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American Pie

Meets

American Idle

Nutritional & Nutraceutical Management of Obesity

Related Eye Disease

A. Paul Chous, MA, OD, FAAO

• If current trends continue, 86% of the US adult population will be overweight or obese by 2030 • At this rate, 100% of the population

will be affected by 2048

Will All Americans Become Overweight or Obese? Estimating the Progression and Cost of the US Obesity Epidemic July 24, 2008

Battling the systemic & ocular complications of obesity is analogous

to keeping an overflowing bathtub from ruining the bathroom floor

Turn Off the Faucet

Pull the Plug Mop Up the Floor

Bail the Tub

Can You Be ‘Fat But Fit’?

YES!!! 1999-2004 NHANES Analysis (n=

5440) Arch Intern Med 2008 August;168(15): 1617-24

Assessed cardiometabolic risk: BP, TG, HDL-C, FPG, insulin sensitivity, CRP

• Normal Weight – 66.5% metabolically fit

• Overweight – 51% metabolically fit

• Obese – 32% metabolically fit

Lower risk in all groups associated with younger age, more physical activity & smaller waist

Why is Obesity Associated With

Ocular & Systemic Disease?

An Unholy Triumvirate

•Inflammation

•Hypertension

•Hypoxia

Inflammation Fat cells (adipocytes) are

endocrine cells, secreting hormones regulating insulin sensitivity & satiety, and are associated with elevated markers of inflammation

PAI-1 Factor VII iNOS

CRP ICAMs IL-6 Fibrinogen TNF-a

Resistan Adiponectin Leptin

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Subcutaneous vs.

Visceral Fat

Fat Cells Are Endocrine Cells!!

Reactive Oxygen Species & Inflammation

Oxidative Stress Endothelial Dysfunction

Disease

Hypercoaguability Vasoconstriction Inflammation

Obesity

VAT Fatty Liver

Inflammatory Cytokines

TNF-a

PAI-1 ICAMs CRP FFAs

Adipokines

Iron Overload

Metabolic Hp Genotype

Diet

Insulin Resistance

Skeletal Muscle Liver

Hypothalamus

Increased Oxidative

Stress

Blunted Satiety Receptors

Hunger & Increased

Caloric Intake

Disease

Hypertension Obesity & BMI are clear and

continuous risk factors for HTN

• IR activates the renin-angiotensin system

Weight loss results in reduced BP in large clinical trials

HTN is a definitive risk factor for CVD and myriad ocular diseases (RVOs, AION, DR)

Blood Press. 2007;16(1): 13-19 Am J Hyperten. 2006 Nov;19(11): 1103-9

Hypoxia

Obesity is THE major risk factor for obstructive sleep apnea syndrome (OSAS)

OSAS causes hypoxic stress and elevates blood pressure

OSAS is associated with endothelial

dysfunction and several eye diseases

J Clin Sleep Med. 2007 Jun 15;3(4): 409-15 Exp Physiol. 2007 Jan;92(1): 51-65

OBSTRUCTIVE SLEEP APNEA Highest risk if Neck Circumference > 17 inches

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Inflammation ROS

Endothelial Dysfunction

Hypertension

Hypoxia

Clinical Entities: Eye Disease

Associated with Obesity

Cataract

AMD

Glaucoma

Diabetic Retinopathy

NAION

Floppy Eyelid Syndrome (FES)

Pseudotumor cerebri (PTC)

Venous Occlusive Disease

Cataract

BMI > 30 increased risk of PSC and cortical cataract (Blue Mountains Eye Study.

Ophthalmic Epidemiol. 2003;10(4):227-40)

Metabolic Syndrome increases risk of cataract by 30-40% (Eur J Ophthal.

2007;17(4): 605-14)

Risk of PSC 2.5X higher for women with waist circumference > 89cm (Am J Clin Nutr 2003;78:400-5)

Did you know all of these are

associated with Obstructive

Sleep Apnea (OSAS)?

