NIHR Southampton
Biomedical Research Centre in nutrition

Omega-3 : The science behind
the headlines
Philip Calder
Profess...
About me
• PhD in Biochemistry (University of Auckland, NZ)
• 1987-1995 in Department of
Biochemistry, University of Oxfor...
Key points to discuss …
•
•
•
•
•

What are “omega-3”?
Where do you get them from?
Why are they good for you?
How much do ...
Omega-3
w-3

n-3
What are omega-3?
• Omega-3 are a type of fat
-> Note: Not all fat is bad!
• One of the polyunsaturated fats
• Some omega-...
More on omega-3
• Much less abundant in the diet than omega-6
fats found in vegetable oils and margarines
• Western diets ...
H3C

COOH
a-Linolenic acid (18:3w-3)
D6-desaturase

H3C

COOH
Stearidonic acid (18:4w-3)

Elongase
H3C

COOH

D5-desaturas...
H3C

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

D6-desaturase
H3C

Synthesised in plants
Found in green leaves, some
seeds, some nut...
EPA & DHA : where do you
get them from?
• The only naturally rich source is seafood, especially oily fish
(salmon, tuna, s...
EPA and DHA content of
different foods and supplements
g/serving
Red meat
Cod & other lean fish
Salmon
Mackerel

< 0.1
0.3...
How much EPA and DHA do
people eat?
How much fat do people eat?

75 grams

Total fat from
all sources

Variation due
to diet
75 grams

Polyunsaturated
fat
Trans fat

Monounsaturated
fat
Total fat from
all sources

Saturated
fat
Omega-3

Polyunsaturated
fat
Trans fat
Omega-6
Monounsaturated
fat

Saturated
fat
Fish omega-3

Omega-3

Plant omega-3

Omega-6
Fish omega-3
75 grams

Total fat from
all sources
How much EPA and DHA do
people eat?
75 grams

Total fat from
all sources

Fish omega-3: Less than 0.2 g each day
Only a qu...
What if people eat fish or take
supplements?
4

Grams per day
3.5

3

2.5

2

1.5

1

0.5

0
1

Normal
diet

2
+ one
stand...
What happens if omega-3 intake
is increased?
DIET
(FOOD OR SUPPLEMENTS)

GUT

Digestion & absorption

LIVER

BLOOD

ADIPOS...
What happens if omega-3 intake
is increased?
EPA in blood plasma

DHA in blood plasma

4

7

3.5

6

3

5

2.5

4

2

3

1...
Increase in EPA

Blood plasma

Red blood cells
Heart tissue
Fat tissue

Time
Increasing EPA+DHA intake increases the EPA
and DHA content of blood lipids, blood
cells, and tissues – effect is dose, ti...
Functions/roles of EPA and DHA
• Energy sources
• Cell membrane components (structure -> function)
[Note: DHA especially i...
Altered w-3
fatty acid supply

Altered composition
of cell membrane

Membrane alterations

Signals leading to gene
express...
The cell membrane
EPA and DHA
take on different
3D shapes
compared with
other fatty acids
EPA and DHA: Why are they good for you?
• Vital for good health
• Improve blood fats, blood flow, blood clotting, inflamma...
Brain growth in humans
Specific need for DHA for brain and
visual development
Concentration (mg total cerebellum)

DHA accumulation into human
br...
Effect of DHA supplementation
on visual function in young infants
Visual acuity (VEP) (log
MAR)

1
0.8

**

0.6

Breast-fe...
EPA and DHA
take on different
3D shapes
compared with
other fatty acids
DHA acts like a spring to enable the conformational
change required for rhodopsin to signal properly

Light

DHA spring
EPA and DHA
and cardiovascular disease
Heart disease
Disease of the vessels supplying blood to the heart
(coronary artery)

Impeded heart function
(heart failure...
Heart disease is one of the
cardiovascular diseases
(diseases of the heart or blood vessels)
These diseases are caused by a build-up of fatty material within the blood
vessel wall (“atherosclerosis” “plaque”)
-> nar...
Atherosclerosis
(Plaque growth)

Threshold where more
serious manifestations
like heart attacks or
strokes begin to occur
...
The Greenland Inuit (“Eskimo”)
Much lower than expected rate
of death from heart attack
100
80
60
40
20
0
Expected

Seen
How could this be?
-> The Inuit diet??
• Ate lots of seal
meat, whale
meat, whale
blubber, fish
• -> Very high intake
of o...
Prospective study
People enter study when they are healthy/disease free

