Metabolism Part 3 - Protein

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Protein 1
2 What’s on the Menu! Some protein basics: turnover, changes with exercise. The practical stuff: how much? protein type coingestion with carbs timing of ingestion changes with training status changes with aging
Protein Turnover and the Various Metabolic Fates of AAs in Skeletal Muscle During post-absorptive state, breakdown is generally ~30% greater than synthesis A protein rich meal increases synthesis and decreases breakdown During prolonged exercise, • increase in protein breakdown and decrease in synthesis • Small increase in oxidation ( only 2 - 6% of total energy) 3 Note that during protein turnover, amino acids are recycled … this explains why daily need aren’t as high as you might expect
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Amino Acids Essential amino acids • cannot be produced by the body in physiologically significant amounts Non-essential • can be produced by the body Branched-chain • leucine*, isoleucine, valine • only AAs oxidized by muscle *potent stimulator of protein synthesis 4 Essential AA’s Leucine Isoleucine Valine Methionine Phenylalanine Threonine Lysine Histidine Tryptophan
Fates of Amino Acids During Exercise Urea production • All oxidized AAs will lead to urea production • Urea is excreted, ↑ with exercise, especially carbohydrate-depleted situations (i.e. greater dependency on AA) Branched chain amino acids (BCAAs, leucine, isoleucine, valine) • Major group of AAs that are oxidized in muscle • Oxidation of BCAAs increases with exercise – Generally not a significant substrate for muscle ATP production Gluconeogenic, ketogenic or oxidized • Glucogenic AAs readily converted to pyruvate, or TCA intermediate e.g. (ketoglutarate, succinate, fumarate); many amino acids are gluconeogenic • Ketogenic AAs readily converted to acetyl-CoA or acetoacetate; leucine, alanine and a few others • Most can be oxidized; in muscle, mainly BCAAs 5
6 What About Resistance Exercise? Tom Platz! 1980s bodybuilder
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RE stimulates both synthesis and breakdown • Increased ‘turnover’ persists for 24-48h post-exercise • Breakdown (MPB) > synthesis (MPS) if nothing is eaten (negative protein balance) Resistance Exercise Increases Protein Turnover 7 3h after exercise (black is pre, grey is post) Biolo et al. Am J Phsiol Endo 268(31):E514-20, 1995.
To build muscle we want to be in positive protein balance … so EAT SOMETHING! Supplementing with AA can increase MPS and decrease MPB to create a positive balance needed for muscle gain AAs can increase MPS and decrease MPB Net protein balance greatest with RE and AA Need to Consume Protein for Positive Balance 8 Resistance exercise ‘sensitizes’ the muscle to hyperaminoacidemia i.e. without RE, the effect of AA on protein balance is much smaller MPS, muscle protein synthesis MPB, muscle protein breakdown
Resistance Exercise Plus Meals Maximizes Difference Between Synthesis and Breakdown 9
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How Much Protein Do You Need? 10 That’s Right …. I’m BAD!!!!!!!! And I Eat Bamboo!!!!!!!!
Do requirements increase with resistance or aerobic training? General Recommendations ~0.85-1.3 g/kg/day for children • ~0.9 g/kg/day for sedentary adults • ~1.3-1.8 g/kg/day for athletes * e.g. 100kg weightlifter, bodybuilder or football player might need 180 g protein (at the very high end) This is normally covered by the consumption of calories! 180g protein is ~750 kcal, or 15%* of a 5000 kcal diet How Much Protein Do You Need? 11 *Recommended intake ~12-15% of total kcal
12 In particular, high protein intake may protect again loss of lean mass during caloric restriction in athletes Hector et al. Int J Sport Nutr Exerc Metab 28:170-77, 2018. More Protein to Prevent Loss of Lean Mass
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Fractional Synthesis Rate is measured by incorporation of 13C-leucine into the total protein pool. Ingestion of 20g complete (egg) protein is sufficient to maximally stimulate MPS after resistance exercise in young adults 13 Moore et al. Am J Clin Nutr 89:161-8, 2009. FSR was measured for 4 h after RE 4 sets of 8-10 reps to failure leg press, knee extension, leg curl 20 g of protein (per meal) should do it Or ~7 g EAA FSR, fractional synthesis rate
14 Fate of Excess AAs More is not necessarily better – MPS is saturable! Dietary protein consumed after exercise in excess of the rate at which it can be incorporated into tissue protein stimulates oxidation and increases plasma urea
