14. J Eur Acad Dermatol Venereol. 2011 Oct;25(10):1140-5. doi: 10.1111/j.1468-3083.2011.04130.x. Epub 2011 May 31.  Natural options for the management of hyperpigmentation.  Leyden JJ, Shergill B, Micali G, Downie J, Wallo W.  University of Pennsylvania, Philadelphia, PA, USA. 

 

Facial hyperpigmented disorders are a common complaint in the adult population of all races. First-line topical treatments are usually hydroquinone or topical retinoids, which can cause irritant reactions. The need for better tolerated, yet effective, skin lightening agents that could be utilized by a wider population has led to the investigation of several potential botanical/natural compounds. There are currently many topical cosmetic formulations claiming skin depigmenting effects. A few of the ingredients (e.g. soy) are supported not only by in vitro results but also by a body of controlled clinical efficacy studies; other ingredients, instead, are backed mostly by in vitro data and a few small uncontrolled clinical studies. In this review, we describe the most common natural ingredients used for skin depigmentation and their major published studies: soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, COFFEEBERRY(™) and green tea.  © 2011 Johnson & Johnson Consumer Companies, Inc. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.  PMID: 21623927  [PubMed - in process]   

 

13. J Dermatol Sci. 2011 Sep;63(3):199-201. Epub 2011 Jun 12.  Disruption of tyrosinase glycosylation by N-acetylglucosamine and its depigmenting effects in guinea pig skin and in human skin.  Hwang JS, Lee HY, Lim TY, Kim MY, Yoon TJ.  PMID: 21723097  [PubMed - in process]   3. Am J Clin Dermatol. 2011 Apr 1;12(2):87-99. doi: 10.2165/11536930-000000000-00000.  Postinflammatory hyperpigmentation: etiologic and therapeutic considerations.  Callender VD, St Surin-Lord S, Davis EC, Maclin M.  Callender Skin and Laser Center, 12220 Annapolis Blvd., Glenn Dale, MD 20769, USA. drcallender@CallenderSkin.com  

 

Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis and sequela of a variety of inflammatory skin conditions. PIH can have a negative impact on a patient's quality of life, particularly for darker-skinned patients. Studies show that dyschromias, including PIH, are one of the most common presenting complaints of darker-skinned racial ethnic groups when visiting a dermatologist. This is likely due to an increased production or deposition of melanin into the epidermis or dermis by labile melanocytes. A variety of endogenous or exogenous inflammatory conditions can culminate in PIH and typically most epidermal lesions will appear tan, brown, or dark brown while dermal hypermelanosis has a blue-gray discoloration. Depigmenting agents target different steps in the production of melanin, most commonly inhibiting tyrosinase. These agents include hydroquinone,  azelaic acid, kojic acid, arbutin, and certain licorice (glycyrrhiza) extracts. Other agents include retinoids, mequinol, ascorbic acid (vitamin C), niacinamide, N-acetyl glucosamine, and soy, and these products depigment by different mechanisms. Certain procedures can also be effective in the treatment of PIH including chemical peeling and laser therapy. It is important to note that these  same therapeutic modalities may also play a role in causing PIH. Lastly, those lesions that are not amenable to medical or surgical therapy may experience some  improvement with cosmetic camouflage.  PMID: 21348540  [PubMed - indexed for MEDLINE]   

 

 

11: Am J Clin Dermatol. 2011 Apr 1;12(2):87-99. doi: 10.2165/11536930-000000000-00000. Postinflammatory hyperpigmentation: etiologic and therapeutic considerations. Callender VD, St Surin-Lord S, Davis EC, Maclin M. Source Callender Skin and Laser Center, 12220 Annapolis Blvd., Glenn Dale, MD 20769, USA. drcallender@CallenderSkin.com

 

Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis and sequela of a variety of inflammatory skin conditions. PIH can have a negative impact on a patient's quality of life, particularly for darker-skinned patients. Studies show that dyschromias, including PIH, are one of the most common presenting complaints of darker-skinned racial ethnic groups when visiting a dermatologist. This is likely due to an increased production or deposition of melanin into the epidermis or dermis by labile melanocytes. A variety of endogenous or exogenous inflammatory conditions can culminate in PIH and typically most epidermal lesions will appear tan, brown, or dark brown while dermal hypermelanosis has a blue-gray discoloration. Depigmenting agents target different steps in the production of melanin, most commonly inhibiting tyrosinase. These agents include hydroquinone, azelaic acid, kojic acid, arbutin, and certain licorice (glycyrrhiza) extracts. Other agents include retinoids, mequinol, ascorbic acid (vitamin C), niacinamide, N-acetyl glucosamine, and soy, and these products depigment by different mechanisms. Certain procedures can also be effective in the treatment of PIH including chemical peeling and laser therapy. It is important to note that these same therapeutic modalities may also play a role in causing PIH. Lastly, those lesions that are not amenable to medical or surgical therapy may experience some improvement with cosmetic camouflage.

