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J Cosmet Dermatol. 2017 Jun;16(2):271-278. doi: 10.1111/jocd.12314. Epub 2017 Feb 2.

The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study.

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Laboratory of Cosmetic Science, Department of Aesthetics and Cosmetology, Technological Educational Institute of Athens, Athens, Greece.
Division of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Athens, Greece.
Department of Medical Laboratories, Technological Educational Institute of Athens, Athens, Greece.



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.


TEWL ; acetyl hexapeptide-3; antiwrinkle efficacy; skin microtopography; tripeptide-10 citrulline

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