Palmitoyl pentapeptide-4 vs Hexapeptide-9
It is put in anti-wrinkle creams, often under the name Matrixyl, to smooth fine lines. One trial of 93 women showed a small gain, but the maker ran it and no one else has repeated it. It is put in anti-ageing creams to smooth wrinkles. The one controlled trial, of 96 adults, tested a changed version and was run by a cosmetics company.
Palmitoyl pentapeptide-4 has the stronger evidence, grade B (some human evidence) against grade C for Hexapeptide-9. Neither is FDA approved.
Evidence
BSome human evidence
CAnimal and cell studies
Human studies cited
Animal or cell studies cited
Why the grade
One randomized, double-blind, placebo-controlled split-face trial in 93 women showed a measurable reduction in fine lines and wrinkles over 12 weeks, backed by a 1993 cell study identifying the five-amino-acid sequence as a stimulator of collagen production. The trial was run by the manufacturer and has not been independently replicated, which caps it at B.
For wrinkle reduction, the evidence for standard hexapeptide-9 is unpublished supplier data, lab and mouse work, and a small split-face volunteer test of a delivery carrier. The one randomised double-blind trial, published in 2025 by employees of a cosmetics company, enrolled 96 adults but tested a chemically modified cyclised version against a low-concentration retinol and vehicle over 56 days, so the standard ingredient stays at C.
FDA
Cosmetic ingredient
Palmitoyl pentapeptide-4 is a cosmetic ingredient, sold under trade names such as Matrixyl. It is not approved by the FDA as a drug for any use; the FDA regulates cosmetics but does not approve their ingredients.
Cosmetic ingredient
Hexapeptide-9 is a cosmetic ingredient. Cosmetics do not go through FDA drug approval, so it has no approved indication and makes no drug claims; it is listed under its INCI name in skincare formulations.
Sold for
Palmitoyl pentapeptide-4, better known as Matrixyl, is the peptide most anti-wrinkle creams point to when they say peptides work.
Hexapeptide-9 is marketed in anti-aging serums as a collagen fragment that signals skin cells to rebuild the dermis and smooth wrinkles.
Studies say
A single sponsor-run randomized trial found modest wrinkle improvement versus the same moisturizer without the peptide, which is better evidence than most cosmetic peptides have and still short of independent confirmation.
The only controlled human trial tested a modified molecule and was run by the manufacturer, and the data for standard hexapeptide-9 are laboratory assays, so the grade is C.
Class
Signal (collagen) peptide
Signal peptide
Route
Topical
Topical