Nutraceuticals, Supplements & Vitamins - Michigan Optometric ...

Nutraceuticals, Supplements & 

Vitamins in Eye Care 

Gary E. Oliver, O.D. 

Associate Clinical Professor 

State University of New York 

State College of Optometry 

geoliver.od@att.net 

goliver@sunyopt.edu 

General Population Data 

• Literature confirms that good nutrition in 

general helps improve: 

• Stem cell activity 

• WBC activity 

• Healing processes 

• Proper gene expression 

Antioxidant-rich vitamin/mineral 

supplements 

• Be aware that most "one-a-day" vitamins, 

usually contain water-soluble vitamin C and Bcomplex 

vitamins which are excreted just 12 

hours after ingestion. 

• Ideally want supplements rich in amino acid 

chelates. This enhances bioavailability and 

reduces the side effects when combined with 

ionic salt forms of the minerals. 

General Population Data 

• 42% use complementary & alternative 

medicines, mostly vitamins 

• 5.4% of glaucoma patients use alternative 

medications 

• 8% use herbal medicines 

Some Side Effects Examples 

• General population usually not aware of some 

of the side effects 

• Excess vitamin D can affect bone metabolism 

• High doses of vitamin A can cause birth 

defects in pregnant women 

• Blood thinning effects of vitamin E 

Clinical Indications 

• Evidence may still be stronger for prophylactic 

than therapeutic usage 

• Antioxidant formulas – most common 

• Clinical Applications 

1

Age Related Macular Degeneration 


Pathophysiology 

– Reactive oxygen, generated through photo-oxidation and 

normal metabolic processes, likely contribute to 

degeneration 

– Accumulation of lipofucion pigment enhances the 

phototoxicity effects 

– Free radical formation following exposure to ionizing 

radiation, UV light, or visible light can enhance lipid perioxidation 

of the photoreceptor outer-segment 

membranes, which are rich in polyunsaturated fatty 

acids 


Epidemiological Studies 

– Observational studies have shown that 

individuals who have higher intake of 

antioxidant nutrients have decreased risks of 

ARMD 

– Beaver Dam Eye Study - large drusen formation 

reduced with intake of pro-vitamin carotenoids 

and vitamin E, higher intake of zinc associated 

with a decreased incidence of retinal pigmentary 

abnormalities 


Randomized Trials and Other Studies 

– Oral Zinc in Macular Degeneration - small pilot 

study, 174 patients randomly received 80 mg 

zinc or placebo, less visual acuity loss with zinc 

intake, study concluded early due to concerns 

about zinc toxicity and incidence of ARMD in 

untreated group unusually high 

– Multicenter Ophthalmic and Nutritional ARMD 

Study - stabilization of ARMD with broad 

spectrum antioxidant formula, possible 

increases in visual function 


– Complex disorder involving genetic, cardiovascular, and 

environmental factors 

– Risk factors include age, ethnicity, gender, genetics, 

cardiovascular disease, smoking and sun exposure 

– Cumulative oxidative stress may contribute to apoptosis of 

the photoreceptors 

– Oxidation, inflammation, neovascularization result 

– Decreased xanthophylls, vitamin E and other antioxidant 

intake emerging as key nutritional factors 


– Physicians Health Study I - men taking vitamin E 

supplements had 13% reduced risk of ARMD, 

multivitamin supplements resulted in 10% 

reduced risk, no reduced risk associated with 

vitamin C supplements 


