A(REDS) to Z(inc) Nutrition for eye health

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Arnold Scott
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All eyes on the macula A(REDS) to Z(inc) Nutrition for eye health Professor Christine Purslow

Lutein Zeaxanthin Meso-Zeaxanthin Macular pigment (MP) The healthy retina Carotenoids

diet but meso-zeaxanthin is made by conversion from lutein Distributed maximum centrally,

Natural aging plus effects from risk factors Bruchs membrane starts to thicken around age 45

for agerelated accumulations of lipid containing materials in the cells of many tissues In the

1 All eyes on the macula A(REDS) to Z(inc) Nutrition for eye health Professor Christine Purslow PhD, MCOptom, FBCLA, FIACLE Macula lutea = yellow spot Colour is determined by 3 carotenoids Lutein Zeaxanthin Meso-Zeaxanthin Macular pigment (MP) The healthy retina Carotenoids collectively referred to as macular pigment (MP) Lutein and zeaxanthin have to come from your diet but meso-zeaxanthin is made by conversion from lutein Distributed maximum centrally, decreases paracentrally Essential functions Why does AMD happen? Natural aging plus effects from risk factors Bruchs membrane starts to thicken around age 45 Slows waste disposal down Drusen can form Drusen build-up Dry AMD Lipofuscin is a generic term for agerelated accumulations of lipid containing materials in the cells of many tissues In the RPE it is mainly composed of partial break-down products of the photoreceptor outer rod segments In later stages of AMD, the RPE may atrophy completely, known as DRY AMD 1

10-15% with drusen will progress to this Inflammatory and neovascular mediators (from drusen formation) invite choroidal vessels to grow into and beyond the fragmented membrane Fluid and blood

4% of adults in UK 513,000 estimated in 2013 rising to 700,000 by 2020 Leading cause of blindness in people over 65 in developed countries (3 rd worldwide) Two main types Wet and dry You can have

Some risk factors we can change and some we can t AMD risk factors (non-modifiable) AMD risk factors (modifiable) Age ++ Family History +++ Fundus Examination ++ Cigarette Smoking Nutrient Deficiency

2 10-15% with drusen will progress to this Inflammatory and neovascular mediators (from drusen formation) invite choroidal vessels to grow into and beyond the fragmented membrane Fluid and blood leakage leads to scarring Wet AMD AMD Age-related macular degeneration 2.4% of adults in UK 513,000 estimated in 2013 rising to 700,000 by 2020 Leading cause of blindness in people over 65 in developed countries (3 rd worldwide) Two main types Wet and dry You can have both Development in one eye increases the risk for the other HOW CAN WE REDUCE THE RISK OF AMD? Some risk factors we can change and some we can t AMD risk factors (non-modifiable) AMD risk factors (modifiable) Age ++ Family History +++ Fundus Examination ++ Cigarette Smoking Nutrient Deficiency General Health AMD increase exponentially with age 1 in 2000 by 60 years 1 in 5 by 90 years F>M Caucasian>South-East Asian>Afro-Caribbean Parent with AMD increase risk by 14% Sibling with AMD increases risk by 21% 'I can't read scripts anymore': Dame Judi Dench reveals that she is battling to save her eyesight AMD in one eye increases the risk for the other Low levels of macular pigment? Multiple soft drusen Smokers are 4 times more likely to have AMD than people who have never smoked A poor diet in key minerals such as zinc, selenium Anti-oxidants vitamins C and E Lutein and zeaxanthin Omega 3 fish oils Obesity Alcohol Blood pressure Fatty diets Diabetes Cardiovascular risks Excess sunlight Blue light hazard 2

Summary of common risk factors Increasing age Cigarette smoking Ethnicity Genetic factors Gender

processes Fatty diets Oxidative stress Free radicals and oxidative stress AMD The role of Oxidative

Free radicals Anti-oxidants Retina is an excellent environment for oxidative stress (rich blood supply,

) How can we improve the protection of the retina from oxidative stress? Be healthy and stay young!

3 Summary of common risk factors Increasing age Cigarette smoking Ethnicity Genetic factors Gender Factors that also may play a role: Exposure to blue light Hypertension and atherosclerotic disease processes Fatty diets Oxidative stress Free radicals and oxidative stress AMD The role of Oxidative stress Oxidative stress: Imbalance between free-radical production and anti-oxidant defences in body Free radicals Anti-oxidants Retina is an excellent environment for oxidative stress (rich blood supply, cell activity, direct exposure to UV light, etc.) How can we improve the protection of the retina from oxidative stress? Be healthy and stay young! Stop smoking Maintain a healthy diet Exercise Control weight Control blood pressure Blue light protection MP? Dietary supplementation How can diet improve the protection of the retina from oxidative stress? Healthy Balanced diet Otherwise there are two options: Supplement the macular pigment (MP) lutein, zeaxanthin Supplement antioxidants vitamins, minerals, Omega 3 fatty acids 3

Diminution of ARMD evolution risk 30% 23% 15% 8% 0% Series1 How do we understand the role of nutrition in eye health?

