Cosmeceutical Ingredients: Natural Approaches


Natural approaches to fighting the signs of aging.


They say the only certainties in life are death and taxes. But what about wrinkles? At the ripe old age of 37, I’m beginning to believe that they, too, belong on the list-though I’m not yet convinced they belong on my face. And while it’s nice to know that facelifts, laser treatments, and Botox injections are there if you need them, their associated risks, recovery, and side effects-not to mention costs-make me want to delay them indefinitely, if possible.

Apparently, I’m not alone. Plenty of consumers seem keen to hold off surgery while holding onto their youthful looks, and they’re turning to cosmeceuticals-topical skincare products formulated to improve appearance-in that pursuit. Domestic sales of cosmeceuticals hit $9.7 billion in 2011, marking a 4% rise over the year before, according to Packaged Facts’ report “Cosmeceuticals in the U.S., 6th Edition.” And with skincare products accounting for 46% of the market, it’s a safe bet that “turning back the hands of time” is a common claim across the category.

Of course, whether any beauty product can kick time into reverse remains dubious. But the more we learn about the biochemistry of skin and the biomechanics of aging, the better equipped the skincare industry will be to formulate safe, effective, and natural cosmeceuticals that, while maybe not turning back time’s hands, can at least help erase its fingerprints.


Booming Market

As Anurag Pande, PhD, vice president of scientific affairs, Sabinsa (East Windsor, NJ), sees it, the growth of the U.S. cosmeceutical market in the last decade has been “phenomenal.” With an aging population, he says, “there is an increase in spending on age-defying or antiaging products.”

Fortunately, cosmeceutical formulators can take advantage of a firmer, and broader, foundation of knowledge upon which to build their products. “The concept of antiaging is now not limited to antioxidants,” Pande says, “but also covers factors like inflammation, which has been recognized as a root cause of several diseases.” Antiglycation ingredients have also attracted attention, he says, for their ability to break up the stiff, crosslinked proteins that form in age-stressed skin.

But before we formulate, we have to understand how antiaging actives interact with the skin, its structures, and the world around it. After all, the skin that we see is only the surface of a very complex organ.


The Skin We’re In

That organ’s uppermost layer is called the epidermis, and within it, cells called keratinocytes form at the base and pile, one upon the other, into stacks of sub-layers. As keratinocytes at the surface die and slough off, they make way for the younger cells beneath them, which themselves eventually shed in an endless cycle of cellular renewal.

Directly below the epidermis lies the dermis, which gives skin its strength and support, says Rod Benjamin, director of technical development, Bergstrom Nutrition (Vancouver, WA). “Unlike the epidermis, the dermis contains nerves, blood vessels, and fibroblasts that supply sensory receptors, deliver nutrients, and maintain the structural foundation of the skin,” he says.

The dermis also contains collagen, a flexible, fibrous protein that makes up fully 70% of skin’s dry weight, helps maintain skin firmness and, in conjunction with the protein elastin, forms a protein complex that lends skin elasticity.

The base of the dermis comprises a collection of complex sugars: glycosaminoglycans, glycoproteins, hyaluronic acid (HA), and chondroitin sulfate. “These substances together form a ‘cementing and gelling base’ that binds water molecules,” Benjamin says, “allowing nutrients and oxygen into the tissue and protecting the dermal structural layer.”


Aging from the Inside Out…

As skin ages, these structures and components deteriorate. Some of the deterioration is preprogrammed into our systems and falls under the category of “intrinsic aging”-essentially, the body’s way of winding down. It’s a natural, progressive process that, on the surface, manifests in thinner, weaker, and less-elastic skin. But what’s going on underneath is much more complex.

Intrinsic aging is characterized by “a decline and/or changes in the chemical structure and three-dimensional organization of collagen and glycosaminoglycans,” Benjamin says. More specifically, adds Deshanie Rai, PhD, FACN, senior scientific leader, DSM Nutritional Products NA (Parsippany, NJ), “The percentage of hyaluronic acid in the skin decreases, which results in the loss of hydration and moisture.” Meanwhile, elasticity and firmness give way to the appearance of wrinkles as collagen and elastin breakdown increases.

