The Science of Cosmetics

They call to us with a siren’s song from the pharmacy shelf. Alluringly packaged in pure and clinical colours, the beauty creams and serums promise to erase the very signs of ageing. They’re hard to resist. And when, despite our better judgment, we zoom in for a closer look, the elegant embossed gold-lettering reveals a dazzling list of scientific claims. Everything from ‘cellular renewal’ and ‘DNA protection’ to lists of complex chemical formulations and biological buzzwords.

But is it really science or just pseudo-scientific snake oil?

There’s no doubt many of the ingredients have potent effects in the test tube. But do they do anything when applied to wrinkled human skin? It turns out there’s simply no easy way to find out. For cosmetics companies, the name of the game is: keep things as murky as possible.

BARRIE FINNIN, a professor at Monash University’s college of pharmacy in Melbourne, and PhD student Anita Schneider, recently tested a new wrinkle cure. Twice daily, 20 male and female volunteers applied a liquid containing Myoxinol, a patented extract of okra (Hibiscus esculentus) seed, to one side of their faces. On the other side they applied a similar liquid without Myoxinol. Every week for a month their wrinkles were tested by self-assessment, photography and the size of depressions made in silicon moulds. The results were impressive. After a month the depth and number of wrinkles on the Myoxinol-treated side were reduced by approximately 27 per cent.

But Finnin’s research, commissioned by a cosmetics company, is unlikely to be published in a scientific journal. It’s hard to even find studies that show the active ingredients in cosmetics penetrate the skin, let alone more comprehensive research on their effects. Even when rigorous studies are commissioned, companies usually control whether the work is published in the traditional scientific literature.

Welcome to the conundrum of ‘cosmeceuticals’. These are a new generation of products that are said to actually banish wrinkles, rather than merely disguising them. And they are doing great business. In 2004, Americans bought US$6.4 billion (around A$7.2 billion) worth of cosmeceutical skincare products.

And competition is stiff: cosmeceutical companies are competing with plastic surgery procedures that are less traumatic than ever. These days, youth-seekers can have a lunchtime Botox injection to iron out wrinkles, or a shot of Restylane to fill them, or a series of laser treatments to regenerate deeper tissue pinhole by pinhole.

According to the cosmeceutical marketing machine, their new active ingredients produce the same results without the hard edge of surgery. Paradoxically, however, they don’t want to ‘prove’ that their ingredients work. If they did, that could put them squarely in the sights of drug regulatory agencies. And that’s the last thing they want. “It’s a Catch-22 situation,” says Finnin.

The costs of marketing a cosmetic are in the hundreds of thousands of dollars already; the costs of bringing a drug to the market are in the hundreds of millions. Pretty much all a cosmetics manufacturer has to do is mix up a batch of chemicals, and as long as they’re all on an approved cosmetics register, the cream can go on sale the next day. By comparison, a new drug has to run a gauntlet of trials to prove it is safe and effective. And before governments will issue a licence, the drug has to be shown to be more effective than existing products.

Just as washing powders are required by law to live up to their claims, so too are skincare products. In May 2007 the makers of Lancôme, Clinique, Estée Lauder, L’Oréal and Payot were ordered to to withdraw advertisements by the Australian Therapeutic Goods Authority after the ads were found to contravene advertising codes. So companies walk a fine line: their claims need to be suggestive enough to ensnare consumers, but not so assertive they get nabbed by the regulators. “The answer is to use artful wordsmiths – the things stated on the label lead people to their own conclusions,” says Finnin.

But many companies make outlandish claims and regularly receive warning letters from regulatory authorities such as the U.S. Food and Drug Administration. “Most companies are willing to take the risk,” says dermatologist Chris Zachary at the University of California, Irvine. “The chances of getting caught are slim and even then, the official sanctions take years to be rendered. Larger companies prefer to pay a fine as the cost of doing business.” And their regular legal defence is that consumers ‘understand’ their claims are not supposed to be taken seriously. So while the companies play a cat and mouse game with regulators, consumers are left in the dark.

SKINCARE PRODUCTS traditionally beautify in a superficial way: creams sit on the surface and create a barrier to prevent skin from drying. Alpha hydroxy acids or abrasives help slough off the scaly outer layers to leave skin smoother. Humectants, such as hyaluronic acid, urea or glycerol, attract water and can plump up the outer layer of the skin. Since these products don’t affect the body’s inner structure or function, they don’t have to meet the requirements that pharmaceuticals do. But none of these products can reverse the ravages of ageing in the way that surgery can. This is where cosmeceuticals step in, with their more potent active ingredients, and correspondingly bold claims.