 

 

10. J Clin Aesthet Dermatol. 2010 Jul;3(7):20-31.  Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color.  Davis EC, Callender VD. 

 

Postinflammatory hyperpigmentation is a common sequelae of inflammatory dermatoses that tends to affect darker skinned patients with greater frequency and severity. Epidemiological studies show that dyschromias, including postinflammatory hyperpigmentation, are among the most common reasons darker racial/ethnic groups seek the care of a dermatologist. The treatment of postinflammatory hyperpigmentation should be started early to help hasten its resolution and begins with management of the initial inflammatory condition. First-line therapy typically consists of topical depigmenting agents in addition  to photoprotection including a sunscreen. Topical tyrosinase inhibitors, such as  hydroquinone, azelaic acid, kojic acid, arbutin, and certain licorice extracts, can effectively lighten areas of hypermelanosis. Other depigmenting agents include retinoids, mequinol, ascorbic acid, niacinamide, N-acetyl glucosamine, and soy with a number of emerging therapies on the horizon. Topical therapy is typically effective for epidermal postinflammatory hyperpigmentation; however, certain procedures, such as chemical peeling and laser therapy, may help treat recalcitrant hyperpigmentation. It is also important to use caution with all of the above treatments to prevent irritation and worsening of postinflammatory hyperpigmentation.  PMCID: PMC2921758 PMID: 20725554  [PubMed]   

 

9. Br J Dermatol. 2010 Feb 1;162(2):435-41. Epub 2009 Aug 28.  Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: results of a  randomized, double-blind, vehicle-controlled trial.  Kimball AB, Kaczvinsky JR, Li J, Robinson LR, Matts PJ, Berge CA, Miyamoto K, Bissett DL.  Harvard Medical School, Boston, MA 02114, USA.

 

BACKGROUND: Topical niacinamide and N-acetyl glucosamine (NAG) each individually  inhibit epidermal pigmentation in cell culture. In small clinical studies, niacinamide-containing and NAG-containing formulations reduced the appearance of  hyperpigmentation. OBJECTIVES: To assess the effect of a combination of niacinamide and NAG in a topical moisturizing formulation on irregular facial pigmentation, including specific detection of changes in colour features associated with melanin. METHODS: This was a 10-week, double-blind, vehicle-controlled, full-face, parallel-group clinical study conducted in women aged 40-60 years. After a 2-week washout period, subjects used a daily regimen of either a morning sun protection  factor (SPF) 15 sunscreen moisturizing lotion and evening moisturizing cream each containing 4% niacinamide + 2% NAG (test formulation; n = 101) or the SPF 15 lotion and cream vehicles (vehicle control; n = 101). Product-induced changes in  apparent pigmentation were assessed by capturing digital photographic images of the women after 0, 4, 6 and 8 weeks of product use and evaluating the images by algorithm-based computer image analysis for coloured spot area fraction, by expert visual grading, and by chromophore-specific image analysis based on noncontact SIAscopy for melanin spot area fraction and melanin chromophore evenness. RESULTS: By all four measures, the niacinamide + NAG formulation regimen was significantly (P < 0.05) more effective than the vehicle control formulation regimen in reducing the detectable area of facial spots and the appearance of pigmentation. CONCLUSIONS: A formulation containing the combination of niacinamide + NAG reduced the appearance of irregular pigmentation including hypermelaninization, providing an effect beyond that achieved with SPF 15 sunscreen.  PMID: 19845667  [PubMed - indexed for MEDLINE]   

 

 

8. Arch Dermatol Res. 2009 Aug;301(7):549-51. Epub 2009 Feb 27.  Exogenous N-acetylglucosamine increases hyaluronan production in cultured human dermal fibroblasts.  Tu CX, Zhang RX, Zhang XJ, Huang T.  Department of Dermatology, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, 116027 Dalian, People's Republic of China. tucx2003@163.com  

