Antioxidants and Human Vision

Antioxidants and Human Vision

Antioxidants and Human Vision"Jeffry D. Gerson, O.D., F.A.A.O."Shawnee, KS and Leeʼs Summitt ,MO""

Disclosure" I do or have worked with/for &/orreceived honorarium from thefollowing industry companies:" Allergan, Alcon, Arctic Dx, Bausch & Lomb, CarlZeiss Meditec, Optos, Optovue, VSP, ZeaVision" My affiliations with these companies has notaffected the content of this lecture, nor willthey affect the way I address any questions"

Further Disclosure" I am really honored and excited to behere" Iʼm hoping Dr. Cordain will signmy copy of “Paleo Diet”" Iʼve lost over 10% of my bodyweight in last 3 mos followinga diet based on his book!"

A friend a few days ago" “What are you talking about on your nexttrip?" “Do Our Eyes Rust?”"

Antioxidants" Do you drink coffee?" Over 50% of Americans drink coffee" Is this important?" Coffee is leading source (by far) forantioxidant intake in the US diet!! 1" Neither coffee nor caffeine intake wereassociated with early AMD per BDES" Beware:" COFFEE and DOUGHNUT Maculopathy 2 "1. As reported by American Chemical Society 8/052. Kerrison J.B. Coffee and Doughnut Maculopathy: Acute Ring Scotomas. BJO.2000 Feb;84(2):158-64.

Why Antioxidants are Important"

St. Patrickʼs dayand antioxidants" Guinness is good for you" Univ. Wisc researchers found that Guinnessprevents clotting and CV disease (in rats,butwho cares, this is Guinness…)…alsohave been human studies" Flavanoid antioxidants felt to be "responsible for this decrease "inflammation"

Objectives" Discuss the importance of antioxidants inthe eye with special emphasis on AMD" Discuss sources, both dietary andsupplementary for antioxidants" Formulate practical protocols for outpatients in order to educate them"

Killer Vitamins….or not" Will vitamins/minerals/supplements kill yourpatients?" Dietary Supplements & Mortality in OlderWomen. Arch Intern Med 10/11" Increased risk in particular w iron" ? Increased risk w MV, B6, Folic, Mg, Z, Cu" After further analysis, only MV and Cu" Vit D and Ca decreased risk" Many questions as to importance/validity"

Zeaxanthin and Visual Function" S. Richer et al. Optometry 11/11" Tested L vs Z vs L&Z in AMD pts" Minimal difference in MPOD " Z better for high contrast VA, shapediscrimination and scotoma resolution" Minimal differences in other metrics"

The Constant BattleFree Radicals are toxinsthat cause cell and DNAdamageAntioxidants combat freeradicals to prevent celldamage and maintainhealth

The PlayersHealthy Cell Free Radical Antioxidant

Free Radical CreationBiological oxidation involves movingelectrons from one oxygen molecule tothe next. However, sometimes anelectron escapes and is now a freeradical.“Scientists now believe that free radicals arecausal factors in nearly every known disease,from heart disease to arthritis to cancer tocataracts. In fact, free radicals are a major culpritof the aging process itself.” - Dr. Lester Packer,PhD

Free Radical DamageBruce Ames, a well-knownscientist in the field ofantioxidants, estimatesthat the number ofoxidative hits daily toDNA per human cell isabout 10,000.

Free Radical Explanation…."

Free Radical explanation"

Sources of Free Radicals• Sunlight• Stress• Toxins• Pollution• X-rays• Radioactivity• Airline travel• Medications• Food additives• Environmental Chemicals• Synthetic materials• Household cleaners• Solvents• Pesticides• HerbicidesLots more…Smoking1 Quadrillion freeradicals per cigarette!

Key Bio-Marker“The amount ofantioxidants that youmaintain in your body isdirectly proportional tohow long you will live.”Dr. Richard Cutler, while Director of the Anti-AgingResearch Department of the National Institutesof Health, Wash D.C.

