Post on 17-Jun-2020
NIHR Southampton
Biomedical Research Centre in nutrition
The NIHR Southampton Biomedical Research Centre in nutrition is funded by the National Institute for Health Research (NIHR) and is a partnership
between University Hospital Southampton NHS Foundation Trust and the University of Southampton
Fats in foods: healthy,
unhealthy or indifferent?
Philip C. Calder
Professor of Nutritional Immunology
University of Southampton
(pcc@soton.ac.uk)
Food & Drink Innovation Network, London, March 2017
Cholesterol lowering drugs (e.g. simvastatin)
lower mortality
• 4444 patients received placebo
or simvastatin
• Followed for 8 years
• Mortality the main outcome
• Cholesterol decreased by 25%
in the statin group
• LDL cholesterol decreased by
35% in the statin group
• HDL cholesterol increased by
8% in the statin group
• Statin treatment lowered risk of
mortality
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
Ch
ole
ste
rol (m
mo
l/L)
+
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¥
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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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ole
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rol (m
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Human Experiments: Meta-Analysis
of 60 Trials
Mensink et al. (2003) Am. J. Clin. Nutr. 77, 1146-1155
Change in Cholesterol when 1% of carbohydrate energy is replaced with fatty acids
But … Not All Saturates Are Equal
-0.01
0
0.01
0.02
0.03
0.04
0.05
0.06
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
Mensink et al. (2003) Am. J. Clin. Nutr. 77, 1146-1155
UK Government recommendation:
• SFA should provide [an average for the
population] of 10% of total dietary energy
(often quoted as SFA should be < 10% of
dietary energy)
EU approved health claim:
• Foods with a low or reduced content of
saturated fatty acids: Reducing consumption
of saturated fat contributes to the
maintenance of normal blood cholesterol
levels
It seems some SFA are protective and some are not
=> Need to think about individual SFA, rather than
treat all SFA equally
Almost all considerations about fat and fatty
acid intake relate to CHD/CVD
But what about other outcomes like obesity,
diabetes, inflammation and cancer?
Effect of increase in blood content (one standard
deviation increase) of myristic + palmitic + stearic
acids on risk of incident type-2 diabetes
Note: Each of these three fatty acids was individually associated with
~ 20% increase in risk per one SD increase in blood content
Omega-6 polyunsaturated fatty acids
Linoleic acid Arachidonic acid
Intake ~ 12g/day Intake ~ 0.5 g/day
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
Ch
ole
ste
rol (m
mo
l/L)
+
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¥
¥
¥ ¥ ¥
0.06
0.02
0.04
0.00
-0.02
-0.04
ΔL
DL
Ch
ole
ste
rol (m
mo
l/L
) ΔH
DL
Ch
ole
ste
rol (m
mo
l/L)
+
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¥
¥
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Human Experiments: Meta-Analysis
of 60 Trials
Mensink et al. (2003) Am. J. Clin. Nutr. 77, 1146-1155
Change in Cholesterol when 1% of carbohydrate energy is replaced with fatty acids
Favours PUFA
Favours Linoleic acid
CHD events CHD deaths
UK Government recommendation:• Cis-PUFA should continue to provide an average of 6% of
total dietary energy and be derived from a mixture of n-6 and
n-3 PUFA
• Dietary intake of PUFA by individuals should not exceed 10%
of total energy
EU approved health claims:• Linoleic acid: Linoleic acid contributes to the maintenance of
normal blood cholesterol levels
• Monounsaturated and/or polyunsaturated fatty acids:
Replacing saturated fats with unsaturated fats in the diet
contributes to the maintenance of normal blood cholesterol
levels [MUFA and PUFA are unsaturated fats]
• Monounsaturated and/or polyunsaturated fatty acids:
Replacing saturated fats with unsaturated fats in the diet has
been shown to lower/reduce blood cholesterol. High
cholesterol is a risk factor in the development of coronary
heart disease
Trans fats
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
Ch
ole
ste
rol (m
mo
l/L)
+
¥
¥
¥
¥ ¥ ¥
0.06
0.02
0.04
0.00
-0.02
-0.04
ΔL
DL
Ch
ole
ste
rol (m
mo
l/L
) ΔH
DL
Ch
ole
ste
rol (m
mo
l/L)
+
¥
¥
¥
¥ ¥ ¥
Human Experiments: Meta-Analysis
of 60 Trials
Mensink et al. (2003) Am. J. Clin. Nutr. 77, 1146-1155
Change in Cholesterol when 1% of carbohydrate energy is replaced with fatty acids
UK Government recommendation:
• Trans fat intake should not increase further
than the current estimated average of 2%
of dietary energy
vs
t10, c12 CLA
c9, t11 CLA
Summary of findings for blood lipids
vs
Origin of trans fats matters!!
