Hypertrophy
Narrative Review
2012
Resistance exercise-induced changes in muscle protein synthesis and their role in muscle hypertrophy
By Daniel W.D. West and Stuart M. Phillips
Sports Medicine, 42(1), pp. 17-27
<h2>Abstract</h2>
<p><a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="Muscle protein synthesis">Muscle protein synthesis</a> (MPS) represents the fundamental cellular process by which resistance exercise drives skeletal <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="muscle hypertrophy">muscle hypertrophy</a>. West and Phillips (2012) conducted a comprehensive review of the mechanistic and temporal characteristics of resistance exercise-induced MPS and its relationship to chronic muscle growth. Acute bouts of resistance exercise elevate MPS by 50-100% above baseline within 1-4 hours post-exercise, with elevated rates persisting for 24-48 hours in trained individuals and potentially longer in novices. This elevation represents a critical <a href="/terms/anabolic-window/" class="term-link" data-slug="anabolic-window" title="<a href="/terms/protein-timing/" class="term-link" data-slug="protein-timing" title="anabolic window">anabolic window</a>">anabolic window</a> during which dietary protein intake most effectively augments muscle protein accretion. Training experience was identified as a key modulator: untrained individuals exhibit larger and more prolonged MPS responses per training session compared to their trained counterparts, partially explaining the accelerated hypertrophic gains characteristic of the early training period. The review also highlighted that mixed MPS — encompassing both myofibrillar and sarcoplasmic fractions — is the most relevant measure for predicting long-term hypertrophy. These findings provide a molecular framework for understanding the protein intake, <a href="/terms/training-frequency/" class="term-link" data-slug="training-frequency" title="training frequency">training frequency</a>, and exercise selection decisions that optimize muscle growth, and have directly informed contemporary evidence-based nutrition and training guidelines.</p>
<h2>Introduction</h2>
<p>Skeletal muscle is a metabolically dynamic tissue, continuously cycling through periods of <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="protein synthesis">protein synthesis</a> and degradation. The balance between these two processes — collectively referred to as protein turnover — determines whether muscle mass is gained, lost, or maintained at any given moment [1]. In the context of resistance training, the goal is to systematically tip this balance toward net protein accretion: a state in which synthesis exceeds degradation, resulting in <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="hypertrophy">hypertrophy</a> over time.</p>
<p>Muscle protein synthesis (MPS) is operationalized experimentally through isotope tracer techniques, in which labeled amino acids (typically deuterium-labeled phenylalanine or <a href="/terms/leucine/" class="term-link" data-slug="leucine" title="leucine">leucine</a> tracers) are infused or ingested, and their incorporation into muscle protein is measured over time using muscle biopsies [2]. This methodology allows researchers to quantify fractional synthetic rates (FSR) — the percentage of the total muscle protein pool that is newly synthesized per unit time — providing a precise window into the anabolic state of muscle tissue following various interventions.</p>
<p>Prior to the systematic examination of resistance exercise-induced MPS, the field largely relied on indirect measures such as <a href="/terms/nitrogen-balance/" class="term-link" data-slug="nitrogen-balance" title="nitrogen balance">nitrogen balance</a> or limb circumference to infer changes in muscle protein metabolism. While these methods were useful, they lacked the specificity and temporal resolution to reveal the dynamic relationship between a single exercise bout and its downstream molecular consequences [3]. The development of stable isotope tracer methodology transformed this limitation, enabling researchers to track MPS responses with hour-by-hour resolution.</p>
<p>West and Phillips assembled a review of this growing literature with two primary objectives. First, they sought to characterize the magnitude and duration of resistance exercise-induced MPS elevations under varying conditions, including different exercise intensities, volumes, and protein feeding states. Second, they aimed to translate these acute MPS responses into a conceptual framework for understanding how repeated training sessions accumulate into chronic muscle hypertrophy — a process unfolding over weeks, months, and years of consistent training [4].</p>
