COMMENTARY
Is Topical Zinc Effective in the Treatment of Melasma? ZOE D. DRAELOS, MD*
The author has indicated no significant interest with commercial supporters.
Z
inc plays an interesting role in the health of the skin, with approximately 11% of the body’s zinc reserve residing in the epidermis. It is an important trace mineral, with a recommended daily allowance (RDA) set at 11 mg for men and 8 mg for women.1 There are approximately 300 zinc-dependent enzymes that have been identified in the body, and zinc is a dominant cofactor in wound healing. Zinc binding proteins, known as metallothioneins with 30% cysteine, are storage proteins upregulated in wound healing. The U.S. Food and Drug Administration (FDA) has approved several zinc compounds for topical use, including zinc acetate, zinc gluconate, and zinc oxide. Zinc oxide is recognized in the skin-protectant monograph and as an inorganic sunscreen. The age-old topical astringent calamine is zinc oxide (ZnO) combined with ferric oxide (Fe2O3). Other zinc preparations in the marketplace include zinc pyrithione,2 found in dandruff shampoos, and zinc undecylenate,3 used as an antifungal agent. There are no topical zinc-based products marketed for skin lightening in the cosmetic or pharmaceutical realm. The article by Alireza and colleagues4 compares the value of a 10% zinc sulfate solution containing 90% water and 10% propylene glycol with that of a 4% hydroquinone solution containing 70% alcohol, 20% water, and 10% propylene glycol applied
nightly in the treatment of facial melasma. All subjects used a sunscreen with a sun protection factor of 60 after application. Alireza and colleagues’ research found that the zinc sulfate solution was ineffective in the treatment of melasma. It is unclear why zinc sulfate would be considered as a melasma treatment, given the lack of zinc in the melanin synthesis pathway, but perhaps it was theorized that the antiinflammatory effects of zinc might have reduced some inflammation that might have led to a worsening of postinflammatory hyperpigmentation that might be overlying facial melasma. The impetus for their research might have been an article published in 2008 in Dermatologic Surgery by Sharquie and colleagues that examined a similar 10% zinc sulfate solution with positive reported results.5 Sharquie used the zinc solution with sunscreen in an uncontrolled study of 28 subjects. This points to an important deficiency in how skin lightening studies are conducted and the results evaluated. When a skin lightening formulation is tested with sunscreen, it may be the sunscreen that is functioning as the active and the test formulation as the inactive. Furthermore, instructions to avoid sun exposure or beginning the study in late summer and ending in early winter might produce skin lightening independent of the applied treatment. Without a control group,
*Consulting Professor, Department of Dermatology, Duke University School of Medicine, Durham, North Carolina © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:38–39 DOI: 10.1111/dsu.12257 38
DRAELOS
using sunscreen alone or another comparator known to be efficacious such as hydroquinone, it is impossible to interpret positive pigment lightening results, which means that dermatologists should insist that cosmetic product studies designed to demonstrate efficacy adhere to the same standards as pharmaceutical research. The authors have added to the dermatologic knowledge of pigment lightening by attempting to replicate the work of prior researchers but adding a control group that used sunscreen and a known pigment lightener. Even though their findings were negative, they have added insight, accounting for the publication of this article. Perhaps the value of negative articles should be reconsidered, especially when they refute previously published work. The dermatologic skin care literature is full of pilot studies ending with the statement that “further work is needed to validate the results.” Unfortunately, when the additional work of other researchers is negative, the manuscript is not published, and the pilot study stands unrefuted.
This is a publishing challenge that merits additional consideration.
References 1. Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowell MA. Zinc intake of the US population. J Nutr 2000;130:1367S–73S. 2. Marks R, Pearse AD, Walker AP. The effects of a shampoo containing zinc pyrithione on the control of dandruff. Br J Dermatol 1985;112:415–22. 3. Chretien JH, Esswein JG, Sharpe LM, Kiely JJ, et al. Efficacy of undecylenic acid-zinc undecylenate powder in culture positive tinea pedis. Int J Dermatol 1980;19:51–4. 4. Yousefi A, Khoozani ZK, Foroshani SZ, Omrani N, et al. Is topical zinc effective in the treatment of melasma? A double-blinded randomized comparative study. Dermatol Surg 2014;40:43–7. 5. Sharquie KE, Al-Mashhadani SA, Salman HA. Topical 10% zinc sulfate solution for treatment of melasma. Dermatol Surg 2008;34:1346–9.
Address correspondence and reprint requests to: Zoe Diana Draelos, MD, Dermatology Consulting Services, 2444 North Main Street, High Point, NC 27262, or e-mail: [email protected]
40:1:JANUARY 2014
39
Is Topical Zinc Effective in the Treatment of Melasma? ZOE D. DRAELOS, MD*
The author has indicated no significant interest with commercial supporters.
