There is a peculiar dynamic in cosmetic marketing where the more recently a class of ingredient has entered the consumer vocabulary, the more confident the claims about it tend to be — and the less the average product label tells you about how much of the ingredient is actually present.

Peptides are the textbook example. Twenty years ago, almost no consumer product mentioned them. Ten years ago, they had begun appearing in a few clinically-led skincare brands. Today, “peptide-rich,” “peptide-powered,” and “advanced peptide complex” are everywhere. Most of those products contain peptides at a concentration somewhere between 0.001% and 0.1%, which is roughly two to three orders of magnitude below the concentrations at which the published evidence shows any meaningful effect.

This essay is an attempt to write about peptides in a register that the chemistry actually supports. What they are. What they do. What the published trials show. Where the honest limits are. And how we use them in our own formulations — at what concentrations, and why.

What a peptide is

A peptide is a short chain of amino acids. Proteins are long chains of amino acids — typically over 100 — folded into specific three-dimensional structures. Peptides are the same chemistry, but smaller. Two amino acids joined together is a dipeptide. Three is a tripeptide. Anything from two to roughly fifty amino acids is conventionally called a peptide; longer than that and it is called a protein.

In the body, peptides are everywhere. They function as signalling molecules — telling cells what to do. Insulin is a peptide. Oxytocin is a peptide. Many of the molecules that coordinate immune response, tissue repair, and metabolic regulation are peptides. The amino acid sequence of a peptide determines its function; small changes in the sequence can produce large changes in what the peptide does.

In cosmetic chemistry, peptides are used because some of them, when applied to skin, can trigger downstream signalling responses that influence collagen synthesis, melanin production, neurotransmitter release at neuromuscular junctions, or the activity of various enzymes involved in skin remodelling.

This is, on paper, a powerful idea. The reality is more complicated.

The penetration problem

The first and most important constraint on cosmetic peptide chemistry is that peptides, on their own, do not penetrate skin very well.

The stratum corneum — the outermost layer of the epidermis — is a structure designed to keep things out. It is roughly 15 to 20 micrometres thick, composed of densely-packed corneocytes embedded in a lipid matrix that is hydrophobic on average but with hydrophilic regions. Small, lipophilic molecules cross it relatively easily. Large or hydrophilic molecules cross it poorly or not at all.

Peptides, being chains of amino acids, tend to be hydrophilic and (relative to small molecules) large. A typical cosmetic peptide is a few hundred to a few thousand daltons in molecular weight. The conventional rule of thumb is that molecules above 500 daltons struggle to cross the stratum corneum without help.

This is why almost every commercially-relevant cosmetic peptide is “modified” — either by attaching a fatty acid chain (palmitoyl peptides, like Matrixyl 3000) to make the peptide more lipophilic, or by complexing the peptide with a metal ion (like the copper in GHK-Cu) to alter its delivery profile. The modification is what gets the peptide into the skin. Without it, the peptide chain stays largely on the surface.

A consequence of this is that “peptides” as a single category in cosmetic marketing is misleading. The penetration profile of a palmitoyl peptide is different from that of a copper peptide is different from that of an unmodified pentapeptide. The dose-response curves are different. The mechanisms downstream are different. Treating them as a single thing is like treating “vitamins” as a single thing.

The signalling step

Once a peptide gets into the skin, the question becomes: what does it do?

The honest answer for most cosmetic peptides is: it depends on the peptide, and we have varying degrees of certainty about the answer.

For a small number of peptides, the in-vitro evidence is strong. GHK-Cu has been studied since the 1970s, originally in the context of wound healing. The peptide-copper complex has demonstrable effects on fibroblast collagen synthesis, antioxidant enzyme activity, and gene expression related to tissue remodelling. Pickart and Margolina’s 2018 review in Oxidative Medicine and Cellular Longevity compiles roughly four decades of supporting research. The mechanisms are reasonably well-characterised.

For another small group of peptides — Matrixyl 3000, Argireline, and a handful of others — the in-vitro evidence is moderate. The mechanism of action is plausible at the molecular level. The supplier-led trials show effects on relevant endpoints. Independent replication is incomplete but not absent. We can describe these peptides as “evidence-supported” without overstating.

For most other cosmetic peptides — the dozens of trade-named complexes that appear in product launches every year — the public evidence is thin. Often the only available data comes from the supplier itself, in formats that have not been peer-reviewed. The mechanism is asserted rather than demonstrated. The dose-response is not characterised.

This range — from “well-established” to “asserted on the basis of supplier marketing” — is what most consumers do not see when they read the word peptide on a product label. The label does not differentiate. The label says “peptide complex” and trusts you to assume it is doing something.

Three peptides we use

We use three peptide actives in our launch range. All three are in our Honeybush Neck & Décolletage Concentrate; one of the three is also in our Marula + Peptide Firming Body Serum. The selection is deliberately narrow.

Matrixyl 3000 (Palmitoyl Tetrapeptide-7 + Palmitoyl Tripeptide-1). This is a synergistic combination of two palmitoylated peptides, sold under trademark by the French ingredient supplier Sederma. The peptides are designed to mimic naturally-occurring fragments of dermal collagen breakdown — fragments that, when the body detects them, signal that the dermal matrix needs repair. Topically applied, the peptides are taken as a signal that the matrix has been damaged, which triggers a fibroblast response that increases collagen, fibronectin, and hyaluronic acid synthesis. The mechanism is biomimetic; the peptides are not adding collagen, they are signalling for the body to make more.

