Journal of Clinical and Aesthetic Dermatology

FEB 2018

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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35 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2 R E V I E W colorimetry, and photography over a 12-week period demonstrated the soy-containing moisturizer to have a more favorable outcome in terms of improving mottled pigmentation, blotchiness, dullness, fine lines, overall texture, overall skin tone, and overall appearance than the vehicle alone. In reference to mottled hyperpigmentation, 28 out of 31 treatment- group patients experienced a certain degree of depigmentation compared to 17 out of 32 control-group patients. Promising results from multiple RCTs support the clinical use of soybean extract in treating hyperpigmentation. Ascorbic acid. Ascorbic acid (AA; vitamin C) is an acidic, hydrophilic antioxidant most commonly found in citrus fruit and serves as a cofactor for several human enzymatic processes. 54 AA plays a notable role in wound healing, catecholamine synthesis, tyrosine degradation, bile acid synthesis, iron absorption, neurotransmitter synthesis, and immune system function. 54 According to in-vitro and in-vivo studies, AA might have antimelanogenic properties and, as a result, might be beneficial in treating hyperpigmentation. 55 With regard to clinical studies, Kim et al 56 investigated a superficial chemical peel (Theraderm®, Therapon Skin Health, LP, Springdale, Arizona), which consists of alpha-hydroxy acid, AA, and oxygen in treating 25 Korean patients with severe melasma. According to photographic assessment during eight weeks of treatment, 96 percent of patients showed improvement in hyperpigmentation. Another clinical study compared the effect of combined topical AA and trichloroacetic acid peel versus trichloroacetic acid peel alone in treating 30 women with bilateral epidermal melasma. 57 Evaluation by digital photography and MASI demonstrated that 87 percent of patients using the combination therapy versus 67 percent of patients using trichloroacetic acid peel alone showed improvement or maintained improvement in their melasma. Unfortunately, all of these studies are limited by the fact that AA was not studied independently. Fortunately, a few studies have investigated vitamin C iontophoresis as a possible treatment for hyperpigmented lesions as it allows for greater AA penetration. Huh et al 59 also utilized vitamin C iontophoresis to treat 29 women with melasma. In this double-blind, placebo- controlled RCT, vitamin C solution was applied to one half of the face and distilled water (control) was applied to the other half. After 12 weeks of iontophoresis treatment, the colorimeter recorded a clinically significant reduction in luminance value on the treated side compared to the control side. Similarly, a controlled study was performed by Taylor et al 60 that involved treating 35 patients with melasma or post- inflammatory hyperpigmentation with a novel full-face iontophoresis mask and ascorbyl glucoside preparation over a 1- to 2-month period. In conjunction with the treatment, patients adhered to a regimen of mandelic/ malic acid skin care regimen, broad-spectrum UVA/UVB sunblock, and basic sun protection. A group of four independent graders determined that there was a mean 73-percent improvement in abnormal pigmentation, greater than 25-percent improvement in 32 patients, and greater than 50-percent improvement in 22 patients. Both these studies support the role of vitamin C iontophoresis in treating melasma. SUMMARY AzA's depigmentation mechanism involves inhibition of mitochondrial oxidoreductase, DNA synthesis, and tyrosinase activity. Two RCTs showed that AzA can be used to treat melasma and PIH. 2,3 Aloesin inhibits tyrosinase, tyrosine hydroxylase, and DOPA oxidase. 4 In a single RCT, Choi et al 7 found that aloesin is effective at treating UVR-induced pigmentation both independently as well as synergistically with arbutin. Mulberry is an ROS scavenger with tyrosinase and other melanogenesis inhibitory properties. 8 Alvin et al 11 showed in a RCT that 7% mulberry extract is beneficial in treating melasma. Licorice extract contains liquiritin, which disperses melanin, and glabridin, an ROS scavenger and tyrosinase inhibitor. Multiple RCTs show that licorice extract components have clinical efficacy in treating melasma and UVR- induced pigmentation. 14–16 Lignin peroxidase, which oxidizes and breaks down melanin, can successfully treat mottled hyperpigmentation and facial dyspigmentation according to two RCTs. 17,18 Mauricio et al 18 revealed that lignin peroxidase had more rapid and observable skin-lightening effect compared to HQ or placebo Kojic acid, an ROS scavenger and tyrosinase inhibitor, shows clinical efficacy in treating facial dyschromia and melasma. 20 In a RCT performed by Monteiro et al, 21 kojic acid was found to work better and faster than HQ for treating melasma. Niacinamide, which inhibits the transfer of melanosomes to keratinocytes, has shown clinical efficacy in treating facial and axillary hyperpigmentation in two separate RCTs. 23–25 Ellagic acid is a tyrosinase inhibitor that can successfully treat melasma, as well as hyperpigmentation and dark spots. 27–30 Arbutin, which is also a tyrosinase inhibitor, has been successful in treating melasma according to two RCTs. 31,32 Green tea and turmeric have been studied for their antioxidant properties. 34–37 Interestingly, green tea and turmeric are clinically efficacious in treating melasma and facial hyperpigmentation, respectively. Soy, an anticarcinogen, inhibits melanosome transfer to keratinocytes. Multiple RCTS have shown soy to have promising results in treating facial hypermelanosis, melasma, and facial photodamage. 45–53 Lastly, ascorbic acid's depigmenting mechanism might involve UVA-mediated catalase inactivation, glutathione depletion, oxidant formation, and nitrous oxide production. Ascorbic acid has been shown to successfully treat severe melasma, bilateral epidermal melasma, melasma, and PIH. 54–63 CONCLUSION The number of patients that visit dermatologists with pigmentary disorders is significant. 61,62 Patients are often overwhelmed with numerous over-the-counter skin lightening agents, many without clinical evidence of efficacy. Botanical and natural ingredients have become popular as depigmenting products and provide an alternative to the current gold standard, hydroquinone. However, evidence-based studies on many of these agents is still lacking. Much of the data that exist for these agents consist primarily of in-vitro studies and a handful of clinical trials. Also, many of the in-vivo studies are limited by the short length of the trials, leaving questions regarding long-term efficacy and safety. Despite the need for more long- term, well-designed, randomized, controlled studies, several botanical and natural ingredients do show inital promise in treating disorders of hyperpigmentation based on the results of clinical trials. These ingredients are AA, soy, lignin peroxidase, ascorbic acid iontophoresis, arbutin, ellagic acid, licorice extracts, niacinamide, and mulberry. In addition to showing promise in treating hyperpigmentation, these agents also provide greater insight into the pathogenesis of dyschromias, thus enhancing our understanding of the many complexities of pigment disorders.

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