Our built-in repair mechanisms also slow, lengthening the time it takes for skin to heal from injuries. The subcutaneous fat layer thins, deflating the plumpness that’s a hallmark of fresh-faced youth. Skin grows drier as the number of sweat and oil glands falls. And thanks to age-related changes in circulation, “less oxygen and nutrients may be delivered to the skin,” Rai says, potentially dulling skin’s appearance. Finally, she notes, “estrogen production decreases with age, and this further contributes to skin thinning, dryness, and itching.”


…And the Outside In

And those declines are just what our own bodies initiate; extrinsic factors only multiply aging’s effects. Principle among them is oxidative stress from ultraviolet (UV) radiation, pollution, cigarette smoke, and more. Such stress generates highly reactive compounds known as free radicals that invade dermal cells and disrupt their structures and functions.

“Structurally, they can cause mutation,” Pande notes. “They can cause the crosslinking of genetic material such as DNA, triggering the effects of aging and sometimes even causing cancer. Sometimes this crosslinking can happen in the fat and protein molecules, causing the glycation of matrix components such as collagen, which also leads to wrinkles and other aging effects.”

Chronic exposure to UVA and UVB radiation is also notorious for releasing damaging reactive oxygen species-free radicals-and stimulating pro-inflammatory reactions, Benjamin says. Pro-inflammatory cytokines, the transcription factor NF-kappa B, and matrix metalloproteinase enzymes (MMPs) all kick into action to commence wreaking havoc.

Particularly vexing, notes Benjamin, is the enzyme MMP-1, which cleaves collagen type 1, the primary form of collagen within the dermis’ extracellular matrix. “It is proposed that elevated levels of MMP-1, along with other metabolites, are responsible for the degradation of connective tissues-collagen, elastin, fibronectin, laminin-of the extracellular matrix,” he explains. “This damage to tissue leads to accelerated aging and wrinkling within the skin.”


Breaking Barriers

It sounds complicated-and is. And it raises the question of whether cosmeceuticals can really put the brakes on such processes, extrinsic or intrinsic. When you consider, as Pande points out, that consumer confidence in cosmeceuticals can increase only if these products actually work, that question takes on paramount importance. “To provide a safe and efficacious product,” he continues, “formulators must choose effective, well evaluated, stable, and clinically proven ingredients.”

Yet those ingredients, as part of a topical product, face a formidable barrier: the skin they’re intended to benefit. Skin essentially evolved as the body’s first line of defense, and as Benjamin points out, “we can’t formulate with something that penetrates to the subcutaneuous layer; that would be classified as a drug.” However, he says, if actives can deliver their benefits through pores or by cellular penetration, their outlook for effectiveness looks good.

One way to aid antiaging actives’ progress is to combine them with compounds like methylsulfonylmethane (MSM), which Benjamin claims can enhance active delivery. “MSM is known to increase cell permeability,” he says, adding that human studies (Zhang et al., Shanmugam et al., Tripathi et al.) demonstrate its capacity to “enhance the cellular penetration of other active ingredients.”

Evidence also indicates that the compound can reduce markers of oxidative damage. “It is proposed that MSM’s anti-inflammatory effect may be due to its ability to inhibit pro-inflammatory transcription factors NF-kappa B and cytokine expression that further damage skin homeostasis and accelerate deterioration,” he says. Unlike garden-variety antioxidants such as vitamins C and E, he adds, the compound “acts in an intracellular way to mitigate generation of reactive oxygen species.”


Natural Advantage

Benjamin notes that his company’s MSM product OptiMSM is biomimetic, or nature-identical. Depending on the target market or commercial venue, that qualification may be good enough. But unambiguously natural beauty actives are becoming more of a non-negotiable with skincare consumers and the manufacturers who cater to them.

“In last few years, the segment of the cosmeceutical industry that has shown remarkable growth is ‘natural’ cosmetics,” Pande says. “People are growing more aware of the ingredients they put on their skin so regularly. The potentially harmful effects of preservatives and chemicals on skin are getting a lot of attention, and as a result people are looking for skincare actives that are both safer and effective.”

However, some may question whether natural beauty actives will ever be as effective as synthetics. In fact, history shows that they can be. “In many instances,” Pande points out, “natural cosmeceuticals are derived from sources that humans have used for ages for skin and healthcare. Hence, their effectiveness and safe use have been time-tested.”

