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5/26/13 1 Department of Nutrition & Metabolism 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?

The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Page 1: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

5/26/13

1

Department of Nutrition & Metabolism

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?

Page 2: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

5/26/13

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Department of Nutrition & Metabolism

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

Protein Degradation Protein Synthesis

Exercise Feeding

Unloading Starvation

Muscle Growth Muscle Atrophy

Page 3: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

The Muscle Biopsy Bergström, 1962

Department of Nutrition & Metabolism

Role of Protein Synthesis

Proteins Muscle Cell

Synthesis Breakdown

Blood

Net Protein Balance = Synthesis - Breakdown

TORC1 Signaling m

Page 4: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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

Page 5: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

Is mTORC1 Activation Required for Muscle Contraction to Increase

Muscle Protein Synthesis?

mTORC1 Rapamycin

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

Page 6: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

5/26/13

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Department of Nutrition & Metabolism

Response to Essential Amino Acids

Control Nutrition

mTO

R (

Ser24

48)

(AU

)

Adapted from Fujita et al. J Physiol, 2007

mTOR Activation

Mus

cle

Prot

ein

Synt

hesi

s (%⋅hr

-1)

Control Nutrition

Muscle Protein Synthesis

Department of Nutrition & Metabolism

EAA is Responsible for the Stimulation of Muscle Protein

Synthesis

Department of Nutrition & Metabolism

Gln

Na+

PAT1 Rag

GTPases

Rheb

S6K1 4E-BP1

eIF4F

BCAA

rpS6

? ?

Translation Initiation

raptor

Gln

K+

hVps34

MAP4K3

mTORC1

raptor

?

?

Rab ?

?

Protein Synthesis

Akt

Insulin

mTORC1

Rapamycin

Page 7: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

Protein / Amino Acids Activate mTORC1 to Increase Muscle Protein Synthesis

Basal

Mus

cle

Prot

ein

Synt

hesi

s (%⋅hr

-1)

P<0.05 vs. Basal

# *

P<0.05 vs. Rapamycin # *

Post EAA

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

Exercise Enhances the Nutrition-Induced Increase in Protein Synthesis

Adapted from Fry et al., Skeletal Muscle, 2011; & Drummond et al. J Appl Physiol, 2008

Mus

cle

Prot

ein

Synt

hesi

s (%

•hr-1

)

Young Older

↑ ~50%

↑ ~100% ↑ ~100%

RE = Resistance Exercise

EAA = Essential Amino Acids

Page 8: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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?

Page 9: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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

Page 10: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

5/26/13

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Department of Nutrition & Metabolism

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

Page 11: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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

Page 12: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

Journal of Nutrition 143: 410-416, 2013

Department of Nutrition & Metabolism

Study Aim

Department of Nutrition & Metabolism

Subjects

Page 13: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

Methods

Department of Nutrition & Metabolism

Methods

Department of Nutrition & Metabolism

Results

Page 14: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

Leucine

Department of Nutrition & Metabolism

Area Under The Curve

Department of Nutrition & Metabolism

Mixed Muscle Protein Synthesis

Whey Blend

Page 15: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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?

Page 16: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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

Page 17: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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

10 grams of EAA or ~20-25 grams of Protein

Cuthbertson et al, FASEB J., 2005

Page 18: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

30-30-30

Maximal

Protein

Synthesis

Breakfast

protein

Lunch

protein

Dinner

protein

Breakfast

~10 g

protein

Lunch

~20 g

protein

Dinner

~60 g

protein

Breakfast

~30 g

Lunch

~30 g

Dinner

~30 g

A. Adequate Protein Distribution B. Inadequate Protein Distribution

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

Page 19: The Role of Protein in Promoting Muscle Growth · " Resistance Exercise & Protein both stimulate muscle protein synthesis primarily through mTORC1 activation! " mTORC1 should be considered

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Department of Nutrition & Metabolism

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

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Department of Nutrition & Metabolism

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

Elena Volpi, MD, PhD

Paul Reidy PhD Student Univ Kentucky Univ Wisconsin Texas A&M Arizona State

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Department of Nutrition & Metabolism

Funding

NIAMS R01 AR049877 NIA P30 AG024832 NICHD T32 HD007539 Solae, LLC

[email protected]