NUTRITIONAL INTERVENTIONS TO AUGMENT RESISTANCE TRAINING INDUCED SKELETAL MUSCLE HYPERTROPHY

The following are excerpts from a  'Frontiers in Physiology' research article entitled, Nutritional Interventions To Augment Resistance Training Induced Skeletal Muscle Hypertrophy, by Robert Morton, Chris McGlory, & Stuart Phillips.

 

Abstract

The magnitude of the RE-induced increase in MPS is dictated by a variety of factors including: the dose of protein, source of protein, and possibly the distribution and timing of post-exercise protein ingestion. In addition, RE variables such as frequency of sessions, time under tension, volume, and training status play roles in regulating MPS.

RE: Resistance Exercise          MPS: Muscle Protein Synthesis          

Introduction

Beyond its role in locomotion, skeletal muscle is the largest site of postprandial glucose disposal, a large site of lipid oxidation, and a substantial contributor to resting metabolic rate (for review see Wolfe, 2006)

What this work has shown us is that the size of human muscle mass is dictated by diurnal changes in rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB) (Phillips, 2004). In the rested, fasted state, rates of MPB exceed those of MPS and thus skeletal muscle is in a state of negative net protein balance (Biolo et al., 1995b). However, in response to amino acid (AA) or protein feeding, there is a significant but transient increase in rates of MPS and no significant change in MPB rendering skeletal muscle in a state of positive net protein balance (Biolo et al., 1997; Phillips, 2004).

MPB: Muscle Protein Breakdown          AA: Amino Acid

Indeed, a single bout of RE in the fasted state significantly increases rates of MPS, however, this rise in MPS is not enough to promote a positive net protein balance (Biolo et al., 1995b). Instead, RE serves to potentiate MPS in response to AA feeding (Biolo et al., 1997), an effect that may persist for up to 24 h (Burd et al., 2011). Therefore, repeated bouts of RE and protein feeding result in skeletal muscle hypertrophy (Cermak et al., 2012).
What remains largely unknown is what the most anabolic or sensitizing RE protocol is. Moreover, data pertaining to the optimal dose, timing and quality of protein intake to optimize post-RE muscle anabolism have only recently enabled appropriate recommendations to be made.
The first study to examine a protein dose-response relationship with MPS following RE was conducted by Moore et al. (2009). Moore et al. (2009) fed whole-egg proteins after a bout of RE to healthy young men with a wide range of resistance-training experience (4 months to 8 years). The authors found that after a bout of unilateral lower-body RE the MPS response plateaued with ingestion of 20 g of protein such that there was no statistically significant benefit toward MPS with the ingestion of 40 g (Moore et al., 2009).

