Nutritional Supplementation in Optometric Care-2 hours - Nutritional Supplementation in... · 9/18/2018 1 Nutritional Supplementation in Optometric Care Beth A. Steele, OD, FAAO [email protected]

9/18/2018

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Nutritional Supplementation in Optometric Care

Beth A. Steele, OD, FAAO

[email protected]

Disclosures: Optos Advisory Board

Photo courtesy of Dr. Jared Cox

MV accounted for $5.7 billion in annual sales, according to NIHOverall market projected to reach $287 billion by 2024

• Patients see it in the news, online, and…

• They will ask

• We need good answers

Aslam R, et al. Frontier in Public Health 2017.

Fundamental Considerations

• Food vs. supplementation

• Vehicle (vegetable capsule, chewable, liquid, …)

• Natural ≠ Safe• There is such a thing as too much of a good thing

• Consider medical conditions, other medications and supplements

• Consult with PCP

Regulation

• Dietary Supplement Health and Education Act – 1994

• FDA • not authorized to review before marketed

• can take dietary supplements off the market if they are found to be unsafe, false/misleading

• Must be notified if new ingredient is added, and will approve for safety

• Manufacturers (and distributors)• Responsible for product quality, safety and accurate labeling

• Must report serious problems to FDA as an adverse event

Safety Concerns – Problems Occur when…

• Combining supplements

• Using supplements with medicines (Rx or OTC)

• Substituting supplements for prescription medicines

• Taking too much of some supplements (e.g. vitamin A, vitamin D, iron)

• Taking before, during, and after surgery

• Often not disclosed in history!

• NIH “Using Dietary Supplements Wisely”: https://nccih.nih.gov/health/supplements/wiseuse.htm

Terminology RE: Dosing

• IU – international unit

• Recommended Daily Allowance (RDA)

• EAR – estimated average requirement

• GRAS – Generally Regarded as Safe [by the FDA]

• …..

• Guidelines based on age, other factors (e.g. pregnancy, lactation)

• www.ods.od.nih/gov/factsheets

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Special Circumstances that May Change Dose

• Age

• Pregnancy

• Lactation

• Disease process • Recommended amounts often much higher when disease present

• Ex ‐ Vitamin A for RP

• Ex ‐ Antioxidants for AMD

Patient Instructions, Compliance, Options

• OTC

• Online

• In‐practice sales • Increases compliance

• Improvement of symptoms

• Reduces confusion

Supplementation for Ocular Surface Disease

Most common ocular complaint

14% of adults in the US

68% of patients 60 and older complain of symptoms related to dryness

Omega‐3s: all convert to long chain Natural Food Source

Benefits/Used For Dose (adult) Contraindications/Adverse Effects

Long chain (DHA,EPA): Cold‐wateroil fish (herring, mackerel, salmon, sardine, trout, tuna)

anti‐inflammatory, augment lipid layer, stimulate tear production• DES• Cataracts• Glaucoma• Uveitis

Reported but not substantiated: • Lower risk CV dz and MI • arrhythmias, cholest,

atheroscl, BP

AHA recommends• Healthy pts–

fish 2x wk• Hrt dz– 1g/d• Hyperchol –

2‐4g/d

Max: 3g/day

Dry eye: 1‐3g/day

Conflicting evidence: risk prostate cancer

High doses PT and bleeding

Better absorption if eaten along with something high in fat

Note: farmed fish eat grain and soy, high in Omega‐6s

Short chain (ALA and SDA): flaxseeds, chia seeds, walnuts

Eicosapentaenoic acid (EPA)Docosahexaenoic acid (DHA)

Alpha linolenic acid (ALA)Stearidonic acid (SDA)

Omega‐3s (DHA/EPA) have been found to offer benefit

• Improvement of objective and subjective findings • tear osmolarity, MMP‐9, TBUT, Schirmer, OSDI scores

• Increase function of MGs

Epitropoulus A, et al. Cornea, 2016.

However…

• Now we question it. DREAM© Study • NIH study, +500 patients, +1 year follow up

• Omega‐3 no different than placebo• 400 mg EPA + 200 mg DHA • placebo = 100 mg refined olive oil (1tsp)

• Conclusions: 1. Omega 3’s for dry eye? 2. Olive oil not a suitable placebo?3. Healthy diet worth considering!

