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PeptideAI
Observationalskin

Matrixyl Synthe'6

A lipopeptide marketed for deeper set wrinkles because it stimulates six matrix constituents at once, including the basement-membrane proteins the other Matrixyls ignore.

Also known as Palmitoyl Tripeptide-38, Pal-Lys-Met(O2)-Lys, Synthe'6, Matrixyl Synthe'6

Observational — Human data without randomisation. Suggestive, and easily confounded.

The six-matrix-constituent story rests on manufacturer explant and fibroblast data plus uncontrolled in-vivo panels. There is no independent randomised trial of palmitoyl tripeptide-38 on human facial wrinkles.

How it works

Palmitoyl tripeptide-38 is a lipidated Lys-Met(O2)-Lys tripeptide developed to broaden the matrikine effect beyond dermal collagen into the dermal-epidermal junction. In fibroblast and skin-explant work it raises collagen I, collagen III, collagen IV, fibronectin, hyaluronic acid and laminin-5 — the last two being the basement-membrane and hydration components that classic collagen-only peptides do not touch. Rebuilding laminin-5 and collagen IV is the argument for its use on deeper nasolabial and forehead lines, where dermal-epidermal junction flattening contributes to the crease. As with the rest of the Matrixyl family, no discrete receptor has been identified.

Targets: Collagen I, III and IV, Laminin-5, Fibronectin, Hyaluronic acid, Dermal-epidermal junction

Dosing

ProtocolDoseFrequencyRoute
Standard leave-on serumWorks fine morning or night; often placed in the same step as other peptides.—once or twice dailytopical
  • · The trade solution is used at 2-4% of the finished formula, which puts actual peptide around 100-200 ppm. From raw powder, target 0.01-0.05% w/w — going higher does not improve results and wastes an expensive material.

Cycling

Continuous daily use.

Work out your exact syringe units →

Pharmacology

Half-life
Not established.
Onset
Manufacturer panels report wrinkle-volume reduction from about 4 weeks, with continued gains through 8-12 weeks.
Routes
topical
Molecule
Palmitoylated tripeptide (oxidised methionine)
Sequence length
3 amino acids
Molecular weight
675.9 Da

Handling

Diluent
Propylene or pentylene glycol first, then water or serum base
Typical mix
10 or 50 mL
Vial sizes
50, 100, 200 mg
Lyophilised
Sealed, cool and dry; freezer for long-term.
Reconstituted
Refrigerated in a preserved base.

Mixing

Palmitoylated, so it needs a glycol or alcohol wetting step before dilution into water.

Side effects

  • rareIrritation— Generally very well tolerated.

Combining it

  • synergymatrixyl-3000 — Sederma positions these as complementary — 3000 for the dermis, Synthe'6 for the junction and deeper folds.
  • redundantmatrixyl — Overlapping collagen signalling.

What to monitor

  • · Standardised photography with consistent lighting and expression at 0, 8 and 16 weeks.

Legal status

Cosmetic ingredient (INCI Palmitoyl Tripeptide-38) approved worldwide.

References

  • Sederma Matrixyl Synthe'6 technical dossier (other)

Mechanism in depth

The selling point is that it reaches the dermal-epidermal junction, and that is worth taking seriously as an idea even though the evidence is thin. Most cosmetic collagen peptides target dermal collagen I and III. But a substantial part of what makes aged skin look creased rather than merely thin is flattening of the dermal-epidermal junction — the rete ridges that interdigitate epidermis and dermis progressively smooth out with age, reducing the surface area of contact, reducing nutrient exchange, and making the epidermis mechanically easier to fold. The junction is built from collagen IV, collagen VII and laminin-332 (still widely called laminin-5). Palmitoyl tripeptide-38 is claimed in supplier explant work to raise collagen I, collagen III, collagen IV, fibronectin, hyaluronic acid and laminin-5 — hence the six in the name. If the laminin and collagen IV effects are real, that would put it in a different functional category from the rest of the Matrixyl family, which only build dermal bulk. The argument for using it on deep nasolabial folds and forehead creases rests entirely on that distinction. As with the whole family, no receptor is identified and there is no independent human trial. Take the mechanism as plausible and the clinical claims as unverified.

What usually goes wrong

People buy this specifically for deep set lines because that is how it is marketed, and deep set lines are the thing topicals are worst at. A nasolabial fold is volume loss plus repeated mechanical folding plus junction flattening; a peptide serum addresses at most one of those three, slowly. Expect subtle. The other recurring error is concentration confusion: 2-4% of the trade solution is the supplier use level, which is roughly 100-200 ppm actual peptide, and DIY makers targeting percentages of raw powder end up hundreds of times over any tested level while spending a lot on an expensive material.

Pharmacokinetics

Crosses blood-brain barrier
no
Metabolism
Esterase and amidase cleavage of the palmitoyl bond, then peptidase degradation of the tripeptide. The oxidised methionine sulfone residue is unusual and is presumably there to prevent the oxidation that would otherwise degrade a methionine-containing peptide in an aerobic formulation.
Elimination
No meaningful systemic exposure.

Receptor targets

  • Unidentified fibroblast and keratinocyte matrikine receptor — No receptor cloned, no Kd published

    Claimed upregulation of collagen I, III and IV, fibronectin, hyaluronic acid and laminin-5 in explant and cell culture.

  • Laminin-332 / collagen IV at the dermal-epidermal junction — Downstream output, not a binding target

    The distinguishing claim. Rebuilding junction proteins would address a different structural failure from dermal collagen loss.

What to expect, and when

Week 4: the earliest point supplier panels report change. Week 8-12: continued gain. Week 16: realistic assessment point for anything involving the dermal-epidermal junction, since junction remodelling is slower than surface hydration by a wide margin.

Stacking and comparisons

No chemical incompatibilities. Sederma positions Synthe'6 and Matrixyl 3000 as complementary rather than redundant, on the argument that one works on dermal bulk and the other on the junction. That is a reasonable story and there is no comparative data testing it, so treat it as an unproven but harmless combination. The more useful partner is a retinoid: retinoids independently thicken the epidermis and improve dermal-epidermal junction morphology, which is the same target Synthe'6 claims, and the retinoid has the evidence. If you are using this for deep static folds, be aware that the intervention with actual evidence for that indication is hyaluronic acid filler, not a topical peptide.

Against Matrixyl and Matrixyl 3000, Synthe'6 has the broadest claimed target list and the weakest independent evidence — there is no randomised trial of palmitoyl tripeptide-38 alone on human facial wrinkles. If you want evidence, use plain Matrixyl. If you want the junction story, use a retinoid, which has actual histological data on dermal-epidermal junction morphology. Synthe'6 is a reasonable third peptide in a routine, not a first one.

Rough cost

$15–$90/month. One of the more expensive cosmetic peptide raw materials. Trade solution runs roughly $30-60 per 100 mL; finished products $20-90 a month. Market observation, not a sourced pricing study.

Genuinely uncertain

  • No independent randomised trial of palmitoyl tripeptide-38 exists. Every clinical number is from Sederma panels or from multi-ingredient formulations.
  • The six-matrix-constituent claim comes from supplier explant work I could not resolve to a primary indexed publication.
  • Whether the laminin-5 and collagen IV effects occur at concentrations achievable in human skin is unknown.
  • The molecular weight of 675.9 Da in the Core record is plausible for Pal-Lys-Met(O2)-Lys but I could not confirm it against a primary source.
  • No permeation data exist for this peptide specifically.

Papers