Ocular Nutrition and the Aging Eye

Advisory Board
Consultancies
◦ TearLab
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Biosyntrx, Inc.
Bausch + Lomb
Vistakon
OmniActive Health Technologies
Jeffrey Anshel, OD, FAAO
Ocular Nutrition Society
Ocular Nutrition Society
Editorial Advisory Board
◦ President, Founding Director
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Optometry Times
Primary Care Optometry News
Optometric Office
Review of Optometry
Integrative medicine is a healing-oriented medicine
that takes account of the whole person, including all
aspects of lifestyle.
It emphasizes the therapeutic relationship and makes
use of both appropriate conventional and alternative
therapies.
A philosophy that neither rejects conventional
medicine nor accepts alternative therapies uncritically
Use of natural, effective, less-invasive interventions
whenever possible
Integrative Optometry follows these same principles.
Age-adjusted Incidence Rate
Life expectancy increased, but quality of life is proving
to be dismal.
1.9 million people are living into their 90’s. This
number has tripled in the past 20 years.
By 2050, there will be 9 million people living this long.
We have a long “life span” but a shorter “health span”.
We die too slowly from chronic processes like stroke,
heart disease, cancer, diabetes, Alzheimer’s and
Parkinson’s.
Females
Males
1973
1999
1
Blindness:1 million over age 40
Visual impairment: 2.4 million
Dry Eyes: 12+ million
Macular Degeneration: 10.6 million
Cataracts: 20.5 million
Diabetic Retinopathy: 5.3 million
Glaucoma: 2.2 million (2 million undiagnosed)
These numbers will double in 20 years!
ALL ARE LINKED TO NUTRITIONAL DEFICIENCIES
Macular Degeneration
Cataract
Glaucoma
Dry Eye
Diabetes/Diet
Age
Gender
Hyperopia
Genetic predisposition
Smoking*
Blue light exposure*
Nutrition*
Obesity*
Cardiovascular Disease*
Hyperlipidemia*
Hypertension*
A condition in which the cells of the macula lutea
degenerate, resulting in blurred vision and
ultimately blindness
YOUR
Management
Co-Management
2
Formulation:
Sponsored the National Eye Institute (NEI)
Started in 1988
The trial included 3,780 participants who had at
least early AMD
Beta Carotene- 15 mg (25,000 IU)
Vitamin C- 500 mg
Vitamin E- 400 IU
Zinc (oxide)- 80 mg
Copper (oxide)- 2 mg
Note: 70% of participants also took full spectrum multiple
vitamin (Centrum) along with the study formula.
For those who initially had early AMD (Category
II), did NOT slow the disease's progression to
intermediate AMD.
Can people with early stage AMD take the AREDS formulation to help
prevent the disease from progressing to the intermediate stage?
There is no apparent need for those diagnosed with early stage AMD to
take the AREDS formulation. The study did not find that the formulation
provided a benefit to those with early stage AMD. If you have early stage
AMD, a comprehensive dilated eye exam every year can help determine if
the disease is progressing. If early stage AMD progresses to the
intermediate stage, discuss taking the formulation with your doctor.
National Eye Institute
Recommendation on Macular Degeneration
Started in 2007- published 2013
The population will involve at-risk patients as well as
patients with advanced AMD
1 gm EPA/DHA from Salmon Oil
Both lutein (10mg) and zeaxanthin (2mg)
10 mg lutein, plus 2 mg zeaxanthin, plus 1 gm
EPA/DHA
The original AREDs formula
◦ No beta-carotene
◦ Less zinc
A placebo????
“Reduces the risk of advanced AMD”
The effect was in 25% of the study population with
stage III AMD.
Slowed progression from stage III to IV.
Did not prevent AMD.
Did not reverse AMD.
Did not halt progression of AMD.
