The Anti-Inflammatory Diet and Cardiovascular Disease

Michael Brown MD, PhD

Inflammation:A common final pathway• Cardiovascular disease• Cancer• Neurodegenerative disease• Autoimmune disease• DM• Obesity

What is Inflammation?• Complex orchestration of pro-

inflammatory and anti-inflammatory events

• Mediated by eicosanoids– Prostaglandins, thromboxanes,

leukotrienes,– Hydroxylated fatty acids, lipoxins,

prostamides, isoprostanoids• Silent inflammation vs. painful

inflammation

Phases of inflammation• Initiating event-• Pro-inflammatory attack

response/cellular destruction• Anti-inflammatory healing

response/Cellular rejuvenation

Omega 6 Fatty Acid (Linoleic Acid)

Omega 3 Fatty Acids(alpha-linolenic acid)

Δ6-DesaturaseGamma-linolenic acid

(GLA)Evening Primrose Oil

Borage OilBlack Current Oil

Arachidonic Acid

LeukotrienesProstaglandins (PGE2)(Inflammatory)

Lipoxygenase

Cyclo-oxygenase

(COX)

Eicosapentaenoic Acid

(EPA)

ProstaglandinsPGE1, PGE3

(Favorable)

Less InflammatoryLeukotrienes

Lipoxygenase

Docosahexaenoic acid

(DHA)

COXΔ5-Desaturase

Arachidonic Acid (in cell membrane)

Free AA

Phospholipase A-2

Cyclo-oxygenase

Pathway

Lipoxygenase

Pathway

Prostaglandins&

ThromboxanesLeukotrienes

Steroids

Aspirin

NSAIDs

COX II Inhibitors:

Celebrex, Vioxx, Mobic

Colchicine

Sulfasalazine

Leukotriene Inhibitors:

Accolate, Singulair, Zyflo

FAT IS GOOD!!• Depending on what kind….– Omega 3 fatty acids (fish oils-EPA, DHA;

plant sources -ALA)– Mono-unsaturated fats (canola and olive

oils)• Decreased fat consumption since the

1960’s associated with obesity epidemic—CHO intake has increased dramatically

• Glycemic index/glycemic load

Types of fats• Saturated:

beef and other animal fats, dairy• Monounsaturated (omega-9):

olive and canola oils

Polyunsaturated fats (essential FA’s):– Omega-6: Linoleic acid (LA)--vegetable oils,

seeds, nuts Gamma Linolenic Acid (GLA)--borage and

primrose oil Arachidonic Acid(AA)--meat products

— Omega-3: Alpha Linolenic Acid (ALA)--legumes, leafy vegetables, flax, flaxseed and canola oils) Eicosopentanoic acid (EPA)-fish oil Docosahexanoic acid (DHA)--fish oil, breast milk

Avoid or Reduce• Trans-fatty acids BAD! • Omega-6 fatty acids• Margarine• Corn oil, cottonseed oil, grapeseed oil, peanut

oil, safflower oil, sesame oil, soybean oil, sunflower oil, partially hydrogenated oils

• Any product with long shelf life (crackers, pastries, chips)

How much Omega-3 fats do you need?• Strive for Omega 6: Omega-3 ratio of 4:1

(usual SAD (Standard American Diet) 16:1

• Maintenance 2.5 g/d• Improve hear function 5 g/d• Treat chronic pain 7.5 g/d• Treat neurological disease >10g/d

Sears, The Anti-Inflammation Zone, 2005

Types of Fish Oil• Fish– Contamination with PCB, dioxin, and Hg– Higher in AA than fish oil

• Crude fish oil– High contamination

• Health food grade– Still some contamination with PCB’s and

dioxins• Ultra-Refined EPA/DHA Concentrates– Removal of PCB’s and other toxins– Can be used in high doses (“weapons

grade”)

Requirements for an Ultra-refined EPA/DHA concentrate

• Total long-Chain Omega-3 >60%• Dioxins< 1 ppt• Mercury <10 ppb• PCB’s<30 ppb

What is an anti-inflammatory diet?• Lose fat• Eat small meals• Have some protein at every meal but reduce

red meat and dairy (Avoid charred, overcooked foods)

