Transcript Age-Related Eye Disease Study (AREDS2)

The Science Behind
Ocular Health and Nutrition
Harvey Richman, OD, FAAO, FCOVD
Age-Related Eye Disease Study (AREDS):
Rationale and Significance
AREDS: NEI Trial Overview
Feature
Description
Objective
To evaluate the effect of high-dose vitamin
supplementation on age-related macular
degeneration (AMD) progression and visual
acuity.
Design
Double-masked, randomized, placebocontrolled trial
Population
3640 high risk patients (55-80 years)
Duration
6.3 years supplementation and follow up
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for
age- related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001.119(10): 1417-36.
AREDS Rationale for Studying AMD
 A leading cause of vision impairment and blindness in the United
States1.
 Common in age 60 or older2.
 Macula damage (for sharp, detailed central vision)2.
 Presentation2
No Pain / Blurred Vision / Drusen
 Advanced Disease3
Drusen 125+ μm / Neovascular AMD /
Geographic atrophy
1. The Age-Related Eye Disease Study (AREDS): Design Implications: AREDS Report No.1 Arch Ophthalmol 1999 December ; 20(6): 573–600.
2. Age-related Eye Diseases and Conditions. NEI Slide Presentation. Available at:
http://www.nei.nih.gov/nehep/programs/visionandaging/materials/VandAToolkit_Mod2_Powerpoint_508.pdf-10-15-2010. Accessed July 20, 2011
3. Potential Public Health Impact of Age-Related Eye Disease Study: AREDS Report No. 11 Arch Ophthalmol 2003 November ; 121(11): 1621–1624..
AREDS Rationale: AMD Risk Factors
 Advanced age
 Race
 Family history
 Female
 Current or former smoker
 Poor diet
 Obesity
www.neh.nih.gov/health/maculardegen/ARMD
Daily Dosage in AREDS
Supplements were manufactured to have the following minimum contents:
Supplement
Beta-carotene
Vitamin C
Zinc
Copper
Vitamin E
Dosage
15 mg
500 mg
80 mg
2 mg
400 IU
A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for
age- related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001.119(10): 1417-36.
AREDS Rationale: Beta-Carotene
• Why is it important?
▫ Body unable to synthesize1
▫ Antioxidant capability1
• How much do I need each day?
▫ 15 mg/day (AREDS)2
• Where can I get it in my diet?
▫ Carrots, broccoli, spinach, kale3
1. Paiva SAR, Russell RM, Dutta SK. β-carotene and other carotenoids as antioxidants. Journal of the American College of Nutrition. 1999;18(5):426–433.
2. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related macular
degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119(10): 1417-36.
3. USDA National Nutrient Database for Standard Reference http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR23/nutrlist/sr23a320.pdf Accessed 21
July 2011
AREDS Rationale: Vitamin C
• Why is it important?
▫ Body unable to synthesize1
▫ Antioxidant capability1
• How much do I need each day?
▫ 500 mg/day (AREDS)2
• Where can I get it in my diet?
▫ Citrus fruits and juices3
1. G. Sotoudeh G, Vitamin C function and status in chronic disease. Nutrition in clinical care. 2002; 5(2): 66-74.
2. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for agerelated macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119(10): 1417-36.
3. USDA National Nutrient Database for Standard Reference
http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR23/nutrlist/sr23w401.pdf Accessed 21 July 2011
AREDS Rationale: Vitamin E
• Why is it important?
▫ Body unable to synthesize1
▫ Antioxidant capability1
• How much do I need each day?
▫ 400 IU/day (AREDS)2
• Where can I get it in my diet?
▫ Nuts, fortified cereals, sweet potatoes3
1. Traber et al. Vitamins C and E: Beneficial effects from a mechanist perspective. Free Radic Biol Med. 2011 May 25. [Epub ahead of print]
2. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related
macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119(10): 1417-36.
3. USDA National Nutrient Database for Standard
Referencehttp://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR23/nutrlist/sr23w323.pdf Accessed 21 July 2011
AREDS Rationale: Zinc
• Why is it important?
▫ Essential trace element1
• How much do I need each day?
▫ 80 mg zinc/day (AREDS)2
• Where can I get it in my diet?
▫ Red meat, poultry, mixed nuts2
1. Grahn, BH, Paterson PG, et al. Zinc and the eye. Journal of the American College of Nutrition 2001; 20(2 Suppl: 106-18.
2. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related
macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119(10): 1417-36.
AREDS Rationale: Copper
• Why is it important?
▫
▫
▫
▫
Essential trace element1
Both an anti-oxidant and pro-oxidant2
Body unable to synthesize2
High zinc may cause copper deficiency3
• How much do I need each day?
▫ 2 mg/day (AREDS)4
• Where can I get it in my diet?
▫ Seafood, Liver, Nuts, Legumes2
1. Determinants of copper needs across the lifespan. Office of Dietary Supplements. National Institues of Health. Accessed at:
http://ods.od.nih.gov/News/Copper.aspx. Accessed August 31, 2011.
2. Copper Overview. University of Maryland Medical Center. Accessed at: http://www.umm.edu/altmed/articles/copper-000296.htm. Accessed August 31, 2011.
3. NIH Dietary Supplement Fact Sheet: Zinc. Available at: http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional / Accessed 21 July 2011
4. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related macular
degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119(10): 1417-36.
AREDS: Observations
• AMD: a nutrition responsive disorder.1-3
• Placebo: 29% progression risk from baseline at 5 years.1
• Antioxidants and zinc: 25% risk-reduction from baseline of visual
acuity loss.1
• Lutein/zeaxanthin and omega-3 fatty acid: Intake was independently
linked with decreased likelihood of:1,2,3
Neovascular AMD (Lutein/zeaxanthin, Omega-3s)
Geographic atrophy (Lutein/zeaxanthin, Omega-3s)
Large extensive intermediate drusen (Lutein/zeaxanthin)
1. .Age-Related Eye Disease Study Research Group. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study:
AREDS Report No. 22 Arch Ophthal 2007. 125(9), 1225-1232.
2. SanGiovanni JP, Chew EY, Clemons TE, et al. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study:
AREDS Report No. 20. Arch Ophthalmol. 2007 May;125(5):671-9
3. Sangiovanni JP, Agrón E, Meleth AD, et al. 6. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central
geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr. 2009 Dec;90(6):1601-7. Epub 2009 Oct 7.
Macular Pigment
Significance of Lutein and Zeaxanthin
• Only dietary carotenoids are found in the
macula1
• Body cannot synthesize2
• 5:1 ratio of lutein to zeaxanthin in the diet3
Yellow macular pigment
composed of
lutein and zeaxanthin
 Powerful Antioxidant4
 Reduces free radical damage in the eye
1.Lutein and Zeaxanthin Alternative Medicine Review 2005; 10(2): 128-135.
2. Nutritional Supplements for Eye Health. Bausch & Laumb Website; Available at: http://www.preservision.co.uk/. Accessed 3 October 2011
3. Thurnham DI. Macular zeaxanthins and lutein—A review of dietary sources and bioavailability and some relationships
with macular pigment optical density and age-related macular disease. Nutr Res Rev. 2007;20:163–179.
4. Subczynski WK, et al. Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes.
Archives of Biochemistry and Biophysics 504 (2010) 61–66.
Meso Zeaxanthin
Converted from Lutein
How much?
 90 males with AMD:
 10 mg FloraGLO® lutein