Z
inc plays an interesting role in the health of the skin, with approximately 11% of the body’s zinc reserve residing in the epidermis. It is an important trace mineral, with a recommended daily allowance (RDA) set at 11 mg for men and 8 mg for women.1 There are approximately 300 zinc-dependent enzymes that have been identified in the body, and zinc is a dominant cofactor in wound healing. Zinc binding proteins, known as metallothioneins with 30% cysteine, are storage proteins upregulated in wound healing. The U.S. Food and Drug Administration (FDA) has approved several zinc compounds for topical use, including zinc acetate, zinc gluconate, and zinc oxide. Zinc oxide is recognized in the skin-protectant monograph and as an inorganic sunscreen. The age-old topical astringent calamine is zinc oxide (ZnO) combined with ferric oxide (Fe2O3). Other zinc preparations in the marketplace include zinc pyrithione,2 found in dandruff shampoos, and zinc undecylenate,3 used as an antifungal agent. There are no topical zinc-based products marketed for skin lightening in the cosmetic or pharmaceutical realm. The article by Alireza and colleagues4 compares the value of a 10% zinc sulfate solution containing 90% water and 10% propylene glycol with that of a 4% hydroquinone solution containing 70% alcohol, 20% water, and 10% propylene glycol applied
nightly in the treatment of facial melasma. All subjects used a sunscreen with a sun protection factor of 60 after application. Alireza and colleagues’ research found that the zinc sulfate solution was ineffective in the treatment of melasma. It is unclear why zinc sulfate would be considered as a melasma treatment, given the lack of zinc in the melanin synthesis pathway, but perhaps it was theorized that the antiinflammatory effects of zinc might have reduced some inflammation that might have led to a worsening of postinflammatory hyperpigmentation that might be overlying facial melasma. The impetus for their research might have been an article published in 2008 in Dermatologic Surgery by Sharquie and colleagues that examined a similar 10% zinc sulfate solution with positive reported results.5 Sharquie used the zinc solution with sunscreen in an uncontrolled study of 28 subjects. This points to an important deficiency in how skin lightening studies are conducted and the results evaluated. When a skin lightening formulation is tested with sunscreen, it may be the sunscreen that is functioning as the active and the test formulation as the inactive. Furthermore, instructions to avoid sun exposure or beginning the study in late summer and ending in early winter might produce skin lightening independent of the applied treatment. Without a control group,
*Consulting Professor, Department of Dermatology, Duke University School of Medicine, Durham, North Carolina © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:38–39 DOI: 10.1111/dsu.12257 38
DRAELOS
using sunscreen alone or another comparator known to be efficacious such as hydroquinone, it is impossible to interpret positive pigment lightening results, which means that dermatologists should insist that cosmetic product studies designed to demonstrate efficacy adhere to the same standards as pharmaceutical research. The authors have added to the dermatologic knowledge of pigment lightening by attempting to replicate the work of prior researchers but adding a control group that used sunscreen and a known pigment lightener. Even though their findings were negative, they have added insight, accounting for the publication of this article. Perhaps the value of negative articles should be reconsidered, especially when they refute previously published work. The dermatologic skin care literature is full of pilot studies ending with the statement that “further work is needed to validate the results.” Unfortunately, when the additional work of other researchers is negative, the manuscript is not published, and the pilot study stands unrefuted.
This is a publishing challenge that merits additional consideration.
References 1. Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowell MA. Zinc intake of the US population. J Nutr 2000;130:1367S–73S. 2. Marks R, Pearse AD, Walker AP. The effects of a shampoo containing zinc pyrithione on the control of dandruff. Br J Dermatol 1985;112:415–22. 3. Chretien JH, Esswein JG, Sharpe LM, Kiely JJ, et al. Efficacy of undecylenic acid-zinc undecylenate powder in culture positive tinea pedis. Int J Dermatol 1980;19:51–4. 4. Yousefi A, Khoozani ZK, Foroshani SZ, Omrani N, et al. Is topical zinc effective in the treatment of melasma? A double-blinded randomized comparative study. Dermatol Surg 2014;40:43–7. 5. Sharquie KE, Al-Mashhadani SA, Salman HA. Topical 10% zinc sulfate solution for treatment of melasma. Dermatol Surg 2008;34:1346–9.
Address correspondence and reprint requests to: Zoe Diana Draelos, MD, Dermatology Consulting Services, 2444 North Main Street, High Point, NC 27262, or e-mail: [email protected]
40:1:JANUARY 2014
39