• Glaucoma prevalence estimated 2-7% (Eye

2007;22(09): 1105-9)

• Floppy Eyelid Syndrome prevalence - 25% (Ophthalmology. 2006;113(9):1669-74)

• Pseudotumor Cerebri (15-40%) J Neuroophthal 2001 21(3):235)

• OSAS is the most frequent disorder in patients with NAION (BJO. 2006;90(7):879-82)

Higher IOP also associated with obesity

(Diab Metab Res Rev. 2005;21(5): 434-40)

AMD

Increased risk with increasing BMI & waist size (Arch Ophthalmol. 2003;121(6): 785-92)

5% increased risk of advanced AMD with every 1 kg/m2 increase in BMI (Am J Ophthalmol. 2007;143(3): 473-83)

In AREDS, BMI > 30 doubled the risk of SRNV (Ophthalmology. 2005;112(4):533-9)

Greater waist circumference and DM associated with lower MPOD (Am J Clin Nutr. 2006;84(5): 1107-22)

Diabetic Retinopathy

Obesity & weight gain are the primary risk factors for T2DM (Ann

Intern Med. 1997;122:481-6)

Marked obesity increases the risk of DR (Diabetes Care. 1986;9(4): 961-9)

6-fold increased risk of PDR when BMI > 30

Invest Ophthalmol Vis Sci. 2011 Jun 22;52(7):4416-21

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Venous Occlusive Disease

Risk of RVO and arterial emboli is 3.8 fold higher for BMI > 30

(Ophthalmology. 2005;112(4): 540-7)

High risk of BRVO reported when BMI > 25 kg/m2 at 25 years of age (Ophthalmology. 1996;114(5): 545-54)

Obesity - Classic Definition

BMI > 25 overweight

BMI > 30 obese

BMI > 35 severely obese

BMI > 40 morbidly obese

Children & Teens

Overweight BMI > 85% percentile

Obese BMI > 95% percentile

Girls Boys

Other measures of obesity

Abdominal Adiposity

• Waist Circumference > 102 cm

(40 inches) in men

• Waist Circumference > 88 cm

(35 inches) in women

• Waist:Hip Ratio >1.0 for men

> 0.8 for women

“There is a charm about the forbidden that makes it unspeakably desirable” -Mark Twain

“My doctor told me to stop having intimate dinners for four. Unless there are three other people” -Orson Welles

Nutritional

Management

Biologic Rationale For Specific

Macronutrients

Dietary Macronutrients are nutrients needed in relatively large quantities

• Fats (glycerin + 3 fatty acids)

• Carbohydrates (sugars)

• Proteins (amino acids joined by peptide bonds)

The goal is to reduce not only weight, but Visceral fat and inflammation

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Dietary Fat

Saturated Fat:

• High intake linked to increased CV risk & inflammation (J Lipid Res. 2006;47: 1661-7)

• Intake > 10% of calories worsens insulin sensitivity and LDL-C (Hepatology. 2003;37: 909-16)

• But intake < 7% of calories has little effect on LDL-C and significantly lowers protective HDL-C, especially in patients with insulin resistance (Obes Surg. 2005;15: 502-5)

Medium Chain Triglycerides (MCTs)

A healthier saturated fat consisting of 6-10 carbon chains

Extracted from coconut oil

Enhance thermogenesis

Promote weight loss

Obes Res. 2003 Mar;11(3):395-402

Am J Clin Nutr. 2008 Mar;87(3):621-6

Dietary Fat

Trans Fat

•partially hydrogenated oils (corn oil & vegetable oil) significantly increase inflammation and CV risk

(N Engl J Med. 1997;337: 1491-99) and induce endothelial dysfunction

(Atheroscler Supp. 2006;7: 29-32)

•Eliminate all trans Fats

Note: trans fats < 0.5 g are reported as “0” on food labels

Monounsaturated Fats - MUFA

Decrease triglycerides, LDL-C and oxidized LDL-C without decreasing HDL-C (J Nutr Biochem. 2006;17: 645-58)

Decrease ICAMs & improve endothelial dysfunction (Ann Intern Med. 2001;134: 1115-19)

High levels of MUFA in macadamia & olive oil, nuts and avocadoes

Polyunsaturated Fats - PUFA n-3 and n-6 subtypes

n-3 PUFA (e.g. a-linolenic acid) tend to decrease inflammation

• The high arginine content of tree nuts (esp. walnuts) also decreases CRP (Nutrition. 2005;21:125-130)

n-6 PUFA (linoleic acid) tend to increase inflammation

Debate: does the ratio of n-6:n-3 PUFA determine the inflammatory effect?