<h2>Evidence Review</h2>
<h3>Temporal Profile of <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="MPS">MPS</a> Following Resistance Exercise</h3>
<p>The MPS response to a single resistance exercise session follows a predictable temporal trajectory. Studies using continuous amino acid infusion protocols have established that:</p>
<ul>
<li><strong>Resting baseline:</strong> MPS occurs continuously at rest at a rate of approximately 0.05-0.10% per hour in healthy adults.</li>
<li><strong>0-4 hours post-exercise:</strong> MPS rises sharply, reaching peak elevations of 50-150% above baseline depending on exercise intensity, training status, and protein feeding [5].</li>
<li><strong>4-24 hours:</strong> MPS remains elevated, though returning progressively toward baseline. The rate and extent of this decline is modulated by protein intake.</li>
<li><strong>24-48 hours:</strong> In untrained individuals, MPS may remain meaningfully elevated for up to 48 hours. In trained subjects, the response is typically resolved within 24 hours.</li>
</ul>
<p>This temporal pattern has direct implications for <a href="/terms/training-frequency/" class="term-link" data-slug="training-frequency" title="training frequency">training frequency</a> recommendations, as it defines the window during which each session contributes maximally to net protein accretion.</p>
<h3>Effect of Training Experience on MPS Response</h3>
<p>One of the most important findings reviewed by West and Phillips is the inverse relationship between training experience and the magnitude of MPS response per session. Untrained individuals experience substantially larger MPS elevations — often 2-fold greater than baseline — compared to trained individuals exercising at equivalent relative intensities [6]. This observation provides a molecular explanation for the well-known phenomenon of "beginner gains," in which novice trainees accumulate muscle at rates rarely achieved by experienced lifters even with optimized training programs.</p>
<p>As training continues, the MPS response per session attenuates through a process of molecular habituation. This necessitates <a href="/terms/progressive-overload/" class="term-link" data-slug="progressive-overload" title="progressive overload">progressive overload</a>: increasing <a href="/terms/training-volume/" class="term-link" data-slug="training-volume" title="training volume">training volume</a>, intensity, or novelty to re-sensitize muscle to hypertrophic stimulation.</p>
<h3>Role of Protein Intake in Augmenting MPS</h3>
<p>Dietary protein is the essential co-factor enabling resistance exercise-induced MPS to translate into net muscle protein accretion. In the fasted state, resistance exercise elevates both MPS and muscle protein breakdown (MPB), with MPS rising proportionally more, but the net balance remains <a href="/terms/eccentric-contraction/" class="term-link" data-slug="eccentric-contraction" title="negative">negative</a> [7]. Protein ingestion provides the amino acid substrate necessary to shift net protein balance into <a href="/terms/concentric-contraction/" class="term-link" data-slug="concentric-contraction" title="positive">positive</a> territory.</p>
<p><a href="/terms/essential-amino-acids/" class="term-link" data-slug="essential-amino-acids" title="Essential amino acids">Essential amino acids</a> (EAAs), and specifically <a href="/terms/leucine/" class="term-link" data-slug="leucine" title="leucine">leucine</a>, appear to be the primary signaling molecules activating <a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTORC1">mTORC1</a>-mediated MPS. The "leucine threshold hypothesis" proposes that a minimum leucine dose — approximately 2-3 g per meal — is required to maximally stimulate mTORC1 and upstream anabolic kinases [8]. This threshold is reached by approximately 20-40 g of high-quality protein in a single serving, providing the basis for current post-exercise protein intake recommendations.</p>
<h3>Myofibrillar vs. Sarcoplasmic MPS</h3>
<p>The review distinguished between myofibrillar MPS (synthesis of contractile proteins, actin and myosin) and sarcoplasmic MPS (synthesis of metabolic enzymes, glycogen-associated proteins, and fluid components). Resistance exercise appears to preferentially elevate myofibrillar MPS, while endurance exercise favors sarcoplasmic and mitochondrial fractions [9]. This specificity supports the notion that resistance training adaptations are primarily contractile in nature, directly relevant to strength and <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="hypertrophy">hypertrophy</a> goals.</p>
