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SYSTEMATIC REVIEW article

Front. Med.

Sec. Dermatology

Oral and Topical Peptides as Anti-Aging Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

  • 1. Batterjee Medical College, Jeddah, Saudi Arabia

  • 2. King Abdulaziz University, Jeddah, Saudi Arabia, Makkah, 21589

  • 3. Bahawal Victoria Hospital, Bahawalpur, Pakistan, Punjab

  • 4. King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia

  • 5. King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia

  • 6. Almada Clinic, Jeddah, Saudi Arabia

  • 7. King Fahd Medical City, Riyadh, Saudi Arabia, Riyadh, 11525

  • 8. Security Forces Hospital, Riyadh, Saudi Arabia

  • 9. Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

  • 10. King Abdullah International Medical Research Center, Jeddah, Saudi Arabia

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Abstract

Abstract Introduction: Skin aging manifests as wrinkles, reduced elasticity, and roughness due to intrinsic and extrinsic factors. Peptide-based therapies enhance collagen synthesis and extracellular matrix integrity. This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of oral and topical peptides in improving hydration, elasticity, wrinkles, and brightness. Methods: A comprehensive search of MEDLINE, CENTRAL, and Web of Science was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) assessing peptide effects on skin aging parameters were included. The Cochrane Risk of Bias Tool (RoB 2) assessed study quality. Data were synthesized using a random-effects model in RStudio (R version 4.1.1). Conclusion: Nineteen RCTs involving 1,341 participants were analyzed. Peptides, particularly oral formulations, significantly improved hydration and brightness, with a modest pooled effect on wrinkle reduction (MD = 0.27, p = 0.04). Subgroup analysis indicated that this benefit was largely driven by oral polypeptides (MD = 1.5, p = 0.01). While effects on elasticity and density were inconsistent, peptides were well tolerated, with minimal adverse events reported across trials. Overall, peptides appear to be safe, non-invasive anti-aging agents, though larger RCTs with standardized outcomes and histopathologic assessment are warranted. Keywords: Skin aging, collagen peptides, topical peptides, oral peptides, anti-aging treatments.

Summary

Keywords

Anti-aging treatments, Collagen peptides, Oral peptides, Skin Aging, topical peptides

Received

25 April 2025

Accepted

12 January 2026

Copyright

© 2026 Nukaly, Halawani, Irtaza, Serafi, Alhawsawi, Bogari, Ahmed, Alturkistani, Alhaddad, Shadid, Alharithy and Jfri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Houriah Y. Nukaly; Abdulhadi Hazzaa Jfri

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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