Omega 3overview-professorphilipcalder-121230045819-phpapp01

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Omega 3overview-professorphilipcalder-121230045819-phpapp01

  1. 1. Omega-3 Fatty Acids :Naming, sources, intakes, metabolism and health benefits Philip Calder Professor of Nutritional Immunology University of Southampton
  2. 2. This lecture will coverFatty acid structure, nomenclature, sources, andintakesMetabolic relationship between α -linolenic acid andlong chain omega-3 fatty acidsOmega-3 fatty acids and cardiovascular healthOmega-3 fatty acids and visual and braindevelopmentRecommendations for omega-3 fatty acid intake
  3. 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. 4. Fatty acid structureH3C COOH
  5. 5. Fatty acid structure and nomenclature H3C COOH 18:0 Stearic acid H3C 9 COOH 18:1ω-9 Oleic acid H3C COOH 18:2ω-6 Linoleic acid 6 H3C 3 COOH 18:3ω-3 α-Linolenic acidMammals cannot insert double bonds in here Omega = ω - = n-
  6. 6. Saturated Monounsaturated PolyunsaturatedSunflower oil Corn oil Soybean oil Olive oil Pig fat Beef fat Butter 0 20 40 60 80 100
  7. 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. 8. Omega-3 PUFAsH3C COOH α -Linolenic acid (18:3ω -3)H3C COOH EPA (20:5ω -3) COOHH3C DPA (22:5ω -3)H3C COOH DHA (22:6ω -3)
  9. 9. These have different dietary sources and their intake differs markedly
  10. 10. α -Linolenic acid (18:3ω -3)Found in green plant tissuesFound in some vegetable oils (e.g. soybean,rapeseed)Found in some nuts (e.g. walnut)Found in linseed (flaxseed) and linseed oilContributes 85 to 95% of ω -3 PUFA intake inUK adults (ca. 2.1 g/day in males; 1.5 g/day infemales)
  11. 11. Long chain ω -3 PUFAs (EPA, DPA, DHA)- oily fish are the only rich sourceof preformed long chain ω -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 ω -3 PUFAintake is < 0.2 g/day (200 mg/day)- long chain ω -3 PUFAs are foundin fish oils
  12. 12. Long chain ω -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. 13. α -linolenic acid is metabolicallyrelated 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. 14. α -Linolenic acid This pathway does not work very well in humans EPA DHA
  15. 15. Key points (so far)ω -6 and ω -3 PUFAs are distinct fatty acidfamiliesMost ω -3 PUFA in the diet is in the form of α -linolenic acidLong chain ω -3 PUFAs are found in oily fish(fish oil capsules)Average intake of long chain ω -3 PUFAs is <0.2 g/dayα -Linolenic acid is poorly converted to longchain ω -3 PUFAs in humans
  16. 16. Omega-3 PUFAs and human health
  17. 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. 18. Many studies report an inverse correlation between fish consumption or ω-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 ω -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 ω -3 PUFA ↓ MI mortalityAlbert et al. 2002 Whole blood ω -3 PUFA ↓ sudden deathHu et al. 2002 Fish and ω -3 PUFA intake ↓ CHD mortalityHu et al. 2002 Fish and ω -3 PUFA intake ↓ non-fatal MITavani et al. 2001 Fish and ω -3 PUFA intake ↓ non-fatal MIGualler et al. 2003 Adipose tissue DHA ↓ first MILemaitre et al. 2003 Plasma EPA and DHA ↓ CHD mortality
  19. 19. Prospective: Long chain ω -3 PUFA status and sudden deathRelative 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
  20. 20. Risk factors for atherosclerosis LDL-cholesterol Elevated blood lipids Hypertension Triglycerides Endothelial dysfunction Inflammation
  21. 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. 22. Relationship between dietary long chainω -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. 23. Endothelium dependent coronary vasodilatation in patients with CHD before and after fish oil (4 months) 300Increase in coronary blood flow (%) 200 CHD patients after fish oil Controls 100 CHD patients before fish oil 0 Acetylcholine
  24. 24. Fish oil and an inflammatory marker (sVCAM-1)Healthy subjects aged > Pre55 y PostSupplemented diet with 1000a moderate amount of sVCAM-1 (ng/ml) 800 *fish oil (= 1.2 g 600EPA+DHA/day) for 12 400weeks 200Plasma soluble VCAM-1 0concentrations Placebo FOmeasured Miles et al. (2001) Clinical Science 100, 91-100
  25. 25. Risk factors for atherosclerosis Elevated blood TAG Hypertension Endothelial dysfunction Inflammation N-3 PUFA
  26. 26. Secondary prevention: DART1015 men aged < 70 y who hadhad a MI Oily fishAdvised to eat oily fish or take 100 No advicefish oil capsules vs. no advice % SurviviorsCardiovascular events and 95mortality followed for 2 yearsRelative risk death 0.77 90Relative risk IHD death 0.84 85 0 200 400 600 800 Time (days) Burr et al. (1989) Lancet ii, 757-761
  27. 27. Secondary prevention: GISSI Study2836 men who had had Relative risk in fish oil groupa MI within the last 3months assigned to fish All fatal events 0.80oil (0.85 g LC ω -3 CV death 0.70PUFA/day) vs. placebo Coronary death 0.65Follow up for two years Sudden death 0.55356 deaths and non-fatalCV events in fish oilgroup vs. 414 in placebogroup GISSI Prevenzione Investigators (1999) Lancet 354, 447-455
  28. 28. There are also non-cardiovascular actions of long chain ω -3 PUFAs
  29. 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. 30. 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
  31. 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 ω -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. 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. 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 for3 monthsThen all onto EPA + DHA for a further 3 months Richardson & Montgomery (2005) Pediatrics 115, 1360-1366
  34. 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. 35. HyperactivityOmega 3 Placebo Placebo then Omega-3 63 61 59 57 55 Baseline 3 mo 6 mo
  36. 36. 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
  37. 37. Long chain ω -3 PUFAs promote- optimal brain growth- optimal visual and neural function
  38. 38. 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
  39. 39. Summary: Long chain ω -3 PUFAsLong chain ω -3 PUFAs have a number of physiologicaleffectsThrough their physiological effects they alter risk of a -wide range of human diseasesLowered disease risk occurs through plausiblebiological mechanismsThere are newly emerging mechanisms of action oflong chain ω -3 PUFAs in some conditionsLong chain ω -3 PUFAs exert health benefits rightthrough the life cycle (womb to tomb!)
  40. 40. Long chain ω -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. 41. What about α -linolenic acid?
  42. 42. Consensus statementSanderson et al. (2002) Brit. J. Nutr. 88, 573-579“The studies …. suggested little, if any, benefitof α -linolenic acid, relative to linoleic acid, onrisk factors for cardiovascular disease ….”
  43. 43. However, α -linolenic acid may exert health benefits through conversion to longer chain derivativesBut, this may require high intakes of α -linolenic acid

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