1. Omega-3 Fatty Acids :
Naming, sources, intakes, metabolism
and health benefits
Philip Calder
Professor of Nutritional Immunology
University of Southampton
2. This lecture will cover
Fatty acid structure, nomenclature, sources, and
intakes
Metabolic relationship between α -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
3. Fats in the diet
CH2.O.CO.R1 CH2.O.CO.R1
R2.CO.OCH R2.CO.OCH
CH2.O.CO.R3 CH2.O.POO.O.Base
Triglycerides Phospholipids
Also sphingolipids
cholesterol and cholesterol esters
10. α -Linolenic acid (18:3ω -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 ω -3 PUFA intake in
UK adults (ca. 2.1 g/day in males; 1.5 g/day in
females)
11. Long chain ω -3 PUFAs (EPA, DPA, DHA)
- oily fish are the only rich source
of preformed long chain ω -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 ω -3 PUFA
intake is < 0.2 g/day (200 mg/day)
- long chain ω -3 PUFAs are found
in fish oils
12. Long chain ω -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
13. α -linolenic acid is metabolically
related to long chain ω -3 PUFAs
α -Linolenic acid (18:3ω -3)
Delta 6-desaturase
18:4ω -3
Elongase
20:4ω -3
Delta 5-desaturase
EPA (20:5ω -3)
DPA (22:5ω -3) DHA (22:6ω -3)
14. α -Linolenic acid
This pathway does
not work
very well in humans
EPA
DHA
15. Key points (so far)
ω -6 and ω -3 PUFAs are distinct fatty acid
families
Most ω -3 PUFA in the diet is in the form of α -
linolenic acid
Long chain ω -3 PUFAs are found in oily fish
(fish oil capsules)
Average intake of long chain ω -3 PUFAs is <
0.2 g/day
α -Linolenic acid is poorly converted to long
chain ω -3 PUFAs in humans
18. From a survey of distribution of
diseases in Greenland Eskimos
Disease Expected Actual
Myocardial infarction 40 3
Psoriasis 40 2
Bronchial asthma 25 1
Diabetes 9 1
Multiple sclerosis 2 0
Kromann & Green (1980) Acta Med. Scand. 208, 410-406
19. Many studies report an inverse correlation between
fish consumption or ω-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 ω -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 ω -3 PUFA ↓ MI mortality
Albert et al. 2002 Whole blood ω -3 PUFA ↓ sudden death
Hu et al. 2002 Fish and ω -3 PUFA intake ↓ CHD mortality
Hu et al. 2002 Fish and ω -3 PUFA intake ↓ non-fatal MI
Tavani et al. 2001 Fish and ω -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
20. Prospective: Long chain ω -3 PUFA
status and sudden death
Relative risk of sudden death
Adjusted for age & smoking
1 Also adjusted for BMI,
diabetes, hypertension,
0.8
hypercholesterolemia, alcohol,
0.6 exercise & family history of MI
0.4
0.2
0
1 2 3 4
Quartile of blood ω -3 PUFAs
Albert et al. (2002) New Engl J Med 346, 1113-1118
22. 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”
23. Relationship between dietary long chain
ω -3 PUFAs and blood TAG concentrations
Review of 72 placebo-controlled human trials
All > 2 weeks duration
Harris (1996) Lipids 31, 243-252
10
0
% Change
Placebo
-10 Fish oil
-20 Difference
-30
TAG < 2 mM TAG > 2 mM
24. Endothelium dependent coronary vasodilatation in
patients with CHD before and after fish oil (4 months)
300
Increase in coronary
blood flow (%)
200 CHD patients after fish oil
Controls
100
CHD patients before fish oil
0
Acetylcholine
25. Fish oil and an inflammatory marker
(sVCAM-1)
Healthy subjects aged > Pre
55 y Post
Supplemented diet with
1000
a moderate amount of
sVCAM-1 (ng/ml)
800 *
fish oil (= 1.2 g
600
EPA+DHA/day) for 12
400
weeks 200
Plasma soluble VCAM-1 0
concentrations Placebo FO
measured
Miles et al. (2001) Clinical Science 100, 91-100
26. Risk factors for atherosclerosis
Elevated blood TAG Hypertension
Endothelial dysfunction
Inflammation
N-3 PUFA
27. Secondary prevention: DART
1015 men aged < 70 y who had
had a MI
Oily fish
Advised to eat oily fish or take
100 No advice
fish oil capsules vs. no advice
% Surviviors
Cardiovascular events and 95
mortality followed for 2 years
Relative risk death 0.77 90
Relative risk IHD death 0.84
85
0 200 400 600 800
Time (days)
Burr et al. (1989) Lancet ii, 757-761
28. Secondary prevention:
GISSI Study
2836 men who had had Relative risk in fish oil group
a MI within the last 3
months assigned to fish All fatal events 0.80
oil (0.85 g LC ω -3 CV death 0.70
PUFA/day) vs. placebo Coronary death 0.65
Follow up for two years Sudden death 0.55
356 deaths and non-fatal
CV events in fish oil
group vs. 414 in placebo
group
GISSI Prevenzione Investigators (1999) Lancet 354, 447-455
29. There are also non-cardiovascular
actions of long chain ω -3 PUFAs
30. DHA concentration in different human tissues
20.0
17.5
% Total fatty acids
15.0
12.5
10.0
7.5
5.0
2.5
0.0
Adipose Erythrocyte Placenta Liver Testis Brain Retina
31. DHA status and infant mental development
(1 year of age)
Development Index
140
Bayley Mental
120
100
80
60
3 6 9 12
Infant red cell DHA (%)
Gibson et al. (1997) Eur. J. Clin. Nutr. 51, 578-584
32. Helland et al. (2003) Pediatrics 111, 39-44
“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 ω -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)
33. Omega-3s in children with ADHD
EPA in plasma phospholipids
0.25
0.2
0.15
0.1
0.05
0
Control Few ADHD Many ADHD
Burgess et al. (2000) Am. J. Clin. Nutr. 71, 327S-330S
34. 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
35. Omega 3 Placebo Placebo then Omega-3
120 105
110 100
100 95
90 90
Baseline 3 mo 6 mo Baseline 3 mo 6 mo
Reading age Spelling age
36. Hyperactivity
Omega 3 Placebo Placebo then Omega-3
63
61
59
57
55
Baseline 3 mo 6 mo
37. Long chain ω -3 PUFAs are important in:
- 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
38. Long chain ω -3 PUFAs promote
- optimal brain growth
- optimal visual and neural function
39. Long chain ω -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
- psychiatric and neurological diseases of children and adults
- neurodegenerative diseases of ageing
- bone loss
- some cancers
40. Summary: Long chain ω -3 PUFAs
Long chain ω -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 ω -3 PUFAs in some conditions
Long chain ω -3 PUFAs exert health benefits right
through the life cycle (womb to tomb!)
41. Long chain ω -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
43. Consensus statement
Sanderson et al. (2002) Brit. J. Nutr. 88, 573-579
“The studies …. suggested little, if any, benefit
of α -linolenic acid, relative to linoleic acid, on
risk factors for cardiovascular disease ….”
44. However, α -linolenic acid may exert health benefits
through conversion to longer chain derivatives
But, this may require high intakes of α -linolenic acid