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44 APRIL 2014 | Med Esthetics BEYOND THE HYPE Yet, there are sev- eral topical ingredients that have undergone rigorous clinical stud- ies that support their effi cacy in reducing fi ne lines and wrinkles, improving skin texture and evening out areas of hyperpigmentation. Below is our roundup of the best-proven topical ingredients for antiaging indications. RETINOIDS Vitamin A-derivatives, better known as retinoids, are the only topical ingredients indicated for antiaging that have approval from the FDA to support their claims of effi cacy. There are different forms of prescription-strength retinoids (or retinoic acid) used in antiaging, and they include tretinoin, tazarotene and adapalene. "The studies supporting retinoids and the benefi ts they offer go all the way back to the mid-1980s," says dermatologist Melanie Palm, MD, director of Art of Skin MD in San Diego and volunteer assistant clinical pro- fessor at the University of California, San Diego. "There are multiple clinical studies, placebo-controlled studies, split-faced and split forearm studies that show retinoids decrease all sorts of aspects of photoaging: wrinkling, skin texture and mottling of skin tone." According to John Kulesza, senior formulating chemist and president of Young Pharmaceuticals (youngpharm.com), retinoids work by penetrating through the stratum corneum into the nuclei of living cells to reach the retinoid receptors. One of the things retinoids do there is tell the cells to create the proteins collagen and elastin. "Retinoids are lipophilic molecules, which means that they are oil-loving. That enables them to penetrate deep into the skin, through the cell wall and into the nucleus where the receptors are," Kulesza explains. "That is why they have a wide range of biological effects." The downside to retinoids has typically been the ir- ritation and infl ammation they cause in some users. But formulators are learning to control some of the unpleas- ant side effects. "Our vehicles for delivering the tretinoin have become better," says Dr. Palm. " The newer vehicles, especially those with an emollient or some that have hyaluronic acid as a carrier, really decrease the red- ness associated with tretinoin." Retinoic acid is available only by prescription, but retinol, also vitamin A-derived, is widely available over- the-counter. Retinol is the alcohol form of vitamin A, which means there's a hydroxyl group—an oxygen and a hydrogen atom—'glued' onto the end of the mol- ecule, Kulesza points out. In contrast, retinoic acid has a carboxyl group—a carbon atom, two oxygens and a hydrogen—attached to the end of the molecule. "That's the key difference between retinol and retinoic acid. It's quite relevant because retinoid receptors inside our skin cells appear to be able to recognize the acid form (the carboxyl group) better than the alcohol form (the hydroxyl group)," says Kulesza. There is less data to support the effi cacy of retinol vs. retinoids, but the evidence is growing. Dr. Palm cites a recent study in the Journal of Drugs in Dermatology (De- cember 2013) by Michael H. Gold, et al, that "showed that retinol can have some benefi t in terms of overall photodamage, but there has never been a head-to-head study comparing retinol to retinoids," says Dr. Palm. "I usually reserve it for patients who have been unable to tolerate any kind of retinoid or for off-the-face areas like the neck, décolletage or backs of the hands. I want my patients to be able to use something that is still in the vitamin A-derivative family that may not have the same potency that you usually use on facial skin." How do the potencies of these two vitamin A- derivatives compare? In her book, Cosmetic Dermatol- ogy, dermatologist Leslie Baumann, MD, notes that while retinol is about 20x less potent than retinoic acid, because retinol penetrates the skin more effectively, the retinol in topical applications may be closer to 10x less potent than retinoic acid. She writes, "Retinol at .25% may be a useful retinoid-like treatment for application without occlusion, because it does not irritate the skin, but does induce cellular and molecular changes similar to those observed with .025% retinoic acid." Her ratios are based, in part, on a September 1997 study in the Journal of Investigative Dermatology by Elizabeth A. Duell, et al, which showed that unoccluded retinol penetrates the skin more effectively then unoc- cluded retinoic acid; however, a greater concentration of retinol is required to affect the same molecular changes seen with retinoic acid. SUNSCREEN The dermatology community has long harped on the Retinoids work by penetrating through the stratum corneum into the nuceli of living cells. Glycolic and lactic acids have the ability to increase collagen and elastin production in aging skin. © THINKSTOCK B e y o n d H y p e M E D 4 1 4 . i n d d 4 4 Beyond Hype MED414.indd 44 3 / 1 3 / 1 4 9 : 2 0 A M 3/13/14 9:20 AM