Reduction in the appearance of facial hyperpigmentation by topical N-undecyl-10-enoyl-L-phenylalanine and its combination with niacinamide.

OBJECTIVES: N-undecyl-10-enoyl-L-phenylalanine (Sepiwhite), N-undecylenoyl phenylalanine), a reported alpha-melanocyte-stimulating hormone (MSH) receptor antagonist, has been observed to reduce melanin production in cultured melanocytes. In other testing, niacinamide has been found to inhibit melanosome transfer in cultured cells and to reduce the appearance of hyperpigmented spots in clinical studies. Since these two agents function by different mechanisms, we conducted two studies to determine if their combination is more effective than niacinamide alone in reducing facial hyperpigmentation. METHODS: Two double-blind, 10-week (2-week washout + 8-week treatment), left-right randomized, split-face clinical studies were conducted. In one, two groups of Japanese women applied one of two pairs of test emulsion formulations: a vehicle control and a 5% niacinamide formulation (n= 40), or a 5% niacinamide and a 5% niacinamide plus 1%N-undecylenoyl phenylalanine formulation (n = 40). Each formulation was applied to the randomly assigned side of the face. In the second study, Caucasian women applied one of three emulsions: vehicle control, 5% niacinamide formulation, or combination 5% niacinamide plus 1%N-undecylenoyl-phenylalanine formulation to the randomly assigned side of the face (n = approximately 60 treatment sites per formulation). In both studies, hyperpigmented spots were evaluated at weeks 4 and 8 by quantitative image analysis. RESULTS: In both studies, the combination formulation was significantly more effective than the vehicle and the 5% niacinamide formulation in reducing the appearance of hyperpigmentation after 8 weeks. CONCLUSIONS: The combination of 5% niacinamide and 1%N-undecylenoyl phenylalanine is an effective anti-aging technology for use on facial skin.

Common cosmeceuticals.

In the cosmetic arena, many materials are used commercially and claim to provide skin effects (eg, antiaging effects) when used topically. Considering there are so many such materials and many skin appearance effects are encompassed, this short contribution must, by necessity, be selective in terms of the number of materials discussed and the depth with which any particular material is overviewed. This presentation, therefore, focuses on only 10 types of cosmeceutical agents: five vitamins (A, B(3), C, E, panthenol), peptides, hydroxyl acids, sugar amines, ceramides, and metals. In particular, this contribution concentrates on those materials for which there are available clinical data that support a reported skin appearance improvement effect.

Latest insights into skin hyperpigmentation.

Hyperpigmentary problems, including postinflammatory hyperpigmentation, solar lentigos, and melasma, occur widely in the human population and are thus of broad interest for control. On the basis of genomic and proteomic understanding of the melanocyte and melanogenesis, there are potentially hundreds of proteins and other effectors involved in pigmentation. This knowledge, although complex, should prove most useful in identifying specific abnormalities that lead to the hyperpigmentary problems. Also available are new laboratory screening methods and skin color measurement tools that are increasing the pace at which materials can be screened and evaluated clinically for their effectiveness. Combined with a clear consumer need for effective pigmentation control agents, advanced pigmentary system understanding and new research capabilities are setting the stage for future technological advancements.

Genomic expression changes induced by topical N-acetyl glucosamine in skin equivalent cultures in vitro.

N-acetyl glucosamine (NAG) has been shown to be effective in reducing the appearance of hyperpigmented spots. From published in vitro mechanistic testing, glucosamine inhibits enzymatic glycosylation, a required processing step in converting inactive human pro-tyrosinase to the active tyrosinase, a key enzyme in the production of melanin. There is also published literature discussing the anti-inflammatory and antioxidant properties of glucosamine compounds. To identify additional mechanisms by which NAG might affect melanin production, an in vitro genomics experiment was conducted in SkinEthic skin equivalent cultures, which were topically dosed with NAG vs. a vehicle control. Relative to vehicle, NAG reduced melanin production, and the expression of several pigmentation-relevant genes were affected (down-regulated or up-regulated) by NAG treatment. Thus, there are several mechanisms that may be operative in the observed pigmentation effects.

Reduction in the appearance of facial hyperpigmentation by topical N-acetyl glucosamine.

Glucosamine has been reported to inhibit melanin production in melanocyte culture. It thus has a potential to reduce hyperpigmentation via topical use. Due to stability limitations of glucosamine, we chose to clinically evaluate the stable derivative N-acetyl glucosamine (NAG). Based on in vitro Franz cell testing, NAG is a good skin penetrant. In an 8-week, double-blind, placebo-controlled, left-right randomized, split-face clinical test, topical 2% NAG reduced the appearance of facial hyperpigmentation. In a second clinical study involving the topical combination of 2% NAG with 4% niacinamide, an agent previously shown to be clinically active, the effect on hyperpigmentation was greater. Both of these agents are well tolerated by the skin. This high tolerance coupled with relative ease of formulation and stability in solution make NAG, especially in combination with niacinamide, a suitable cosmetic ingredient for use in skin care products dealing with issues of skin hyperpigmentation.

Glucosamine: an ingredient with skin and other benefits.

Both glucosamine and its derivative N-acetyl glucosamine are amino-monosaccharides that serve key biochemical functions on their own and as substrate precursors for the biosynthesis of polymers such as glycosaminoglycans (e.g., hyaluronic acid) and for the production of proteoglycans. Glucosamine has an excellent safety profile and has been shown to provide benefits in several clinical disorders. Glucosamine compounds have been reported to have several beneficial effects on the skin or skin cells. Because of its stimulation of hyaluronic acid synthesis, glucosamine has been shown to accelerate wound healing, improve skin hydration, and decrease wrinkles. In addition, as an inhibitor of tyrosinase activation, it inhibits melanin production and is useful in treatment of disorders of hyperpigmentation. Mechanistically, glucosamine also has both anti-inflammatory and chondroprotective effects. Clinical trials have shown benefit in using oral glucosamine supplementation to improve symptoms and slow the progression of osteoarthritis in humans. Glucosamine has also been used to prevent and treat osteoarthritis in animals. Based on other observations, glucosamine has been suggested for additional clinical uses, including treatment of inflammatory bowel disease, migraine headaches, and viral infections. The current clinical uses for topical and oral glucosamine compounds and the mechanistic rationale for these uses are reviewed here.

Niacinamide: A B vitamin that improves aging facial skin appearance.

BACKGROUND: In multiple chronic clinical studies, topical niacinamide (vitamin B3) has been observed to be well tolerated by skin and to provide a broad array of improvements in the appearance of aging facial skin (eg, reduction in the appearance of hyperpigmentated spots and red blotchiness). OBJECTIVE: To clinically determine the effect of topical niacinamide on additional skin appearance and property end points (wrinkles, yellowing, and elasticity). METHODS: Female white subjects (N = 50) with clinical signs of facial photoaging (fine lines and wrinkles, poor texture, and hyperpigmented spots) applied 5% niacinamide to half of the face and its vehicle control to the other half twice daily for 12 weeks (double blind, left-right randomized). Facial images and instrumental measures were obtained at baseline and at 4-week intervals. RESULTS: Analyses of the data revealed a variety of significant skin appearance improvement effects for topical niacinamide: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing). In addition, elasticity (as measured via cutometry) was improved. Corresponding mechanistic information is presented. CONCLUSION: In addition to previously observed benefits for topical niacinamide, additional effects were identified (improved appearance of skin wrinkles and yellowing and improved elasticity).