Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials

Nukaly, Houriah Y.; Halawani, Ibrahim R.; Irtaza, H. M.; Alturkistani, Talah; Serafi, Mohammed Rehab; Alhawsawi, Waseem; Bogari, Hassan Omar; Ahmed, Ferdous A.; Alhaddad, Yara; Shadid, Asem; Alharithy, Ruaa; Jfri, Abdulhadi

doi:10.3389/fmed.2026.1618306

Cited by 4Skin Protection and AgingFacial Rejuvenation and Surgery TechniquesDermatologic Treatments and Research

Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials

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Nukaly, Houriah Y., Halawani, Ibrahim R., Irtaza, H. M., Alturkistani, Talah, Serafi, Mohammed Rehab, Alhawsawi, Waseem, Bogari, Hassan Omar, Ahmed, Ferdous A. +4 more·2026·Frontiers in Medicine

DOI 10.3389/fmed.2026.1618306

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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. Systematic review registration: identifier CRD420250652779.

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Recent randomized controlled trials evaluating oral or topical bioactive compounds-including collagen peptides and other nutraceutical ingredients-have demonstrated improvements in wrinkle-related parameters assessed using validated quantitative techniques.
“Consistent with this, recent randomized controlled trials evaluating oral or topical bioactive compounds—including collagen peptides and other nutraceutical ingredients—have demonstrated improvements in wrinkle-related parameters assessed using validated quantitative techniques [43,44,45,46,47,48].”
From A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Effects of Oral Centella asiatica Extract on Skin Aging-Related Parameters in Middle-Aged Korean Women. (2026) · cites this paper as [47]
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Previous randomized controlled trials and meta-analyses have reported improvements in skin elasticity following oral or topical interventions, including collagen peptides and other bioactive compounds.
“Although previous randomized controlled trials and meta-analyses have reported improvements in skin elasticity following oral or topical interventions, including collagen peptides and other bioactive compounds [43,44,45,46,47,48]”
From A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Effects of Oral Centella asiatica Extract on Skin Aging-Related Parameters in Middle-Aged Korean Women. (2026) · cites this paper as [47]
The direction of change observed in the present study (increased skin hydration following supplementation) is generally consistent with previous reports.
“Although the direction of change observed in the present study (i.e., increased skin hydration following supplementation) is generally consistent with previous reports [43,44,45,46,47,48]”
From A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Effects of Oral Centella asiatica Extract on Skin Aging-Related Parameters in Middle-Aged Korean Women. (2026) · cites this paper as [47]

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Authors: Nukaly, H. Y., Halawani, I. R., Irtaza, H. M., Alturkistani, T., Serafi, M. R., Alhawsawi, W., Bogari, H. O., Ahmed, F. A., Alhaddad, Y., Shadid, A., Alharithy, R., & Jfri, A.
Affiliations: McGill University Health Centre (CA)
King Abdulaziz University (SA)
Bahawal Victoria Hospital (PK)
King Saud bin Abdulaziz University for Health Sciences (SA)
Faculty of Medicine, King Abdulaziz University
King Fahd Armed Forces Hospital (SA)
Batterjee Medical College (SA)
King Fahd Medical City (SA)
Princess Nourah bint Abdulrahman University (SA)
Corresponding author: Jfri, Abdulhadi
ORCID: Nukaly, Houriah Y.
Halawani, Ibrahim R.
Alhawsawi, Waseem
Bogari, Hassan Omar
Ahmed, Ferdous A.
Alhaddad, Yara
Shadid, Asem
Alharithy, Ruaa
Jfri, Abdulhadi
Venue: Frontiers in Medicine
Publisher: Frontiers Media SA
Published: 2026-03-17
Volume: 13
Pages: 1618306-1618306
ISSN: 2296-858X (ISSN-L)
DOI: 10.3389/fmed.2026.1618306
OpenAlex: W7137967974
Cited by: 3
References: 34
Citations by year: 2026: 3
FWCI: 4.81
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Medicine (publishedVersion, cc-by)
PubMed (publishedVersion)
PubMed Central (publishedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: European Academy of Dermatology and Venereology
Institute of Microbiology, Chinese Academy of Sciences
Topics: Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Health Sciences › Medicine › Dermatology › Facial Rejuvenation and Surgery Techniques
Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
Keywords: skin aging, polypeptides, wrinkle reduction, skin hydration, skin elasticity, skin brightness, collagen synthesis, extracellular matrix, anti-aging therapy, safety and tolerability

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Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials

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