Soy Protein. Muscle health benefits: for Sports Nutrition Recovery and during aging. May 9, Mark Cope, PhD

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Soy Protein Muscle health benefits: for Sports Nutrition Recovery and during aging May 9, 2017 Mark Cope, PhD

Blending Proteins to Provide Better Muscle Health Importance of Muscle Health The Benefits of Soy Protein Hypothesis for Blending Proteins Pre-clinical Study Recovery and Muscle Synthesis in Active Adults Improved Muscle Synthesis and Reduced Muscle Breakdown in Older Adults Summary and Take Away Message

Why blend proteins? Combining unique attributes of soy & dairy proteins Beverages Made with Blends of Soy & Dairy Are Preferred for Taste Blending soy, casein, whey proteins may increase the anabolic window for increased muscle growth G. Paul: The Rationale for Consuming Protein Blends in Sports Nutrition. Journal of the American College of Nutrition, 2010 High Quality Protein Sources that Deliver Essential Amino Acids, including Leucine DuPont Sensory Research findings support flavor advantages of blending soy and dairy proteins. Of the top 7 scoring beverages, 6 were formulated with soy and dairy proteins.

Fractional Synthetic Rate (%/day) Pre-Clinical Animal Study Clin Nutr. 2013 Aug;32(4):585-91 Study Aim: What is the optimal protein blend that can stimulate muscle protein synthesis over a prolonged period of time compared to a single protein Blend 1 Blend 2 ab a Using proteins of varying digestion and absorption rates Whey, soy & casein Using an unexercised rat model of muscle protein synthesis Soy ab Whey b Time Blend 2 (25:25:50 soy:whey:caseinate) showed the greatest FSR & extended muscle synthesis in this combination

Study Design PRODUCTS Protein Blend (25% whey isolate, 25% soy isolate and 50% casein) Whey (100% whey isolate) Healthy, young adults (n=19) PRO (g) EAA (g) LEU (g) Blend 1 19.3±1.1 8.7±0.5 1.8±0.1 Whey 17.7±0.9 9.0±0.4 1.9±0.1 1 The PB was 50% sodium caseinate, 25% WPI, and 25% SPI Reidy, et al. J Nutr. 2013 Reidy et al. J Appl Physiol. 2014

Acute Study in Young Adults Soy-dairy blend extends muscle protein synthesis Whey rapidly increased BCAAs early, although dropped after 2 hours. Soy-dairy blend modestly elevates BCAAs early & maintains a steady level of BCAAs up to 4 hours. Only the soy-dairy blend maintained higher muscle protein synthesis during the last 2 hours measured. Soy-dairy blend vs. whey protein alone provides a prolonged delivery of amino acids to the muscles, making it optimal for consumption following resistance exercise Reidy et al., J Nutr. 2013. 143(4): 410-6

Acute Study in Young Adults Post-exercise muscle anabolism prolonged with soy-dairy blend + - Time Post-Ingestion (min) Net balance significantly more positive at 1 & 2 hrs post-ingestion compared to whey Net Balance = (Arterial Phe Venous Phe ) x Leg Blood Flow Reidy et al., J Appl Physiol. 2014. 116(11):1353-64

Extended Study in Young Adults Effect of soy-dairy blend supplementation on metabolic & muscle adaptations during resistance exercise training Double-blind, parallel-design, randomized clinical trial Study Aims To determine the effect of soy-dairy protein blend supplementation during resistance exercise training on lean body mass, muscle thickness, and strength in young, active men.

