A small study with 24 healthy volunteers showed that a skin cream containing acetyl‑hexapeptide‑3 (a peptide often called Argireline) reduced wrinkle‑related skin measurements and improved the skin’s water barrier. The related peptide tripeptide‑10‑citrulline also showed anti‑wrinkle effects, and the two together might work better, though the exact benefit of the combo wasn’t clear.

Bioactive peptides have beneficial effects on the skin. We investigated to evaluate the effect of acetyl hexapeptide-3 and tripeptide-10 citrulline and the possible synergism between these two peptides. Twenty-four healthy volunteers were randomized to receive combination of acetyl hexapeptide-3 with tripeptide-10 citrulline (Group G1), tripeptide-10 citrulline (Group, G2), acetyl hexapeptide-3 (Group G3), or neither peptide (Group G4) for 60 days. Skin properties evaluated included skin microtopography, parameters cR2 and cR3, and transepidermal water loss (TEWL) using a skin visioscan and a tewameter, respectively. After 20 days, the measurements between G1 and G2 groups (cR2 P=.045, cR3 P=.044), G2 and G3 groups (cR2 P=.017, cR3 P=.017), G3 and G4 groups (CR2 P=.022), and G2 and G4 groups (cR3 P=.028) from baseline were significant. After 60 days, measurements between groups G1 and G3 (cR2 P=.016, cR3 P=.025), groups G2 and G3 (cR2 P=.044, cR3= P=.044), and groups G1 and G4 (cR2 P=.025) were significant. After 20 days, changes in TEWL between groups G1 and G3 (P=.03), groups G2 and G3 (P=.045), and groups G3 and G4 (P=.025) were significant. After 40 days, changes between groups G2 and G3 (P=.028) and groups G3 and G4 (P=.01) from baseline were significant. Our results confirm the antiwrinkle activity of acetyl hexapeptide-3. A significant decrease in TEWL with acetyl hexapeptide-3 treatment is observed. We provided clinical evidence for the antiwrinkle efficacy of tripeptide-10 citrulline and possibly TEWL. The underlying mechanism by which these two peptides can act synergistically was not clear in this study.