The observational study of large populations and their dietary intake, and their association with disease Pros: Large samples Cons: Relies on food diaries mostly 2.

Cons: Volunteers tend to be health-conscious so not perhaps people who benefit most; compliance may be poor; people drop out AREDS1 The first Age Related Eye Disease Study (AREDS1): 3640 enrolled

3 years The supplement mixture containing high doses of antioxidant vitamins and zinc: Reduced their risk of developing advanced AMD (wet AMD) by 25% Reduced moderate vision loss by 19% AREDS 2

4 Diminution of ARMD evolution risk 30% 23% 15% 8% 0% Series1 How do we understand the role of nutrition in eye health? AREDS studies are large and noteworthy Evidence tends to come from two types of research: 1.The observational study of large populations and their dietary intake, and their association with disease Pros: Large samples Cons: Relies on food diaries mostly 2.The studies where an intervention has been applied and the people followed for a period of time Pros: More control? Cons: Volunteers tend to be health-conscious so not perhaps people who benefit most; compliance may be poor; people drop out AREDS1 The first Age Related Eye Disease Study (AREDS1): 3640 enrolled participants with intermediate stage of dry AMD, followed for average 6.3 years The supplement mixture containing high doses of antioxidant vitamins and zinc: Reduced their risk of developing advanced AMD (wet AMD) by 25% Reduced moderate vision loss by 19% AREDS 2 AREDS2 study: 4,203 people ages years, who were at high risk for advanced AMD participated in AREDS2; followed for 5 years Designed to determine if they could improve the AREDS formulation AREDS2 study added lutein and zeaxanthin; omega-3 fatty acids to the original AREDS formula; removing beta-carotene and reducing zinc The AREDS 1 supplement mixture daily dose Zinc (oxide) - 80mg Copper (cupric oxide) 2mg Vitamin C - 500mg Vitamin E 400 IE Beta Carotene 15mg 5 to 15 times higher than the RDA 25% 21% 17% Antioxidants Zinc Antioxidants + Zinc Results AREDS2 The addition of Lutein, Zeaxanthin and Omega-3 to the original AREDS supplement did not further reduce the progression of AMD However, two groups of participants did show a greater benefits than those just taking the original AREDS formula. These were people who: Took lutein and zeaxanthin without the beta carotene and People who had little lutein and zeaxanthin in their diets at the start of the study Two levels of zinc were tested and both showed the same effect so either dose is acceptable Findings related to omega-3 were neutral, although other trials have reported a benefit AREDS2 AREDS2 investigators say that a new AREDS formula supplement should contain: Nutrient Recommended Intake Dietary Equivalent Vitamin C 500mg 7 oranges Vitamin E 400IU (268mg) 874 almonds Copper 2mg 1 dressed crab Lutein Zeaxanthin 10mg 2mg 5 ½ portions of broccoli Zinc 25mg or 80 mg ~ 4 rump steaks or ~ 13 rump steaks 4

A family of naturally occurring polyunsaturated fatty acids (PUFA) Essential fatty acids Scientifically proven health benefits The omega-3 family includes: Long-chain omega-3 fatty acids - EPA

5 AREDS studies are large and noteworthy, but Healthy volunteers Most of them already taking a general supplement What about omega-3 and AMD? Already had AMD Some ingredients well in excess of the NRV, particularly for Zinc and Vitamin E Omega 3 fatty acids Which fish are the best sources of Omega 3? A family of naturally occurring polyunsaturated fatty acids (PUFA) Essential fatty acids Scientifically proven health benefits The omega-3 family includes: Long-chain omega-3 fatty acids - EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). These are plentiful in oily fish Short-chain omega-3 fatty acids - ALA (alpha-linolenic acid). Found in plants, such as flaxseed/linseeds and their oils, walnuts, chia seeds Monkfish 140mg Haddock 280mg Cod 342mg Lobster 580mg DHA and EPA are important for eye health DHA is vital for the development of infants visual acuity before and after birth High levels of DHA are found in the membranes of photoreceptors in the retina Anti-inflammatory action DHA facilitates absorption of lutein If you are deficient, you may suffer dry, uncomfortable eyes Atlantic salmon 2380mg Sardines 2660mg Mackerel 2804mg Herring 2817mg Omega 3 s and AMD The Alienor Study High intake of long chain omega-3 PUFA s associated with significantly reduced risk of AMD 50% of reduction in patients with high omega-3 levels in plasma Omega 3 and AMD At baseline AREDS2, participants reporting highest intake of DHA or EPA were less likely to have more severe AMD Increasing Omega-3 intake may protect against the development of early AMD (Blue Mountain) Regular fish intake reduces the risk of AMD by 35% (Cho et al., 2001) Participants in the highest quintile for DHA intake (Omega- 3) had a risk of AMD that was 25% lower than participants in the lowest quintile (Cho et al, 2001) 5