 

Application of hyaluronan (HA) containing cosmetic products to the skin is reported to moisturize and restore elasticity thereby achieving an antiwrinkle effect. In the skin, HA can be synthesized by dermal fibroblasts and N-acetylglucosamine (NAG) is a precursor for HA biosynthesis in the body. To study the effects of exogenous NAG on HA production in human dermal fibroblasts,  HA production and HA-synthesizing enzymes 1, 2 and 3 mRNA expression in cultured  human dermal fibroblasts were measured by ELISA and RT-PCR, respectively. The results showed that NAG promoted HA production while had no effect on the expression of HA-synthesizing enzymes 1, 2 and 3 mRNA in human dermal fibroblasts.  PMID: 19247681  [PubMed - indexed for MEDLINE]   

 

7. J Cosmet Sci. 2009 Jul-Aug;60(4):423-8.  The effect of N-acetyl-glucosamine on stratum corneum desquamation and water content in human skin.  Mammone T, Gan D, Fthenakis C, Marenus K.  Estee Lauder Research Laboratory, Melville, NY 11747, USA.  

 

Alpha-hydroxy acids have been used topically to treat skin for both dermatological and cosmetic problems for many years. Though there are many known  benefits of the use of alpha-hydroxy acids on skin, there have been recent reports that topical treatments with alpha-hydroxy acids increase skin damage resulting from UVB. Additionally, high concentrations of alpha-hydroxy acids by themselves have also been found to cause skin irritation. In order to find alternatives to alpha-hydroxy acids, we investigated a variety of amino sugar compounds that were previously reported to inhibit the reaggregation of dissociated corneocytes by modulating cellular adhesion. In vivo, we observed that topical treatments with a formulation containing N-acetyl-glucosamine (NAG)  led to an increase in skin moisturization, a decrease in skin flakiness, and the  normalization of stratum corneum exfoliation. In vitro, we observed an upregulation of differentiation markers, keratin 10 and involucrin, in keratinocytes treated with NAG. CD44 is a lectin cell adhesion molecule that is also expressed in keratinocytes. Amino sugars such as NAG may competitively bind  to CD44, modulating keratinocyte cellular adhesion. We hypothesize that these amino sugars modulate keratinocyte cellular adhesion and differentiation, leading to the normalization of stratum corneum exfoliation. We propose the use of amino  sugars such as NAG as alternative compounds to replace the use of alpha-hydroxy acids in skin care.  PMID: 19691938  [PubMed - indexed for MEDLINE]   

 

6. Semin Cutan Med Surg. 2009 Jun;28(2):77-85.  Management of hyperpigmentation in darker racial ethnic groups.  Grimes PE.  Vitiligo and Pigmentation Institute of Southern California, Los Angeles, CA. pegrimesmd@earthlink.net  

 

Dyschromias, in particular hyperpigmentation, are major issues of concern for people of color. Pigmentary disorders such as melasma and postinflammatory hyperpigmentation (PIH) can cause psychological and emotional distress and can pose a negative impact on a person's health-related quality of life. The precise  etiology of these conditions is unknown. Therapies for melasma and PIH target various points during the cycle of melanin production and degradation. Therapies  for these conditions include topical agents and resurfacing procedures. Hydroquinone remains the gold standard of topical agents. Other efficacious agents include kojic acid, azelaic acid, mequinol, and retinoids. Cosmeceutical agents include licorice, arbutin, soy, N-acetyl glucosamine, and niacinamide. Resurfacing procedures that have been used to treat melasma and PIH include chemical peels, microdermabrasion, lasers, and intense pulsed light. These procedures are best used in combination with topical bleaching agents. Given the  propensity of darker skin to hyperpigment, resurfacing procedures should be used  with care and caution. Maximal results are best achieved with repetitive, superficial, resurfacing modalities. In addition, ultraviolet protective measures such as broad-spectrum sunscreens are fundamental to the successful management of these conditions.  PMID: 19608057  [PubMed - indexed for MEDLINE]   

 

5. J Cosmet Dermatol. 2007 Dec;6(4):232-8.  Genomic expression changes induced by topical N-acetyl glucosamine in skin equivalent cultures in vitro.  Bissett DL, Farmer T, McPhail S, Reichling T, Tiesman JP, Juhlin KD, Hurley GJ, Robinson MK.  Procter & Gamble Company, Cincinnati, OH, USA. bissett.dl@pg.com  

