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* Fats & fatty acids

Risk factors for cardiovascular disease: Focus on Dietary Fats R. Uauy 2014. * Fats & fatty acids. The Lipid Hypothesis. Dietary fats and fatty acids Health effect of cis vs trans unsaturated fatty acids Quality of Dietary fat has a significant effect on CVDs

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* Fats & fatty acids

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  1. Risk factors for cardiovascular disease: Focus on Dietary Fats R. Uauy 2014 * Fats & fatty acids

  2. The Lipid Hypothesis • Dietary fats and fatty acids • Health effect of cis vs trans unsaturated fatty acids • Quality of Dietary fat has a significant effect on CVDs • Conclusions and Recommendations

  3. Total Fat – Ecological Data Seven Countries Study

  4. Associations Between the Percent of Calories Derived from Specific Foods and CHD Mortality in the 20 Countries Study* Food Source Correlation Coefficient† Butter 0.546 All dairy products 0.619 Eggs 0.592 Meats 0.561 Sugar and syrup 0.676 Grains, fruits, and vegetables -0.633 *1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD. New York, Raven, 1979. †All coefficients are significant at the P<0.05 level.

  5. Men Participating in the Ni-Hon-San Study* Residence Japan Hawaii California Age (years) 57 54 52 Weight (kg) 55 63 66 +20% Serum cholesterol (mg/dL) 181 218 228 +26% Dietary fat (% of calories) 15 33 38 +253% Dietary protein (%) 14 17 16 Dietary carbohydrate (%) 63 46 44 -30% Alcohol (%) 9 4 3 -67% 5-yr CHD mortality rate 1.3 2.2 3.7 +285% (per 1000 persons) *Data from Kato et al., Am J Epidemiol 97:372, 1973. CHD, coronary heart disease.

  6. Epidemiologic Studies* • Populations on diets high in total fat, saturated and trans fats, cholesterol, and sugar have high age-adjusted CHD death rates as well as more obesity, hyperlipidemia, and diabetes • The converse is also true *Results from Seven Countries, 18 countries, 20 countries, 40 countries, and Ni-Hon-San Studies

  7. Total Fat and CHD - Cohort Evidence 28.3% 32.6% 35.6% 38.7% 44.0% 77,878 women in the Nurses Health Study, 1980-2002, Oh et al, AJE 2005

  8. Simopoulos AP. Am J Clin Nutr. 1999;70:560-9S. Changes in dietary fat sources during Evolution Industrial Agricultural Hunter-Gatherer

  9. Saturated Fatty Acid Stearic acid 18:0 melting point 70 o C Unsaturated Fatty Acid(cis) Oleic acid c 18:1 n-9 melting point 16 o C Unsaturated Fatty Acid (trans) Elaidic acid t 18:1 n-9 melting point 43 o C

  10. Dietary fatty acids There are 3 types of dietary fatty acids Saturated fatty acids (no double bond) COOH CH3 Mono-unsaturated fatty acids (one double bond) CH3 COOH Polyunsaturated fatty acids (two or more double bonds) COOH CH3

  11. w- COOH Stearic acid (C18:0 ) CH3 n- COOH COOH Elaidic acid (C18:1 n-9 trans) Oleic acid (C18:1 n-9) Essential Fats COOH COOH a - Linolenic acid (C18:3n-3) Linoleic Acid (18:2 n-6) COOH COOH Docosahexaenoic acid DHA(C22:6 n-3) Arachidonic acid AA(C20:4 n-6)

  12. Quality of Fats in Modern Nutrition • Saturated fats (C12:0, C14:0, C16:0, C18:0) • Trans fatty acids (hydrogenated fats) • Monounsaturated fatty acids (18:1) • Sats/MUFA/PUFA • Cholesterol • Essential fatty acids w -3 and w -6 • Long Chain PUFAs (AA, EPA, DHA) • Energy Density of diet (fats and carbohydrates)

  13. n - 6 / n - 3 LCPUFA ratio modulates inflammation and thrombosis Linoleate Arachidonic Eicosapentaenoic Linolenate n-6 PUFA n-3 PUFA Membrane Phospholipids Arachidonic ac / Eicosapentaenoic ac Leukotrienes Prostacyclins Thromboxanes Prostaglandin Inflammation Inmune response Thrombosis Bronchoconstriction Vascular reactivity Bronchoconstriction Chemotaxis Citokines Inflammation

