optimizing macronutrient composition for health · optimizing macronutrient composition for health....
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Optimizing Macronutrient Composition for Health
Walter C. Willett, MD, DrPHDepartment of Nutrition
Harvard School of Public Health
May 12, 2009
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Sponsored by the University of Arizona College of Medicine at the Arizona
Health Sciences Center
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Walter Willett has nothing to disclose and no conflicts of interest. Dr. Willett will not be discussing the off-label or investigational use of any drugs, products or devices.
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10-Year Coronary Incidence Per 10,000 Men
Keys, 1980
Incidence
0
1000
2000
3000
0 5 10 15 20 25% Diet Calories from Saturated Fat
DalmatiaVelika Krsna
Zrenjanin
BelgradeRome railroad
MontegiorgioCrevalcore
Corfu
Crete
Slavonia
Zutphen
west Finland
east Finland
Ushibuka
Tanushimaru
y=77+78xr=0.73
9.006
(Keys 1980)
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Carroll, 1975
TaiwanJapan
Ceylon
El SalvadorThailand
Panama
PhilippinesMexico
ColumbiaSpain
Greece
Poland
Puerto Rico
ChileVenezuela
Hong Kong
RomaniaYugoslavia
CzechoslovakiaItaly
Portugal
Bulgaria
Australia
NorwayFrance
FinlandHungary
BelgiumSwitzerland
SwedenGermanyAustria
CanadaUKNetherlands
USA Ireland
New ZealandDenmark
0.001
0
5
10
15
20
25
0 20 40 60 80 100 120 140 160Animal Fat Intake (g/day)
Bre
ast C
ance
r Dea
ths
/ 100
,000
pop
Animal Fat and Breast Cancer Mortality
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21.004
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To reduce your fat intake:
Eat more fruits, vegetables, and their juices. Most are naturally low in fat…and high in vitamins and minerals.
Here are some other ways to reduce fat in your food.
TRY INSTEAD OF
Butter-flavored granules Butter or margarine Nonfat yogurt Regular yogurt Nonfat salad dressings Regular salad dressings Angel food cake Devil’s food cake Fat-free cookies and crackers High-fat cookies and crackers
1: Use Nonfat Products
9.071
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21.031
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21.038
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0.248
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(Howard et al. 2006)9.152
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Breast Cancer Incidence in WHI
P=0.09
(Prentice et al. 2006)0.246
HR, 0.91 (95% CI, 0.83-1.01)
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9.010
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Omni Heart Study: Effect on Blood Pressure
(Appel et al. 2005)
OverallP-Value .002 .005 .90
9.191
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Change (%) in Estimated 10-year Risk of Coronary Heart Disease Using Framingham Score
(Omni Heart Study)
Protein Unsaturated Fat
MenChange from carbohydrate
-5.6% -3.9%
WomenChange from carbohydrate
-11.1% -12.9%
(Appel et al. 2005)9.192
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-0.15
-0.1
-0.05
0
0.05
0.1
0.15
0.2
Carbohydrates
ButterShortening
Margarine (stick)
Palm Oil
Chocolate Fat
Average US Dietary Fat
Coconut Fat
Margarine (Tub)
Palm Kernel Fat
Mayonnaise
Olive Oil
Soybean Oil
Rapeseed Oil
(Mensink RP, et al, 2003)
9.140
Total:HD
L Cholesterol
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Blood lipids
Blood pressure
Thrombotic tendency
Insulin resistance
Oxidation
Homocysteine
Inflammation/endothelial dysfunction
Ventricular irritability & arrhythmia
Diet CHD
9.105R
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Nurses’ Health Study (n=121,700)
Health Professionals Follow-up Study (n=52,000)
Nurses’ Health Study II (n=116,000)
Investigators: Frank Speizer, Bernie Rosner, Meir Stampfer, Graham Colditz, David Hunter, JoAnn Manson, Sue Hankinson, Eric Rimm, Edward Giovannucci, Alberto Ascherio, Gary Curhan, Charlie Fuchs, Fran Grodstein, Michelle Holmes, Frank Hu
1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000
DietOcsSmokingWeight/HtMed. Hist.
