salter aberystwyth 2011
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Dietary Fatty Acids and Cardiovascular Disease
Professor Andrew SalterDivision of Nutritional Sciences
School of BiosciencesUniversity of Nottingham
United Kingdom
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70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 2010
Death
s /100,0
00 (
ag
e-s
tan
dard
ised
)
Year
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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Pre
vela
nce
(%
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male
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
0.06
0.02
0.04
0.00
-0.02
-0.04
ΔL
DL
Ch
ole
ste
rol (m
mo
l/L
) ΔH
DL
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l/L)
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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
-0.01
0
0.01
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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
ota
l fat
ty a
cid
milk
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
Lesi
on
are
a (m
icro
ns
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/
0
0.5
1
1.5
2
Ris
k R
atio
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
0
0.5
1
1.5
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MUFA PUFA Carb
Haz
ard
Rat
io
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
0
0.5
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1.5
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RR
of
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r C
HD
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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.”
-35
-30
-25
-20
-15
-10
-5
0
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
ctio
n in
CH
D E
ven
ts
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
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