Protein supplements Maltodextrin Placebo (MDP) Protein Blend (PB) Whey Protein (WP) Serving g Serving g 25.2 26.2 25.2 25.2 26.2 25.2 % g % g Protein Supplemental Table 87.0 1 Composition Supplemental Protein 82.1 <0.10 of the Table nutritional 21.9 87.0 1 Composition treatments 21.5 82.1 0.0 <0.10 of 1 the nutritional 21.9 treatments 21.5 1 0.0 Fat 2.8 Fat 2.5 0.3 0.7 2.8 0.6 2.5 0.1 0.3 0.7 0.6 0.1 PB WP MDP PB WP MDP PB WP MDP Ash 3.7 Ash 2.5 <0.2 0.9 3.7 0.7 2.5 0.0 <0.2 0.9 0.7 0.0 Moisture 5.9 g/100g product Moisture 7.0 5.4 g/100g 1.5 per 5.9 serving product 1.8 7.0 1.4 5.4 per 1.5 serving 1.8 1.4 Carbohydrate 0.6 Carbohydrate 5.8 94.2 0.2 0.6 1.5 5.8 23.7 94.2 0.2 1.5 23.7 Serving g Serving g 25.2 26.2 25.2 25.2 26.2 25.2 Calories Calories 95 98 96 95 98 96 % % g g Protein mg 87.0 Protein 82.1 <0.10 87.0 21.9 mg 82.1 21.5 <0.10 0.0 21.9 mg 21.5 0.0 Sodium Fat 874.0 2.8 Fat Sodium 174.0 2.5 59.3 0.3 2.8 220.2 0.7 874.0 2.5 45.6 174.0 0.6 0.3 14.9 59.3 0.1 0.7 220.2 0.6 45.6 0.1 14.9 Potassium Ash 545.7 3.7 Ash Potassium 631.7 2.5 10.4 <0.2 3.7 137.5 0.9 545.7 2.5 165.5 631.7 0.7 <0.2 2.6 10.4 0.0 0.9 137.5 0.7 165.5 0.0 2.6 Calcium Maltodextrin Moisture 141.7 5.9 Moisture Calcium 390.0 7.0 <0.01 5.4 5.9 35.7 1.5 141.7 7.0 102.2 390.0 1.8 5.4 <0.01 1.4 1.5 35.7 1.8 102.2 1.4 0.0 Magnesium Carbohydrate 32.2 0.6 Carbohydrate Magnesium 75.8 4.8 94.2 0.6 8.1 0.2 32.2 5.8 19.9 75.8 1.5 94.2 1.2 4.8 23.7 0.2 8.1 1.5 19.9 23.7 1.2 Phosphorus Calories 614.0 Calories Phosphorus 259.7 <0.01 154.7 95 614.0 68.0 259.7 98 <0.01 96 95 154.7 98 68.0 96 0.0 25% whey protein isolate, 25% soy g g g mg mg mg protein, 50% caseinate Alanine 3.45 Alanine 4.54-0.87 3.45 1.19 4.54-0.87 1.19 - Sodium 874.0 Sodium 174.0 59.3 874.0 220.2 174.0 45.6 59.3 14.9 220.2 45.6 14.9 Arginine 3.74 Arginine 1.95-0.94 3.74 0.51 1.95-0.94 0.51 - Aspartic Potassium Acid 7.92 545.7 Potassium Aspartic 9.17 631.7-10.4 Acid 545.7 2.00 137.5 7.92 631.7 2.40 9.17 165.5 10.4-2.6 137.5 2.00 165.5 2.40 2.6-100% whey protein isolate Cysteine Calcium 1.02 141.7 Calcium Cysteine 2.20 390.0 - <0.01 141.7 0.26 35.7 1.02 390.0 0.58 2.20 102.2 <0.01-35.7 0.26 102.2 0.58 0.0 - Glutamic Magnesium Acid 18.27 32.2 