Topical Retinyl Palmitate May Increase Risk of Ultraviolet Radiation-Induced Skin Cancer

by | Sep 9, 2019 | 2017, Cancer, Skin Health, Vitamin A

Written by Angeline A. De Leon, Staff Writer. Compared to the control cream groups, mice who were exposed to SSL and were administered the retinyl palmitate creams developed skin tumors earlier and had increased incidences of multiple squamous cell skin neoplasms.

vitamin D - sunSkin is highly sensitive to vitamin A and the various compounds derived from it, the dermis and epidermis containing endogenous vitamin A and retinyl esters as well as their metabolites 1,2. Studies on ultraviolet radiation (UVR) indicate that vitamin A and its esters are photosensitive, particularly to UVR with wavelengths between 300 and 350 nm 3. Upon UVR exposure, endogenous vitamin A and its retinal esters become depleted, leading to aging of the skin and potentially, certain forms of skin cancer 4,5. UVR-induced depletion of vitamin A is also accompanied by formation of reactive oxygen species (ROS) and cellular damage 6. Retinyl palmitate, the primary form in which vitamin A is stored in the epidermis of the skin, is commonly included in cosmetic products and anti-aging skin treatments, however, evidence suggests that topical application of retinyl palmitate, in the presence of UVR exposure, may increase risk of skin tumor development 7,8. In a 2017 study published in Photochemistry and Photobiology, researchers tested the photo-toxicology of retinyl palmitate, examining the effects of topical application on UVR-induced photo-carcinogenesis in a mouse model.

A group of 72 7-week-old male and female SKH-1hairless mice were irradiated with UVR emitted from a simulated solar light (SSL) source daily 5 days per week for 40 weeks. Another group of 72 mice were treated using the same protocol except using light emitted from UVA or UVB lamps. All groups received 75 µL of control cream, retinyl palmitate cream (0.1, 0.5, 1.0, or 2.0%), or no cream at all. Following a 12-week recovery/observation period, mice were euthanized and digitally photographed for skin trace gross lesions (TGLs). Samples of skin were removed and fixed, and TGLs were microscopically examined and identified as either neoplastic (abnormal cell growth) or non-neoplastic and further classified by type of skin neoplasm. Period of latency to skin lesion onset was also recorded for each mouse over the course of the study.

Test results revealed that daily application of retinyl palmitate cream (at all dose levels), relative to control cream, significantly reduced the survival time of mice exposed to the same level of SSL (Hazard Ratio > 1.00; p < 0.05 for all). In the presence of SSL irradiation, onset time of skin lesions occurred earlier for mice receiving retinyl palmitate (at doses of 1.0% and 2.0%), in comparison to control mice (p < 0.05 for all). Researchers also observed significantly higher incidences of squamous cell carcinoma in mice exposed to SSL at a dose of 6.85 mJ cm-2 and treated with 0.5% retinyl palmitate (p = 0.002 for females, p = 0.030 for males). Finally, a significant dose-related increase was detected in the multiplicities of squamous cell papilloma and in total squamous cell neoplasms for mice treated with retinyl palmitate (at doses of 0.1% and 0.5%) and exposed to SSL at doses of 6.85 and 13.70 mJ cm-2 (p < 0.001 for all).

Findings from the study demonstrate that topical application of retinyl palmitate may augment the carcinogenic effects associated with exposure to UVR sources. Histopathological tests indicated that SSL-exposed mice treated with 0.1% and 0.5% retinol palmitate incurred a higher incidence and multiplicity of squamous cell neoplasms. At higher doses (1.0% and 2.0%), retinyl palmitate was also associated with earlier onset of skin lesions, and across all doses, appeared to significantly reduce average survival time of mice exposed to SSL. Evidence suggests that topical application of cosmetic creams containing retinyl palmitate may increase the likelihood of skin cancer in the presence of UVR. Additional studies are needed to confirm findings in human subjects, however, current results call to question the potential health benefits vs. costs of using dermatological products containing retinyl palmitate for cosmetic and other anti-aging treatments.

Source: Boundreau MD, Beland FA, Felton RP, et al. Photo-co-carcinogenesis of topically applied retinyl palmitate in SKH-1 hairless mice. Photochemistry and Photobiology. 2017; 93: 1096-1114. DOI: 10.1111/php.12730.

 Posted September 9, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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