Omega 3 overview - professor philip calder
-
Upload
mecompany -
Category
Health & Medicine
-
view
526 -
download
3
Transcript of Omega 3 overview - professor philip calder
![Page 1: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/1.jpg)
Omega-3 Fatty Acids :
Naming, sources, intakes, metabolism
and health benefits
Philip Calder
Professor of Nutritional Immunology
University of Southampton
![Page 2: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/2.jpg)
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
![Page 3: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/3.jpg)
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
![Page 4: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/4.jpg)
COOH
H3C
Fatty acid structure
![Page 5: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/5.jpg)
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-
![Page 6: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/6.jpg)
0 20 40 60 80 100
Sunflower oil
Corn oil
Soybean oil
Olive oil
Pig fat
Beef fat
Butter
Saturated Monounsaturated Polyunsaturated
![Page 7: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/7.jpg)
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
![Page 8: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/8.jpg)
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)
![Page 9: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/9.jpg)
These have different dietary sources
and
their intake differs markedly
![Page 10: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/10.jpg)
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)
![Page 11: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/11.jpg)
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
![Page 12: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/12.jpg)
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
![Page 13: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/13.jpg)
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)
![Page 14: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/14.jpg)
a-Linolenic acid
EPA
DHA
This pathway does
not work
very well in humans
![Page 15: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/15.jpg)
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
![Page 16: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/16.jpg)
Omega-3 PUFAs and human health
![Page 17: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/17.jpg)
![Page 18: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/18.jpg)
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
![Page 19: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/19.jpg)
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
![Page 20: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/20.jpg)
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
![Page 21: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/21.jpg)
Risk factors for atherosclerosis
Elevated blood lipids
Endothelial dysfunction
Inflammation
LDL-cholesterol
TriglyceridesHypertension
![Page 22: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/22.jpg)
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”
![Page 23: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/23.jpg)
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
ha
ng
e
Placebo
Fish oil
Difference
![Page 24: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/24.jpg)
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
![Page 25: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/25.jpg)
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
*
![Page 26: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/26.jpg)
Risk factors for atherosclerosis
Elevated blood TAG
Endothelial dysfunction
Inflammation
N-3 PUFA
Hypertension
![Page 27: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/27.jpg)
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
![Page 28: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/28.jpg)
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
![Page 29: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/29.jpg)
There are also non-cardiovascular
actions of long chain w-3 PUFAs
![Page 30: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/30.jpg)
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
![Page 31: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/31.jpg)
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
![Page 32: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/32.jpg)
“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
![Page 33: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/33.jpg)
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
![Page 34: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/34.jpg)
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
![Page 35: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/35.jpg)
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
![Page 36: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/36.jpg)
Omega 3 Placebo Placebo then Omega-3
Baseline 3 mo 6 mo
Hyperactivity
63
61
59
57
55
![Page 37: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/37.jpg)
- 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:
![Page 38: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/38.jpg)
- optimal brain growth
- optimal visual and neural function
Long chain w-3 PUFAs promote
![Page 39: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/39.jpg)
- 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
![Page 40: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/40.jpg)
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!)
![Page 41: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/41.jpg)
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
![Page 42: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/42.jpg)
What about a-linolenic acid?
![Page 43: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/43.jpg)
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
![Page 44: Omega 3 overview - professor philip calder](https://reader033.fdocuments.us/reader033/viewer/2022052508/5597773e1a28ab98698b481a/html5/thumbnails/44.jpg)
However, a-linolenic acid may exert health benefits
through conversion to longer chain derivatives
But, this may require high intakes of a-linolenic acid