Throughout history, men and women have sought to use the medicinal power of natural compounds to increase their health, enhance their looks and fight off aging. The Egyptians used aromatic essences and resins in religious ceremonies and embalming, as well as for cosmetic purposes. Cleopatra, for one, was renowned for her baths of camels’ milk and honey—the milk providing a moisturizing, exfoliating and whitening effect. Across the desert and the Arabian Sea, the Vaidyas in India were practicing integrated holistic health as Ayurveda, incorporating botanicals, oils and massage into whole body support; and there are countless other examples across the continents. But in “modern society”, consumers moved away from traditional practices and products to embrace the promises of futuristic technology. Fortunately, today there is a melding of traditional knowledge and scientific advancement in the world of “cosmeceuticals”.

This term, coined in the 1960s by Raymond Reed and popularized by Albert M. Kligman, a dermatological researcher, has no official or regulatory definition. In fact, the Food and Drug Administration (FDA) does not recognize the category cosmeceutical—in its mind, products can be drugs, cosmetics or a combination of both, often defined by product claims or consumer perception. “Cosmeceutical products promote not only external beauty, but overall whole health and wellness,” said Mario Kahn, vice president, Toyo Bio-Pharma. “Our cosmeceutical ingredients often draw on ancient historic beauty uses, but are also backed by modern scientific support.

Cosmeceuticals combine the best of both worlds: wellness and beauty, ancient traditions and new science.” At this intersection, marketers are seeking to help define the term cosmeceutical. Karen E. Todd, R.D., director of marketing, Kyowa Hakko USA Inc., said the term tends to imply a product that is neither a drug, nor a cosmetic, but one that has a desired impact inside the skin. And Doug Lynch, vice president of sales and marketing, Unigen USA, agreed there are inherent expectations in this area. “To product developers, it has come to mean any nutritional supplement that demonstrably improves health and beauty, with a particular focus on skin health,” he said.

Ron Udell, president, Soft Gel Technologies Inc. (SGTI), agreed the term “cosmeceutical” may have initially encompassed topical formulation but has expanded. “Initially, the term referred to topical cosmetics that contained functional ingredients,” he said. “Large, mainstream cosmetic companies and a few natural products companies were including traditional dietary supplement ingredients, such as coenzyme Q10 [CoQ10] and green tea catechins, in their formulas—similar to the way food companies were adding those ingredients into food formulations and creating ‘functional foods’. As a nutrition company first, SGTI defines cosmeceutials in the strictest sense. To us, a cosmeceutical is a product or formula that contains an important nutritional component such as an herb, mineral or functional dietary nutrient that is ingested for the specific health benefits and appearance of the consumer.”

And the appeal of “natural” is certainly helping the growth of the market. “From what the past few years have indicated, consumers show a strong leaning toward the natural versus the synthetic, especially if the natural may work just as well or better,” said Blake Ebersole, marketing director, Verdure. “Consumers are starting to understand, at least on a basic level, what researchers have been seeing for years—components that protect the plant, and the mechanisms by which they do this, are frequently the same as that which protect the human.”

It is this interest in nutrition supporting both internal health and outward appearance that is helping drive consumer awareness. “More recently, consumers appear to understand that what they eat also plays an important role in how they look,” said Barbara Apps, director of business development and marketing, Aloecorp. “As a result, we’re seeing functional foods positioned for their skin and beauty benefits, such as yogurt with aloe vera, which has been introduced in Europe and Asia.”

Adding to the drive is the increased focus on men’s personal care. The Natural Marketing Institute (NMI) said it’s “Reigning Men”, in its 2007 Trends Report. NMI noted men’s personal care is the fastest growing segment in the bath and body care category, driven by what they called “The Massification of Metrosexuals”, which allows a broad range of men across demographic and generational lines to explore product offerings. Apps agreed with NMI’s assessment, and added, “Men are realizing that their health and appearance can enhance their success in many aspects of life.”

Obviously, then, the market for cosmeceuticals is expanding rapidly. Lakshmi Prakash, vice president of innovation and business development, Sabinsa Cosmetics, cited market research showing the cosmeceuticals market, including skin care, makeup and hair care products, will surpass $17 billion by 2010. She added, “At $7 billion in 2005, skin care, such as anti-aging creams, microdermabrasion home kits and wrinkle remedies, is the largest segment.”

