Role of Dietary Fats and Cardiovascular Risk Julie Lovegrove Hugh Sinclair Unit of Human Nutrition & Institute for Cardiovascular and Metabolic Research University of Reading, UK Alpro Student Symposium 24 th October 2017 University of Reading 2014 www.reading.ac.uk
Leading cause of global deaths Heart & Circulatory Disorders WHO. Global Health Estimates: Deaths by Cause, Age, Sex and Country, 2000-2012. Geneva, WHO, 2014. 2
Dietary fat recommendations Nutrient Total fat < 33 % Saturated fat < 10 % UK (% total energy) Polyunsaturated fat 0.2% - 10% Monounsaturated fat 12% EPA/DHA > 0.45 g Trans fat < 2 % X X 1991 1994 currently assessing saturated fat guidance 3
SFA GUIDANCE MET BY ONLY 11% COUNTRIES ID = Indonesia; BE = Belgium; DK = Denmark; SI = Slovenia; AT = Austria; DE = Germany; CM = Cameroon; FR = France; RU = Russia; IE = Ireland; FI = Finland; NL = Netherlands; GR = Greece; NZ = New Zealand; CZ = Czech Republic; SK = Slovakia; AU = Australia; SE = Sweden; BG = Bulgaria; NO = Norway; ES = Spain; UK = United Kingdom; PL = Poland; SG = Singapore; US = United States; HU = Hungary; IT = Italy; CA = Canada; MY = Malaysia; MX = Mexico; GT = Guatemala; IL = Israel; PT = Portugal; ZA = South Africa; JP = Japan; HK = Hong Kong; IN = India; KP = South Korea; CN = China; BD =Bangladesh. Harika et al., Ann Nutr Metab. 2013;63;229 4
CONFUSION OVER SATURATES GUIDANCE 5
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Relative risk for coronary outcomes for SFA intake - Meta-analysis of prospective cohort studies Reduced risk higher intake Increased risk higher intake ++ corrected for lipid Chowdhury et al., Annals of Internal Medicine. 2014:160;398-406 7
Hierarchy of Scientific Evidence HIGH Level of evidence Meta-analysis Randomly Controlled Trials (RCTs) Prospective Cohort Trials Prevalence Studies Ecological (cross-cultural) Studies Evidence based medicine Epidemiology LOW Animal Studies 8
SFA reduction vs usual diet on CVD events - Meta-analysis of randomised control trials Reduced risk low SFA Increased risk low SFA Hooper et al. Cochrane Library. 2015, Issue 6 CD011737 9
Dietary manipulation is complex! 10
Saturation fat substitution with carbohydrates and unsaturated fat Saturated with polyunsaturated fat Saturated fat with carbohydrates 26% lower risk Reduced risk Increased risk Reduced risk Increased risk Substitution of saturated for polyunsaturated fats significantly reduces hazard ratios for coronary deaths Jakobson M et al. Am. J. Clin. Nutr. 2009:89;1425-32 11
Change in CHD associated with isocaloric substitution of dietary components Substitution of SFA Nurses Health Study (84,628) and Health Professionals Follow-up (42,908) 24-30 years of follow-up (FFQ every 4 years) Li et al. J Am Coll Cardiol 2015;66:1538 48 12
Sources of unsaturated fats Polyunsaturated fats cis PUFA cis n-3 PUFA (alpha linolenic acid) cis n-6 PUFA (linoleic acid) Long chain cis n-3 PUFA (eicosapentaenoic acid docosahexaenoic acid) 13
Sources of unsaturated fats Polyunsaturated fats cis PUFA cis n-6 PUFA (linoleic acid) 14
Linoleic acid associated with lower CHD 0.79 (0.71, 0.89) Favours Linoleic acid Farvid et al., Circulation. 2014:130;1568-78 15
Sources of unsaturated fats Polyunsaturated fats cis PUFA cis n-3 PUFA (alpha linolenic acid) 16
Alpha linolenic associated with lower risk CVD Dietary ALNA intake Biomarker ALNA intake Overall 0.86 (0.77, 0.97) 100 Pan et al., AJCN 2012;96:1262-73 Higher ALNA associated with a moderately lower risk CVD (1g/day increase in ALNA associated with 10% lower risk CAD death) 17
Sources of unsaturated fats Polyunsaturated fats cis PUFA Long chain cis n-3 PUFA (eicosapentaenoic acid docosahexaenoic acid) 18
Regular fish or LC n-3 PUFA reduces CVD Total mortality CVD ~20% reduction in relative risk CHD death CHD Mozzaffarian & Wu., JACC. 2011:58;2047-67 Reduced risk Increased risk 19
Sources of unsaturated fats Monounsaturated fats cis MUFA Oleic acid Oleic acid 20
Relative risk for coronary outcomes for MUFA intake - Meta-analysis of prospective cohort studies Reduced risk higher intake Increased risk higher intake ++ corrected for lipid Chowdhury et al., Annals of Internal Medicine. 2014:160;398-406 21
Pooled RR for combined CVD events (top vs bottom tertile) MUFA MUFA: 0.95 (0.89, 1.02) P = 0.14 MUFA:SFA ratio MUFA:SFA: 0.93 (0.86, 1.01) P = 0.07 Olive oil Olive oil: 0.72 (0.57, 0.91) P = 0.007 Oleic acid OVERALL Oleic acid: 0.87 (0.76, 1.00) P = 0.04 Overall: 0.91 (0.86, 0.96) P = 0.0001 Schwingshackl and Hoffmann Lipids in Health and Disease 2014, 13:154 22