Indisputable!30 &Years30,000Published Papersdocument the linkbetween FreeRadical activityand Cell damage** Cell damage is the basis of manydegenerative diseases cancer and aging.

The best source of nutrients…"

USA Dietary Patterns (1890-2010)" High simple carbohydrate consumption"" "Soda -3.5 cans/day (only 25 % diet) - started in 1890"" "White Flour Baked goods - started in 1890"" "Potatoes - French Fries as #1 “vegetable”" Low Fruit & Vegetable (micronutrient/fiber) consumption" 20:1 imbalance W6:W3 fatty acids" 5-10 % calories from trans fats" Grain-fed & fattened cows, pigs, chickens -and stable,(perhaps slightly lower %) saturated fat consumption" Progressive increase in calories to 3700/capita in 1990s(fast food , meal super-sizing and nocturnal 24/7 eating)"

And Finally … It’s UnanimousAfter decades,the AmericanMedicalAssociationdoes a 180º turnRDAs “Enough toprevent deficiency,but not enough toprevent disease”June 19,2002“We recommend that ALL ADULTS take amulti-vitamin daily”Patients are now under doctors orders!

*Recommended Daily Allowance" RDA is not a maximum orminimum, but a place tostart" RDA for AREDS nutrients" IU = International Units" Conversion factor different fordifferent nutrients" IU = quantity that producesdesired affect""A"C"RDA"900/700mcg"E" 15mg22.5 IU"Zinc"Cu"AREDS"8600mcg"3000/231028,640IU"IU"75/90mg" 452mg"400IU"11/8 mg" 69.6 mg"2 mg" 1.6mg"Lutein" 6mg*" 10mg"

Multivitamins"Fairy Dust Formulations!!!" Valuable regardlessof eye status" *“With Lutein” doesnot equal with lutein*" Should continuealong with eyeformulations*" Rarely will also needsingle supplements"

Now on to A-Z primer"

Vitamin A" Summary: Fat soluble so need to prevent either excess or shortage" Anterior Seg: Important in conjunctival, meibomian and lacrimalgland health. May help prevent nuclear cataractsPost Seg: Important for overall retinal health/function and preventionof night blindnessSources: Apricots, cantaloupe, carrots, peppers, kale, spinach andsweet potatoes, liver, milk.. Amount: RDA 2310/3000 IU women/men" Deficiency: mucin deficient dry eyes, short TBUT, difficulty withdark adaptation" Excess: compete with Vit D in bone health, skin coloration changes "

Vitamin A cont." The most efficient pro-Vitamin ACarotenoid is Beta Carotene" Beta Carotene: Converted in body toVitamin A in controlled manner" High Doses Beta Carotene often foundin eye formulations" Questionable at best benefit for AMD" *Avoid Beta Carotene in smokers*" Can cause lung cancer" Can be substituted with other carotenoids"

α - Lipoic Acid" Water and fat-soluble" Improves insulin sensitivity! " Boosts protective intracellular glutathione" Regenerates all other network antioxidants" i.e vitamins C and E" Powerful protection against stroke, heartdisease, and cataracts " Helps break down sugar in the production of ATP ! Used in Europe for 25 years in diabetes treatment " -i.e peripheral neuropathy"

Alpha Liopoic Acid" Sometimes referred to as “Master Antioxidant”" Anterior Segment: Prevention of corneal damage from UV,improved visual function in glaucoma, prevention of cataract" Posterior Segment: Reduction/prevention of DR, possibly beneficial inRP, beneficial in ischemic disease" Deficiency: Not noted in humans, as we can synthesize adequate amount formitochondrial functioning" Excess: Few problems with 1200mg/d x 2 yrs, can cause GI or skin sx" Note: Supplementation at 200-600mg/d common. Quickly metabolized andexcreted so time release formulations recmd."