A 2:1 to 6:1 ratio is recommended to maximize CV benefit

Typical US Diet has an inflammatory 20:1 ratio

Benefits of PUFA

Decrease rates of Heart Disease

EPA + DHA decrease TGs, FFAs, blood glucose & insulin levels, visceral fat mass and many inflammatory markers

Both marine and plant sources Plant sources inefficiently converted to

EPA/DHA

Marine sources (cold water fatty fish) naturally high in DHA/EPA

Arch Intern Med. 2005;165: 193-7

J Nutr Biochem. 2006;17: 1-13

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Take Home on Fats

Keep SFA between 7% and 9% of calories (favor MCTs)

Eliminate all trans fats

Increase consumption of MUFA

Substitute PUFA for SFA

Increase consumption of n-3 PUFA as well as DHA & EPA

Carbohydrate

High intake of simple sugars (glucose, fructose & sucrose) increases serum FFAs and oxidative stress (Am J Clin Nutr. 2001;74: 737-46)

By a mass effect, post-prandial hyperglycemia increases cellular glucose uptake, production of ROS and pro-inflammatory cytokines (Nature.

2001;414:813-20; Circulation. 2002;106: 2067-72)

Production of reactive oxygen species (Superoxide) by mitochondria exposed to any glucose

Intracellular Glucose & FFAs

ATP + hSuperoxide (O2

-) Mitochondrian

Inflammatory Cytokines

HFCS and Obesity? HFCS and Obesity?

Fructose is metabolized by hepatocytes to produce triacylglycerol and uric acid

Uric acid reduces NO levels

NO is requisite for insulin receptor function

HFCS elevates triglycerides and fosters hyperuricemia-induced insulin resistance

HFCS contributes to the Metabolic Syndrome (Am J Physiol Renal Physiol 2006;

290(3):f625-31)

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Uric Acid & Metabolic Syndrome Metabolism. 2008 Jun;57(6):845-52

6 7 8 9 10

Serum Uric Acid (mg/dl)

Prevalence

of

Metabolic

Syndrome

%

Per NCEP

ATP-III

Criteria

100

80

60

40

20

0

FPG > 110 HDL < 40 (male) or < 50 (female)

BP > 130/85 TG > 150

Waist > 40 inches (male) or 35 inches (female)

The Case for Fruits & Vegetables

Diets with high intake of fruits & vegetables are consistently associated with lower CV risk (JAMA 2002;288: 2569-78)

• Rich in antioxidants • High in fiber

Fiber increases insulin sensitivity Fiber reduces inflammation Fiber reduces BP

The Case for Pomegranates?? • Juice, seeds and extract all reduce

biomarkers of oxidative stress (J Agric Food

Chem. 2007;55(24): 10050-4)

• PJ reduced systolic BP 21% and oxidized LDL-C by 90% in patients with CAS

• PJ + statin decreased carotid intima media thickness by an average of 30% at one year (Clin Nutr. 2004;23(3): 423-33)

Carotid IMT before and after 1 year of daily PJ consumption (50 ml) in

a patient with carotid artery stenosis (CAS)

Control subjects on 40 mg simvistatin had a mean carotid IMT increase of 9%

30% mean decrease at 12 months

Fermentable Carbs: The Case for Alcohol

Moderate intake of all alcoholic beverages lowers CRP and is associated with lower rates of fatal & non-fatal CV disease (Am J

Cardiol. 2005;96(1): 83-88)

½ drink per day confers protection by increasing insulin sensitivity and HDL-C (J Am Coll

Cardiol. 2007;50(11): 1009-14)

Do particular dietary sources of carbohydrate influence glucose homeostasis and inflammation?

Good Carb: Bad Carb

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Glycemic Index (GI)

& Glycemic Load (GL)

GI is the incremental area under the blood glucose response curve of a 50g portion of test food compared to a standard (white bread or glucose)

GL = GI x portion size (gms) 100

Criticisms: Many

Are GI & GL useful? Low dGI/dGL diets reduce fasting

blood glucose, glycated protein and insulin resistance (Am J Clin Nutr. 2008 Jan;87(1):258S-268S)

dGL specifically influences CV risk in obese patients (Am J Clin Nutr. 2007;85(3): 724-34)

High dGI increases the risk of

developing T2DM (Diab Technol Ther 2006;8(1):

45-54) & AMD (large drusen, GA, CNVM) (Am J Clin Nutr. 2007;86(1): 180-8)

100,000 cases of severe AMD would have been prevented if dGI

had been < sex median

(Am J Clin Nutr. 2007;86(1): 180-8)

Take Home Take Home on Carbs & Fiber

Decrease intake of refined carbs (avoid white food)

Reduce & diffuse the glycemic load (smaller, more frequent meals)

Eat a variety of lower GI/GL fruits & vegetables; increase intake of dietary fiber to > 25g/day

