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Dairy Fat and CVD Risk: Dairy Fat and CVD Risk: A Rather Complex IssueA Rather Complex Issue
BenoBenoîît Lamarche, PhDt Lamarche, PhD
INAF, UniversitINAF, Universitéé Laval Laval QuQuéébec, Canadabec, Canada
Colloque STELA / Colloque STELA / SymposiumSymposium
QuQuéébec, Qcbec, Qc
29 Sept, 201029 Sept, 2010
Seven Country StudySeven Country Study
Finlande Est
Finlande OuestHollande
Slavonie
États-Unis
RomeMontegiorgio
CrevalcoreCorfou
Japon CrêteVelnika Krsna
DalmatieZrenjanin
Dea
th b
y C
HD
(/100
,000
)
Saturated Fat (% kcal)
Adapted from Keys. Am J Epidemiol. 1986
0 10 20 300
200
400
600
800
1000
1200
1400
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HDL-CHDL-C
* * *
Change in dietary lipids:Change in dietary lipids:CHO (1% energy) replaced by SAT, cis MUFA, cis CHO (1% energy) replaced by SAT, cis MUFA, cis PUFA, or trans PUFA, or trans Mensink, R. P et al. Am J Clin Nutr 2003;77:1146Mensink, R. P et al. Am J Clin Nutr 2003;77:1146--11551155
SATSATPUFAPUFA
MUFAMUFATransTrans
LDL-CLDL-C
**
**
Chol/HDL-CChol/HDL-C
**
*
mm
ol/l
mm
ol/l
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Change in plasma lipids:Change in plasma lipids:CHO (1% energy) replaced by lauric acid (12:0), CHO (1% energy) replaced by lauric acid (12:0), myristic (14:0), palmitic (16:0) or stearic (18:0)myristic (14:0), palmitic (16:0) or stearic (18:0)Mensink, R. P et al. Am J Clin Nutr 2003;77:1146Mensink, R. P et al. Am J Clin Nutr 2003;77:1146--11551155
Chol/HDL-CChol/HDL-C LDL-CLDL-C HDL-CHDL-C
LauricLauricPalmiticPalmitic
MyristicMyristicStearicStearic
*
* **
**
*
mm
ol/l
mm
ol/l
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Composition of dairy fat, USDA National Nutrient Composition of dairy fat, USDA National Nutrient Database for Standard Reference, Release 20 (2007)Database for Standard Reference, Release 20 (2007)
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Contribution (%) of dairy products to daily intake Contribution (%) of dairy products to daily intake Dutch National Food Consumption Surveys, 1998Dutch National Food Consumption Surveys, 1998German et al, German et al, Eur J Nutr (2009) 48:191Eur J Nutr (2009) 48:191––203203
Meta-analysis of prospective cohort studies evaluating the association
of saturated fat with CVDSiri-Tarino et al Am J Clin Nutr 2010
Meta-analysis of prospective cohort studies evaluating the association
of saturated fat with CVDSiri-Tarino et al Am J Clin Nutr 2010
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Milk and dairy consumption and incidence of CVD and Milk and dairy consumption and incidence of CVD and allall--cause mortality: dosecause mortality: dose--response metaresponse meta--analysis of analysis of prospective cohort studiesprospective cohort studiesSoedamahSoedamah--Muthu SS et al, Muthu SS et al, AJCN 2011;93:158AJCN 2011;93:158––7171
Relative risk, CVD
Protection Increase
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Milk and dairy consumption and incidence of CVD and Milk and dairy consumption and incidence of CVD and allall--cause mortality: dosecause mortality: dose--response metaresponse meta--analysis of analysis of prospective cohort studiesprospective cohort studiesSoedamahSoedamah--Muthu SS et al, Muthu SS et al, AJCN 2011;93:158AJCN 2011;93:158––7171
Relative risk, CHD
Protection Increase
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Milk and dairy consumption and incidence of CVD and Milk and dairy consumption and incidence of CVD and allall--cause mortality: dosecause mortality: dose--response metaresponse meta--analysis of analysis of prospective cohort studiesprospective cohort studiesSoedamahSoedamah--Muthu SS et al, Muthu SS et al, AJCN 2011;93:158AJCN 2011;93:158––7171
Relative risk, Stroke
Protection Increase
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Biomarkers of dairy intake and the risk of heart diseaseBiomarkers of dairy intake and the risk of heart diseaseAslibekyan S et al, Nutr Metab Cardiovasc Disease 2011, in pressAslibekyan S et al, Nutr Metab Cardiovasc Disease 2011, in press
