The effect of dietary bioactive compounds on skin health in humans in vivo

The skin is the largest organ in the body and is readily visible. The consumer is often very aware of his/her skin and it is a sign to the outside world of health status. Ultraviolet (UV) radiation in sunlight is an important environmental agent that is responsible for short and longer-term negative aspects of skin health, including sunburn and most of the features associated with skin ageing. Behavioural changes have resulted in exposure to higher levels of UV, such that related health issues are increasing, and anticipated to increase further due to predicted climate change. Many previous studies have examined negative effects of food on skin, for example allergy or other diseases, or vitamin or mineral deficiency. There is also a substantial body of evidence showing beneficial effects of drugs and some nutrients on animals and when applied topically to the skin. However, there is surprisingly little information on the effect of orally taken bioactive compounds on skin in humans clinically, despite much supporting evidence for an effect from cell culture, animal, topical and mechanistic studies. The range of expertise provided by our 3-centre collaboration makes us ideally placed to address this area. To underpin the concept of nutrition for a healthy skin, we propose to examine the effect of bioactive compounds for which information in other systems is already available, on humans in vivo using state of the art techniques for measuring biomarkers of skin health directly in the skin, and further to measure nutrient uptake into the skin. Specifically, the data from laboratory studies on human skin cells shows that the compounds in green tea protect very efficiently against UV radiation stress. In addition, a large number of pre-clinical studies on rats and mice have shown a protective effect of green tea against cancers of many types. There are also many papers that report a protective effect of green tea against inflammation when applied directly (topically) to the skin. Taken together, this evidence suggests that a human study where the green tea is given orally is urgently needed and very timely. The importance of vitamin C to skin and connective tissues has been known for a long time. During UV and other stresses, the requirement of vitamin C increases. The study will be conducted over 3 months since the skin takes several months to replenish itself (turnover). The study has been designed to demonstrate a protective effect, and, if results are as expected, the study will be useful to both consumers and industry since it will validate the use of green tea in oral skin care formulations, and also provide the consumer with a choice to drink green tea for improving skin quality and even slowing ageing. It is anticipated that the results will also receive substantial press coverage with good publicity for the researchers and for the BBSRC DRINC programme.

There is little information on effect of oral catechin, a nutritionally relevant bioactive compound, on skin health in humans in vivo, despite considerable evidence for protective effects, including against UV stresses, in experimental studies. Vitamin C is essential for skin health, and also stabilises catechins in the gut lumen. Ultraviolet in sunlight is a key environmental stressor impacting on skin health, effects including acute inflammation and longer-term photodamage. Our collaborative group has established: (i) Quantitative systems for assessing UV-induced inflammation in human skin in vivo and protective effects of oral nutrients (ii) Effects of polyphenols in humans and evidence of abrogation of UV-stress in vitro (iii) Expertise in measurement of bioavailability of nutrients, especially polyphenols (iv) Short-term model for longer-term photodamage Our primary objective, to examine protection by a combination of dietary catechin and vitamin C on UV-induced inflammation, will be achieved through a double-blind study where 75 healthy humans are randomised to high or low dose bioactive or placebo. Before and after 3 months' supplement, protection against UV-induced inflammation will be examined through clinical, histological and biochemical end-points. Specifically, we will examine for skin erythema, leucocytic infiltration, and for molecular mediators of these processes in samples of skin and skin fluid. We will determine bioavailability of catechin in unexposed and inflamed skin and determine relationships between its skin levels and levels of UV protection. Further, skin samples taken will also be used to assess for immunohistochemical evidence of protection against UV-induced changes in MMP-1, fibrillin-1 and pro-collagen-1, in a short/term model of photoageing. Overall, this project will establish efficacy of bioactives against UV-inflammation, the oral and skin nutrient levels required, and indicate potential against longer-term skin damage.