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

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

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.

Technical Summary

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.

Publications


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Charoenchon N (2016) 288 Dietary green tea catechins protect dermal elasic fibers from UV-induced remodeling in Journal of Investigative Dermatology
Clarke KA (2014) High performance liquid chromatography tandem mass spectrometry dual extraction method for identification of green tea catechin metabolites excreted in human urine. in Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Nicolaou A (2013) Eicosanoids in skin inflammation. in Prostaglandins, leukotrienes, and essential fatty acids
 
Description Significant new knowledge:
This research has shown for the first time that green tea catechin (GTC) metabolites are incorporated into human skin following 3 months oral supplementation. An open intervention study demonstrated GTC intake was associated with abrogated ultraviolet radiation (UVR)-induced production of 12-HETE (associated publication Rhodes et al, 2013, Br J Nutr). In a randomised controlled trial, we investigated the impact of oral GTC on leukocyte infiltration and eicosanoid production in response to UVR-inflammatory challenge. This is published in the top nutrition journal, Am J Clin Nutrition, Farrar M et al. We additionally assessed impact on DNA damage/repair and parameters of photoageing. This work is in the final stage of analysis and we are preparing manuscripts for publication. In a further sub-study, we assessed bioavailability of GTCs and their metabolites in greater detail and also the impact of ultraviolet radiation on this. Two manuscripts reporting this work have benn published, J Nutr Biochem: Clarke et al 2016 and J Chromatogr B: Clarke et al 2014.

New research collaborations/partnerships:
A range of opportunities for discussion with industrial groups were presented and taken up at Dissemination events. Prof Rhodes was subsequently invited for discussions by PepsiCo for potential collaborative research. The investigators also established collaboration with the group of Prof John Mathers in Newcastle to fulfil an additional objective of examining the potential impact of bioactives in prevention of the longer term UV damage of skin carcinogenesis.
Exploitation Route We envisage further mechanistic studies could examine the impact of GTC on other inflammatory mediators in basal and UVR-exposed skin. Future research could also help identify factors that influence skin uptake and metabolism of GTC. This may assist in the optimisation of GTC formulations by the food, drink and healthcare industry.
The human skin samples taken in the RCT provided the material for a successful project for a further PhD student.
Sectors Agriculture, Food and Drink,Healthcare
 
Description Many findings from this research have been published and through a follow on PhD studentship further research is in the process of being presented and published. Thus, full economic and societal impacts will continue to be realised.
 
Description 10th Eurofed Lipid Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Professor Anna Nicolaou presented findings
Year(s) Of Engagement Activity 2012
 
Description European Society For Photobiology 2011 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gemma Darby presented findings
Year(s) Of Engagement Activity 2011
 
Description European Society for Dermatological Research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Raqib Huq presented findings at the European Society for Dermatological Research Conference
Year(s) Of Engagement Activity 2014
 
Description European Society for Photobiology Congress 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dr Mark Farrar presented findings to the Congress of the European Society for Photobiology
Year(s) Of Engagement Activity 2015
 
Description International Society for the Study of Fatty Acids and Lipids 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dr Karen Massey presented findings
Year(s) Of Engagement Activity 2012