Dr LeWinn’s ‘Perfection Peptide P3’, Payot’s ‘Bioxilift’, Lancôme’s ‘Pro-Xylane’ – the latest cosmetic ingredients sound like they come from a mad scientist’s lab. Still, browsing the pharmacy shelves or the department store counters, it’s difficult not to respond with a glimmer of genuine hope. Has science actually found a way to erase those crow’s feet and Joker-esque smile lines?

One thing is for sure: the active ingredients of cosmeceuticals are based on an advanced understanding of the science of skin ageing.

Skin can be likened to a thin sheet spread across an inner-sprung mattress. When the mattress is new, the sheet lies flat and smooth. But as the mattress ages, its springs and struts break, the stuffing slowly disintegrates, and the sheet sags and wrinkles.

The thin sheet is the skin’s epidermis (see diagram). Just 0.02 mm thick on the face, the epidermis is made up of cells called keratinocytes, glued together by an extracellular matrix. The epidermis is continually regenerated by stem cells at its base. These spawn new keratinocytes, which move up, and after a month, slough off – producing the major ingredient of house dust. Along the way, melanocyte cells infuse keratinocytes with the pigment melanin, to a degree dependent on their UV exposure.

The thick mattress that underlies the epidermis is called the dermis. While the epidermis is predominantly composed of cells with a thin smear of extracellular matrix in between, in the dermis, things are reversed. The extracellular matrix becomes a gelatinous sea within which floats the occasional cell and blood capillary. Woven though is a protein mesh with rope-like collagen fibres that provide tensile strength, while feathery coils of elastin give skin its elasticity.

If collagen and elastin provide the strength and springiness of the dermal mattress, then the stuffing is made of gigantic molecules called glycosaminoglycans (GAGs), the most common of which being hyaluronic acid. GAGs absorb huge amounts of water to form the jelly consistency of the dermis. This gives the dermis its ability to resist compression and provides a medium through which nutrients can diffuse from capillaries to nourish the cells. The mesh, springs and stuffing of the dermal mattress are produced by fibroblast cells. As the skin ages, both the epidermis and dermis thin out and the orderly architecture disintegrates. Instead of regularly arrayed ropes and coils, the collagen frays and the elastin clumps.

The skin is constantly being regenerated by resident stem cells. Some 300 million out of the total two billion skin cells are replaced daily. With all that regeneration going on, what causes skin to age? Judith Campisi at the Buch Institute for Ageing, in California, says researchers haven’t nailed the culprits yet. But there are prime suspects.

Sunlight is a major factor. UV light generates highly reactive free radicals that can damage the fabric of the dermis. For evidence of this process, simply compare the skin on your bottom with that on your face. “Dermatologists tell us it’s about 20 years younger”, for a middle-aged or older individual, says Campisi. Free radicals also directly damage DNA. Cells with damaged DNA are potentially cancerous and therefore dangerous. As if aboard a sabotaged starship Enterprise, inbuilt safety circuits command damaged cells to self-destruct. Stem cells are among those occasionally hit, and when one of their number goes down, the skin’s ability to regenerate is compromised. But a decline in stem cells is probably not the only cause. Some cells don’t self-destruct when damaged; they merely shut down. The technical term is ‘senescence’, the cell’s equivalent of drifting into old age.

Until 10 years ago, researchers had only observed senescence in the culture dish, and the relevance of the phenomenon to living tissue was unclear. But in 1995, Campisi and her colleagues identified senescent cells in aged human skin. The older the person, the greater the number. It turns out these senescent cells are not just harmless pensioners: they have a nasty tendency to release enzymes that digest collagen. Melanocytes are also damaged. For some reason, when these cells age, they lose their fine control; instead of drip-feeding melanin to keratinocytes, they release it in large dollops which leads to the unflattering liver spots (solar lentigines) that appear on the face and the backs of hands of older people.

