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Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
Omega 3 overview - professor philip calder
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Omega 3 overview - professor philip calder

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  • 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 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
  • 3. Fats in the diet CH2.O.CO.R1 CH2.O.CO.R1R2.CO.OCH R2.CO.OCH CH2.O.CO.R3 CH2.O.POO.O.Base Triglycerides Phospholipids Also sphingolipids cholesterol and cholesterol esters
  • 4. Fatty acid structureH3C COOH
  • 5. Fatty acid structure and nomenclature H3C COOH 18:0 Stearic acid H3C 9 COOH 18:1w-9 Oleic acid H3C COOH 18:2w-6 Linoleic acid 6 H3C 3 COOH 18:3w-3 a-Linolenic acidMammals cannot insert double bonds in here Omega = w- = n-
  • 6. Saturated Monounsaturated PolyunsaturatedSunflower oil Corn oil Soybean oil Olive oil Pig fat Beef fat Butter 0 20 40 60 80 100
  • 7. Latest fatty acid intake data for adults in UK (g/day) Males FemalesTotal fat 87 (36% energy) 61 (35% energy)Saturated 33 23Trans 3 2Monounsaturated 29 20Omega-6 PUFA 13 9Omega-3 PUFA 2.3 1.7
  • 8. Omega-3 PUFAsH3C COOH a-Linolenic acid (18:3w-3)H3C COOH EPA (20:5w-3)H3C COOH DPA (22:5w-3)H3C COOH DHA (22:6w-3)
  • 9. These have different dietary sources and their intake differs markedly
  • 10. 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)
  • 11. Long chain w-3 PUFAs (EPA, DPA, DHA)- oily fish are the only rich sourceof preformed long chain w-3PUFAs- adults in the UK consume onaverage 1/3 of a portion of oilyfish per week (53 g/week)- fish consumers consume 1.3portions of oily fish per week(about 195 g/week)- average long chain w-3 PUFAintake is < 0.2 g/day (200 mg/day)- long chain w-3 PUFAs are foundin fish oils
  • 12. Long chain w-3 PUFA content of fish EPA DPA DHA Total (g/100 g food) g/portionCod 0.08 0.01 0.16 0.30Haddock 0.05 0.01 0.10 0.19Herring 0.51 0.11 0.69 1.56Mackerel 0.71 0.12 1.10 3.09Salmon 0.55 0.14 0.86 1.55Crab 0.47 0.08 0.45 0.85Prawns 0.06 0.01 0.04 0.06
  • 13. a-linolenic acid is metabolicallyrelated to long chain w-3 PUFAs a-Linolenic acid (18:3w-3) Delta 6-desaturase 18:4w-3 Elongase 20:4w-3 Delta 5-desaturase EPA (20:5w-3) DPA (22:5w-3) DHA (22:6w-3)
  • 14. a-Linolenic acid This pathway does not work very well in humans EPA DHA
  • 15. 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
  • 16. Omega-3 PUFAs and human health
  • 17. From a survey of distribution of diseases in Greenland EskimosDisease Expected ActualMyocardial infarction 40 3Psoriasis 40 2Bronchial asthma 25 1Diabetes 9 1Multiple sclerosis 2 0 Kromann & Green (1980) Acta Med. Scand. 208, 410-406
  • 18. Many studies report an inverse correlation between fish consumption or w-3 PUFA status and CHDKromhout et al. 1985 Fish  CVD mortalityShekelle et al. 1985 Fish  CVD mortalityNorelle et al. 1986 Fish  CVD mortalityDolecek et al. 1992 Dietary w-3 PUFA  CVD mortalityFeskens et al. 1993 Fish  CVD mortalitySiscovik et al. 1995 Fish  CVD mortalityKromhout et al. 1995 Fish  CVD mortalityDaviglus et al. 1997 Fish  CVD mortalityAlbert et al. 1998 Fish  sudden cardiac deathPedersen et al. 2000 Adipose tissue w-3 PUFA  MI mortalityAlbert et al. 2002 Whole blood w-3 PUFA  sudden deathHu et al. 2002 Fish and w-3 PUFA intake  CHD mortalityHu et al. 2002 Fish and w-3 PUFA intake  non-fatal MITavani et al. 2001 Fish and w-3 PUFA intake  non-fatal MIGualler et al. 2003 Adipose tissue DHA  first MILemaitre et al. 2003 Plasma EPA and DHA  CHD mortality
  • 19. Prospective: Long chain w-3 PUFA status and sudden deathRelative risk of sudden death Adjusted for age & smoking 1 Also adjusted for BMI, 0.8 diabetes, hypertension, hypercholesterolemia, alcohol, 0.6 exercise & family history of MI 0.4 0.2 0 1 2 3 4 Quartile of blood w-3 PUFAs Albert et al. (2002) New Engl J Med 346, 1113-1118
  • 20. Risk factors for atherosclerosis LDL-cholesterol Elevated blood lipids Hypertension Triglycerides Endothelial dysfunction Inflammation