Test #1Test #2Cataract ExampleNewborn rats given a glutathionesuppressingdrugResults:All had cataracts when their eyes firstopened at six weeks of ageNewborn rats given a glutathionesuppressingdrug + Lipoic AcidResults:No rats had cataracts when their eyesfirst opened at six weeks

B Family of vitamins"

B Family RDA, deficiency and OD"B1!Thiamine!B2!Riboflavin!B3!Niacin!B4!Niacinamide!B5!PantothenicAcid!B6!Pyridoxine!B7!Biotin!B9!FolicAcid!B12!hydroxy!B8!Inositol!B11Choline!B10!PABA!1.5mb" 1.7mg" 15-20mg"10mg"2-2.5mg"300mcg"400mcg"4-6mcg"100-3000mg"25mg"GI,nausea,depression"Photophobia"dizzy"Dimentia,nausea,dermatitis"Insomnia,edema,joint pain"Numbness,insomnia,HA"Hair loss,brittlenails,Cholest"Anemia,lowenergy,HTN,confusion"Perniciousanemia,SOB, HA"CVD,HDL,mooddisorders"Vitiligo,hyperthyroid"Insomnia"HTN"Nausea"Vomit""Flush,jaundice,sweat"Fatigue,jointpain,VLDL"Seeabpve"Slowinsulinrelease,needingVit c"Kidneydz,LDL/HDL"Anemia,anxiety,numbness"CVD,KidneyDZ, "Liver Dz,nausea,hypothyroid"

B Vitamins and Folic acid in AMD:Womans Health (WAFACS)" Arch Intern Med. 2009;169(4):335-341." Self reported AMD and Food Frequencyquestionaire" Lower levels of homocysteine with Bʼs and Folic" 37 incident cases in 5200 participants" Women on B supplements 34% decrease risk" Folid 2.5mg/d, B6 50mg/d, B12 1mg/d"

Benfotiamine " Benfotiamine: a cheap, lipid soluble analog of thiamine (Vit B1) Blocks all four injurious pathways invivo in DM Normalized biochemical pathways in humans withT1DM Diabetologia 2008;51(10): 1930-2

Oral Dry Eye Supplement –Team Players! Vit B6" Metabolism of proteins in lacrimal gland" GLA synthesis" Vit C" PGE1 production" CHO synthesis" ↓ Oxidative stress" ↓ Inflammation" Folic Acid" AA and nucleic acid synthesis" improved TBUT (Dr Ben Lane)"

Vitamin C (Ascorbic Acid)" Most mammals synthesize on their own…humans do not" Part of antioxidant network: helps regenerate otherantioxidants" Found in nearly all eye tissues" Only known affect of overdose is diarrhea" Serial dosing superior to bolus" People that are “stressed” require more: diabetes, pregnant,smokers, chronic disease, etc." Severe deficiency: Scurvy: bleeding mucous membranes,spots on skin, pallor, depression, weakness and loss of teeth"

VITAMIN C: Localization"• Eye: In nearly all tissues• Brain: Protective• Liver• Lung• Heart: Protects blood vesselsConcentrated in tissues / fluids ofthe body with a high potential forradical generation:• SemenIn the BODY:• LeukocytesIn the EYE:concentrated in AQUEOUS HUMOR morethan in other body fluids(20-30 fold higher than plasma)Macula: AREDS showed that in combo.preventative of AMD progressionLens: Can slow NS devel/pogression

Vitamin D…Emerging importance" Very commondeficiency/insufficiency" Synthesized from UV" Most common in thosewith darkly pig. Skin andthose in north lattitudes" Affects immunesystem" Linked to MS" Linked to Myopia" May affect cornealintegrity" Studies showingprotective from AMD"

