Cosmeceutical combos: Synergy trumps monotherapy

Brooklyn, N.Y. - Like many antiaging skin treatments, cosmeceuticals work best in combination, an expert says.

No single cosmeceutical active ingredient is likely to fulfill a patient's wish list, says Hilary E. Baldwin, M.D., vice chairman and associate professor of dermatology, State University of New York Downstate, Brooklyn.

Therefore, she says, "Combining retinoids, sunscreens, antioxidants, collagen stimulating peptides, bleaching agents and hydroxy acids will be more effective than any agent alone."

Similarly, she advises combining cosmeceuticals with cosmetic dermatological procedures wherever possible.

Topical antioxidants

Antioxidants reduce free radical formation and oxidative stress to the skin, which can result in cellular DNA damage, slower skin cell turnover and other consequences, Dr. Baldwin says. Research shows that topical antioxidants help reduce the signs of intrinsic aging while restoring and protecting skin from extrinsic aging (Dreher F, Maibach H. Curr Probl Dermatol. 2001;29:157-64 Review).

Another study suggests that topical melatonin, vitamin C and vitamin E used alone and in combination might provide short-term photoprotective effects in human skin in vivo (Dreher F et al. Br J Dermatol. 1998 Aug;139(2):332-9).

Somewhat similarly, idebenone (Prevage M.D., Allergan; Prevage, Elizabeth Arden) appears to be a more potent antioxidant than vitamins C and E, as well as alpha-lipoic acid, kinetin and coenzyme Q10 (McDaniels et al. J Cosm Dermatol. 2005;4:167-173).

In this six-week, 21-patient study, patients using idebenone experienced a 33 percent improvement in overall appearance and a 29 percent reduction in fine lines and wrinkles.Coffee berry extract (Revaleskin, Stiefel) comes from coffee beans harvested before they're ripe and is particularly rich in polyphenol antioxidants, Dr. Baldwin says.

In a six-week, split-face trial involving 10 subjects, those who used coffee berry experienced a nearly 30 percent improvement in overall appearance, versus about 5 percent for vehicle-treated subjects, she says.

Collagen-stimulating cosmeceuticals

Conversely, Dr. Baldwin says that for collagen-stimulating cosmeceuticals, including peptides, copper and growth factors, there's considerable scientific rationale but little clinical evidence of efficacy.

These cosmeceuticals would undeniably deliver benefits if they're capable of reaching the dermis and accomplishing their intended task, but this has yet to be proven, Dr. Baldwin says.

For example, "Growth factors are very large molecules, but there's no evidence that they're able to penetrate the epidermis," she says.

Signal peptides such as Matrixyl (pal-pentapeptide, Sederma), on the other hand, available in products including StriVectin-SD (Klein-Becker) and Regenerist (Olay), flood the dermis with collagen breakdown products, signaling cellular damage, she says.

"In response," Dr. Baldwin says, "fibroblasts increase collagen and decrease collagen production."

Botanical agents

Among the nearly 70 botanical agents used by cosmeceutical makers, she adds, only six have clinical trials behind them. One such ingredient is soy (Aveeno, Johnson & Johnson). In two tests, soy has been shown to have anti-inflammatory, moisturizing, cleansing, photorejuvenating and lightening/brightening properties, along with the ability to decrease appearance of hair growth (Liu J-C et al. Poster presented at 59th Annual American Academy of Dermatology/AAD Meeting: March 2-7, 2001; Washington, D.C., Nebus J et al. Poster presented at 61st Annual AAD Meeting: March 21-26, 2003; San Francisco), Dr. Baldwin says.

Sunscreen

But amid all the marketing hype for the newest cosmeceutical ingredients, Dr. Baldwin says, "Don't let patients forget their sunscreens."

Most women ask dermatologists to recommend the best wrinkle cream, she says, "But nothing is more important than obsessive-compulsive use of well-formulated sunscreen."

Frequently, she adds, patients need help selecting sunscreens and knowing how to use them. "Not all sunscreens are created equal," she says.

Evidence base

For dermatologists who wish to recommend only cosmeceuticals backed by strong science, Dr. Baldwin says, "Stick with topical retinoids and sunscreens."

That's because, overall, the evidence base for cosmeceutical use remains a work in progress, she says.

"The FDA’s distinction between drugs, which treat and prevent disease, and cosmetics, which impact the appearance, proved adequate until modern researchers uncovered new concepts of skin function," she says.

Meanwhile, Dr. Baldwin says worldwide cosmeceutical sales for 2008 are projected at $7.2 billion.

"Baby boomers don't think there's anything graceful about the aging process," she says.

Working knowledge

Accordingly, Dr. Baldwin says all dermatologists require a working knowledge of cosmeceuticals, if only to prevent patients from getting misinformation elsewhere. The mass of cosmeceutical products available confuses many women, she says, and research has shown that women tend to believe cosmetic claims, cosmetic salespeople and dermatologists equally.

For physicians, it might never be possible to evaluate cosmeceutical agents as rigorously as the Food and Drug Administration evaluates drug candidates, she says.

For starters, vehicles commonly used as placebos function as moisturizers and, therefore, could perform as well as the ingredient or product being tested.

Furthermore, evaluating cosmeceuticals frequently requires lengthy studies that seek subtle outcomes, which may or may not achieve statistical significance.

Botanicals introduce additional problems, not the least of which is that widely varying growing conditions make consistent quality assurance nearly impossible, she says.

Finally, Dr. Baldwin says, the science behind many cosmeceuticals amounts to in vitro studies, "and in vitro success does not mean in vivo success." DT

Disclosure: Dr. Baldwin is an investigator, consultant and/or speaker for Allergan, L'Oreal, OrthoNeutrogena and Stiefel.