Dietary Fatty Acids and Cardiovascular Disease

Professor Andrew SalterDivision of Nutritional Sciences

School of BiosciencesUniversity of Nottingham

United Kingdom

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Death

s /100,0

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e-s

tan

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Death rates from CHD, stroke and all other diseases of the circulatory system, people aged under 75, 1969 to 2007, England,

Our Healthier

Nation target

www.heartstats.org.uk

Prevalence of Cardiovascular disease

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vela

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female

2008

Myocardial Infarction: 1.5milionStroke: 1.2millionAngina: 2.1million

Scarborough et al (2010) Coronary Heart Diseases Statistics, www.heartstats.org

The Key’s EquationΔTC = 1.35(2ΔSFA – ΔPFA) + 1.5 ΔCHOL1/2

Keys A et al (1980) In: Seven countries - a multivariate analysis of death and coronary heart disease. A Commonwealth Fund Book. Cambridge, MA: Harvard University Press, 1-381.

cis Polyunsaturated fatty acids

cis Monounsaturated fatty acids

trans Monounsaturated fatty acids

Saturated fatty acids

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0.02

0.04

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Meta-Analysis of 60 Trials

Mensink et al., 2003

Δ Cholesterol when 1% of carbohydrate energy is replaced with fatty acids

All Saturates Are Not Equal

Mensink R P et al. Am J Clin Nutr 2003;77:1146-1155

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Lauric (C:12:0)

Myristic (C14:0)

Palmitic (C16:0)

Stearic (C18:0)

ΔC

ho

leste

rol LDL

HDL

Effect of replacing 1% of energy as carbohydrate with different saturated fatty acids-meta-analysis of 60 controlled trials

Interim Summary of Conclusions and Dietary Recommendations on Total Fat & Fatty AcidsFrom the Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, 10-14November, 2008, WHO, Geneva

WHO Adult Recommended Dietary Intakes for Total Fat and Fatty Acids

Fat/Fatty Acid Recommendation(% of Energy)

Total Fat 20-35

SFA <10

MUFA 15-20

Total PUFA 6-11

n-6 PUFA 2.5-9

n-3 PUFA 0.5-2

TFA <1

Sources of Saturated Fatty Acids

Cereals and Cereal products, 18

Milk & Milk Products, 22

Butter, 4

Fat Spreads, 4

Meat & Meat Products, 26

Vegetables, Potatoes, 7

Confectionery, 5

National Diet & Nutrition Survey 2008-2009, Dept of Health

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% t

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meat

Fatty Acid Composition of Milk and Meat from Ruminant Species

Meat, Milk & Cardiovascular Disease

• Prospective Cohort Studies have generally failed to show any link between red meat consumption and CVD.

• Prospective Cohort Studies have, if anything, shown a protective effect of milk consumption on CVD.

• That does not mean that there is no benefit in altering the fatty acid of these foods

Impact of Beef Fat on development of atherosclerosis

Section # 1

Oil Red O stained sections

ApoE*3 Leiden Mouse

Mice fed diets containing 36% freeze-dried beef rapeseed oil

Fatty Acid Composition of Beef Diets

*Interim Summary of Conclusions and Dietary Recommendations on Total Fat & Fatty Acids. From the Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, 10-14 November, 2008, WHO, Geneva

Fat/Fatty Acid Beef Rapeseed oil Supplemented

Recommendation*

(% of Energy) (% of Energy) (% of Energy)

Total Fat 30 34 20-35

SFA 13.5 11.1 <10

MUFA 11.4 15.1 15-20

Total PUFA 2.7 5.8 6-11

n-6 PUFA 2.2 4.3 2.5-9

n-3 PUFA 0.5 1.5 0.5-2

TFA 0.6 0.7 <1

Aortic Atherosclerosis

Rapeseed Oil -Supplemented

Concentrate-Fed Beef

Forage-Fed Beef

Rapeseed oil Supplemented

Plasma Chol 10.27 1.96a 7.14 0.97b

Chylo/VLDL Chol 6.84 1.37a 4.38 0.61b

LDL Chol 2.29 0.47a 1.38 0.24b

HDL Chol 1.14 0.20 1.38 0.31

nonHDL/HDL 8.04 1.15a 4.32 0.93b

Plasma TAG 2.49 0.70 2.58 0.78

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-20 -15 -10 -5 0 5 10 15

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Section no.

Beef Rape

Aortic archHeart

P-value SED

Diet <0.001 14

Section <0.001 25

Diet*Section 0.799 44

Atherosclerosis in Beef- Fed Animals

Epidemiological Studies of Dietary Fat & CVD

• Prospective Cohort Studies– Large numbers/Long time period

– Relatively large number of CVD Events

– Often able to have mortality as outcome

– Poor measures of dietary intake

– Highly vulnerable to confounding

• Randomized Control– More control of dietary intake

– Measures response to a change

– Less vulnerable to confounding

– Smaller numbers/Shorter time periods

– Smaller number of CVD Events

– Often rely on risk factors or morbidity as outcome

Systematic Reviews & Meta-Analyses

• A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question

• Meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses.