The emphasis on the anti-aging skin care sector is almost to be expected, given the aging Boomer population. In addition, Yasuko Kuroda, vice president, Fuji Health Science Inc., said, “The consumer is recently becoming more interested in products that could help them to achieve their cosmetic goals without surgery or treatment with harsh chemicals.”

Udell noted it’s not just the boomers who are driving interest. “People live longer and are not willing to accept the natural signs of aging—they are seeking the proverbial ‘fountain of youth’ and are willing to spend hardearned dollars on natural anti-aging moisturizers and supplements that may erase those fine lines that crop up over time,” he said. “And the Generation-X, 30-something consumers are striving to maintain their youthful looks. They are spending thousands of dollars on cosmetic products and procedures to help reverse, or at least suspend, the aging process.”

Those cosmetic procedures, however, do come with their risks. “So many mainstream beauty treatments today utilize harsh chemicals and can cause negative side effects,” Kahn said. “From BOTOX® to parabens, consumers are increasingly aware of the hazards involved in everything from medispa treatments to hand lotion. They want effective beauty treatments, but, understandably, they don’t want the dangers. Cosmeceuticals have therefore entered the market at the perfect time, with such a growing interest in solutions that are both effective and natural.”

Bob Capelli, vice president sales and marketing, Cyanotech, said natural cosmeceuticals really came onto the market in the 1990s, but are on the cutting edge in today’s personal care arena. “Even mainstream cosmetic companies are looking for natural actives to incorporate into their formulas, basically because consumers want the products they put on their skin to be as natural as possible.”

Of course, as consumers seek “natural” ingredients, they are also expecting the products to be both efficacious and safe. Lynch noted suppliers therefore have to take steps to ensure this is the case. “There are risks with being all-natural, namely microbial contamination risk, ensuring consistent supply, and fluctuating pricing pressures,” he said Unigen has addressed the concerns by vertically integrating its operations, purchasing farmland for growing its botanicals to control the soil and prevent contamination. The company can harvest at peak season to ensure consistency and efficacy, and produce the extracts under close watch.

Topical Opportunity

“There are several natural ingredients common in cosmeceutical products: spice extracts as aroma constituents, gums for modifying viscosity, fruit acids for pH adjustment, vegetable oils as emollients and vehicles, waxes as thickeners and emollients, plant extracts as conditioners, and vitamins and fatty acids as moisturizers and antioxidants,” Prakash said. However, there are challenges in incorporating natural compounds into topical formulations without compromising the activity. “Aesthetics is a particularly important concern,” she said. “For example, a color that is too dark, a gritty texture or dispersibility problems could render the ‘healthy and natural’ ingredient unattractive. Uptake of actives from formulations is another concern.” Sabinsa offers a full range of clinically studied cosmeceutical compounds, including its branded natural extract, Cosmoperine®, that improves the uptake and permeation of other co-formulated actives.

Aloe vera is a natural compound that has been used for centuries for its skin health benefits, and has been shown in a more recent study to serve as a carrier of topical ingredients into the skin and tissues, increasing efficacy, according to Apps. “This is in addition to its roles as a detoxifying/antioxidant ingredient, immuno-regulatory ingredient that helps the skin and immune system recover from negative impact of UV light, and compound that helps the skin to counteract its lack of  resilience and tone from natural, age-related loss of collagen and reinforce the skin’s supportive network for a firmer look.”

Antioxidants also play a key role in the cosmeceutical market. “Many natural skin care manufacturers are adding antioxidants to their facial creams and moisturizers, such as grapeseed extract, green tea, CoQ10, alpha lipoic acid, vitamin C, lycopene and other botanicals, vitamins and minerals that act as ‘natural age fighters’,” Udell said. “More Americans are becoming aware of the antioxidant and moisturizing properties of these natural ingredients.”

There is some research on the use of topical antioxidants for skin health. Topical application of vitamins C and E has shown significant photoprotection against UV damage, possibly by scavenging reactive oxygen species (J Cosmet Dermatol, 4, 1:4-9, 2005). Used topically, C and E may also be able to reverse mottled pigmentation and photoaging-related wrinkles (J Cosmet Dermatol, 3, 3:149-55, 2004).

Carotenoids also offer antioxidant support to the skin. Topical application of lycopene, for example, was found in one study to significantly reverse UVB-induced photodamage (Nutr Cancer, 47, 2:181-7, 2003). And in vitro work with an astaxanthin-rich algal extract found the compound could protect against UVA-induced DNA alterations in human skin cells (J Dermatol Sci, 30, 1:73-84, 2002).