Take information about diet and lifestyle; Take b...
Two different prospective studies from the US
Likelihood of fatal heart disease

Likelihood of sudden death

100

100

80
...
EPA and DHA intake and future heart disease :
a study from the US
1.0
0.8
0.6

Total CHD (P < 0.001)
Fatal CHD (P = 0.01)
...
Relative risk of sudden death

EPA+ DHA in blood and future sudden death :
a study from the US
Adjusted for age & smoking
...
How can this be?
-> Risk factors
Primary Risk Factors
Hypertension

Hyperlipidaemia Smoking

Cardiovascular Disease
Family Medical
History of CVD
Lack of e...
Primary Risk Factors
Hypertension

Hyperlipidaemia Smoking

Cardiovascular Disease
Family Medical
History of CVD
Lack of e...
Higher omega-3 intake

Time

Atherosclerosis
(Plaque growth)
What about people who already have heart or
cardiovascular disease??
• Can study effect of omega3 given as supplements jus...
Illness and death outcomes

With oral omega-3

Time
Arch. Int. Med. (2005) 165, 725-730
Considered: 97 intervention trials with lipid lowering strategies (incl.
EPA+DHA) and ...
Conclusion “statins and w-3 fatty acids are the most favourable lipid
lowering interventions with reduced risks of overall...
How can this be?
-> Probably not about the same risk factors
as before because they relate to building up
the plaque – her...
Inflammation causes plaque rupture
Omega-3 are anti-inflammatory
-> Maybe omega-3 reduce deaths in at
risk patients by dec...
We wished to study the effects of
omega-3 on plaque stability in humans
• Needed a source of plaques ->
there is a surgica...
Difference from control group in:
Unstable plaques

0
-10
-20
-30
-40
-50
-60

One key marker
of plaque inflammation
Our results may explain how omega-3
stop people from having heart attacks
and how they stop people from dying
=> A higher EPA+DHA intake and status is
protective against CVD risk and against
CVD mortality
Omega-3 Index = EPA + DHA as a % of all fatty acids in red
blood cell membranes
Inflammation has two phases:
initiation and resolution
Initiation
phase

Resolution
phase

TIME
EPA and DHA are precursors of
pro-resolving lipid mediators
To sum up …..
EPA and DHA are important in:
- cell membrane structure & function
- brain and visual development
- maintenance of cogniti...
EPA and DHA are
vital throughout
the life course
Key points to discuss …
•
•
•
•
•

What are “omega-3”?
Where do you get them from?
Why are they good for you?
How much do ...
Recommendations for fat and fatty acid
intakes for adults in the UK








Total fat intake should not exceed 35% o...
EPA & DHA : how much do you need?
• The UK Government says all adults need at least 0.45
g EPA+DHA per day to maintain hea...
EPA & DHA : how do you know if you get
enough
• The amount of EPA and DHA in the blood increases
when more is eaten in the...
Thank you!
Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014
Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014
Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014
Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014
Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014
Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014
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Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014

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Prof. Philip Calder speaking about Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014.

His research focuses on understanding the influence of dietary fatty acids on aspects of cell function and human health, in particular in relation to cardiovascular disease, inflammation and immunity.

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Prof Philip Calder on Omega 3 at Isle Of Wight Cafe Scientifique on 10 Feb 2014

