Skin & aging Signal (collagen) peptide
Palmitoyl pentapeptide-4
Regulatory status
Status at a glance
503A compounding status
Not nominated
We found no pending nomination for the 503A bulks list. Unless the substance has another legal pathway (for example, a USP monograph or use in an FDA-approved drug), 503A pharmacies generally may not compound with it.
- Also known as
- Matrixyl
- FDA approval
- Not FDA-approved for any use
- 503B outsourcing
- Not determined
- Anti-doping (WADA)
- Not on the WADA Prohibited List
- DEA schedule
- Not a controlled substance
About peptide status
Most peptides discussed here are not FDA-approved for any use, and products labeled “research use only” are not for human use. Removal from Category 2 does not authorize compounding. PCAC votes are non-binding recommendations; FDA and HHS make the final decisions.
This is not medical or legal advice, and we do not publish dosing, sourcing or reconstitution information. Talk with a licensed clinician before using any peptide.
If you think you are having a medical emergency, call 911.
Key takeaway
Palmitoyl pentapeptide-4, sold in skincare as Matrixyl, is a matrikine: a fragment of type I collagen (KTTKS) attached to a fatty acid so it can be used topically. In lab studies the KTTKS fragment signals fibroblasts to produce collagen, and a 2005 double-blind trial found a topical product improved the appearance of fine lines over 12 weeks. It is a cosmetic ingredient rather than a drug, so it does not require FDA approval, and its evidence is rated Moderate.
At a glance
- What it is
- Synthetic peptide used as a cosmetic skin-conditioning ingredient, sold under trade names such as Matrixyl
- How it works
- A matrikine, a fragment of collagen that signals skin cells to produce more collagen
- FDA status
- Does not require FDA approval, as a cosmetic ingredient rather than a drug
- Evidence strength
- Moderate research
Summary
Palmitoyl pentapeptide-4 (Matrixyl) is a collagen-fragment peptide used in skincare. Learn how it works, what trials show, and its cosmetic status.
What is palmitoyl pentapeptide-4?
Palmitoyl pentapeptide-4, often written pal-KTTKS, is a synthetic peptide designed as a topical skincare agent. Its active core, KTTKS, is a five amino acid sequence (lysine-threonine-threonine-lysine-serine) taken from the propeptide of type I collagen. A palmitic acid chain is attached to that core to create the palmitoylated form, pal-KTTKS, which is the version used on skin.
It is sold as a cosmetic ingredient under trade names such as Matrixyl, and it is included in serums and moisturizers for skin conditioning, smoothing, and anti-aging purposes.
How does it work?
KTTKS is a fragment released when type I collagen is processed in the skin, and in laboratory studies, it stimulates fibroblasts to produce type I collagen, type III collagen, and fibronectin, the main components of the skin's supportive matrix. Researchers proposed that this fragment acts as a feedback signal, with the released collagen piece prompting cells to make more matrix.
The plain KTTKS peptide is not well suited to topical use on its own, so a palmitic acid group is attached to create pal-KTTKS, the form developed as a topical agent to stimulate collagen production for an anti-wrinkle benefit. Applied to the skin, it is used to support the appearance of firmer skin and reduce the look of fine lines and wrinkles.
Is palmitoyl pentapeptide-4 FDA-approved?
Safety note
Status: Does not require FDA approval, as a cosmetic ingredient rather than a drug
Category: Cosmetic and topical · Primary body area: Skin & aging
No, and it does not need to be. The FDA does not approve cosmetics or most cosmetic ingredients before they go on the market. Cosmetics are regulated and must be safe when used as directed and properly labeled, but there is no pre-market approval step the way there is for drugs, so no anti-aging peptide in a serum is "FDA-approved."
The line that actually matters for an ingredient like this is the difference between a cosmetic and a drug. A product is a cosmetic when it is intended to improve appearance, but if it claims to change the structure or function of the skin, the FDA can regulate it as an unapproved drug. This is why skincare claims are usually written around the appearance of the skin rather than a promised physiological change.
What is it used for?
Palmitoyl pentapeptide-4 is used almost entirely in topical anti-aging products, where it is included for skin conditioning, smoothing, and soothing. In its main clinical study, it was tested for improving the appearance of fine lines and wrinkles in photoaged facial skin.
What does the research show?
Editor’s note
Evidence strength: Moderate research (1 human · 0 animal/cell studies)
It has human trial evidence, including a 2005 double-blind, placebo-controlled study, but that evidence is limited: the trials are small, largely manufacturer-associated, and have not been replicated in large independent studies or pooled into a meta-analysis.
The main controlled evidence is a trial, and the rationale for its effect traces to earlier laboratory work.
| Study | Model or population | Finding |
|---|---|---|
| 2005 double-blind, placebo-controlled trial | 93 women aged 35 to 55, over 12 weeks | A moisturizer containing 3 ppm pal-KTTKS produced significant improvement in fine lines and wrinkles compared with placebo |
| Earlier laboratory work | Fibroblasts | KTTKS fragment stimulates collagen production in fibroblasts |
The evidence base is real but limited:
- The key trial was conducted by researchers at Procter & Gamble.
- Sample sizes are small.
- There is little large, independent, or long-term data.
That supports a modest cosmetic benefit rather than a dramatic effect, which is why it sits at Moderate research on the evidence scale.
What are the side effects?
In its clinical study, pal-KTTKS was well tolerated by the skin. As with any skincare ingredient, some people can still experience mild redness, irritation, or an allergic reaction, so a patch test before regular use is sensible. Because the peptide is applied to the skin rather than injected, the safety considerations are those of a typical cosmetic ingredient.
Sources: the 2005 double-blind, placebo-controlled trial of pal-KTTKS in the International Journal of Cosmetic Science (DOI: 10.1111/j.1467-2494.2005.00261.x); the 1993 laboratory study of the KTTKS collagen fragment (indexed on PubMed); and cosmetic ingredient references. This document is educational and does not constitute medical advice or a treatment claim.
Registered human trials
1 registered human trial on ClinicalTrials.gov that we reviewed
Sources
- [1]
- [2]
- [3]
- [4]
- [5]
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