Omega-3 Fatty Acids :

Naming, sources, intakes, metabolism

and health benefits

Philip Calder

Professor of Nutritional Immunology

University of Southampton

This lecture will cover

Fatty acid structure, nomenclature, sources, and

intakes

Metabolic relationship between a-linolenic acid and

long chain omega-3 fatty acids

Omega-3 fatty acids and cardiovascular health

Omega-3 fatty acids and visual and brain

development

Recommendations for omega-3 fatty acid intake

Fats in the diet

CH2.O.CO.R1

R2.CO.OCH

CH2.O.CO.R3

Triglycerides

Also sphingolipids

cholesterol and cholesterol esters

CH2.O.CO.R1

R2.CO.OCH

CH2.O.POO.O.Base

Phospholipids

COOH

H3C

Fatty acid structure

Fatty acid structure and nomenclature

COOH

H3C

H3C COOH

H3C

COOH

Stearic acid 18:0

Oleic acid 18:1w-9

Linoleic acid 18:2w-6

a-Linolenic acid 18:3w-3H3CCOOH

Mammals cannot insert double bonds in here

9

6

3

Omega = w- = n-

0 20 40 60 80 100

Sunflower oil

Corn oil

Soybean oil

Olive oil

Pig fat

Beef fat

Butter

Saturated Monounsaturated Polyunsaturated

Latest fatty acid intake data for adults in UK

(g/day)

Males Females

Total fat 87 (36% energy) 61 (35% energy)

Saturated 33 23

Trans 3 2

Monounsaturated 29 20

Omega-6 PUFA 13 9

Omega-3 PUFA 2.3 1.7

H3C COOH

H3CCOOH

H3C

COOH

H3CCOOH

Omega-3 PUFAs

a-Linolenic acid (18:3w-3)

EPA (20:5w-3)

DPA (22:5w-3)

DHA (22:6w-3)

These have different dietary sources

and

their intake differs markedly

a-Linolenic acid (18:3w-3)

Found in green plant tissues

Found in some vegetable oils (e.g. soybean,

rapeseed)

Found in some nuts (e.g. walnut)

Found in linseed (flaxseed) and linseed oil

Contributes 85 to 95% of w-3 PUFA intake in

UK adults (ca. 2.1 g/day in males; 1.5 g/day in

females)

Long chain w-3 PUFAs (EPA, DPA, DHA)

- oily fish are the only rich source

of preformed long chain w-3

PUFAs

- adults in the UK consume on

average 1/3 of a portion of oily

fish per week (53 g/week)

- fish consumers consume 1.3

portions of oily fish per week

(about 195 g/week)

- average long chain w-3 PUFA

intake is < 0.2 g/day (200 mg/day)

- long chain w-3 PUFAs are found

in fish oils

Long chain w-3 PUFA content of fish

EPA DPA DHA Total

(g/100 g food) g/portion

Cod 0.08 0.01 0.16 0.30

Haddock 0.05 0.01 0.10 0.19

Herring 0.51 0.11 0.69 1.56

Mackerel 0.71 0.12 1.10 3.09

Salmon 0.55 0.14 0.86 1.55

Crab 0.47 0.08 0.45 0.85

Prawns 0.06 0.01 0.04 0.06

a-linolenic acid is metabolically

related to long chain w-3 PUFAs

Delta 6-desaturase

Elongase

Delta 5-desaturase

a-Linolenic acid (18:3w-3)

18:4w-3

20:4w-3

EPA (20:5w-3)

DPA (22:5w-3) DHA (22:6w-3)

a-Linolenic acid

EPA

DHA

This pathway does

not work

very well in humans

Key points (so far)

w-6 and w-3 PUFAs are distinct fatty acid families

Most w-3 PUFA in the diet is in the form of a-linolenic acid

Long chain w-3 PUFAs are found in oily fish (fish oil capsules)