In young, resistance-trained (≥6 months previous weight-lifting experience) men 20 g of whey protein following unilateral RE was also shown to sufficiently stimulate post-absorptive MPS with no further increase ingesting 40 g (Witard et al., 2014a).
It appears that 20 g of whey protein (or ~0.25 g protein/kg) is an ample amount of protein to ingest for healthy young men both at rest (Cuthbertson et al., 2005) and after exercise (Moore et al., 2009) regardless of training status (Witard et al., 2014a).
Altogether, these results suggest that 20 g is the maximally effective protein dose per meal in healthy, young individuals. Protein consumed beyond this level is oxidized at a higher rate (Moore et al., 2009; Witard et al., 2014a) and results in urea production (Witard et al., 2014a) indicating there is a limit of AAs that can be used for MPS. The theory behind why, with increasing protein doses, there is a ceiling on MPS has been termed the “muscle full effect” (Atherton et al., 2010). It is important to acknowledge that these dose-response studies have been limited to lower limb RE and thus it remains unknown as to whether the absolute dose of protein required to maximally stimulate rates of MPS following whole-body RE is >20 g.
Using a two-phase linear regression model we reported that the dose of protein beyond which there was no further increase in MPS in young men was 0.25 g/kg/meal (90% confidence interval 0.18–0.3 g/kg/meal). To account for inter-individual variability we propose the addition of two standard deviations to our estimate, yielding a dose of protein that would optimally stimulate MPS at intake of 0.4 g/kg/meal. In our view, ingestion of protein beyond this dose would result in no further stimulation of MPS. The effects of AA ingestion beyond that needed to maximally stimulate MPS may include metabolic feedback regulation (Layman et al., 2015), satiety (Leidy et al., 2015), and thermogenesis (Acheson et al., 2011).
Citing data from whole-body protein turnover Deutz and Wolfe made the case that larger doses of protein can still be more anabolic than smaller doses due to a marked suppression of protein breakdown (Deutz and Wolfe, 2013).
We have known for some time that RE alone results in a long-lasting elevation in MPS for at least 48 h and MPB for 24 h (Phillips et al., 1997); thus, even in the basal fasted state there is a subsequent increase in the turnover of muscle proteins. RE alone elevating basal MPS will “prime” the muscle to be responsive, in terms of an increased sensitivity of MPS, to aminoacidemia.
Given the sensitizing effect of RE, we conclude it is most advantageous to ingest protein and generate hyeraminoacidemia in the post-RE period.
Considering the synergistic response of aminoacidemia following RE (Biolo et al., 1997; Burd et al., 2011), we see it as being optimal to ingest protein immediately following RE. Moreover, we speculate pre-exercise aminoacidemia may blunt the subsequent post-RE MPS response to AAs due to an overlap in the aminoacidemic responses and a muscle full effect (Atherton et al., 2010).
How protein should be consumed throughout the day is matter of debate. In an acute study, an “intermediate” pattern of whey protein ingestion (4 × 20 g every 3 h) throughout a 12 h recovery period post-RE was found to be more effective than ingestion of large boluses (2 × 40 g every 6 h) or a pulse (8 × 10 g every 1.5 h) protocol at stimulating MPS (Areta et al., 2013). These results are in agreement with the muscle full effect where, when AA delivery is sufficient (~20 g), AAs are no longer used for MPS and are targeted for oxidation (Moore et al., 2009; Atherton et al., 2010; Witard et al., 2014a).
The macronutrient composition and form of meal intake may influence both the meal-induced rise in hyperaminoacidemia and protein synthesis (Burke et al., 2012b).
Pre-sleep feeding is a time when protein provision may provide a marked benefit to remodel muscle proteins. Ingestion of 40 g of casein protein before bed stimulates MPS and improves net protein balance overnight in healthy young men (Res et al., 2012).
Altogether, we propose that the timing of protein intake is an important variable to consider in optimizing skeletal muscle recovery and hypertrophy. It appears optimal to ingest protein in the post-exercise period though the purported “anabolic window” for protein ingestion lasts at least 24 h. (Burd et al., 2011)
Lastly, ingesting AAs in larger doses of protein (40 g casein or up to 0.6 g/kg/meal) pre-sleep appears to augment both acute overnight MPS (Res et al., 2012) and chronic skeletal muscle adaptations (Snijders et al., 2015). We wish to emphasize, however, that the magnitude of gains that are attributable to protein supplementation compared to the overall gains made as a result of the RE training program itself appear to be relatively small.
Proteins such as whey and soy are digested relatively rapidly, resulting in rapid aminoacidemia, and induce a larger but more transient rise in MPS than casein (Tang et al., 2009; Reitelseder et al., 2011). Whole-body protein synthesis is stimulated more with whey protein whereas whole-body protein breakdown is suppressed with ingestion of casein (Boirie et al., 1997).
It appears that the leucinemia (and quite possibly the ensuing intramuscular leucine concentration) is the driver of the MPS response and thus the recovery process. The addition of isoleucine and valine (the other branched-chain AAs) does not improve MPS (Churchward-Venne et al., 2014). This response is an underappreciated result considering many supplements contain combinations of the branched-chain AAs, which, based on our data, would not be advantageous to consume co-temporally because they share the same transporter (Hyde et al., 2003). Thus, as we speculated (Churchward-Venne et al., 2014), consumption of crystalline BCAA resulted in competitive antagonism for uptake from the gut and into the muscle and was actually not as effective as leucine alone in stimulating MPS.

