Current Thoughts on Nutrition

With Emphasis on Treating the Cause of Degenerative Eye Disease, Safety Issues, B Vitamins and Essential Fatty Acids and Dry Eyes

Presented by:

Ellen Troyer, MT MA

Course Learning Objectives:

• To Review Current Science• To Separate Fact From Marketing Fiction• To Identify Safety Issues and Possible

Complications

Financial Disclosure & Other Info

• Biosyntrx CEO / Chief Research Officer• Founding Board Member, Ocular Nutrition

Society• Board Member, Ophthalmic Women Leaders• Scientific Advisory Board – MDSupport.org• ARVO Member• Board Member – Falls & Fractures Alliance• Voting Member – Council for Responsible

Nutrition

U.S. Visual Impairment and Disease

• Dry Eyes: 20+ million • Macular Degeneration: 10.6 million• Cataracts: 20.5 million• Diabetic Retinopathy: 5.3 million • Glaucoma: 2.2 million (2 million

undiagnosed)

• These numbers are projected to double in 20 years!

The Cost of Visual Impairment

• Total financial burden of major adult visual disorders is $35.4 billion

• $6.8 billion for cataracts• $5.5 billion for refractive error• $2.9 billion for glaucoma• $575 million for AMD• $493 million for diabetic retinopathy

Lifestyle Matters Most Where Eye, Body and Mental Health is Concerned

• Nutrient-dense Quality Food Intake• Protection From Sun• Weight Control• Adequate Exercise• Nutritional Supplementation to Prevent Deficiencies • Supportive Relationships• Passion for Life and Causes• Sense of Belonging• Concern for Society

Nutrient Deficiencies

• Most people are micronutrient deficient.

• Bruce Ames, PhD. (one of the most published nutrition scientists in the world) triage theory posits that the slightest deficiency of any of the essential vitamins and minerals, over time, increases the risk of degenerative disease, including eye disease.

Why Eye Care Professional Care

• HHS data collected from phone interviews found that most people over-estimate fruit and vegetable consumption during phone interviews.

• The CDC released data in 2007 suggesting that fewer than 15% of the population consume 5 servings of fruits and vegetables a day.

• The current HHS recommendation is 9-13 servings a day.

Multiple Vitamin / Mineral Safety

• According to the latest research published in the Feb. 2013 American Journal of Clinical Nutrition, multi-vitamin /mineral / antioxidant supplements at levels that do not exceed the Academy of Medicine Safe Upper Level (UL) does not increase mortality risk, in spite of the poorly-designed studies or meta-analysis that suggest it does.

US National Poison Data System

• Data collected by NPDS and published by the American Association of Poison Control Centers in Clinical Toxicology reported NO deaths from multiple vitamins; zero deaths from any of the B vitamins; zero deaths from vitamins A, C D, or E.

Nutritional Genomics Views

• The Reductionist Approach-tries to identify THE ONE gene that causes a particular disease, or THE ONE dietary chemical or supplement that will prevent it.

• The Systems Approach-uses methods from genetics, molecular biology, physiology and nutrition to study how diets affect an individual person: instead of analyzing only genes, it analyzes blood chemistries, enzymes, and metabolites, etc.; instead of looking at one gene, it considers many.

Genetic Role in Aging

Why our cells respond to our nutritional status

Our body’s cellular response to RNA decoded messages is dependent on our environmental status, including nutritional status.

Nutritional deficiencies cause cells to respond to degenerative or toxic genetic messages that may be ignored when the body is properly nourished.

B- Vitamins• B vitamins are water soluble and our needs change on a daily

basis based on environmental conditions. Our bodies remove any extra without risk of overdose.

• B1 is a big player in type-2 diabetes• B-2 in crosslinking• B3 in cholesterol control

• Vitamins B6, B12, and folic acid are suggested to protect women against age-related macular degeneration, as well as required to prevent the body from producing excessive amounts of homocysteine, a marker for disease including eye disease.

Folate, B6, B12 and Methionine Metabolism

Water Soluble B Vitamin FACTS

Adequate B Vitamin intake is critical for those who are at risk ofgene-related degenerative diseases like AMD and Alzheimer’s.