  14. Fatty acids % total n-3 PUFA n-6 PUFA Monounsaturated Saturated

  15. Diet and Fats Influence Risk of Coronary Heart Disease • Effects on Lipoprotein and Cholesterol metabolism receptor systems, gene expression and regulation (LDL, HDL, Lp(a), TG) : TRANS FATS, SATS, PUFAs n-3 and n-6, • Prostanoids:(Eicosanoids and Docosanoids) related functions Inflammation/cytokines depend on: PUFAs n-3 & n-6, • Blood pressure. SODIUM POTASSIUM & PUFAs n-3 & n-6, • Thrombosis and thrombolytic mechanisms PUFAs n-3 & n-6 • Oxidative stress and re-perfusion injury PUFAs n-3 & n-6 • Endothelial function & adhesion molecules PUFAs n-3 & n-6 • Cardiac Rhythm (arrhythmias) PUFAs n-3 • Insulin Sensitivity PUFAs n-3 & n-6; Trans

  16. WHO TRS 916 Report : strength of evidence on nutritional factors and risk of developing CVD Evidence Decreased risk No relationship Increased risk Convincing Regular physical activity Vitamin E Myristic and palmitic acids Linoleic acid 18:2n-6Supplements 14:0 16:0 Fish and fish oils Trans fatty acids (EPA &DHA) High sodium intake Vegetables & fruits (including Overweight berries) High alcohol intake Potassium Low to moderate alcohol intake Probableα-Linolenic acid18:3 n-3 Stearic acidDietary cholesterol Oleic acid 18:1 n-918:0 Unfiltered boiled coffee Fibre Nuts (unsalted) Plant sterols/stanols Folate Possible Flavonoids Fats rich in lauric acid Soy products Impaired fetal nutrition Beta-carotene supplement TRS 916 WHO 2003

  17. WHO TRS 916 Report : risk of developing CVD Evidence Decreased risk No relationship Increased risk Convincing Regular physical activity Myristic and palmitic acids Linoleic acid 18:2n-6 Vitamin E 14:0 16:0 Fish and fish oils (EPA &DHA) Supplements Trans fatty acids Vegetables & fruits High sodium intake (berries) Overweight Potassium Low to moderate High alcohol intake alcohol intake Probable α-Linolenic acid 18:3 n-3 Stearic acid Dietary cholesterol Oleic acid 18:1 n-9 18:0 Unfiltered boiled coffee Fibre Nuts (unsalted) Plant sterols/stanols Folate PossibleFlavonoids Fats rich in lauric acid Soy productsRestricted fetal growth Beta-carotene supplement TRS 916 WHO 2003

  18. Observed and Predicted Declines in Coronary Mortality in Eastern Finland, Men Population dietary changes explain much of the reduction in heart disease mortality in Finland. % Decline in mortality 0 -10 -20 Observed Predicted Cholesterol Blood pressure Smoking -30 -40 -50 -60 72 76 80 84 88 92 74 78 82 86 90 Vartiainen, Puska et al BMJ 1995

  19. UK White Paper 04 Dept Health

  20. Causal relationship web Physical Age Activity Diabetes DIET Fat & Salt - LDL HDL CHD Chol BMI Diastolic BP Smoking A B marks a postulated influence from A to B

  21. Saturated or Trans fatty acids Diet effects on LDL receptor activity High saturated or trans fat diets Healthy fats

  22. The Lipid Hypothesis • Dietary fats and fatty acids • Health effect of cis vs trans unsaturated fatty acids • Quality of Dietary fat has a significant effect on CVDs • Conclusions and Recommendations

  23. Associations Between the Percent of Calories Derived from Specific Foods and CHD Mortality in the 20 Countries Study* Food Source Correlation Coefficient† Butter 0.546 All dairy products 0.619 Eggs 0.592 Meats 0.561 Sugar and syrup 0.676 Grains, fruits, and vegetables -0.633 *1973 data, all subjects. From Stamler J: Population studies. In Levy R: Nutrition, Lipids, and CHD. New York, Raven, 1979. †All coefficients are significant at the P<0.05 level.

  24. Total Fat – Ecological Data Seven Countries Study

  25. Men Participating in the Ni-Hon-San Study* Residence Japan Hawaii California Age (years) 57 54 52 Weight (kg) 55 63 66 +20% Serum cholesterol (mg/dL) 181 218 228 +26% Dietary fat (% of calories) 15 33 38 +253% Dietary protein (%) 14 17 16 Dietary carbohydrate (%) 63 46 44 -30% Alcohol (%) 9 4 3 -67% 5-yr CHD mortality rate 1.3 2.2 3.7 +285% (per 1000 persons) *Data from Kato et al., Am J Epidemiol 97:372, 1973. CHD, coronary heart disease.