Age Related Eye Disease Study (AREDS) – broad 

based clinical trial looking at antioxidant & vitamin 

supplementation intake on age related macular 

degeneration 

Lutein Antioxidant Supplementation Trial (LAST) – 

clinical trial studied lutein supplementation and 

lutein with antioxidants supplementation 

LAST II – clinical trial to determine which 

patients benefit the most 

2


Taurine, Omega-3 fatty acid, Zinc, Antioxidant, 

Lutein Study (TOZAL) – trial examined effects 

of omega-3 fatty acids and other nutrients on 

reducing the progression of ARMD 

Nutritional Supplements for Prevention 

of ARMD 

Carotenoids 

• Lutein - primary macular pigment with antioxidant 

activity, increased intake (10-30 mg/day) increases 

accumulation in macula 

– Some studies found 6 mg/day initially, 2 mg/day 

maintenance reduced risk 

– More recent study – no increase in MPOD with 6 

mg/day lutein, need at least 10 mg 

• Zeaxanthin - primary macular pigment with antioxidant 

activity, increased intake (2-6 mg/day) increases 

accumulation in macula 

• Elevated intakes reduce risks of ARMD 

• Yellow xanthophyll plant pigments 

Nutritional Supplements for Prevention of 

ARMD 

• Macular pigment decreased in smokers, 

females > males, light color iris 

• Macular pigment may result directly from 

dietary origins with healthy and diseased 

macula capable of accumulating and 

stabilizing both lutein and zeaxanthin 


• Age Related Eye Disease Study 2 (AREDS 2) – broad 

based study similar design to AREDS to investigate 

effects of lutein, zeaxanthin and omega-3 fatty acid 

(EPA, DHA) supplementation on ARMD disease 

progression 

• Patients with intermediate or advanced ARMD 

• AREDS 2 to refine original AREDS formula 

• AREDS 2 to assess the effects of reducing zinc and 

eliminating beta-carotene on progression of ARMD 


of ARMD 

• Lutein - concentrated in the macula lutea, acts as 

antioxidant, also found in the aqueous 

• Zeaxanthin - primary macular pigment, acts as 

antioxidant, predominant pigment in central fovea 

• Zeaxanthin – 11 double bonds compared to 10 for 

lutein, possibly greater protection against blue and 

near ultraviolet light 

• Pigments also found in inner layers of retina, may 

protect against photo-induced (blue light) retinal 

damage, increased pigment concentrations 

associated with higher visual sensitivity 


ARMD 

Lutein Antioxidant Supplementation Trial 

• 15mg lutein, 20 mg vitamin E 

• Positive effect on macular function 

AREDS Report 22 – Higher dietary intake of 

lutein/zeaxanthin independently associated with 

decreased likelihood of having neovascular ARMD, 

geographic atrophy, and large or extensive 

intermediate drusen 

3


ARMD 

• CAREDS 

– diets rich in lutein plus zeaxanthin may protect 

against intermediate ARMD in healthy women 

younger than 75 years of age 


ARMD 

Beta Carotene, Retinols 

• Beta carotene not found in significant amounts in the 

eye but still important in rod photo-physiology, binds 

with protein opsin in rods to form rhodopsin 

• Retinol essential for proper wound healing and 

immune function 

• Important for goblet cell metabolism and production 

of mucins in tear film 

• No significant benefits for prevention of ARMD by 

itself 

• High levels linked to increased incidence of lung 

cancer in heavy smokers 


ARMD 

• Omega 3 supplementation eicosapentaenoic acid 

(EPA) 