Hydro Carbon Beta Carotene – Not So Much

• Not an appropriate source of Vitamin A where eye health is concerned.

• Does not as readily covert to pre-formed Vitamin A (retinol) in the older population as it does in younger people

• Does not quench the singlet oxygen associated with AMD if other singlet oxygen quencher antioxidants like Bilberry are available through diet or other supplementation

• Inhibits the absorption of the two xanthophyll carotenoids, lutein and zeaxanthin, which are vital for optimal macula pigment density and UV lens protection

• Synthetic beta carotene associated with increased cancer risk

Vitamin E• A 2005 study in the JAMA suggested that excessive (400 IU) synthetic

Vitamin E can be dangerous. • A closer look shows that the isolated finding applied only to an older

group of patients (over the age of 70) with a long history of heart disease, stroke or diabetes, who 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.

• A significant percentage of study participants were also cigarette smokers, further clouding the issue.

• Always look for nutrition products that include only natural vitamin E tocopherols and tocotrienols – the d-form is natural, the dl-form is synthetic.

• Vitamin C regenerates Vitamin E so 200-300 mg of daily natural vitamin E including all 8 forms of the Vitamin E molecule is adequate.

Vitamin D – The Sunshine Vitamin

• Lowers the risk of many cancers• Improves bone calcium absorption• Reduces blood pressure in hypertensive

patients• Helps prevent chronic renal failure• Reduces risk of multiple sclerosis• Lowers risk of skin infections

Zinc, Copper, & Manganese Magic

• Zinc can biochemically shut down the nuclear factor kappa-B (NFk-B) pathway, which shuts off production of inflammation and pain-causing compounds (cytokines). It becomes even more efficient when presented with a balanced amount of copper and manganese, which creates mn(SOD) enzymes that create antioxidant defense in cells exposed to oxygen.

Why we must include nutritional antioxidants in

our diets? Specific plant-based antioxidants

scavenge free radical damaged molecules from inside cells, thereby protecting DNA.

Vitamins C and E help to prevent intra- and extra-cellular oxidative damage to oxidized lipid molecules.

Macula Pigment Nutrients

Lutein, Zeaxanthin, Meso-zeaxanthin

Lutein and Zeaxanthin also possess antioxidant properties

Bilberry: Fact or Fiction?• Anecdotal evidence of improved night vision of

pilots in WWII.

• Since the structure of anthocyanins is consistent with an ability to donate hydrogen atoms, it has been concluded that these compounds have powerful antioxidant capability.

• Accordingly, anthocyanins have been shown to scavenge chemically-generated superoxide and nitric oxide radicals, as well as quench destructive singlet oxygen.

N-Acetyl CysteinePrecursor to glutathione- an amino acid

complexGlutathione is the “master” antioxidantGlutathione is destroyed by digestive

process, therefore must be created internally.

Glutathione is depleted in cataractous lenses

NFk-B, Antioxidants & Inflammation

The generation of reactive oxygen species (ROS) by phagocytic leukocytes is one of the most important hallmarks of the inflammatory process.

In addition to promoting general cytotoxicity, ROS may also act to up-regulate pro-inflammatory gene expression by activating nuclear factor kappa b (NFk-B).

A variety of antioxidant molecules, such as

N-acetylcysteine (NAC) glutathione and vitamin E can inhibit NFk-B activation associated with eye disease.

↑ Mitochondrial FunctionMitochondria are dependent on water based amino acids, particularly

• acetyl-l-carnitine• lipoic acid, •COQ-10• small amounts of Omega-3 DHA

…for ATP energy and mitochondrial housekeeping. Small amounts of DHA is vital for membrane permeability that allows nutrients in and waste material out.

A powerful antioxidant that has been proven in new clinical studies to improve brain function, alter mood, and increase

cellular energy when taken with a balanced amount of Lipoic Acid.

This is particularly important to the AMD patient because most suffer from low to

medium grade depression.

Acetyl-L-Carnitine

Lipoic Acid

• Lipoic Acid is the nutrient that intracellularly regenerates most all other nutrients.

• Along with acetyl-L-carnitine, it increases ATP cellular energy.

• Both fat and water soluble antioxidant.

