Reduction of Facial Redness With Resveratrol Added to Topical Product Containing Green Tea Polyphenols and Caffeine

July 2013 | Volume 12 | Issue 7 | Original Article | 770 | Copyright © July 2013

Georgina Ferzli MD MS, Mital Patel MD, Natasha Phrsai BS, and Neil Brody MD PhD

State University of New York Downstate Medical Center, Brooklyn, NY

cancer development. The topical application of caffeine to human skin provides protection from UV light via DNA repair mechanisms.27 Caffeine has been shown to prevent or reverse UV damage by inhibiting the ataxia-telangiectasia and Rad3- related protein (ATR)-checkpoint kinase 1 (Chk1) pathway28 involved in cell cycle control.29 By inhibiting the ATR-Chk1 pathway, caffeine prevents tumor growth and promotes apoptosis. Lastly, should UV-damage occur, topical caffeine can eliminate UV-damaged keratinocytes30 and subsequently inhibit skin cancer development. While this discussion frequently uses UV light as the inducer of ROS, it has been shown that both visible light and infrared also induce ROS.31
Our product provides a “second line” of defense in that its components also directly inhibit various inflammatory pathways. The cyclooxygenase (COX)-2 and lipoxygenase (LOX) pathways catalyze the production of pro-inflammatory substances, including prostaglandins and leukotrienes.32,33 Various biochemical pathways are also associated with the induction of inflammatory cytokines (tumor necrosis factor-α, IL-6, and IL-1β) that stimulate the growth of tumor cells.34 Resveratrol works to diminish inflammation by stopping COX-2 activity,35 likely by inhibition of the protein kinase C (PKC) signal transduction suppressing COX-2 expression.36 This finding is important because PKC is up regulated in some types of cancer.37,38,39 Green tea phenols (GTPs) have also been shown to have an effect on the COX pathway. GTPs in drinking water reduced inflammation markers COX-2, prostaglandin E2, proliferating cell nuclear antigen, and cyclin D1 in mice with skin damage that developed after exposure to UV radiation.40 Other studies showed that GTPs: (1) inhibit ornithine decarboxylase, COX, and LOX; and (2) inhibit release of interleukins 1, 8, 10, and 12,41 which are all pro-inflammatory molecules. The third compound in our product, caffeine, takes yet another approach in countering inflammation. Topical caffeine inhibits cyclic AMP phosphodiesterase, which results in increased levels of cAMP in skin, which, in turn, reduces inflammatory reactions.42,43
Lastly, it is important to consider that an increase in cutaneous blood supply would carve a convenient pathway for inflammatory markers to reach the skin. Angiogenesis is defined as the production of new blood vessels and/or altered permeability of existing blood vessels. A key element that stimulates angiogenesis is vascular endothelial growth factor (VEGF). Resveratrol, GTPs, and caffeine down regulate angiogenesis. A study by Pietrasik and colleagues44 demonstrated that resveratrol modulates normal somatic cells, leading to a decrease of the angiogenic activity of endothelial cells. Mesothelial cells treated with resveratrol created an angiogenesis-suppressive milieu, reflected by the inhibited proliferation and migration of endothelial cells. This suppressive effect continued even after the cells were removed from resveratrol exposure. Endothelial cells treated directly with resveratrol also showed anti-angiogenic activity. The anti-angiogenic effect of resveratrol may be associated with its activation of glycogen-synthase kinase 3b (GSK3b), which results in decreased production of VEGF via down-regulation of b-catenin.45 GTPs play an anti-angiogenic role by inhibiting phosphorylation of VEGF receptors46 required for VEGF binding. Meanwhile, pretreatment of cells with caffeine significantly reduces adenosine-induced VEGF promoter activity and VEGF and IL-8 expression.47 The antiangiogenic effects of all three compounds in our product may directly reduce redness.


The skin product’s unique combination of resveratrol, green tea polyphenols, and caffeine reduces facial redness in most patients after 3 to 6 weeks of continuous treatment and may provide further improvement with additional treatment.


The study was initiated and funded by one of the authors (N.I.B.). That author contributed to the conceptualization and design of the product but holds no patents and does not benefit from its sale. This product is commercialized as Replenix Power of Three by Topix Pharmaceuticals.


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