Kalisa Lum BS a*, Milan M. Hirpara BA b*, Christine Pham MD b, Megan Nguyen BS b, Natasha Mesinkovska MD PhD b
a School of Medicine, Loma Linda University Health, Loma Linda, CA
b Department of Dermatology, University of California, Irvine, CA
Acetyl hexapeptide-8, marketed as Argireline® (Lipotec, Barcelona, Spain), is a six-amino-acid biomimetic of botulinum toxin promoted as a wrinkle-reducing compound. It entered the market in 2001 and has grown in popularity, as evidenced by a progressively increasing volume of Google searches from 2013 to 2023.1
Acetyl hexapeptide-8 is applied topically as a cream or serum and is marketed as a less invasive and less expensive alternative to botulinum toxin. Compared to botulinum toxin, acetyl hexapeptide-8 is both less potent (12 vs 0.003 AAUs) and less toxic (2000 mg/kg vs 20 ng/kg).2 Additionally, consumers may pay from $10 to $30 per ounce for drugstore products to $100 to $300 per ounce for premium formulations containing acetyl hexapeptide-8.3 Comparatively, full-face applications of botulinum toxin can cost $1000 to 3000.3 Our objective was to review the current literature on acetyl hexapeptide-8 and its efficacy in wrinkle minimization.
A literature search was conducted in August 2024 utilizing PRISMA guidelines using the PubMed, Cochrane Library, and Embase databases with search terms, '"acetyl hexapeptide-8" OR "acetyl hexapeptide-3" OR "argireline"'. Inclusion criteria included human studies evaluating cutaneous effects of acetyl hexapeptide-8. Exclusion criteria included non-human studies, non-English studies, studies not analyzing the cutaneous effects of acetyl hexapeptide-8, and articles without available full text.
Ten studies (302 females, and 10 males) met our inclusion criteria (Table 1).4-12 Four studies 4-7 analyzed the isolated effect of acetyl hexapeptide-8. Five studies 8-12 explored the efficacy of multi-ingredient formulations, and 1 study 13 assessed both its isolated effects and in combination with other compounds. All 10 studies reported decreases in wrinkle and scar prominence although significance varied. No significant adverse effects were reported in any trial.
All 4 studies describing the isolated effects of acetyl hexapeptide-8 reported significant changes in wrinkle appearance. Blanes-Mira et al 4 used Confocal Microscopy and 3D analyses to measure topography. Ruiz et al 5 measured skin hydration and wrinkle size using Clinipro Antiaging SD with the IMAGE DB system. Wang et al 6 measured topography with Skin-Visioline VL 650® and SPSS 17.0 software. Tadini et al 7 used the Corneometer® CM for skin hydration, and the CutometerSEM 575 and ReviscometerRV600 for anisotropy.
Four of 5 studies that utilized multi-ingredient formulations showed statistically significant changes in wrinkle and scar appearance. An et al 8 utilized Antera 3D® (Miravex, Ireland). Henseler 9 created wrinkle scores and biologic age comparisons with the Visia® Complexion Analysis camera. Palmieri et al 10 measured scar hydration (DermaLabR USB), skin elasticity (ElastiMeter R), sebum levels (Sebumeter SM 815), and used photos and SF-36 quality of life questionnaires. Li et al 11 used the Corneometer CM825, Skin Elastometer MPA580, PRIMOS CR technique, and self-assessment questionnaires. Draelos et al 12 used investigator evaluations, subject evaluations, and facial photographs. Raikou et al 13 measured both the isolated and adjunctive effects of acetyl hexapeptide-8 on microtopography (Skin Visioscan VC98) and transepidermal water loss (tewameter).
Keywords: Acetyl hexapeptide-8, Argireline®, botulinum toxin, wrinkle reduction, topical application, cosmetic dermatology, Aesthetics & Cosmetics