The published Sederma data shows fibroblast collagen synthesis stimulation in the 100–200% range over baseline, in vitro, at concentrations between 1% and 5% in finished formulation. We use Matrixyl 3000 at 3% — toward the upper end of the supplier-recommended range. The peptide complex is light- and oxidation-sensitive, so we package the body serum in opaque PCR-aluminium tubes with metered pumps, and the neck concentrate in fully airless Quadpack systems.

GHK-Cu (Copper Tripeptide-1). This is the most extensively-studied cosmetic peptide. It is a tripeptide — glycyl-histidyl-lysyl — bonded to a copper ion. It occurs naturally in human plasma at decreasing concentrations with age (the literature suggests roughly 200 ng/ml at age 20, declining to around 80 ng/ml by age 60). Topical application has demonstrable effects on collagen synthesis, antioxidant defence, and tissue remodelling.

The most commonly cited clinical trial — Leyden et al., 2002, presented at the American Academy of Dermatology — used 0.05% GHK-Cu in a facial moisturiser and showed visible improvements in skin elasticity, fine line depth, and hyperpigmentation over 12 weeks. Subsequent work has been generally supportive, though the public clinical literature is less abundant than the in-vitro mechanism research.

We use GHK-Cu at 0.05% in the neck concentrate. The packaging is fully opaque and airless because the copper-peptide bond is photosensitive. The product is also formulated without high-strength vitamin C, retinol, or AHA/BHA acids, which can degrade the peptide.

Argireline (Acetyl Hexapeptide-8). This is the peptide that is most commonly mythologised. It is a synthetic hexapeptide modelled on the N-terminal end of SNAP-25, a protein involved in neurotransmitter release at neuromuscular junctions. The peptide partially inhibits SNAP-25-mediated acetylcholine release, producing a mild, localised reduction in muscle contraction at the application site.

The honest evidence on Argireline is mixed. The 2002 International Journal of Cosmetic Science trial that first established cosmetic interest showed a 17% reduction in wrinkle depth around the eyes after 30 days at 10% concentration. Subsequent independent work has produced more variable results — some trials show modest effects, others show none. The mechanism is plausible at the molecular level, but the in-vivo penetration through skin is the limiting factor; you can demonstrate the effect at the receptor in a Petri dish much more easily than you can demonstrate it on a forehead.

We use Argireline at 2% in the neck concentrate as one component of a peptide blend, not as a standalone hero. We are explicit in our product copy that this peptide has the most uncertain evidence base of the three. We include it because the peptide blend appears to perform better in formulation than any of the three peptides alone, and because the safety profile is strong. We do not claim it is “Botox in a bottle.” It is not.

Why we don’t use more

A reasonable question, given the depth of the peptide-marketing landscape, is why we don’t use more peptides. The honest answer is two-fold.

First, peptide chemistry is expensive. The trade-named peptide complexes from Sederma, Lipotec, and the other major suppliers are not cheap raw materials. Using them at evidence-supported concentrations — 3% Matrixyl, 0.05% GHK-Cu, 2% Argireline — adds significantly to the formulation cost. Most “peptide-rich” products on the mass market use the same peptides at concentrations that are an order of magnitude lower, because the cost differential is substantial. We chose to use a small number of peptides at meaningful concentrations rather than a long list at trace concentrations.

Second, peptide formulation is genuinely difficult. The peptides have specific compatibility requirements. They degrade in the wrong pH range. They oxidise on contact with air. They lose activity in the presence of certain other actives. Building a formulation that delivers the peptides intact and stable for 24 months of shelf life is technically demanding, and adding more peptides multiplies the difficulty. We would rather do three peptides well than seven peptides badly.

Where peptides fit in a broader skincare system

Peptides are useful. They are not a complete skincare regimen.

The skin’s longevity profile depends on several mechanisms — barrier integrity, microbiome health, collagen and matrix synthesis, oxidative defence, and inflammatory load. Peptides primarily address the third of these, with some additional support for the fifth in the case of GHK-Cu. They do not fix a damaged barrier. They do not balance the microbiome. They do not significantly contribute to oxidative defence, except inasmuch as healthier skin tissue is generally more resilient.

A skincare system built entirely around peptides is, like a skincare system built entirely around any single class of active, incomplete. We use peptides as one component of a longevity-aware approach that also includes ceramides (in the Aloe Ferox & Oat Barrier Cream), antioxidant polyphenols (in our use of rooibos and honeybush extracts), and barrier-respecting cleansing chemistry (in the Rooibos & Glucoside Body Wash). The peptides do their part. The rest of the system does the rest.

A short reading list

If you want to verify any of the above:

  • Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Oxidative Medicine and Cellular Longevity, 2018.
  • Robinson LR, Fitzgerald NC, Doughty DG, et al. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. International Journal of Cosmetic Science, 2005.
  • Reygagne P, Bastien P, Couavoux MP, et al. The positive benefit of Lactobacillus paracasei NCC2461 ST11 in healthy human scalp. Beneficial Microbes, 2017. (For the broader microbiome context.)
  • The Sederma technical dossier on Matrixyl 3000 is available on request from the supplier.

Most of the rest of what is written about peptides on the consumer-facing internet is, charitably, marketing.