ABCD of AMD" Vit D varies with diet, season, sun exposure, race" People with the highest blood levels of vitamin D were36% less likely to have early macular degeneration thanwere people with the lowest levels" no affects on advance stage of AMD" Vitamin D deficiency has been linked to AMD" People who drank milk had higher vitamin D levels andlower risk of early macular degeneration." compared to those who drank less than one serving of milk perday "#1 source is milk"Recommend 1000 IU D3"Parekh Arch Ophthalmol 2007;125:661–9 (NHANES III)

Vitamin D" Anti-Inflammatory. A daily dose of 2000IU of Vitamin D significantly increasesanti-inflammatory cytokine IL- 10, anddecreases pro-inflammatory TNF-alphain CHF patients.. Schleithoff SS et al Vitamin D supplementation improves cytokineprofiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J ClinNutr. 2006 Apr;83(4):731-2"".""

Vitamin D" Anti-Angiogenic. Vitamin D suppress retinalneovascularization in a mouse model, and in apopulation-based study decreases risk of earlyAMD especially at serum levels of ∼ 104 nmol/LAlbert DM, Scheef EA, Wang S, et al. Calcitriol is a potent inhibitor of retinal neovascularization.Invest Ophthalmol Vis Sci (United States), May 2007, 48(5) p2327-34; Parekh N, Chappell RJ, Millen AE, et al. Association betweenvitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994.Arch Ophthalmol (United States), May 2007, 125(5) p661-9" A dose of about 2500-4000 IU a day increasesserum vitamin D levels above 100 nmol/L." When dieting, Vit D supplementation canincrease weight lossVieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999; 69:842-56Vieth R, Chan PCR, MacFarlane GD. Efficacy and safety of vitamin D 3 intake exceeding the lowest observed adverse effect level Am J Clin Nutr2001;73:288-94.Aloia JP et al Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration American Journal of Clinical Nutrition, Vol. 87, No.6, 1952-1958, June 2008"

Vitamin D and RetinopathyMean Serum 25-OH vitamin D (ng/ml)DM (n=123) 22.9No DM (n=98) 30.3DM without DR 23.2DM with NPDR 21.5DM with PDR 18.044% of pts taking a multivitamin were vit D insufficient83% of pts not taking a multivitamin were insufficientAmerican Academy of Ophthalmol:Abstract PO223. Presented October 17, 2010.

Vitamins C & E -Improve insulin sensitivity & bloodvessel health-Positive affect on Atherosclerosis"Extra - cellularWater solubleAqueous PhaseProtectionIntra - cellularLipid solubleLipid phaseprotection

Vitamins C & E & AtherosclerosisRandomized Control Trials primarily support a benefit""" "The Antioxidant Supplementation in"Atherosclerosis Prevention (ASAP) Study"" "Harvard Intravascular Ultrasonography"(IVUS) Study"" "HDL-Atherosclerosis Treatment Study (HATS) "" "Multi-Vitamins and Probucol (MVP) Study"" "Heart Protection Study"" " ""

Vitamin E" 8 different forms, most active in humans is Alpha Tocopherol" Maintains cell membrane integrity, protects Vitamin A from oxidation andpromotes a healthy circulatory system and RBC formation" Helps body use Vitamin K as a more efficient clotting factor, but can alsocompete with Vitamin K if too much is taken" Dosing important in those on blood thinning agents" May help glucose control in diabetes" Deficiency most common in malabsrption conditions (Crohnʼs) and cancause poor nerve conduction and weakness" Risks of overdose: hemorrhagic events &/or stroke" Good sources: nuts, seeds, green leafy veges "

RETINA AND OXIDATIVE DAMAGEVITAMIN E: Mechanism of Action & ActivitiesThe most important lipophylic ANTIOXIDANT of the body Protects all biological cell membranes from oxidation Is uniquely suited to intercepting free radicals and preventinglipid destruction due to lipid chain-breaking oxidative reactions In the retina, protects PUFAs from oxidation and Vitamin A fromoxidative degeneration Protects lipids in Low Density Lipoproteins (LDLs) fromoxidation Inhibits platelet aggregation and enhance vasodilation Enhances immune systemGlobal Pharmaceuticals Category