• Believed to regulate levels of Omega 6 amino acid 

• Omega 6 implicated in abnormal retinal 

neovascularization, vascular permeability, and retinal 

inflammation 

• EPA also depresses VEGF receptor activation and 

expression 


ARMD 

Lycopene 

– Strong antioxidant activity 

– Protective effect against aging of retinal pigment 

epithelial cells 

– Although not involved in macula, found in high 

concentrations in the ciliary body and RPE 


ARMD 

• Omega 3 supplementation docosahexaenoic acid 

(DHA) 500 mg/day may improve cell biogenesis and 

neuronal signaling 

• Major component of retinal photoreceptors outer 

segment membranes 

• Synaptic membranes and photoreceptors have 

highest concentration of DHA 

• DHA (docosahexaenoic acid) - concentrated in 

phospholipids of retina and brain 


ARMD 

• AREDS researchers surveyed subjects on dietary 

components 

• Subjects with the highest levels of omega-3 fatty acid 

intake had decreased risk of neovascular ARMD 

• Those with higher levels of serum vitamin D less 

likely to develop early dry ARMD 

4


ARMD 

• TOZAL Study 

• Vision stabilized or improved in 67% of patients who 

used nutritional supplements with omega-3 fatty 

acids and antioxidants 


of ARMD 

Vitamins 

• Vitamin E 400 IU/day 

– May protect retina from oxidative damage due 

to excessive sunlight exposure 

• Vitamin C 200-1,000 mg/day 

– Antioxidant and anti-inflammatory properties, 

questionable as single agent for prevention of 

ARMD 

– May improve synergy of antioxidants 


ARMD 


• Vitamin D - patients with higher levels of serum 

vitamin D appear less likely to develop early dry 

ARMD 

• Vitamin D early data 200-400 IU for younger and 

older adults respectively, today higher amounts 

considered important 2,500-4,000 IU to increase 

blood serum levels 

• 2,000 IU daily increases anti-inflammatory cytokine 

IL-10 and decreases pro-inflammatory TNF-alpha 

• Suppresses retinal neovascularization in mouse 

model 


of ARMD 

Minerals 

• Zinc 25-50 mg/day (typically 25-30 mg/day) - 

reduced rate of visual acuity loss, no benefit or 

protection of the fellow eye in patients with 

choroidal neovascularizaiton in one eye 

• Monomethionine zinc is the most bioavailable 

form, only form that does not interfere with copper 

• Zinc toxicity associated with genitourinary and 

gastrointestinal disorders 


ARMD 


• B-Complex vitamins (B6, B12, folate) 

• Helps keep homocysteine levels within a normal 

range 

• Elevated plasma homocysteine levels associated with 

exudative neovascular ARMD 

• Should always be taken together as a complex 


ARMD 

• Lowers the risk for some cancers including breast, 

prostate and colon 

• May also lower blood pressure in hypertensive 

patients 

• Improves bone calcium absorption which also lowers 

amount of calcium plaques 

5


ARMD 

Age Related Eye Disease 

Study (AREDS) 

• Antioxidant formula – daily 

• 500 mg vitamin C 

• 400 IU vitamin E 

• 25,000 IU beta carotene 

• 80 mg zinc oxide 

• 2 mg copper oxide 

AREDS 10 Yr Results 

Those patients with extensive intermediate size 

drusen, at least 1 large drusen, noncentral 

geographic atrophy in 1 or both eyes, or 

advanced AMD or vision loss due to AMD in 1 

eye and without contraindications such as 

smoking, should consider taking a supplement 

of antioxidants plus zinc such as that used in 

the AREDS study. 


• Persons who smoke are at increased risk for 

both ARMD and lung cancer. 

• Results from 2 other randomized clinical trials 

suggested increased risk of mortality among 

smokers supplementing with beta carotene. 

• Prudent for smokers to avoid taking beta 

carotene. 


Patients taking antioxidants alone or zinc alone 

reduced their risk by 17% and 21% 

respectively. 

Patients taking antioxidants plus zinc reduced 

their risk by 25%. 


• Studies using similar doses of beta carotene in 

persons at high risk for lung cancer (cigarette 

smokers and asbestos workers) have 

demonstrated an increased incidence of 

cancer and mortality. 

ARMD Categories 

• Category 1 – no ARMD, fewer than five small drusen 

(less than 63 um), visual acuity 20/30 or better in 

both eyes 

• Category 2 – mild ARMD, multiple small drusen or 

medium drusen (63-124um) in one/both eyes or RPE 

abnormalities, visual acuity 20/30 or better in both 

eyes 

6

ARMD Categories 

• Category 3 – at least one eye with visual acuity of 

20/30 or better with at least one large drusen 

(125um or greater), extensive intermediate drusen, 

absence of geographic RPE changes in center of 

macula or any combination 

• Category 4 – advanced ARMD or visual acuity less 

than 20/30 in one eye with the degenerative changes 

as the cause of the reduced vision, fellow eye visual 

acuity 20/30 or better 

Patient Criteria for AREDS Antioxidant 

Supplements 

• Extensive intermediate size drusen (63um to 125um) 

• At least 1 large drusen (greater than 125um) 