Magnesium Glutamic 15.90 75.8-4.8 Acid 32.2 4.60 8.1 18.27 75.8 4.17 15.90 19.9 4.8-1.2 8.1 4.60 19.9 4.17 1.2 - Glycine Phosphorus 2.11 614.0 Phosphorus Glycine 1.48 259.7 - <0.01 614.0 0.53 154.7 2.11 259.7 0.39 1.48 68.0 <0.01-154.7 0.53 68.0 0.39 0.0 - Histidine 2 2.28 g Histidine 1.51 - g 0.57 2.28 0.40 1.51 - g 0.57 0.40 - Isoleucine Alanine 4.72 3.45 Alanine Isoleucine 5.64 4.54-3.45 1.19 0.87 4.72 4.54 1.48 5.64 1.19 - - 0.87 1.19 1.19 1.48 -- Leucine Arginine 7.95 3.74 Arginine Leucine 8.81 1.95-3.74 2.00 0.94 7.95 1.95 2.31 8.81 0.51 - - 0.94 2.00 0.51 2.31 - - Lysine Aspartic Acid 6.77 7.92 Lysine 7.78 9.17-1.71 2.00 2.04 2.40 Aspartic 6.77 7.78 - Acid 7.92 9.17-1.71 2.04-2.00 2.40 - Methionine Cysteine 2.05 1.02 Methionine 1.92 2.20-0.52 0.26 2.05 0.50 1.92 0.58-0.52 0.50 - Phenylalanine Glutamic Acid Cysteine 1.02 2.20-0.26 0.58-4.14 18.27 Phenylalanine 2.65 15.90-1.04 4.60 4.14 0.70 2.65 4.17 - Glutamic Acid 18.27 15.90-1.04 0.70-4.60 4.17 - Proline 7.23 Proline 5.55-1.82 7.23 1.45 5.55-1.82 1.45 - Glycine 2.11 Glycine 1.48 2.11 0.53 1.48 0.39-0.53 0.39 - Serine Histidine 2 4.63 Serine 4.22-1.17 1.11 2.28 1.51 0.57 0.40 Threonine 2 Histidine 2 4.63 4.22-1.17 1.11-2.28 1.51-0.57 0.40 - Isoleucine 2 4.37 Threonine 6.24-1.10 1.63 4.72 5.64 1.19 1.48 Tryptophan 2 Leucine 2 1.14 Isoleucine 1.32-4.37 6.24-1.10 1.63 - Tryptophan 2 4.72 0.29 1.14 5.64 0.34 1.32 - - 1.19 0.29 1.48 0.34 - - 7.95 8.81 2.00 2.31 Tyrosine Lysine 2 3.97 Leucine Tyrosine 2.53-7.95 1.00 3.97 8.81 0.66 2.53 - - 2.00 1.00 2.31 0.66 -- 6.77 7.78 1.71 2.04 Valine 2 Methionine 2 5.40 Lysine Valine 5.20-6.77 1.36 5.40 7.78 1.36 5.20 - - 1.71 1.36 2.04 1.36 -- 2.05 1.92 0.52 0.50 Total EAA Phenylalanine 2 38.83 Methionine Total 41.07 EAA - 2.05 9.78 38.83 1.92 10.76 41.07 - - 0.52 9.78 0.50 10.76 -- 4.14 Phenylalanine 2.65-4.14 1.04 2.65 0.70 -- 1.04 0.70 - Proline 7.23 Proline 5.55-7.23 1.82 5.55 1.45 -- 1.82 1.45 - Serine 4.63 Serine 4.22 - Reidy et al J 4.63 1.17 Nutr. 2016 4.22 1.11 Jul 27. - pii: - jn231803. 1.17 1.11 - Supplements daily for 12 wks ingested with 300 ml water: Immediately following workout 3x / wk Between meals on non-workout days 4x / wk Extended Study in Young Adults 2

