Nutritional Supplementation in Optometric Care Beth A. Steele, OD, FAAO Disclosures: NONE

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1 Nutritional Supplementation in Optometric Care Beth A. Steele, OD, FAAO Disclosures: NONE

2 Wow. Multivitamins are the most commonly used dietary supplements, accounting for $5.7 billion in annual sales, according to the National Institutes of Health Prevalence in US Bailey et al. NHANES survey Any Female: 53% Male: 44% Multivitamin Female: 36% Male: 31%

General Overview and Fundamental Rules Supplements available for Ocular surface disease AMD Diabetes Considerations Food vs. supplementation Aslam R, et al. Frontier in Public Health 2017.

3 General Overview and Fundamental Rules Supplements available for Ocular surface disease AMD Diabetes Considerations Food vs. supplementation Aslam R, et al. Frontier in Public Health Stick with eyecare specific products Vehicle (vegetable capsule, chewable, liquid, ) There is such a thing as too much of a good thing Consider medical conditions, other medications and supplements Consult with PCP

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

5 The basis for treatment 1956 Harman proposed the free radical theory of aging Oxidation shown to play a role in ocular disease Reactive oxygen species (ROS) = damaging forms of oxygen Free radicals Singlet oxygen Hydrogen peroxide Free Radicals have an unpaired electron in their outer orbit, making them damaging to the body They pluck electrons from other molecules to achieve stability and create more ROS Fuels disease generating chain reaction Speeds up aging process

6 Antioxidants Our body s defense system Neutralize ROS Vitamin C Vitamin E Alpha lipoic acid DHLA (dihydrophylic acid) Glutathione

7 With that said. Most clinical studies of antioxidant supplements have not found them to provide substantial health benefits AREDS is one of the VERY FEW that did Why not? Benefit of diet high in vegetables and fruits or other antioxidant rich foods may actually be caused by other substances present in the same foods, other dietary factors, or other lifestyle choices rather than antioxidants. large doses of antioxidants used in supplementation studies may be different from those of the smaller amounts of antioxidants consumed in foods. Differences in the chemical composition of antioxidants in foods versus those in supplements

8 Terminology IU international unit Recommended Daily Allowance (RDA) EAR estimated average requirement

10 Vitamin A (beta carotene) Natural Food Source Benefits/Used For Recommended Dietary Allowance (adult) Contraindications/ Adverse Effects Liver Fish oils Milk Egg yolk Green leafy, orange and yellow vegetables Tomatoes Sweet potatoes Fruits Immune function Cellular communication Vision (rhodopsin) Original AREDS study RP 3,000 IU (m) 2,300 IU (f) 15,000 IU for RP Tx? Upper limit: IU Increased risk of lung cancer avoid in smokers Interference with some anticonvulsant agents (valproic acid) Vit A Toxicity Low intake needed for Stargardt s patients?

11 Vitamin A Toxicity Reported Intracranial hypertension (likely to occur in large doses)

12 Vitamin C Natural Food Source Benefits/Used For RDA (adult) Contraindications/ Adverse Effects Berries Broccoli Citrus fruits Red cabbage Wound healing Immune function Protein metabolism AMD AREDS 90 (m) 75 mg (f) 85 mg (preg) 120 (lact) Upper limit: 2000 mg Interference with some cancer therapies Impaired blood coagulation time ; interferes with coagulation therapy Can cause liver damaging accumulation of Tylenol

13 Vitamin E Natural Food Source Benefits/Used For RDA (adult) Contraindications/ Adverse Effects Wheat germ oil Almonds Hazelnuts Sunflower oil Green leafy vegetables vitamin E might help prevent or delay the chronic diseases associated with free radicals AMD AREDS 15 mg (22.4 IU) Acts as a blood thinner Hemorrhagic stroke reported 17x Increase risk of prostate cancer reported

14 Zinc Natural Food Source Benefits/Used For RDA (adult) Contraindications/ Adverse Effects Oysters Red meat Poultry Beans, nuts Immune function Wound healing DNA/protein synthesis AMD AREDS 11mg (m) 8mg (f) Increases risk of AMD in some genetic make ups? Interferes with some antibiotics

15 Lutein and zeaxanthin Natural Food Source Benefits/Used For Dose (adult) Turnip Greens Kale Collard Greens Spinach Goji Berries Antioxidants AMD AREDS II 10mg lutein 2mg zeaxanthin

16 Omega 3s: all convert to long chain Natural Food Source Benefits/Used For Dose (adult) Contraindications/ Adverse Effects Long chain (DHA, EPA): Cold water oil fish (herring, mackerel, salmon, sardine, trout, tuna) Short chain (ALA and SDA): flax seeds, chia seeds, walnuts Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Lower risk CV dz and MI (J Nutr 2010) d/c arrhythmias, cholest, atherosclerosis, BP (AHA) DES RP (Am J Ophth 2004) Cataracts Glaucoma Uveitis *no standard mg day alpha linolenic acid (ALA) Stearidonic acid (SDA) i/c risk prostate cancer (?) Doses greater than 3g/day can i/c PT and bleeding Note: farmed fish eat grain and soy, high in Omega 6s Better absorption if eaten along with something high in fat