Average intake of long chain w-3 PUFAs is < 0.2 g/day

a-Linolenic acid is poorly converted to long chain w-3 PUFAs in humans

Omega-3 PUFAs and human health

Disease Expected Actual

Myocardial infarction 40 3

Psoriasis 40 2

Bronchial asthma 25 1

Diabetes 9 1

Multiple sclerosis 2 0

From a survey of distribution of

diseases in Greenland Eskimos

Kromann & Green (1980) Acta Med. Scand. 208, 410-406

Many studies report an inverse correlation between

fish consumption or w-3 PUFA status and CHD

Kromhout et al. 1985 Fish CVD mortality

Shekelle et al. 1985 Fish CVD mortality

Norelle et al. 1986 Fish CVD mortality

Dolecek et al. 1992 Dietary w-3 PUFA CVD mortality

Feskens et al. 1993 Fish CVD mortality

Siscovik et al. 1995 Fish CVD mortality

Kromhout et al. 1995 Fish CVD mortality

Daviglus et al. 1997 Fish CVD mortality

Albert et al. 1998 Fish sudden cardiac death

Pedersen et al. 2000 Adipose tissue w-3 PUFA MI mortality

Albert et al. 2002 Whole blood w-3 PUFA sudden death

Hu et al. 2002 Fish and w-3 PUFA intake CHD mortality

Hu et al. 2002 Fish and w-3 PUFA intake non-fatal MI

Tavani et al. 2001 Fish and w-3 PUFA intake non-fatal MI

Gualler et al. 2003 Adipose tissue DHA first MI

Lemaitre et al. 2003 Plasma EPA and DHA CHD mortality

Prospective: Long chain w-3 PUFA

status and sudden death

1

0.8

0.6

0.4

0.2

01 2 3 4

Rela

tiv

e r

isk o

f su

dd

en

death

Quartile of blood 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

Risk factors for atherosclerosis

Elevated blood lipids

Endothelial dysfunction

Inflammation

LDL-cholesterol

TriglyceridesHypertension

Meta-analysis of trials of fish oil and blood pressure

Geleijnse et al. (2002) J. Hypertens. 20, 1493-1499

36 controlled trials reviewed incl. 22 double blind

Fish oil:

- decreased systolic BP by 2.1 mm Hg

(95% CI 1.0, 3.2; P < 0.01)

- decreased diastolic BP by 1.6 mm Hg

(95% CI 1.0, 2.2; P < 0.01)

Effects greater in older subjects

Effects greater in hypertensive subjects

Conclusion “increased intake of fish oil may lower BP,

especially in older and hypertensive subjects”

Relationship between dietary long chain

w-3 PUFAs and blood TAG concentrations

Review of 72 placebo-controlled human trials

All > 2 weeks duration

Harris (1996) Lipids 31, 243-252

TAG < 2 mM TAG > 2 mM

-30

-20

-10

0

10

% C

han

ge

Placebo

Fish oil

Difference

Endothelium dependent coronary vasodilatation in

patients with CHD before and after fish oil (4 months)

Acetylcholine

300

200

100

0

CHD patients after fish oil

Controls

CHD patients before fish oil

Fish oil and an inflammatory marker

(sVCAM-1)

Healthy subjects aged >

55 y

Supplemented diet with

a moderate amount of

fish oil (= 1.2 g

EPA+DHA/day) for 12

weeks

Plasma soluble VCAM-1

concentrations

measured

Placebo FO

0

200

400

600

800

1000

sV

CA

M-1

(n

g/m

l)

Pre

Post

Miles et al. (2001) Clinical Science 100, 91-100

*

Risk factors for atherosclerosis

Elevated blood TAG

Endothelial dysfunction

Inflammation

N-3 PUFA

Hypertension

Secondary prevention: DART

1015 men aged < 70 y

who had had a MI

Advised to eat oily fish

or take fish oil capsules

vs. no advice

Cardiovascular events

and mortality followed

for 2 years

Relative risk death 0.77

Relative risk IHD death

0.84

8006004002000

85

90

95

100

Time (days)

% S

urv

ivio

rs

Burr et al. (1989) Lancet ii, 757-761

Oily fish

No advice

Secondary prevention:

GISSI Study

2836 men who had had

a MI within the last 3

months assigned to fish

oil (0.85 g LC w-3

PUFA/day) vs. placebo

Follow up for two years

356 deaths and non-

fatal CV events in fish

oil group vs. 414 in

placebo group

GISSI Prevenzione Investigators (1999) Lancet 354, 447-455

Relative risk in fish oil group

All fatal events 0.80

CV death 0.70

Coronary death 0.65

Sudden death 0.55

There are also non-cardiovascular

actions of long chain w-3 PUFAs

DHA concentration in different human tissues

Adipose Erythrocyte Placenta Liver Testis Brain Retina0.0

2.5

5.0

7.5

10.0

12.5

15.0

17.5

20.0

% T

ota

l fa

tty a

cid

s

DHA status and infant mental development

(1 year of age)

