Traditional Asian Soyfoods. Proven and Proposed Cardiovascular Benefits of Soyfoods. Reduction (%) in CHD Mortality in Eastern Finland ( )

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1 Proven and Proposed Cardiovascular Benefits of Soyfoods Mark Messina, PhD, MS Soy Nutrition Institute Loma Linda University Nutrition Matters, Inc Reduction (%) in CHD Mortality in Eastern Finland ( ) Men (aged 30-59) Women (aged 30-59) 45% 21% Years Jousilahti et al. BMJ. 2016; 352: i721 10% Homocysteine Hypertension Inflammation (CRP) Lipid abnormalities LDL-C HDL-C TG Impaired endothelial function (FMD) LDL- Oxidation Arterial stiffness Platelet aggregation Proven and Proposed Cardiovascular Benefits of Soyfoods Effect of soy on: 1. LDL-Cholesterol 2. Blood pressure 3. Inflammation 4. Endothelial function 5. Arterial stiffness 6. Insulin resistance 7. CVD events Traditional Asian Soyfoods Unfermented Edamame Soy milk Tofu Fermented Miso Tempeh Rarely used in clinical trials Natto 1

2 Soy protein products Soybean Isoflavone Aglycones OH O 1 7 A C 2 Phytoestrogens Isolate: ~90% protein Concentrate: ~70% protein Flour: ~50% protein Routinely used in clinical trials R 1 5 R2 4 O OH % of Isoflavone R 1 R 2 total Genistein H OH 50 Daidzein H H 40 Glycitein OCH 3 H 10 B Genistein Estradiol Isoflavones OH O A C R 1 5 R2 4 B O OH Found primarily in soybeans Phytoestrogens but different from estrogen Sometimes effects opposite to estrogen Macronutrient Composition vs. Sometimes no effects in estrogen-sensitive tissues Estrogen-independent effects Macronutrient (% calories) Composition of Soybeans in Comparison to Common Beans Macronutrient Soybeans Common beans Carbohydrate 27 * 70 Protein Fat 40 3 *Mostly oligosaccharides (poorly digestible); Capable of functioning as prebiotics AJCN 70: 439S, 1999 Fatty Acid Composition of Soybean Oil Fatty acid Percent Saturated 12 Monounsaturated 29 Omega-6 PUFA (LA)* 53 Omega-3 PUFA (ALA)* 6 *Essential fatty acids. LA, linoleic acid; ALA, -linolenic acid J. Agric. Food Chem , 5322; 57: 11174,

3 The Controversy over Dietary Fat & Coronary Heart Disease the macronutrient substituted J Am Coll Cardiol 66: 1538, 2015 for SFAs [saturated fatty acids] is critically important. Effects of Replacing 5% of Calories from Saturated Fat with 5% of Calories from: Nutrient Coronary heart disease risk Refined carbohydrates 2%22 * Carbohydrates, whole grains 9%2 * Monounsaturated fat 15% * Polyunsaturated fat 25% * Based on 127,536 study participants who were followed for up to 30 years. 7,667 cases of CHD identified J Am Coll Cardiol 66: 1538, 2015 Lancet 2: 693, 1968 Effects of Soy Oil Supplementation (85 g/d) on Cholesterol () in Men with CHD Soy oil Ordinary diet Lancet 2: 693, 1968 BL 6 mo 1 y 2 y 3 y 4 y 5 y 6 y Time points Soy oil: n=173, 175, 177, 166, 118, 89, 46, 10. Usual: n=171, 174, 170, 158, 127, 88, 41, 12 Health Claim 3

4 Effects of Isolated Soy Protein on Serum Cholesterol in Six Healthy Men American Journal of Clinical Nutrition 20: 198, Soybean protein 50 0 AJCN 20: 198, Weeks on study Soy products & Serum Lipids: A Metaanalysis of 50 Randomized Controlled Trials Product or group Subjects (n) LDL TG HDL Cont. Soy All Sub-analysis High risk 2 32 studies Healthy 18 studies Whole soyfoods 3 12 studies BJN 114: , 2015 LDL (-6.97%) & TG (-9.39%) more in non-casein/milk control trials (n=22) 1 All products and subjects 2 Elevated LDL, hypertensive or diabetic 3 Nuts, milk, oil, whole bean flour BJN. 114, , 2015 Soy products & Serum Lipids: A Metaanalysis of 50 Randomized Controlled Trials Product or group Subjects (n) LDL TG HDL Cont. Soy All Sub-analysis High risk 2 32 studies Healthy 18 studies Whole soyfoods 3 12 studies LDL (-6.97%) & TG (-9.39%) more in non-casein/milk control trials (n=22) 1 All products and subjects 2 Elevated LDL, hypertensive or diabetic 3 Nuts, milk, oil, whole bean flour BJN. 114, , 2015 Soy products & Serum Lipids: A Metaanalysis of 50 Randomized Controlled Trials Product or group Subjects (n) LDL TG HDL Cont. Soy All Sub-analysis High risk 2 32 studies Healthy 18 studies Whole soyfoods 3 12 studies LDL (-6.97%) & TG (-9.39%) more in non-casein/milk control trials (n=22) 1 All products and subjects 2 Elevated LDL, hypertensive or diabetic 3 Nuts, milk, oil, whole bean flour BJN. 114, ,