• Noncentral geographic atrophy in one or both eyes 

• Advanced AMD or vision loss due to AMD in one eye 

• No contraindications such as smoking 

Age Related Cataracts 

• Ultraviolet light (particularly UVB) and 

oxidative stress may lead to development 

Patient Criteria for Lutein/Antioxidant 

Supplements 

• At risk patients 

• Pigmentary abnormalities 

• Pigment changes with few small drusen 

• Extensive small drusen (less than 63um) 

• One or few intermediate size drusen (less than 

125um) 

Retinitis Pigmentosa 

Clinical Trials 

– Randomized clinical trial over 4-6 year period 

– 15,000 IU vitamin A (retinal palmitate 

formulation) beneficial in preserving vision 

– 400 IU vitamin E detrimental 

– Slower rate of decline in cone ERG amplitudes 

and visual field changes 

– All groups had 1 letter loss of vision per year 

– Recent study also found that 12 mg lutein daily 

further slowed mid-peripheral visual field loss in 

patients taking vitamin A 


Antioxidant formulations with Vitamin C, E & beta 

carotene investigated 

AREDS – initial analysis little benefit 

Physicians Health Study I - randomized clinical trial looked at 

incidence of age related cataracts in physicians found no 

overall benefit, did reduce risk in smokers by 25% 

Roche European American Cataract Trial (REACT) – 

showed decreased cataract progression using similar beta 

carotene formula, earlier treatment with higher dosage 

compared to physician study, more sensitive measurement 

techniques 

7


• Observational data from AREDS suggest that 

use of multivitamin may delay the progression 

of lens opacities 

• NEI Trial studying use of Centrum and cataract 

development 


• Vitamin E may protect against UVB light 

induced cataract 

• Journal of Nutrition study found that 

xanthophyll carotenoids, lutein and zeaxanthin 

were more protective than Vitamin E 


• Journal of Cataract and Refractive Surgery 

published a study which demonstrated that 

grape seed pranthocyanidin supplements 

suppressed experimental cataracts in animal 

model 


High dose Vitamin C Supplementation Study 

– may have benefits, reduced risk of cataracts by 60% after 

10 years of supplementation 

– reduced risk of cortical cataracts in women under 60 years 

of age 

Increased total vitamin A - including carotenoids, and 

lutein/zeaxanthin consumption may reduce overall risk for 

cataract extraction 


• One study indicates taking a broad based 

multivitamin supplement may reduce cataract 

risk by 33% 

• Another study found that patients taking 

regular doses of Vitamin E and maintained 

high blood levels reduced risk by 50% 


• The Longitudinal Study of Cataract – reduction 

in nuclear cataract development with users of 

multivitamins or vitamin E separately 

• Lycopene - nutritional antioxidant, reduced 

incidence of nuclear cataract in animal model with 

restoration of normal lens physiology 

• EPA omega-3 - essential fatty acid found in the 

lens, supplementation may help maintain clarity 

8

Diabetic Cataracts 

• Bioflavonoids – bilberry, quercetin and its 

derivatives help inhibit aldose reductase 

Diabetic Retinopathy 

• Lower levels of antioxidants in diabetic patients 

• Diabetes induced oxidative damage and nitrative 

stress in eyes with diabetic retinopathy 

• Study demonstrated that zeaxanthin 

supplementation may prevent the damage 

Optic Nerve Abnomalities 

• Study reported at ARVO 

• Folic acid, B6 and B12 may enhance growth 

and possibly repair damaged mechanisms in 

the adult central nervous system 

• Previously known that supplementation 

helped neuronal tube development in embryo 

Diabetic Neuropathy 

• Alpha-lipoic acid 100-300 mg day - mimics 

antioxidants may reduce frequency and symptoms of 

diabetic neuropathy 

• ? Benefits for diabetic cataract 

Optic Nerve Abnomalities 

Nutritional Amblyopia and Tobacco Alcohol 

Amblyopia 

• B-complex vitamins formulations have been 

shown to have therapeutic effects 

• B-complex formulations – B-6, B-12, niacin, 