  1. 1. NIHR Southampton Biomedical Research Centre in nutrition Omega-3 : The science behind the headlines Philip Calder Professor of Nutritional Immunology University of Southampton (pcc@soton.ac.uk) 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
  2. 2. About me • PhD in Biochemistry (University of Auckland, NZ) • 1987-1995 in Department of Biochemistry, University of Oxford • Since 1995 at University of Southampton • Research focus: fatty acid nutrition and functionality -> implications for public health and for clinical practice
  3. 3. Key points to discuss … • • • • • What are “omega-3”? Where do you get them from? Why are they good for you? How much do you need? How do you know if you get enough?
  4. 4. Omega-3 w-3 n-3
  5. 5. What are omega-3? • Omega-3 are a type of fat -> Note: Not all fat is bad! • One of the polyunsaturated fats • Some omega-3 come from plants and some come from fish • We are interested in fish omega-3 (EPA and DHA)
  6. 6. More on omega-3 • Much less abundant in the diet than omega-6 fats found in vegetable oils and margarines • Western diets have too much omega-6 and not enough omega-3 • The most important omega-3 for human health are EPA and DHA from seafood
  7. 7. H3C COOH a-Linolenic acid (18:3w-3) D6-desaturase H3C COOH Stearidonic acid (18:4w-3) Elongase H3C COOH D5-desaturase COOH H3C Eicosapentaenoic acid (20:5w-3) Retroconversion Elongase Elongase D6-desaturase b-oxidation H3C COOH Docosahexaenoic acid (22:6w-3)
  8. 8. H3C COOH a-Linolenic acid (18:3w-3) D6-desaturase H3C Synthesised in plants Found in green leaves, some seeds, some nuts, some plant oils Intake of a-linolenic acid is typically 1 to 2 g/day COOH Stearidonic acid (18:4w-3) Elongase H3C COOH D5-desaturase COOH H3C Found in seafood (especially oily fish), in fish oils and lean fish liver oils, in algal oils, in concentrated pharmaceutical preparations Eicosapentaenoic acid (20:5w-3) Retroconversion Elongase Elongase D6-desaturase b-oxidation H3C  intakes are usually low COOH Docosahexaenoic acid (22:6w-3)
  9. 9. EPA & DHA : where do you get them from? • The only naturally rich source is seafood, especially oily fish (salmon, tuna, sardines, herring, mackerel …) • Different seafood provides different amounts of EPA+DHA • One meal of salmon or mackerel can provide up to 3 grams of EPA+DHA • One meal of white fish like cod or one standard fish oil capsule can provide about one-tenth of this • Supply is limited -> novel sources (algae, plants ..)
  10. 10. EPA and DHA content of different foods and supplements g/serving Red meat Cod & other lean fish Salmon Mackerel < 0.1 0.3 1.5 3.0 g/capsule (1 gram) Standard fish oil Concentrated fish oil Pharmaceutical grade 0.3 0.45-0.65 0.9 11
  11. 11. How much EPA and DHA do people eat?
  12. 12. How much fat do people eat? 75 grams Total fat from all sources Variation due to diet
  13. 13. 75 grams Polyunsaturated fat Trans fat Monounsaturated fat Total fat from all sources Saturated fat
  14. 14. Omega-3 Polyunsaturated fat Trans fat Omega-6 Monounsaturated fat Saturated fat
  15. 15. Fish omega-3 Omega-3 Plant omega-3 Omega-6
  16. 16. Fish omega-3 75 grams Total fat from all sources
  17. 17. How much EPA and DHA do people eat? 75 grams Total fat from all sources Fish omega-3: Less than 0.2 g each day Only a quarter of one percent of dietary fat!
  18. 18. What if people eat fish or take supplements? 4 Grams per day 3.5 3 2.5 2 1.5 1 0.5 0 1 Normal diet 2 + one standard fish oil capsule 3 + one concentrated fish oil capsule 4 + one Omacor capsule 5 One meal of salmon 6 +4 Omacor capsules
  19. 19. What happens if omega-3 intake is increased? DIET (FOOD OR SUPPLEMENTS) GUT Digestion & absorption LIVER BLOOD ADIPOSE (FAT) Metabolism Transport Storage CELLS AND TISSUES Cell membranes (Important for cell & tissue function)
  20. 20. What happens if omega-3 intake is increased? EPA in blood plasma DHA in blood plasma 4 7 3.5 6 3 5 2.5 4 2 3 1.5 1 2 0.5 1 0 0 1 0 2 1 3 2 Capsules per day 4 4 1 0 2 1 3 2 Capsules per day 4 4
  21. 21. Increase in EPA Blood plasma Red blood cells Heart tissue Fat tissue Time
  22. 22. Increasing EPA+DHA intake increases the EPA and DHA content of blood lipids, blood cells, and tissues – effect is dose, time and tissue dependent
  23. 23. Functions/roles of EPA and DHA • Energy sources • Cell membrane components (structure -> function) [Note: DHA especially important in brain and retina] • Signaling molecules • Regulators of gene expression • Precursors of lipid mediators (prostaglandins, leukotrienes, resolvins etc.)