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Omega‐6

Natural Food Source Benefits / Used for Recommended Intake

Seeds, grains, sunflower, corn oils

Red meat Processed foods

Ocular surface disease ? healthy ratio Omega 6 : Omega 3 is 1:1

Linoleic acid (LA)Arachadonic acid (AA)Gamma‐linolenic acid (GLA)Dihomo‐gamma‐linolenic acid (DGLA) Sheppard et al. Cornea 2013

Omega‐6 over Omega‐3 ?

• Gamma‐linolenic acid (GLA)

• Science Based Health HydroEye®

Omega‐3 Supplementations

• Typical Sources • Fish oil• Flaxseed oil • Evening primrose oil• Cod liver oil

• Other common additives• Mucin complex • Curcumin (yellow substance in turmeric)• Bilberry extract• Vit A, E, D3

• Many options…

TheraTears Eye Nutrition®

• Fish oil – total 1.2g• EPA 450 mg

• DHA 300 mg

• ALA 450 mg

• 1000mg Flaxseed oil

• Vitamin E – 183 IU

• 3 softgels qam www.theratears.com

Does Form Matter?

• Ethyl ester Omega‐3 • Most products are

• Vs…. Re‐esterified Omega‐3 • More bio‐available triglyceride form

• Better efficacy

• $$

• Documented on label as “rTG”

Prnomegahealth.com

Epitropoulus A, et al. Cornea, 2016.

Other additives…

• Mucin complex

• Curcumin (yellow substance in turmeric)

• Bilberry extract

• Vit A, E, D3

https://maxivision.com

https://lunovus.com

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Lovaza®(omega‐3‐acid ethyl esters) • Rx only

• 465 mg EPA

• 375 mg DHA

• To reduce triglyceride levels in adults with very high triglycerides (>500 mg/dL)

• 4 g daily (or 2 g bid)

• expensive

• Retaine OM3™: • Fish oil, Evening primrose oil, bilberry extract

• 2 pills per day

• Retaine Flax™: • Flaxseed oil, Evening primrose oil, bilberry extract

• 4 pills per day

http://www.ocusoft.com

Other Considerations…

• # pills per day• Size of pills• Sensitivity to fish oil• Quality of product • Medical Hx! 2‐3g/day!

Sensitivity to Fish Oil

• 30% have one of the following • Fishy taste in mouth• Indigestion/stomach upset • Can depend on product quality, freshness

• Some may experience….• Skin rash• Back pain• Flu‐like symptoms • Hives• Difficulty breathing, etc• Can be relative to other ingredients/vehicle (e.g. soy)

Nutritional Considerations for Cataracts

• EPA/DHA intake • 12% lower risk for cataract extraction

• >3 servings of fish/week 19% lower risk Lu M et al. Am J Epidemiol.2005.

• NS associated with obesity and smoking

• Healthy diet = strongest modifiable predictor

And glaucoma ?

• Increased intake of EPA/DHA associated with reduced risk of glaucoma

• Wang et al. JAMA Ophth 2018

Supplementation for AMDHistorically based on AREDS 1/2

Controversy

Practical Considerations

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AREDS Archives of Ophth 2001

• 4 groups – looking at ability of different supplementations to progression of moderate/advanced AMD1. Placebo2. Antioxidants (Vitamins A, C, Beta‐Carotene)3. Zinc/copper4. Antioxidants + zinc/copper

• Conclusion: antioxidants + zinc: progression of intermediate to advanced AMD (high

risk group) by 25% risk of moderate vision loss for those at high risk for

geographic AMD or CNVM by 19%

Daily Dose

Vitamin C , 500 mg Vitamin E , 400 IU Beta‐carotene, 15 mg ( 25,000 IU Vitamin A) Zinc, 80 mg Copper, 2mg

Became AREDS formula!

LAST Study (Lutein Antioxidant Supplementation Trial)Richer S et al. Journal of the American Optometric Association, 2004

• Basis: Lutein is the primary dietary carotenoid xanthophyll pigment• responsible for Macular Pigment Optical Density (MPOD)• More lutein ‐‐MPOD

• 12monthstudy/N=90

• Three groups 1. Lutein (10 mg)2. Lutein (10 mg) + Antioxidants3. Placebo

• MPOD increased in groups 1 and 2• Acuity• Contrast sensitivity

• Conclusion: Lutein associated with… • MPOD• visual acuity • contrast sensitivity

