Background 8/11/2012. Key nutrients = Healthy balanced diet. Blindness: <6/60 in Australia. Structure of the eye. Age-related Macular Degeneration
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1 ILSI SEA Region - Optimum Health & Nutrition for our Ageing Population. Australia - October ( Age-related macular degeneration and diet: the protective role of antioxidants and omega-3 polyunsaturated fatty acids Background Associate Professor Vicki Flood vflood@uow.edu.au Key nutrients = Healthy balanced diet Structure of the eye Lutein (and zeaxanthin) Vitamin C Vitamin E Zinc Long-chain omega-3 polyunsaturated fatty acids Low Glycemic Index foods Effect of AMD Age-related Macular Degeneration Blindness: <6/60 in Australia Two recognised Late forms: more frequent (2/3) neovascular new blood vessels invades inner retina haemorrhage and cause a scar on the retina Others 4,370 Neurological 8% 1,404 3% Other Retinal and Diabetes 11% 5,676 Refractive Error 1,882 4% 49% Total 50,548 Macular Degeneration 24, less frequent (1/3) atrophic progressive loss of macular pigment Cataract 6,111 Glaucoma 6,901 12% 14% MVIP and BMES Blue Mountains Eye Study/ Visual Impairment Project data, incorporating contribution from nursing home residents, pooled & standardised to 2004 Australian population. Prevalence early ARM 4%; after 5 years follow-up (incidence): 8% AMD. 1
2 AREDS: Randomised Controlled Trial of antioxidants and zinc Rotterdam Cohort Study, n=4765 at baseline with dietary data Estimated Probability 40% 30% 20% Rate to Advanced AMD AMD Categories 3 and 4 by Treatment Group Placebo Antioxidants Zinc 28% Antioxidants + Zinc 20% 10% 0% 0 P vs. A+Z p<0.01 P vs. Z p< Years 6 Antioxidants: Vit C (500mg), B-carotene 15mg, Vit E 400 IU, Zinc 80mg Van Leeuwen et al. JAMA 2005 Antioxidants and eye disease Retina susceptible to oxidative stress: high exposure to oxygen, high concentration of PUFA s, exposure to light Phagocytosis of retinal pigment pg epithelium: oxidative stress Therefore antioxidants likely to be important for healthy cell function Macula also concentrated in carotenoids: lutein and zeaxanthin and zinc Zinc is a co-factor for antioxidant enzymes: superoxide dismutase and catalase Possible mechanism of omega-3 protection in eye disease DHA found in high concentrations in the human retina DHA particularly high in photoreceptor cells of the retina; frequently shed and require sufficient DHA Likely to be important in cell membrane maintenance and retinal repair following oxidative stress Omega-3 may inhibit development of plaque and blood clots (assists retinal vessel health) Relationship between AMD and CVD and stroke Among people <75 years: early AMD predicted doubling of CVD mortality y( (RR 2.32, 95%CI ) late AMD predicted fivefold CVD mortality (RR 5.57, 95%CI ) late AMD predicted 10-fold higher stroke mortality (RR 10.21, 95%CI ) Blue Mountains Eye Study Population based cohort study of residents 49 years and older Complete census (door-knock) of 2 postcode areas in the Blue Mountains. Baseline: (n=3654) Population similar to Australian population older people, except higher SES and more Caucasians. FFQ used to measure dietary intake in ~ 80% of people with clinical examinations (Tan et al, BJOphthal, 2008) 2
3 Study population n=3654(exam)(86%) n=2895(ffq) n=2334 (75%) n= n=1952 (75%) n= n=1500 n=1150 Survey questions Socio-demographic Medications Measured weight, height, BP SR health status (CVD, cancer, etc) Mini-mental Eye examination Blood assays: lipids, glucose, Hb, Hcyst Dietary data: FFQ 15 year mortality: n=1047 (28.7%) The Food Frequency Questionnaire Number of times used this amount over last 12 months DAIRY FOODS Less Never than per per per per per per per per month week week week day day day Foods Amount month Skim milk 250 ml (8oz.) glass 6 _ Low fat milk 250 ml (8oz.) glass _ Whole milk 250 ml (8oz.) glass _ Cream e.g. thickened, pouring 1 tblsp. _ Ice cream ½ cup 10 _ Yoghurt, flav/plain 1 small carton _ Yoghurt, low fat, flav/plain 1 small carton _ Cottage or ricotta cheese ½ cup _ Other cheese, 1 slice or _ e.g. Coon 1 oz. serving Analyses Nutrient analyses: NUTTAB, fatty acids (Man et al, US Carotenoid Database) Logistic regression: risk of AMD (and other health outcomes), by quintiles of diet intake at baseline, adjusted for confounding variables Data linked to Australian National Death Index Margarine, added to food or bread: Exclude use in cooking Butter, added to food or bread: Exclude use in cooking 1 teasp. 