15 What Does 20g of Protein Look Like?
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• At a cellular level, an increased requirement for protein in strength-trained athletes might arise due to the extra protein required to support muscle protein accretion through elevated protein synthesis and increased breakdown during exercise • At the same time, several studies have shown that strength training , consistent with the anabolic stimulus for protein synthesis it provides, actually increases the efficiency of use of protein, which reduces dietary protein requirements • Various studies have shown that strength-trained athletes habitually consume protein intakes higher than required • At present there is no evidence to suggest that supplements are required for optimal muscle growth or strength gain. Strength-trained athletes should consume protein consistent with general population guidelines, or 12% to 15% of energy from protein 16 Protein Requirements and Supplementation in Strength Sports Stuart M. Phillips. Nutrition (7-8):689-95, 2004
Does Protein Source Matter? Different types of proteins • Whey protein – “fast” digestion leading to rapid increase in plasma amino acids • Soy • Casein – “slow” digestion 17
• Whey causes greatest FSR at rest and after RE. Soy is next. • This may be due to increase in leucine, which stimulates protein synthesis • Whey and soy cause greater increases in insulin Groups matched for total EAA content Whey vs. Casein vs. Soy 18
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19 Leucine Trigger Hypothesis Phillips. Nutrition and Metabolism. 13, 2016 ~5g leucine is considered to maximize protein synthesis (~2g is the threshold to elicit a response ….of course, all EAA need to still be present!
20 Leucine Stimulates Protein Synthesis via mTOR Pathway
• Mixed AA (MAA) = 6g non-essential AA, 6g EAA • EAA = 12g of EAA • CHO = 35g sucrose *consumed 1-2h post resistance exercise protein synthesis Adding CHO had no significant effect on MPS! As long as adequate EAAs are consumed (~6 g), it doesn’t matter if they are “ pure ” or “ mixed ” with other AAs Does Carbohydrate Make a Difference? 21 Premise: the CHO-induced spike in insulin will increase net protein synthesis
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PRO = 25g whey protein PRO + CHO = 25g whey protein + 50g CHO Despite the large insulin spike, MPS is not further increased by CHO … and MPB is not decreased Sufficient protein already maximally stimulates MPS; insulin is likely a factor only at rest (NOT following RE) 22 Does Carbohydrate Make a Difference? Staples et al. Med Sci Sports Ex. 43(7):1154-61, 2011. +CHO
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23 Net Phe uptake across leg over 3 hr (indicative of protein synthesis) Muscle free intracellular concentration of Phe Importance of Timing of Ingestion Tipton et al. Am J Physiol Endocrinol Metab 281:E197, 2001. Subjects consumed EAA plus CHO Phe uptake/content used an an index of protein synthesis Pre = ingestion prior to exercise Post = ingestion after exercise Suggests timing may be important!
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24 Investigators repeated this study in 2007 using whey protein drink instead. Tipton et al. Am J Physiol Endo 292(1), 2007 And guess what? They saw NO BENEFIT!!!!! ??? Importance of Timing of Ingestion
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25 “While there is some debate about the “critical” nature of the timing of post-exercise protein consumption, a simple message may be that the earlier after exercise an athlete consumes protein the better. ” “So while a crucial “window of anabolic opportunity” is not, at least currently, well defined, it would make sense that protein provision should begin as soon as possible after exercise to promote recovery and possibly to enhance the rate of – or absolute level of – adaptation.” Phillips and Van Loon. J Sports Sciences 29(1), 2011. A meta-analysis (J International Society of Sports Nutrition 10 (53), 2013) concluded there was no effect of protein timing on strength or hypertrophy • Examined a total of about 500 subjects for each variable
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Timing and Distribution of Protein Ingestion During Recovery from Resistance Exercise 26 What’s Best? One big bolus of protein? Or smaller and spread out?