folic acid 

• Therapeutic benefits possible by reestablishing 

healthy metabolism 

Glaucoma 

Gingko Biloba 

• NMDA blocker (N-methyl-D-aspartate) - 

neuroprotective activity 

Actions 

• Physiological actions - increases blood flow to 

neurological tissues 

• Antioxidant activity, increased platelet activating 

factor, nitric oxide inhibition 

• May result in neuroprotection of retinal ganglion 

cells in glaucoma 

9

Glaucoma 

• Gingko Biloba 

Improves blood flow to optic nerve 

Reduces blood serum viscosity 

Antioxidant activity 

Increases platelet activating factor activity 

Inhibition of apoptosis 

Inhibition of excitotoxicity 

Dry Eye Syndrome 

• More women than men have dry eye 

• Androgen deficiency may lead to meibomian 

gland dysfunction 

• Androgen deficiency and estrogen 

replacement therapy may increase ocular 

surface inflammation 

Nutritional Alternatives 

• Omega 3 essential fatty acid sources 

• Flaxseed oil – alpha-linolenic acid omega 3 (57%), 

linolenic acid omega 6 (15%), oleic acid omega 9 

(18%) 

• Other plant derived omega 3 fatty acid – gamma 

linolenic acid (GLA) 

• Fish oil – rich in omega 3 EPA & DHA essential fatty 

acids (sardines), most products have 1.5 EPA to 1 

DHA ratio 

• Be careful of fish oil quality. Needs to be free of or 

have acceptable levels of mercury or other toxins. 

Glaucoma 

• Ginkgo Biloba 

One study indicated increased end diastolic velocity 

within optic nerve with no effects on arterial 

blood pressure, heart rate, or IOP 

Another study found improvement of pre-existing 

VF defects in normal tension glaucoma patients 

Dosage in both studies was 40mg tid / day 


• Omega 3 supplementation beneficial 

• Recent study at Brigham and Women’s 

Hospital found that improving the ratios of 

omega 3 fatty acids to omega 6 fatty acids 

improved dry eye syndrome in women 

• Opposite made it worse 

Nutritional Alternatives 

• Depending on formulation, need 1,000-2,000 mg 

omega 3 essential fatty acids per day to have 

therapeutic effect 

• Stimulate tear production, rebalance tear film 

physiology and improve meibomian gland secretion 

quality 

• No benefits in drug induced dry eye syndrome 

10

Omega 3 Fatty Acids 

• Sjogren's patients tend to have lower dietary levels 

of omega-3 fatty acids, including EPA & DHA than 

matched controls 

• Optimum ratio of omega-3 to omega-6 ratio for good 

health typically is 1:4 

• Severity of dry eye in Sjogren's syndrome is inversely 

proportional to membrane and serum levels of DHA 

• Omega 3 fatty acids affect the lipid profiles of 

meibomian gland secretions in Sjogren’s patients 


Gamma-linoleic acid (GLA) may be beneficial in 

Sjogren’s syndrome 

Diets with proper levels of Vitamins A, B6, C; 

potassium; zinc also important for normal tear film 

function 

Potassium – improves tear film osmolarity (TheraTears 

artificial tear formulation) 

Albumin – ocular surface disorders with tear deficiency 

Omega 3 Fatty Acids 

• Omega-3 fatty acids help suppress meibomianitis, 

decrease apoptosis, improve neural signal 

transduction, stimulate tear production, augment 

the tear film oily layer and have anti-inflammatory 

properties 

• Increased essential fatty acids, particularly omega 3 

stimulates tear production and rebalances tear film 

physiology 

• May also benefit acne rosacea patients with 

associated dry eye syndrome 

Contact Lens Related Infections 

• Contact lens biofilms may be associated with low 

levels of tear lactoferrin 

• Hydroxyl radicals, a by-product of oxidative stress 

superoxide and H2O2 catalyzed by free iron, may 

exacerbate damage to cornea 

• Adequate levels of iron-binding tear lactoferrin is 

suggested to lower corneal opportunistic risks for 

related infections. 

• Site-specific lactoferrin proteins are also 

produced and immediately released by neutrophils, 

the first white blood cells to appear in infection 

11

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