CoQ10 An enzyme that is required for electron

transport in ATP synthesis (facilitates energy production at the cellular level)

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

RESVERATROL for Eye & Body Health

• Resveratrol regulates protective sirtuin protein (SIRT1) gene expression in a dose dependent manner.

• SIRT1 is also referred to as the rescue gene, longevity gene, or skinny gene.

• A combination of SIRT1 and resveratrol are suggested to be the regulators needed to protect our eyes against UVB damage and our bodies against heart attack, stroke, diabetes, arthritis, osteoporosis and obesity.

Systemic Treatments for Dry Eyes

Orals Essential Fatty Acids

• HydroEye• BioTears• Hydrate Essential• TheraTears Nutrition• Fish Oil• Dry Eye Formula• EyePromise EZ Tears

Possible Effects of OmegaEFA on Dry Eyes

• Provide overall anti-inflammatory effect• Increase fluidity of meibomian gland

secretions• Alter polar characteristics of lipid layer

and decrease evaporative loss• Optimize function of goblet cells• Improve epithelial cells microvilli

expression and adhesion

What’s So Great About Fish?

Protein, Iron, Vitamins / Minerals and Omega-3 Fatty Acids

Every patient does not require the same amount of fish or fish oil. The American Heart Association recommendation is still two servings of fish per week for disease prevention, which is about 3,500 mg of Omega-3 fatty acids EPA / DHA per week.

Omega-3

Omega-3

Omega-3Omega

-3

Omega-3 Omega-3

Omega-3

Omega-3

Omega-3

Omega-3Omega-3

Omega-3

Omega-3

Grade School LogicThe most scientifically sound way to properly balance Omega-6 / Omega 3 fatty acid rationsis to simply consume fewer empty-calorie processedjunk foods and make the following Dietary changes:

Consume three or four daily small servings of nutrient-dense foods.

Include small servings of cold-water fish two or three times a week.Take one concentrated fish oil capsule a day on the days you don’t eat fish.

Anti-Inflammatory Omega-3 Fatty Acids From Fish Oil

Excessive Amounts Not Recommended to Compensate for Nutrient-Empty High Omega-6 Junk Food Diets.

Too Many Fish Being Removed From the Seas for This Reason.

KRILL OIL: Antarctic krill oil may be superior to fish oil because it contains phospholipids, carotenoid antioxidants and omega-3 bonded together in a way that keeps them safe from oxidation and easily absorbed in your body.

7 things to know about Omega-3 EFAs from HHS-2013

1. Results of studies provide moderate evidence that people who eat seafood once a week are less likely to die of hear disease

2. Supplemental EPA / DHA has NOT shown to protect against heart disease.

3. A 2012 review of studies suggest EPA / DHA may be modestly helpful in relieving symptoms of rheumatoid arthritis.

4. The nutritional value of seafood is important during fetal growth and development, particularly DHA.

5. Ongoing research in omega-3 fatty acids and brain and eye disease is not yet conclusive about effectiveness.

6. Conflicting evidence about omega-3 link to prostate disease7. Bottom line: including seafood in diet is healthful. Omega-3 supplements

benefit is still uncertain.

Fish Oil & Coagulation Status

• CASE REPORT– Omega-3 fatty acids may lower thromboxane A(2) supplies

within the platelet as well as decrease factor VII levels. This case report illustrates that fish oil can provide additive anticoagulant effects when given with Warfarin

Ann Pharmacother. 2004 Jan;38(1):50-2.

• STUDY – Effects of Marine Fish Oils on the Anticoagulation Status of

Patients Receiving Chronic Warfarin Therapy….. “Fish oil supplementation in doses of 3-6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic Warfarin therapy”.

J Thromb Thrombolysis. 1998 Jul;5(3):257-261.

Fish Oil Safety & Prostate Cancer• Blood level omega-3 fatty acids as risk determinant molecular biomarker for prostate cancer.