17 Omega 6 Natural Food Source Recommended Intake Seeds, grains, sunflower, corn oils healthy ratio 6:3 is 1:1 to 5:1 Red meat Linoleic acid (LA) Arachadonic acid (AA) Gamma linolenic acid (GLA) Dihomo gamma linolenic acid (DGLA)

18 Others? Yes. Many.

19 Food vs. Supplementation Practical considerations Sometimes amounts are impossible to achieve Enzymes and bioflavinoids not found in most supplements Raw best: Warming better than cooking

20 Safety Concerns Problems Occur when Combining supplements Using supplements with medicines (whether prescription or over thecounter) Substituting supplements for prescription medicines Taking too much of some supplements, such as vitamin A, vitamin D, or iron Taking before, during, and after surgery Often not disclosed in history! NIH Using Dietary Supplements Wisely :

21 Pertinent Examples Beta carotene: Increased risk of lung cancer avoid in smokers Vitamin E: increased risk of bleeding/stroke Vitamin K: increased risk of bleeding/stroke

22 Adverse Effects Pertinent Examples Vitamin K can reduce the ability of the blood thinner Coumadin to prevent blood from clotting. Antioxidant supplements, like vitamins C and E, might reduce the effectiveness of some types of cancer chemotherapy.

23 Regulation Dietary Supplement Health and Education Act 1994 FDA is not authorized to review dietary supplement products for safety and effectiveness before they are marketed. If NEW ingredient, manufacturers must notify FDA, who will approve for safety manufacturers and distributors are responsible for making sure their products are safe before going to market Manufacturers are required to produce quality products which are accurately labeled manufacturers must report serious problems to FDA as an adverse event FDA can take dietary supplements off the market if they are found to be unsafe or if the claims on the products are false and misleading.

24 Resources USDA FDA NIH US Food and Nutrition Board HMD/Leadership Staff/HMD Staff Leadership Boards/Food and Nutrition Board.aspx National Medicines Comprehensive Database spxautodetectcookiesupport=1 National Registry of Drug induced Ocular Side Effects

25 Supplementation for Ocular Surface Disease

26 Dry eye Most common ocular complaint 68% of patients 60 and older complain of symptoms related to dryness Omega 3s (DHA and EPE) have been found to offer benefit Antiinflammatory May decrease RBC and plasma ratios of omega 6 to omega 3 Increase function of MGs Improvement of objective and subjective findings OSDI score, TBUT, Schirmer, meibum score

27 Omega 3s and Other Common additives Active Fish oil Flaxseed oil Borage Seed Oil Evening primrose oil Cod liver oil Bilberry extract Tumeric root Mucin complex Considerations # pills per day Size of pills Sensitivity to fish oil Maxivision.com

28 Considerations Considerations # pills per day Size of pills Enteric coated? Sensitivity to fish oil

29 Ocusoft ( 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

30 Lunovus Tear Support

31 Maxi Vision MaxiTears Dry Eye Formula Omega 3 formula

32 Supplementation for AMD

33 1988 National Health and Nutrition Examination Survey Diets high in fruits, vegetables with vitamins (A) were less associated with AMD Many studies since then

34 AREDS Review AREDS Archives of Ophth 2001 Looked at the ability of different supplementations to decrease progression of moderate/advanced AMD 1. Placebo 2. Antioxidants 3. Zinc 4. Both antioxidants and zinc AREDS formula reduced progression of intermediate to advanced AMD by 25% and 19% reduction in moderate vision loss for those at high risk for geographic AMD or CNVM AREDS 2 JAMA Ophth 2013 Looked at the effect of the following in regards to progression: 1. adding zinc/zeaxanthin or Omega 3s or both 2. Eliminating beta carotene, lowering zinc Zinc/zeaxanthin/Omega 3s + AREDS did not further reduce progression ; Eliminating beta carotene and lowering zinc do not pose a problem

35 Many formulas available AREDS A, C, E, zinc AREDS II AREDS (+) lutein and zeaxanthin and ( ) beta carotene AREDS + multivitamin AREDS based Other additives Meso zeaxanthin Billberry

36 B and L Preservision AREDS2 builds on the original AREDS formula, with lutein and zeaxanthin replacing betacarotene based on the AREDS2 study

37 Lunovus AREDS II Capsule Berry flavored chewable Premier Formula

38 Ocusoft Vision AREDS2 Formula

ICAPS ICAPS Eye Vitamin Multivitamin Formula [tablet]: vitamin C 128 mg; vitamin D 100 IU; vitamin E 107.5 IU; vitamin K 7.25 mcg; thiamin 0.375 mg; riboflavin 2.5 mg; niacin 2.5 mg; vitamin B6 0.

