Omega-3 Fatty Acids: An Untapped Resource for Improving Health R. Curtis Ellison, MD Professor of Medicine & Public Health Director, Institute on Lifestyle & Health Boston University School of Medicine Boston, MA,

Omega-3 Fatty Acids * Certain plants contain alpha-linolenic acid (ALA) (plankton, flaxseed, canola oil, soy bean oil) * When fish eat plankton, ALA is changed into “fish oils” (EPA and DHA) * Humans get omega-3 from fish or fish oils (EPA, DHA), or from plants, especially canola oil (ALA)

Omega-3 Fatty Acids & CHD Many studies have shown that fish consumption decreases coronary heart disease (CHD) Many studies have shown that taking fish oils decreases CHD, especially sudden death Limited studies on ALA, but ALA has potential advantages over fish oils

Diet & Coronary Heart Disease (CHD) Before WWII, CHD uncommon In 1950’s-60’s, CHD became an “epidemic,” killing 2 million/yr in US Stimulated research on CHD by epidemiologists

Epidemiologists? What Do Epidemiologists Do? We count bodies! 400 dead bodies in one group 200 dead bodies in another group

What Else Do Epidemiologists Do? We try to determine what is causing the difference? (Are differences in diet explaining the differences in deaths between the two groups?)

The Seven Countries Study * Cohorts of healthy men recruited in 7 countries (Greece, Italy, Yugoslavia, Holland, Finland, USA, Japan) * Diet and other lifestyle factors assessed, laboratory tests done in early 1960s * Subjects followed over > 25 years

Dietary Promoting Factors? Saturated fatty acids Coronary Heart Disease: Seven Dietary Factors (Ulbricht and Southgate, Lancet, 1992) Dietary Promoting Factors? Saturated fatty acids * Hypercholesterolemic Fatty Acids (12:0, 14:0, 16:0) * Thrombogenic Fatty Acids (14:0, 16:0, 18:0)

Lowering Saturated Fat & CVD: Results from 27 Randomized Trials Total mortality RR = 0.98 (0.86-1.12) CV mortality RR = 0.91 (0.77-1.07) CV events RR = 0.84 (0.72-0.99) BMJ 2001;322:757-63

Coronary Heart Disease: Seven Dietary Factors (Ulbricht and Southgate, Lancet, 1991) Protective Factors Polyunsaturated Fatty Acids, n-6 Series 18:2 – linolenic acid Polyunsaturated Fatty Acids, n-3 Series 18:3 – alpha-linolenic acid 20:5 – eicosapentanoic acid (EPA) 22:6 – docosahexanoic acid (DHA) Monounsaturated Fatty Acids 18:1 – oleic acid Dietary Fiber Antioxidants

Seven Countries Study Review by Professor Serge Renaud CR E T 9 M ED ZU PH N U S CO H ORT HO L LAND O TA 5 1 4 9 3 y e a r s / . C D 84 20 57 h o l t 2 94 32 23 6 ( mg d l) 8 16 52 7 18 RAILROAD Mortality Bread Legume 1 F o o d s tuff F r u it 4 6 4 1 30 82 23 3 ( g / d a y ) Meat 3 5 1 40 1 38 27 3 Fish 1 8 34 12 3 Edible Fat 9 5 60 79 3 3 A l c o h o l 1 5 43 3 6 A dap t ed f r om A . K ey s (19 7 0) a n d D . Kr omh o ut (1 9 89)

Fatty Acids from Cholesterol Esters

The Lyon Diet Heart Study Professor Serge Renaud • A clinical trial of post-MI patients comparing a Cretan-based “Mediterranean diet” with the usual diet advised, a low-fat & cholesterol diet. • Used a Canola-oil based margarine to replace butter; urged use of olive or canola oil instead of vegetable oils high in linoleic acid.

