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Caffeine is structurally similar to adenosine, a compound with important biochemical roles including energy transfer, as it is a component of adenosine triphosphate (ATP). It also acts as an antagonist of adenosine receptors [43]. Caffeine stimulates the sympathetic nervous system, and it has been shown to induce increased energy expenditure and lipid turnover in humans [44]. Caffeine when given both orally and topically has been shown to inhibit UVB-induced carcinogenesis in mice [45, 46]. Data from the Nurses' Health Study and the Health Professionals Follow-up Study (prospective observational studies), with a total of 173?229 participants, showed that those in the highest quintile of caffeine intake compared with those in the lowest quintile had a reduced BCC risk (relative risk 0.82 for women and 0.87 for men, P?U0126 in vitro for both), although no association with SCC or melanoma was found [47]. Another prospective observational study with 1325 eligible participants found no statistically significant association between caffeine intake and BCC risk or SCC risk. However, when the authors stratified for prior skin cancers, a 25% lower risk of BCC was found for participants in LMTK2 the highest tertile of caffeine intake (?4 cups of coffee per day) compared with those in the lowest tertile (P?=?0.025) [48]. A case-control study compared 166 patients with BCC to 158 cancer-free patients. It did not find a significant effect of coffee drinking on BCC risk [49]. Another case-control study with 33 pairs of same-sex twins, one with BCC and the other without, found a nonsignificant increased BCC risk with drinking more than 3 cups of coffee per day (odds ratio 1.75, 95% confidence interval 0.73�C4.17) [50]. The results from these observational studies are somewhat contradictory; however, as a whole they suggest a favorable effect on skin carcinogenesis from caffeine, which Romidepsin is consistent with experimental murine observations that it is photoprotective. Support for the protective role of plant-based dietary components was provided by a study showing that humans with a past history of skin cancer who consumed relatively large amounts of green leafy vegetables were protected from developing new SCC [51]. Similarly consumption of vegetables and fruit has been associated with protection from AKs [52]. Another study of the diets of 1119 adults in Queensland, Australia, found an association between a reduced incidence of AK and moderate consumption of wine [52]. In this study the average wine consumption was one glass every 2 days and therefore is relatively moderate. It was not determined whether it was white, red or either type of wine that provided the protection. Both studies provide support that polyphenols, antioxidants or some other plant components can protect from the damaging effects of UV radiation.