Palmitoyl pentapeptide-4 vs Pentapeptide-18
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 a cream ingredient sold as a Botox alternative for expression lines. Two small studies of 20 people each had no comparison group, so the proof is weak.
Palmitoyl pentapeptide-4 has the stronger evidence, grade B (some human evidence) against grade C for Pentapeptide-18. 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.
The human evidence is two small uncontrolled studies: a 20-volunteer, two-month test of pentapeptide-18 creams at three strengths, in which only the strongest reduced measured wrinkle length, and an eight-week test in 20 women of a cream that also contained retinol. Neither had a vehicle or placebo control, and the manufacturer has not published its own trial data. Uncontrolled series put it at C for expression lines.
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
Pentapeptide-18 is a cosmetic ingredient, sold under the trade name Leuphasyl. Cosmetic ingredients in the United States are not reviewed or approved by the FDA before sale, so there is no FDA approval to cite for or against it.
Sold for
Palmitoyl pentapeptide-4, better known as Matrixyl, is the peptide most anti-wrinkle creams point to when they say peptides work.
Pentapeptide-18 is sold as a topical alternative to botulinum toxin that softens expression lines, usually paired with acetyl hexapeptide-8 (Argireline).
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.
Two small uncontrolled studies in 20 volunteers each report shorter or fewer wrinkles after weeks of use, one of them with retinol in the same cream, which is grade C support at best.
Class
Signal (collagen) peptide
Neurotransmitter-inhibiting peptide
Route
Topical
Topical