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

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0.02

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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

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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

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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

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