• Meta-analyses are often, but not always, important components of a systematic review procedure.

http://en.wikipedia.org/wiki/

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Ris

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CHD STROKE TOTAL

p= 0.22 p= 0.11 p= 0.95

Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease

Siri-Tarino et al (2010) Am J Clin Nutr 91: 535-46

Meta-analysis of 21 studies including 347,747 subjects of whom 11,006 developed CHD or Stroke

Author’s Conclusion: A meta-analysis of prospective epidemiological studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD

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MUFA PUFA Carb

Haz

ard

Rat

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Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies

Jakobsen et al (2009) Am J Clin Nutr 89:1425-32

Hazard Ratio for Coronary Deaths per replacement of 5% energy from SFA with MUFA, PUFA or Carbohydrate

2155 Coronary Deaths among 344696 persons

Author’s Conclusion: Replacing SFAs with PUFA rather than MUFA or Carbohydrates prevents CHD over a wide range of intakes

Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Mozaffarian et al (2010) PLoS Medicine 7: e1000252

8 trials including 13,614 participants with 1,042 CHD EventsAverage PUFA intake - low: 5.0, high: 14.9

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Author’s Conclusion: Consuming PUFA in place of SFA reduces CHD events in RCTs

Reduced or modified dietary fat for preventing cardiovascular disease

Hooper I et al (2011) Cochrane Database of Systematic Reviews 7: CD002137

• 25 studies (61,958 participants) of fat reduction and 15 studies (13,004) of fat modification

• No clear effect on total mortality or CVD mortality

• 14% decrease in risk of CVD events (RR 0.86, 95%CI 0.77-0.96– Associated with substitution of SFA with UFA not reduction

– Related to degree of effect on total and LDL cholesterol

– Only in studies of at least 2 years and only in men.

F.D.A. Announces Label Requirement

For Artery Clogger

By MARIAN BURROS (NYT)

“Food and Drug Administration will require food processors

to include amount of artery-clogging trans fatty acids on nutrition

labels. …………………Dr Walter Willett of Harvard School of

Public Health suggests that fast food restaurants that serve foods

high in trans fats with no warning label may be sued by customers

who later have heart attacks; some scientists think trans fats, which

are actively added to foods, are at least as bad as saturated fats, and

some think trans fats are worse.”

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Palm Oil Butter Lard Cottonseed Oil High Oleic Sunflower

Soya Bean Oil Canola Oil

-22.5 -14.4 -21 -31 -28.3 -33.4 -32.3

% r

edu

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CH

D E

ven

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Predicted reduction in CHD Events associated with replacing PHVO with different fats/oils

Mozaffarian & Clarke (2009) Eur J Clin Nutr 63: 522-533

Effect of replacing 7.5% of energy from a PHVO containing 35% TFA

Cereals and Cereal

products, 19

Milk & Milk Products, 22

Butter, 4

Fat Spreads, 4

Meat & Meat Products, 25

Vegetables, Potatoes, 9

Confectionery,4

Sources of Trans Fatty Acids1.6g/day (0.8% food energy)

National Diet & Nutrition Survey 2008-2009, Dept of Health

Meta-Analysis of Impact of trans fatty acids on LDL cholesterol in humans

Citation: Brouwer IA, Wanders AJ, Katan MB (2010) Effect of Animal and Industrial Trans Fatty Acids on HDL and LDL Cholesterol Levels in Humans – A Quantitative Review. PLoS ONE 5(3): e9434. doi:10.1371/journal.pone.0009434

Omega-3 Fatty AcidsC18:3, n-3

C18:4, n-3

C20:4, n-3

C20:5, n-3

C22:5, n-3

C22:6, n-3

6 desaturase

5 desaturase

linolenic acid (ALA)

eicosapentaenoic acid (EPA)

Marine Algae

docosahexaenoic acid (DHA)

Terrestrial Plants, e.g. Flax/Linseed

WHO Recommendations on Omega-3 PUFA

“Whilst ALA may have individual properties in its own right, there is evidence that the Omega-3 LCPUFA (EPA & DHA) may contribute to the prevention of CHD and possibly other degenerative diseases of aging. “

Interim Summary of Conclusions and Dietary Recommendations on Total Fat & Fatty Acids. From the Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition, 10-14 November, 2008, WHO, Geneva

• Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included

• No reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega-3 fats

• No effect of fish-based omega 3 fats, or short chain omega-3s on mortality or cardiovascular events.

• Authors Conclusion: It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population.

Omega-3 fatty acids for prevention and treatment of cardiovascular disease

Hooper et al (2004) Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD003177. DOI: 10.1002/14651858.CD003177.pub2.

Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review.

Marik & Varon (2009) Clin Cardiol 32:365-72.

• 11 randomized controlled trials that included a total of 39 044 patients

• Included patients after recent myocardial infarction, those with an implanted cardioverter defibrillator, and patients with heart failure, peripheral vascular disease, and hypercholesterolemia

• In high risk patients Omega-3 fatty acids significantly reduced the risk of cardiovascular and nonfatal cardiovascular events

• Authors conclusion: Dietary supplementation with omega-3 fatty acids should be considered in the secondary prevention of cardiovascular events

Conclusions

•There is little evidence to support replacing dietary SFA with carbohydrate•Substituting SFA with UFA (particularly n-6 linoleic acid) reduces risk of CVD•Trans fatty acids associated with Partially Hydrogenated Vegetable Oil increase risk of CVD•Insufficient evidence to decide whether trans fatty acids from animal sources impact on CVD•There is reasonable evidence that Omega 3 LCPUFA may be important in secondary prevention of CVD•Evidence for a role of Omega 3 LCPUFA in primary prevention is less convincing

Implications for the Animal Industry

• Despite the lack of evidence that consuming red meat and milk is associated with increased CVD, their contribution to total SFA intake will continue to make them a target for reduction.

• Replacing SFA in these products with n-6 PUFA (or possibly MUFA) could improve their impact on cardiovascular health.

• The impact of ruminant TFA on CVD remains unclear.

• We have probably spent too much time, and money, worrying about the n-6/n-3 PUFA ratio within animal products.

Acknowledgements

• Nottingham

– Laura Tonge

• Aberystwyth

– Nigel Scollan

• Bristol

– Ian Richardson