Diet Diet DietBlood
Diet Diet
1986 1988 1990 1992 1994 1996 1998 2000
Diet Diet DietBlood
Diet
1989 1991 1993 1995 1997 1999
Diet Diet DietBlood
0.198R
Nails
Nails
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Percent of Energy from Fatand Plasma Triglyceride Level
020
406080
100120
140160
20% 20.1 - 25% 25.1 - 30% 30.1 - 35% 35.1 - 40% > 40%
NHS (n=185)HPFS (n=269)
% of Energy from Fat by FFQ
Mean TG
Level
20.091
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100
80
60
40
20
0
-20
-40
1%E 2%E 3%E 4%E 5%E
Trans
Sat
Mono
Poly
% C
hang
e in
CH
D
(Hu et al. 1997)9.131
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1
0.7
0.880.8
0.710.92 0.91
0.63 0.73 0.71
1.05
0.870.71
0.360.320.81
0.66 0.55 0.630.31
0
1.2
Q5
(hig
hest
)
Q4
Q3
Q2
Q1
(low
est)
Q5 (highest)
Q4
Q3
Q1&Q2
Quintiles of poly
Quintiles of trans fat
Mul
tivar
iate
RR
of C
HD
(Hu et al, 1997)
(lowest)
9.049
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“Intake of total fat per se, independent of the relative content of different types of fatty acids, is not associated with high blood cholesterol levels and coronary heart disease”.
Diet and Health, 1989, page 7
9.030
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0.6
0.8
1
1.2
1.4
Q1 Q2 Q3 Q4 Q5
Saturated FatMonoPolyTrans
Multivariate RRs of type 2 diabetes according to quintiles of Multivariate RRs of type 2 diabetes according to quintiles of specific types of dietary fat (mutually adjusted)specific types of dietary fat (mutually adjusted)
(Salmeron et al, 1999)
Quintiles of Fat Intake
Mul
tivar
iate
RR
25.004
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% of Energy from Fat
Rel
ativ
e R
isk
0.133(Hunter et al. 1996)
0.0
0.5
1.0
1.5
<20 (
n=84)
<25 (
n=278
)<3
0 (n=8
24)
<35 (
n=117
1)<4
0 (n=1
173)
<45 (
n=802
)45
+ (n=4
95)
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Fat & Postmenopausal Breast Cancer in NHS, 1980-2000 (3537 cases)
0
0.5
1
1.5
2
<=20
20.1-25
25.1-3030.1-35
35.1-4040.1-45
45.1-50>50
P, trend test 0.11
RR
of B
reas
t Can
cer
Cumulative Average Fat Intake (%E)
(Kim et al. 2006)0.255
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Bray and Popkin prediction
26.063
Low-Fat Weight Loss Trials
-10
-5
0
5
10
0 6 12 21
Length of Follow-up (months)
Wei
ght L
oss D
iffer
ence
(kg)
NDH (1968)(35 vs 30% E)Boyd (1990) (37 vs 21% E)Jeffery (1995) (33 vs 26% E) Black (1994) (40 vs 21% E)Sheppard (1991) (38 vs 20% E)Kasim (1993) (36 vs 17% E)Simon (1997) (34 vs 18% E)Knopp (1997) (27 vs 22% E)McManus (2001) (35 vs 20% E) Bray and Popkin(10% E) (1998)
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(Dansinger et al. 2005)
29.167
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Protein Fat Carb
-5
-4.5
-4-3.5
-3
-2.5
-2
-1.5-1
-0.50
Cha
nge
in b
ody
wei
ght f
rom
bas
elin
e to
2 y
ears
, kg
High
Low oraverage
High-average:-0.6 (-1.6,0.4)
(P=0.22)
High-low:0.04 (-0.9,1.0)
(P=0.94)
Highest vs. lowest0.6 (-0.8,1.9)
(P=0.42)
PoundsLost: Primary Trial Outcome, 2 yearsBody Weight Change: All randomized participants
26.099
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α-linolenic acid (α-LNA, 18:3)
EPA (20:5)
DHA (22:6)
N-3
anti-inflammatory
linoleic acid (LA, 18:2)
arachidonic acid (20:4)
thromboxanes, prostaglandins leukotrienes
Human eicosanoid synthesis
Δ-6-desaturase, elongase, Δ-5-desaturase
cyclooxygenase lipoxygenase
N-6
pro-inflammatory9.146 (Pischon et al. 2003)
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Blood lipids
Blood pressure
Thrombotic tendency
Insulin resistance
Oxidation
Homocysteine
Inflammation/endothelial dysfunction
Ventricular irritability & arrhythmia
Diet CHD
9.105R
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Keys
Serum chol = 1.35 (2 S - P) + 1.5 C0.5
Hegsted
Serum chol = 2.16 S – 1.65 P + 0.176 C
9.008
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Total cholesterol = 1.51 (carb sat) – 0.12 (carb mono) – 0.60 (carb poly)
LDL-C = 1.28 (carb sat) – 0.24 (carb mono) – 0.55 (carb poly)
HDL-C = 0.47 (carb sat) + 0.34 (carb mono) + 0.28 (carb poly)
Triglycerides = -2.22 (carb sat) – 1.99 (carb mono) – 2.47 (carb poly)
All equations predict change expected as a result of 1% daily dietary energy intake as carbohydrate replaced by a particular fatty acid. Changes in lipids are in mg/dl.
