Proven and Proposed Cardiovascular Benefits of Soyfoods Mark Messina, PhD, MS Soy Nutrition Institute Loma Linda University Nutrition Matters, Inc. markjohnmessina@gmail.com Alpro Foundation 20 years symposium 1
1000 80 20 60 40 40 60 20 80 100 0 Reduction (%) in CHD Mortality in Eastern Finland (1972 2012) Men (aged 30-59) Women (aged 30-59) 72 77 82 87 92 97 02 07 12 Jousilahti et al. BMJ. 2016; 352: i721 Years 1000 80 20 60 40 40 60 20 80 100 0 Reduction (%) in CHD Mortality in Eastern Finland (1972 2012) Men (aged 30-59) Women (aged 30-59) 72 77 82 87 92 97 02 07 12 Jousilahti et al. BMJ. 2016; 352: i721 Years Alpro Foundation 20 years symposium 2
Change in Risk Factors Accounts Two thirds to 100% of the Decreased CHD Mortality in Eastern Finland Measure Men Women 1972 2012 1972 2012 Smoking prevalence (%) 53 29 11 19 Cholesterol (mmol/l) 6.6 5.4 6.7 5.3 Systolic blood pressure (mmhg) 147 136 149 129 Smoking: Men, 45% ; Women, 72% Cholesterol: Men, 21% ; Women, 21% Blood pressure: Men, 8% ; Women, 13% Jousilahti et al. BMJ. 2016; 352: i721 Homocysteine Impaired endothelial function (FMD) Insulin resistance LDL- Oxidation Hypertension Inflammation (CRP) Lipid abnormalities LDL-C HDL-C TG Arterial stiffness Platelet aggregation Alpro Foundation 20 years symposium 3
Proven and Proposed Cardiovascular Benefits of Soyfoods Effect of soy on: 1. LDL-Cholesterol 2. Blood pressure 3. Inflammation 4. Endothelial function 5. Insulin resistance 6. CVD events Traditional Asian Soyfoods Unfermented Fermented Edamame Tofu Miso Natto Soy milk Tempeh Rarely used in clinical trials Alpro Foundation 20 years symposium 4
Soy protein products Isolate: ~90% protein Concentrate: ~70% protein Flour: ~50% protein Routinely used in clinical trials Isoflavones OH R 1 R2 Found primarily in soybeans 7 A 5 O 1 C 4 O 2 B OH Alpro Foundation 20 years symposium 5
Soybean Isoflavone Aglycones OH 7 A O 1 C 2 Phytoestrogens R 1 5 R2 4 O B OH % of Isoflavone R 1 R 2 total Genistein H OH 50 Daidzein H H 40 Glycitein OCH 3 H 10 Genistein Estradiol Isoflavones OH R 1 7 A 5 R2 O 1 C 4 O 2 B OH Found primarily in soybeans Phytoestrogens but different from estrogen Sometimes effects opposite to estrogen Sometimes no effects in estrogen-sensitive tissues Estrogen-independent effects Alpro Foundation 20 years symposium 6
Macronutrient Composition vs. Macronutrient (% calories) Composition of Soybeans in Comparison to Common Beans Macronutrient Soybeans Common beans Carbohydrate 27* 70 Protein 33 27 Fat 40 3 *Mostly oligosaccharides (poorly digestible); Capable of functioning as prebiotics AJCN 70: 439S, 1999 Alpro Foundation 20 years symposium 7
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. 2004 52, 5322; 57: 11174, 2009 The Controversy over Dietary Fat & Coronary Heart Disease Alpro Foundation 20 years symposium 8
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 Refined carbohydrates Carbohydrates, whole grains Monounsaturated fat Polyunsaturated fat Coronary heart disease risk Based on 127,536 study participants who were followed for up to 30 years J Am Coll Cardiol 66: 1538, 2015 Alpro Foundation 20 years symposium 9
Effects of Replacing 5% of Calories from Saturated Fat with 5% of Calories from: Coronary heart Nutrient disease risk Refined carbohydrates 2%22 * Carbohydrates, whole grains Monounsaturated fat Polyunsaturated fat Based on 127,536 study participants who were followed for up to 30 years J Am Coll Cardiol 66: 1538, 2015 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 J Am Coll Cardiol 66: 1538, 2015 Alpro Foundation 20 years symposium 10
Proven and Proposed Cardiovascular Benefits of Soyfoods Effect of soy on: 1. LDL-Cholesterol 2. Blood pressure 3. Inflammation 4. Endothelial function 5. Insulin resistance 6. CVD events Lancet 2: 693, 1968 Alpro Foundation 20 years symposium 11
Effects of Soy Oil Supplementation (85 g/d) on Cholesterol (mg/dl) in Men with CHD 300 280 260 240 Soy oil Ordinary diet 220 200 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 American Journal of Clinical Nutrition 20: 198, 1967 Alpro Foundation 20 years symposium 12
Effects of Isolated Soy Protein on Serum Cholesterol in Six Healthy Men 300 250 mg/dl 200 150 100 50 Soybean protein 0 AJCN 20: 198, 1967 0 4 8 16 20 24 28 32 36 Weeks on study BJN 114: 831-843, 2015 Alpro Foundation 20 years symposium 13