VITAMIN E: Localization"In the BODY:Vit E is ubiquitous:In the EYE:Vit E is concentrated in:Located in all cell membranes, fatdeposits, circulating lipoproteins*Maintains cell membraneintegrity and protects Vitamin Afrom oxidation and promotes ahealthy circulatory system*RETINARod PhotoreceptorOuter SegmentsRetinal PigmentEpithelium (4-7 fold morethan in rod outhersegments)LENSConflicting evidenceconcerning cataract

n-3 Fish Oils &health! Incorporate into biological membranes" Cardio protective" ↑ Nitric Oxide (NO) endothelial cell production" Anti platelet, decrease triglycerides & apoB; " ↓ Cardiac Arrhythmia --- diabetics ! ; increaseHDLs" Anti-inflammatory" Anti-cancer" Colon, breast, skin" ↓ blood pressure" Bactericidal"

Omega-3ʼs and the Eye! DHA is the most ubiquitous polyunsaturatedFA (PUFA) in the mammalian retina" ↑ Dietary n-3 FAʼs leads to ↑ Retinal DHA" DHA required for optimal retinal function" n-3 fish oil seems to protect against lightinducedretina damage despite ↑susceptibility to lipid peroxidation" n-3 FAʼs seem to provide protection againstAMD" Also a role for ↑ dietary vitamin E (food,supplements) as ↑ dietary n-3ʼs! Benefit AMD patients"

Omega-3 PUFAs: Overview"Polyunsaturated Fatty AcidsLocalization: all cell membranes, neuronal tissues (Body); rod outer segmentdisks (Eye)MoA: Antioxidant; Promote RPE survival; Modulate cell signaling processes;*Reduce blood lipids*; Reduce pro-inflammatory molecules productionActivities:• Neuroprotctive• Vasoprotective• Cardioprotective• AntiinflammatoryRDA: Unknown; Special Requirements: AMD patientsSafety: 3 g

Omega-3 PUFAs: RDA levels &Special Requirements"Recommended Daily Allowed (RDA): UNKNOWNResults of the baseline analysis of the NAT-2 Study showedthat patients with exudative AMD had low plasma levels of DHA• omega-6, omega-3, DHA reduced blood levels in healthy subjects (p

Omega-3 PUFAs: Safety"The US FDA (1997) has formally stated that consumption of up to3 g/d of marine-based ω-3 fatty acids is generally regarded as safeThis has been approved on the basis of specific considerations aboutthe three possible adverse effects of ω-3 PUFAs:• increase in LDL-cholesterol levels• excess bleeding• worsening of glycemic controlIt has been established that at doses of 1 g/d, which is the welladviseddose for patients with coronary heart disease, no adverseeffects are observed

Omega 3 intake & Risk of Dry Eye*95 % CIs (ARVO 2003) " 32,470 nurses " Age 45-84" Womenʼs Health Study—Schepens & HarvardUniversity" Adjust for age, hormone therapy, total fat intake" Food frequency questionnaires & dry eye selfassessments" Highest vs. Lowest OR=0.83 (CI 0.70-0.98) P=.04"Tuna Fish OR=0.82 (CI 0.67-1.00) 2-4 four ounce servings/wk;OR=0.34 (CI0.13-0.81) 5-6 servings/wk P=.004"*Trivedi K, Dana M, Gilbard J, Buring J, Schaumberg D, ARVO, 2003, poster #811"

Prospective Study of Dietary Fatand the risk of AMD Am J Clin Nutr 2001;Feb 73(2) 209-18" Prospective follow-up Nurses Health Study! 1974 baseline; 42,743 women & 29,746 men; >50yrs!CONCLUSIONS! TOTAL FAT WAS POSITIVELY ASSOCIATEDWITH AMD………………..but! Greater than 4 servings per week of fish wasassociated with a 35 % lower risk ofAMD: OR 0.65 !

