The cardioprotective diet: carbohydrate vs fat and the ketogenic diet

Transcription

1 The cardioprotective diet: carbohydrate vs fat and the ketogenic diet Professor Derick Raal FCP(SA), FRCP, FRCPC, Cert Endo, MMED, PHD Head, Division of Endocrinology & Metabolism Director, Carbohydrate and Lipid Metabolism Research Unit University of the Witwatersrand

2 Lipoprotein metabolism TRIGLYCERIDE Energy Storage Energy Production Steroid Synthesis CHOLESTEROL Cell Membranes Bile Acids

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4 Hypertension Smoking Atherosclerosis Obesity Diabetes mellitus DYSLIPIDAEMIA

5 Cardiovascular Risk Factors a changing landscape! Smoking Hypertension Hypercholesterolaemia CARDIOMETABOLIC DISEASE Obesity Metabolic syndrome Type 2 diabetes 1950s -1990s 1990s to 2000s

6 Two Faces of Atherosclerosis Familial Hypercholesterolaemia Single gene defect Incidence 1: Metabolic Syndrome Commonest cause of atherosclerosis worldwide Incidence 1:4

7 Cholesterol, particularly LDL- cholesterol is the pivotal risk factor for atherosclerosis

8 In the absence of a hypercholesterolaemia (raised LDL-cholesterol or remnants) it is virtually impossible to cause atherosclerosis in an experimental model

9 Framingham heart study MR FIT study 4 16 CHD risk ratio CHD mortality rate per Plasma cholesterol (mmol/l) Plasma cholesterol (mmol/l)

10 INTERHEART: Nine modifiable risk factors predict 90% of acute MI N = (262 sites across 52 countries) LDL/HDL Current smoking Diabetes Hypertension Abdominal obesity 2.57 Psychosocial Fruit & veg daily Exercise Alcohol intake Odds Ratio Salim Yusuf Lancet 2004;364:

11 Proportional reduction in event rate (SE) Relation between proportional reduction in incidence of major CAD and vascular events and mean absolute reduction in LDL cholesterol at 1 year 50% 40% 30% 20% 10% Major coronary events N= subjects from 26 statin trials For every 1 mmol/l reduction in LDL cholesterol there is : a) a % reduction in major CAD or vascular events b) a 12% reduction in overall mortality 0% -10% 50% 40% 30% 20% 10% Major vascular events CTT Collaborators Lancet 2005;366: ; n=90000 CTT Collaborators Lancet 2010;376: ; n= % -10%

12 CHD deaths/1000/annum Are carbohydrates the cause of atherosclerosis? Prevalence % Serum cholesterol (mmol/l) 0 Rose G, Br Med J 1981;282:

13 Increased Energy Density of Food Standard food portions have increased over the last 20 years 20 years ago Today 210 calories 610 calories 500 calories 850 calories 333 calories 590 calories

14 Kcal per day U.S. trends in per capita calories from beverages Children Milk Sugar-sweetened beverages Juices Adults Brownell, N Engl J Med 2009;361:

15 Usual intake of added sugars (in teaspoons) Age (years Males 9-13 Males Males 19 Females 9-13 Females Females 19 All persons 1 Mean Circulation 2009;120:

16 The effects of high intake of refined carbohydrates on lipid metabolism Increased refined carbohydrate intake results in increased TG Production Remnant Cholesterol LPL ApoB Large LDL LDL-C High Low Non-HDL-C HDL HL TG Renal clearance shdl CETP Large VLDL CE LPL Remnants LPL/HL slow TG Small LDL HL TG Very small LDL TRL-C, apob, ApoC3, Small LDL-C and LDL-P ApoB ApoE ApoB ApoE ApoC-III ApoC-III Triglyceride-rich lipoprotein Cholesterol Non-HDL-C ApoB ApoC-III LDL-C ApoB ApoC-III Cholesterol Triglycerides Davidson M. Eur Heart J 2018;39:620-22