  26. Epidemiologic Studies* • Populations on diets high in total fat, saturated and trans fats, cholesterol, and sugar have high age-adjusted CHD death rates as well as more obesity, hyperlipidemia, and diabetes • The converse is also true *Results from Seven Countries, 18 countries, 20 countries, 40 countries, and Ni-Hon-San Studies

  27. Total Fat and CHD - Cohort Evidence 28.3% 32.6% 35.6% 38.7% 44.0% 77,878 women in the Nurses Health Study, 1980-2002, Oh et al, AJE 2005

  28. Reduction in the Consumption of Trans Fatty Acids and the Risk of CHD in The Netherlands-Zutphen TFA 2.4%  CHD 23% Oomen CM, et al. Lancet 2001; 357: 746-51

  29. Health benefits of polyunsaturated fatty acids

  30. Dietary Intervention Studies • Significant benefit in CHD risk reduction and mortality • in primary and secondary prevention noted with: • Decreasing saturated fat and increasing • polyunsaturated fat (Finnish Mental Hospital, LA-VA, • and Oslo Diet Heart Studies) • Increasing fish or fish oil intake (DART, GISSI) • Increasing alpha linolenic acid intake (Lyon Diet • Heart Study) • Dietary Counseling can work, but it must be intensive and sustained Circulation 59:1,1979; Acta Med Scand 466:1,1966; Circulation 40:1,1969; Lancet 2:757,1989, Lancet 343:1454,1994; Lancet 354:447,1999.

  31. SAFA MUFA PUFA Dietary fatty acids and blood cholesterol TC=1.2(2S'-P) S'=C12+C14+C16 change in TC (mg/dL) change in fat intake (en%) Source: Keys et al. Metabolism, 1965

  32. 0.02 0.01 0.01 0 0 -0.01 -0.01 changes per en% -0.02 -0.02 mmol/ L change per % energy -0.03 -0.03 -0.04 -0.04 -0.05 monounsaturated FAs polyunsaturated FAs carbohydrates trans FAs Effect on lipoproteins of replacing saturated fat with specific fatty acids or carbohydrates LDL-chol HDL-chol TC/HDL-chol ratio Source: Mensink et al Am J Clin Nutr 2003

  33. In summary, our results provide evidence that high intake of trans-fat increases the risk of CHD in women, the effects are stronger among younger women. Our findings also support a benefit of polyunsaturated fat intake, at least up to approximately 7 percent of energy, in preventing CHD, particularly among women who are younger or overweight. Am J Epidemiol 2005;161:672–679

  34. Nurses’ Health Study: changes in risk of coronary heart disease associated with iso-energetic diet substitutions Source: Hu et al, JAMA, 2002 Decreased Risk Increased Risk

  35. 0.4 Nestel Mensink Judd LDL Lichtenstein 0.2 Zock Judd Change in (mmol/L) 0 HDL -0.2 0 2 4 6 8 10 12 Adverse effects of trans FAs on blood cholesterol % of energy as trans fatty acids (C18:1 trans) Zock et al Am J Clin Nutr, 1995

  36. Changes in serum lipids (mmol/L by replacing 1% E individual fatty ac for carbohydrate based on meta-analysis [EFSA J (2004) 81, 1-49]

  37. Relative risk was after adjusting for dietary fiber intake. Saturated Fat Intake Quintiles (% of calories) Alpha Linolenic Fatty Acid Intake Quintiles (% of calories) 1.72 0.41 a 1% increase in calories from linolenic acid (2-3 grams/day). Ascherio et al BMJ 1996

  38. ORs for Risk of Nonfatal Acute MI by tercile of Linolenic & Trans FA content of Adipose Tissue in Costa Rica Odds Ratio Adipose Tissue trans fatty acids Adipose Tissue n-3 alpha-linolenic acids A Baylin et al Circulation 107:1586-91 2003

  39. Small reduction in blood cholesterol  significant reduction in CHD A reduction in total blood cholesterol level by each percent leads to a reduction of : Data from a meta analysis including 10 prospective cohort studies, 3 large international trial and 28 intervention studies Law et al, British Medical Journal 1994

  40. Fat quality versus quantity USA 2005 dietary recommendations: “…increasing consensus that it is the quality rather than the quantity of fat that counts….” Limiting calories is more important to health than cutting fats

  41. D. Mozaffarian JAMA, 2006 Vol 296: 1885-97

  42. D. Mozaffarian JAMA, 2006 Vol 296: 1885-97

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