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5/26/13 The Role of Protein in Promoting Muscle Growth Blake B. Rasmussen, PhD Professor & Chair Department of Nutrition & Metabolism University of Texas Medical Branch Department of Nutrition & Metabolism Presentation Outline • Building Muscle - Why is it Important? • Role of Protein Synthesis • Effect of Resistance Exercise on Protein Synthesis • Effect of Dietary Protein on Protein Synthesis • Protein Supplementation and Exercise Training • What Protein Source is Best? • Timing of Protein Supplementation? • How Much Protein Should Athletes Consume? • Summary & Recommendations Department of Nutrition & Metabolism Why Study Muscle Biology? Department of Nutrition & Metabolism 1 5/26/13 Muscle Wasting Conditions " Injury " Following Surgery " Elderly (Sarcopenia) " Forced Inactivity / Bed Rest " Cancer, AIDS, Space Flight, Muscular Dystrophy " Trauma, Burns, Type 1 Diabetes Department of Nutrition & Metabolism Sports Nutrition - Protein Department of Nutrition & Metabolism Building Muscle Muscle Growth Muscle Atrophy Protein Synthesis Protein Degradation Exercise Feeding Unloading Starvation Department of Nutrition & Metabolism 2 5/26/13 The Muscle Biopsy Bergström, 1962 Department of Nutrition & Metabolism Role of Protein Synthesis Muscle Cell Proteins Synthesis Breakdown Blood Net Protein Balance = Synthesis - Breakdown Department of Nutrition & Metabolism m TORC1 Signaling 3 5/26/13 Effect of Resistance Exercise on Muscle Protein Synthesis Exercise Department of Nutrition & Metabolism Resistance Exercise Increases Muscle Protein Synthesis Department of Nutrition & Metabolism mTORC1 Activation Department of Nutrition & Metabolism 4 5/26/13 Is mTORC1 Activation Required for Muscle Contraction to Increase Muscle Protein Synthesis? Rapamycin mTORC1 Muscle Protein Synthesis Department of Nutrition & Metabolism Yes! - mTORC1 is Required to Increase Muscle Protein Synthesis Department of Nutrition & Metabolism Effect of Dietary Protein on Muscle Protein Synthesis Leucine Essential Amino Acids Department of Nutrition & Metabolism 5 5/26/13 Response to Essential Amino Acids mTOR Activation mTOR (Ser2448) (AU) Muscle Protein Synthesis (%⋅hr-1) Muscle Protein Synthesis Control Control Nutrition Nutrition Adapted from Fujita et al. J Physiol, 2007 Department of Nutrition & Metabolism EAA is Responsible for the Stimulation of Muscle Protein Synthesis Department of Nutrition & Metabolism Gln Na+ Insulin BCAA Gln K+ ? ? Rag GTPases raptor mTORC 1 Rab? MAP4K3 ? mTORC 1 ? ? Akt PAT1 raptor 4E-BP1 Rheb Rapamycin S6K1 hVps34 eIF4F Protein Synthesis rpS6 Translation Initiation Department of Nutrition & Metabolism 6 5/26/13 Protein / Amino Acids Activate mTORC1 to Increase Muscle Protein Synthesis Muscle Protein Synthesis (%⋅hr-1) * Basal # Post EAA vs. Basal *# P<0.05 P<0.05 vs. Rapamycin Dickinson et al, Journal of Nutrition, 2011! Dickinson et al, Metabolism, 2012! Department of Nutrition & Metabolism Stimulating Muscle Growth with Protein Department of Nutrition & Metabolism Muscle Protein Synthesis (%•hr-1) Exercise Enhances the Nutrition-Induced Increase in Protein Synthesis ↑ ~50% Young RE = Resistance Exercise ↑ ~100% ↑ ~100% Older Adapted from Fry et al., Skeletal Muscle, 2011; & Drummond et al. J Appl Physiol, 2008 EAA = Essential Amino Acids Department of Nutrition & Metabolism 7 5/26/13 Effect of Protein + Exercise Department of Nutrition & Metabolism Summary " " " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation mTORC1 should be considered a target when designing nutritional supplements to enhance muscle growth Consuming Protein After Exercise Enhances Muscle Protein Synthesis Department of Nutrition & Metabolism Protein Supplementation During Exercise Training Does it Enhance Muscle Growth? Department of Nutrition & Metabolism 8 5/26/13 Protein Supplementation and Exercise Training Department of Nutrition & Metabolism Whey and Soy Protein Supplementation Improves Muscle Mass Department of Nutrition & Metabolism Milk vs Soy Supplementation During Training Department of Nutrition & Metabolism 9 5/26/13 What Protein Source is Best? Must Consider Protein Quality Which Means a Sufficient Amount of Essential Amino Acids Especially Leucine Department of Nutrition & Metabolism Why is Whey Considered the Gold Standard? Department of Nutrition & Metabolism Whey vs Soy: Effects on Muscle Protein Synthesis Fasting N=6 per group Department of Nutrition & Metabolism 10 5/26/13 Comparing Apples to Oranges? 