Purpose of Review
Systemic photoprotection is an attractive concept; however, its use has been limited by a lack of robust evidence. We performed a review to evaluate the evidence for systemic photoprotection and skin cancer prevention in humans by vitamins C, D and E, carotenoids, nicotinamide, retinoids, polyphenols, Polypodium leucotomos extract, NSAIDs and afamelanotide.
In a randomized controlled trial, compared with placebo, a 13% reduction in actinic keratoses and a 23% reduction in keratinocyte carcinoma were found with continued nicotinamide use over 12 months, although the result should be interpreted with caution. A synthetic melanotropin, Nle4-D-Phe7-a-MSH, showed promising results in photoprotection but was limited by its side effect profile.
Various photoprotective agents have shown promise in the reduction of the acute response to UV radiation, but there is insufficient evidence for their mainstream use presently. There is evidence for keratinocyte skin cancer prevention with the use of retinoids and nicotinamide in certain populations.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Stahl W, Sies H. β-Carotene and other carotenoids in protection from sunlight. Am J Clin Nutr. 2012;96(5):1179S–84S.
Fernández-García E. Skin protection against UV light by dietary antioxidants. Food Funct. 2014;5(9):1994–2003.
González S, Pathak M, Cuevas J, Villarrubia V, Fitzpatrick T. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin. Photodermatol Photoimmunol Photomed. 1997;13(1–2):50–60.
Middelkamp-Hup MAPM, Parrado C, Goukassian D, Rius-Diaz F, Mihm MC, et al. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. J Am Acad Dermatol. 2004;51(6):910–8.
Stahl WSH. Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future development. Mol Nutr Food Res. 2012;56(2):287–95.
Parrado CPN, Gilaberte Y, Juarranz A, Gonzalez S. Oral photoprotection: effective agents and potential candidates. Front Med. 2018;5:188.
Mireles-Rocha HGI, Huerta M, Trujilloherna B, Elizalde A, Cortes-Franco R. UVB photoprotection with antioxidants: effects of oral therapy with d-a-tocopherol and ascorbic acid on the minimal erythema dose. Acta Derm Venereol. 2002;82:21–4.
Eberlein-König BPM, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-a-tocopherol (vitamin E). J Am Acad Dermatol. 1998;38(1):45–8.
Fuchs JKH. Modulation of UV-light-induced skin inflammation by d-alpha-tocopherol and l-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med. 1998;25(9):1006–12.
Mason RSRJ. Sunlight vitamin D and skin cancer. Anti Cancer Agents Med Chem. 2013;13(1):83–97.
Scott JF, Das LM, Ahsanuddin S, Qiu Y, Binko AM, Traylor ZP, et al. Oral vitamin D rapidly attenuates inflammation from sunburn: an interventional study. J Invest Dermatol. 2017;137(10):2078–86.
Chang YJ, Myung SK, Chung ST, Kim Y, Lee EH, Jeon YJ, et al. Effects of vitamin treatment or supplements with purported antioxidant properties on skin cancer prevention: a meta-analysis of randomized controlled trials. Dermatology. 2011;223(1):36–44.
Bardia A, Tleyjeh IM, Cerhan JR, Sood AK, Limburg PJ, Erwin PJ, et al. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 2008;83(1):23–34.
Chang YJMS, Chung ST, Kim Y, Lee EH, Jeon YJ, et al. Effects of vitamin treatment or supplements with purported antioxidant properties on skin cancer prevention: a meta-analysis of randomized controlled trials. Dermatology. 2011;223(1):36–44.
Balwani M, Desnick RJ. The porphyrias: advances in diagnosis and treatment. Blood. 2012;120(23):4496–504.
Mathews-Roth MM, Pathak MA, Parrish J, Fitzpatrick TB, Kass EH, Toda K, et al. A clinical trial of the effects of oral beta-carotene on the responses of human skin to solar radiation. J Invest Dermatol. 1972;59(4):349–53.
Carrascosa JM, Floriach N, Sala E, Aguilera J. Increase in minimal erythemal dose following oral administration of an antioxidant complex based on a mix of carotenoids: double-blind, placebo-controlled trial. Photodermatol Photoimmunol Photomed. 2017;33(5):284–6.
Omenn GSGG, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334(18):1150–5.
Heinonen OPHJ, Albanes D, Haapakoski J, Palmgren J, Pietinen P. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330(15):1029–35.
Green AWG, Nèale R, Hart V, Leslie D, Parsons P, et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet. 1999;354(9180):723–9.
Frieling UMSD, Kupper TS, Muntwyler J, Hennekens CH. A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician’s health study. Arch Dermatol. 2000;2:179–84.
Greenberg ERBJ, Stukel TA, Stevens MM, Mandel JS, Spencer SK, et al. A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. N Engl J Med. 1991;323(12):789–95.
Stahl WHU, Wiseman S, Eichler O, Sies H, Tronnier H. Dietary tomato paste protects against ultraviolet light–induced erythema in humans. J Nutr. 2001;131(5):1449–51.
Aust O, Stahl W, Sies H, Tronnier H, Heinrich U. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res. 2005;75(1):54–60.
Juturu V, Bowman JP, Deshpande J. Overall skin tone and skin-lightening-improving effects with oral supplementation of lutein and zeaxanthin isomers: a double-blind, placebo-controlled clinical trial. Clin Cosmet Investig Dermatol. 2016;9:325–32.
Nishino A, Sugimoto K, Sambe H, Ichihara T, Takaha T, Kuriki T. Effects of dietary paprika xanthophylls on ultraviolet light-induced skin damage: a double-blind placebo-controlled study. J Oleo Sci. 2018;67(7):863–9.
Roberts RL, Green J, Lewis B. Lutein and zeaxanthin in eye and skin health. Clin Dermatol. 2009;27(2):195–201.
