Palmitoyl Tripeptide-38

What is Palmitoyl Tripeptide-38?

Palmitoyl tripeptide-38 is a lipidated cosmetic matrikine: the tripeptide lysine-methionine-lysine, with the methionine present in oxidised form as the sulfone, conjugated to palmitic acid. Written out it is Pal-Lys-Met(O2)-Lys, commonly abbreviated Pal-KMK, with the molecular formula C33H65N5O7S and a molecular weight of about 676. It reaches formulators as Matrixyl synthe'6, developed by Sederma — the French active-ingredient house that is part of Croda — and it is the third molecule to carry the Matrixyl name. That lineage matters for keeping the family straight, because the Matrixyl products are not variants of one peptide. The original Matrixyl is palmitoyl pentapeptide-4 (Pal-KTTKS), a fragment of collagen I. Matrixyl 3000 is a pairing of palmitoyl tripeptide-1 (Pal-GHK) with palmitoyl tetrapeptide-7. Matrixyl synthe'6 is palmitoyl tripeptide-38, a different sequence drawn from different parent proteins. A fourth near-neighbour, palmitoyl tripeptide-5, is a separate ingredient sold as Syn-Coll and is not a Matrixyl product at all. Confusing any of these for the others is the most common error in this corner of cosmetic chemistry. The sequence is attributed to collagen VI and to laminin — both components of the dermal-epidermal junction region rather than of the bulk dermal matrix, which makes this a junction-directed matrikine in the same broad territory as hexapeptide-9 rather than a dermal collagen I mimic like the original Matrixyl. The palmitoyl chain serves one purpose: a bare tripeptide of a few hundred daltons is hydrophilic and partitions poorly into the lipid-rich stratum corneum, and the C16 fatty acid makes the molecule amphipathic enough to get in. The name 'synthe'6' refers to a supplier claim that the ingredient stimulates six matrix constituents. The peer-reviewed literature does not document which six, and no primary publication verifies the claim — so the number is best read as trade positioning rather than as a characterised mechanism.

What Palmitoyl Tripeptide-38 Is Investigated For

Palmitoyl tripeptide-38 has three published human studies and an unusually clean problem: none of them can tell you what the peptide does. All three are open-label, and all three test it inside a multi-ingredient formula. The most cited is Lintner, Gerstein and Solish (J Cosmet Dermatol 2020), in which women aged 40 and over applied a serum containing 15% L-ascorbic acid, tocopheryl acetate and 5 ppm palmitoyl tripeptide-38 once daily for 56 days. Skin roughness fell 8-9% (P<.05), isotropy increased, and photographic analysis showed a 9% reduction in redness and an 8% increase in homogeneity (both P<.0001). Those are real, instrumented results — and the formula contains 15% vitamin C, an active with its own substantial evidence base, at 30,000 times the peptide's concentration. Attributing the outcome to 5 ppm of peptide is not supportable from that design. Herndon and colleagues (J Drugs Dermatol 2015) ran 37 women through 12 weeks of a moisturiser containing a peptide blend including palmitoyl tripeptide-38, plus Astragalus membranaceus root extract, rosemary-derived ursolic acid, tetrahexyldecyl ascorbate and coenzyme Q10, and reported significant improvement across every clinical grading parameter at 8 and 12 weeks. Sanz and colleagues (J Cosmet Dermatol 2016) tested a serum combining apple stem cell extract, urea, creatine and palmitoyl tripeptide-38 in 32 women with sensitive skin twice daily for 28 days, reporting an anti-wrinkle effect in 71% of subjects, visible effects in 68% by day 7, and increased dermal density and elasticity. Both are open-label and both stack the peptide with several other actives. So the fair summary is this: the three formulations containing palmitoyl tripeptide-38 performed reasonably in open-label testing, which is weak evidence that the formulations work and essentially no evidence about the peptide. The mechanistic case rests on matrikine theory and supplier in vitro data, with genuinely interesting parent-protein biology behind it — collagen VI regulates dermal matrix assembly and fibroblast motility, and laminin-332 regulates epidermal stem cell differentiation — but no published work connects the fragment to those pathways at 5 ppm.