OMEGA-3 PUFAs Intake & AMD RISK"AMD RiskPeople consuming high fat in diet showed an > AMD riskResults of Observational StudiesAMD ProtectionPeople with high fish intake showed a < risk of AMDStudy #1: Mares-Perlman et al, Arch Ophthalmol 1995 - Beaver Dam Eye Study80% increased risk of AMDStudy #2: Smith et al, Arch Ophthalmol 2000 - Blue Mountain Eye Study171% increased risk of AMD 54% reduced risk of AMDStudy #3: Heuberger et al, Arch Ophthalmol 2001 - NHANES Survey40% increased risk of AMD 60% reduced risk of AMDStudy #4: Seddon et al, Arch Ophthalmol 2003 - EDCCS Study44% increased risk of AMD 40% reduced risk of AMDStudy #5: Cho et al, Am J Clin Nutr, 200154% increased risk of AMD 35% reduced risk of AMDStudy #6: Seddon et al, Arch Ophthalmol 2003190% increased risk of AMD 64% reduced risk of AMDStudy #7: SanGiovanni et al, ARVO 2003 - AREDS Study51% reduced risk of AMD59Global Pharmaceuticals CategoryStudy #8: Chua et al, Arch Ophthalmol 200642% reduced risk of early AMD; 75% reduced risk of late AMD

KEY LECTURE POINT Omega 3 fatty acids" Diminish inflammatory cornealsurface & meibomian glanddysfunction.! Augment the lipid component ofthe tear film (prevent evaporation).! Indirectly stimulate tear lacrimalsecretion.!

omega-3 intake recommended byauthorities"AgencyorGroupISSFALInternationalSoc for Studyof Fatty Acidsand LipidsADAAmericanDiabetesAssoc.AHAAmericanHeart Assoc.JDGPJeffry DavidGerson ProtocolDailyintake ofomega-3advised(in mg)500-650 400-600At least2-3 fishservingsweekly(equiv toabout400-600)Min. 400Everyone:at least 2serv/week(about 400)CHD: 1 g ofomega-3daily1g/dayDHA/EPArealisticrecommendationFish >1x/wk*Salad Baranalogy

AREDS Report # 20 The relationship of dietary lipid intake AMDArch Ophthalmol. 2007 May;125(5):671-9. "Dietary total omega-3 long-chain polyunsaturated fatty acid(LCPUFA) intake was inversely associated with "neovascular(NV) AMD (OR 0.61; 95% CI 0.41-0.90) as (DHA)docosahexaenoic acid, a retinal omega-3 LCPUFA (OR, 0.54;95% CI, 0.36-0.80), comparing highest vs lowest quintile ofintake, after adjustment for total energy intake and covariates. "Higher fish consumption, both total and broiled/baked,was also inversely associated with NV AMD (OR 0.61; 95%CI, 0.37-1.00 and OR 0.65; 95% CI, 0.45-0.93, respectively)."Dietary arachidonic acid was directly associated with NVAMD prevalence (OR 1.54; 95% CI, 1.04-2.29). "

CAROTENOIDS: Localization"Lutein and Zeaxanthin in the EYE:MaculaLUTEA ‘Macula lutea’ possesses the highestconcentration of photoreceptors -- responsible forcentral vision. L/Z form the Macular Pigment (MP) (yellowpigment) of the macula luteaThe concentration ratio between L/Zchanges with eccentricity(Z is the dominant pigment in the innerregion, whereas L is predominantperipherally)InnerL/Z ratio 1:2.4MedialOuterL/Z ratio over 2:1