<h2>Discussion</h2>
<h3>Bridging Acute <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="MPS">MPS</a> and Chronic <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="Hypertrophy">Hypertrophy</a></h3>
<p>A central challenge in interpreting MPS data is whether acute post-exercise elevations in MPS meaningfully predict chronic muscle hypertrophy. Early enthusiasm for MPS as a direct surrogate marker of hypertrophy has been tempered by evidence that the correlation between single-session MPS responses and long-term muscle mass gains is imperfect [10]. Factors including training history, dietary protein sufficiency, total <a href="/terms/training-volume/" class="term-link" data-slug="training-volume" title="weekly volume">weekly volume</a>, and <a href="/terms/sleep-hygiene/" class="term-link" data-slug="sleep-hygiene" title="sleep quality">sleep quality</a> all modulate the translation of repeated MPS stimulation into cumulative protein accretion.</p>
<p>Nonetheless, West and Phillips argue that the cumulative MPS signal across multiple weekly training sessions — rather than any single acute response — is the more biologically relevant predictor of long-term hypertrophy. Each training session generates an MPS pulse; the sum of these pulses over weeks and months, minus the degradation that occurs between sessions, determines net muscle protein accretion. This cumulative model aligns with the empirical observation that <a href="/terms/training-frequency/" class="term-link" data-slug="training-frequency" title="training frequency">training frequency</a> and volume are positively associated with hypertrophic outcomes.</p>
<h3>Implications for Post-Exercise Protein Nutrition</h3>
<p>The MPS evidence provides the mechanistic foundation for post-exercise protein nutrition recommendations. The findings that: (1) MPS is acutely elevated post-exercise; (2) protein ingestion amplifies this elevation; and (3) a <a href="/terms/leucine/" class="term-link" data-slug="leucine" title="leucine">leucine</a> threshold governs <a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTORC1">mTORC1</a> activation together justify consuming 20-40 g of high-quality protein within the post-exercise period [11]. While the "<a href="/terms/anabolic-window/" class="term-link" data-slug="anabolic-window" title="<a href="/terms/protein-timing/" class="term-link" data-slug="protein-timing" title="anabolic window">anabolic window</a>">anabolic window</a>" concept has been refined — protein timing around exercise is less critical than total daily intake — ensuring protein availability during the 4-hour post-exercise period aligns with the MPS data.</p>
<h3>Training Status and Protein Requirements</h3>
<p>The observation that trained individuals exhibit smaller per-session MPS responses than untrained individuals does not imply that their muscles are less responsive overall. Rather, trained muscle requires greater mechanical stimulation (more volume, closer <a href="/terms/proximity-to-failure/" class="term-link" data-slug="proximity-to-failure" title="proximity to failure">proximity to failure</a>) to elicit equivalent MPS responses [12]. This explains why protein requirements may be marginally higher for trained individuals engaged in high-volume training, and why the <a href="/terms/dose-response-relationship/" class="term-link" data-slug="dose-response-relationship" title="dose-response">dose-response</a> between protein intake and MPS is not identical across experience levels.</p>
<h3>mTORC1 as the Central Anabolic Hub</h3>
<p>The review centers mTOR complex 1 (mTORC1) as the convergence point for mechanical and nutritional anabolic signals. Resistance exercise activates mTORC1 through <a href="/terms/mechanical-tension/" class="term-link" data-slug="mechanical-tension" title="mechanical tension">mechanical tension</a>-sensitive pathways, while protein ingestion activates it through amino acid sensing. The synergistic activation of mTORC1 by both stimuli simultaneously — exercise plus protein — produces greater MPS than either stimulus alone [13]. This mechanistic insight directly supports concurrent protein ingestion with training as an evidence-based strategy.</p>
