361–367. (In Russ.) https://doi.org/10.17116/klinderma202221031361.