Carotenoids: Mechanism of Action & Activities"L U T E I N & Z E A X A N T H I NANTIOXIDANT - OPTIC FILTERS Protect retina from free radicals: act as antioxidantsUltraviolet380 nmInfrared760 nm Protect retina against light-induced damage: act as optic filters through which light passesbefore attaching the photoreceptor cells. absorb blue light (400-550nm, peak at460nm) which is the most toxic wavelength inthe visible light spectrum

Chemical Structure of Lutein and Zeaxanthin"LUTEIN Found in most fruits and vegetables "Role of lutein well known in plants"Beta Carotene and Lutein are predominant carotenoids found in higher greenplants"ZEAXANTHINRelatively minor component of higher green plantsVery limited data for ZX content of foodsConjugated double bonds are highly effective in quenching singletoxygenZX has an extra conjugated double bond, as compared to lutein, whichmay make it a better antioxidant (

3 Human Macular PigmentsLutein, Zeaxanthin & Meso-zeaxanthin! Lutein is 5x more common in the US diet.! Carotenoid ratios, L:Z:M! Blood: ! ! 3:1:0! Whole retina: ! 2:1:0.5! Fovea: ! ! 1:2:1! meso-zeaxanthin is uniquely found in theposterior fovea (only synthesized from lutein)and may be very important.!!Photomicrograph courtesy of Dr. Joanne Curran-Celentano.

“Enhancing Vision”(with the carotenoids Lutein & Zeaxanthin)*" LAST – April 2004 ! TOZAL – Feb 2007 " LUXEA – April 2006 & Feb 2007 " LUNA – April 2007" TOZAL – Feb 2007 " LAST II – May 2007" CARMIS – Feb 2008"*AREDS II is not formally evaluating Macular Pigment

Lutein preventscataracts"Lyle (1999) Beaver Dam Study, Am J Epidemiology 1;149:801-9Chasan-Taber (1999) Am J Clin Nutr 70(4):509-516 (women)Brown et al (1999) Am J Clin Nutr 70(4):517-24 (men) Lutein is deposited in the lens." Lutein may have protective role on the development ofnuclear cataracts and a diet high in lutein may slow cataractprogression." Increased MPOD is associated with decreased lens density.(Hammond et al)"

LUTEIN and CATARACTSBrown et al (1999) Am J Clin Nutr 70(4):517-24"36,344 men age 45-75"Dr Seddon, Harvard School of Public Health" After controlling for risk factors such as smokingand age, men with the highest consumption oflutein and zeaxanthin had a 19 % lower risk ofcataract."Men

AREDS Report # 22Arch Ophthalmol. 2007 Sep;125(9):1225-32. " Demographic, lifestyle, and medical characteristics were ascertained on4519 AREDS participants aged 60 to 80 years at enrollment. " Dietary lutein/zeaxanthin intake was inversely associated" Large or extensive intermediate drusen (OR 0.73; 95% CI,0.56-0.96). " Neovascular AMD (OR 0.65; 95% CI 0.45-0.93)." Geographic atrophy (OR 0.45; 95% CI, 0.24-0.86)" Highest vs lowest quintiles of intake, after adjustment for total energyintake and non-nutrient-based covariates. "

L/Z Dietary Intake & AMD Risk?"Higher dietary intake of L/Z seems associated witha lower risk of AMD*Lutein and Zeaxantin are found in the Macula*Results of Observational StudiesSeddon et al, JAMA 1994Highest dietary intake of L/Z was associated with a 57% reduced risk of AMDSnellen et al, Acta Ophthalmol Scand 2002The prevalence rate of AMD in patients with low L/Z intake was about twice as high asthat in patients with high L/Z intake (OR=2.4)Moeller et al, Arch Ophthalmol 2006 – Carotenoids in Age-Related Eye Disease StudyHighest dietary intake of L/Z was associated with a 43% reduced risk of AMD

L/Z Dietary Intake & AMD Risk?"Highest L/Z dietary intake (3-6 mg/day) is associated with a reduced risk(43%-57%) of AMD compared to lowest L/Z intake (less than 1 mg/day)AMD Risk (Odds Ratio)10,50.8 mg0.5 mg43%ÔAMDRisk3 mgMoeller et al.Seddon et al.57%ÔAMDRisk6 mg0Low intakeHigh IntakeMoeller et al, Arch Ophthalmol 2006; Seddon et al, JAMA 1994.

