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

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


Background: Bioactive peptides have beneficial effects on the skin.

Objective: We investigated to evaluate the effect of acetyl hexapeptide-3 and tripeptide-10 citrulline and the possible synergism between these two peptides.

Methods: 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.

Results: 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.

Conclusion: 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.

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

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Citrulline / administration & dosage*
  • Cosmetic Techniques*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Middle Aged
  • Oligopeptides / administration & dosage*
  • Prospective Studies
  • Skin Aging / drug effects*
  • Treatment Outcome


  • Oligopeptides
  • Citrulline
  • acetyl-glutamyl-glutamyl-methionyl-glutaminyl-arginyl-argininamide