AREDS 1
Younger- avg. age 69
All AMD stages
Typical SAD diet
AREDS 2
Older- avg. age 74
Sicker- stage ¾
“Well-nourished”
Diabetes- 7%
67% taking Centrum Silver
(no lutein)
Demographic- unclear
Took placebo pills
Diabetes- 13%
89% taking Centrum Silver
(with some lutein)
Few Hispanics (2%)
No placebo (AREDS1)
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Placebo
Lutein/Zeaxanthin
Original
AREDS
formula
Lutein- 10mg
Zeaxanthin- 2mg
EPA/DHA
L/Z and
EPA/DHA
EPA- 650mg
DHA- 350mg
AREDS plus
L/Z and
EPA/DHA
Formulations Vitamin C
Vitamin E
Beta-carotene Zinc Oxide
Cupric
Oxide
1 (Original)
500 mg
400 IU
15 mg (25,000 IU)
80 mg
2 mg
2
500 mg
400 IU
0 mg
80 mg
2 mg
3
500 mg
400 IU
0 mg
25 mg
2 mg
4
500 mg
400 IU
15 mg (25,000 IU)
25 mg
2 mg
Progression to Advanced AMD
(AAMD)
Hazard
Ratio Tree Favors Favors
Treatment
CONCLUSION: “Addition of lutein + zeaxanthin, DHA+EPA or both to
the AREDS formulation in primary analyses did not further reduce risk
of progression to advanced AMD. However, because of potential
increased incidence of lung cancer in former smokers, lutein +
zeaxanthin could be an appropriate substitute in the AREDS
formulation.”
AREDS1 formulation with L/Z but no beta-carotene, their
risk of developing advanced AMD … was reduced by
about 18%, compared with participants who took an
AREDS formulation with beta-carotene but no L/Z.
Participants with low dietary intake of L/Z, but who took
an AREDS formulation with L/Z during the study, were
about 25% less likely to develop advanced AMD
compared with participants with similar dietary intake
who did not take L/Z.
Placebo
Lutein/Zeaxanthin
p=0.12
DHA/EPA
p=0.70
Lutein/Zeaxanthin+DHA/EPA
p=0.10
Placebo (reference)
0.7
Probabilities of progression to advanced AMD:
Placebo: 31%
L/Z: 29%
EPA/DHA: 31%
L/Z+EPA/DHA: 30%
0.8 0.9 1 1.1 1.21.3
1.21.3
Hazard Ratio (98.7%CI)
AREDS2 Research Group. (2013) JAMA, In Press.
Progression to AAMD by Primary and Secondary
Randomization Main Effects
Favors
Treatment
p = 0.02
L/Z vs. No L/Z
p = 0.01
DHA/EPA vs. No DHA/EPA
Favors
Favors
Control
Placebo
p=0.05
p=0.1
2
p=0.7
0
p=0.1
0
Low Zinc vs. High Zinc
BetaBeta-Carotene Yes vs. No
0.8
0.9
1
1.1
1.2
Hazard Ratio (95%CI)
AREDS2 Research Group. (2013) JAMA, In Press.
4
Formulation:
Beta Carotene- 15 mg (25,000 IU)
Vitamin C- 500 mg
Vitamin E- 400 IU
Zinc (oxide)- 80 mg ?
Copper (oxide)- 2 mg
Lutein/Zeaxanthin- 10mg/2mg
AREDS2
“The main study objective is to determine if these
nutrients will decrease a person’s risk of
progression to advanced AMD, which often leads
to vision loss.”
Still does NOT address prevention, halting or
reversal!
5,205 women without AMD, average age 63
All were permitted to take multivitamins with B-6, B-12 and folate up
to, but not exceeding, recommended daily allowance (RDAs).
Those getting the B-6, B-12 and folate supplements received much
larger amounts: 2.5 mg of folate (folic acid), 50 mg of vitamin B6
(pyridoxine) and 1 mg of B12.
After an average of 7.3 years of treatment and follow-up, there were
55 cases of AMD in the combination treatment group and 82 in the
placebo group (relative risk, 0.66; 95% confidence interval, 0.470.93 [P = .02]). For visually significant AMD, there were 26 cases in
the combination treatment group and 44 in the placebo group
(relative risk, 0.59; 95% confidence interval, 0.36-0.95 [P =.03])
Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular
Degeneration in women.
Christen W, Glynn R, Chew E, et al.
