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Palmitoyl tripeptide-5 and Argireline (acetyl hexapeptide-8) are two of the most requested peptides in my formulating work, and the question I hear most is which one belongs on which line. This page covers the two areas where people use them most outside the brow: horizontal forehead lines and crow's feet. I explain what each peptide is, what the published research measured and where it was measured, and then give a combined formula at each ingredient's highest recommended usage rate.
If your concern is the vertical "11" lines between the brows or vertical lines above the lip, read our Tripeptide-5 vs Argireline guide for vertical lines. This page does not repeat that comparison.
The Two Peptides in One Paragraph Each
Argireline (acetyl hexapeptide-8)
Argireline is a six amino acid sequence, first described by Blanes-Mira and colleagues in 2002. Its research centers on the SNARE complex, the protein assembly involved in the signal that tells facial muscles to contract. That is why it is grouped with expression-line peptides and why it is so often compared with Botox. It is not Botox, it is not injected, and its effect on the look of lines is far milder. The older INCI name is acetyl hexapeptide-3; both names refer to the same sequence.
Palmitoyl tripeptide-5 (Syn-Coll)
Palmitoyl tripeptide-5 is a three amino acid sequence attached to palmitic acid, a fatty acid that helps it sit in the skin's outer layers. The supplier, DSM, sells it as Syn-Coll and describes it as a firmness peptide that works through TGF-beta signaling. Its job in a formula is different from Argireline's: the look of firmness and support under a line, rather than the look of the movement that creases it.
Why Forehead Lines and Crow's Feet Behave Differently
| Horizontal forehead lines | Crow's feet | |
|---|---|---|
| Muscle involved | Frontalis, which raises the brows | Orbicularis oculi, which closes and squints the eye |
| Skin thickness | Thicker, more oil glands | Among the thinnest skin on the face |
| Line pattern | Long, parallel horizontal lines | Fan of short lines at the outer eye corner |
| Typical first appearance | Only when the brows are raised | Only when smiling or squinting |
| Later stage | Lines stay visible at rest | Lines stay visible at rest, often with crepey texture |
Both areas start with lines that appear only during movement and, over years, progress to lines that remain at rest. That is the key to choosing a peptide. Lines that show mostly with movement point toward Argireline. Lines visible at rest, along with thin or crepey texture, point toward adding a firmness peptide such as palmitoyl tripeptide-5.
What the Research Measured Around the Eyes
The published human studies on Argireline were run on the eye area, which makes crow's feet the best-documented use.
- Blanes-Mira and colleagues, 2002. A 10% acetyl hexapeptide-3 emulsion was applied twice daily to the outer eye area of 10 healthy women for 30 days, with the plain emulsion on the other side. Wrinkle depth, measured with silicone replicas, decreased by 30%. This is a small study, and it measured lines at rest rather than lines during movement.
- Wang and colleagues, 2013. In a randomized, placebo-controlled study, 60 Chinese adults with lines around the eyes were assigned 3:1 to Argireline or placebo and applied it twice daily for 4 weeks. Visual grading showed a total anti-wrinkle efficacy of 48.9% in the Argireline group and 0% in the placebo group. Roughness measured on silicone skin replicas decreased in the Argireline group (p < 0.01) and did not change significantly with placebo. The abstract does not state the concentration used, and blinding is not described in the abstract.
For palmitoyl tripeptide-5, I was not able to find a published, peer-reviewed human study with numbers to quote. The supporting information comes from the supplier. I describe it as supplier-supported and do not attribute specific results to it.
What the Research Says About Forehead Lines
Honestly, very little. I did not find a published study testing either peptide specifically on horizontal forehead lines. Using Argireline on the forehead is a reasonable extension of the eye-area data, because both areas form lines through repeated muscle movement, but it is an extension, not a tested result. If a product claims proven results on forehead lines for either peptide, ask to see the study.
Choosing by Line Type
| What you see | Lead peptide | Support peptide |
|---|---|---|
| Forehead lines only when raising brows | Argireline 10% | Optional |
| Forehead lines visible at rest | Argireline 10% | Palmitoyl tripeptide-5 3%, plus Matrixyl 3000 8% |
| Crow's feet only when smiling | Argireline 10% | Optional |
| Crow's feet at rest with crepey texture | Argireline 10% | Palmitoyl tripeptide-5 3% |
Every rate in this table is the manufacturer's highest recommended usage rate for that booster. I do not formulate these peptides at starter rates.
The Combined Formula: Forehead and Eye Peptide Serum
This blend uses both peptides at their highest recommended rates. Drop counts use our house rate of 9 drops = 1% per fluid ounce.
