Impact of oral green tea catechins on UVR-induced skin inflammation

Acute exposure of human skin to ultraviolet radiation (UVR) results in oxidative stress and an acute inflammatory response (sunburn), manifest clinically as erythema, histologically by a dermal leukocytic infiltrate and biochemically by upregulation of pro-inflammatory mediators. Green tea catechins (GTC) are potent antioxidants and anti-inflammatory agents with potential to offer systemic photoprotection. We hypothesised that oral GTC are bioavailable in human skin and through cyclooxygenase (COX) and lipoxygenase (LOX) inhibition may reduce the production of UVR-induced pro-inflammatory eicosanoids prostaglandin (PG)E2 and 12-hydroxyeicosatetraeonic acid (12-HETE), and also the UVR-induced erythema response. UVR spectrum and dosimetry study: This small preparatory study involved 3 subjects (2 female, mean age 36; range 29-50 yr, white Caucasian, phototype II). The aim was to assess the UVR-spectrum and dose to be used in the oral intervention study. UVB and solar simulated radiation (SSR) were compared by assessing the levels of PGE2 they induced in skin blister fluid. Subjects were given 3x and 4x their sunburn threshold dose (minimal erythema dose, MED) to upper buttock skin using both UVR sources. Suction blisters were raised after 24 hours (hr) and the fluid extracted was assayed for PGE2 by ELISA. Equivalently elevated levels of PGE2 were found for both UVR-spectra. Since SSR provides a UVR emission that closely mimics sunlight, this was chosen for the intervention study. PGE2 levels were very similar for 3x and 4x MED. Less biological variation between subjects was seen with 3x MED and therefore this dose was selected. Oral GTC intervention study: 16 healthy white Caucasian (male and female) volunteers, mean age 42 (range 29-56 yr), phototype I/II were supplemented with encapsulated GTC (550mg/day) and a small dose of vitamin C (50mg/day) which acted as a stabiliser, for 12 weeks. Pre- and post-supplementation, the volunteer’s MED to SSR was assessed visually, the UVR-erythema was quantified with a reflectance instrument, and their UVR-erythema dose response analysed. Buttock skin was irradiated with 3x the MED of SSR and after 24hr, skin punch biopsies and suction blister fluid were taken from un-irradiated and irradiated skin. Urine samples were also collected. Skin, blister fluid and urine samples were analysed for catechin and catechin metabolite content, and blister fluid for PGE2 and 12-HETE levels, using liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC/ESI-MS/MS). Following supplementation, no change in MED compared with baseline was seen. However, the UVR-erythema dose response showed a reduction in skin erythema at the highest UVR dose (P=0.006) and there was a reduction in area under the curve (P=0.033). Levels of PGE2 and 12-HETE were significantly upregulated following UVR, both pre- and post- supplementation. Post-supplementation, a reduction in UVR-induced 12-HETE expression occurred (P=0.015) while PGE2 was not altered. Intact catechins and catechin metabolites were seen in both skin and skin fluid samples, with more metabolites evident following supplementation although with considerable inter-individual variability. Good compliance with supplementation was evident through urinary catechin analysis. This pilot study showed that oral GTC are bioavailable in human skin. Evidence of protection against UVR-induced skin inflammation was seen after 12-weeks supplementation with GTC combined with vitamin C, both in the erythemal response, and in production of the pro-inflammatory eicosanoid 12-HETE. Randomised controlled studies are warranted to further explore the use of oral GTC in human photoprotection.