Archives of Internal Medicine. Vol 169 (4): Feb 23, 2009
“Vitamin D Status and Early Age-Related
Macular Degeneration in Postmenopausal
Women”
Conclusion: High serum 25(OH)D concentrations
may protect against early AMD in women younger
than 75 years.
Yellow, orange, red lipophilic pigments
~ 600 known carotenoids
40-50 in typical human diet
14 found in serum
◦ Lutein
Lutein, β-Carotene, Lycopene,
α-Carotene, Zeaxanthin,
Zeaxanthin β-Cryptoxanthin
Amy E. Millen, PhD, et al
Arch Ophthalmol. 2011;129(4):481-489
© Kemin Industries, Inc. 2006 All rights reserved. ® ™ Trademarks of Kemin Industries, Inc., U.S.A.
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Beta carotene is an effective antioxidant
It is not an appropriate source of Vitamin A
◦ Does not as readily covert to pre-formed Vitamin A (retinol) in the
older population as it does in younger people
◦ Does not convert to vitamin A if there are sufficient stores of Vitamin
A in the system.
Increased risk of cancer in smokers and SECOND-HAND
smokers!
Interferes with the absorption of lutein and zeaxanthin
“Higher beta-carotene intake was
associated with an increased
risk of AMD.”
Dietary Antioxidants and the Long-term Incidence
of Age-Related Macular Degeneration
(The Blue Mountain Eye Study)
Jennifer, SL Tan, et al. Ophthalmology 2008; 115:334-341
“Cage-Free” Chickens
6
CageCage-Free: This label simply means the absence of a cage. It doesn’t mean
the absence of fences or enclosures in general. Birds that qualify as cagefree can still be packed tightly into an overpopulated and darkened barn.
FreeFree-Range: Required to have access to the outdoors—but that may amount
to a narrow patch of dirt. Access to it can be a tiny door cut into the back of
the shed, which in an overcrowded barn stuffed with hens, the birds may not
ever notice, let alone use.
Organic: Birds are antibiotic and hormone-free, in addition to being provided
with access to the outdoors. Still, some organic farms abuse the system by
housing their hens in overcrowded sheds—with a small, unused door.
Certified Humane: According the Humane Society, even this certification
allows for farmers to house chickens indoors at all times if they choose, and
also permits beak cutting. A similar term, "American Humane Certified"
allows laying hens to be caged.
What to Look for Instead
PasturePasture-raised is a label used increasingly by smaller, sustainable chicken
farms to indicate that they legitimately raise their birds outside, on an actual
pasture. Hens also enjoy access to shelter when they choose to take it, and
they’re raised without the use of harmful chemicals or painful procedures.
Not a naturally occurring nutrient in
traditional diets
Is generated from the metabolism of
lutein
Does not convert from zeaxanthin
Meso-zeaxanthin
Zeaxanthin
Lutein
The second most abundant mineral in the body (calcium).
Critical in most metabolic processes, including DNA
replication.
Zinc oxide is the type that was used in the AREDS studies,
and the type which is still used by most formulators.
Monomethionine zinc is the most bioavailable form of zinc
and the only form that does not interfere with copper
absorption.
80 mg of zinc oxide is too much for long term daily
consumption.
High concentrations of zinc have been found in sub-retinal
pigment epithelial deposits, and have been associated with
urinary tract disorders.
Recommended daily intakes are:
Infants: 5 mg
Children:10 mg
Women:12 mg
Pregnant Women:15 mg
Lactating Women:16 mg
Men:15 mg
The tolerable upper limit for zinc was set at 40
mg per day for adults over 19.
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Vitamin E
A 2005 study in the JAMA suggested that excessive (400
IU) Vitamin E can be deadly!
A closer look shows that the isolated finding applied only
to an older group of patients (over the age of 70), had a
long history of heart disease, stroke or diabetes, and
were also taking a combination of medications, including
ACE inhibitors, calcium channel blockers, anti-platelet
agents and lipid-lowering agents during the course of the
study.
Vitamin E Family
Tocopherol (T)
Tocotrienol (T3)
Delta-T
Gamma-T
A significant percentage were also cigarette smokers!!