Consider moderate alcohol consumption (1 drink QOD), preferably red wine, 3 oz. pomegranate juice daily and a small square of dark chocolate twice/week

Dietary Protein Increased protein intake results in

heightened satiety and weight loss (J Nutr. 2004;134:975S-979S; Cell Metab. 2006;4:223-33)

• Triggers release of gut hormones (adiponectin, GLP-1) that iappetite

• Increases thermogenesis (body heat)

BUT

Appears to worsen insulin sensitivity and may contribute to kidney disease (Annu Rev Nutr. 2007;27:293-310; Clin J Am Soc Nephrol. 2006;1(6): 1293-9)

hIGF which may shorten lifespan (Aging Cell. 2008;7(5): 681-7)

Take Home on Protein

Increased protein consumption decreases appetite and assists in weight loss

These benefits must be weighed against the risk of kidney dysfunction and worsened insulin resistance

Increased consumption of cold water, fatty fish and some fermented soy protein is preferable

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Dietary Recommendations for

Overweight & Obese Patients

Eat an anti-inflammatory, calorie restricted diet consisting of a variety of low GL fruits & vegetables, nuts, whole grains and plentiful fiber, favoring cold water, fatty fish and some soy protein, with minimal, regular alcohol consumption (1/2 glass of red wine daily)

Modify based on clinical history

What sort of diet fulfills most of these criteria?

The Mediterranean Diet

Multiple studies show greater adherence to a Mediterranean-type or Paleolithic-type diet lowers inflammation, insulin resistance, CV events, cancer and mortality

The Mediterranean Diet

Nurses Health Study showed reduced biomarkers of inflammation & endothelial dysfunction (Am J Clin Nutr. 2005;82: 163-73)

Lyon Heart Study showed a 70% reduction in MI and unstable angina

EPIC showed an inverse correlation between adherence to a Med style diet and death (N Engl J Med. 2003;348: 2599-2608)

The NIH-AARP study (n= 380,000) showed a 20+% reduction in CVD & Cancer mortality (Arch Intern Med. 2007 Dec 10;167(22):2461-8 )

83% reduced risk of T2DM over 4 years (BMJ 2008, May 29 – EPub June 1)

Little proof of ocular benefit – but good probability

Eat (Real) Food

Not Too Much

Mostly Plants

Micronutrient/Nutraceutical

Supplements to Mitigate

Obesity and Eye Disease

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Do Obese Patients Need

Antioxidants?

Oxidative stress in obese persons is greater in those with insulin resistance (Obesity.2009Feb;17(2):240-6.)

Low levels of vitamin B-6, vitamin C, 25-hydroxyvitamin D, and vitamin E is prevalent in morbidly obese patients (Am J Clin Nutr.

2008 Feb;87(2):362-9)

YES Vitamins/Minerals/Cofactors

Vitamin C decreases insulin resistance, cataract & cancer risk

Vitamin E improves BV and neuron health

Vitamins K reduces inflammation & improve insulin resistance

CoQ10 is requisite for fatty acid metabolism and may assist weight loss

Chromium (polynicotinate) lowers body weight and improves IR & TGs

Niacin raises HDL-C and slows atherosclerosis

How to Raise HDL-C:

“NEAF”

Niacin

Exercise

Alcohol

Fish Oil

Supportive Synergy of Vitamin C & E

Randomized Control Trials The Antioxidant Supplementation in Atherosclerosis

Prevention (ASAP) Study

Vits. C & E: 500 mg; 182 mg

Harvard Intravascular Ultrasonography (IVUS) Study

Vits. C & E: 1000 mg; 536 mg

HDL-Atherosclerosis Treatment Study (HATS)

Vits. C & E: 1000 mg; 536 mg

*Multi-Vitamins and Probucol (MVP) Study

Restenosis s/p balloon angioplasty; Vit C, E,

& β-carotene- 500 mg, 700 IU (637 mg), 30000 IU

*Heart Protection Study

Mortality; Vit C, E & β-carotene- 250 mg, 600 mg, 20 mg

Vitamin D Multiple studies show inverse

relationship between obesity and serum vitamin D

Supplemental D3 assists with weight loss and reduces fat mass while reducing inflammation, BP, IR

Nutr J. 2012 Sep 22;11:78.

Nutr J. 2012 Sep 9;11:68

Am J Clin Nutr. 2012 Jul;96(1):24-9 J Clin Endocrinol Metab. 2012 Jul;97(7):2456-65.

