Cardio
Narrative Review
2016
Interference of Cardiorespiratory Training on Resistance Exercise-Induced Muscle Hypertrophy
By Kevin A. Murach and James R. Bagley
Journal of Strength and Conditioning Research, 30(7), pp. 1991-2004
<h2>Abstract</h2>
<p>The compatibility of cardiorespiratory exercise with resistance exercise-induced skeletal <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="muscle hypertrophy">muscle hypertrophy</a> is a topic of significant practical relevance. The "<a href="/terms/concurrent-training/" class="term-link" data-slug="concurrent-training" title="interference effect">interference effect</a>"—wherein aerobic training attenuates anabolic adaptations to resistance exercise—has been documented at both phenotypic and molecular levels. This narrative review examines the mechanistic basis for interference and synthesizes evidence on the practical conditions under which cardiorespiratory training meaningfully impairs hypertrophic outcomes.</p>
<p>At the molecular level, aerobic exercise activates AMPK, which phosphorylates raptor and thereby attenuates <a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTORC1">mTORC1</a> signaling, the primary anabolic pathway for <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="muscle protein synthesis">muscle protein synthesis</a>. The magnitude of this molecular interference depends on exercise intensity, duration, and the temporal proximity of aerobic and resistance training sessions within the same day. At the phenotypic level, concurrent training studies demonstrate that the interference effect on hypertrophy is real but dose-dependent—low-to-moderate volumes of aerobic exercise produce minimal impairment, while high volumes substantially attenuate hypertrophic outcomes.</p>
<p>Practical recommendations are provided for organizing concurrent training programs to minimize interference while preserving cardiovascular health benefits, including modality selection, volume guidelines, session ordering, and inter-session recovery timing.</p>
<h2>Introduction</h2>
<p>The relationship between cardiorespiratory training and resistance exercise-induced <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="muscle hypertrophy">muscle hypertrophy</a> has been a subject of scientific inquiry for over four decades. The landmark work of Hickson [1] provided the first systematic evidence that simultaneously training for endurance and strength produces inferior strength outcomes compared with resistance training alone—a phenomenon he termed the "<a href="/terms/concurrent-training/" class="term-link" data-slug="concurrent-training" title="interference effect">interference effect</a>." Subsequent research has extended this concept to hypertrophy outcomes and identified the molecular signaling pathways through which aerobic exercise may antagonize anabolic adaptations to resistance exercise [2].</p>
<p>Despite these mechanistic insights, the practical relevance of the interference effect for most resistance-trained individuals remains contested. Many athletes combine aerobic and resistance training not from theoretical choice but from practical necessity—health guidelines recommend both forms of exercise, sport training requires both capacities, and many individuals exercise for multiple goals simultaneously [3]. The question is therefore not whether aerobic and resistance training can coexist, but rather under what conditions the interference effect is clinically meaningful and how program design can minimize its impact.</p>
<p>The molecular biology of concurrent training interference has advanced considerably in the past decade. The discovery that AMPK—the cellular energy sensor activated by aerobic exercise—phosphorylates and inhibits components of the <a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTOR">mTOR</a> signaling complex provided a compelling molecular mechanism linking aerobic exercise to attenuation of <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="muscle protein synthesis">muscle protein synthesis</a> [4]. However, the in vitro demonstration of this pathway inhibition does not necessarily predict phenotypic outcomes, as the in vivo regulation of these pathways involves complex temporal dynamics and compensatory mechanisms.</p>
<p>This review synthesizes the molecular and phenotypic evidence for cardiorespiratory training interference with hypertrophy, with particular emphasis on the <a href="/terms/dose-response-relationship/" class="term-link" data-slug="dose-response-relationship" title="dose-response relationship">dose-response relationship</a> between aerobic <a href="/terms/training-volume/" class="term-link" data-slug="training-volume" title="training volume">training volume</a> and hypertrophic impairment, and practical strategies for program organization.</p>
<h3>References</h3>
<p>[1] Hickson RC. Interference of strength development by simultaneously training for strength and endurance. <em>Eur J Appl Physiol</em>. 1980;45:255–263.
[2] Fyfe JJ, et al. Interference between concurrent resistance and endurance exercise. <em>Sports Med</em>. 2014;44:743–762.
[3] Haskell WL, et al. Physical activity and public health. <em>Med Sci Sports Exerc</em>. 2007;39:1423–1434.