5 Combined Effects of Soy on LDL cholesterol (LDL C) and Risk of Coronary Heart Disease J Nutr 140: 2302S, 2010 Direct (Soy protein) Indirect (Displacement) 4% LDL-C 4% (in theory) 8-16% risk JAMC 173: 486, 2005 Effects of Milk (1 liter/day) on Blood Pressure (mmhg) in Hypertensive Patients over a Three Month Period Blood Cow s milk Soymilk pressure Initial Change Initial Change Systolic Diastolic Differences between groups statistically significant J. Nutr 132: 1900, 2002 BJN 106: 317,

6 Effects of Soy on Blood Pressure: Meta analysis of 27 Clinical Trials* Blood pressure mmhg 95% CI Systolic , Diastolic , Blinded trials (n=15) Systolic , Diastolic , *Secondary endpoint in most trials BJN 106: 317, 2011 Soy, Blood Pressure and Cardiovascular Disease J Hypertens Suppl 23, S3 S8., mm Hg SBP 1.5 mm Hg DBP 10% stroke 5% CHD 4% mortality Decrease (mmhg) in Blood Pressure in Response to Soy Protein in Postmenopausal Women (N=1,551) Food & Function 8: 2663, 2017 Group Trials SPB DPB All trials * 0.71* Soy protein <25 g/day * 0.47* 25 g/day * 1.63* *Statistically significant Decrease (mmhg) in Blood Pressure in Response to Soy Protein in Postmenopausal Women (N=1,551) Group Trials SPB DPB All trials * 0.71* Control diet Dairy * 0.06 Non-dairy * 0.85* *Statistically significant 6

7 Inflammation CRP Markers TNF- IL-6 LTC4 Etc. Menopause 18: 1256, 2011 Effects of Soy* on Levels of C Reactive Protein (mg/l) in Postmenopausal Women: Meta analysis of Clinical Trials Baseline CRP No. of studies Change 95% CI , 0.22 > , J Hypertension 32:2355, 2014 Differences between groups statistically significant *Includes soy protein & isoflavones. Menopause 18: 1256, 2011 Effects of Isoflavones on FMD 1 in PostM Women: Meta analysis Results Studies (N) WMD 2 P value All studies Impaired endothelium (baseline FMD <5.2%) Healthy endothelium (baseline FMD 5.2%) European Heart J 27: 2588, Flow mediated dilation 2 Weighted mean difference. AJCN 91: 480,

8 The beneficial effect of soy intakes on arterial stiffness may partly explain why populations that consume high amounts of soy have a low incidence of heart disease. AJCN 93: 446, 2011 Link between Insulin Resistance and CHD Insulin resistance Inadequate insulin secretion Compensatory hyperinsulinemia Type 2 diabetes Syndrome X* ATVB 32: 1754, 2012 Coronary heart disease Liu et al. Maturitas 97: 44, 2017 *1) Resistance to insulin-mediated glucose disposal 2) Hyperinsulinemia 3) Glucose intolerance 4) plasma triglycerides 5) HDL 6) Blood pressure Effects of Genistein on Glucose, Insulin and Insulin Resistance in Postmenopausal Women: Meta analysis of 7 Clinical Studies Measure N Mean diff. 95% CI Fasting glucose , Fasting insulin , Insulin resistance , Six of seven studies involved Italian women 1 2 uiu/ml 3 HOMA-IR Liu et al. Maturitas 97: 44,

9 Homocysteine Impaired endothelial function (FMD) Hypertension LDL- Oxidation PLoS Med 13, e , 2017 most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity. 102 trials, including 239 diet arms and 4,220 adults PLoS Med 13, e , 2016 Inflammation (CRP) Lipid abnormalities LDL-C HDL-C TG Arterial stiffness Platelet aggregation Eur J Prev Cardiol 24: 735, 2017 Eur J Prev Cardiol 24: 735, cohort, 7 case-control studies China (6), Japan (5), USA (2), Holland (1), Norway (1), Italy (1), Singapore (1) 17,265 total CVD events 10,806 heart attacks 6,265 strokes Standardized Relative Risk for the Association between Soy Intake and Risk of Cardiovascular Disease, Coronary Heart Disease and Stroke Disease SRR 95% CI CVD , 0.93 CHD , 0.99 Stroke , 0.95 Yan et al. Eur J Prev Cardiol 2017 Stratified Analyses for the Association between Soy Intake & Risk of CVD Disease No. SSR 95% CI Adjustments Model 2 Model 3 Study location Asia Not Asian Gender Male Female , , , , , , 0.99 Model 2: Sociodemographics + CVD risk factors. Model 3: Model 2 + diet 9

10 Proven and Proposed Cardiovascular Benefits of Soyfoods Summary: May decrease CVD risk through multiple mechanisms Protective components include fat, protein and isoflavones LDL-C and BP: ~25 g/d protein (~2-3 servings) Proven and Proposed Cardiovascular Benefits of Soyfoods Summary: CRP, FMD, arterial stiffness: ~50 mg/d isoflavones (~2 servings) Gender and health status may be important considerations Epidemiologic studies may underestimate benefit (insufficient intake) 15 Percent Reduction in LDL Cholesterol in 13 Hypercholesterolemic Men and Women Consuming the Portfolio Diet 5 Portfolio diet: comprehensive approach that dramatically lowers blood cholesterol Metabolism 51: 1596, * * -25 * * Weeks on study Metabolism 51: 1596, 2002 Components of the Portfolio Diet Almonds Low saturated fat Soluble fiber Soyfoods Phytosterols Fruits/vegetables High quality protein High PUFA Low saturated fat Protein directly LDL-cholesterol Thank you for your attention markjohnmessina@gmail.com 10

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