History & Discovery

Palmitoyl tripeptide-38 is the third act in Sederma's Matrixyl franchise, and the franchise is the best way to understand it. Sederma — the French active-ingredient subsidiary now part of Croda — introduced the original Matrixyl, palmitoyl pentapeptide-4 (Pal-KTTKS), in the late 1990s, lifting a five-residue fragment from the C-terminal propeptide of collagen I and conjugating palmitic acid to it so it could cross the stratum corneum. Matrixyl 3000 followed in the mid-2000s, pairing palmitoyl tripeptide-1 with the anti-inflammatory palmitoyl tetrapeptide-7 and extending the pitch from pure collagen stimulation to collagen stimulation plus reduction of inflammatory aging. Matrixyl synthe'6 arrived around 2012-2013 with a different strategy: rather than a bigger collagen I fragment or another combination, it took a shorter sequence from different parent proteins — collagen VI and laminin — and positioned itself on breadth, claiming six matrix constituents stimulated at once. The methionine in the sequence appears as the sulfone, a modification consistent with stabilising a readily oxidised residue, though no published rationale accompanies it. The name positioned it as a 'wrinkle filling' active aimed at deep lines, particularly on the forehead and crow's feet. The published record has stayed thin, and in a specific way. Rather than accumulating independent efficacy studies, the ingredient has appeared in three open-label multi-ingredient trials run by or with product manufacturers — ISDIN's apple-stem-cell serum in 2016, a US multi-ingredient moisturiser in 2015, and the vitamin C serum reported by Lintner in 2020. Karl Lintner is a long-standing figure in cosmetic peptide research whose consultancy KAL'IDEES S.A.S. holds the copyright on that 2020 paper, and who also co-authored the 2026 Current Research in Toxicology framework for peptide safety evaluation in cosmetics. That continuity is worth knowing when reading the literature, because the cosmetic peptide field is small and the same names recur on both the ingredient and the evidence side. A decade on, the structural facts are settled — Pal-Lys-Met(O2)-Lys, roughly 676 daltons, CAS 1101448-24-1 — and the central efficacy question is exactly where it started: what the peptide contributes on its own has never been measured.

How It Works

When the scaffolding inside skin breaks down, the fragments released act as a signal — a message to the cells that build that scaffolding to make more. Palmitoyl tripeptide-38 is a synthetic copy of one such fragment, taken from two proteins that sit where the epidermis meets the dermis. A fatty-acid tail is bolted on so the molecule can cross the skin's water-resistant outer layer. The theory is sound and widely used; what has not been shown is that this particular fragment, at the few parts per million actually used, produces the effect.

The matrikine hypothesis is the foundation. Peptide fragments liberated when extracellular matrix proteins are degraded act as signals that fibroblasts and keratinocytes interpret as a call to rebuild, upregulating synthesis of collagens, glycosaminoglycans and adhesion proteins. Synthetic matrikines present the fragment without the preceding damage. It is the mechanism behind palmitoyl pentapeptide-4, palmitoyl tripeptide-1 and most of the lipidated cosmetic peptide family, and it is credible — though effect sizes in this class are consistently modest. Palmitoyl tripeptide-38's Lys-Met-Lys core is attributed to sequences in collagen VI and laminin. Both are biologically substantial. Type VI collagen forms a distinct beaded microfibrillar network in the dermis and has been shown experimentally to regulate dermal matrix assembly and fibroblast motility — it organises matrix rather than merely occupying it — and its distribution and expression are demonstrably altered in photoaged human skin. Laminin, specifically laminin-332 (formerly laminin-5), is the principal adhesion ligand of the dermal-epidermal junction, is indispensable for homeostatic epidermal differentiation programs, and regulates differentiation of human interfollicular epidermal stem cells. Proteomic work has documented that the protein composition of the dermal-epidermal junction changes with intrinsic aging. Choosing these parents rather than collagen I is a defensible piece of design. Where the chain of reasoning breaks is the step from sequence to signal. Supplier materials claim stimulation of six matrix constituents, with collagens, fibronectin, hyaluronic acid and laminin typically named in secondary summaries, and in vitro increases at low parts-per-million concentrations are reported in trade literature. No primary peer-reviewed publication specifies the six constituents or demonstrates the effect, and no independent group has reproduced it. The methionine sulfone in the sequence is presumably a stability modification — a free methionine thioether is readily oxidised — but no published rationale explains the choice. The palmitoyl group is the one unambiguous element. Palmitic acid conjugation raises the molecular weight to roughly 676 while making the molecule amphipathic, improving partitioning into the stratum corneum's lipid lamellae. This is the same delivery strategy used across the lipidated matrikines, and it works better than nothing while still leaving only a modest fraction of applied peptide reaching the viable epidermis and papillary dermis. That delivery ceiling is the standard explanation for why cosmetic-peptide effect sizes are measurable but small.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about Palmitoyl Tripeptide-38:

