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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28 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2 R E V I E W D Disorders of hyperpigmentation such as melasma and post-inflammatory hyperpigmentation are common reasons for visits to dermatology practices. Dyschromias can occur due to alterations in the various biochemical processes that regulate melanogenesis. Such alterations might lead to an increase in melanocytes, melanosome production, melanin synthesis, or melanocyte hyperplasias, which cause more melanin deposition in the skin. Research exploring the pathophysiology of hyperpigmentation disorders has expanded greatly over the past decade, leading to the investigation and development of a number of skin lighteners. Botanical and other naturally occurring ingredients for the treatment of pigment disorders have gained increasing popularity. Despite their increasing use, many lack in-vivo and/or in-vitro studies to validate their efficacy. The objective of this review is to examine the literary evidence supporting the clinical utility of natural ingredients in the treatment of hyperpigmentation. METHODS In March 2016, systematic searches of PubMed and SCOPUS databases were performed using "melasma," "hyperpigmentation," and the following ingredient names: "azelaic acid," "aloesin," "mulberry," "licorice extracts," "lignin peroxidase," "kojic acid," "niacinamide," "ellagic acid," "arbutin," "green tea," "turmeric", "soy," and "ascorbic acid." Only clinical studies that evaluated the effect of herbal and natural supplements on pigmentation disorders were included. Two reviewers independently screened titles, leading to the selection of 30 clinical studies based on inclusion criteria. RESULTS Studies that met inclusion criteria are summarized in Table 1. DISCUSSION Azelaic acid. Azelaic acid (AzA) is a saturated 9-carbon dicarboxylic acid derived from the fungus Pityrosporum ovale and can be found in rye, wheat, and barley. Azelaic acid interferes with deoxyribonucleic acid (DNA) synthesis, inhibits mitochondrial oxidoreductase, competitively inhibits tyrosinase, and decreases free radical formation. This agent preferentially targets abnormal and highly active melanocytes with minimal effect on uninvolved skin. 1,2 Most clinical trials study azelaic acid as an acne treatment. However, one recent open-label clinical trial performed over two months compared 20% azelaic acid to 4% hydroquinone cream in 29 melasma patients. Based on Melasma Area Severity Index (MASI) scores used to quantify treatment response, the authors concluded that melasma pigmentation was improved more in those using azelaic acid A B S T R A C T BACKGROUND: Hyperpigmentation disorders are commonly encountered in dermatology clinics. Botanical and natural ingredients have gained popularity as alternative depigmenting products. OBJECTIVE: We sought to review clinical studies evaluating the use of different natural products in treating hyperpigmentation so clinicians are better equipped to educate their patients. Specific ingredients reviewed include azelaic acid, aloesin, mulberry, licorice extracts, lignin peroxidase, kojic acid, niacinamide, ellagic acid, arbutin, green tea, turmeric, soy, and ascorbic acid. METHODS: Systematic searches of PubMed and SCOPUS databases were performed in March 2016 using the various ingredient names, "melasma"and "hyperpigmentation." Two reviewers independently screened titles, leading to the selection of 30 clinical studies. RESULTS: Review of the literature revealed few clinical trials that evaluated the treatment of hyperpigmentation with natural ingredients. Despite the limited evidence-based research, several natural ingredients did show efficacy as depigmenting agents, including azelaic acid, soy, lignin peroxidase, ascorbic acid iontophoresis, arbutin, ellagic acid, licorice extracts, niacinamide, and mulberry. CONCLUSION: The aforementioned ingredients show promise as natural treatments for patients with hyperpigmentation disorders. These agents might also provide clinicians and researchers with a way to further characterize the pathogenesis of dyschromia. However, the paucity of clinical studies is certainly a limitation. Additionally, many of the in-vivo studies are limited by the short length of the trials, and questions remain about the long-term efficacy and safety of the ingredients used in these studies. Lastly, we suggest a standardized objective scoring system be implemented in any further comparative studies. KEYWORDS: melasma, hyperpigmentation, natural ingredients Are Natural Ingredients Effective in the Management of Hyperpigmentation? A Systematic Review by JASMINE C. HOLLINGER, MD; KUNAL ANGRA, MD; and REBAT M. HALDER, MD Dr. Hollinger is with the Department of Dermatology, University of Mississippi Medical Center in Jackson, Mississippi. Drs. Angra and Halder are with the Department of Dermatology, Howard University College of Medicine in Washington, DC. J Clin Aesthet Dermatol. 2018;11(2):28–37 FUNDING: No funding was provided for this article. DISCLOSURES: The authors have no conflicts of interest to relevant to the content of this article. CORRESPONDENCE: Jasmine C. Hollinger, MD; Email:

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