Sorongon-Leqaspi MK, Chua M, et al. Prostate Cancer. 2013;: 8756 [abstract]

Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. Brasky TM, Darke AK, et al. J Natl Cancer Inst. 2013 Aug 7;105(15): 1132-41 [abstract]

The relevance of serum levels of long chair omega-3 polyunsaturated fatty acids and prostate cancer risk: A meta-analysis. Chua ME, Sio MC. et al. Can Urol Assoc J. 2013 May-June;7(5-6): E333-43 [abstract]

Consumption of fish products across the lifespan and prostate cancer risk. Torfadottri JE, Valdimarsdotti UA, et al. Plos One 2012 Apr 17;8(4): e59799 [abstract]

Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Dahm CC, Gorst-Rasmussen A, et al. Am J Clin Nutr. 2012 Dec; 96(6): 1354-61

Omega-3 fatty acids and cancers: a systemic update review of epidemiological studies. Gerber M. Br J Nutr 2012 Jun; 107 [abstract]

Another Fish Oil Safety Big Concern• Immunomodulation by dietary long chain omega-3 fatty acids

and the potential for adverse health outcomes. Denton JL, Hord NG, Ghosh S, Gurzell EA. Prostaglandins Leukot Essential Fatty Acids. 2013 – Nov-Dec: 89(6): 379-90

• This study demonstrated that excessive Omega-3 long chain fatty acids EPA / DHA dampens immunity and alters cellular membrane pathogen clearance during acute infection resulting in adverse health outcomes and reduced survival.

• This calls for biomarker development and validation as rational first steps towards setting recommended dietary intake levels.

Short-term consumption of oral omega-3 and dry eye syndrome. Kangari H. Efekhari MH, et al. Ophthalmology 2012 Nov (30 days)

Effects of dietary supplementation with fish oil on dry eye syndrome subjects: randomized controlled trial. Kawakita T, Dawabata F, et al. Biomed Res 2013 (90 days)

Polyunsaturated fatty acids induce modification in the lipid composition and the prostaglandin production of the conjunctival epithelium cells. Vial S, Leclere L, et al. Graefes Arch Clin Exp Ophthalmol 2012 Feb. (Omega 6 GLA affected PGE1 and 2, Omega-3 showed no effect).

Dry Eye Fish Oil Studies May be Too Short for Long Term Therapy Consideration

Oil Omega-3 Omega-6 Gamma-Linolenic

Acid (GLA)

FLAX 85% 15% NONE

EPO NONE 75% 9%

Borage 75% NONE 23%

BlackCurrant Seed Oil

15% 65% 18%

Sources of Plant Based EFAs

Omega-6 vs. Omega-3

“Omega-6 administration increases the PGE1 levels in tears of patients with Sjögren’s Syndrome and improves ocular surface signs and symptoms of ocular discomfort.”

Systemic Omega-6 EFA Treatment and PGE1 Tear Content in Sjögren’s Syndrome Patients.

Aragona, P., Bucolo,C., et al

IOVS 2005; 46:4474-4479

Omega-6 vs. Omega-3“This study provides evidence for a beneficial

effect of particular orally administered omega-6 fatty acids in alleviating dry eye symptoms and improving overall lens comfort in patients suffering from contact lens associated dry eye.”

Oral omega-6 essential fatty acid treatment in contact lens associated dry eye, Kokke KH, et al.,

Contact Lens Anterior Eye (2008), doi:10.1016/j.clae.2007.12.001

Metabolic Pathways of Omega-3 and Omega-6 Fatty AcidsOmega-6 Omega -3

Black Currant, EPO, Borage (18-24% GLA)

Linoleic Acid (LA)

Delta--6-desaturase

Gamma-Linolenic Acid (GLA)

Dihomo-Gamma-Linolenic Acid (DGLA)

PGE1Delta-5-desaturase

Arachidonic Acid (AA)

Series One ProstaglandinAnti-inflammatory

Cylooxygenase (COX2)Lipoxgenase

LBT--4Pro--inflammatory

PGE-2Pro- inflammatory

Black Currant (15%) Flax (85%)Alpha-Linolenic-Acid (ALA)

Delta--6-desaturase

Steridonic Acid (SDA)

Eicosatetiaenoic Acid (ETA)

Delta-5-desaturase

Fish Oil &Cod Liver Oil

PGE3Anti-inflammatory

LBT-5Anti-inflammatory

Delta 6 enzymes impaired by aging, alcohol and nutrientdeficiencies, trans fatty acids and elevated cholesterol.