There is one substance that, when smeared onto skin, has been proven to reverse aging. However, it’s not a cosmetic, but a drug. That substance is retinoic acid, also known as Retin-A. It can only be obtained on prescription, and for good reason; it affects the early stages of embryo development and, even when applied as a cream, can produce birth defects in pregnant mothers. Not surprisingly, it has multiple effects on skin: it stimulates the epidermis to thicken, stimulates the fibroblasts to produce more collagen and hyaluronic acid (fortifying and restuffing the dermal mattress), and puts a damper on the activity of melanocytes (reducing liver spots). It even treats acne by reducing the production of sebum, the skin’s natural oil.

But there are drawbacks. It takes at least four months of treatment before the desired effects are visible, during which time skin can become tender, red, flaky and sun-sensitive. Cosmeceuticals aiming to copy the effects of retinoic acid use weaker relatives such as vitamin A (retinol), which is converted to retinoic acid in living cells. The effects are not as irritating – but not as effective either.

The active ingredients in the vast majority of cosmeceuticals can be roughly divided into four categories: those that neutralize free radicals; those that regenerate components of the dermis; those that coax senescent cells from retirement; and those that relax the tiny face muscles that cause wrinkling.

Anti-oxidant molecules employed to neutralize free radicals include vitamin E, vitamin C, coenzyme Q10, niacinamide (B3), biotin (B8), and a vast array of plant extracts.

One example of a contemporary cosmeceutical is Lancôme’s new product, ‘Primordiale Neutral’, which targets women in their thirties.
Its six key ingredients, including biotin, promise to absorb 99 percent of free radicals generated in the skin. According to Lancôme’s scientific director Véronique Delvigne, based in Paris, “it is a preventative treatment that reduces the first lines”.

So do antioxidants work to prevent skin aging? They certainly soak up free radicals when added to cells in the test tube, but just how effective they are in a cream applied to skin is another matter. For example, vitamin C is unstable and not very good at penetrating skin. According to Monash University’s Finnin, “there’s a much more reliable way to get vitamins to the skin: just eat them”.

Refurbishing the skin’s mattress is another key goal of cosmeceuticals. Yesterday’s creams contained collagen, elastin and hyaluronic acid, and marketing led the consumer to believe that these gigantic molecules could somehow penetrate the surface of skin, find their way into the dermal mattress, and weave themselves into the fabric. Hardly likely, according to Finnin. More likely they exert their effects at the surface, where their water-absorbing properties create a filling effect, “like Spakfilla” – a product used to smooth out cracks in walls – he says.

Today, cosmetic companies champion a new generation of small molecules known as peptides, which, they claim, penetrate the dermis to boost collagen and reverse deterioration by rebuilding from the inside out. The prototype is palmitoyl pentapeptide, also known as Pal-KTTKS or Matrixyl. In the test tube, these molecules do indeed stimulate fibroblasts to produce collagen. Numerous cosmetics include palmitoyl pentapetpide. Dermatologic’s California-based scientific director Diana Howard hails it as the “future of skincare”. Lancôme also uses a peptide derived from rice in its R.A.R.E. technology to help stop collagen bundles from disintegrating.

Another way to regenerate the dermal mattress is to re-stuff it with the sort of molecules that normally do the job: the jelly-like GAGs. While many products contain hyaluronic acid, this gigantic molecule won’t penetrate the upper layers of the skin and get to where it’s needed. Lancôme’s Absolute range relies on a small sugar-like molecule, Pro-Xylane, that it claims is a building block for making GAGs. Lancôme’s in-house literature states that it penetrates all layers of the skin and plumps the skin by increasing the amount of gelling, as well as improving the overall architecture. Still, says Finnin, “it’s very difficult to assess the validity of these claims. In the scientific literature, you don’t see articles about Pro-Xylane”.

One way to bring senescent fibroblasts out of retirement is to restore their levels of an enzyme called telomerase. In the laboratory the results have been impressive. María Blasco, who heads the Telomerase Group at the Spanish National Cancer Research Centre in Madrid, bred a strain of genetically engineered mice whose skin cells carried extra telomerase. She found that as they aged, their skin retained a youthful ability to heal wounds. But that’s not all. As she reported in the journal Science in 2005, the mice also had a greater tendency to form skin cancers.

Jerry Shay, a professor at Southwestern Medical Centre in Texas, also restored telomerase to aged human fibroblasts and showed they give rise to more youthful skin in reconstituted skin models.

One product to capitalize on telomerase research is RéVive Peau Magnifique. Its advertisement claims: “Telomerase converts resting adult stem cells to newly minted skin cells, ie recruits youth. The results are indelible and life-changing.”