39 ICAPS ICAPS Eye Vitamin Multivitamin Formula [tablet]: vitamin C 128 mg; vitamin D 100 IU; vitamin E IU; vitamin K 7.25 mcg; thiamin mg; riboflavin 2.5 mg; niacin 2.5 mg; vitamin B6 0.5 mg; folic acid 100 mcg; vitamin B mcg; biotin 7.5 mcg; pantothenic acid 2.5 mg; calcium 82.5 mg; phosphorus 35 mg; iodine 37.5 mcg; magnesium 25 mg; zinc mg; selenium 10 mcg; copper 0.9 mg; manganese 0.5 mg; chromium 30 mcg; molybdenum mcg; potassium 20 mg; lutein 1.66 mg; zeaxanthin 0.83 mg; lycopene mg

40 MaxiVision Products Eye Formula Macula Formula

41 MaxiVision Products Lutein Formula Meso Plus

42 The meso zeaxanthin debate Lutein Zeaxanthin Meso Zeaxanthin?? No natural dietary source Body converts from lutein

43 Who are these recommendations for??

44 Is it safe to prescribe when patients don t meet the AREDS criteria?..who knows!?!

45 Awh, et al So should we be genetically testing everyone with intermediately advanced AMD? 7 year progression of AMD based on supplement used, divided by genotype

46 Simple cheek swab No CLIA certification required Macula Risk PGx/Vita Risk (Arctic Medical) Test kit with buccal cytology brushes and sterile collection bag

47 So should we be genetically testing everyone with intermediately advanced AMD? No Clinically Significant Association between CFH and ARMS2 Genotypes and Response to Nutritional Supplements AREDS Report Number 38 Chew EY, et al. Ophthalmology June 2014

48 Ophthalmology, 2014 Sep 4. Zinc increases progression Most common genotypes looked at again for 7 year progression

49 Results of test tell you. 1. Risk of progression low, moderate, high How closely should you follow? Patient education/counseling 2. Genetic classification Recommendation for vitamin therapy 1. AREDS II formula 2. Zinc only 3. Antioxidants only

50 Results of test tell you. 1. Risk of progression low, moderate, high How closely should you follow? Patient education/counseling 2. Genetic classification Recommendation for vitamin therapy 1. AREDS II formula 2. Zinc only 3. Antioxidants only

51 Sifting through the outcomes. What was different about the two studies? Chew, et al : used all 9 genotypic combinations, some very rare Awh, et al: focused on the 4 genotypic combinations What do we do now? Latest opinions.. 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

52 Supplementation for Retinitis Pigmentosa

Vitamin A for Retinitis Pigmentosa 15000 IU Vit A Avoid high dose Vit E Archives of Ophthalmology, 1993 Associated with.

53 Vitamin A for Retinitis Pigmentosa IU Vit A Avoid high dose Vit E Archives 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 Sofi F, et al. BMC Ophthalmol 2016

54 Vs Stargardt s patients with low vitamin A intake showed significantly better visual acuity vs. those with higher Sofi F, et al. BMC Ophthalmol 2016

55 Supplementation for Diabetes

56 Patient Education! A A1C /blood glucose is individualized B 140/80 or less C LDLs 100 or <70 if CVD D Diet E Exercise 150 min per week S Smoking increases risk of retinopathy Diabetes Prevention Plan (DPP) Knowler et al, NEJM 2002

57 Nutrition for Diabetics.Weight Control The most significant factor in diabetes prevention Mayer Davis et al, JAMA 1998 The sugar discussion Caloric intake Processed foods Glycemic index

58 Nutritional Supplementation: The diabetic formula?? Believed to Control glucose levels Protect and restore endothelial function Some include: Vitamin C, D, E Nicotinamide Taurine Glutamine Lunovus Glucose II

59 What Else?

60 Cataracts Increased prevalence of NS associated with obesity and smoking Healthy diet was the strongest modifiable predictor of NS EPA/DHA intake had 12% lower risk for cataract extraction Those with >3 servings of fish per week had 19% lower risk Lu M et al. Am J Epidemiol.2005.

61 Glaucoma Compared to non glaucomatous healthy individuals ed blood volume, flow, and velocity True for nasal NRR, temporal PP are, and retrobulbar vascular areas Associated with progression in structural change and VF loss Harris, A Acta Ophthalmol Ginko biloba Reduces peripheral vasospasm, so improves ocular perfusion Alternative treatment for glaucoma improvement in VF? Avoid in patients using anticoagulant therapies high dose omega 3 supplements Reported: intraretinal hemorrhages, hyphema, retrobulbar hemorrhage

62 Nicotinamide made from vitamin B3 (niacin) niacin rich foods include poultry, beef, fish and fortified cereal for prevention of glaucoma? Promising results in study with mice Niacin: reported CME side effect Jeffrey M. Liebmann, M.D., and George A. Cioffi, M.D. N Engl J Med 2017

63 Bilberry Contains antioxidants: resveratrol, anthocyanosides Antiangiogenic properties : may decrease blood vessel permeability in diabetic ret and AMD For atherosclerotic conditions Adverse effects: bleeding, GI upset

64 Ocular Formula

65 Eye and Body Formula

Everything You Need to Know about Vitamins and Minerals

Everything You Need to Know about Vitamins and Minerals A Beta-Carotene Thiamine (B 1 ) Riboflavin (B 2 ) Vitamin A is needed for new cell growth. Helps fight infection. Essential for healthy skin, good