The antioxidant vitamins Vitamins Properties Vitamin C Water soluble vitamin Helps the body produce collagen Helps absorb iron Powerful antioxidant Synergistic action with

Vitamin E Fat soluble vitamin The key antioxidant vitamin Protects cell membranes High concentration in photoreceptors of retina What other vitamins should you focus on to

Vitamins Properties Vitamin A - Often referred to a the eye vitamin - Fat soluble vitamin - Supports the immune system - Helps keep skin, hair and eyes healthy - Needed for

B12 - essential for normal nerve function Contribute to the release of energy from food B9 (folic acid) works together with vitamin B12 to form healthy red blood cells Often

powerful cofactor for antioxidant enzymes - Contributes to maintenance of normal vision - Supports the immune system - Anti-inflammatory Selenium Supports the immune system A

6 The antioxidant vitamins Vitamins Properties Vitamin C Water soluble vitamin Helps the body produce collagen Helps absorb iron Powerful antioxidant Synergistic action with vitamin E VITAMINS AND MINERALS WHAT ARE THEY THERE FOR? Vitamin E Fat soluble vitamin The key antioxidant vitamin Protects cell membranes High concentration in photoreceptors of retina What other vitamins should you focus on to keep your eyesight sharp and healthy? Vitamins Properties Vitamin A - Often referred to a the eye vitamin - Fat soluble vitamin - Supports the immune system - Helps keep skin, hair and eyes healthy - Needed for healthy vision and in dim light - Needed for tear secretion and mucin production - The vitamin A family has several members B Vitamins B6, B9, B12 Support the immune system B12 - essential for normal nerve function Contribute to the release of energy from food B9 (folic acid) works together with vitamin B12 to form healthy red blood cells Often included in dry eye formulations to improve tear secretions Essential eye minerals Minerals Properties Zinc - Highly concentrated at ocular level - Free radical scavenger and powerful cofactor for antioxidant enzymes - Contributes to maintenance of normal vision - Supports the immune system - Anti-inflammatory Selenium Supports the immune system A major antioxidant mineral Cofactor of Glutathione peroxidase, a key antioxidant enzyme Completes the antioxidant function of Vitamin E and Zinc Load up on Lutein & zeaxanthin Other antioxidants - polyphenols Reducing oxidative damage and hyperproliferation of the RPE Dark chocolate Red wine Berries Spices UK daily consumption is generally well below the levels of intake found to be most beneficial to macular pigment levels (10 mg L + 2 mg Z) 6

Resveratol Polyphenol found in red wine and nuts Resveratrol increases life expectancy and prevents the incidence of age-related diseases (like heart

Rotterdam study Study with 2167 participants, age 55 years or older, with no AMD, with susceptibility variant genes, median follow-up 8.

excessive) amounts of nutrients. *Source: Ho L et al. Arch Ophthalmol.

Consider their: age, risk factors, current diet, health, medications, stage of AMD Summary Like the prevalence, awareness of AMD is increasing

7 Resveratol Polyphenol found in red wine and nuts Resveratrol increases life expectancy and prevents the incidence of age-related diseases (like heart disease) Proven to be Antioxidant Anti-angiogenic Anti-inflammatory Diet versus food supplements? So what about patients with no visible signs of AMD? Rotterdam study Study with 2167 participants, age 55 years or older, with no AMD, with susceptibility variant genes, median follow-up 8.6 years Higher dietary intakes of zinc, omega-3 and lutein/zeaxanthin resulting in a 35% lower risk of AMD Such benefits were achieved with high (but not excessive) amounts of nutrients. *Source: Ho L et al. Arch Ophthalmol. 2011: 129(6): Communication to patients Discuss modifiable risk factors of AMD Your advice should be tailored to the individual. Consider their: age, risk factors, current diet, health, medications, stage of AMD Summary Like the prevalence, awareness of AMD is increasing Understanding the pathogenesis of AMD helps us to understand how nutrition and nutritional supplements can affect risk Thank you for listening Useful resources: Macular Society nutrition pages It is our duty of care to offer patients appropriate evidence-based advice 7

The Age Related Eye Disease Study

The Age Related Eye Disease Study Fatoumata Yanoga, MD Assistant Professor of Ophthalmology Ohio State University Wexner Medical Center 04/13/2018 No Relevant Financial Relationships with Commercial Interests