The Lyon Diet Heart Study The Six Dietary Commandments - More bread - More vegetables and legumes - More fish - Less meat (beef, lamb, pork), replaced by poultry - No day without fruit - No more butter and cream, replaced by supplied margarine made from canola oil.

The Lyon Diet Heart Study Results • Trial stopped early by Monitoring Board because of unacceptably higher CVD rates in control group (low-fat diet). • Mediterranean alpha-linolenic acid rich diet in the secondary prevention of coronary heart disease. De Lorgeril M, Renaud S, Mamelle N, et al. Lancet 1994;343:1454-9. • Cretan Mediterranean diet for prevention of coronary heart disease. Renaud S, de Lorgeril M, Delaye J, et al. Am J Clin Nutr 1995;61:1360S-7S.

The Lyon Diet Heart Study CVD Recurrence During 27-mth Follow Up

The Lyon Diet Heart Study Intake of Foodstuffs (g/day)

The Lyon Diet Heart Study Plasma Fatty Acids at 8 Weeks

The Lyon Diet Heart Study Cardiac Death and Non-fatal MI (46 months follow up) Cretan diet 0.28 (95 % C.I. 0.15-0.53) 18:3 (n-3)* 0.20 (95 % C.I. 0.05-0.84) * 18:3(n-3) plasma levels at 2 months, adjusted for age, sex, smoking, cholesterol, BP, other risk factors

ALA and CHD Studies Showing Protective Effects Proc Soc Exp Biol Med 1992;200:177-82. Prospective study in 6,250 men (death ) BMJ 1996;313:84-90. Prospective study in health professionals (non-fatal MI ) Am J Clin Nutr 1999;69:890. Prospective study in 70,000 nurses (cardiac death )

Dietary Linolenic Acid and Coronary Heart Disease The NHLBI Family Heart Study Luc Djoussé, James S. Pankow John H. Eckfeldt, Aaron R. Folsom Paul N. Hopkins, Michael A. Province Yuling Hong, R. Curtis Ellison

Odds Ratio of CHD by Linolenic Acid Intake (Men)

Odds Ratio of CHD by Linolenic Acid Intake (Women)

Odds Ratio of CHD by Fish Intake

Clinical Trials Showing that N-3 Fatty Acids Prevent CHD Intervention trials demonstrate the inverse association between n-3 fatty acids and CHD without changes in serum cholesterol Risk Ratio N N-3 Cardiac Death Non fatal MI DART 2,000 Fish 0.70 1.00 GISSI 11,000 Fish oil 0.80 0.96 Lyon 600 Canola oil 0.24 0.27 India 1,000 Mustard oil 0.33 0.47

Advantages of Canola Oil Over Fish Oils for Preventing CHD * Many people do not like to eat fish * The usual fried fish consumed in US has very low levels of fish oil (and who likes mackerel?) * Increasing concerns about organic chemical contamination of fish and fish oil * Data are beginning to show better protection against CHD from ALA rather than fish oils

Time to Change to a Mediterranean-type Diet with Canola Oil? Yes!

Mediterranean-type Diet * A diet that is preferable to the very low-fat diets of the American Heart Association * Preferable to the very low-carbohydrate diets (Atkins, South Beach, etc.) * Canola Oil and canola oil-based margarine belong on the Med-Diet (avoid trans fats!)

Is the “Mediterranean-type Diet” Acceptable in North America? Our Institute developed such a diet Used olive oil and canola oil-based margarine Tested in people in Boston on a strict low-fat diet following heart surgery Tested among African-Americans with heart disease in South Carolina

Testing a Med-Diet in South Carolina Comments from 27 African-American Subjects “ I was very pleasantly surprised how delicious the meal was.” “ It contained more fats and oils that my current diet, so the meal was a treat!” “ This diet is something I can live with.”

Summary * Diet affects the risk of CHD and death * The “Mediterranean-type diet” seems to be the healthiest option * Canola oil & canola oil-based margarine: key components of this “Healthy Diet”