Med diet & incidence of composite CVD endpoints Predimed study 7447 participants (288 events) 55 80 years 4 year follow-up Group: a. MD & virgin olive oil (1l/wk) b. MD & nuts (30g/d) c. Low fat diet No change in activity or weight Years Estruch R et al (2013) New Engl J Med 368, 1279-90 23
Sources of unsaturated fats Trans unsaturated fatty acids trans Industrial trans t-elaidic acid Ruminant trans t-vaccenic acid t-palmitoleic acid 24
Relative risk of CHD with trans fat intake Risk of CHD Risk of CHD Little impact on CHD risk at current mean UK dietary intakes BUT important to minimise TFA in food chain and monitor intake Trans fatty acid intake (g/day) UK Women (2017) (0.7 %E, 1.2 g/day) UK Men (2017) (0.7 %E, 1.6 g/day) SACN. Update on trans fatty acids report 2007 25
RR of total, industrial & ruminant TFA on mortality Total TFA Industrial TFA Ruminant TFA Trans fats are associated with all cause mortality, total CHD, and CHD mortality probably due to i-trans de Souza et al. BMJ 2015;101h;3978 26
Macronutrients & CVD mortality PURE study. 18 non-western countries (n=135,335 men and women. 7.4 yrs follow-up) No association between between macronutrients and CVD SFA (%E) MUFA (9%E) PUFA (%E) CARB (%E) <10%E 45-50%E Dehghan et al., PURE study. Lancet 29 Aug 2017 1-13 [online] 27
CVD Risk Factors Obesity Gender Raised LDL chol Genetic determination Raised blood pressure Ethnicity Raised triacylglycerol Age Diabetes Menopausal status Vascular function Inflammation DIET Smoking Alcohol Physical activity Non-modifiable Stress Modifiable Lifestyle 28
Blood Cholesterol Coronary Heart Disease LDL-cholesterol 29
MUFA & carbohydrate replacement of SFA - RCT SFA MUFA Carbohydrate 0,2 0,1 0 n = 543 6 month 0,1 0,2 0.05 0,3 0,4 0.001 0.000 LDL-C 0.003 TC:HDL-C Jebb et al, Am J Clin Nutr. 2010;92:748-58 30
MUFA & n-6 PUFA replacement of SFA - RCT 0,3 SFA rich diet MUFA rich diet SFA MUFA PUFA TC:HDL C change from baseline 0,2 0,1 0 0,1 0,2 *** ** ** *** n = 183 4 months 0,3 TC:HDL LDL:HDL Vafeiadou et al, Am J Clin Nutr 2015:102:40-80 31
Predicted change in plasma lipids with replacement of dietary carbohydrates Micha & Mozzaffarin. Lipids 2010:45;893-905. 32
Risks leading to death 33
MUFA & n-6 PUFA replacement of SFA - RCT SFA MUFA PUFA Absolute difference in mean night SBP (mmhg) 6,0 5,0 4,0 3,0 2,0 1,0 0,0 1,0 Appel L J et al. Hypertension 2006;47:296-308 2,0 3,0 * Overall time x treatment P=0.019 n = 183 4 months Vafeiadou et al, Am J Clin Nutr 2015:102:40-80 34
Importance of food based recommendations versus Nutrients Whole Foods 35
Impact of replacing 10% US dietary fat Mensink et al., Am J Clin Nutr 2003:1146;55. 36
Contribution of foods to SFA in UK diet Milk & milk products 24% Butter 6% NDNS (2016) 37
Effect of SFA food source on CVD risk Multi-ethnic Study of Atherosclerosis (MESA) 5209 45-84 Years Follow-up 2000-2010 MEAT FAT +5g/d +5% of energy +48% DAIRY FAT +26% CVD RISK +5g/d +5% of energy -21% -38% de Oliveira Otto et al., Am J Clin Nutr 2012;96:397 404. 38
RR of CVD for every 244g/d milk intake 1.01 (0.93, 1.10) / 244g/d Guo et al., Eur. J Epidemiol. 2017:32;269-287 39
RR of CVD for every 20 g/d of fermented dairy 0.97 (0.97, 0.99) / 244g/d Guo et al., Eur. J Epidemiol. 2017:32;269-287 40
Dairy potential mechanisms Potential mechanisms for dairy Blood pressure Bioactive Magnesium, peptides Potassium and Calcium Ma, K and Ca Bioactive peptides Peptides Minerals Regulation van Meijl et al. (2008) Nutr Res Rev; Turpeinen et al. (2004) Annals of Medicine FitzGerald et al. (2004) J Nutr;134:980S-988S. Arterial stiffness Similar to blood pressure? L-arganine precursor of nitric oxide? Similar to blood pressure? 41
Conclusions Replacement of SFA with PUFA reduces CHD mortality and risk factors Replacement of SFA with MUFA reduces CVD risk factors Increased LC n-3 PUFA associated with reduction in CHD mortality and CVD risk factors Benefit in mini-mising itfa intake for reduction in CHD risk Different fat-rich foods impacts on response to fats 42
ACKNOWLEDGEMENTS 43
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THANK YOU 45
LDL-chol after consumption of ~80 g/d fat (~36g/d SFA) as cheese or butter Cheese vs butter Hjerpsted et al. Am J Clin Nutr 2011;94:1479 84. 46
Dose response and time course for altering clinical events from fish and fish oil Mozaffarian D & Rimm EB. JAMA. 2006:296;1885-1899. 47