1 teasp. 15 Dietary antioxidants and the long-term incidence of age-related macular degeneration Main findings People with highest tertile of lutein and zeaxanthin had 65% reduced risk for neo-vascular AMD (RR 0.35; CI ), compared to the remainder People with highest decile zinc intake reduced risk for early AMD (0.54; 95% CI ) (Highest decile >15.8mg/day) People with highest tertile of vegetables, reduced risk of any AMD (0.64; 95% CI ) Tan, Wang, Flood, Mitchell. Ophthalmol Incident cases of age-related macular degeneration (ARM) in BMES (5 yrs) People in highest quintile of n-3 3PUFA vs the lowest quintile n-3 PUFA had 60% reduced risk of developing incident ARM over 5 years (OR 0.4, CI ) (Chua, Flood, Mitchell, Archives Ophthalmol 2006) Fish and nuts Odds of 5-year incident Early ARM Late ARM Total Fish* <1 /month 1.00 (ref) 1.00 (ref) 1 /week 0.58 ( ( ) 1.21) 3 /week 0.62 ( ) Nuts 0.25 ( ) Never 1.00 (ref) 1.00 (ref) <1 /week 0.80 ( ) 1 /week 0.79 ( ) 0.82 ( ) 0.55 ( ) adjusted for age, sex, current smoking, antioxidants (diet & supplements) * Includes sardines, tuna, other fish 3
4 1 serve fish /wk and risk early AMD = 0.69 ( ); <median linoleic acid RR=0.57 ( ), not sig among >median linoleic acid 10-year cohort (Tan, Wang, Flood, Mitchell; Arch Ophthal. 2009) Quartiles of long-chains omega-3s Early AMD Linoleic acid, Q1 and Q ( ) ( ) P trend= ( ) Linoleic acid Q3 and Q ( ) ( ) ( ) Nuts and AMD, 10 year cohort Current Research RCT AREDS-2 Lutein/zeaxanthin 10mg/2mg (or L/Z placebo) and two soft- gel capsules (DHA/EPA 350mg/650mg or DHA/EPA placebo). Translating research into practice Review the evidence Consider current dietary guidelines and nutrient content of foods, and consider whether younger older people or older older people What s feasible / realistic / sensible? Lutein and zeaxanthin Food (serve) Lutein and zeaxanthin (μg) (no current RDI; mean intake BMES 914 ug) Spinach, cooked ½ cup 5282 Broccoli, cooked, medium 1669 serve Green beans, ½ cup 525 Egg, enriched, 1 medium* 179 Tomatoes, 75g 97 Egg, regular, 1 medium 28 Lutein and zeaxanthin, main food sources, BMES Mean intake = 914ug USDA national nutrient database, release 1998 * based on Australian fortified product Manzi, Flood et al, 2002, PHN 4
5 Fish and Eggs Both increased significantly Vegetables No change in mean intake of veg s over 10 years mean intake (g) Potatoes (F) Potatoes (M) ** Brassica (F) * Brassica (M) Avocado (F) *** Avocado (M) *** 0 Baseline 5 years 10 years *** p< Flood 2010, EJCN *p<0.05, **p<0.001, ***p< Summary diet recommendations 1. Eat fish regularly, about twice a week (especially oily fish types with higher omega-3 concentrations, such as salmon). 2. Consume plenty of vegetables and fruit. Include a variety of vegetables, especially green leafy vegetables / soups. 3. Consider important sources of lutein. These include green leafy vegetables, and also found in enriched eggs. 4. Include nuts and seeds 1-2 times per week, if practical, higher in PUFA and mono-unsaturated fats (consider dental health). 5. Include 3-4 small serves of lean red meat as an excellent source of highly bioavailable zinc. 6. And what about butter vs margarine? Butter increases the saturated fat concentration of the diet. Use margarines / oils high in omega-3, and include alternative sources of fat, such as olive oil or linseed (flaxseed oil). If older, and enjoy butter, don t change. Acknowledgments Other investigators On BMES: - Professor Paul Mitchell - A/Prof Jie Jin Wang - Dr Bamini Gopinath - Dr Shweta Kaushik - Dr Jennifer Tan - Ms Elena Rochtchina 5
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