“Astaxanthin is the world’s strongest antioxidant and is also a safe, natural antiinflammatory,” Capelli said. “Some companies are putting our BioAstin® astaxanthin into rejuvenating and anti-aging skin creams, while another company is putting it into a line of natural lipsticks. Four different sunscreen manufacturers are also putting BioAstin into sunscreen products and marketing them as ‘anti-aging’ formulas.”

Another powerful antioxidant with cosmeceutical benefits is pine bark extract. Frank Schonlau, Ph.D., director of scientific communications, Natural Health Science, stated: “Pycnogenol® French maritime pine bark extract is an evidence-based product, and its benefits as a cosmeceutical stem from its selective binding affinity to collagen and elastin. Pycnogenol inhibits destruction of collagen and elastin by oxidative stress such as during sunburn and also from degenerative enzymes in the skin.”

Topical Pycnogenol was also shown to dose-dependently protect the body from UV radiation-induced inflammation, immunosuppression and carcinogenesis, when applied after daily irradiation (Photochem Photobiol, 79, 2:193-8, 2004), and shortened wound healing time in rats (Phytother Res, 18, 7:579-81, 2004) The effects of Pycnogenol also extend to improvements of skin elasticity. A complex formulation (as Evelle®, from Pharmanord) that contained Pycnogenol, vitamin C, biotin, zinc, selenium, blueberry and lycopene was tested in a double blind, placebo-controlled six-week study in 62 women over age 40 (J Dermatolog Treat, 15, 4:222-6, 2004). Topical application of Evelle improved skin elasticity by 9 percent, compared to the placebo group.

Kahn noted Toyo Bio-Pharma has conducted internal studies showing its TOYO-FVG™ pine bark extract also works to promote dermal health and reduce the appearance of age spots. “The extract is truly natural, derived through our patented hot-water extract process,” he added.

Toyo also offers fermentation-processed products. The newest release is a facial mask delivery system created from the micro-fibers of Nata de Coco. “NouriMask™ is a 100-percent natural coconut product designed through a unique fermentation process, in which the resulting superfine fibers are pressed and cut into a facial mask that is clinically proven to penetrate far deeper into the skin than other non-woven masks or lotion alone,” Kahn said. “This offers a mask delivery system base that can be infused with custom skin nutrients or anti-aging treatments. The NouriMask ensures the treatment actually penetrates to the deepest layer of the skin, the stratum corneum, where real transformation occurs.”

Skin nourishing products must deliver benefits from the epidermis through the dermal and sub-cutaneous connective layers. Michael Wang product manager, NuLiv Science USA, noted oxidation from pollution or UV radiation has been linked to decreased collagen biosynthesis in the skin’s dermal layers, leading to sagging, wrinkling and a general loss of tone. “For skin to look young and firm, sufficient amounts of collagen in the skin are critical,” he said. “There are two ways to accomplish this: increase the biosynthesis of collagen or inhibit the decomposition of existing collagen in the dermal layer.”

Formulators are therefore looking to specialty compounds that can help in this fight. Among the possibilities Wang cited were proline to assist collagen biosynthesis, the polysaccharide hyaluronic acid (HA) for lubrication, and compounds to inhibit matrix metalloproteinases (MMPs), the enzyme responsible for decomposing collagen.

NuLiv has conducted in-house studies on its ASTRION™ patentpending botanical extract, and has found it may enhance proline absorption and HA biosynthesis, and inhibit collagen decomposition. The company also conducted a small-scale human study that found ASTRION application could reduce wrinkles by 20 percent and melanin by 22 percent, leading to a lightening effect.

Kyowa Hakko has also developed a specialty ingredient, Resilen™-200, a low-molecular weight HA, that may help increase penetration of actives into the skin and support HA biosynthesis. Todd noted, “ The main challenge in formulati ng cosmeceuticals is delivering actives into the skin in proper levels to ensure activity.” The company also supplies Lhydroxyproline, as Lumistor™, and holds several patents on the use of hydroxyproline and N-acetylhydroxyproline derivatives or salts in combination with water-soluble or oil-soluble vitamins.