  • 21. Meta-analysis of trials of fish oil and blood pressure Geleijnse et al. (2002) J. Hypertens. 20, 1493-149936 controlled trials reviewed incl. 22 double blindFish 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 subjectsEffects greater in hypertensive subjectsConclusion “increased intake of fish oil may lower BP,especially in older and hypertensive subjects”
  • 22. Relationship between dietary long chainw-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
  • 23. Endothelium dependent coronary vasodilatation inpatients with CHD before and after fish oil (4 months) 300 200 CHD patients after fish oil Controls 100 CHD patients before fish oil 0 Acetylcholine
  • 24. Fish oil and an inflammatory marker (sVCAM-1) Healthy subjects aged > Pre 55 y Post Supplemented diet with 1000 sVCAM-1 (ng/ml) a moderate amount of 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
  • 25. Risk factors for atherosclerosis Elevated blood TAG Hypertension Endothelial dysfunction Inflammation N-3 PUFA
  • 26. Secondary prevention: DART 1015 men aged < 70 y Oily fish who had had a MI 100 No advice % Surviviors Advised to eat oily fish 95 or take fish oil capsules vs. no advice 90 Cardiovascular events and mortality followed 85 for 2 years 0 200 400 600 800 Time (days) Relative risk death 0.77 Relative risk IHD death Burr et al. (1989) Lancet ii, 757-761 0.84
  • 27. 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 w-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
  • 28. There are also non-cardiovascular actions of long chain w-3 PUFAs
  • 29. 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
  • 30. DHA status and infant mental development (1 year of age) 140 120 100 80 60 3 6 9 12 Infant red cell DHA (%)Gibson et al. (1997) Eur. J. Clin. Nutr. 51, 578-584
  • 31. Helland et al. (2003) Pediatrics 111, 39-44“Maternal supplementation with very long chain n-3 fatty acidsduring pregnancy and lactation augments childrens IQ at 4 years ofage”Placebo vs. 2.4 g long chain w-3 PUFAs/day (50:50 EPA & DHA)from week 18 of pregnancy until 3 months post partumKaufman Assessment Battery for Children performed at 4 years ofage - a measure of intelligence and achievement designed forchildren aged 2.5 to 12.5 yearsAt 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)
  • 32. 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 ADHDBurgess et al. (2000) Am. J. Clin. Nutr. 71, 327S-330S
  • 33. The Durham TrialA randomised controlled trial of fish oilsupplementation (vs. placebo) in children (5 –12 years old) with developmental co-ordinationdisorder (n = 117)Placebo vs. 550 mg EPA + 175 mg DHA/day for 3monthsThen all onto EPA + DHA for a further 3 months Richardson & Montgomery (2005) Pediatrics 115, 1360-1366
  • 34. Omega 3 Placebo Placebo then Omega-3120 105110 100100 9590 90 Baseline 3 mo 6 mo Baseline 3 mo 6 mo Reading age Spelling age
  • 35. HyperactivityOmega 3 Placebo Placebo then Omega-3 63 61 59 57 55 Baseline 3 mo 6 mo
  • 36. Long chain w-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
  • 37. Long chain w-3 PUFAs promote- optimal brain growth- optimal visual and neural function
  • 38. Long chain 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- psychiatric and neurological diseases of children and adults- neurodegenerative diseases of ageing- bone loss- some cancers
  • 39. 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!)
  • 40. Long chain w-3 PUFAsCurrent intakes vs. Recommendations (g/day)Current av. UK intake < 0.2ISSFAL 1999 0.65BNF 1999 1.0-1.4AHA 2003* 1.0AHA 2003** 2 to 4SACN/COT 2004 0.45 (minimum)*For patients with CHD**For patients with hypertriglyceridaemia
  • 41. What about a-linolenic acid?
  • 42. Consensus statementSanderson et al. (2002) Brit. J. Nutr. 88, 573-579“The studies …. suggested little, if any, benefitof a-linolenic acid, relative to linoleic acid, onrisk factors for cardiovascular disease ….”
  • 43. However, a-linolenic acid may exert health benefits through conversion to longer chain derivativesBut, this may require high intakes of a-linolenic acid

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