AREDS 2 – JAMA Ophth 2013

• Effect on progression when….1. Adding 10mg lutein + 2mg zeaxanthin

2. Adding Omega 3s

3. Eliminating beta carotene, lowering zinc

• Conclusions: Lutein/zeaxanthin and/or Omega‐3 + AREDS did not further reduce

progression

Eliminating beta carotene did not increase risk

Lowering zinc did not increase risk

Vitamin C Natural Food Source

Benefits/UsedFor

RDA (adult) Contraindications/Adverse Effects

PeppersGuavaKiwiBerriesBroccoli Citrus fruitsRed cabbage PotatoesStrawberriesTomatoes

Antioxidant • Wound healing• Immune function• Protein metabolism

AMD‐ AREDS

90 (m)75 mg (f)85 mg (preg)120 (lact)

Upper limit: 2000 mg

Smokers: need 35mg higher dose

Not enough – scurvy Too much ‐ Low toxicity

Can exacerbate iron overload

Interactions: • Avoid during

chemo/radiation• Statins: may lipid levels

Antioxidants ‐‐ The basis for treatment

• Oxidation – shown to play a role in ocular disease

• Reactive oxygen species (ROS) such as free radicals are damaging forms of oxygen

• Free radicals have an unpaired electron in their outer orbit, making them damaging to the body

• → pluck electrons from other molecules to achieve stability → create more ROS

• → fuels disease‐generating chain reaction • → speeds up aging process

• Antioxidants neutralize ROS

Vitamin E (Tocopherol)

Natural Food Source

Benefits/UsedFor

RDA(adult)

Contraindications/Adverse Effects

Wheat germ oilAlmondsHazelnutsSunflower oilGreen leafy vegetablesEgg yolksBeans

AntioxidantAMD‐AREDS

15 mg(22.4 IU)

Not enough: neurologic abnormalities Too much: • High doses inhibit platelet aggregation • Fatigue, nausea/vomitting/GI upset,

blurry vision, H/A

Conflicting evidence of: Increased risk of prostate cancer

Interactions: • Coumadin, blood thinners (bleeding, hemorrhagic stroke reported)

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Zinc

Natural Food Source

Benefits/UsedFor

RDA (adult) Contraindications/Adverse Effects

Oysters Red meatPoultryBeans, nuts

Immune functionWound healingDNA/proteinsynthesis

AMD ‐ AREDS

11mg (m)8mg (f)

Interferes with some antibiotics: • Fluoroquinolones• Tetracyclines

Other interactions: • Diuretics • Penicillamine

Increases risk of AMD in some genetic make ups?

Xanthophyll Carotenoids in MaculaLutein and Zeaxanthin

Natural Food Source Benefits/Used For Dose (adult)

Greens (eg collard, turnip, kale, spinach)Goji Berries

*occur naturally in the body as antioxidants

AMD – AREDS 2

10mg – lutein

2mg‐ zeaxanthin

Meso‐Zeaxanthin

Potential Food Source?? Benefits/Used For Dose (adult)

Salmon skin, sardine skin, trout skin

*Converted from lutein in the body

Macular health – AMD ?

10mg

AREDS 2 Formulas

• Added lutein and zeaxanthin

• Removed beta‐carotene

• Many available options…

• PreserVision® AREDS2 by B&L• Now available in chewables

• AREDS II Visual Advantage by Lunovus

• Available in Berry flavored chewable

• MaxiVision® Eye Formula

http://www.preservision.com/

http://www.lunovus.com/


Saffron?

• Antioxidant carotenoid

• Neuroprotective effects

But manymodifications of this formula are available

• AREDS – A, C, E, zinc

• AREDS 2 + multivitamin

• AREDS 2‐”based” ± ….. • Reduced Vit C,E, zinc

• Reduced lutein/zeaxanthin

• Meso‐zeaxanthin

• ….etc

• Capsules, chewable, dissolvable strip

• MacuHealth®

• MaxiVision® Meso‐Plus

• The Meso‐Zeaxanthin Debate… • 1 of 3 xanthophyll carotenoids in macula

• Body converts from lutein

• No natural dietary source

• Suggestions of significantly increased MPOD

http://www.macuhealth.com/

Some have meso‐zeaxanthin


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Some are combined with multivitamins…

• I‐Caps® Eye Vitamin Formula• AREDS 2 plus

• Multi‐vitamin and mineral supplementation

• Careful history….

