Transcript Alcohol, Breast Cancer Risk, and Total Mortality

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
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
CRETE
Mortality
10 years/10.000
TOTA L
CHD
Cholesterol
(mg/dl)
Foodstuff
(g/day)
Bread
Legume
Fruit
Meat
Fish
Edible Fat
Alcohol
9 MED
ZUTPHEN
US
COHORTS HOLLAND RAILROAD
514
9
204
1090
184
194
1091
420
232
1153
574
380
30
464
35
18
95
15
416
18
130
140
34
60
43
252
2
82
138
12
79
3
97
Adapted fromA. Keys (1970) and D. Kromhout (1989)
236
1
233
273
3
33
6
Fatty Acids from Cholesterol Esters
n
16:0
18:0
18:1
(n-9)
18:2
(n-6)
18:3
(n-3)
Crete
92
11.1
±0.1
0.7
±0.0
31.0
±0.3
41.9
±0.4
0.9
±0.1
Zutphen
97
11.9
±0.1
1.1
±0.0
21.4
±0.4
53.1
±0.7
0.3
±0.0
Mean ± S.E. ***p<0.001
Adapted from Sandker et al Europ J Clin Nutr 1993
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
Control Exper
(303)
(302)
Cardiac Death
(Sudden Death)
16
(10)
3
(0)
Acute Myocardial Infarction
17
5
Total Cardiac Events
33
8
Non-Cardiac Death
4
5
Overall Mortality
20
8
Total CV events
70
14
(including stroke, unstable AP, CHF)
RR
p
0.24 <0.02
0.27 <0.001
0.30 <0.02
0.24 <0.0001
The Lyon Diet Heart Study
Intake of Foodstuffs (g/day)
Foodstuffs
Bread
Legume
Vegetable
Fruit
Meat
Poultry
Cheese
Butter & Cream
Margarine
Oil
Fish
Control Experimental
145
167
10
20
288
316
200
241
74
47
53
58
35
32
17
3
5
19
17
16
40
47
P
0.01
0.07
0.07
0.007
0.01
0.42
0.25
<0.001
<0.001
0.65
0.16
The Lyon Diet Heart Study
Plasma Fatty Acids at 8 Weeks
Fatty acids
18:0
18:1 (n-9)
18:1 (trans)
18:2 (n-6)
18:3 (n-3)
20:4 (n-6)
20:5 (n-3)
Mean ± S.E.
Control
6.81
19.00
0.23
29.80
0.39
6.80
0.75
±
±
±
±
±
±
±
0.05
0.20
0.01
0.40
0.01
0.10
0.04
Experimental
6.49
22.10
0.26
27.30
0.65
6.29
0.92
±
±
±
±
±
±
±
0.05
0.20
0.01
0.30
0.02
0.09
0.03
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)
1.3
1
0.7
0.4
0.1
Q1
Q2
Q3
Q4
Q5
Odds Ratio of CHD by
Linolenic Acid Intake (Women)
1.3
1
0.7
0.4
0.1
Q1
Q2
Q3
Q4
Q5
Odds Ratio of CHD
by Fish Intake
1.2
1
0.8
0.6
0.4
0.2
0
0/wk
1/wk
2+/wk
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
N
DART 2,000
GISSI 11,000
Lyon
600
India
1,000
Risk Ratio
N-3
Cardiac Death
Non fatal MI
Fish
0.70
1.00
Fish oil
0.80
0.96
Canola oil
0.24
0.27
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”