20 grams = 1.9 g leucine 20 grams = 1.5 g leucine 27 grams = 1.9 g leucine Department of Nutrition & Metabolism Protein Blends Department of Nutrition & Metabolism The Theory Department of Nutrition & Metabolism 11 5/26/13 Journal of Nutrition 143: 410-416, 2013 Department of Nutrition & Metabolism Study Aim Department of Nutrition & Metabolism Subjects Department of Nutrition & Metabolism 12 5/26/13 Methods Department of Nutrition & Metabolism Methods Department of Nutrition & Metabolism Results Department of Nutrition & Metabolism 13 5/26/13 Leucine Department of Nutrition & Metabolism Area Under The Curve Department of Nutrition & Metabolism Mixed Muscle Protein Synthesis Whey Blend Department of Nutrition & Metabolism 14 5/26/13 mTORC1 Signaling Department of Nutrition & Metabolism Conclusions A soy-dairy protein blend ingested following exercise is capable of prolonging in human skeletal muscle: • blood aminoacidemia • mTORC1 signaling • protein synthesis Protein blends are an effective postexercise nutritional supplement Department of Nutrition & Metabolism When Should an Athlete Supplement with Protein? Is Timing Important? Department of Nutrition & Metabolism 15 5/26/13 EAA Ingestion 1 or 3 hours After Exercise Produces the Same Response in Muscle Protein Synthesis Rasmussen et al, J Appl Physiol 88: 386-392, 2000 Department of Nutrition & Metabolism Ingesting EAA Before Exercise Has No Additional Benefit on Muscle Protein Synthesis Fujita et al, J Appl Physiol 106: 1730-1739, 2009 Department of Nutrition & Metabolism After Exercise is Best Department of Nutrition & Metabolism 16 5/26/13 Muscle Remains Sensitive to Protein For At Least 24 Hours After Exercise Burd et al, Journal of Nutrition 141: 568-573, 2011 Department of Nutrition & Metabolism How Much Protein Does it Take to Maximize Muscle Protein Synthesis? Department of Nutrition & Metabolism Dose-Response Study Cuthbertson et al, FASEB J., 2005 10 grams of EAA or ~20-25 grams of Protein Department of Nutrition & Metabolism 17 5/26/13 30-30-30 A. Adequate Protein Distribution B. Inadequate Protein Distribution Maximal Protein Synthesis Breakfast Lunch Dinner Breakfast ~30 g ~30 g ~30 g ~10 g Lunch ~20 g Dinner ~60 g protein protein protein protein protein protein Paddon-Jones & Rasmussen, Current Opinion in Clinical Nutrition & Metabolic Care, 2009 Department of Nutrition & Metabolism Concept of Protein Distribution Department of Nutrition & Metabolism 24 Hour Protein Synthesis Preliminary data from D. Paddon-Jones Department of Nutrition & Metabolism 18 5/26/13 Bolus = 40 g x 2 Intermediate = 20 g x 4 Pulse = 10 g x 8 Department of Nutrition & Metabolism Summary Exercise and Protein Both Increase Muscle Protein Synthesis by Activating the mTORC1 pathway Ingesting Protein After Exercise is Best for Enhancing Muscle Protein Synthesis Protein Supplementation During Exercise Training can Enhance Muscle Growth High Quality Protein Sources Produce Similar Increases in Muscle Protein Synthesis and Muscle Growth During Exercise Training Department of Nutrition & Metabolism Summary (cont.) Best to Eat Protein After Exercise but Muscle Remains Sensitive for at Least 24 hours post-ex Ingesting a Large Amount of Protein is not Necessary for Maximizing Muscle Protein Synthesis Distributing Protein Intake Evenly and Moderately Throughout the Day is Likely to Improve Muscle Growth During Training Department of Nutrition & Metabolism 19 5/26/13 Recommendations Use a High Quality Protein Source to Supplement within the First Hour Post-Exercise. Eat a Sufficient Amount of High Quality Protein at Each Meal - Distributed Evenly Throughout the Day. 20-30 grams for Most Athletes. More for Larger Athletes? Moderation is the Key - Avoid Excessive Protein Intake. Practical Example Considering Glycogen Replenishment Department of Nutrition & Metabolism Acknowledgments Univ of Utah Department of Nutrition & Metabolism Acknowledgments Univ Kentucky Arizona State Texas A&M Univ Wisconsin Paul Reidy PhD Student Elena Volpi, MD, PhD Department of Nutrition & Metabolism 20 5/26/13 Funding NIAMS R01 AR049877 NIA P30 AG024832 NICHD T32 HD007539 Solae, LLC [email protected] Department of Nutrition & Metabolism 21