• Cold water fish (salmon, mackerel, sardines, herring)

• Eat primarily fruits and vegetables• Leafy green vegetables, nuts, flaxseeds or oil• Take your fish oil

Anti-inflammatory Lifestyle• Exercise• Quit smoking• Weight loss• Stress management• Vagal nerve stimulation via abdominal

breath work• Treatment of depression• Social support

Arachidonic Acid (in cell membrane)

Free AA

Phospholipase A-2

Cyclo-oxygenase

Pathway

Lipoxygenase

Pathway

Prostaglandins&

ThromboxanesLeukotrienes

Onions/Apples Quercetin

Turmeric Curcumin,

Feverfew Perthenolides

Onions/ Apples Quercetin

Turmeric Curcumin

Rosemary

Ursolic acid

Red Pepper Capsaicin

Ginger

Onions/Apples Quercitin

Boswellia Bosellic Acid

Rosemary Carnosol

Mediterranean Diet

• More tolerable than low fat diets and associated with improved long term weight loss (McManus 2001)

• Risk reduction of death from CAD = 0.67 compared to usual AHA diet (Trichopoulou et al, 2003)

Something fishy?

American Heart Association Recommendations

Healthy individuals should take two servings of fish(salmon, sardines, tuna, mackerel, trout) weekly along with flaxseed, canola, and soybean oil

Patients with CHD should consume higher doses, 1 g/d of EPA + DHA, which may require fish oil supplementation

• Utilize complex carbohydrates, higher in fiber and lower in glycemic load to reduce risk of CHD

AHA Recommendations: Intake of omega-3 fatty acids. Women’s Health in Primary Care. 2003.6(1): 25-26 (Consensus opinion)

Hu F, Willett W.Optimal diets for prevention of coronary heart disease. JAMA. 2002;288:2569-2578 {Systematic review}

Indications from other studies• Eating fish as little as once a week reduces the

risk of sudden death in men• Eating fish twice a week reduces CHD risk in

women• Fish intake reduces Alzheimer’s risk

Harper, Beyond the Mediterranean Diet: the Role of Omega-3 Fatty Acids in the Prevention of CAD, Prev Cardiol, 2003

Morris, Consumption of fish and n-3 fatty acids and risk of Alzheimer dz,. Arch Neurol, 2003

How intake of Omega-3 Fatty Acids is helpful

• Stabilization of atherosclerotic plaques• Reduction of inflammation by mediation prostaglandin

synthesis pathway• Improved ratio of omega-3 to omega 6 FA reduces

arachidonic acid and pro-inflammatory, pro-platelet aggregatory cytokines

• Enhances PGE1 and PGE 3 and less inflammatory leukotrienes(see diagram)

Thies F, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaque: RCT, Lancet, 2003;361:477-85

Harper, Beyond the Mediterranean Diet: the Role of Omega-3 Fatty Acids in the Prevention of CAD, Prev Cardiol, 2003;6(3):134-46

Fish Oil for secondary prevention• 240 pts with suspected Acute MI• 2 gms fish oil vs. placebo• After 1 year, 54% reduction in serious

ventricular arrhythmia, 30% total reduction in cardiac events

Singh, Cardiovasc Drugs Ther 1997

GISSI• More than 11,000 patients on 1 gm fish

oil/d < 3mos post MI• 20% reduction in total mortality• 10% reduction in recurrent MI• 40% reduction in sudden death

Lancet 1999;354

AHRQ report Overall, the evidence from the primary and

secondary prevention studies supports the hypothesis that consumption of omega-3 fatty acids,fish, and fish oil reduces all-cause mortality. Reduction was observed in CVD outcomes such as sudden death, cardiac death (coronary or MI) and MI although the evidence is strongest for fish or fish oil.