Gentle, targeted extraction also helps optimize a natural active’s potency. As Pande says, “One needs to select the right solvent and conditions. As long as there is no chemical alteration in the active compound of choice, its effectiveness should remain intact.”

Granted, the term natural carries no legal or regulatory weight, as the Federal Food, Drug and Cosmetic Act neglects to define it with respect to skincare products-and a whole lot of other products. But as Supreme Court Justice Potter Stewart once said of another notoriously slippery term, consumers know “natural” when they see it-especially when they’re reading skincare labels.


The Healing Plant

One ingredient that readily fits the natural profile is Aloe vera. While not the newest antiaging active on the scene, “it’s still one of those ingredients that consumers are looking for in their skincare products,” says Jeff Barrie, eastern regional sales manager, Aloecorp (Seattle, WA). “People associate it with ‘the healing plant,’” he says, which may account for its appeal. But so, too, does its general effectiveness.

The reason, according to Barrie, is Aloe vera’s naturally occurring polysaccharides. These short-, medium-, and long-chain carbohydrates are humectants, attracting moisture and holding it in the skin. Given that “the key to looking young is moisturizing,” Barrie says, that moisture-attracting potential is a boon to cosmeceuticals that use Aloe vera as an ingredient.

“For a finished skincare product to be certified by the IASC-the International Aloe Science Council-it has to have at least 15% Aloe vera in it,” Barrie notes. That’s not a hard bar to clear; aloe is 99.5% water and 0.5% solids, he says, “so working with aloe is very simple when you’re manufacturing cosmetics because it goes easily into the water phase.”

But pure Aloe vera straight from the leaf won’t do. Enzymes in the plant cleave its polysaccharides into smaller mono- and oligosaccharides with less moisturizing potency. To render Aloe vera effective in skincare products, suppliers “turn off” these enzymes by applying specific time-temperature treatments to the botanical, heating it just enough for sanitation without compromising polysaccharide stability. Barrie’s company uses a patented process called MAP-for “modified aloe polysaccharides”-to make its branded product ACTIValoe effective for the long haul.


We Are What We Eat

Barrie notes that the “biggest part of our business is in drinks”-confirming that the old adage, “You are what you eat,” applies as much to skin maintenance as to other aspects of health. Indeed, poor nutrition plus age-related declines in the body’s ability to harvest nutrients from the diet exacerbate the signs of aging. And given oxidation’s toll on the face, it stands to reason that dietary antioxidants can serve in the antiaging arsenal.

“Scientific and clinical research has shown that balanced nutrition plays an instrumental role in supporting the appearance of the skin throughout the life cycle, including during aging,” Rai says. And while nutritional intervention may be the principle driving ingestible nutricosmetics (see sidebar on page 44 for more on nutricosmetics), it’s an effective strategy for formulating cosmeceuticals, as well.

DSM produces a premix called AgeWell that delivers antioxidant vitamins and nutrients critical to supporting skin cell structure and metabolism. “A combination of select mixed carotenoids-beta-carotene, FloraGLO lutein, redivivo lycopene, and Optisharp zeaxanthin-helps to protect the skin from the damaging effects of the sun,” says Marlena Hidlay, marketing analyst at DSM Nutritional Products. The premix also provides All-Q coenzyme Q10 and resVida resveratrol, which she says are “two potent, protective antioxidants with emerging skin health science.”


Strengthening the Foundation

Vitamin C is another antioxidant with demonstrated skin benefits, notably as a cofactor in collagen and elastin synthesis. But to give our aging collagen a more direct boost, manufacturers have also responded with natural collagen actives for cosmeceuticals formulation. One such product is BioCell Collagen CG, which Joosang Park, vice president of scientific affairs, BioCell Technology LLC (Newport Beach, CA), says is his company’s flagship ingredient.

The product is a natural, patented, cosmetic-grade collagen formulated for topical use. Biochemically speaking, it’s a “naturally occurring matrix of hydrolyzed collagen peptides and low-molecular-weight glycosaminoglycans,” Park says, designed to support skin health and appearance through several actions.

First, it replenishes the dermis’ extracellular matrix with low-molecular-weight collagen and HA, essential dermal components that degrade with age. “Second,” Park continues, “collagen-derived peptides are biologically active to stimulate the dermal fibroblasts to produce molecules, such as HA, required for the healthy maintenance of the dermal matrix.”

