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

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Presentation on theme: "* Fats & fatty acids Risk factors for cardiovascular disease: Focus on Dietary Fats R. Uauy 2014."— Presentation transcript:

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

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3 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

4 Seven Countries Study Total Fat – Ecological Data

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

6 Age (years) Weight (kg) % Serum cholesterol (mg/dL) % Dietary fat (% of calories) % Dietary protein (%) Dietary carbohydrate (%) % Alcohol (%) % 5-yr CHD mortality rate % (per 1000 persons) *Data from Kato et al., Am J Epidemiol 97:372, CHD, coronary heart disease. Residence Japan HawaiiCalifornia Men Participating in the Ni-Hon-San Study*

7 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

8 77,878 women in the Nurses Health Study, , Oh et al, AJE 2005 Total Fat and CHD - Cohort Evidence 28.3%32.6% 35.6% 38.7% 44.0%

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

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

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

12 Docosahexaenoic acid DHA (C22:6 n-3) Linoleic Acid (18:2 n-6) COOH Oleic acid (C18:1 n-9) Elaidic acid (C18:1 n-9 trans) COOH Arachidonic acid AA (C20:4 n-6)  - Linolenic acid (C18:3n-3) COOH Stearic acid (C18:0 ) CH 3  n- Essential Fats

13 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)

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

15 Saturated Monounsaturated n-6 PUFA Fatty acids % total n-3 PUFA

16 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

17 Evidence Decreased risk No relationshipIncreased risk Myristic and palmitic acids Convincing Regular physical activityVitamin E Myristic and palmitic acids Linoleic acid 18:2n-614:0 16:0 Linoleic acid 18:2n-6 Supplements 14:0 16:0 Fish and fish oils Trans fatty acids (EPA &DHA (EPA &DHA) High sodium intake Vegetables & fruits (including Overweight berries) High alcohol intake Potassium Low to moderate alcohol intake α-Linolenic acid18:3 n-3 Stearic acidDietary cholesterol Probable α-Linolenic acid 18:3 n-3 Stearic acid Dietary cholesterol Oleic acid 18:1 n-918:0 Oleic acid 18:1 n-918:0 Unfiltered boiled coffee Fibre Nuts (unsalted) Plant sterols/stanols Folate Fats rich in lauric acid Possible Flavonoids Fats rich in lauric acid Soy products Impaired fetal nutrition Beta-carotene supplement WHO TRS 916 Report : strength of evidence on nutritional factors and risk of developing CVD TRS 916 WHO 2003

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

19 Population dietary changes explain much of the reduction in heart disease mortality in Finland. Vartiainen, Puska et al BMJ 1995 Observed Predicted Cholesterol Blood pressure Smoking Observed and Predicted Declines in Coronary Mortality in Eastern Finland, Men % Decline in mortality

20 UK White Paper 04 Dept Health

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

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

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30 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

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

32 Seven Countries Study Total Fat – Ecological Data

33 Age (years) Weight (kg) % Serum cholesterol (mg/dL) % Dietary fat (% of calories) % Dietary protein (%) Dietary carbohydrate (%) % Alcohol (%) % 5-yr CHD mortality rate % (per 1000 persons) *Data from Kato et al., Am J Epidemiol 97:372, CHD, coronary heart disease. Residence Japan HawaiiCalifornia Men Participating in the Ni-Hon-San Study*

34 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

35 77,878 women in the Nurses Health Study, , Oh et al, AJE 2005 Total Fat and CHD - Cohort Evidence 28.3%32.6% 35.6% 38.7% 44.0%

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

37 Health benefits of polyunsaturated fatty acids

38 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.

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

40 LDL-cholHDL-chol mmol/ L change per % energy monounsaturated FAs polyunsaturated FAs carbohydrates trans FAs TC/HDL-chol ratio Source: Mensink et al Am J Clin Nutr changes per en% Effect on lipoproteins of replacing saturated fat with specific fatty acids or carbohydrates

41 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

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

43 Zock et al Am J Clin Nutr, 1995 % of energy as trans fatty acids (C18:1 trans) Change in (mmol/L) HDL LDL Zock Mensink Judd Nestel Judd Lichtenstein Adverse effects of trans FAs on blood cholesterol

44 44 Fatty acid (1% energy exchange) Total cholesterol LDL cholesterol HDL cholesterol Total:HDL cholesterol Lauric acid (12:0) Myristic acid (14:0) Palmitic acid (16: Stearic acid (18:0) Elaidic acid (18:1 trans) Oleic acid (18:1 cis) Linoleic acid) (18:2n-6) 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]