<h3>Limitations and Future Directions</h3>
<p>MPS measurement protocols — particularly muscle biopsies from vastus lateralis — sample a limited region of a single muscle, raising questions about whole-body and inter-muscle generalizability. The assumption that MPS measurements from one muscle reflect systemic anabolic state remains contested. Future research should continue to improve the resolution of MPS-to-hypertrophy predictive models.</p>
<h2>Practical Recommendations</h2>
<h3>Protein Intake to Maximize <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="MPS">MPS</a></h3>
<p>The MPS evidence supports the following protein intake guidelines for individuals engaged in resistance training:</p>
<ul>
<li><strong>Daily protein target:</strong> 1.6-2.2 g per kilogram of body weight provides a robust stimulus for MPS across training experience levels [14].</li>
<li><strong>Per-meal dose:</strong> Each meal should contain 0.4-0.5 g of protein per kilogram of body weight to reach or exceed the <a href="/terms/leucine/" class="term-link" data-slug="leucine" title="leucine">leucine</a> threshold. For a 75 kg individual, this translates to approximately 30-38 g of protein per meal.</li>
<li><strong>Protein source quality:</strong> Prioritize complete proteins rich in <a href="/terms/essential-amino-acids/" class="term-link" data-slug="essential-amino-acids" title="essential amino acids">essential amino acids</a> — lean meats, fish, eggs, dairy, and high-quality plant-based combinations. Leucine content above 2-3 g per serving is a useful quality marker.</li>
</ul>
<h3>Optimizing Post-Exercise <a href="/terms/protein-timing/" class="term-link" data-slug="protein-timing" title="Protein Timing">Protein Timing</a></h3>
<p>While total daily protein intake is the primary determinant of MPS-driven <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="hypertrophy">hypertrophy</a>, consuming protein within the post-exercise period (0-4 hours) aligns with the MPS elevation window:</p>
<ul>
<li>A post-exercise meal or shake containing 25-40 g of high-quality protein within 1-2 hours of training is a practical and evidence-supported strategy.</li>
<li>Pre-exercise protein ingestion can extend amino acid availability into the post-exercise period, making the precise timing of post-exercise protein less critical when a solid pre-workout meal is consumed within 3-4 hours.</li>
</ul>
<h3>Leveraging <a href="/terms/training-frequency/" class="term-link" data-slug="training-frequency" title="Training Frequency">Training Frequency</a> for Cumulative MPS</h3>
<p>Given that MPS returns toward baseline within 24-48 hours, training each muscle group more than once per week maximizes the number of weekly MPS pulses and thereby maximizes cumulative anabolic signaling:</p>
<ul>
<li><strong>Beginners:</strong> 2-3 sessions per week per muscle group is sufficient to take advantage of the extended MPS response characteristic of untrained muscle.</li>
<li><strong>Intermediate and advanced trainees:</strong> 2-4 sessions per week per muscle group, distributed to ensure the muscle is re-stimulated before MPS from the previous session fully resolves.</li>
</ul>
<h3>Managing the MPS Attenuation in Experienced Trainees</h3>
<p>Advanced trainees should address the attenuated per-session MPS response through:</p>
<ol>
<li><strong><a href="/terms/progressive-overload/" class="term-link" data-slug="progressive-overload" title="Progressive overload">Progressive overload</a>:</strong> Regularly increasing load, volume, or exercise difficulty to re-sensitize <a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTORC1">mTORC1</a> to mechanical stimulation.</li>
<li><strong>Exercise variation:</strong> Periodically introducing novel movement patterns that challenge muscle at different lengths or angles, preserving the novelty-driven component of MPS elevation.</li>
<li><strong>Optimizing nutrition:</strong> Ensuring protein sufficiency at every meal, particularly surrounding training sessions, to fully capitalize on each MPS pulse.</li>
</ol>
<h3>Pre-Sleep Protein</h3>
<p>Emerging evidence suggests that consuming 30-40 g of <a href="/terms/casein/" class="term-link" data-slug="casein" title="casein">casein</a> protein before sleep extends MPS through the overnight fasting period, when protein synthesis would otherwise decline due to reduced amino acid availability [15]. For individuals seeking to maximize hypertrophy, this represents an additional practical opportunity to increase cumulative weekly MPS exposure.</p>