17 Ketogenic diet Carbohydrates 2 5% Proteins 8 25% Fat 70 90%

18 The ketogenic diet Initially described over 100 years ago for the treatment of epilepsy as fasting/ketosis has seizure suppressing effects Gasior M, et al. Behav Pharmacol 2006;17:

19 The Ketogenic diet Encourage intake of: Beef/pork/poultry Fish Eggs Cheeses Full cream milk/yogurt Eggs Coconut oil Limit Grains and grain products rice./wheat/rye/oats barley/quinoa/cereal pasta/pizza Starchy vegetables /tubers potatoes/corn/peas High carb fruits/dried fruits bananas/apples/oranges Low fat dairy products Sugar Alcohol Abbasi J. JAMA 2018;319:

20 A high-fat ketogenic diet causes the body to switch from burning carbohydrates to burning fat Benefits Ketosis has a hunger-suppressing effect No significant decline in metabolic rate Initial diuretic like effect with rapid water weight loss Improves glycaemia/insulin sensitivity Risks/ Side effects Ketosis or keto-flu light-headedness/dizziness fatigue/poor sleep constipation Ketotic breath Hypokalemia Gout Renal stones Decreased Increase in LDL-C ( with saturated fats) Abbasi J. JAMA 2018;319:

21 DIETFITS randomized clinical trial: Effect of low-fat vs low-carbohydrate on 12-month weight loss in overweight adults 12 month study in 609 participants Weight change at 12 months -5.3 kg for the low-fat diet vs -6.0 kg for the low carbohydrate diet No significant difference in weight change between a healthy low-fat diet versus a healthy low carbohydrate diet Calorie restriction is most important determinant Gardner CD et al. JAMA 2018;319(7):667-79

22 Hazard ratio U-shaped association between percentage of energy from carbohydrate and all-cause mortality in the ARIC and PURE cohort studies ARIC PURE 95% CI 95% CI Energy from carbohydrate (%) Seidelmann. Lancet Public Health Aug 16, 2018

23 Serum cholesterol ng/100 ml CHD deaths per 100 Ecological relations of saturated fat with cholesterol levels and CHD death T G V K M D Z C r = Saturated F.A % calories B S U W N E G V K M C D B Z % Calories, Saturated fatty acids S U W r = 0.84 N E B Belgrade Faculty C Crevalcore D Dalmatia E East Finland C Corfu K Crete N Zutphen M Montegiorgio S Slavonia U US Railroad V Velika Krsna W West Finland Z Zrenjanin Keys et al. The Lancet Nov 1957

24 Replacement of saturated fat with other types of fat or carbohydrates Isocaloric substitution of SFA by equivalent energy from Trans fat (2%) 5 MUFA (5%) -15 PUFA (5%) -25 Carbohydrates from refined starches/sugars (5%) 1 Carbohydrates from whole grains (%) Changes in risk (%) Sacks et al. Circulation 2017 Jul 18;136(3):e1-e23

25 Effects of dietary fat and carbohydrates on blood LDL-C triglycerides, and HDL-C (mmol/l) in metaregression analysis LDL-Cholesterol Triglycerides HDL-Cholesterol Sat to Poly Sat to Mono Sat to Carb Sat to Poly Sat to Mono Sat to Carb Sat to Poly Sat to Mono Sat to Carb Sacks et al. Circulation 2017 Jul 18;136(3):e1-e23

26 Significant reduction in CHD from analysis of core trials replacing saturated with polyunsaturated fat Sub-groups Cases (n) 99 (95% CI) % Weight Dayton (0.57, 1.12) Oslo (0.55, 0.92) MRC (0l.62, 1.07) Finnish (0.46, 0.72) Overall I 2 = 20.3%, P = (0.62, 0.81) RR (95% CI) Sacks et al. Circulation 2017 Jul 18;136(3):e1-e23

