Oral green tea catechins do not provide photoprotection from direct DNA damage induced by higher dose solar simulated radiation: A randomized controlled trial
Authors: Mark D. Farrar, Raqib Huq, Sarah Mason, Anna Nicolaou, Kayleigh A. Clarke, Tristan P. Dew, Gary Williamson, Rachel E.B. Watson, Lesley E. Rhodes
Journal: Journal of the American Academy of Dermatology (2018)

To the Editor: Exposure to ultraviolet radiation (UVR) in sunlight is the principal cause of most skin cancers. Despite topical sunscreen availability, skin cancer incidence continues to rise with substantial financial burden to health care. Systemic photoprotection through safe dietary means has gained interest. Green tea catechins (GTC) administered topically or orally are chemopreventive in mouse models of UVR-induced skin cancer, potentially through reduced DNA damage or enhanced DNA repair.1Nichols J.A. Katiyar S.K. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.Arch Dermatol Res. 2010; 302: 71-83Crossref PubMed Scopus (724) Google Scholar Topical GTC protected against UVR-induced cyclobutane pyrimidine dimers (CPD) in human skin,2Katiyar S.K. Perez A. Mukhtar H. Green tea polyphenol treatment to human skin prevents formation of UV light B-induced pyrimidine dimers in DNA.Clin Cancer Res. 2000; 6: 3864-3869PubMed Google Scholar but no information exists regarding the impact of oral GTC in humans. We performed a double-blind, randomized, placebo-controlled trial in healthy white adults (13 male and 37 female; 18-65 years of age; Fitzpatrick skin phototypes I and II) who received 1080 mg GTC (equivalent to 5 cups/day) with 100 mg vitamin C (n = 25) or placebo maltodextrin (n = 25) daily for 12 weeks.3Farrar M.D. Nicolaou A. Clarke K.A. et al.A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation.Am J Clin Nutr. 2015; 102: 608-615Crossref PubMed Scopus (40) Google Scholar Vitamin C was used as previously3Farrar M.D. Nicolaou A. Clarke K.A. et al.A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation.Am J Clin Nutr. 2015; 102: 608-615Crossref PubMed Scopus (40) Google Scholar to stabilize GTC in the gut lumen.4Chen Z. Zhu Q.Y. Wong Y.F. et al.Stabilizing effect of ascorbic acid on green tea catechins.J Agric Food Chem. 1998; 46: 2512-2516Crossref Scopus (140) Google Scholar A high dose proinflammatory (3 × minimal erythema dose [MED]) challenge with solar simulated UVR (5% UVB, 95% UVA) was applied to buttock skin pre- and postsupplementation. Immunohistochemical staining with CPD-positive cell quantification was performed in skin samples taken 24 hours after UVR exposure. In a further, before-after time-course pilot study, 5 subjects (2 male and 3 female; 21-31 years of age, Fitzpatrick skin phototype II) received GTC with vitamin C for 4 weeks with UVR-induced (2MED) CPD assessed pre- and postsupplementation. Urinary epigallocatechin glucuronide analysis assessed compliance.3Farrar M.D. Nicolaou A. Clarke K.A. et al.A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation.Am J Clin Nutr. 2015; 102: 608-615Crossref PubMed Scopus (40) Google Scholar CPD-positive cells/1000 μm2 in UVR-irradiated epidermis postsupplementation was compared between active and placebo groups by analysis of covariance with baseline data as the covariate. UVR induced CPD-positive cells in the epidermis and to a much lesser extent the dermis (Fig 1). Following the 12-week intervention, there was no difference between active and placebo groups in number of CPD-positive cells in UVR-irradiated epidermis at 24 hours (P = .81; Fig 1), the active group showing mean (SD) 3.4 (1.3) cells/1000 μm2 at both baseline and postsupplementation (P = .74), and placebo 3.7 (1.8) and 3.2 (1.5) cells/1000 μm2 at baseline and postsupplementation, respectively (P = .20). Evaluation of a moderate (2MED) UVR dose and further time points similarly found no effect of supplement on CPD (Fig 2).Fig 2Time course of ultraviolet radiation–induced cyclobutane pyrimidine dimers (CPD) in skin at baseline and after 4 weeks supplementation with green tea catechins and vitamin C. Data are mean + SD number of CPD-positive cells/1000 μm2 epidermis in unexposed skin (0 hours) and at 0.25, 6, and 24 hours after UVR exposure of skin. n = 5 subjects.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Our findings contrast with oral studies in mice1Nichols J.A. Katiyar S.K. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.Arch Dermatol Res. 2010; 302: 71-83Crossref PubMed Scopus (724) Google Scholar and topical human studies which found that GTC protected against direct DNA damage.2Katiyar S.K. Perez A. Mukhtar H. Green tea polyphenol treatment to human skin prevents formation of UV light B-induced pyrimidine dimers in DNA.Clin Cancer Res. 2000; 6: 3864-3869PubMed Google Scholar Oral green tea consumption is difficult to control in mice, and topical human studies potentially have higher local skin concentrations of GTC than those after ingestion. We previously showed GTC and metabolites are bioavailable in human skin but with intersubject variability in both the range of specific metabolites and concentrations detected,5Rhodes L.E. Darby G. Massey K.A. et al.Oral green tea catechin metabolites are incorporated into human skin and protect against UVR-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-HETE.Br J Nutr. 2013; 110: 891-900Crossref PubMed Scopus (61) Google Scholar and further studies may examine means to enhance skin uptake/bioavailability. Strengths include the robust study design, tablet count and biochemically determined subject compliance, and use of solar-simulating UVR giving more relevance to natural sun exposure than studies using primarily UVB radiation.1Nichols J.A. Katiyar S.K. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.Arch Dermatol Res. 2010; 302: 71-83Crossref PubMed Scopus (724) Google Scholar, 2Katiyar S.K. Perez A. Mukhtar H. Green tea polyphenol treatment to human skin prevents formation of UV light B-induced pyrimidine dimers in DNA.Clin Cancer Res. 2000; 6: 3864-3869PubMed Google Scholar Our study scope is limited to erythemal UVR and direct DNA damage; we demonstrate that oral GTC is no substitute for topical sunscreen but have not excluded an adjunctive role to sunscreen. Protection against low-dose UVR exposure as in everyday life, and against oxidative DNA damage, warrants future study.