Lutein + Zeaxanthin & AMD*6 mg. intake per day led to a 43% reduction insevere AMD prevalence* - Adapted from Seddon JM et al.JAMA 1994; 272: 1413 -1420.

MPOD / Lutein Quiz" How much Lutein does the average Americanconsume on a daily basis?" .5-2mg" How much lutein is thought to be an adequate level?" 6mg"OHOH How much lutein is in Centrum silver?" 250micro grams"HOHO How much lutein is safe?" 38mg/day or up to 2mg/kg/day"

Safety of Zeaxanthin and Lutein(no safety data available for meso-zeaxanthin)! " NO Adverse Effect Level (NOAEL) ">20 mg/kg/bw)Equivalent to 1,590 mg for a 175 lb. man" UN/WHO Acceptable Daily Intake (ADI) " 2 mg/kgbw" Equivalent to 160 mg for a 175 lb. man"

Zeaxanthin vs. Lutein in the Diet!10090100807060LuteinZeaxanthin(1 cup serving - cooked)5040302020.214.813.311.7100Kale0.30.6CollardGreens0.4Spinach0.4TurnipGreens3.4 0.6 1.2 0.5Broccoli Corn OrangePepper0 1.5 0GojiBerry

Lycopene" Carotenoid found in tomatoes" Ten times more potent than Vitamin E" Inherent putative anti-inflammatory effects" Thought to be protective for:" AMD" Prostate disease" Cancers" Cardiovascular disease "

Pycnogenol" Found in French maritime pine barkextract : And is Expensive as supplement" Protective against hyperglycemia inducedoxidative damage" Minimal if any affect on BG" Has been shown in studies to prevent and/or reverse diabetic retinopathy"

ZINC: Localization"In the BODY:in all body organs, tissues and fluidsIn the EYE:more concentrated than in otherparts of the body (RPE)• LensAppeared to be the“driver” in AREDS• Iris• Cornea• Sclera• Choroid• Retina• Optic Nerve

Zinc cont." Essential trace mineral important in ATP production, immunity,brain & retinal function, growth, development and fertility" RDA is 11mg/day with safe upper limit of 40mg***Sources: oysters, seafood, meat, eggs, tofu, wheat germ andblack eyed peas" Excess: *Can cause urinary tract infections, immune systemproblems and copper deficiency*, impaired kidneys and neovasc."Over 300mg/day impairs immune function and blood formation" Deficiency: Can cause poor wound healing, mental sluggishnessand susceptibility to infections" Zinc prevents night blindness due to normal zinc levelsenhancing activity of retinol dehydrogenase" Alzheimerʼs: Conflicting data, likely not significan either way "

Sorting through it all" There are SO many differentformulations" Some are found in stores and others inprofessional offices only" Beware of formulations and claims" Multivitamins vs single vitamins vs eyeformulations"An ounce of prevention is worth a pound of cure!!A pound of prevention may be worth the same pound of cure!

Are there more?" Cinnamon" Circumin" Bilberry" Green-Tea Extract" Genistein" Grape Seed Extract"

Take Home Message"1.Average patient"2. ”Worried well”"Patient with early AMD orFamily hxand worried"3. Intermediate or advanced AMD"Value of Lutein"Not in AREDS but studies have "shown benefit (LAST)"Either by supplement or green leafyvegetables"DISCUSS DIET and"SMOKING!"

Conclusion" Educate yourselves and your patients asto importance of antioxidants/nutrition" Donʼt be afraid to ask questions andmake recommendations"

Thank You" Jeffry Gerson, O.D., F.A.A.O.""

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