Am J Clin Nutr. 2012 Jan;95(1):101-8

DO YOU ASK YOUR PATIENTS IF

THEY CONSUME FISH / FISH OIL ???

↑ HDL

↓ triglycerides

↓ Blood pressure

↓ Heart Beat rate

↓ arrhythmias

• (studies show as effective as a pacemaker)

• ↓ sudden death heart attack

↓ Violent Behavior; ↑ Mood

↑ Cognitive function

↓ MI, CVA, CA & AMD

Fish (sardines, herring, salmon, tuna) 2x per week or 1000mg EPA + DHA/day

Use products without Retinyl Palmitate?

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Fiber Supplement

Benefits:

Controls & balances blood sugar levels

Lowers glycemic index of meals by up to 50%

Supports healthy weight loss

Promotes satiety & ↓ food cravings

↓ total and LDL cholesterol

Irvingia gabonensis Ground seeds of the African Mango

Multiple MOA: blocks amylase, blocks uptake of TGs by adipocytes, increases satiety

10 week, placebo-controlled RCCT • Mean weight loss of 28 lbs

• Mean reduction in waist circumference of 6 inches

• Significantly decreased blood glucose, body fat, LDL-C and CRP

(Lipids Health Dis. 2009;8:7)

Figure 3

Percentage decrease in body weight (WT), Waist size (WS), Fat (FAT), Total Cholesterol (TCHOL),

LDL cholesterol (LDL), Glucose (GLU), Leptin (LEP), C-reactive protein (CRP) and Adiponectin (ADIP)

after 10 weeks of use of extract IGO131.

Lipids Health Dis. 2009; 8: 7.

Published online 2009 March 2. doi: 10.1186/1476-511X-8-7.

IGOB131, a novel seed extract of the West African plant

Irvingia gabonensis, significantly reduces body weight and

improves metabolic parameters in overweight humans in a

randomized double-blind placebo controlled investigation

Communication

Obese patients find the terms ‘fat’ and ‘obese’ highly derogatory, preferring ‘excess weight’ or ‘high BMI’ (Obes Res. 2003;11(9): 1140-6)

The vast majority of overweight (84%) and obese patients (97%) believe they need to lose weight, but fewer than 25% had discussed weight loss with their PCPs (J Fam Pract. 2001;50(6): 513-18)

Effective Patient Communication

Ask for permission to discuss weight status • Be careful to distinguish between the weight

problem and the person • Focus on specific health risks (AMD, DR,

• Build a partnership by helping patients set a few realistic goals

• Walk 5,000 steps daily, lose 7% of weight, reduce BP by 10/5, increase MPOD, etc.

My Recommendations Eat a Mediterranean-type diet

Take a quality multivitamin/mineral capsule

Get your vitamin D level at 60-80 ng/ml

Take EPA + DHA = 1000 mg daily

Eat ½ cup berries and 3 oz. of pomegranate juice daily

Walk 8K steps (1 hour – 4 miles)/day

If you snore get tested for sleep apnea

Don’t eat when it’s time to sleep: 2.5X the weight gain in mice (Obesity (Silver Spring). 2009 Sep 3. Circadian Timing of Food Intake Contributes to Weight Gain)

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Avoid Being McNaughty Nutrients For Specific Conditions

AMD: AREDS formula + L/Z + O-3….

DR: L/Z/Lyc + curcumin + D3 + benfotiamine + Pycnogenol…..

Glaucoma: Mirtogenol® (patented combo of Pycnogenol® + bilberry)

• Lowers IOP 3-9 mmHg over 16 wks

• Additive effect to latanoprost & improves CRA blood flow

Mol Vis. 2008 Jul 10;14:1288-92

Clin Ophthalmol. 2010; 4: 471–476.

•Caloric restriction •Increase energy expenditure •BG and BP control •CPAP for OSAS

•Targeted Antioxidants •Targeted micronutrients • Anti-inflammatory Diet

•Caloric restriction •Exercise •Pharmacotherapy

•Sibutramine, Orlistat, rimonabant

•Bariatric Surgery

TURN OFF the FAUCET

MOP UP the FLOOR

BAIL the BATH/Pull the Plug

THANK YOU for

Your Kindness TOA !

A. Paul Chous, O.D. dr.chous@diabeticeyes.com

www.diabeticeyes.com

A Society Focused on

Ocular Nutrition Education

www.ocularnutritionsociety.org