And the ingredient also acts on hyaluronidase, the enzyme that degrades HA. “HA is essential for skin hydration,” Park points out, “and its levels are maintained by the balance of HA synthases and hyaluronidases.” As we age, hyaluronidase activity rises, accelerating HA breakdown. The “unique matrix form” of the company’s collagen inhibits this activity and protects HA from excessive degradation, helping further improve skin hydration and prevent wrinkles, Park says.

He notes that internal studies of the ingredient demonstrate its ability to inhibit hyaluronidase in a dose-dependent manner. “This data suggests that BioCell Collagen CG has multiple biological properties in addition to replenishment of collagen and HA in aging skin, helping to maintain the integrity and amount of HA for younger-looking skin,” he concludes. For skincare preparations, he recommends adding the ingredient at 3–6% levels to ensure optimal inhibition of hyaluronidase.


A Stable Environment

Formulating effectively with beauty actives involves more than just determining optimal use levels. As Arnoldo Fonseca, personal care marketing manager, Air Products & Chemicals Company (Allentown, PA), says, “Active ingredient stability is a big challenge. What’s more, it is sometimes a factor that formulators underappreciate.”

Stability goes beyond protecting the color and odor that consumers immediately notice against oxidation. ”Stability can also be a problem because of what consumers don’t see,” Fonseca says-namely, performance. For example, retinol can lose more than 40% of its stability over 24 weeks, he notes, triggering consumer disaffection and a potential loss in sales. “One way to address stability is through encapsulation,” he points out. “Our Rovisome Retinol Moist product, for instance, loses only 10% of its stability after 24 weeks and therefore can have a better chance of meeting consumer expectations.“

Processing conditions also threaten stability, “particularly the thermal profile, shear rate, and in-process pH of an operation,” Fonseca continues. Thus, processors might batch sensitive actives after processing, if possible, or employ encapsulated ingredients. “Vitamins such as A, C, and E are well known to be sensitive to environmental factors,” Fonseca says.

And if that translates into age defiance that consumers can feel and see, it may justify their spending on a product that rewards their confidence and loyalty. And clearly, consumers are finding justifications for the added expense of cosmeceuticals purchase, even in today’s austere economy. Notes Christina L. Fiduccia, vice president, sales, Horn (La Mirada, CA), some consumers are even “trading up, versus trading down, when it comes to antiaging.”

“They’re seeking products that really work,” she continues, “whether at prestige pricing or-even better-‘masstige’ pricing. When there are fewer funds to spend, you seek something special: a sensory indulgence that also makes you feel better about yourself and creates a satisfying purchase experience.” And if it can put the hands of time in consumers’ pockets, all the better. 



Sidebar: Cosmeceuticals versus Nutricosmetics

Like their cosmeceutical cousins, nutricosmetics target their formulations toward improving appearance. But rather than delivering the goods topically, nutricosmetics are designed to be consumed as supplements or functional foods and beverages. According to research firm Frost & Sullivan, the global market for nutricosmetics should hit $5.6 billion by 2015, with Japan purchasing the lion’s share and Europe following close behind.

Yet the United States consistently has been cool to nutricosmetics, generating only 2–5% of total sales. Indeed, notes Anurag Pande, PhD, vice president of scientific affairs, Sabinsa, “We have yet to see the nutricosmetic market reach the potential it was initially thought to [reach] a decade ago.”

Lack of evidence for nutricosmetics’ efficacy could be one explanation for the market’s torpor; or perhaps the slow sales simply reflect the association Americans have long made between topical products-rather than ingested ones-and skincare.

As Marlena Hidlay, marketing analyst, DSM Nutritional Products NA, points out, “Topical products are well received. Consumers connect with them by applying them and looking forward to seeing the results: a reduction in dark circles, a decrease in puffiness, minimized fine lines and wrinkles.” And we shouldn’t neglect the experiential appeal of such products: their texture, their fragrance, even their package design.

Still, American consumers may be warming to beauty from within. Hidlay cites a 2011 Health Focus survey that found 85% of consumers declaring interest in nutrition for healthy skin. “Though claims are focused on the clinical results, like ‘decreased skin lipid peroxidation’ or ‘helps support collagen building and maintenance,’” she says, “consumers are able to enjoy a fortified beverage or soft chew and improve skin hydration or support their skin’s firmness.”

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