AHRQ study• Most studies show very low

cardiovascular mortality in populations with high fish consumption

• Strongest, most consistent effect of omega-3 fatty acids was reduction in triglycerides from 10-33%

A word about…• Glycemic Index (rate of absorption of

glucose)• Glycemic Load (ratio between GI and

CHO content)

• www.glycemicindex.com

High Glycemic/Load Foods Increase:

• Inflammation• Risks of heart disease, diabetes• Examples include: – White bread, glucose (GI= 100)– Potatoes, white rice– Pastries, white flour– Sweets, carbonated soft drinks

Lower GI/GL reduces risk• Whole grains• Fruits• Vegetables• Legumes• Or…mixing high GI/GL foods with those

with lower GI/GL

Superfoods to decrease inflammation

•BEANS•Pinto, navy, Great Northern, lima, garbanzo(chickpeas), black beans, lentils, green beans, sugar snap peas, and green peas

•BLUEBERRIES•Purple grapes, cranberries, boysenberries, raspberries, strawberries, currants, blackberries, cherries, and all other varieties of fresh, frozen, or dried berries

•BROCCOLI•Brussel sprouts, cabbage, kale, turnips, cauliflower, collards, bok choy, mustard green, Swiss chard

•OATS•Wheat germ, ground flaxseed, brown rice, barley, wheat, buckwheat, rye, millet, bulgur, wheat, amaranth, quinoa, triticale, kamut, yellow corn, wild rice, spelt, couscous

•ORANGES•Lemons, white, and pink grapefruit, kumquats, tangerines, limes

•PUMPKIN•Carrots, butternut squash, sweet potatoes, orange bell peppers

Superfoods to decrease inflammation

SALMON•Alaskan halibut, canned albacore tuna, sardines, herring, trout, sea bass, oysters, and clams

SOY•Tofu, soymilk, soy nuts, edamame, tempeh, miso SPINACH•Kale, collard, Swiss chard, mustard greens, turnip greens, bok choy, romaine lettuce, orange bell peppers

TEA – GREEN OR BLACK

TOMATOES•Red watermelon, pink grapefruit, Japanese persimmons, red-fleshed papaya, strawberry, guava

TURKEY•Skinless chicken breast

WALNUTS•Almonds, pistachios, sesame seeds, peanuts, pumpkin, and sunflower seeds, macadamia nuts, pecans, hazelnuts cashews

YOGURT•Kefir

  SUPERFOOD #7:

WILD SALMONWILD SALMON

 • Lowers the risk of heart disease and cancer.• The more omega-3 fish oils you eat; the lower your blood

pressure• In one study eating the oil in fish cut cancer incidence by over

60%• 4x weekly risk for and progression of AMD• Studies suggest that fish consumption is associated with a

lower risk for depression, violent behavior, Alzheimer’s disease, Attention Deficit Disorder, Atrial fibrillation.

• SPF nutrients• TRY TO EAT Wild salmon, halibut, sardines, etc. 2 to 4 times

per week

  SUPERFOOD #13:

WALNUTSWALNUTS

• A handful a day can cut your risk of cardiovascular event by as much as 51%

• Two tablespoons of peanut butter 5 times/week cuts risk of type II diabetes by 20%

• Along with tea, the easiest way to improve your heath

• Risk/progression of AMD

• SPF nutrients

• TRY TO EAT a handful of nuts, five times a week

* Skip the salt and added oils

WALNUT SIDEKICKSWALNUT SIDEKICKS• Almonds• Pistachios• Sesame Seeds• Peanuts• Pumpkin and Sunflower Seeds• Macadamia Nuts• Pecans• Hazelnuts• Cashews

10 Foods to Avoid10 Foods to Avoid• Donuts• White Bread• Bread with < 3 grams fiber/ slice• Soda• Stick Margarines• White Pasta• Full Fat Dairy• Movie Theatre Popcorn• Luncheon Meats• Sugar Coated Cereal

References• Rakel D, Rindfleisch A. Inflammation: nutritional,

botanical, and mind-body influences. South Med J 2005;8(3):303-310

• Liu S, Willett W, Stampfer M, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr 2000;71:1455-1461

• Ascherio A, Katan, M, et al. Trans fatty acids and coronary heart disease. NEJM 1999;340;1994-1998