MAY-JUN 2014

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treated with 4% HQ." (Balina LM, Graupe K. "The treatment of melasma: 20% azelaic acid versus 4% hydroquinone cream," Int J Dermatol 1991;30:893-5.) Dimethylmethoxy chromanyl palmitate (Chrom- abright, Lipotec) is a patented synthetic molecule designed for skin brightening. "Unlike HQ, this synthetic molecule is not at all cytotoxic," says Loretta Ciraldo, MD, Dr. Loretta Skincare ( "Clinical trials show it is a stronger tyrosinase inhibitor than kojic acid, producing more effective lightening in a study of 20 Asian women. It also includes a UVA absorber, which offers some photoprotective effect, whereas HQ is a photo- sensitizer. It not only helps fade hyperpigmentation but it also increases skin luminosity. We use it in a number of our products." Kojic acid, a natural metabolite of certain fungal species, including Acetobacter, Aspergillus and Penicillium, is a tyrosinase inhibitor. "It functions by chelating copper at the active site of the tyrosinase enzyme," says Bidari, "and also acts as an antioxidant preventing the conversion of the o-quinone to DL-DOPA and dopamine to its corresponding melanin. "Recently, some stable kojic acid derivatives have been synthe- sized for better penetration through the skin," adds Bidari, "but it has also been found to cause allergic reactions and has shown only modest effectiveness in clinical trials." Licorice root extract include two actives: glabridin, a ty- rosinase inhibitor with anti-infl ammatory properties, and liquiritin, which may play a role in depigmentation. In one small 8-week, blinded split-face trial, it proved to be as effective as 4% hydro- quinone in treating hyperpigmentation (McDaniel, DH, Wu, J., Cosmetic Dermatology 21:596-602, 2008). Researchers at Nishtar Medical College and Hospital in Pakistan followed 90 patients with melasma: Thirty were treated with 4% HQ, 30 treated with 2% liquiritin and 30 treated with 4% liquiritin. After 16 weeks, the researchers found that the 29 patients who received the 4% liquiritin improved, compared to 26 receiving 2% liquiritin, and just 22 receiving the 4% HQ. The 2009 study was published in the Journal of the Pakistan As- sociation of Dermatologists. Niacinamide 2% to 5% "has shown some effi cacy when used alone or in combination with N-acetyl glucosamine (which inhibits tyrosinase glycosylation) for the treatment of melasma and UV-induced hyperpigmentation in fair-skinned and Asian patients," says Bidari. A co-enzyme precursor, nia- cinamide appears to benefi t aging skin in several ways including improved barrier function, reduced hyperpigmentation and redness, improved skin texture and a reduction in fi ne lines. "It is believed to infl uence cutaneous pigmentation by down- regulating transfer of melanosomes from the melanocytes to the keratinocytes without inhibiting tyrosinase activity or cell proliferation, and it may also interfere with the cell-signaling pathway between keratinocytes and melanocytes to decrease melanogenesis," Bidari says. Peptides, such as oligopeptide 68 (ß-White, Lucas Myer), are another option. "The challenge with peptides is they are water loving and don't penetrate the skin well," says Kulesza. "Oligopeptide 68 does inhibit tyrosinase if it can get deep enough into the skin. ß-White encapsulates it in a phospholipid envelope for better penetration." Another peptide, decapeptide-12 (Lumixyl, Envy Medical), a synthetic, 10-amino acid peptide, has been shown in in vitro stud- ies to be more potent than hydroquinone at inhibiting tyrosinase. A topical emulsion of decapeptide-12 applied twice daily result- ed in a 50% improvement in melasma among patients who had previously used a hydroquinone therapy for six months without success, according to a 2009 four-month pilot study co-authored by Jimenez and published in the Journal of Drugs in Dermatology. "Phenylethyl resorcinol, also known as SymWhite 377 (Symrise) is one of a variety of phenolic compounds that are used as alternatives to HQ," says Kulesza. "It is approved for cosmetic use around the world." Retinoids include prescription tretinoin or tazarotene. "Hy- perpigmentation is a sign that the machinery for making pigment is damaged. A retinoid is the only compound known to man that can get inside living skin cells to fi x the problem," says Kulesza. "Several of these compounds have received FDA approval for photoaging, including age spots." "Vitamin C (L-ascorbic acid) interferes with pigment syn- thesis at various oxidative steps of melanin production. It causes skin lightening by interacting with copper ions at the tyrosinase active site and by reducing oxidized dopaquinone, a substrate in the melanin synthetic pathway," says Bidari. "In addition to skin lightening, vitamin C also offers antioxidant effects, anti-infl amma- tory and photoprotective properties." COMBINING INGREDIENTS FOR BETTER EFFICACY Most lightening/brightening products combine several ingredients that may include antioxidants, anti-infl ammatories and ingredients like alpha hydroxy acids or salicylic acid that encourage keratolysis. "When addressing hyperpigmentation, I always include anti- oxidants," says Dr. Ciraldo. "When the skin forms free radicals, it © ISTOCKPHOTO.COM Formulators are using combinations of non-HQ actives to reduce hyperpigmentation. "Niacinimide has shown some effi cacy when used alone or in combination with N-acetyl glucoamine for the treatment of melasma." | MAY/JUNE 2014 37 C y c l i n g O f f M E D 5 - 6 1 4 . i n d d 3 7 Cycling Off MED5-614.indd 37 4 / 1 6 / 1 4 4 : 3 9 P M 4/16/14 4:39 PM

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