140

120

100

80

603 6 9 12

Infant red cell DHA (%)

Gibson et al. (1997) Eur. J. Clin. Nutr. 51, 578-584

“Maternal supplementation with very long chain n-3 fatty acids

during pregnancy and lactation augments childrens IQ at 4 years of

age”

Placebo vs. 2.4 g long chain w-3 PUFAs/day (50:50 EPA & DHA)

from week 18 of pregnancy until 3 months post partum

Kaufman Assessment Battery for Children performed at 4 years of

age - a measure of intelligence and achievement designed for

children aged 2.5 to 12.5 years

At 4 years of age:

Children of mothers in control group = 102.3 (11.3)

Children of mothers in fish oil group = 106.4 (7.4)

Helland et al. (2003) Pediatrics 111, 39-44

Omega-3s in children with ADHD

Burgess et al. (2000) Am. J. Clin. Nutr. 71, 327S-330S

0.25

0.2

0.15

0.1

0.05

0

Control Few ADHD Many ADHDEP

A in

pla

sm

a p

ho

sp

ho

lip

ids

The Durham Trial

A randomised controlled trial of fish oil

supplementation (vs. placebo) in children (5 –

12 years old) with developmental co-ordination

disorder (n = 117)

Placebo vs. 550 mg EPA + 175 mg DHA/day for 3

months

Then all onto EPA + DHA for a further 3 months

Richardson & Montgomery (2005) Pediatrics 115, 1360-1366

Reading age Spelling age

Baseline 3 mo 6 mo

120

110

100

90

Omega 3 Placebo Placebo then Omega-3

Baseline 3 mo 6 mo

105

100

95

90

Omega 3 Placebo Placebo then Omega-3

Baseline 3 mo 6 mo

Hyperactivity

63

61

59

57

55

- membrane structure

- brain and visual development

- maintenance of cognitive and neurological function

(during development & with aging)

- regulation of

- blood pressure

- platelet function, thrombosis, fibrinolysis

- blood lipid concentrations

- vascular function

- cardiac rhythmn

- inflammation

- immune response

- bone health

- insulin sensitivity

Long chain w-3 PUFAs are important in:

- optimal brain growth

- optimal visual and neural function

Long chain w-3 PUFAs promote

- hypertension

- hypertriglyceridemia

- thrombosis

- vascular dysfunction

- cardiac arrhythmias

- cardiovascular disease

- inflammatory conditions

- allergic conditions

- immune dysfunction

- insulin resistance

- psychiatric and neurological diseases of children and adults

- neurodegenerative diseases of ageing

- bone loss

- some cancers

Long chain w-3 PUFAs are (or may be)

protective against

Summary: Long chain w-3 PUFAs

-

Long chain w-3 PUFAs have a number of physiological

effects

Through their physiological effects they alter risk of a

wide range of human diseases

Lowered disease risk occurs through plausible

biological mechanisms

There are newly emerging mechanisms of action of

long chain w-3 PUFAs in some conditions

Long chain w-3 PUFAs exert health benefits right

through the life cycle (womb to tomb!)

Long chain w-3 PUFAs

Current intakes vs. Recommendations (g/day)

Current av. UK intake < 0.2

ISSFAL 1999 0.65

BNF 1999 1.0-1.4

AHA 2003* 1.0

AHA 2003** 2 to 4

SACN/COT 2004 0.45 (minimum)

*For patients with CHD

**For patients with hypertriglyceridaemia

What about a-linolenic acid?

Sanderson et al. (2002) Brit. J. Nutr. 88, 573-579

“The studies …. suggested little, if any, benefit

of a-linolenic acid, relative to linoleic acid, on

risk factors for cardiovascular disease ….”

Consensus statement

However, a-linolenic acid may exert health benefits

through conversion to longer chain derivatives

But, this may require high intakes of a-linolenic acid

Оmegame®

(MeCompany AG, Switzerland)

is the source of omega-3 PUFAs for health

and happiness of the whole family!

Not each omega is Оmegame®!