Results: Dietary protein intake Extended Study in Young Adults Protein Intake, g/day Baseline 6 wk 12 wk PB 101 ± 7 129 ± 7 a* 122 ± 7 a* WP 102 ± 7 126 ± 8 a* 135 ± 8 a* MDP 95 ± 7 95 ± 8 b 93 ± 8 b Protein Intake, g/kg BW per d PB 1.33±0.10 1.68±0.10 a* 1.54±0.10 a* WP 1.29±0.10 1.54±0.11 a* 1.64±0.11 a* MDP 1.27±0.10 1.22±0.11 b 1.23±0.11 b The mean habitual energy and macronutrient intake was not significantly different between treatments at baseline. Protein intake was significantly greater for PB and WP compared to MDP at 6 wk and 12 wk Reidy, et al. J Nutr. 2016

Extended Study in Young Adults All groups increased lean body mass (LM) from baseline No significant differences between groups, although the soy-dairy blend group tended to have greater increases (p<0.10) Reidy et al J Nutr. 2016 Jul 27. pii: jn231803. [Epub ahead of print]

Extended Study in Young Adults Individual changes in LM favor soy-dairy blend Subjects receiving soy-dairy protein blend exhibited a trend for increased LM compared to control (p=0.09). There was no difference in LM between whey protein isolate & control (p=0.55). Inter-individual variability evident Soy-dairy blend had a higher percentage of subjects who gained muscle over the expected 1.5 kg gain from exercise Reidy et al J Nutr. 2016 Jul 27. pii: jn231803. [Epub ahead of print]

Results: Arm lean mass Further analysis of the data suggest that only the PB continued to increase whole body, arm, and trunk lean mass over the final 6 weeks of the study. Comparisons at 12 wk showed that PB treatment trended (P=0.08) to have higher arm lean mass than MDP treatment. This was not demonstrated with WP vs. MDP treatment PB treatment was not different from WP treatment. Extended Study in Young Adults Majority of the effect of PB supplementation on lean mass occurs in the upper body. Reidy, et al. J Nutr. 2016

Change in Lean Mass (kg) Change in Lean Mass (kg) Extended Study in Young Adults Soy-dairy blend continued to improve LM gains beyond initial 6 weeks of training LM LM-Arms LM-Legs LM-Trunk LM-App LM LM-Arms LM-Legs LM-Trunk LM-App Pre-Mid (0-6 wks) Mid-Post (6-12 wks) Only the soy-dairy blend had a significant increase in lean body mass during the last 6 weeks of resistance exercise training Reidy et al J Nutr. 2016 Jul 27. pii: jn231803. [Epub ahead of print]

Extended Study in Young Adults All groups increased muscle thickness and 1-RM from baseline, although no differences between groups Increase in muscle thickness similar among groups All groups improved 1-RM for squats, knee extensions, and bench press. Gains observed were as expected for a resistance training program Reidy et al J Nutr. 2016 Jul 27. pii: jn231803. [Epub ahead of print]

Results: Serum testosterone concentration Extended Study in Young Adults PB WP MDP Baseline, ng/dl 376 ± 21 b 394 ± 21 b 405 ± 20 b 6 wk, ng/dl 406 ± 21 a 411 ± 22 a 454 ± 20 a 12 wk, ng/dl 385 ± 21 b 390 ± 22 b 439 ± 21 b Data are means ± SEM For this age group 270 ng/dl is the normal reference value* Results similar at baseline among treatments No significant treatment effect *http://education.endocrine.org/system/files/esap%202015%20laboratory %20Reference%20Ranges.pdf

Borack et al. J Nutr Dec 2016,. Clinical design Group n Age BMI Lean Mass Fat y kg/m 2 kg % Whey 10 69.3 ± 2.1* 26.5 ± 0.5 53.9 ± 1.2 31.5 ± 2.2 Blend 9 62.5 ± 1.6 25.1 ± 1.0 53.3 ± 3.0 27.2 ± 1.5 Data are mean ± SEM ; * Difference between groups (p< 0.05) Acute Study in Aging Adults Subjects Men 55-75y, n=19 Generally healthy, BMI< 30, no tobacco usage, no chronic diseases, no protein supplement usage, recreationally active Participated in resistance exercise- 8 sets of 10 leg extensions at ~70% 1RM Investigational products Whey or Protein Blend (25% whey, 25% soy, 50% casein) supplement (double blind) Whey= 30g protein (3.26g leucine) Blend= 30g protein (2.78g leucine)

Acute Study in Aging Adults No difference between protein treatments for support of muscle protein synthesis. No difference between groups in muscle protein breakdown. Fractional Muscle Protein Synthesis in the Aging Muscle Synthesis Muscle Breakdown Muscle Maintenance Borack et al, J Nutr Dec 2016.

Summary and Take Away Message In young adults, soy-dairy protein blend: Prolongs muscle protein synthesis and muscle protein net balance. Provides marginal but probable enhancement in total LBM and upper body LM. Has no effect on serum testosterone. Improves blood lipid profile. In older adults, whey protein isolate and soy-dairy protein blend: Similarly enhance post exercise: mtorc1 signaling, hyperaminoacidemia, muscle protein synthesis, and attenuation of muscle protein breakdown. Use of a soy-dairy protein blend may be a useful nutritional strategy for maintaining muscle mass and function through aging process potentially reducing the disability associated with development of sarcopenia later in life.