[4] Bolster DR, et al. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle. <em>J Biol Chem</em>. 2002;277:23977–23980.</p>
<h2>Molecular Mechanisms of Interference</h2>
<h3>The AMPK-<a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTOR">mTOR</a> Antagonism</h3>
<p>The central molecular mechanism underlying cardiorespiratory training interference with <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="hypertrophy">hypertrophy</a> is the antagonism between AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) [1]. AMPK functions as a cellular energy sensor, activated by the increased AMP:<a href="/terms/adenosine-triphosphate/" class="term-link" data-slug="adenosine-triphosphate" title="ATP">ATP</a> ratio that occurs during sustained aerobic exercise. Once activated, AMPK promotes catabolic pathways (glycolysis, fatty acid oxidation) while simultaneously phosphorylating and inhibiting anabolic processes, including mTORC1.</p>
<p>mTORC1 is the master regulator of skeletal <a href="/terms/muscle-protein-synthesis/" class="term-link" data-slug="muscle-protein-synthesis" title="muscle protein synthesis">muscle protein synthesis</a>. Phosphorylation of mTORC1's downstream substrates—p70S6K1 and 4E-BP1—drives ribosomal translation of muscle structural proteins including myosin heavy chain and actin [2]. When aerobic exercise activates AMPK within the same temporal window as resistance exercise-induced mTORC1 signaling, the competing phosphorylation events attenuate the net anabolic signal.</p>
<h3>PGC-1α and the Fiber Type Shift</h3>
<p>Endurance exercise also activates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a transcriptional co-activator that drives mitochondrial biogenesis and promotes a slow-twitch (Type I) fiber phenotype [3]. Concurrent activation of both AMPK/PGC-1α and mTOR signaling creates competing transcriptional programs, as Type I fibers have lower maximal force and power-producing capacity than Type II fibers. Chronic aerobic training may therefore promote a fiber type shift toward Type I characteristics that is counterproductive to hypertrophy.</p>
<h3>Temporal Dynamics of Molecular Interference</h3>
<p>The magnitude of molecular interference depends critically on the temporal proximity of aerobic and resistance training sessions [4]. Aerobic exercise-induced AMPK activation typically peaks within 30–60 minutes post-exercise and declines substantially over 3–6 hours. Resistance exercise-induced mTORC1 signaling peaks at approximately 1–3 hours post-exercise and remains elevated for 24–48 hours. Same-session or closely spaced training ( 3 hours apart) creates the greatest overlap between AMPK activation and the mTOR-dependent protein synthesis window, maximizing molecular interference.</p>
<h3>Myostatin and Inflammatory Signaling</h3>
<p>Aerobic exercise also transiently elevates myostatin, a member of the TGF-β superfamily that acts as a <a href="/terms/eccentric-contraction/" class="term-link" data-slug="eccentric-contraction" title="negative">negative</a> regulator of muscle mass [5]. Concurrent elevation of myostatin during the post-exercise <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> may further attenuate hypertrophic signaling. Additionally, the accumulated inflammatory burden from high-volume aerobic training may overwhelm the anabolic repair processes that normally accompany resistance <a href="/terms/muscle-damage/" class="term-link" data-slug="muscle-damage" title="exercise-induced muscle damage">exercise-induced muscle damage</a>.</p>
<h3>References</h3>
<p>[1] Bolster DR, et al. AMPK suppresses protein synthesis. <em>J Biol Chem</em>. 2002;277:23977–23980.
[2] Laplante M, Sabatini DM. mTOR signaling in growth. <em>Cell</em>. 2012;149:274–293.
[3] Lin J, et al. Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres. <em>Nature</em>. 2002;418:797–801.
[4] Baar K. Using molecular biology to maximize <a href="/terms/concurrent-training/" class="term-link" data-slug="concurrent-training" title="concurrent training">concurrent training</a>. <em>Sports Med</em>. 2014;44:117–125.