However, despite the rhetoric, just how cosmeceuticals activate the telomerase enzyme in the fibroblasts of the dermis is far from clear. “I am very sceptical about cosmetics that claim to rejuvenate skin via telomerase activation,” says Shay.

At a meeting of American dermatologists in 1991, cosmetic dermatologic surgeon Alastair Carruthers astonished his colleagues by announcing that in the future they would soon be using one of the most deadly known toxins for the treatment of wrinkles. He was right. Frowning and smiling eventually etches deep furrows into overlying skin; skillfully injected Botox (a toxin made from the bacteria that causes botulism) smooths out wrinkles by paralyzing discrete muscle groups.

Cosmeceutical companies are not taking this lying down, however, and are mounting a challenge using peptides that mimic the paralyzing effects of Botox. Argireline and Myoxinol, found in Payot’s Rides Relax Regard, for instance, are claimed to have this effect. Studies show that in the test tube, these agents can interfere with the signals that trigger muscle contraction. But how they work when applied to intact skin is another issue. The chemicals would have to traverse not just the epidermis, but the dermis, then the fatty hypoderm layer beneath to reach the muscles beneath. Even other cosmetic companies find this preposterous. Says Dermatologic’s Howard: “the claims for Botox alternatives are all bogus”. Lancôme’s Delvigne adds, “It’s wrong to claim an effect on the nerve endings and muscles; these are under the hypoderm, they are very, very deep.”

THERE’S NO DOUBT the active ingredients of some cosmeceuticals have effects on cells in test tubes or mice. You can trawl through volumes of this research in journals such as the International Journal of Cosmetic Science or Dermatologic Surgery, much of it carried out by the cosmetic giants L’Oréal, Unilever, and Proctor & Gamble. But the big question for consumers is: do the skincare products we buy off the shelf have the same effects on human skin?

“The short answer is there isn’t any evidence”, says Stephen Shumack, the Honorary Secretary of the Australasian College of Dermatologists. Shumack doubts that today’s cosmeceuticals do anything different from yesterday’s cosmetics. “Personally I would recommend people save their money for a nice holiday and use vaseline and sunscreen,” says Shumack. Choice magazine, published by the Australian Consumers’ Association, supports Shumack’s view. In June 2007 it published a 12-week road test of 11 cosmeceuticals. “Any improvements were considered only ‘slight’ and there was no relationship between the type of active ingredient and overall performance, nor did price relate to performance,” the report said.

Barrie Finnin agrees it’s unlikely that the active ingredients in most cosmeceuticals can penetrate skin. It takes small molecules with exceptional water and oil solubility characteristics to breach this layer. When it comes to something like palmitoyl pentapeptide, which would need to wend its way through multiple cell layers all the way down to the dermis to stimulate collagen synthesis, Finnin says, “I’d be surprised if it does penetrate.” Even with his study on Myoxinol, during which Finnin used special techniques to coax the chemical into the skin of volunteers, he has no idea why it produced results. He says the effects were too fast to be explained by new collagen synthesis.

All of this is highly frustrating for Finnin, whose research over the years has focussed on developing techniques to deliver drugs to the skin and verify that they are effective. But few companies are jumping at the chance to prove that their products really work. “My only explanation is that they’re afraid the authorities will jump on it,” says Finnin.

So it’s not just consumers being left in the dark. Not even scientists know what these products actually do. The cosmeceutical industry operates outside of accepted scientific methodology. The in-house studies of cosmetic companies have to be taken with a grain of salt, and the scientific literature that does exist doesn’t seem to address the fundamental questions: do the active ingredients penetrate human skin? Do they do it in the mixtures found in creams? What concentrations do they reach? What effects do they have when they get there?

At best, cosmeceuticals do no harm, apart from relieving beauty seekers of surplus income. At worst, if they are truly active, then their safety and long-term effects remain quite unknown. “If you feel muddled by this, you’re getting the right picture,” says Finnin. “None of this is black and white.”

As for whether they’re 21st century snake oil, there’s no question the products are peddled by a mammoth marketing machine: one that is exceptionally adroit at exploiting our insecurities and skilled at making authentic and scientific sounding claims while skirting the regulatory authorities. Should we continue to indulge in treating ourselves to anti-aging elixirs and their like? If they make us look a little better and feel a little more confident, then they could well be worth the expense. Just take their scientific claims with a pinch of NaCl.

by Elizabeth Finkel – Cosmos

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