27 PERIMED STUDY: Features of the Med diet Olive oil as main culinary fat - unrestricted intake Abundant vegetable products - Cereals (bread, pasta and rice) - Fresh vegetables and fruits - Legumes - Tree nuts - Aromatic herbs and spices Frequent intake of fish and shellfish Moderate consumption of wine with meals - Meat and animal products Low intake of milk and milk products and simple sugars

28 PREDIMED STUDY: Nutrient composition of the diet in the treatment group Energy restricted Mediterranean diet Nutrients Calories Total fat Saturated fatty acids Monounsaturated fatty acids Polyunsaturated fatty acids Cholesterol Protein Carbohydrate Dietary fibre Sodium chloride Calcium Alcohol Recommended intake Reduction of 600 kcal/day ( 30% of energy from usual intake) 35-40% of energy 8-10% of energy Up to 20% of energy Up to 10% of energy < 300 mg/day 20% of energy 40-45% of energy (low glycaemic index) g/day 100 mmol/l/day ( 2.4 g sodium or 6 g of salt) mg/day up to 1 glass of wine for men and ½ for women

29 Cumulative incidence PREDIMED Study Primary end point (acute myocardial infarction, stroke, or death from cardiovascular causes) Med diet, EVOO: HR 0.69 (95% CI, ) Med diet, nuts: HR 0.72 (95% CI, ) No. at risk Control diet Med diet, EVOO Med diet, nuts Years Control diet Med diet, EVOO Med diet, nuts EVOO = extra virgin olive oil Estruch R et al. N Engl J Med June 2018

30 Total mortality PREDIMED Study Total mortality Med diet, EVOO: HR 0.90 (95% CI, ) Med diet, nuts: HR 1.12 (95% CI, ) No. at risk Control diet Med diet, EVOO Med diet, nuts Med diet, nuts Years Control diet Med diet, EVOO EVOO = extra virgin olive oil Estruch R et al. N Engl J Med June 2018

31 Number of double bonds Plasma lipidomic profiles and cardiovascular events in a randomized intervention with the Mediterranean diet Triacylglycerols Polyunsaturated fats Low Risk HR for CHD for 1 SD of a 1-year change in lipid concentration 1.4 p value Saturated fats High Risk > < < < < <0.9 <0.8 >0.05 <0.05 <0.01 < Number of carbon atoms Am J Clin Nutr 2017;106:973 83

32 Lifestyle interventions for the prevention and treatment of coronary disease Unsaturated Fat Mediterranean Diet Vegetables, extra virgin olive oil, nuts, oily fish Moderate intake of cheese & yoghurt Low in sugar & refined carbohydrates Regular physical activity (walking 22 minutes/day) Stress reduction (eg. meditation, Yoga) Smoking cessation Hypertension Suboptimal omega 3 Too much omega 6 Insulin Resistance and/or Systemic Inflammation Type 2 diabetes Excess fructose + refined carbohydrates Other Factors Atherogenic Dyslipidaemia Malhotra A et al. Brit J Sports Med August 2017, Vol 51 No 15

33 Meta-analysis of associations of Omega-3 fatty acids and cardiovascular risk No. of events (%) Source Coronary heart disease Nonfatal myocardial infarction Coronary heart disease death Any Treatment 1121 (29) 1301 (3.3) 2085 (7.9) Treatment 1155 (3.0) 1394 (3.6) 3188 (8.2) Rate Ratios (CI) 0.97 ( ) 0.93 ( ) 0.96 ( ) P=0.12 Favours treatment Favours control Stroke Ischaemic Haemorrhagic Unclassified/other Any 573 (1.9) 117 (0.4) 142 (0.4) 870 (2.2) 554 (1.8) 109 (0.4) 135 (0.3) 843 (2.2) 1.03 ( ) 1.07 ( ) 1.05 ( ) 1.03 ( ) P=0.60 Revascularisation Coronary 3040 (9.3) 3044 (9.3) 1.00 ( ) Noncoronary Any 305 (2.7) 3290 (10.0) 330(2.9) 3313 (10.2) 0.92 ( ) 0.99 ( ) p=0.60 Any major vascular event 5830 (15.2) 6071 (15.6) 0.97 ( ) P= Rate ratio Aung T et al. JAMA Cardiology 2018;3(3):225-34