Another ingredient with specific skin benefits is pomegranate. “Published research indicates topical benefits with several parts of the pomegranate-fruit, including seed components,” Ebersole said, noting Verdure recently released a cosmeceutical ingredient, Pu nicinol-5™ made from 100 percent pomegranate and standardized to 80 percent essential fatty acids (EFAs) and 75 percent punicic acid.

Indeed, an in vitro study from the University of Michigan found aqueous extracts from pomegranate peel could help regenerate the dermis, while pomegranate seed oil promoted regeneration of the epidermis (J Ethnopharmacol, 103, 3:311-8, 2006). Animal studies have further found topical application of pomegranate seed oil (J Med Food, 6, 3:157-61, 2003) and pomegranate fruit extract (Int J Cancer, 113, 3:423-33, 2005) could work as chemopreventive agents, blocking chemical-induced tumors. And a methanolic extract from dried pomegranate peels, incorporated into a water-soluble gel, worked to significantly accelerate wound healing in rats, simultaneously increasing levels of hydroxyproline in the healing area (J Med Food, 7, 2:256-9, 2004).

Expanding the Market

The largest organ of the body, the skin is an external manifestation of internal health and wellness. For years, consumers have tried detoxification regimens or ingested compounds from silica to vitamin C to improve the appearance of the skin. The growing market for “cosmeceuticals” has a significant crossover into the ingestibles area.

“There’s a lot of potential for the cosmeceutical world, whether as a whole health and beauty supplement or topical treatment,” Kahn said. “And we’re also seeing a lot of interest in combining the two— both topical and oral—to intensify benefits.”

Capelli noted Cyanotech has seen greater interest in combination systems. “Astaxanthin is proven to protect the skin from UV light damage both when applied topically as well as when taken internally, so we have a few companies that are considering developing an inside-out, two product system,” he said.

Kuroda echoed the sentiment, adding Fuji Health Science has a patent pending on the use of internal astaxanthin for wrinkle reduction, and sponsored two human studies to support the application. In a Japanese study, researchers randomized 16 healthy women over age 40, all with dry skin, to receive a supplement of 5-percent astaxanthin (as AstaReal) and palm oil with 37.5-percent vitamin E (as Tocomin, from Carotech). After four weeks, significant improvement was seen in skin moisture content, self-assessment of skin condition, and inspection/palpitation by a cosmetic specialist. Improvement of wrinkles was also noted based on skin observation. A second study, conducted on 49 healthy women in Rockland, Maine (age about 47), provided subjects with a placebo soft gel or one with astaxanthin for six weeks. After intervention, subjects taking astaxanthin had significant improvements in fine lines/wrinkles and elasticity by dermatologist assessment, and in moisture content by instrumental assessment. The researchers suggested astaxanthin may protect fresh collage from oxidative stress.

Also exploring the synergistic effects of internal and external nutrition is SGTI, which Udell noted looks at cosmeceuticals as encompassing both areas. “While external treatments may provide a more youthful appearance, people need to realize that they are the same age on the inside,” he said. To address part of the issue, SGTI supplies several antioxidant ingredients that may help quench free radicals that can accelerate the aging process. “Accumulating evidence strongly suggests oxidative stress is linked to almost every disease of aging,” Udell added.

The company also markets Injuv®, a 9-percent, low molecular weight HA dietary supplement in a soft gelatin capsule for softening skin. “Supplementation with Injuv can increase the HA content throughout the body, including the dermis,” Udell said. “HA exists in both the dermis and epidermis, therefore Injuv moisturizes from the deeper layer to the upper layer.” In a company-supported clinical trial conducted in Japan on 96 women, ages 22 to 65 years, Injuv increased skin smoothness and firmness.

Whether delivering cosmeceuticals orally, topically or synergistically, suppliers note there is great opportunity for companies that develop effective products that can meet consumer expectations. “Buyers should be sure they understand the marketability of the finished product—what will trigger consumers to actually buy the product,” Capelli said. “Buying a cutting-edge, natural, efficacious nutraceutical to put in a cosmeceutical product is certainly the best way to go.”

Udell concluded: “It is difficult for the natural products industry to compete with cosmetic surgeons and dermatologists who administer BOTOX treatments and facial peels, because these are both highly visible industries whose results are seen weekly on makeover ‘reality’ shows. However, for those individuals who are not looking to undertake such ‘extreme’ measures to change their appearance and fight aging, the natural health industry can provide alternatives.”