The Skin Cancer Foundation Journal

MAY 2015

The 2012 edition of The Skin Cancer Foundation Journal features medically reviewed, reader-friendly articles such as tanning, the increasing incidence of skin cancer diagnoses among young women, & the prevalence of melanoma among white males over 50.

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Page 34 of 115

PRECEDENTS FOR RETINOIDS The earliest account of vitamin A application dates back to ancient Egypt 3,500 years ago. In the US, dermatologists began using tretinoin (retinoic acid) as an acne treatment decades ago. 3 The treated patients were noted to have fewer wrinkles and smoother skin tone. Today, in our practice, new patients are instructed to apply a retinol or another retinoid product as part of their regular skin care regimen. Vitamin A is also essential for healthy eyes, teeth and bones, as well as skin. In addition to being applied topically, it may be acquired through dietary sources such as animal products (e.g., liver and eggs) and plants (e.g., carrots and spinach). Once absorbed, it is converted to retinol, which is transported to the tissues, including the skin, where it is stored as retinyl palmitate until needed. Most of the skin's supply of vitamin A is stored in this form. When needed, it is converted to its meta- bolically active form, retinoic acid. 1,4 While vitamin A from our diet serves most of the aforementioned physiological purposes, it is the topical derivatives of the vitamin that serve most of the therapeutic purposes for the skin. Luckily, there are many choices, which differ in potency (e.g., 0.25% vs. 0.5% concen- trations), delivery method (e.g., gel or cream), and their ability to act immediately. 1 The OTC preparations, such as the compounds typically found in cosmeceuticals, most commonly contain retinol, whereas prescription strength retinoids contain retinoic acid, the active form of vitamin A. Because retinol and other precursors of retinoic acid have to be con- verted in the skin to retinoic acid to become active and have a therapeutic effect, they work less immediately and are much less potent; basically, your skin has to do some work first to oxidize the precursor into retinoic acid. Meanwhile, prescription retinoic acid/tretinoin is active from the start and immediately available for your skin to reap the benefits. 4 [See Table 1 on pg.34] RETINYL PALMITATE: TEMPEST IN A TEAPOT? One particular derivative of vitamin A, retinyl palmitate (RP), has been the eye of the storm of recent sunscreen controversies. It is used in minute amounts as a kind of preservative in sunscreens to help keep their active ingredi- ents from breaking down in the sun. RP is also naturally occurring in many foods, as well as in our liver and skin, as the main stored formed of vitamin A. Given how much of it we already naturally encounter, it came as some surprise a few years back when the Envi- ronmental Working Group (EWG), a consumer watchdog, classified the tiny trace amounts of RP in many sunscreens as a potential carcino- gen. The EWG claimed--and still claims-–that the RP in sunscreens might lead to skin cancers when exposed to ultraviolet light. The furor raised by the EWG on this issue prompted sensational media coverage frightening consumers with questions like, "Is your sunscreen giving you skin cancer?" THE REAL STORY The EWG based this alleged effect of RP on its own interpretation of research performed by the National Toxicology Program (NTP), a fed- erally funded program that evaluates the human health effects of chemical agents in our environment ( The NTP performed tests on laboratory mice, applying various strengths of retinyl palmitate and irradiating the mice with varying doses of artificial ultraviolet radiation. However, it is curious that they particularly targeted retinyl palmitate, since it is the natural way in which vitamin A is stored in the skin, and since it is a natural antioxidant that functions as protection against damaging molecules called free radicals. It normally works alongside other antioxidant vitamins such as C and E, and non-vitamin antioxidants like glutathiones and catalases. All these substances work as a team to protect the skin against free radicals. What the NTP studied was not a team of antioxidants, but a lone player. Without the insulation from its counterparts, retinyl palmitate when damaged by ultraviolet radiation might indeed promote the activation of free radicals that can promote carcinogenesis. 5-7 However, that is not the way it works, either in nature or in sunscreens. No study in humans has ever shown that retinyl pal- mitate is a carcinogen in humans. Nor did the NTP data show conclusive evidence that RP exposed to UV light is cancer-causing even in mice. The trace amount of retinyl palmitate used in most sunscreens is a minute fraction of the amount that was used in the study (0.1 grams per oz in the study compared to 0.0000029 grams per oz. in a sample sunscreen), and despite this, only one group of the four RP-treated test mice showed a statistical difference in the formation of skin tumors compared to its counterpart treated with a placebo cream. 8 Furthermore, the particular strain of mice used for these studies was highly susceptible to forming skin cancers after UV exposure. In fact, many of the study mice treated with the placebo cream also developed both benign and malignant skin tumors. 5 Another deficiency in the study: the researchers did not determine whether a sunscreen containing retinyl palmitate applied prior to ultraviolet exposure pre- vented the development of tumors. In the end, the data in the study were con- sidered so weak that they were never peer-re- viewed and never published. So, in short, the EWG based its alarms to humans on a much- flawed, unpublished rodent study. 33 A They are among the great anti-aging tools of the past several decades, yet some critics consider them a threat. What's the reality?

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