BCAA: Branch Chain Amino Acid

Despite the popularity of BCAA supplements we find shockingly little evidence for their efficacy in promoting MPS or lean mass gains and would advise the use of intact proteins as opposed to a purified combination of BCAA that appear to antagonize each other in terms of transport both into circulation and likely in to the muscle (Churchward-Venne et al., 2014).
It appears that post-exercise MPS, measured within 3 h, is optimized by protein ingestion that contains a high leucine content where proteins are rapidly digested (Tang et al., 2009).
Lastly, there appears to be a leucine “threshold” for stimulation of MPS that is around ~3 g of leucine per meal (Churchward-Venne et al., 2014), which may be determining the per meal protein recommendation of ~0.4 g protein/kg.
The purpose of carbohydrate (CHO) co-ingestion with protein is to stimulate insulin release beyond that seen with AA ingestion alone with the idea that insulin improves net protein balance. Indeed, local insulin infusion at rest increases MPS (Biolo et al., 1995a, 1999; Hillier et al., 1998) and blood flow (Biolo et al., 1999). However, following RE, insulin infusion has no effect on blood flow or MPS, though the slight suppression of MPB remains (Biolo et al., 1999).
However, co-ingesting CHO with AA/protein following RE has no further stimulatory effects on MPS and does not suppress MPB so long as protein is adequate (~25 g) (Koopman et al., 2007; Glynn et al., 2010; Staples et al., 2011).
These results indicate that when performing RE and providing adequate protein there is no benefit of co-ingesting CHO on stimulating MPS. This is most likely because the level of insulin required for optimal stimulation of MPS is remarkably low (Greenhaff et al., 2008; Trommelen et al., 2015) (i.e., 10–15 IU/ml), only 2–3 times basal resting levels for most healthy persons, which is easily reached with even a small dose of protein.
It appears that even in a glycogen-depleted state protein is still effective at stimulating MPS following resistance exercise (Camera et al., 2012) and that only a minimal level of insulin is required to achieve optimal rates of MPS (Greenhaff et al., 2008).
Training “age” may be an important variable impacting the quantity and duration of the anabolic response following RE. Compared to untrained participants, trained individuals have attenuated post-RE MPS and MPB resulting in less total muscle protein turnover (Phillips et al., 1999).
The general conclusion from this review is that RE training reduces not the amplitude but the duration of the MPS response (Damas et al., 2015). This may in fact highlight that maximizing hypertrophic potential in the trained state may require greater focus on the post-exercise period for protein provision.
Despite the wealth of studies relating to the role of protein in augmenting the adaptive response to resistance exercise, relatively little has been conducted to identify whether resistance-trained individuals require greater relative post-exercise or daily protein consumption compared to those who are untrained. Data exist to suggest that athletes performing intensive periods of training may benefit from increased protein intake from the perspective of supporting immune function (Witard et al., 2014b).
However, as mentioned above, the post-RE MPS response reaches a maximum at 20 g or ~0.25 g/kg in both untrained (Moore et al., 2009) and trained (Witard et al., 2014a) young men. Whether or not these results hold true when performing whole-body RE has yet to be determined.
The opinions of these reviews suggest that resistance-training athletes may benefit from larger protein intakes higher than the recommended dietary allowance in the range of 1.3–1.8 g/kg/day (Phillips and van Loon, 2011; Phillips, 2012, 2014b).
Different skeletal muscle adaptations are induced by RE training than endurance training (Egan and Zierath, 2013). In this regard, we have shown that after 10 week of RE training, performing a single bout of RE increases myofibrillar, but not mitochondrial, protein synthesis whereas synthesis in both protein pools were acutely stimulated by RE in the pre-trained state (Wilkinson et al., 2008). Furthermore, with resistance training mixed MPS may decrease but fraction-specific adaptations (in this case myofibrillar MPS) may actually be enhanced (Kim et al., 2005). Indeed, it appears that the remodeling process following exercise is specific to the type of exercise performed (Wilkinson et al., 2008) and is tailored with training (Kim et al., 2005).