(Mensink & Katan, 1992)9.075
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sTN
F-R
2 (p
g/m
L)
Omega 3-fatty acid intake (quartile)
Omega 6-fatty acid intake (Quartile)
Association between omega-3 and omega-6 fatty acid intake and inflammation (HPFS+NHS2, n=859)*
*adjusted for age, gender, smoking status, physical activity, alcohol consumption, NSAID, BMI, energy intake, intake of protein, saturated fats, monounsaturated fats, and cholesterol; n=859
Pischon et al, Circulation 2003; 108: 155
1400
1500
1600
1700
1800
1900
1 2 3 4
12
34
p=0.002 for interaction
9.144
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Trial of LA (N-6) on Inflammatory Factors
High LA (N-6) Low LA (N-6)
Percent of Energy 10.5% E 3.8% E
N-6/N-3 10:1 4:1
CRP (ng/L) 0.56 (± 0.15) 0.60 (± 0.21)
IL-6 (ng/L) 0.96 (± 0.33) 0.93 (± 0.30)
Platelet aggregation 85 (± 2.51) 81 (± 1.63)
(Liou YA, J Nutrition 2006)9.194
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The Effect of Dietary Intervention with 5-week Periods of SFA or PUFA Diet in 17 Subjects ± SD
PUFA Diet SFA DietBody weight (kg) 80.8 ± 3.6 81.2 ± 3.7
BMI (kg/m2) 29.6 ± 1.6 29.7 ± 1.6
Total cholesterol (mmol/l) 5.0 ± 1.2 5.5 ± 1.4*
HDL-Cholesterol (mmol/l) 1.1 ± 0.27 1.1 ± 0.32
LDL-Cholesterol (mmol/l) 3.1 ± 1.1 3.6 ± 1.2**
Insulin sensitivity (μmol • 1 • mU-1 • kg-1 • min-1 ) 0.64 ± 0.43 0.51 ± 0.35****p = 0.001 **p = 0.002 ***p = 0.02
(Summers et al. 2002)
25.040
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-50
-40
-30
-20
-10
0
10
0 2 4 6 8 10 12 14
Turpienen
9.043R
Low-fat diets High-polyunsaturated-fat-diets
MRC low fat
DartMRC Soy Oil
DaytonLeren
% o
f CH
D D
iffer
ence
-3 -4 -5 -6 -7 -8 -9 -10 -11 -12 -13 -14 -15
% Change in Serum Cholesterol
(Sacks, 1994)
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Prospective Studies of PUFA & CHD(Summarized in Nutritional Epidemiology, 1998)
• A significant inverse association was seen in 5 of 13 studies (Shekelle 1981; McGee 1984; Goldbourt 1993; Dolecek 1992; Hu 1997)
• In no study was a positive association observed
9.149
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Nurses’ Health StudyDietary Fats and Risk of CHD
-80 -60 -40 -20 0 20 40 60 80
Sat -->Carbo (5%E)
Mono -->Carbo (5%E)
Poly --> Carbo (5%E)
Sat--> Mono (5%E)
Sat--> Poly (5%E)
Sat-->Unsat (5%E)
Trans--> Mono (2%E)
Trans --> Poly (2%E)
Trans --> Unsat (2%E)
Change in CHD Risk (%)
Hu et al, 19979.052
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CHD Mortality
9.195(Jakobsen et al. 2009)
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CHD Mortality
(Jakobsen et al. 2009)9.196
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Ratio of ALA to LA & Risk of Fatal CHD in NHS (Hu, F. et al. AJCN 1999)
0
0.5
1
1.5
1 2 3 4 5
P, trend = 0.40Rel
ativ
e R
isk
Quintiles9.147
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Dwyer & Hetzel, 1980
Mortality per 103
Coronary Heart Disease Mortality
100
200
300
400
500
600
700
1950
1954
1958
1962
1966
1970
1974
1978Fe
mal
eM
ale
United States United Kingdom Australia
9.112
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Consumption of Animal and Vegetable Fat (g/day)
Dwyer & Hetzel, 1980
10
20
30
40
50
1935 1950 1954 1958 1962 1966 1970 1974
80
90
100
110
120
130
United States United Kingdom Australia
Veg
etab
le F
atA
nim
al F
at
9.113