 10 mg FloraGLO® lutein
+ antioxidants
 Placebo
 Improvements in visual
Macular pigment optical density
Lutein Antioxidant Supplementation Trial (L.A.S.T.) and
Macular Pigment Optical Density (MPOD)
0.6
36%
improvement
0.5
43%
improvement
*
*
*
0.4
0.3
0.2
0.1
0 Right eye
Left eye
Lutein
function
Baseline
Right eye Left eye
Right eye Left eye
Lutein +
antioxidants
Placebo
Final visit
*P<0.05
Richer et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic agerelated macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr;75(4):216-230.
*FloraGlo is a registered trademark of Kemin Industries, Inc.
Long-term FloraGLO® Lutein and Zeaxanthin
Supplementation Improves MPOD in AMD
LUTEGA STUDY
 172 subjects (50+, AMD)
MPOD CHANGES
 Double-masked, randomized:
1 mg Zeaxanthin /
255 mg Omega-3 QD
10 mg FloraGLO® Lutein /
1 mg Zeaxanthin /
255 mg Omega-3 BID
 Placebo
 4 evaluations over 12 months
Placebo
Absolute Change in ODU*degree²
10 mg FloraGLO® Lutein /
QD Daily supplementation
Supplementation in Months
Jentsch S, et al. The Lutega- Study: Lutein And Omega- 3- Fatty Acids And Their Relevance For Macular Pigment In Patients With Age-related
Macular Degeneration (AMD) . Poster presented at: 2011 Association Research in Ophthalmology Meeting. May 1-5, 2011. Ft. Lauderdale, FL.
P3623/A624.
*FloraGLO is a registered trademark of Kemin Industries, inc.
Increased MPOD May Have an Effect on Visual
Performance
• Improvement of visual performance associated with increase MPOD
include:
 Glare tolerance1
 Glare recovery1
 Contrast sensitivity2
 Amsler defect and
improvement3
 Chromatic aberration2
 Photophobia4
VA
1.Stringham JM, Garcia PV, Smith PA, et al. Macular Pigment and Visual Performance in Glare: Benefits for Photostress Recovery, Disability Glare, and
Visual Discomfort. Invest Ophthalmol Vis Sci. 2011 Feb 4..
2. Loughman J, Akkali MC, Beatty S, et al. The relationship between macular pigment and visual performance.. Vision Res. 2010 Jun 18;50(13):1249-56.
Epub 2010 Apr 13..
3. Richer et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST
study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr;75(4):216-230.
4. Wenzel et al., 2006 A.J. Wenzel, K. Fuld, J.M. Stringham and J. Curran-Celentano, Macular pigment optical density and photophobia light threshold. Vision Research, 46 28 (2006), pp. 4615–
4622.
ICP11003SK
Omega-3 Fatty Acids (DHA/EPA)
 Important for proper visual development and
retinal function.
 Docosahexaenoic acid (DHA) is
in the highest concentration
retina.
 Eicosapentaenoic acid (EPA) is used
found
in the
in
DHA biosynthesis.
 Low levels of DHA and EPA have also been
associated with chronic eye conditions such as
diabetic retinopathy, age-related macular
degeneration (AMD), and retinopathy of
prematurity.
Figure accessed at:
http://lancastria.net/blog/omega-3-and-obesity.html
Accessed July 18, 2011.
American Optometric Association. Essential Fatty Acids; Available at: http://www.aoa.org/x11853.xml. Accessed 3 October 2011
Age-Related Eye Disease Study
(AREDS2): Key Issues
AREDS2*
Feature
Objective
Description
Assess effect of a alternative combination of
vitamins and minerals on the progression of
AMD and vision loss
Design
NEI 5 year, multi-center, randomized,
double-masked, placebo-controlled trial
Population
4000 patients at higher risk of developing
AMD (Men and women; 50 – 85 years)
Age-Related Eye Disease study 2 Protocol. Available at: www.emmes.com/study/areds2 . Accessed July 14, 2011.
AREDS2 Study Overview. Available at: http://clinicaltrials.gov/ct2/show/NCT00345176?term=AREDS2&rank=1. Accessed July 21, 2011.
AREDS2: To Evaluate…
Ingredients being studied in AREDS2:

FloraGLO® lutein (10mg)

OPTISHARP® zeaxanthin (2mg)

Omega-3 fatty acids (350 mg DHA, 650 mg EPA)

No β-carotene

Decreased zinc levels (80mg vs. 25mg)
Patients in the AREDS2 study are assigned to different
combinations of ingredients
Age-Related Eye Disease study 2 Protocol. Available at: www.emmes.com/study/areds2 . Accessed July 14, 2011.
AREDS 2 Study Overview. Available at: http://clinicaltrials.gov/ct2/show/NCT00345176?term=AREDS2&rank=1. Accessed July 21, 2011.
*FloraGlo is a registered trademark of Kemin Industries, Inc.
* Optisharp is a registered trademark of DSM IP Assets B.V.
AREDS2: To Evaluate…

Progression to advanced AMD

Progression to moderate vision loss

Progression of lens opacity

Effective cognitive function

Cardiovascular morbidity/mortality
Age-Related Eye Disease study 2 Protocol. Available at: www.emmes.com/study/areds2 . Accessed July 14, 2011.
AREDS 2 Study Overview. Available at: http://clinicaltrials.gov/ct2/show/NCT00345176?term=AREDS2&rank=1. Accessed July 21, 2011.
AREDS2 Disposition
Randomized Participants
~4200
Placebo
L/Z
DHA/EPA
L/Z+DHA/EPA
• No smoker can be in an
arm with beta-carotene
• The AREDS2 ATS meets
DSHEA requirements
• The original AREDS ATS
met USP requirements
ATS* Options
No ATS*
ATS*
AREDS2 Vitamin /
Mineral Evaluation
No ß-C
Low Zn
Original ATS*
No ß-C & Low Zn
Age-Related Eye Disease study 2 Protocol. Available at: www.emmes.com/study/areds2 . Accessed July 14, 2011.
AREDS 2 Study Overview. Available at: http://clinicaltrials.gov/ct2/show/NCT00345176?term=AREDS2&rank=1. Accessed July 21, 2011.
*AREDS type supplements.
Dietary Supplementation Recommendations:
Daily Intake of Key Ingredients
NEI AREDS2 Dosage Options
Lutein
(FloraGLO®)
Zeaxanthin
(OPTISHARP®)
10 mg/day
2 mg/day
Age-Related Eye Disease study 2 Protocol. Available at: www.emmes.com/study/areds2 . Accessed July 14, 2011.
AREDS2 Study Overview. Available at: http://clinicaltrials.gov/ct2/show/NCT00345176?term=AREDS2&rank=1. Accessed July 21, 2011.
FloraGLO is a registered trademark of Kemin Industries, Inc.
Optisharp is a registered trademark of DSM IP Assets B.V.
Dietary Sources of Lutein/Zeaxanthin
Romaine
lettuce
Spinach
Kale
Photos Courtesy of www.shutterstock.com
The U.S. Department of Agriculture National Nutrient Database for Standard Reference, Release 23. http://www.nal.usda.gov/fnic/foodcomp/search/ Accessed October
3rd, 2011.
Spirulina
A single dose of spirulina (an cyanbacteria) can increase
mean serum zeaxanthin concentration
Lutein + zeaxanthin
intake (mg/day)
Consumption of Lutein/Zeaxanthin in the US
10
9
8
7
6
5
4
3
2
1
0
19-30
Suggested intake
Women
31-50
Age
Men
51-70
Figure courtesy of Kemin Health, Inc.
71+
The average American only gets between 1 to 2.3mg per day of combined lutein and
zeaxanthin in their diet which is below the suggested intake of 10mg
CDC. National Health and Nutrition Examination Survey Data 2001-2002. Available at: http://www.cdc.gov/nchs/about/major/nhanes/nhanes01-02.htm.
Accessed July 14, 2011.
29 | ICP11001SK Ocular Nutrition | October 2011 | Business Use Only
Single Supplements Recommended Most Often by
Eye Care Specialists
Rank #1
Rank #2
Omega-3/
Fish Oil
48%
Lutein
29%
Lutein
31%
Omega-3/
Fish Oil
25%
Flaxseed oil
5%
Flaxseed oil
0% 20% 40% 60% 80% 100%
2010 (n=534)
20%
0%
20% 40% 60% 80% 100%
Base: Recommend Singe Supplement or Both Ocular Vitamins and Single Supplement
Q1555: When recommending supplements with specific ingredients, which of the following do you recommend most often? Please rank the three you
recommend most often by putting a 1 next to your most recommended, a 2 next to your second most recommended, and a 3 next to your third most
recommended. Alcon Data on File
30 | ICP11001SK Ocular Nutrition | October 2011 | Business Use Only
Ocular Vitamin Consumer Profile
 People who take ocular vitamin take an average of 364
tablets/capsules a year
 Thus people who take ocular vitamins take one
tablet/capsule per day
What opportunity exists to optimize ocular health
and increase patient compliance?
Homescan Product Library March 2011. Nielsen HH Panel Data.
Conclusions
 AREDS identified AMD as a nutrition responsive disorder, particularly in
relationship to high levels of lutein/zeaxanthin and omega-3.
 AREDS2 is accessing additional dietary ingredients including lutein, zeaxanthin
and omega-3s.
 Most Americans do not ingest 10 mg lutein and 2 mg of zeaxanthin
(the dose
evaluated in AREDS2) on a daily basis.
 Physicians recommend lutein and omega-3s, as the most commonly
recommended single supplements.
 Data shows that patients who take ocular vitamins, take on average
tablet/capsule per day.
one
Discussion / Questions