 

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.  PMID: 18047607  [PubMed - indexed for MEDLINE]   

 

4. Dermatol Ther. 2007 Sep-Oct;20(5):308-13.  Skin lightening preparations and the hydroquinone controversy.  Draelos ZD.  Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. zdraelos@northstate.net  

 

Skin lightening preparations are widely used in dermatology by persons of all Fitzpatrick skin types. Fitzpatrick skin types I-III require local pigment lightening for the treatment of hormonally induced melasma and postinflammatory hyperpigmentation caused by acne and trauma. Fitzpatrick skin types IV and darker have an even greater need for skin lightening for social reasons, as well as pigmentary changes that occur around the eyes, in the intertriginous areas, following dermatitis, or with acne and trauma. The gold standard dermatologic agent for skin lightening was hydroquinone, until regulatory agencies in Japan, Europe, and most recently in the United States questioned the safety of this substance. This has encouraged research into alternative agents to inhibit skin pigmentation such as retinoids, mequinol, azelaic acid, arbutin, kojic acid, aleosin, licorice extract, ascorbic acid, soy proteins, and N-acetyl glucosamine. The efficacy and safety of each of these ingredients is examined as possible topical alternatives to hydroquinone.  PMID: 18045355  [PubMed - indexed for MEDLINE]   

 

3. J Cosmet Dermatol. 2007 Mar;6(1):20-6.  Reduction in the appearance of facial hyperpigmentation by topical N-acetyl glucosamine.  Bissett DL, Robinson LR, Raleigh PS, Miyamoto K, Hakozaki T, Li J, Kelm GR.  Procter & Gamble Company, Cincinnati, Ohio 45252, USA. bissett.dl@pg.com  

 

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.  PMID: 17348991  [PubMed - indexed for MEDLINE]   

 

2. J Cosmet Dermatol. 2006 Dec;5(4):309-15.  Glucosamine: an ingredient with skin and other benefits.  Bissett DL.  Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, OH 45252, USA. bissett.dl@pg.com  

 

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.  PMID: 17716251  [PubMed - indexed for MEDLINE]   

 

1. Skin Pharmacol Physiol. 2004 Mar-Apr;17(2):77-83.  Synergistic effect of N-acetylglucosamine and retinoids on hyaluronan production  in human keratinocytes.  Sayo T, Sakai S, Inoue S.  Basic Research Laboratory, Kanebo Ltd., Odawara, Japan.  

 

Hyaluronan (HA) is well known to reside in the extracellular matrix as a water-sorbed macromolecule. The aims of this study were twofold: to investigate the regulation of HA synthesis in keratinocytes, and to develop a method to modulate this regulatory process. We found that N-acetylglucosamine (NAG) increased the production of HA by cultured keratinocytes dose dependently, but had no effect on the production by skin fibroblasts. The effect of NAG in keratinocytes was found to be specific for HA production, as there was no change  in sulfated glycosaminoglycan formation. The copresence of NAG with either of two retinoids, retinoic acid (RA) or retinol, exerted a synergistic effect on HA production. To investigate whether human HA synthase (HAS) genes were regulated by NAG or retinoids, total RNA extracted from cells treated with these agents was subjected to Northern blot analysis. We observed that RA and retinol markedly induced the expression of HA synthase-3 (HAS3) mRNA. Moreover, beta-carotene, a provitamin A, influenced HA production and HAS3 gene expression in a manner similar to the retinoids. Conversely, NAG had no effect on the expression of HAS3 transcripts. Pretreatment of cells with RA stimulated the activity of membrane-associated HAS, whereas pretreatment with NAG did not. These results suggest that HA production is regulated by at least two pathways: one involving the regulation of HAS gene expression, and the other independent of such a regulatory effect. Taken together, our findings suggest that NAG is a new modulator of HA synthesis.  Copyright 2004 S. Karger AG, Basel  PMID: 14976384  [PubMed - indexed for MEDLINE]      

Advanced skin care research has shown that Glucosamine (N-acetyl-D) is useful for HA production, and for its skin lightening and brightening qualities. It is known to reduce the appearance of facial hyperpigmentation.

N-acetyl glucosamine research