“Diet Heart Hypothesis”
12, 14 & 16 C Saturated Fatty Acids
Industrial Trans Fatty AcidsDietary Cholesterol
Monounsaturated Fatty Acids
Polyunsaturated Fatty Acids
Blood Cholesterol
Atherosclerosis
Coronary Heart Disease/Stroke
Very long chain (“marine”) w-3
polyunsaturated fatty acids
Eicosapentaenoic acid (EPA) 20:5w-3
Docosapentaenoic acid (DPA) 22:5w-3
Docosahexaenoic acid (DHA) 22:6w-3
H3C COOH
H3CCOOH
H3C
COOH
Typical intakes of marine
w-3 PUFAs are low
• Mean UK adult intake is about 0.2 g/day (but
bimodal distribution since only 25% of the
population consumes oily fish)
• Australian data (Meyer et al. (2003) Lipids 38,
391-398):
– Mean daily intakes of EPA, DPA and DHA = 0.056,
0.026, and 0.106 g (Total = 0.188 g/d)
– Median daily intakes of EPA, DPA and DHA =
0.008, 0.006, and 0.015 g DHA (Total = 0.029 g/d)
Effect on EPA + DHA intake by eating
oily fish or taking supplements
Grams per day
Normal
diet
+ one
concentrated
fish oil
capsule
+ one
standard
fish oil
capsule
+ one
Omacor
capsule
One meal
of salmon
+ 4
Omacor
capsules
Increased marine w-3 PUFA supply in diet
Altered fatty acid composition of cell membranes
(more EPA & DHA)
Improved cell & tissue “phenotype”
Improved health or clinical outcome
Prospective study of w-3 PUFA intake
and CHD outcomes:
The Nurse’s Health Study
Total CHD (P < 0.001)
Fatal CHD (P = 0.01)
Non-fatal MI (P = 0.003)
Hu et al. (2002) J. Am. Med. Assoc. 287, 1815-1821
1.0
0.8
0.6
0.4
0.2
0
Lowest Highest
Quintile of marine w-3 fatty acid intake
Prospective study of w-3 PUFA status
and sudden death:
The Physician’s Health Study
1
0.8
0.6
0.4
0.2
01 2 3 4
Re
lati
ve
ris
k o
f s
ud
de
n d
ea
th
Quartile of whole blood marine w-3 PUFAs
Adjusted for age & smoking
Also adjusted for BMI, diabetes,
hypertension, hypercholesterolemia,
alcohol, exercise & family history of
MI
Albert et al. (2002) New Engl. J. Med. 346, 1113-1118
CVD : Classic and emerging risk factors
CLASSIC:
Age
Sex
Family history (genetics)
Smoking
High alcohol consumption
High blood pressure
Diabetes
Obesity
Lack of physical activity
High serum (LDL) cholesterol
EMERGING:High serum triglycerides
Elevated post-prandial lipaemia
Endothelial dysfunction
Tendency towards thrombosis
Inflammation
Elevated plasma homocysteine
Poor antioxidant status
CVD : Classic and emerging risk factors
CLASSIC:
Age
Sex
Family history (genetics)
Smoking
High alcohol consumption
High blood pressure
Diabetes
Obesity
Lack of physical activity
High serum (LDL) cholesterol
EMERGING:High serum triglycerides
Elevated post-prandial lipaemia
Endothelial dysfunction
Tendency towards thrombosis
Inflammation
Elevated plasma homocysteine
Poor antioxidant status
= Improved by n-3 PUFAs
2.5
2.0
1.5
1.0
0.5
0
0 0.2 0.4 0.6 0.8 1.0Increase in supplemental EPA (g/day)
Incre
ase in p
lasm
a P
C E
PA
(% o
f to
tal fa
tty a
cid
s)
One SD increase
2.5
2.0
1.5
1.0
0.5
0
0 0.2 0.4 0.6 0.8 1.0 1.2Increase in supplemental DHA (g/day)
Incre
ase in p
lasm
a P
C D
HA
(% o
f to
tal fa
tty a
cid
s)
One SD increase
How much EPA
and DHA is
needed?