• Vs. others that assume a MV is already being consumed…

Vitamin K (Phytonadione)

Natural Food Source Benefits/Used For Contraindications/Adverse Effects

Leafy greensKiwiavocado

Blood clotting

Often added to multivitamins

Not enough –blood clotting factors

Interactions: Prevents coumadinactivity

83 year old WF

• Hx TIA, taking Coumadin

• Cataracts

• OD: 20/50 OS: 20/25

• Recommendation?

• Considerations?

And some just have other stuff…

• MaxiVision® Lutein Formula• 10 mg lutein

• 2mg zeaxanthin

• 355 mg powdered spinach


Bilberry

• Contains antioxidants: resveratrol, anthocyanosides

• Anti‐angiogenic properties : may decrease blood vessel permeability

• Suggested for• diabetic retinopathy

• AMD

• atherosclerotic conditions

• Adverse effects: bleeding, GI upset

Zinc Only and Zinc Free Options..?

Awh, et al

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Should we be performing genetic testing on our patients with with intermediate ‐ advanced AMD?

No Clinically Significant Association betweenCFH and ARMS2 Genotypes and Response toNutritional SupplementsAREDS Report Number 38Chew EY, et al. Ophthalmology June 2014

• Simple cheek swab

• No CLIA certification required

Most common genotypes looked at again for 7‐year progression

Ophthalmology, 2014 Sep 4. Zinc increases progression

New Standard?

• American Academy of Ophthalmology • No evidence to support genetic testing

• Remains to be an area of interest ….• Chew E. Ophth, 2015

• Stone EM. JAMA Ophthalmol, 2015

• Wittes J, Musch DC. Ophthalmology, 2015

• A of Pharmacotherapy, 2016

• Csaky KG, et al. Journal of VitreoRetinal Diseases, 2017

Genetic testing results could tell us…..

1. Genetic classification –Recommendation for vitamin therapy

• AREDS 2 formula• Zinc only• Antioxidants only

2. Risk of progression – low, moderate, high

• How closely should you follow? • Patient education/counseling

“Despite low risk levels, many participants reported making changes as a result of the genetic testing. Twenty‐seven people reported making specific changes, including wearing sunglasses and brimmed hat and taking vitamin supplements.”

McCarty et al. Optometry and Vision Science, March 2018

A tough call…. ?

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AREDS recommendations are for …. Who?

1. Intermediate AMD in one or both eyes• Multiple intermediate drusen

• 1 large druse

• Non‐central geographic atrophy

OR

2. Advanced AMD in one eye

Is it safe to prescribe when patients don’t meet the AREDS criteria?

• We don’t know. • Should we anyway?

• Considerations…• Risk factors

• Findings

• Family hx

• Dark Adaptation

• Genetic profile???

• Just xanthophylls?

Treatment Recommendations for All Stages of AMD

Smoking cessation

Nutritional supplementation

Lifestyle modifications including diet

Systemic disease management

Blue light / UVA / UVB protection

1

2

3

4

5

October 2017

Take‐Aways….

1. We are missing or failing to dx AMD – damage is far done

1. Impairment in dark adaptation is specific for AMD and can precede clinical findings by 3 years

• “Subclinical AMD”

• Even earlier “early AMD”

2. All stages of AMD should be treated with nutritional supplementations: • Option 1: Xanthophylls

• Option 2: Antioxidants + Xanthophylls (AREDS 2)

• Option 3: Option 1 for subclinical/early and Option 2 for Intermediate +

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What Else to Consider…?

Vitamin A for Retinitis Pigmentosa

• 15000 IU Vit AAvoid high dose Vit EArchives of Ophthalmology, 1993

• Associated with….• Higher age of onset (~5 years)

• Improved function of cone ERG amplitudes

• Slowed progression

• High dose Omega 3 will boost Vit A affect Archives of Ophthalmology 2012

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Vitamin A (e.g. beta‐carotene)Natural Food Source

Benefits/UsedFor

RecommendedDietary Allowance (adult)


LiverFish oilsDairyEgg yolkGreen leafy, orange and yellow vegetables TomatoesSweet potatoes Fruits

Immune functionCellularcommunicationVision (rhodopsin)

Original AREDS study

RP

3,000 IU (m)2,300 IU (f)

15,000 IU for RP Tx

Upper limit: 10000 IU

Low intake needed for Stargardtpatients?

