Do wrinkle smoothing peptide creams really work?

Dr Haran Sivapalan

The market is awash with peptide products claiming everything from boosting collagen to botox-like wrinkle smoothing, but how well to they actually work? Dr Haran Sivapalan finds out.

Everyone seemingly wants younger looking skin. In 2013, consumers in the U.S. alone spent a massive $2.1 bn on anti-ageing creams. And in the UK research shows that women spend, on average, a whooping £140,000 over their lives on hair and skincare.  With such high demand, there is clearly a pressure on cosmetics manufacturers to continually produce innovative products to secure their share of this ever-growing market.

Tea extract, vitamins, collagen extracts – anti-ageing products have incorporated all of these ingredients in an effort to preserve youth; alas with mixed success. But more recently, manufacturers have tried to stimulate the skin to rejuvenate itself by using another class of ingredient: peptides.

Peptides are molecules made from amino acids – the building blocks of protein. They’re naturally found in the body, where they act as signallers,  telling cells how to function – when to divide and when to produce more proteins. In the skin, a class of peptide called ‘matrikines,’ can stimulate the production of melanin (the pigment responsible for skin colour and sun protection), as well as the structural proteins collagen, elastin and fibronectin – all of which give younger-looking skin its wrinkle-free bounce.

It’s not surprising then that scientist began to ask: if naturally occurring peptides could exert these beneficial anti-ageing effects, could synthetically engineered ones do the same? In 1999, the cosmetic company Sederma did exactly this. They patented a matrikine peptide called ‘palmitoyl-pentapeptide 3’, more commonly known to you and me under the trade name ‘Matrixyl.’



Matrixyl, it was claimed, could stimulate collagen production, reduce wrinkles and generally rejuvenate the skin. Clearly they were onto something. Soon after, other companies brought out a range of other topically-applied matrikine peptides with similar collagen-boosting, anti-wrinkle and anti-ageing claims. These peptides include names such as: tripeptide-1 (Kollaren), palmitoyl tripeptide-5 (Syn-coll) and oligopeptide-10 (Invisaskin-64).

Newer peptides have also been created to mimic the effects of Botox. For example, acetyl-hexapeptide-3 (trade name Argireline) causes muscle relaxation and aims to combat wrinkles, fine lines and crow’s feet.

So, there are lots of cleverly designed peptides out there; but do the studies show that they actually work?


The evidence 


As we age, collagen, the protein that gives skin its firmness and elasticity, gets degraded. Can peptides offset this process? There are several in vitro studies – that is, studies of cell cultures in test tubes and petri dishes rather than in, or on, living animals and humans – that show peptides to indeed increase collagen production. For example, a 2013 study by R.R. Jones and colleagues, published in the journal Molecular Pharmaceutics, showed that Matrixyl can stimulate human fibroblast cells to produce collagen.

Needless to say, there’s a difference between studies on isolated cells in a dish and studies in a complex, living, breathing human being. The most useful studies have what scientists dub ‘ecological validity’ – they mirror real life circumstances.

With this in mind, the most realistic study in the literature is a randomised controlled trial of Matrixyl conducted on 93 Caucasian women. Over a 12-week period, the subjects applied either a normal moisturiser or a moisturiser containing Matrixyl to one side of their face. Compared to skin treated with the normal moisturiser, skin treated with Matrixyl showed a significant reduction in wrinkles and fine lines. These results are encouraging.


A smaller trial of a different peptide, tetrapeptide-GEKG, analysed skin biopsies taken from subjects’ forearms and buttocks, after they had topically applied the peptide for 8 weeks. The biopsies revealed a significant increase in the production of collagen, fibronectin and hyaluronic acid by the skin.


Sound great doesn’t it? But we scientists are a cautious lot. While these human studies are promising, larger and longer-term studies are required to fully establish the collagen-boosting, wrinkle-busting properties of topical peptides. Indeed, a 2012 review of the scientific literature by the Linus Pauling Institute concluded that, “Although these results suggest that topical peptides may improve clinical features of aged skin, additional, long-term clinical trials employing histological measures of skin health are needed.”


Melanin Production

Peptides have also been used to stimulate our skin’s production of melanin – the dark pigment that protects the skin from UV rays. This could come in handy for tanning and improving the skin’s natural sun protection. Studies show that some synthetic peptides can also bind to receptors and stimulate the production of melanin. Nevertheless, there is a distinct lack of studies in humans: more research is needed.


Botox-like effects

Most people have heard of botox injections. Botulinum toxin works to reduce wrinkles by causing muscle paralysis. It does this by blocking the signal from nerves to muscle. Less known, however, is that certain synthetic peptides in topical cosmetics can also bring about muscle relaxation. Using topically-peptides has several possible advantages over botulinum toxin, the latter of which is potentially dangerous and must be administered by a trained health professional.

One study of topically-applied acetyl-hexapeptide-3 (Argireline) showed that it reduced the depth of wrinkles by 30% over a period of 30 days. Currently, however, there are far too few studies of topical peptides with a botox-like effect: more research is needed in this area.


So, what do we think?

Peptides, specifically matrikine peptides, carry out all sorts of rejuvenating processes in the skin, including tissue remodelling, producing melanin, wound healing and destroying bacteria. While we still need more studies on real people to thoroughly assess their benefits, laboratory studies show the synthetically produced matrikines such as Matrixyl are safe to use and have a good body of evidence to back them up.



Castelletto, V., Hamley, I. W., Perez, J., Abezgauz, L., & Danino, D. (2010). Fibrillar superstructure from extended nanotapes formed by a collagen-stimulating peptide. Chemical Communications, 46(48), 9185-9187. 

Chirita, R. I., Chaimbault, P., Archambault, J. C., Robert, I., & Elfakir, C. (2009). Development of a LC–MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics. Analytica chimica acta, 641(1), 95-100.

Farwick, M., Grether‐Beck, S., Marini, A., Maczkiewitz, U., Lange, J., Köhler, T., … & Jaenicke, T. (2011). Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Experimental dermatology, 20(7), 602-604.

Jones, R. R., Castelletto, V., Connon, C. J., & Hamley, I. W. (2013). Collagen Stimulating Effect of Peptide Amphiphile C16–KTTKS on Human Fibroblasts. Molecular pharmaceutics, 10(3), 1063-1069.

Linus Pauling Institute (2012). Peptides and Skin Health. Available online at:

Robinson, L. R., Fitzgerald, N. C., Doughty, D. G., Dawes, N. C., Berge, C. A., & Bissett, D. L. (2005). Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin1. International journal of cosmetic science, 27(3), 155-160.

Zhang, L., & Falla, T. J. (2009). Cosmeceuticals and peptides. Clinics in dermatology, 27(5), 485-494.

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