Chen AC, Martin AJ, Choy B, Fernandez-Penas P, Dalziell RA, McKenzie CA, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373(17):1618–26.
Gilmore SJ. Nicotinamide and skin cancer chemoprevention: the jury is still out. Australas J Dermatol. 2018;59(1):6–9.
Chen AC, Martin AJ, Dalziell RA, McKenzie CA, Lowe PM, Eris JM, et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J Dermatol. 2016;175(5):1073–5.
Drago F, Ciccarese G, Cogorno L, Calvi C, Marsano LA, Parodi A. Prevention of non-melanoma skin cancers with nicotinamide in transplant recipients: a case-control study. Eur J Dermatol. 2017;27(4):382–5.
Yiasemides E, Sivapirabu G, Halliday GM, Park J, Damian DL. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis. 2009;30(1):101–5.
George RWW, Russ G, Bannister K, Mathew T. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol. 2002;43:269–73.
Chen AC, Damian DL, Halliday GM. Oral and systemic photoprotection. Photodermatol Photoimmunol Photomed. 2014;30(2–3):102–11.
Bavinck JNTL, Van Der Woude FJ, Tegzess AM, Hermans J, ter Schegget J, et al. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind. Placebo-Controlled Study J Clin Oncol. 1995;13(8):1933–8.
De Sévaux RGSJ, De Jong EM, Van de Kerkhof PC, Hoitsma AJ. Acitretin treatment of premalignant and malignant skin disorders in renal transplant recipients: clinical effects of a randomized trial comparing two doses of acitretin. J Am Acad Dermatol. 2003;49(3):407–12.
Kadakia KC, Barton DL, Loprinzi CL, Sloan JA, Otley CC, Diekmann BB, et al. Randomized controlled trial of acitretin versus placebo in patients at high-risk for basal cell or squamous cell carcinoma of the skin (North Central Cancer Treatment Group Study 969251). Cancer. 2012;118(8):2128–37.
Heinrich UNK, Tronnier H, Sies H, Stahl W. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women. J Nutr. 2006;136(6):1565–9.
Perez-Sanchez A, Barrajon-Catalan E, Caturla N, Castillo J, Benavente-Garcia O, Alcaraz M, et al. Protective effects of citrus and rosemary extracts on UV-induced damage in skin cell model and human volunteers. J Photochem Photobiol B. 2014;136:12–8.
Farrar MD, Nicolaou A, Clarke KA, Mason S, Massey KA, Dew TP, et al. A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation. Am J Clin Nutr. 2015;102(3):608–15.
Farrar MD, Huq R, Mason S, Nicolaou A, Clarke KA, Dew TP, et al. Oral green tea catechins do not provide photoprotection from direct DNA damage induced by higher dose solar simulated radiation: a randomized controlled trial. J Am Acad Dermatol. 2018;78(2):414–6.
Lim HW A-MM, Stengel F. Current challenges in photoprotection. J Am Acad Dermatol. 2017;76(3S1):S91-S9.
Kohli I, Shafi R, Isedeh P, Griffith JL, Al-Jamal MS, Silpa-Archa N, et al. The impact of oral Polypodium leucotomos extract on ultraviolet B response: a human clinical study. J Am Acad Dermatol. 2017;77(1):33–41 e1.
Aguilera PCC, Puig-Butille JA, Badenas C, Lecha M, Gonzalez S, et al. Benefits of oral Polypodium Leucotomos extract in MM high-risk patients. J Eur Acad Dermatol Venereol. 2013;27(9):1095–100.
Nestor MBB, Swenson N. Safety and efficacy of oral Polypodium leucotomos extract in healthy adult subjects. J Clin Aesthet Dermatol. 2015;8(2):19–23.
Muranushi COC, Green AC, Pandeya N. Can oral nonsteroidal antiinflammatory drugs play a role in the prevention of basal cell carcinoma? A systematic review and metaanalysis. J Am Acad Dermatol. 2016;74(1):108–19.
Zhu Y, Cheng Y, Luo RC, Li AM. Aspirin for the primary prevention of skin cancer: a meta-analysis. Oncol Lett. 2015;9(3):1073–80.
Zhang BLX, Ye L, Wang Y. No chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancer: evidence from meta-analysis. PLoS One. 2014;9(5):e96887.
Elmets CA, Viner JL, Pentland AP, Cantrell W, Lin HY, Bailey H, et al. Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2010;102(24):1835–44.
Torti DCCB, Storm CA, Fortuny J, Perry AE, Zens MS, et al. Analgesic and nonsteroidal anti-inflammatory use in relation to nonmelanoma skin cancer: a population-based case-control study. J Am Acad Dermatol. 2011;65(2):304–12.
Pandeya N, Olsen CM, Thompson BS, Dusingize JC, Neale RE, Green AC, et al. Aspirin and nonsteroidal anti-inflammatory drug use and keratinocyte cancers: a large population-based cohort study of skin cancer in Australia. Br J Dermatol. 2019;181(4):749–60.
Szeto CC, Sugano K, Wang JG, Fujimoto K, Whittle S, Modi GK, et al. Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations. Gut. 2020;69:617–29.
Barnetson RS, Ooi TK, Zhuang L, Halliday GM, Reid CM, Walker PC, et al. [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers. J Invest Dermatol. 2006;126(8):1869–78.
Jennifer Taylor is supported by the Krembil Foundation, Canada.
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Photodermatology
About this article
Cite this article
Taylor, J.H., Rosen, C.F. Systemic Photoprotection. Curr Derm Rep (2020). https://doi.org/10.1007/s13671-020-00306-1
- Systemic photoprotection
- Oral photo protection
- Polypodium leucotomos extract