34 Patients with event (%) The ASCEND STUDY: Effect of n-3 fatty acid supplements on major cardiovascular events First serious vascular event Ratio ratio, 0.97 (95% CI, ) P=0.55 Placebo 70 Fatty acids Years of follow-up Ascend Study Collaborative Group. N Engl J Med, online Aug 2018

35 Omega-3 fatty acids in cardiovascular prevention

36 Evidence for cardiovascular health impact of foods review Summary of heart-harmful and heart-healthy foods/diets Evidence of harm; limit or avoid? Inconclusive evidence; for harm or benefit Evidence of benefit: recommended Coconut oil and palm oil are high in saturated fatty acids and raise cholesterol Eggs have a serum cholesterol-raising effect Juicing of fruits/ vegetables with pulp removal increases caloric concentration Southern diets (added fats and oils, fried foods, eggs, organ and processed meats. sugarsweetened drinks) Sunflower oil and other liquid vegetable oils High-dose antioxidant supplements Juicing of fruits/ vegetables without pulp removal Gluten-containing foods (for people without gluten-related disease) Extra-virgin olive oil reduces some CVD outcomes when consumed in moderate quantities Blueberries and strawberries (>3 servings/week) induce protective antioxidants 30 g serving of nuts/day. Portion control necessary to avoid weight gain. Green leafy vegetables have significant cardioprotective properties when consumed daily Plant-based proteins are significantly more hearthealthy compared to animal products Freeman AM et al. J Am Coll Cardiol 2017;60(9):

37 75 th Percentile CAC score 75 th Percentile of CAC score in women (A) and men (B) across populations A B 700 US women (UIC) 1800 US men (MAHI) US women (MAHI) US men (UIC)) 600 US white women (MESA) Korean women 1600 US white men (MESA) US black men (MESA) US black women (MESA) 1400 US Hispanic men (MESA) 500 European women (HNR) US Hispanic women (MESA) 1400 European men (HNR) Korean men 400 US Chinese women (MESA) Japanese women 1000 US Chinese men (MESA) Japanese men 300 Tsimane women 800 Tsimane men Age (years) Tsimane 200 Tsimane Age (years) Kaplan H, et al. Lancet 2017;389:

38 Proportion of individuals (%) CAC scores by age for US MESA and Tsimane populations % 1% 92% 75% 6% 83% 55% MESA CAC >100 17% 2% Tsimane CAC = 0 MESA CAC = 0 Tsimane CAC > Age group (years) 72% 36% 34% 8% 8% 65% 51% 19% Kaplan H et al. Lancet 2017;389:

39 CAD in the Tsimane Tribe Anthropometry Proportion of men (%) Mean weight (kg) Height (cm) BMI (kg/m 2 ) Body fat (%) Physiology Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (beats/min) Lipids Total cholesterol (mmol/l) LDL-C (mmol/l) HDL-C (mmol/l) Triglycerides (mmol/l) ApoA (mg/dl) ApoB (mg/dl) ESR (mm/h) hs-crp (mg/dl) Total (n=705) 50 (0.5) 58.4 (9.9) (7.8) 24.1 (3.5) 22.1 (8.2) (12.5) 73.4 (10.0) 65.9 (9.3) 3.9 (0.8) 2.4 (0.7) 1.0 (0.2) 1.2 (0.5) (84.9) 97.2 (41.5) 22.0 (13.9) 3.7 (3.2) Kaplan H, et al Lancet 2017;389:

40 Tsiname Tribe Diet 72% Carbohydrate 14% Protein 14% Fat Martin. Matern Child Nutr 2012;8:404-18