Dairy intake (FFQ)Adipose Tissue 15:0Adipose tissue 17:0
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Dairy fat in cheese raises LDL cholesterol less than that Dairy fat in cheese raises LDL cholesterol less than that in butter in mildly hypercholesterolaemic subjectsin butter in mildly hypercholesterolaemic subjectsNestel PJ et al, EJCN 2005;59:1059Nestel PJ et al, EJCN 2005;59:1059––10631063
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Dairy fat in cheese raises LDL cholesterol less than that Dairy fat in cheese raises LDL cholesterol less than that in butter in mildly hypercholesterolaemic subjectsin butter in mildly hypercholesterolaemic subjectsNestel PJ et al, EJCN 2005;59:1059Nestel PJ et al, EJCN 2005;59:1059––10631063
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MetaMeta--analysis of RCTs evaluating effects of increasing analysis of RCTs evaluating effects of increasing PUFA consumption in place of SFA and CHD eventsPUFA consumption in place of SFA and CHD eventsMozaffarian D et al, PLoS Mozaffarian D et al, PLoS 2010; 7:e10002522010; 7:e100025220112011
Protection Increase
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Conclusions: SATConclusions: SAT
• PUFA is better than SAT• Further research is needed to clarify the role of
SFA in CVD risk compared with that of different forms of carbohydrates rather than carbohydrates as a whole. Astrup (AJCN 2010)
• We eat foods, not nutrients…
Trans fatty acids (TFA)Trans fatty acids (TFA)
1 3 5 7 9 13 15 1711
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IntroductionIntroduction(Mozaffarian N Engl J Med.2006)
Change in the TFA content of french fries in CanadaSecond Set of Trans Fat Monitoring Data - July 2008
Change in the TFA content of french fries in CanadaSecond Set of Trans Fat Monitoring Data - July 2008
0
10
20
30
40
50
McDonald A&W KFC BKing
200620072008%
of f
at
Mean intake of iTFA and rTFA in Denmark from 1978 to 2005
Stender et al, Food Nutr Res 2008
Mean intake of iTFA and rTFA in Denmark from 1978 to 2005
Stender et al, Food Nutr Res 2008
012345678
1975 1980 1985 1990 1995 2000 2005 2010
Inta
ke o
f TFA
(g/d
ay)
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Dietary vaccenic acid has anti-atherogenic effects in LDLr-/- miceDietary vaccenic acid has anti-atherogenic effects in LDLr-/- mice
(Bassett et al, J Nutr 2010;140:18-24)
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Dietary vaccenic acid has anti-atherogenic effects in LDLr-/- miceDietary vaccenic acid has anti-atherogenic effects in LDLr-/- mice
(Bassett et al, J Nutr 2010;140:18-24)
• iTFA enhances the progression of atherosclerosis even in the absence of chol in this LDLr KO mice model.
• rTFA intake is not associated with atherosclerotic plaque formation athérosclérotique in this model.
• rTFA intake attenuates plaque formation following chol intake in this model.
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Evidence from epidemiologyEvidence from epidemiology
Adapted from Weggemans et alEur. J. Lipid Sci. Technol. 2004
2.0
1.51.0
0.5
030 1 2
rTFA intake (g/day)
ATBCCase-control studyNHSZutphen
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0.5 0.6 0.7 0.8 0.9 1 1.1 1.2
All
Women
<60yr
>60yr
Men
<60yr
>60yr
HR (0.5g rTFA, energy-adjusted)
1.09
0.94
0.81
0.77
0.59
1.05
1.05
Study design• 4 isoenergetic diets of 4 weeks each :
1. High in TFA from ruminants (10.2 g/2500 kcal)2. Moderate in TFA from ruminants (4.2 g/2500 kcal)3. High in TFA from industrial sources (10.2 g/2500 kcal)4. Control (minimal quantities of TFA) (2.2 g/2500 kcal)
Methods
A B C D
Controlled diets
Wash out
Motard-Bélanger, AJCN 2008;87:593-599
Nutritionnal value of the dietsMethods
4.03.54.44.6PUFA
rTFA% of energy
3.73.71.50.8TFA
10.110.011.811.8MUFA
18.019.418.318.5Saturated fat
37.038.137.437.0Lipids
14.014.014.014.0 Proteins
50.248.849.750.1 Carbohydrates
iTFAHighModerateControl
Motard-Bélanger, AJCN 2008;87:593-599
% change from the control diet
LDL-C HDL-C C/HDL-C
rTFA (moderate)rTFA (high)iTFA
Motard-Bélanger, AJCN 2008;87:593-599