Increased risk of lung cancer –avoid in smokers

Interactions:• Orlistat (Xenical) for weight

loss: Vit A abs• Retinoids: Vit A toxicity

Vit A Toxicity

Vitamin A Toxicity• Increased ICP, dizziness, nausea, headache, joint pain

• Reported Intracranial hypertension (most likely to occur in large doses)

Vs…

• Stargardt patients with low vitamin A intake showed significantly better visual acuity vs. those with higher

Sofi F, et al. BMC Ophthalmol 2016

Vitamin A Deficiency

• Malnourishment

• Chronic alcoholism

• Ocular manifestations: • Nyctalopia

• Dry eyes – severe

• Bitot's spots: Plaque like formation that forms on the conjunctiva

Case Rep Ophth, 2015

Nutritional Supplementation for Diabetics??

Believed to Control glucose levels

Protect and restore endothelial function

Some include:• Vitamin C, D, E

• Zinc

• Carotenoids

• Nicotinamide

• Taurine

• Glutamine Lunovus Glucose II

Nutrition for Diabetics

• ….Weight Control• The most significant factor in diabetes prevention Mayer‐Davis et al, JAMA 1998

http://www.drannwellness.com

• The “sugar” discussion • Caloric intake

• Processed foods

• Glycemic indexDiabetes Prevention Plan (DPP)

Knowler et al, NEJM 2002

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Ginko for Glaucoma?

• Open‐angle glaucoma patients…. • ↓ed blood volume, flow, and velocity • Associated with progression in structural change and VF loss

• Antioxidants showed in blood flow velocities for retrobulbar vessels • Improvement in VF ??

Harris, A Acta Ophthalmol. 2017

• Reduces peripheral vasospasm, so improves ocular perfusion

• Also suggested for…• AMD• Vascular retinopathies

Many many others…..

• Careful history of conditions, medications

• Consult with PCP

Focusing on Side Effects Nutritional and Herbal Supplements

Adverse Reactions and Contraindications ‐Key Examples

• Beta‐carotene: increased risk of lung cancer – avoid in smokers

• Vitamin E, Omega‐3s: increased risk of bleeding/stroke

• Vitamin K: can reduce the ability of the blood thinner Coumadin® to prevent blood from clotting

• Antioxidants: might reduce the effectiveness of cancer therapy

Fraunfelder, F. AJO, 2004.

Remember the Differentials for Tamoxifen Retinopathy?

• Canthaxanthine is an oral sun‐tanning agent


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Vitamin B3/4 Complex (Niacin, niacinamide)

Natural Food Source

Benefits/UsedFor


Lean meatsEggsWhole grainsLeafy greens

ATP synthesis

B3 may lower serum cholesterol

Deficiency‐Pellagra

Overdose‐• Skin flushing• Blood sugar• Cystoid macular edema

Niacin‐macular toxicity

• Cystoid‐like maculopathy

• Cystoid Macular Edema


ASCRS, 2013

Peripheral Vascular Dilators

• Pseudo‐Cystoid macular edema• More common in men between 30‐50 years old

• Vision loss is reversible in 1‐2 days after drug discontinuation

• Decreased aqueous – dry eye symptoms

ASCRS, 2013

Nicotinamide also suggested for Glaucoma Prevention….

• Promising results in study with mice

• Made from niacin• poultry, beef, fish and fortified cereal

• Niacin: reported CME side effect

Jeffrey M. Liebmann, M.D., and George A. Cioffi, M.D. N Engl J Med 2017

Resources• USDA https://www.nal.usda.gov/fnic

• FDA http://www..fda.gov

• NIH https://ods.od.nih.gov/HealthInformation/DS_WhatYouNeedToKnow.aspx

• US Food and Nutrition Boardhttp://www.nationalacademies.org/hmd/About‐HMD/Leadership‐Staff/HMD‐Staff‐Leadership‐Boards/Food‐and‐Nutrition‐Board.aspx

• National Medicines Comprehensive Databasehttp://naturaldatabase.therapeuticresearch.com/home.aspx?cs=&s=ND&AspxAutoDetectCookieSupport=1

• National Registry of Drug‐induced Ocular Side Effectshttp://www.eyedrugregistry.com

Documents

Nutritional Supplementation in Optometric Care-2 hours - Nutritional Supplementation in... · 9/18/2018 1 Nutritional Supplementation in Optometric Care Beth A. Steele, OD, FAAO [email protected]