©1995-2003 by Michael W. Davidson
Delta-T3
GammaT3
Beta-T
Beta-T3
Alpha-T
AlphaT3
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Are blocked by tocopherols- especially alphatocopherol
Super-antioxidant (anti-cataract)
Increases tear production
Reduces diabetic retinopathy
Targets angiogenesis (AMD)
Best source- annatto beans: contain gamma and deltatocotrienol (best for cardio-protection, cancer and diabetes)
Fundus alterations:
pre treatment
A 24 month Italian double-blind AMD study
showed an improvement of visual functions and
fundus alterations in early AMD.
Phototrop® is a combination of:
◦
◦
◦
◦
DHA: increases cellular permeability
EPA: anti-inflammatory
Acetyl-L Carnitine: drives CoQ10 across the membrane
CoQ10: cleans out the mitochondria (antioxidant)
Fundus alterations:
post treatment
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The aqueous humor, which feeds the lens, has the
highest amount of Vitamin C of any fluid in the
body (26x more than in serum).
The lens has the highest concentration of protein
of any organ.
Recent studies have found significant amounts of
lutein and zeaxanthin in the lens.
Carbohydrate intake
Water Content
Protein
Sodium
Potassium
Calcium
Glutathione
Higher ALA (omega-3 alpha-linolenic acid)
intake is associated with a greater age-related
change in lens nuclear density.
BMI
◦ BMI > 30 or waist size > 35" is associated with two fold
increase in prevalence of PSC opacities
◦ Diabetes increases the odds for PSC opacities 4-fold.
Decrease
Ascorbic Acid
◦ Is related to increased odds for cortical opacities
Increase
Lu M, Taylor A. Chylack LT, Rogers G, et al. J Am Coll Nutr 2007 Apr;26(2):133-40
Alcohol
◦ Consumption of hard alcohol is associated with increased
risk for nuclear and cortical opacities.
◦ In contrast, moderate wine drinking decreases the risk for
cortical opacities.
(Flax seed oil is 85% ALA)
Age-related cataract is associated with
type 2 diabetes and statin use
1991
In this population, statin use was substantially higher in
patients with type 2 diabetes and was associated with agerelated cataracts.
Machan CM, Hrynchak P, Irving EL.
Optom Vis Sci. 2012 Aug;89(8):1165-71K
Vitamin E protects the lens against UVB-induced
cataract. (Leske, MC, et al. Ophthalmology 1998;105:831-6)
Canadian study found 200mg C, 400 IU E
protective for cataracts.(McRoberston J, et al. Am J Clin Nutr,
Antioxidant vitamins linked to a reduced risk of
cataract by 1/3 (Leske, MD, et al. Ophthal. 1998)
Vitamin E reduced cataract by half (Leske, MD, et al.
Ophthal. 1998)
17,000 physicians found daily multivitamin
reduced cataracts by 25% (Schaumberg D, et al. Am J Clin
Nutrition 2000;72:1417-8)
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Network Antioxidants
•Lipoic Acid
•CoQ10
Network Antioxidants greatly
enhance the power of one another.
They are particularly effective in
slowing down the aging process and
boosting the body’s ability to fight
disease.
•Glutathione
•Vitamin E
•Vitamin C
“Dietary omega 3 fatty acids
decrease intraocular pressure
with age by increasing aqueous
outflow”
CONCLUSION: Dietary manipulation may provide a
modifiable factor for IOP regulation.
“α-Tocopherol deserves attention beyond
its antioxidant properties for protecting
retina from glaucomatous damage”
Clinical evaluation of the neuroprotective effect of alpha-tocopherol against
glaucomatous damage
Eur J Ophthalmol 2007; 17: 528 - 533
Cellini M, et al. Fatty acid use in glaucomatous optic neuropathy
treatment. Acta Ophthalmol Scand Suppl . 1998;227:41-42.
The combination of a standardized extract of
bilberry and French maritime pine bark can
reduce the risk of glaucoma.
