Hexapeptide-9 vs Pentapeptide-18
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. 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.
Both sit at grade C: animal and cell studies. Neither is FDA approved.
Evidence
CAnimal and cell studies
CAnimal and cell studies
Human studies cited
Animal or cell studies cited
Why the grade
For wrinkle reduction, the evidence for standard hexapeptide-9 is unpublished supplier data, lab and mouse work, and a small split-face volunteer test of a delivery carrier.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.
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
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.
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
Hexapeptide-9 is marketed in anti-aging serums as a collagen fragment that signals skin cells to rebuild the dermis and smooth wrinkles.
Pentapeptide-18 is sold as a topical alternative to botulinum toxin that softens expression lines, usually paired with acetyl hexapeptide-8 (Argireline).
Studies say
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.
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 peptide
Neurotransmitter-inhibiting peptide
Route
Topical
Topical