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FoodBioSystems DTP - Investigation of the capacity of a diet rich in lutein and zeaxanthin to increase macular pigment density, thereby potentially reducing the risk of age-related macular degeneration by dietary means.


Project Description

Research Group: FOODBIOSYSTEMS BBSRC DTP

Research question
Can consuming a healthy plant food, rich in protective macular pigments, be a lifestyle strategy that has the potential to reduce the risk of age-related macular degeneration (AMD)?

Hypothesis
Consumption of a diet rich in the xanthophylls, lutein and zeaxanthin, can increase protective macular pigment as effectively as a lutein/zeaxanthin supplement, thus potentially reducing the risk or progression of AMD by dietary means.

Background and Justification
AMD is the leading cause of blindness in developed countries1 . In early AMD, waste material, known as drusen, builds up under the retina, the light-detecting layer in the eye1 . Increasing size and number of drusen is associated with development of the late forms of AMD: geographic atrophy (GA) where there is gradual death of light-detecting cells and neovascular AMD (nAMD) where fragile blood vessels grow below and into the retina, causing bleeding. Both types lead to permanent vision loss and can occur together. Currently, the only effective treatment for nAMD is eye injections that help reduce vision loss. There are no known treatments to prevent the development of GA1 .

The macula is a specialised part of the retina, mediating central vision, providing the sharpest visual acuity and facilitating the best colour discrimination2 . Macular pigment, as measured by macular pigment optical density (MPOD), is concentrated in the inner and central layers and is believed to protect against AMD2 . It is mainly composed of the xanthophylls, lutein, zeaxanthin and meso-zeaxanthin (synthesised in situ from lutein)2 . The concentration of these xanthophylls in the macula is 1000-fold greater than in the blood, demonstrating high selectivity. This suggests a pivotal role for the xanthophylls which are believed to play a major role in protecting the retina and retinal pigment epithelium from light-initiated oxidative damage by scavenging reactive oxygen species and filtering blue light2 . The xanthophylls are transported on HDL and polymorphisms in HDL-related loci have been associated with AMD and plasma lutein/zeaxanthin3 .

Data from epidemiological studies suggests that dietary lutein and zeaxanthin intake are inversely associated with the risk of AMD. The AREDS2 randomised trial, carried out in the US, supplemented patients with early AMD with an antioxidant supplement that included lutein (10 mg) and zeaxanthin (2 mg). In a secondary analysis of that study, supplementation with lutein and zeaxanthin was protective against progression to late AMD in individuals with low lutein/zeaxanthin intake4 . A meta-analysis of 19 studies showed that supplementation with lutein and/or zeaxanthin and/or meso-zeaxanthin improved MPOD both in AMD patients and healthy subjects, with a dose-response relationship2 . However, not all studies have shown an effect of lutein/zeaxanthin supplementation on MPOD5,6. The proposed research will address that uncertainty.

What the student will do:
 Search the literature to review the evidence for an effect of lutein/zeaxanthin and associated factors on AMD risk and progression.
 In collaboration with Professor Paul Fraser, Head of the Plant Molecular Sciences group at Royal Holloway (and Syngenta), select non-GMO Capsicum varieties that are rich in lutein and zeaxanthin.
 Analyse the two selected Capsicum varieties for lutein, zeaxanthin, beta-carotene and vitamin C.
 Work with Odysea to produce jars of the selected flame-roasted dark-orange Capsicum in brine.
 Recruit volunteers with a family history (therefore at significantly increased risk) of AMD who will agree to consume approximately ½ a Capsicum per day (either the selected fresh or bottled variety), or a lutein/zeaxanthin supplement (as a comparator).
 Measure their dietary intake (including lutein/zeaxanthin) by food-frequency questionnaire (FFQ).
 Organise the measurement of macular pigment optical density (MPOD) at baseline and after 13 and 26 weeks of consumption of the Capsicum-rich diet vs. the supplement in the volunteers.
 Measure lutein, zeaxanthin and cholesterol in blood serum at baseline, 3 and 6 months.

 Syngenta has agreed to provide the Capsicum varieties specially bred to be high in xanthophylls.
 The student will spend some time in Prof Paul Fraser’s laboratory at Royal Holloway to gain an understanding of how the Capsicums are bred in collaboration with Syngenta and to analyse the two selected varieties for lutein, zeaxanthin, beta-carotene and vitamin C.
 Odysea will arrange harvesting, preparation and bottling of the dark-orange Capsicum in brine.

Training opportunities: With Prof Paul Fraser’s group in Royal Holloway, University of London (RHUL), to learn about strategies used in crop breeding (in collaboration with Syngenta); With RHUL to carry out the analysis of carotenoids/xanthophylls pigments in Capsicum by HPLC-PDA; With Odysea to learn about Capsicum harvesting, preparation and bottling.

The student will:
 learn the principles of breeding Capsicum to optimise xanthophyll production
 obtain ethics permission for a human study
 recruit at-risk volunteers to a dietary intervention
 measure: − Capsicum concentrations of lutein/zeaxanthin, carotene and vitamin C − plasma lutein/zeaxanthin − fat mass (a confounder of lutein/zeaxanthin bioavailability) by bioelectrical impedance
 organise measurement of MPOD by state-of-the-art method (see figure)
 modify and analyse an existing UK-validated FFQ so it can capture lutein/zeaxanthin intake
 design and analyse other questionnaires that can identify confounders
 learn how to harvest, process and bottle Capsicum in brine
 learn the methodology of public health/epidemiology/medical statistics
 understand the pathology, causes and treatment of AMD

Student profile: This project is suitable for a student with a degree in nutrition, chemistry, agriculture, food science or a closely related science who has an interest in diet and health. He/she should have laboratory skills, be able to write well and already have, or expect to obtain, a 1st class honours degree. The student will be based at the University of Surrey but will need to spend up to one year in total at QUB.

Funding Notes

This project is part of the FoodBioSystems BBSRC Doctoral Training Partnership (DTP), it will be funded subject to a competition to identify the strongest applicants. Due to restrictions on the funding, this studentship is only open to UK students and EU students who have lived in the UK for the past three years.

The FoodBioSystems DTP is a collaboration between the University of Reading, Cranfield University, Queen’s University Belfast, Aberystwyth University, Surrey University and Brunel University London. Our vision is to develop the next generation of highly skilled UK Agri-Food bioscientists with expertise spanning the entire food value chain. We have over 60 Associate and Affiliate partners. To find out more about us and the training programme we offer all our postgraduate researchers please visit View Website.

References

1. SanGiovanni & Neuringer. Am J Clin Nutr 2012;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471204/pdf/ajcn9651223S.pdf
2. Ma et al. Nutrients 2016; https://www.mdpi.com/2072-6643/8/7/426
3. Koo et al. Am J Clin Nutr 2014; https://academic.oup.com/ajcn/article/100/suppl_1/336S/4576438
4. Chew et al. JAMA Opthalmol 2014;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636082/pdf/nihms720274.pdf
5. Korobelnik et al. JAMA Ophthalmol 2017; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710391/
6. Lin et al. Opthalmic Epidemiol 2017;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025894/pdf/nihms975420.pdf

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