dairy fat and cvd risk: a rather complex issue · benoît lamarche, phd inaf, université laval...

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Dairy Fat and CVD Risk: Dairy Fat and CVD Risk: A Rather Complex Issue A Rather Complex Issue Beno Beno î î t Lamarche, PhD t Lamarche, PhD INAF, Universit INAF, Universit é é Laval Laval Qu Qu é é bec, Canada bec, Canada Colloque STELA / Colloque STELA / Symposium Symposium Qu Qu é é bec, Qc bec, Qc 29 Sept, 2010 29 Sept, 2010

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Page 1: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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

Page 2: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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

Page 3: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 4: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 5: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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)

Page 6: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 7: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

Meta-analysis of prospective cohort studies evaluating the association

of saturated fat with CVDSiri-Tarino et al Am J Clin Nutr 2010

Page 8: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

Meta-analysis of prospective cohort studies evaluating the association

of saturated fat with CVDSiri-Tarino et al Am J Clin Nutr 2010

Page 9: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 10: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 11: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 12: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 13: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 14: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 15: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 16: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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…

Page 17: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

Trans fatty acids (TFA)Trans fatty acids (TFA)

1 3 5 7 9 13 15 1711

Page 18: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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IntroductionIntroduction(Mozaffarian N Engl J Med.2006)

Page 19: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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

Page 20: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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)

Page 21: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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)

Page 22: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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.

Page 23: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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

Page 24: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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

Page 25: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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

Page 26: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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

Page 27: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

% change from the control diet

LDL-C HDL-C C/HDL-C

rTFA (moderate)rTFA (high)iTFA

Motard-Bélanger, AJCN 2008;87:593-599

Page 28: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

• 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

Page 29: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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

Page 30: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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)

Page 31: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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%

Page 32: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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%

Page 33: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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

Page 34: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 35: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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

Page 36: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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Characteristics of participantsCharacteristics of participants

Page 37: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

Results (N=61)Results (N=61)

Page 38: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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Results (N=61)Results (N=61)

Page 39: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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ResultsResults∆

LD

L-C

, %

Baseline LDL-C (mmol/l)

Pinteraction= 0.21

Page 40: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

<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

Page 41: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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ResultsResults

Pinteraction= 0.18

∆H

DL-C

, %

P≤0.01

Menopausal statusYES

59±6 yrs NO

26±5 yrs

Page 42: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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

Page 43: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

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)

Page 44: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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).

Page 45: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

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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

Page 46: Dairy Fat and CVD Risk: A Rather Complex Issue · Benoît Lamarche, PhD INAF, Université Laval Québec, Canada Colloque STELA / Symposium Québec, Qc 29 Sept, 2010. Seven Country

www.ulaval.ca

AcknowledgementsAcknowledgements

Chair in Nutrition and Cardiovascular

Health