  24. 24. Altered w-3 fatty acid supply Altered composition of cell membrane Membrane alterations Signals leading to gene expression Altered cell and tissue behaviour Health vs disease Lipid mediators
  25. 25. The cell membrane
  26. 26. EPA and DHA take on different 3D shapes compared with other fatty acids
  27. 27. EPA and DHA: Why are they good for you? • Vital for good health • Improve blood fats, blood flow, blood clotting, inflammation -> Heart healthy • Improve immune function • Reduce inflammation – arthritis • Good for bones • Very important for the brain & eye – Vital in early life for good brain and visual development – May be important for optimal childhood learning – May have a role in preventing psychiatric and psychological disorders – May slow cognitive decline
  28. 28. Brain growth in humans
  29. 29. Specific need for DHA for brain and visual development Concentration (mg total cerebellum) DHA accumulation into human brain Brain growth spurt 300 250 200 150 100 50 N 0 0 5 10 15 20 25 30 35 40 45 50 Post conceptual age (weeks) N = neuritogenesis
  30. 30. Effect of DHA supplementation on visual function in young infants Visual acuity (VEP) (log MAR) 1 0.8 ** 0.6 Breast-fed * 0.4 Control DHA-suppl 0.2 0 16 wks 30 wks Human milk & DHA formula better than control; ** p<0.001, * p<0.01 Makrides 1995
  31. 31. EPA and DHA take on different 3D shapes compared with other fatty acids
  32. 32. DHA acts like a spring to enable the conformational change required for rhodopsin to signal properly Light DHA spring
  33. 33. EPA and DHA and cardiovascular disease
  34. 34. Heart disease Disease of the vessels supplying blood to the heart (coronary artery) Impeded heart function (heart failure) Poor blood supply to other tissues Other tissues stop functioning Heart attack Heart stops functioning
  35. 35. Heart disease is one of the cardiovascular diseases (diseases of the heart or blood vessels)
  36. 36. These diseases are caused by a build-up of fatty material within the blood vessel wall (“atherosclerosis” “plaque”) -> narrowing or hardening of the arteries -> occurs over a prolonged period of time -> can impede blood flow -> pieces of tissue can fall off (“plaque rupture”) blocking the blood vessel or initiating a clot Coronary artery Narrowing of the arteries Plaque rupture & clot formation
  37. 37. Atherosclerosis (Plaque growth) Threshold where more serious manifestations like heart attacks or strokes begin to occur Time Threshold where manifestations like chest pain or temporary loss of vision begin to occur
  38. 38. The Greenland Inuit (“Eskimo”) Much lower than expected rate of death from heart attack 100 80 60 40 20 0 Expected Seen
  39. 39. How could this be? -> The Inuit diet?? • Ate lots of seal meat, whale meat, whale blubber, fish • -> Very high intake of omega-3 fats 16 Marine omega-3 intake (g/day) 12 100 x difference in intake! 8 4 0 Greenland Inuit Average UK adult
  40. 40. Prospective study People enter study when they are healthy/disease free Take information about diet and lifestyle; Take blood etc. Follow up over many years (10, 20, 30 ….) Measure disease outcome (e.g. how many have heart attacks or strokes, how many die from heart disease) Relate the disease outcome back to the earlier diet etc.
  41. 41. Two different prospective studies from the US Likelihood of fatal heart disease Likelihood of sudden death 100 100 80 80 60 60 40 40 20 20 0 0 Low High Omega-3 Intake From Diet Low High Omega-3 in Blood
  42. 42. EPA and DHA intake and future heart disease : a study from the US 1.0 0.8 0.6 Total CHD (P < 0.001) Fatal CHD (P = 0.01) Non-fatal MI (P = 0.003) 0.4 0.2 0 Lowest Highest Quintile of EPA+DHA intake Hu et al. (2002) J. Am. Med. Assoc. 287, 1815-1821
  43. 43. Relative risk of sudden death EPA+ DHA in blood and future sudden death : a study from the US Adjusted for age & smoking 1 0.8 Also adjusted for BMI, diabetes, hypertension, hypercholesterolemia, alcohol, exercise & family history of MI 0.6 0.4 0.2 0 1 2 3 Quartile of blood EPA+DHA 4 Albert et al. (2002) New Engl J Med 346, 1113-1118
  44. 44. How can this be? -> Risk factors
  45. 45. Primary Risk Factors Hypertension Hyperlipidaemia Smoking Cardiovascular Disease Family Medical History of CVD Lack of exercise Maleness Other genetics Bad diet Low birth weight Infections Obesity Diabetes Inflammation Homocysteinaemia Secondary Risk Factors
  46. 46. Primary Risk Factors Hypertension Hyperlipidaemia Smoking Cardiovascular Disease Family Medical History of CVD Lack of exercise Maleness Other genetics Bad diet Low birth weight Infections Obesity Diabetes Inflammation Homocysteinaemia Secondary Risk Factors