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Timing and Distribution of Protein Ingestion During Recovery from Resistance Exercise Resistance exercise bout followed by 80g of whey protein over 12h recovery : • 8 × 10 g - every 1.5h ( PULSE ) • 4 × 20 g - every 3h ( INT /intermediate) • 2 × 40 g - every 6h ( BOLUS ) *all of these began immediately after completion of RE. Muscle biopsies taken @ rest and 1, 4, 6, 7 and 12h post-RE. Measured resting and post-exercise MPS. 27 Areta et al. J Physiol. 591(9): 2013
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Timing and Distribution of Protein Ingestion During Recovery from Resistance Exercise Different ingestion protocols produced different insulin and AA profiles Bolus led to greatest insulin spike and hyperaminoacidemia 28
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All ingestion protocols increased MPS (above rest) throughout 1-12h recovery MPS : INT > PULSE = BOLUS 20g whey protein every 3h was superior to either PULSE or BOLUS patterns for stimulating MPS throughout the day. 29 So, timing may be a factor … Start soon, Get in 20g, Spread it out.
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Muscle protein fractional synthetic (FSR) and breakdown (FBR) rate in response to RE in untrained ( UT ) and trained ( T ) individuals. But less breakdown during RE in T! Effect of Training Status on Protein Turnover Synthesis increased in both T and UT 30 Phillips et al. Am J Physiol Endocrinol Metab 276:E118, 1999. Measured over 6 hrs No meal provided
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Effect of Training Status on Protein Turnover RT individuals have reduced protein turnover … which implies less protein requirement 31 Hartman et al. Appl Physiol Nutr Metab. 31(5), 2006. 12 wks of RT Turnover assessed at rest for 12 hrs with normal daily pattern PS, protein synthesis PB, protein breakdown Pre and post training
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32 Do Older Adults Need More Protein? Loenneke et al. Clinical Nutr 35(6): 1506-11, 2016 Ages 50-85 y Training status not controlled for 2+ meals per day at ~45-50g protein associated with greatest knee extensor strength and leg lean body mass. This suggests older adults need more protein! 2 meals at 45g protein 1 meal at 45g protein
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33 Moore at al. J Gerontology 70(1): 57-62, 2015 older younger per body mass per lean mass Thresholds for maximizing protein synthesis are HIGHER in older individuals! Do Older Adults Need More Protein? Note: this was not a training study
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34 Anabolic Resistance in Older Individuals Anabolic response to an exercise stimulus is reduced in older adults. Kumar et al. J Physiol. 587(1):211-17, 2009
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BCAA Supplementation to Increase MPS This is a VERY popular means to stimulate muscle anabolic activity i.e. protein synthesis But does it??? 35
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BCAA Supplementation Alone Does Not Stimulate Muscle Protein Synthesis Results (data not shown here) • BCAA infusion for 3 hours caused large rise in arterial BCAA levels • Muscle BCAA uptake rose dramatically but there was no increase in muscle protein synthesis • An increase in muscle BCAA oxidation accounts for the increased disposal of BCAA 36 Louard et al. Clin Sci. 79(5):457-66, 1990. MPS (phenylalanine uptake) MPB (phenylalanine loss) Q: Why is phenylalanine uptake a better index of protein synthesis than leucine? 3 hr BCAA infusion
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Summary of Nutritional Impact on Protein Metabolism Fasting - increases protein degradation Protein-rich meal, amino acids • Stimulate protein synthesis, reduce protein degradation • Whey > soy > casein Leucine • Particularly effective at stimulating protein synthesis in the presence of sufficient protein (or all EAA); BCAA by themselves do not work! Carb ingestion with protein does not enhance protein synthesis following RE Spreading out 20g of protein every 3 hrs after RE is probably optimal timing Anabolic response to protein AND RE is reduced in older individuals 37
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38 Final Thought …. Most studies just look at acute periods of time (3 to 48 hrs) after resistance exercise Question: Do the changes observed in terms of MPS in this period translate to actual improvements in muscle mass, strength, etc over a period of 6 to 12 months? Not a ton of information on that!!!!
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