ORLANDO – A two-step regimen of high-potency topical antioxidants followed by a mineral-based sunscreen may help repair light-induced skin damage and protect against new damage in patients with melasma.

Recent studies suggest that the antioxidants tamp down inflammatory cytokines and damage of oxidative stress, Maria Ivonne Arellano-Mendoza, MD, said during a special focus session on Latino skin held at the annual meeting of the American Academy of Dermatology.

“Many compounds are being studied for this purpose,” said Dr. Arellano-Mendoza, head of the dermatology department of the General Hospital of Mexico, Mexico City. “One combination is vitamin C, vitamin E, ubiquinone, and grape-seed extract. This effectively prevented infrared-A radiation–induced matrix metalloproteinase-1 messenger RNA expression in human skin. This combination can be found now in some sunscreens and daily care products.”

Another effective combination seems to be a mixture of ferulic acid, tocopherol, and vitamin C, she said.

The two-step process of regularly using a topical product with antioxidants before applying a sunscreen is all there is for now, she added, because so far it’s been impossible to combine the agents in a single product.

“The challenge will be how to create a product that stays on the surface of the skin to protect it from light, while liberating the antioxidants to penetrate the skin,” she commented.

The antioxidants’ benefits, however, will be obliterated by the continued effects of some light wavelengths that aggravate melasma unless they are used in sequence with a light-scattering sunscreen.

Sunscreens are critical components of a melasma treatment regimen, Dr. Arellano-Mendoza said. “Sunscreens are a cornerstone of treatment. We clearly tell our patients that sunscreens have to be used every day, forever, and if they are not used properly, they will have no improvement.”

Patients with hyperpigmentation disorders are susceptible to longer wavelengths that aren’t covered by chemically derived sunscreens. Longer wavelengths, including infrared light and visible light, have been shown to increase expression of matrix metalloproteinase (MMP) -1 and -9, decrease expression of type 1 procollagen, and can induce macrophage infiltration. These wavelengths also increase reactive oxygen species and proinflammatory cytokines in vitro, Dr. Arellano-Mendoza noted.

Visible light can cause erythema, transient and long-lasting hyperpigmentation, thermal damage, free radical production, and premature photoaging. It also can stimulate the production of reactive oxygen species that can damage DNA.

Mineral-based, inorganic sunscreens, however – like those with titanium dioxide, zinc oxide, and iron oxide – scatter all wavelengths.

“These micronized forms of metal oxides not only scatter and reflect light, they also absorb ultraviolet radiation. The compounds aren’t new,” she said. In 1991, Dr. Elaine Kaye of Harvard University, Boston, and associates described (Arch Dermatol. 1991;127:351-5) opaque physical sunscreens that were useful blockers of visible light and found that transmittance of light can be lowered by adding iron oxide, Dr. Arellano-Mendoza pointed out.

The inorganic sunscreens have never been widely adopted because they are highly pigmented with white or, in the case of iron oxide, with red. “Not many people accepted [the iron-containing compounds] because of the redness, but now different shades are going to be hitting the market soon,” and the hope is that consumers will find them more appealing, she said.

This is good news, as the data emerging around iron oxide are intriguingly positive. A 2015 study showed that a sunscreen with iron oxides prevented melasma relapse during the summer months. Patients were randomized to the same ultraviolet filter topical sunscreen, but for one group, micronized iron oxide was added to it. After 6 months, the median melasma area severity index score was significantly better in the group using the iron oxide compound (J Am Acad Dermatol. 2015 Jan;72[1]:189-90.e1).

Support for the two-step regimen appeared in 2014, when a small study randomized 30 healthy volunteers to an SPF 30 sunscreen or the same sunscreen supplemented with an antioxidant cocktail of grape seed extract, vitamin E, ubiquinone, and vitamin C. The endpoint was MMP-1 upregulation after exposure to infrared-A light. Skin treated with the combination regimen showed significantly lower MMP-1 activation, leading the authors to conclude that the combination of topical antioxidants conferred protection against the irradiation (Photochem Photobiol. 2015 Jan-Feb;91[1]:248-50).

Those same authors published a companion article (Photodermatol Photoimmunol Photomed. 2014;30:167-74) suggesting that another antioxidant mixture (ferulic acid, tocopherol, and vitamin C) was similarly effective.

Using a combination of antioxidants is important, Dr. Arellano-Mendoza said, because different antioxidants work differently. Some (catalase, glutathione peroxidase, and superoxide dismutase) are enzymatic, catalyzing reactions that convert free radicals to oxygen and water. Others terminate free radicals by preventing the propagation of oxidative chain reactions (vitamins A and C, flavonoids, uric acid, bilirubin, albumin, and members of the thiol group). A third group consists of metal-binding proteins that sequester free iron or copper to prevent free radical production (ferritin, transferrin, lactoferrin, and ceruloplasmin).

“I think we can now consider antioxidants a part of the tools we use in treating some pigmentary disorders as melasma,” she said. “We need to choose the compounds carefully, and we definitely need more in vivo research, but the findings are very encouraging.”

Dr. Arellano-Mendoza had no relevant financial disclosures.

This article was updated 3/20/17.

msullivan@frontlinemedcom.com

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Antioxidants plus sunscreens may be two-punch knockout for melasma