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Conclusions
• Both N-3 & N-6 fatty acids are essential• Ratio of N-6 to N-3 is not helpful• Many diets are more deficient in N-3 than N-6• Reducing N-6 to “improve” the ratio is likely to
increase the risk of CHD & diabetes• The upper limit for N-6 is not clear, but up to
roughly 10% of total energy intake appears to be increasingly beneficial
9.148
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0
0.5
1
1.5
Women ( 591cases )Wolk et al. 1999
Men ( 734 cases )Rimm et al. 1996
RRof
CHD
Cereal Fiber, Energy- Adjusted, g/day
0
0.5
1
1.5
2.2 3.1 4.93.8 7.7 2.2 3.7 5.0 6.8 9.7
8.064
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Blood Glucose
Insulin
Easily Digested Carbohydrate
-
Blood Glucose
Insulin
Slowly Digested Carbohydrate
0
0 1 2 3 4 5 0 1 2 3 4 5 Time (hr) Time (hr)
25.027
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Relative Risk of Type 2 Diabetes by Different Levels of Cereal Fiber and Glycemic Load
2.5 2.32.05
2.171.8 1.62
1.511.28 1
0
1
2
3
High Medium Low
High
Medium
LowRelativeRisk
>165 165-143 <143Glycemic Load
>5.8 g/day
2.5 -5.8 g/day
<2.5 g/day
(Salmeron et al,1997)
(ref)
WOMEN
9.038
Cereal Fiber
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1.501.85
1.061.001.39 1.41
1.00 1.11
0.00.51.01.52.02.5
<1/mo 1-4/mo 2-6/wk >=1/dSugar-sweetened soft drink consumption
Rel
ativ
e R
isk
multivariate adjusted multivariate + BMI
P<0.001 for trend
Regular Soft Drinks and Type 2 Diabetes, NHS2
(Schulze et al. 2004 JAMA)25.080
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Correlation between baseline insulin resistance and increase in postprandial glucose, insulin, and triacylglycerol after increasing
dietary carbohydrate from 40-60% of energy
(n = 10 postmenopausal women)
Variables r P
Glucose 0.68 0.06
Insulin 0.82 < 0.02Plasma triacylglycerol 0.77 < 0.05
(Jeppesen et al. 1997)9.079R
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Liu et al., 2000
Glycemic Load
9.072
Body Mass Index (kg/M2)
Rel
ativ
e R
isk
1.16
2 2
0.94 1.19
1.81
1 1.1 1.42
0
0.5
1
1.5
2
2.5
<23 23-29 >29
Tertile 1 (lowest)Tertile 2
Tertile 3 (highest)
Relative Risk of Coronary Heart Disease
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Optimal macronutrients: Considerations
• Whole grains: CHO: fiber = about 6:1• for 30 gm of fiber/day, 180 gm CHO =
720 kcal• For 2500 kcal/day this is about 30% E• Fruits/vegetables add 10 to 15%
carbohydrate, or 40 to 45% E from CHO• Add 35 to 45% E from fat and 15 to 20% E
from protein
9.193
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Lowfat products whenever possible; calcium supplements are and effective substitute for preventing fractures
Importance is well-documented; greens and dark orange vegetables should be included. Even more frequent servings may be desirable
Whole-grain, minimally processed products should be emphasized
Ignores critical differences in types of fat. Monos appear desirable
Misleading as 2-3 servings of meat/day is probably unhealthy
Support for generous intake is well documented
21.002
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21.090
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Healthy Eating Pyramid
Healthy Eating Pyramid
21.092
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21.055
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21.056