Molecular Vision 2008; 14:1288-1292
"Effects of Mirtogenol® on ocular blood flow and intraocular hypertension
in asymptomatic subjects"
Robert Steigerwalt Jr, et. al
Mirtogenol ® lowered elevated IOP in patients
almost as effectively as latanoprost, however,
it takes much longer (24 vs 4 weeks). The
combination of both was more effective for
lowering IOP and the combination yielded
better retinal blood flow
Mirtogenol® potentiates latanoprost in lowering intraocular pressure and improves ocular blood flow
in asymptomatic subjects
Robert D Steigerwalt Jr, Gianni Belcaro, Paolo Morazzoni, et al
Clinical Ophthalmology, May 2010 , Volume 2010:4
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“Our results suggested that oral administration of
BCACs may induce a beneficial decrease in IOP
levels in healthy subjects as well as in patients with
glaucoma.”
Effects of Black Currant Anthocyanins on Intraocular Pressures in Healthy
Volunteers and Patients with Glaucoma
Hiroshi Ohguro, Ikuyo Ohguro, and Saeko Yagi
Journal of Ocular Pharmacology and Therapeutics.
doi:10.1089/jop.2012.0071.
Age-adjusted Prevelence of Diagnosed Diabetes
Among US Adults
1994
Missing
Missing
data
data
4.5%–5.9%
4.5%–5.9%
7.5%–8.9%
7.5%–8.9%
Eat foods rich in carotenes and bioflavonoids, such as dark leafy
greens, yellow and orange vegetables and dark berries.
Avoid stimulating foods (ex. Sugar and refined foods), alcohol,
drugs, smoking, coffee, and salt
Vitamin C (500 mg four times a day)
Vitamin E (400 IU a day), vitamin A (5,000 IU a day), and
thiamine (10 mg a day)
Lipoid Acid (150 mg a day)
Acetyl-L-carnitine (200-500 mg a day)
Taurine (500 mg a day)
Selenium (200 mcg a day) and zinc (30 mg a day)
Omega-3 fatty acids (300 to 500 mg daily)
Ginkgo (120 mg a day) to improve blood circulation
Black Current Seed extract- (50 mg daily)
Age-adjusted Prevelence of Diagnosed Diabetes
Among US Adults
2010
<4.5%
<4.5%
6.0%–7.4%
6.0%–7.4%
≥9.0%
≥9.0%
Missing
data
Missing
data
4.5%–5.9%
4.5%–5.9%
7.5%–8.9%
7.5%–8.9%
<4.5%
<4.5%
6.0%–7.4%
6.0%–7.4%
≥9.0%
≥9.0%
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The Glycemic Index (GI) is a ranking of
carbohydrates on a scale from 0 to 100
according to the extent to which they raise
blood sugar levels after eating.
High GI Foods are those which are rapidly
digested and absorbed and result in marked
fluctuations in blood sugar levels.
Low GI foods, by virtue of their slow digestion
and absorption, produce gradual rises in blood
sugar and insulin levels, and have proven
benefits for health.
Chromium
Magnesium
Calcium
Potassium
Vitamin B3
Antioxidants
In patients with type 2 diabetes, researchers show a
6-month treatment with a low-glycemic index diet
may lower HbA(1c) levels compared with a highcereal fiber diet.
Effect of a Low-Glycemic Index or a High-Cereal Fiber Diet on Type 2 Diabetes
Jenkins, D, et al
JAMA, 2008; 300(23):2742-2753
◦ Vitamin C
◦ Vitamin E
◦ Selenium
THEN
NOW
Balance of saturated and
unsaturated fats
Overly saturated fats
Complex carbohydrates
Simple and refined carbohydrates
High quality plant and animal
protein
Corn-fed beef and poor quality
proteins
Nutrient dense foods supply
vitamins, minerals and
phytochemicals that create
antioxidants.
Chemically and genetically
modified, denatured and
“fortified” foods
CONTROLS INFLAMMATION
PROMOTES INFLAMMATION
Omega-3 PUFA
An enzyme that is required for electron transport in ATP
synthesis (facilitates energy production at the cellular
level)
95% of human body’s energy is generated this way!!