Calder (2017) J
Public Health
Emerg, in press
The benefits of marine w-3 PUFAs
go beyond cardiovascular health
- membrane structure
- growth
- development and function of brain, neural tissue and eye
(-> VERY IMPORTANT IN EARLY LIFE)
- regulation of
- blood pressure
- platelet function, thrombosis, fibrinolysis
- blood lipid concentrations
- vascular function
- cardiac rhythm
- inflammation
- immune response
- bone health
- insulin sensitivity
Marine w-3 PUFAs are important in:
Marine w-3 PUFAs are or may be protective against:
- hypertension
- hypertriglyceridemia
- thrombosis
- vascular dysfunction
- cardiac arrhythmias
- cardiovascular disease
- inflammatory conditions
- allergic conditions
- immune dysfunction
- insulin resistance
- neurodegenerative diseases of ageing
- bone loss
- some cancers
- psychological and psychiatric disorders
Marine w-3 PUFAs (ESPECIALLY DHA) promote:
- optimal brain growth & optimal visual and neural function
UK Government recommendation:• Consumption of fish, particularly oily fish, should be encouraged
• People should eat at least two portions of fish a week, of which
one should be oily
• This recommendation (also) applies to pregnant and lactating
women subject to restrictions on certain fish – marlin, swordfish,
shark and, to a lesser extent, tuna – due to methylmercury
contamination
• Guideline range:
• Women past reproductive age, boys and men should aim to
consume in the range of one to four portions of oily fish a
week
• Women of reproductive age and girls should aim to
consume within the range of one to two portions of oily fish
per week [note that elsewhere the guideline range in
pregnant women is quoted as 2-3 portions of oily fish per
week]
• It might be beneficial for some subgroups to consume more than
the guideline recommendation
• The population average consumption of EPA+DHA should be 0.45
g/day
EU approved health claims:
• Docosahexaenoic acid and Eicosapentaenoic acid
(DHA/EPA): DHA and EPA contribute to the
maintenance of normal blood pressure
• Docosahexaenoic acid and Eicosapentaenoic acid
(DHA/EPA): DHA and EPA contribute to the
maintenance of normal blood triglyceride levels
• Docosahexaenoic acid and Eicosapentaenoic acid
(DHA/EPA): EPA and DHA contribute to the normal
function of the heart
EU approved health claims:
• Docosahexaenoic acid:DHA contributes to maintenance of normal brain function.
DHA contributes to the maintenance of normal vision.
DHA contributes to the maintenance of normal blood
triglyceride levels.
Docosahexaenoic acid (DHA) maternal intake contributes to
the normal brain development of the foetus and breastfed
infants.
Docosahexaenoic acid (DHA) intake contributes to the normal
visual development of infants up to 12 months of age.
Docosahexaenoic acid (DHA) maternal intake contributes to
the normal development of the eye of the foetus and breastfed
infants.
Can we make sense of all this?
Industrial trans FA
Lauric, myristic
& palmitic acids
a-Linolenic acid
EPA, DPA & DHA
MORE LESS
Linoleic acid
Dairy-derived odd-chain
saturated FA (& dairy trans?)
Cis-Monounsaturated FA