• 01What the peptide does on its own. All three published human studies combined it with other actives and none had a peptide-omitted arm, so no study isolates its contribution. A vehicle-controlled trial of palmitoyl tripeptide-38 alone has never been published and would settle the central question.
• 02The six matrix constituents. The trade name's core claim is not documented in any primary peer-reviewed publication, and no independent work specifies which six are stimulated or demonstrates the effect at cosmetic concentrations.
• 03Collagen VI and laminin engagement. The parent-protein biology is sound — collagen VI regulates dermal matrix assembly and fibroblast motility, laminin-332 governs epidermal differentiation — but nothing published shows that a three-residue fragment modulates either pathway at 5 ppm.
• 04Independent, non-industry data. Every human study is open-label and manufacturer-associated, with the most-cited one copyrighted to a cosmetic-ingredient consultancy. Independent replication at relevant concentrations does not exist.
• 05Randomised or blinded design. No trial of this ingredient has been randomised, blinded or vehicle-controlled. By contrast, the related cosmetic peptide hexapeptide-9 now has a randomised, double-blinded, active- and vehicle-controlled trial, which shows such designs are achievable in this category.
• 06Head-to-head against its own siblings. Whether palmitoyl tripeptide-38 offers anything over palmitoyl pentapeptide-4 or the Matrixyl 3000 combination has never been tested, despite all three being marketed by the same supplier under one brand.
• 07Quantified penetration from commercial formulations. Delivered dose to the papillary dermis has not been measured for any retail product, although two-dimensional chromatography methods for determining cosmetic peptides in skin homogenates are now emerging and could answer this.
• 08Use beyond 12 weeks. No study extends past 12 weeks, so whether chronic multi-year use alters the skin-aging trajectory differently from a three-month course is unknown — a gap shared by essentially the whole cosmetic peptide category.

Forms & Administration

Topical only, in serums, creams and lotions. Supplied as a diluted trade material (Matrixyl synthe'6) incorporated at a few percent of a finished formula, which corresponds to roughly 5 to 10 parts per million of the peptide itself — the Lintner serum used 5 ppm, and that is the only concentration with published human data behind it. Applied once or twice daily to cleansed skin; the published protocols used once daily for 56 days, twice daily for 28 days and twice daily for 12 weeks respectively. Routinely co-formulated with vitamin C derivatives, other peptides, niacinamide, hyaluronic acid and antioxidants, and in practice almost never used alone. No oral, injectable or compounded form exists, and injecting a cosmetic lipopeptide preparation has no rationale and real risk.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

Palmitoyl tripeptide-38 is a cosmetic ingredient, not a drug. It is not approved to treat or prevent any medical condition, cosmetic claims are limited to appearance-related language, and no Cosmetic Ingredient Review report or SCCS opinion specific to this ingredient has been published.

Timeline of Effects

Common Questions

Who Palmitoyl Tripeptide-38 Is NOT For

Drug & Supplement Interactions

No pharmacological drug interactions are documented or expected. Systemic absorption from a topical lipopeptide applied at roughly 5 parts per million is negligible, the molecule does not reach clinically relevant plasma concentrations, and there is no plausible interaction with oral or injected medications. The interaction space is entirely topical and formulation-level. Compatibility is broad. Palmitoyl tripeptide-38 layers without difficulty alongside hyaluronic acid, glycerin, ceramides, niacinamide and other peptides including the rest of the Matrixyl family and the neuropeptide-signalling inhibitors. Retinoids are regarded as complementary rather than antagonistic — retinoids act through retinoic acid receptors and global epidermal turnover, matrikines through fibroblast signalling — and the two are commonly paired. The one conventional caution is low-pH actives. High-concentration L-ascorbic acid can destabilise peptide actives in the same layer, so vitamin C is typically used at a different time of day, and strong alpha- or beta-hydroxy acid exfoliation applied simultaneously may degrade surface peptide while compounding irritation. It is worth stating the obvious tension here: the most cited study of this peptide deliberately formulated it with 15% L-ascorbic acid and reported measurable improvement, which suggests the incompatibility is less absolute than the standard advice implies — or, less charitably, that the vitamin C was doing the work either way. Patients on prescription topical dermatologic therapy — tretinoin, tazarotene, hydroquinone, topical antibiotics — should coordinate routines with their dermatologist, primarily to manage irritation rather than because of any true interaction.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions