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Photoprotection via oral or injectable antioxidant shows promise as adjuvant to sun protection, but can’t replace it

“Can’t I just take a pill and forget about the rest of this?” The number-one question of dieters everywhere is a relevant one for dermatologists as well, as their patients would often prefer a use-once-and-forget-it solution to photoprotection. While some antioxidants have shown promise as adjuvant therapies, however, particularly in patients with photosensitive conditions, none have yet demonstrated that they can do more than supplement the protection offered by shade, sun-protective clothing, hats, sunglasses, and sunscreens. Whether taken orally or injected, neither polypodium leucotomos, vitamins C and E, nor injectable afamelanotide has been shown to provide enough protection to replace them.

Polypodium leucotomos

According to Henry W. Lim, MD, chair of the department of dermatology at Henry Ford Hospital and a consultant to Ferndale, which markets it, polypodium leucotomos is the most-studied form of oral photoprotection. “It has a broad level of activity and the thought is that this activity is because of its antioxidant and anti-inflammatory properties,” he said. “We know it is not a typical sunscreen because the sun protection factor is very low for this particular compound.” 

Studies have been conducted to determine whether it could protect against the development of polymorphous light eruption, the most common form of photosensitivity, and solar urticaria, a rarer form of photosensitivity. Those studies have shown that taking the extract of fern plants, which is available as a capsule, orally “would suppress all the effects that are seen with UV exposure,” Dr. Lim said. The minimum erythema dose, the dose of UV radiation that will produce minimally perceptive redness on the skin, increases, as does the minimal phototoxic dose, the minimal dose of light that would induce a phototoxic reaction with psoralens, he said. “The pigment darkening we see following immediate exposure to UVA, where one gets a darkening of the skin, is decreased,” he said. [pagebreak]

Unfortunately, polypodium leucotomos is not the most user-friendly product, according to Zoe Diana Draelos, MD, a clinical and research dermatologist in High Point, N.C., and chair of the AAD Council on Communications. “You have to consume it half an hour before you go outside,” she said. “And then it gets in the skin, but it only lasts half an hour, so you have to continue to eat it.” Its mechanism is sound, she said: “It donates electrons, functioning as an antioxidant, to regenerate vitamin C and vitamin E. The electrons are passed like a hot potato until they reach the reactive oxygen species (ROS). Once the ROS gets an electron it’s no longer reactive and no longer causes damage.”

Still, she said, it’s not a replacement for sunscreens. “For people who have lupus or other photo-sensitizing diseases, this is something they could add to sunscreens to increase their protection so they can have at least a bit of outdoor time,” she said. But patients should be hearing from their dermatologists that clothing is by far the best sun protection, followed by sunscreens, and then oral supplements, she said.

Vitamins C and E, orally

The other method of oral photoprotection that has been studied and published on, according to Dr. Lim, is oral supplementation with vitamins C and E. “Taken orally, they seem to help suppress UV-induced changes in the skin,” he said.

But the best way to get vitamins C and E orally is the old-fashioned way, according to Dr. Draelos: by eating foods that contain them. “When you think about the skin, the most important vitamin in the skin is vitamin E. It is the main electron donor to give electrons to reactive oxygen species to protect the body from DNA damage due to UV radiation,” she said. But because the body stores vitamin E in fat, patients generally don’t need to supplement the limited amount of it they consume via nuts and grains; indeed, too much vitamin E can be harmful, turning it from an antioxidant into a pro-oxidant. [pagebreak]

Instead, she said, patients should be advised to eat a continuous supply of vitamin C through their diets.

“It’s actually very hard to consume a lot of vitamin E, so the human body was designed to run on vitamin C,” she said. “It’s a secondary antioxidant; it donates an electron to vitamin E, which donates an electron to the ROS. And Vitamin C is hugely abundant. It’s in every yellow, orange, and red fruit and vegetable. So what you really want to be sure of is that you have plenty of vitamin C. Because once vitamin E donates an electron, it becomes inactive — but it can become active again if it gets an electron from vitamin C.”

One fruit- and vegetable-filled meal or heroic doses of vitamin C via a supplement will not do the trick, and dermatologists should tell their patients as much, Dr. Draelos said. “The body uses the vitamin C it needs and then flushes the rest down the toilet.” But 10 minutes in the sun can exhaust a fair-skinned person’s reserves of the vitamin, she added. “So people who say, well, I’m going to eat a tomato on Monday and that should provide all the antioxidants I need until next week are misled. You need a continuing source of vitamin C. The best advice for people is that they should eat some fruits and vegetables of every color every day, and preferably several times a day.”

Injectable afamelanotide

Another potential delivery mechanism for photoprotective agents that is being tested is injection of afamelanotide, according to Dr. Lim, who serves as a consultant for Clinuvel, which is working on the product. “This is an injectable medication, an analog of melanocyte-stimulating hormone, which is a natural hormone that we all produce. It results in the tanning of the skin, so it protects the skin from some of the side effects of UIV exposure,” he said. “It also has antioxidant effect which is another potential mechanism for the action of the afamelanotide.” [pagebreak]

Studies so far have been done in erythropoietic protoporphyria and solar urticaria, Dr. Lim said.

“These two conditions were chosen because the action spectrum of both is in the visible light range and we know that typical sunscreens do not block visible light very well, while they do work against UV light. That’s why this is a very potentially helpful addition to our therapeutic options for this group of patients.” Studies are ongoing, with protoporphyria patients receiving intermittent injections and some urticaria patients receiving a single injection.

“There are definitely reasons to try these alternative therapies,” Dr. Draelos said. “But they’re not a replacement for sunscreen, and they don’t allow you to go out all day and forget your sunscreen. Oral photoprotection has a place in certain medical conditions, and patients should consult their dermatologists in those cases to plan out the sun-protection for the particular needs of the individual.” Dr. Lim agreed. “While all of the oral photoprotection regimens are fine to be used as adjuvant treatments, the data does not suggest that they should be used to replace the usual photoprotective measures, such as the use of sunscreens, the use of clothing, the wearing of hats, and putting on sunglasses,” he said. “That package of methods should still be communicated. But this is potentially another addition that can be used to protect the skin.”  [pagebreak]

Vitamins C and E, topically

While supplementing vitamin C and E orally is not a pathway to adequate photoprotection (see article above), the vitamins have a role to play in topical formulations, according to Steven Q. Wang, MD, director of dermatologic surgery and dermatology at Memorial Sloan Kettering Cancer Center at Basking Ridge, N.J.

“UVA generates free radicals, which can damage the cellular membrane and the protein machinery as well as the DNA. In order to neutralize the free radicals, the body has an inherent antioxidant defense mechanism comprised of both enzymatic and non-enzymatic network,” Dr. Wang said. “If there is an excessive amount of free radicals generated by prolonged UV exposure, the innate antioxidants and vitamins can be consumed quickly. So the idea of replenishing them by topical means is of interest.”

Most topical products on the market that tout their vitamin C and E contents don’t actually have either enough of the vitamins or the right forms, Dr. Wang cautioned. Adding antioxidants to sunscreens also creates formulation challenges, he said.

“You need to deliver those vitamins into the skin in order to protect the cells from free radicals,” he said, because antioxidants need to penetrate the stratum corneum. “But in formulating sunscreen, there are competing demands. You want to keep the UV actives out of the skin.” This challenge, he said, may be resolved with nanotechnology. “One can encapsulate vitamin C and vitamin E in separate nanoparticle carriers that can prevent degradation and enhance penetration.”

Currently, the most common example of nanotechnology use in sunscreens, he said, is the use of the nanoparticle TiO2 and zinc oxide. “In the past, if you look back to the 70s and 80s, sunscreens made with inorganic filters actually turn people white. By reducing the size into the micro or nano-size range, the absorption profile of those particles is changed. They no longer absorb visible light spectrum and that reduces the white color. Also, by reducing the size of TiO2 into the 55-60 nm range, you can enhance the UVB protection without making the consumer look white.”

In the future, it may be possible to use similar nanotechnology to deliver more of the right forms of vitamin C and E to the skin to help repair UVA damage, Dr. Wang said. For now, though, the best way to reduce UVA damage is to engage in recommended sun-protection behavior, including a broad-spectrum sunscreen that protects against UVA damage. As he and two co-authors wrote in the Journal of the American Academy of Dermatology in 2012 (67:1013-24), studies have shown that even in products that claim to offer topical antioxidant protection against free radicals, “the radical protection is entirely from the UVA filters in the sunscreens.”

 

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Vitamins C and E, topically