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

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

47 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 Small reduction in blood cholesterol  significant reduction in CHD Law et al, British Medical Journal 1994

48 “…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 USA 2005 dietary recommendations: Fat quality versus quantity

49 D. Mozaffarian JAMA, 2006 Vol 296:

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51 Overview of beneficial effects of PUFA Omega 6 (Linoleic acid) –Blood lipids: clearly protective Omega 3 (Linolenic acid) –Blood lipids: probably similar to linoleic acid –Other risk factors: mostly inconsistent Omega 3 (EPA/DHA) –Blood lipids: in high dose lowers TG, but LDL up –Other risk factors: blood pressure ? reduced thrombosis and likely improved endothelial relaxation, lowers inflammation and risk of fatal cardiac arrhythmias

52 Design: a follow-up study of 11 pooled American and European cohort studies including 344,696 persons; outcome CHD over a 4–10 yr FU, 5249 coronary events and 2155 coronary deaths occurred Results: For a 5%lower energy intake from SFAs and a concomitant higher energy intake from PUFAs risk of coronary events HR: 0.87 (95% CI: ); HR for coronary deaths 0.74 ( ). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from CHO there was a significant association with coronary events (HR 1.07; (CI: ); for coronary deaths 0.96 ( ). MUFA intake was not associated with CHD. Jakobsen et al Am J Clin Nutr 89:1–8 2009

53 coronary eventscoronary deaths Jakobsen et al Am J Clin Nutr 89:1– ( ) 0.74 ( )

54 coronary eventscoronary deaths Jakobsen et al Am J Clin Nutr 89:1–8 2009;. coronary eventscoronary deaths 1.07 ( ) 0.96 ( )

55 Coronary Heart Disease Stroke Total CVDs Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to coronary heart disease & stroke Am J Clin Nutr doi: /ajcn (0.96, 1.19)P = ( )P = ( )P = 0.11

56 We aimed to investigate the risk of myocardial infarction (MI) associated with a higher energy intake from carbohydrates and a concomitant lower energy intake from SFAs. Carbohydrates with different glycemic index (GI) values were also investigated. Design: Our prospective cohort study included 53,644 women and men free of MI at baseline. Conclusion: This study suggests that replacing SFAs with carbohydrates with low-GI values is associated with a lower risk of MI, whereas replacing SFAs with carbohydrates with high-GI values is associated with a higher risk of MI. Am J Clin Nutr 2010;91: 1764–8.

57 Pooled Analysis of 11 Major Cohort Studies Jakobsen et al, AJCN 2009 Total of 344,696 individuals with 5,249 CHD events. *p<0.05 SFA → PUFA SFA → Carb SFA → MUFA * *

58 Saturated Fat vs. CHO Quality Jakobsen et al, AJCN 2010 Risk of CHD among 53,644 adults followed for 12 years. *p<0.05 SFA → Low GI CHO SFA → Med GI CHO SFA → High GI CHO *

59 A More Complete Diet-Heart Paradigm

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61 Key messages for Health Professionals Strong Convincing Evidence that a diet low in saturate and trans fats, and high polyunsaturated fats lowers cholesterol and reduces risk of CVD Diet can reduce LDL - cholesterol up to 30 % Simple dietary changes can make a significant difference to the CVD risk Changes in Diet and Physical activity are the cornerstone of primary prevention of CVDs

62 Recommendations on PUFA and trans General international agreement on absolute levels. - Total PUFA: 4-15 en% (8-10 en% most common) - Linoleic acid n-6 :up to 14 en% (8 en% most common) - Linolenic acid n-3:0.2 to 1.0 en% - EPA+DHA : mg/day Trans fatty acids: as low as possible, lower than 1-2 % Some give recommendations for omega-6:omega-3 ratio, others do not. Most often not to exceed ~ 5:1 In many societies the intake of Omega 3 is lower and that of trans is higher than recommended

63 % Type of Fat Consumed on Bread in North Karelia, 1972 – 2000 (25–59-year-old) Year

64 Saturated Fat from Milk and Fat on Bread Saturated Fat from Milk and Fat on Bread gr/day Year North Karelia Kuopio province Southwest Finland Helsinki area

65 Butter & Margarine Consumption Finland 1979 – 01

66 Age-adjusted Mortality Rates of CHD in North Karelia and the all of Finland in males aged 35 – 64 years 1969 to Mortality per population Year North Karelia All Finland start of the North Karelia Project - 82 % - 75% extension of the Project nationally 6th ICPC, Iguassy Falls (3.)


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