Immune system support
Provides antioxidative-bioenergetic balance
Useful in maintaining energy levels
Oxidative protection for cellular membranes and plasma
lipoproteins
Neuro-protective
Low level linked to decreased cardiovascular function
Decreased with statin use!
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Manufactured in the liver (only 25% from food)
Responsible for cellular health, hormone formation
and Vitamin D metabolism.
High Density Lipoprotein (HDL) removes cholesterol
from the cells and transports back to the liver.
Low Density Lipoprotein (LDL) transports cholesterol
and fat from the liver to the cells.
Found in every cell of your body, especially in the
membranes of these cells, where it helps maintain the
integrity of these membranes, and plays a role in
facilitating cell signaling
Molecule for molecule, cholesterol can make up nearly
half of the cell membrane.
Also present in membranes of organelles inside the cells.
About 25% of total body cholesterol is located in the
brain!!
Is the backbone of vitamin D (not really a vitamin)
LDL is harmless. It becomes a problem when
unstable free radicals oxidize it.
When LDL settles on artery walls, the wall
membranes release damaging free radicals.
The resulting oxidized LDL draws white blood
cells to the site. These form plaque and trigger
inflammation of the endothelium.
50% Calcium
3% Cholesterol
Statin
Reduce
Cholesterol
Increase
Blood Flow
Depletes
Enzyme CoQ10
CoQ10 Supports
Mitochondria Energy
Production
Statins*
Bile Acid Sequestrants*
Fibric Acid Derivatives*
Niacin (Nicotinic Acid)
Red
yeast rice
Fiber
Soy
Plant
Sterols
E (tocotrienols)
Intestinal Absorption Inhibitors Fish Oils/Omega-3s
Vitamin
Depleted Energy
Required For
Cells in Muscles
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“Reduction in inflammation has been shown to
have as beneficial an effect in reducing future
cardiovascular events as lowering cholesterol.”
Ridker, PM., et al, C-reactive protein levels and outcomes after statin
therapy, N. Engl. J. Med., 352, 20, 2005
Not really a vitamin- more like a steroid (a pro-hormone)
Formed from cholesterol!
D3 (cholecalciferol) is 70% more effective than D2
(ergocalciferol)
Regulates calcium and phosphorus levels in blood
(promotes absorption)
Reduces plaque deposits
Promotes phagocytosis, anti-tumor activity and
immunomodulatory functions.
Recommended: about 2,000 IU daily (sun UVB- is best
source)
What We Need
Calorie Restriction
Complex Carbohydrates
Reduce Cholesterol
Exercise
Nutrient Dense Foods
Portion Control
What We Do
Resveratrol
Fortified Foods
Take Statins
“Exercise in a Pill”
Genetically Modified
Food
SUPERSIZE ME!
RANK DRUG
Manufacturer Target
1
Lipitor
Pfizer
2
Advair
GSK
Asthma
3
Plavix
Bristol-Myers
Thrombotic Events
4
Nexium
AstraZeneca
GI disorders
5
Norvasc
Pfizer
Hypertension
RANK
CONDITION
# DEATHS
1
Heart Disease
616,067
562,875
Cholesterol
2
Cancer
3
Stroke (CV disease) 135,952
4
Respiratory disease 127,924
5
Accidents
123,706
6
Alzheimers
74,632
7
Diabetes
71,382
“Persons receiving 2.5 mg of folic acid, 25 mg
vitamin B6, and .5 mg vitamin B12 showed
regression of atherosclerosis evidenced by a
decrease in the thickness of the arterial wall, while
the those in the placebo group experienced an
increase.”
Decrease of Carotid Intima-Media Thickness in Patients at Risk to Cerebral Ischemia
after Supplementation with Folic Acid, Vitamins B6 and B12,
U Till et al., Atherosclerosis, July 2005
Be Critical!
There is no “magic bullet”
It matters not what you do once in a while, but
what you do every day.
You can’t throw a few pills after a bad diet and
expect miracles.
Balance is needed
because more is not
better…
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Thank you
Focusing on Nutrition Education
www.ocularnutritionsociety.org
Jeffrey Anshel, OD, FAAO
Ocular Nutrition Society
[email protected]
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