  47. 47. Higher omega-3 intake Time Atherosclerosis (Plaque growth)
  48. 48. What about people who already have heart or cardiovascular disease?? • Can study effect of omega3 given as supplements just like you would study a drug: randomised, placebocontrolled trial • Several large studies have been done tracking patients over several years • Death in patients who survived a previous heart attack Likelihood of death from heart disease over 3.5 years 100 80 60 40 20 0 Control group Omega-3 group
  49. 49. Illness and death outcomes With oral omega-3 Time
  50. 50. Arch. Int. Med. (2005) 165, 725-730 Considered: 97 intervention trials with lipid lowering strategies (incl. EPA+DHA) and with follow-up of at least 6 months (for EPA+DHA considered 14 studies) N = 10138 in control group; 10122 in w-3 PUFA group Findings for w-3 PUFA: Risk of cardiac mortality = 0.68 (P < 0.001) of mortality = 0.77 (P = 0.01)
  51. 51. Conclusion “statins and w-3 fatty acids are the most favourable lipid lowering interventions with reduced risks of overall and cardiac mortality”
  52. 52. How can this be? -> Probably not about the same risk factors as before because they relate to building up the plaque – here we are seeing an effect in people who already have plaques
  53. 53. Inflammation causes plaque rupture Omega-3 are anti-inflammatory -> Maybe omega-3 reduce deaths in at risk patients by decreasing the likelihood that plaques will rupture (i.e. increasing plaque stability) Rupture and subsequent clot formation Inflammatory activity in the vessel wall Thinning of protective cap
  54. 54. We wished to study the effects of omega-3 on plaque stability in humans • Needed a source of plaques -> there is a surgical procedure for removal of plaques from the carotid artery • Needed to be able to give patients omega-3 for a period of time before collecting the plaques -> waiting time for surgery is (was) many weeksmonths • Two randomised controlled trials of omega-3 in these patients
  55. 55. Difference from control group in: Unstable plaques 0 -10 -20 -30 -40 -50 -60 One key marker of plaque inflammation
  56. 56. Our results may explain how omega-3 stop people from having heart attacks and how they stop people from dying
  57. 57. => A higher EPA+DHA intake and status is protective against CVD risk and against CVD mortality
  58. 58. Omega-3 Index = EPA + DHA as a % of all fatty acids in red blood cell membranes
  59. 59. Inflammation has two phases: initiation and resolution Initiation phase Resolution phase TIME
  60. 60. EPA and DHA are precursors of pro-resolving lipid mediators
  61. 61. To sum up …..
  62. 62. EPA and DHA are important in: - cell membrane structure & function - brain and visual development - maintenance of cognitive and neurological function (during development & with aging) - regulation of - blood pressure - platelet function, thrombosis, fibrinolysis - blood triglyceride concentrations - vascular function - cardiac rhythm - inflammation - immune response - bone health - insulin sensitivity
  63. 63. EPA and DHA are vital throughout the life course
  64. 64. Key points to discuss … • • • • • What are “omega-3”? Where do you get them from? Why are they good for you? How much do you need? How do you know if you get enough?
  65. 65. Recommendations for fat and fatty acid intakes for adults in the UK       Total fat intake should not exceed 35% of dietary energy Average contribution of energy from saturated fatty acids should be < 10% Average contribution of energy from polyunsaturated fatty acids should be 6 to 10% (linoleic [18:2w-6] at least 1% and a-linolenic [18:3w-3] at least 0.2%) Trans fatty acids should NOT provide > 2% of energy Trans fatty acid intake should be decreased Marine w-3 fatty acid [EPA+DHA] intake should be at least 450 mg/day
  66. 66. EPA & DHA : how much do you need? • The UK Government says all adults need at least 0.45 g EPA+DHA per day to maintain health -> this is probably an underestimate • Most adults in the UK probably consume less than 0.1 g per day and many will consume less than onetenth of what is recommended! • Intake can be increased by eating more seafood, especially oily fish, or by taking fish oil type supplements
  67. 67. EPA & DHA : how do you know if you get enough • The amount of EPA and DHA in the blood increases when more is eaten in the diet • Therefore blood tests can be used to monitor intake and changes in intake and to provide an increased assurance of receiving the health benefit
  68. 68. Thank you!
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