Burd et al. (2012) found that sarcoplasmic MPS between 0 and 6 h, mitochondrial protein synthesis between 0–6 and 24–30 h, and myofibrillar protein synthesis between 24 and 30 h were all elevated with a longer time under tension beyond that of the repetition-matched group.
Indeed, the electromyography of the vastus lateralis indicated that the group exercising with a longer time under tension had increased muscle activity, and presumably muscle fatigue, toward the end of set completion (Burd et al., 2012). We speculate that the elevated MPS response to the longer time under tension is a result of increased motor unit recruitment which may be linked to muscle damage/remodeling (Proske and Morgan, 2001)
Interestingly, we have reported that when recreationally-active participants performed leg extensions at either 30 or 90% of their one-repetition max (1RM) to contractile failure there was an equal increase in mixed MPS (Burd et al., 2010). Additionally, 24 h after the RE bouts there was elevated myofibrillar MPS in only the 30% group (Burd et al., 2010). Not surprisingly, the 30% group had to perform more repetitions to achieve contractile failure and thus accumulated significantly more time under tension.
In contrast to current recommendations (American College of Sports Medicine, 2009), we propose that an important variable to consider in regards to the optimization of MPS and the subsequent hypertrophic response is to ensure, regardless of the load lifted, that loads are lifted to the point of contractile failure. Contractile failure, particularly when lifting lighter loads, often occurs when there is significant muscle fatigue and motor unit activation.
Significant muscle fatigue is reached by activating and exhausting a full cadre of motor units (and thus fiber types) and, regardless of any RE variable, requires a high degree of effort.
Relatively high (70–100% 1RM) training loads have been proposed to induce greater muscle hypertrophy (Campos et al., 2002; American College of Sports Medicine, 2009) than lower loads due to the increased mechanical loading and demand for fiber recruitment. However, as muscle fibers fatigue their motor units drop out and cease firing; a process that necessitates different motor units to be recruited to preserve the required force (Dorfman et al., 1990; Moritani et al., 1992).
Though lower loads may not initially need to recruit the larger motor units (innervating fast-twitch fibers) like higher loads may, with significant muscle fatigue there is an accompanied “dropout” of the smaller motor units (innervating slow-twitch fibers) such that subsequent contractions will be obliged to recruit additional (larger) motor units.
However, we hypothesize that muscle fatigue (inability to generate maximal force) is not as important as motor unit activation in inducing muscle hypertrophy. For example, to reach contractile failure exercising at ~30% 1RM one would have to achieve ~70% muscle fatigue. In contrast, to reach contractile failure at ~70% 1RM, an individual would only achieve ~30% muscle fatigue. Thus muscle fatigue, albeit rendering an increase in motor unit activation, cannot be the most important determinant of the skeletal muscle response to RE if low- and high-load RE are inducing similar MPS (Burd et al., 2010) and hypertrophy (Mitchell et al., 2012).
Instead, we hold on to the hypothesis that reaching contractile failure is what drives skeletal muscle adaptation (see Figure Figure1).1). We emphasize that it is naïve to prescribe moderate-heavy loads as the only way to induce muscle hypertrophy (American College of Sports Medicine, 2009).
Contrary to popular belief, muscle hypertrophy may not be significantly influenced by resistance exercise load (Schoenfeld et al., 2014).
Instead of any particular medley of RE variables, we propose that muscular hypertrophy is fundamentally driven by maximal motor unit recruitment and exercising until contractile failure.
Aaron TanasonComment