[5] Hittel DS, et al. Myostatin decreases with aerobic exercise. <em>Med Sci Sports Exerc</em>. 2010;42:2157–2164.</p>
<h2>Practical Considerations for <a href="/terms/concurrent-training/" class="term-link" data-slug="concurrent-training" title="Concurrent Training">Concurrent Training</a></h2>
<h3>Volume Is the Primary Determinant of Interference</h3>
<p>The available phenotypic evidence consistently demonstrates a <a href="/terms/dose-response-relationship/" class="term-link" data-slug="dose-response-relationship" title="dose-response relationship">dose-response relationship</a> between aerobic <a href="/terms/training-volume/" class="term-link" data-slug="training-volume" title="training volume">training volume</a> and the magnitude of hypertrophic impairment. Aerobic training volumes of ≤2 sessions per week with durations of ≤30 minutes appear to produce minimal interference with resistance training-induced <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="hypertrophy">hypertrophy</a> [1]. At these volumes, the molecular interference mechanisms described above are likely insufficient to overcome the potent anabolic stimulus from well-designed resistance training.</p>
<p>In contrast, aerobic training volumes of ≥4 sessions per week, particularly with session durations exceeding 45 minutes, consistently attenuate hypertrophic outcomes in concurrent training studies [2]. Practitioners should therefore view aerobic training volume—rather than the mere presence of aerobic exercise—as the critical variable to manage when hypertrophy is a primary goal.</p>
<h3>Modality Selection</h3>
<p>The type of aerobic exercise has a substantial impact on interference magnitude. Running produces greater interference with lower body resistance training adaptations than cycling, due to the mechanical similarity and eccentric loading overlap between running and lower body resistance exercises [3]. For individuals prioritizing lower body hypertrophy, cycle ergometry, swimming, or rowing represent preferable aerobic modalities that minimize direct muscle group overlap. Upper body resistance training outcomes appear relatively insensitive to most forms of aerobic exercise.</p>
<h3>Session Ordering and Temporal Separation</h3>
<p>When aerobic and resistance training must be performed in the same session, resistance exercise should generally precede aerobic exercise [4]. This ordering preserves maximal neuromuscular recruitment for resistance exercise and ensures that the primary anabolic signaling window occurs before AMPK activation from subsequent aerobic work. However, the most effective strategy remains separating sessions by at least 6–8 hours when daily concurrent training is unavoidable, or training on different days where scheduling permits.</p>
<h3>Intensity of Aerobic Training</h3>
<p>Lower intensity aerobic exercise (Zone 2; 60–70% HRmax) produces substantially less AMPK activation than <a href="/terms/hiit/" class="term-link" data-slug="hiit" title="high-intensity interval training">high-intensity interval training</a> at equivalent durations. For individuals whose primary goal is hypertrophy but who need to maintain cardiovascular health, low-intensity steady-state aerobic exercise on separate days from resistance training represents the minimum-interference strategy [5].</p>
<h3>References</h3>
<p>[1] Murach KA, Bagley JR. Skeletal muscle hypertrophy with concurrent exercise training. <em>J Strength Cond Res</em>. 2016;30:1991–2004.
[2] Wilson JM, et al. Concurrent training <a href="/terms/meta-analysis/" class="term-link" data-slug="meta-analysis" title="meta-analysis">meta-analysis</a>. <em>J Strength Cond Res</em>. 2012;26:2293–2307.
[3] Fyfe JJ, et al. Interference between concurrent resistance and endurance exercise. <em>Sports Med</em>. 2014;44:743–762.
[4] Chtourou H, Souissi N. The effect of training at a specific time of day. <em>J Strength Cond Res</em>. 2012;26:1984–2005.
[5] Baar K. Minimizing interference: practical strategies. <em>Sports Med</em>. 2014;44:117–125.</p>
<h2>Conclusions</h2>
<p>The interference of cardiorespiratory training with resistance exercise-induced <a href="/terms/muscle-hypertrophy/" class="term-link" data-slug="muscle-hypertrophy" title="muscle hypertrophy">muscle hypertrophy</a> is a real and mechanistically supported phenomenon, but its practical magnitude is highly context-dependent and is not an inevitable consequence of combining aerobic and resistance training. The following evidence-based conclusions can be drawn:</p>
<p><strong>Molecular interference is real but not deterministic.</strong> The AMPK-<a href="/terms/mtor/" class="term-link" data-slug="mtor" title="mTOR">mTOR</a> antagonism provides a compelling mechanistic foundation for the <a href="/terms/concurrent-training/" class="term-link" data-slug="concurrent-training" title="interference effect">interference effect</a>, but in vivo regulation involves complex temporal dynamics that can be managed through program design.</p>
<p><strong>Volume is the critical modifiable variable.</strong> Low-to-moderate aerobic training volumes (≤2–3 sessions per week, ≤30 minutes per session) produce minimal impairment of hypertrophic outcomes when resistance training programming is otherwise optimized. Hypertrophy-focused athletes can maintain cardiovascular fitness within these parameters without meaningful sacrifice of muscle development.</p>
<p><strong>Modality matters.</strong> Running imposes greater interference with lower body hypertrophy than cycling or other low-impact modalities. This finding should directly inform modality selection for athletes who prioritize lower limb development.</p>
<p><strong>Temporal separation mitigates interference.</strong> Separating aerobic and resistance sessions by at least 6–8 hours, or ideally performing them on different days, substantially reduces the temporal overlap of antagonistic signaling cascades.</p>
<p><strong>Cardiorespiratory fitness supports rather than undermines long-term training capacity.</strong> Adequate aerobic capacity improves recovery between resistance training sets, enhances nutrient delivery to working muscles, and supports general health and longevity. The goal is not to eliminate aerobic exercise but to optimize its integration with resistance training in a manner that minimizes interference while preserving its substantial health and performance benefits.</p>
<p>Future research should examine individual variation in interference susceptibility, the long-term effects of different concurrent training configurations on hypertrophy, and whether nutrition strategies (e.g., carbohydrate timing, <a href="/terms/leucine/" class="term-link" data-slug="leucine" title="leucine">leucine</a> supplementation) can pharmacologically attenuate molecular interference pathways.</p>