Formula A: Crow's Feet and Forehead Serum (1 fl oz)
| Ingredient | Rate | Drops | Grams |
|---|---|---|---|
| Argireline, Acetyl Hexapeptide 8 | 10% | 90 | 3.0 g |
| Syn-Coll Peptide Serum Booster (palmitoyl tripeptide-5) | 3% | 27 | 0.9 g |
| Preserved hyaluronic acid serum base | 87% | Fill to 1 fl oz | About 26 g |
Formula B: Forehead Lines Visible at Rest (1 fl oz)
| Ingredient | Rate | Drops | Grams |
|---|---|---|---|
| Argireline, Acetyl Hexapeptide 8 | 10% | 90 | 3.0 g |
| Syn-Coll Peptide Serum Booster | 3% | 27 | 0.9 g |
| Matrixyl 3000 Serum Booster | 8% | 72 | 2.4 g |
| Preserved hyaluronic acid serum base | 79% | Fill to 1 fl oz | About 24 g |
Formula B suits the forehead, where the skin is thicker. For the eye area, I use Formula A, because thinner skin does better with a simpler blend.
How to mix
- Sanitize a 1 oz dropper or airless bottle and your work surface.
- Add the base first. A preserved base, such as our Hyaluronic Acid Plumping Serum, keeps the finished blend fresh. Do not use plain water.
- Count in each booster. Weigh in grams if you want an exact repeat batch.
- Cap and shake for 30 seconds. Label with the formula name and date.
- Refrigerate. These boosters are water-based and will not blend into an oil-only base.
How to Apply to Each Area
Crow's feet
- Use one pump or 2 to 3 drops for both eyes.
- Tap along the outer corner and upper cheekbone with your ring finger, staying on the orbital bone, not on the eyelid.
- Apply morning and night, then eye cream or moisturizer on top.
Forehead
- Use 2 to 3 drops spread across the forehead, working upward from the brows to the hairline.
- Apply morning and night, then moisturizer.
- Sunscreen every morning. Daily sun exposure adds to the look of lines at rest on both areas.
What Results Look Like and When to Judge
The two published Argireline studies measured results at 4 weeks and at 30 days. I tell clients to judge the eye area at 4 weeks and the forehead at 8 weeks, since the forehead result is not backed by its own study. Photograph both areas in the same light with your face relaxed, then again while smiling and raising your brows. That gives you a record of both at-rest and in-motion lines.
For more on how Argireline compares with its close relative, see Snap-8 vs Argireline, and for every expression-line peptide in one place, our guide to peptide serums for the look of expression lines.
Frequently Asked Questions
Is Argireline or tripeptide-5 better for crow's feet?
Argireline has the published eye-area data: two human studies, one of 10 women over 30 days and one of 60 adults over 4 weeks. Palmitoyl tripeptide-5 is a useful support peptide for crepey texture, but I found no published human study numbers for it. Lead with Argireline at 10% and add palmitoyl tripeptide-5 at 3%.
Does Argireline work on forehead lines?
No published study I found tested it specifically on the forehead. Forehead lines form through repeated muscle movement, as crow's feet do, so using it there is a reasonable extension of the eye-area data, not a proven result.
Can I use Argireline and tripeptide-5 together?
Yes. They do different jobs, so they complement each other. Formula A above combines Argireline at 10% and palmitoyl tripeptide-5 at 3% in one serum.
Is Argireline the same as Botox?
No. Argireline is a topical amino acid sequence applied to the skin's surface. Botox is a prescription injectable. Argireline is often compared with Botox because both relate to muscle signaling, but the topical effect on the look of lines is much milder.
Can I use these peptides with Botox?
Many people use topical peptides between appointments. Ask your injector how long to wait after an appointment before applying anything to the area.
These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
About the Author
Written by Kari Thomas, cosmetic formulator and founder of Skin Perfection.
Sources
- Blanes-Mira C, Clemente J, Jodas G, et al. A synthetic hexapeptide (Argireline) with antiwrinkle activity. International Journal of Cosmetic Science. 2002;24(5):303-310. 10 women, 30 days, eye area.
- Wang Y, Wang M, Xiao S, Pan P, Li P, Huo J. The anti-wrinkle efficacy of Argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study. American Journal of Clinical Dermatology. 2013. PubMed 23417317. 60 adults, 4 weeks, eye area.
- DSM. SYN-COLL Formulation Guidelines. Supplier technical document for palmitoyl tripeptide-5: recommended use level 1% to 3%, pH 3.0 to 7.0, add below 40°C.