Lipoxgenase

EPA/DHA

EPA appropriately blocks Omega 6delta-5-desaturasedownstream conversion

Cylooxygenase

Polyunsaturated oils, including flax, corn and safflower

Natural Anti-Inflammatories

• Quercetin- bioflavonoids

• Ginger- gingerols (anti-inflammatory)

• White Willow Bark- extracted as salicin

• Curcumin- Tumeric

Vitamin A

• Vital for the health of epithelial cells of the cornea and conjunctiva, as well as the function of the immune system.

• It is also necessary for goblet cell and lacrimal gland production of the large variety of mucins now associated with the base layer of the tear film.

Vitamin B6

• One of the nutrient co-factors required to push the metabolic pathway conversion of GLA to DGLA.

• Required for the neuronal blink response.

Vitamin C

• Absorbyl palmitate (fat-soluble) modulates PGE1 synthesis due to the extended half-life of the fat-soluble vitamin C over ascorbic acid.

• This vitamin C combination also enhances the production of IgE concentrates in tears, the first line of basophil and mast cell defense against invading pathogens and allergens that frequently cause dry eye symptoms.

Vitamin D

It should be included in all nutraceutical formulations that include Vitamin A due to an increased risk of fractures in older patients taking large amounts of supplemental Vitamin A.

Vitamin E

• Vitamin E should be included in all fatty acid-based nutraceutical formulations to help prevent or slow lipid oxidation.

• This particularly includes any formulation that includes flax seed oil or any type of fish oil.

Lactoferrin

• The replication and biofilm formation of fungi, bacteria and viruses in mucosal tissues are iron-dependent. Growth of these pathogens becomes almost impossible if adequate amounts of iron-binding proteins, particularly lactoferrin, are concentrated in these fluids.

• Adequate levels of tear lactoferrin, naturally produced by the lacrimal gland and neutrophils, are particularly important for the eye surgery or contact lens patient with an increased risk of infection.

Additional Tear Support

• Minerals– Zinc and Magnesium- important in immune functions

• Mucin Enhancers– Aloe Vera Oil– Hyaluronic Acid

Flax Seed Oil• Does contain a large amount of Omega-3 EFA• Highly unstable, must be refrigerated• Contains NONE of the nutrient co-factors

necessary to ensure conversion to PGE1 anti-inflammatory

• Does not enhance production of lactoferrin• Excess now linked to cortical opacities and

prostate cancer.• May cause intestinal blockage, thyroid

problems and reduce platelet aggregation.

Metabolic Pathways of Omega-3 and Omega-6 Fatty AcidsOmega-6 Omega -3

Black Currant, EPO, Borage (18-24% GLA)

Linoleic Acid (LA)

Delta--6-desaturase

Gamma-Linolenic Acid (GLA)

Dihomo-Gamma-Linolenic Acid (DGLA)

PGE1Delta-5-desaturase

Arachidonic Acid (AA)

Series One ProstaglandinAnti-inflammatory

Cylooxygenase (COX2)Lipoxgenase

LBT--4Pro--inflammatory

PGE-2Pro- inflammatory

Black Currant (15%) Flax (85%)Alpha-Linolenic-Acid (ALA)

Delta--6-desaturase

Steridonic Acid (SDA)

Eicosatetiaenoic Acid (ETA)

Delta-5-desaturase

Fish Oil &Cod Liver Oil

PGE3Anti-inflammatory

LBT-5Anti-inflammatory

Delta 6 enzymes impaired by aging, alcohol and nutrientdeficiencies, trans fatty acids and elevated cholesterol.

Lipoxgenase

EPA/DHA

EPA appropriately blocks Omega 6delta-5-desaturasedownstream conversion

Cylooxygenase

Polyunsaturated oils, including flax, corn and safflower

Supplements

Common Misconceptions

They are “natural”, so completely safeThey are ineffectiveThey are all the sameMore is better

$28.7 Billion spent annually just in dietary supplements, vitamins and minerals

Summary

• Multi-pronged approach recommended• Minimize adverse environmental conditions,

anticholinergic medications, visual strain• Nonpreserved artificial tears• Use topical corticosteroids only for short periods

because of side effects• Topical cyclosporine- for severe cases• Treatment should not cause disruption in patient’s

lifestyle• Many patients prefer the “natural” approach