• iTFA: 1 donut= 2.3 g 1 popcorn = 10.0 g
• Moderated rTFA4 servings of cheese 33% = 1.64 g 2 servings of whole milk= 0.52 g 175 g yogurt 3.25 % = 0.14 g 40 g butter = 1.9 g
• High rTFA is unachievable…
4.2 g rTFA
12.3 g iTFA
Implications
Study of the impact of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease in women
Study of the impact of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease in women
EB 2011
April 2011
Washington, DC
EB 2011
April 2011
Washington, DC
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LDLLDL--C % change from baselineC % change from baselineTRANSFACT. AJCN 2008:87:558TRANSFACT. AJCN 2008:87:558––6666
Men Women AlliTFArTFA
(P=0.99) (P=0.001) (P=0.02)
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Study designStudy design
rTFA CTL
Isocaloric feeding4 weeks
Wash out
rTFACTL
ScreeningRandomization
High rTFA: 4.8 g/2500 kcal, 1.5Control: 1.5 g/2500 kcal, 0.6%
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2 x 250ml whole milk: 0.8 g
4 x 50g cheddar 30%fat: 2.0 g
2 x175g yogurt 1.5%fat: 0.4 g
34 g butter: 1.6g
2 x 250ml whole milk: 0.8 g
4 x 50g cheddar 30%fat: 2.0 g
2 x175g yogurt 1.5%fat: 0.4 g
34 g butter: 1.6g
4.8 g rTFA4.8 g rTFA
High rTFA…High rTFA…
High rTFA: 4.8 g/2500 kcal, 1.5Control: 1.5 g/2500 kcal, 0.6%
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High rTFA butter•Dairy cows fed with carthame oil for 4 weeks•Highest producers were selected to yield the high rTFA butter
Control butter•Selected to contain low values of rTFA
Study designStudy design
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Diet compositionDiet composition
Control High rTFA
Energy (kcal) 2279±268 2280±233
CHO (%) 54.4 54.3
Proteins (%) 15.0 15.0
Lipids (%) 33.0 33.0
SAT (%) 10.2 10.5
cis-MUFA (%) 14.3 12.9
PUFA (%) 6.0 5.9
Trans (%) 0.6 1.7
Fibres (g/2500 kcal) 28.2 28.2
Chol (mg/2500 kcal) 320.6 322.1
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Study flow sheetStudy flow sheetScreeningn = 111
Randomizedn = 72
Completersn = 61
Exclusionn = 39
Drop outs n=8: too demandingWithdrawnn=2: menopausal statusn=1: missing data
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Characteristics of participantsCharacteristics of participants
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Results (N=61)Results (N=61)
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Results (N=61)Results (N=61)
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ResultsResults∆
LD
L-C
, %
Baseline LDL-C (mmol/l)
Pinteraction= 0.21
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<1.5 1.5-1.8 ≥1.8
ResultsResults∆
HD
L-C
, %
Baseline HDL-C (mmol/l)
Pinteraction= 0.74
P<0.05 P<0.05
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ResultsResults
Pinteraction= 0.18
∆H
DL-C
, %
P≤0.01
Menopausal statusYES
59±6 yrs NO
26±5 yrs
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InterpretationInterpretation
Dietary intake of 4.8g/day rTFA (/2500kcal):
• Has no impact on LDL-C, TG and blood pressure in women;
• Is associated with a small but significant reduction in HDL-C, particularly among older women, or with high baseline values
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InterpretationInterpretation
Dietary intake of 4.8g/day rTFA (/2500kcal):
• Among women who show reduced HDL-C with rTFA, values remain high;
• Changes in HDL-C are unrelated to effects on CETP, Endothelial Lipase and Hepatic lipase (not shown)
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Conclusion, rTFAConclusion, rTFA
The impact of very high but yet achievable intake of rTFA has minimal impact, if any, on CHD risk among women (and men).
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ConclusionsConclusions
• Saturated fat may not be as much a problem as perceived
• rTFA should not be an issue• We eat foods, not nutrients and
isolated fats. • More studies on:
• Whole dairy products• Risk factors other than LDL
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AcknowledgementsAcknowledgements
Chair in Nutrition and Cardiovascular
Health
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