Soy products & Serum Lipids: A Metaanalysis of 50 Randomized Controlled Trials Product or group Subjects (n) Percent LDL Percent TG Percent HDL Cont. Soy All 1 1687 1679 4.83 4.92 1.40 Sub-analysis At risk 2 32 studies Healthy 18 studies W. soy 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, 831-843, 2015 Soy products & Serum Lipids: A Metaanalysis of 50 Randomized Controlled Trials Product or group Subjects (n) Percent LDL Percent TG Percent HDL Cont. Soy All 1 1687 1679 4.83 4.92 1.40 Sub-analysis At risk 2 32 studies 7.47 3.91 1.15 Healthy 18 studies 2.96 5.13 1.96 W. soy 3 12 studies 11.06 1.03 1.06 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, 831-843, 2015 Alpro Foundation 20 years symposium 14
Proven and Proposed Cardiovascular Benefits of Soyfoods Effect of soy on: 1. LDL-Cholesterol 2. Blood pressure 3. Inflammation 4. Endothelial function 5. Insulin resistance 6. CVD events JAMC 173: 486, 2005 Alpro Foundation 20 years symposium 15
BJN 106: 317, 2011 Effects of Soy on Blood Pressure: Meta analysis of 27 Clinical Trials* Blood pressure mmhg 95% CI Systolic -2.21-4.10, -0.33 Diastolic -1.44-2.56, -0.31 Blinded trials (n=15) Systolic -2.90-5.49, -0.31 Diastolic -1.93-3.53, -0.34 *Secondary endpoint in most trials BJN 106: 317, 2011 Alpro Foundation 20 years symposium 16
Inflammation CRP TNF- IL-6 LTC4 Etc. Alpro Foundation 20 years symposium 17
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 2.2 7-0.02-0.26, 0.22 >2.2 7-0.70-1.17, -0.23 Differences between groups statistically significant *Includes soy protein & isoflavones. Menopause 18: 1256, 2011 Alpro Foundation 20 years symposium 18
Proven and Proposed Cardiovascular Benefits of Soyfoods Effect of soy on: 1. LDL-Cholesterol 2. Blood pressure 3. Inflammation 4. Endothelial function 5. Insulin resistance 6. CVD events J Hypertension 32:2355, 2014 Alpro Foundation 20 years symposium 19
Effects of Isoflavones on FMD 1 in PostM Women: Meta analysis Results Studies (N) WMD 2 P value All studies 9 525 1.75 0.0002 Impaired endothelium (baseline FMD <5.2%) 5 233 Healthy endothelium (baseline FMD 5.2%) 4 292 1 Flow mediated dilation 2 Weighted mean difference. AJCN 91: 480, 2010 Effects of Isoflavones on FMD 1 in PostM Women: Meta analysis Results Studies (N) WMD 2 P value All studies 9 525 1.75 0.0002 Impaired endothelium (baseline FMD <5.2%) 5 233 2.22 0.0001 Healthy endothelium (baseline FMD 5.2%) 4 292 0.24 0.87 1 Flow mediated dilation 2 Weighted mean difference. AJCN 91: 480, 2010 Alpro Foundation 20 years symposium 20
Proven and Proposed Cardiovascular Benefits of Soyfoods Effect of soy on: 1. LDL-Cholesterol 2. Blood pressure 3. Inflammation 4. Endothelial function 5. Insulin resistance 6. CVD events Alpro Foundation 20 years symposium 21
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 *1) Resistance to insulin-mediated glucose disposal 2) Hyperinsulinemia 3) Glucose intolerance 4) plasma triglycerides 5) HDL 6) Blood pressure Liu et al. Maturitas 97: 44, 2017 Alpro Foundation 20 years symposium 22
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 1 629-6.35-10.79, -1.93 Fasting insulin 2 591-1.92-3.04, -0.79 Insulin resistance 3 591-0.74-1.21, -0.28 1 mg/dl 2 uiu/ml 3 HOMA-IR Liu et al. Maturitas 97: 44, 2017 Six of seven studies involved Italian women Alpro Foundation 20 years symposium 23
Homocysteine Impaired endothelial function (FMD) Insulin resistance Hypertension Inflammation (CRP) Lipid abnormalities LDL-C HDL-C TG LDL- Oxidation Arterial stiffness Platelet aggregation Eur J Prev Cardiol 2017 Alpro Foundation 20 years symposium 24
Eur J Prev Cardiol 2017 10 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 0.83 0.75, 0.93 CHD 0.82 0.68, 0.99 Stroke 0.83 0.72, 0.95 Yan et al. Eur J Prev Cardiol 2017 Alpro Foundation 20 years symposium 25
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 16 7 13 4 7 9 0.84 0.74 0.77 0.98 0.91 0.83 0.75, 0.94 0.58, 0.95 0.67, 0.90 0.89, 1.08 0.79, 1.05 0.69, 0.99 Model 2: Sociodemographics + CVD risk factors. Model 3: Model 2 + diet 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) Alpro Foundation 20 years symposium 26
Proven and Proposed Cardiovascular Benefits of Soyfoods Summary: Inflammation & endothelial function: ~50 mg/d isoflavones (~2 servings) Gender and health status may be important considerations Epidemiologic studies may underestimate benefit (insufficient intake) Portfolio diet: comprehensive approach that dramatically lowers blood cholesterol Metabolism 51: 1596, 2002 Alpro Foundation 20 years symposium 27
15 5-5 -15-25 -35 Percent Reduction in LDL Cholesterol in 13 Hypercholesterolemic Men and Women Consuming the Portfolio Diet Metabolism 51: 1596, 2002 * * * -1 0 1 2 3 4 Weeks on study * Components of the Portfolio Diet Almonds Low saturated fat Soluble fiber Soyfoods Phytosterols Fruits/vegetables High quality protein Favorable fatty acid profile Protein directly LDL-cholesterol Alpro Foundation 20 years symposium 28
Thank you for your attention markjohnmessina@gmail.com Alpro Foundation 20 years symposium 29