Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men
Open accessAbstract
BACKGROUND: We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen men (21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition. CONCLUSIONS/SIGNIFICANCE: These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.
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The translational capacity bottleneck possesses a high activation threshold: a minimal mechanical volume is required to sustain the Pol I transcription spark long enough to outpace the basal decay rate of existing ribosomes.
“This strongly indicates that the translational capacity bottleneck possesses a high activation threshold: a minimal mechanical volume is strictly required to sustain the Pol I transcription spark long enough to outpace the basal decay rate of existing ribosomes [35,87,88].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [88]
The Results (Muscle protein synthesis; page unavailable) report that myofibrillar protein synthesis remained elevated at 24 hours only after the low-load, high-volume condition, supporting a link between exercise volume and a sustained response. The paper does not establish a strict minimum-volume threshold or show that Pol I transcription must outpace ribosome decay; its Discussion says the mechanisms maintaining synthesis remain relatively undefined. (LLM, conf=0.84)
Experimental — accuracy not yet measuredResearch where participants expended a high level of effort suggests that the muscle protein synthetic response to low-load training is at least as robust as when training with heavier loads.
“Consistent with this line of evidence, research where participants expended a high level of effort suggests that the MPS response to low-load training is at least as robust as when training with heavier loads [39].”
From Loading recommendations for muscle strength, hypertrophy, and local endurance: a re-examination of the repetition continuum. (2021) · cites this paper as [39]
Some studies show an impaired acute muscle protein synthetic response when training with lower loads, while others report similar increases in mixed and myofibrillar protein synthesis rates.
“Some studies show an impaired acute MPS response when training with lower loads [37,38] while others report similar increases in mixed and myofibrillar protein synthesis rates [39].”
From Loading recommendations for muscle strength, hypertrophy, and local endurance: a re-examination of the repetition continuum. (2021) · cites this paper as [39]
Post-exercise cold-water immersion attenuates markers associated with ribosome biogenesis compared with active recovery.
“Figueiredo et al. showed that post-exercise cold-water immersion attenuated markers associated with ribosome biogenesis compared with active recovery [88].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [88]
The Methods and Results describe resistance-exercise loads and muscle protein synthesis, not post-exercise cold-water immersion versus active recovery. Searches for cold-water immersion, ribosome biogenesis, and Figueiredo found no passage in our copy addressing the attributed finding. The paper text provides no basis to confirm or contradict it. (LLM, conf=0.78)
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Nutritional interventions to augment resistance training-induced skeletal muscle hypertrophy
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Self-citationNutritional modulation of training-induced skeletal muscle adaptations
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Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise
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Self-citationMuscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy
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Theoretical and Practical Aspects of Different Cluster Set Structures: A Systematic Review
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Self-citationMechanisms Behind Blood Flow–Restricted Training and its Effect Toward Muscle Growth
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Self-citationERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling
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Exercise-induced skeletal muscle signaling pathways and human athletic performance
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Self-citationOptimising the ‘Mid-Stage’ Training and Testing Process After ACL Reconstruction
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Murphy, C. H., Churchward-Venne, T. A., Mitchell, C. J., Kolar, N. M., Kassis, A., Karagounis, L. G., Burke, L. M., Hawley, J. A., & Phillips, S. M. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00550.2014 · Cited by 124 · see citing works
Self-citationSatellite Cells Contribution to Exercise Mediated Muscle Hypertrophy and Repair.
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Nutrient-rich meat proteins in offsetting age-related muscle loss
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Self-citationBell, K. E., Séguin, C., Parise, G., Baker, S. K., & Phillips, S. M. (2015) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu313 · Cited by 118 · see citing works
Self-citationSong, Z., Moore, D. R., Hodson, N. W., Ward, C., Dent, J. R., O’Leary, M. F., Shaw, A. M., Hamilton, D. L., Sarkar, S., Gangloff, Y., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-05483-x · Cited by 120 · see citing works
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Self-citationTraining to Fatigue: The Answer for Standardization When Assessing Muscle Hypertrophy?
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Donges, C. E., Burd, N. A., Duffield, R., Smith, G. C., West, D. W. D., Short, M. J., Mackenzie, R., Plank, L. D., Shepherd, P. R., Phillips, S. M., et al. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00166.2012 · Cited by 114 · see citing works
Self-citationReturning to Play after Prolonged Training Restrictions in Professional Collision Sports
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Frequency: The overlooked resistance training variable for inducing muscle hypertrophy?
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Self-citationIs repetition failure critical for the development of muscle hypertrophy and strength?
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Time course for arm and chest muscle thickness changes following bench press training
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Mechanisms of Blood Flow Restriction: The New Testament
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Self-citationHome-based resistance training for older adults: a systematic review.
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Burd, N. A., Mitchell, C. J., Churchward-Venne, T. A., & Phillips, S. M. (2012) · Applied Physiology Nutrition and Metabolism · doi:10.1139/h2012-022 · Cited by 99 · see citing works
Self-citationNóbrega, S. R., Ugrinowitsch, C., Pintanel, L., Barcelos, C., & Libardi, C. A. (2018) · Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000001787 · Cited by 97 · see citing works
The Challenge of Maintaining Metabolic Health During a Global Pandemic
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Optimising the Early-Stage Rehabilitation Process Post-ACL Reconstruction
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Is There a Minimum Intensity Threshold for Resistance Training-Induced Hypertrophic Adaptations?
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Keeping Older Muscle “Young” through Dietary Protein and Physical Activity
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Self-citationBlood flow restriction: An evidence based progressive model (Review)
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Regulation of muscle protein synthesis in humans
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Self-citationMaximizing Post-exercise Anabolism: The Case for Relative Protein Intakes
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- Authors
- Burd, N. A., West, D. W. D., Staples, A. W., Atherton, P. J., Baker, J. M., Moore, D. R., Holwerda, A. M., Parise, G., Rennie, M. J., Baker, S. K., & Phillips, S. M.
- Affiliations
- McMaster University (CA)
- University of Nottingham (GB)
- Corresponding author
- Phillips, Stuart M.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-08-09
- Volume
- 5
- Issue
- 8
- Pages
- e12033
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2918506
- OpenAlex
- W2160436389
- Cited by
- 531
- References
- 54
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 37 · 2023: 21 · 2022: 40 · 2021: 31 · 2020: 37 · 2019: 45 · 2018: 30 · 2017: 37 · 2016: 44 · 2015: 38 · 2014: 34 · 2013: 26 · 2012: 37
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- resistance training, exercise intensity, exercise volume, muscle protein synthesis, myofibrillar protein synthesis, Akt signaling, mTOR signaling, ERK1/2, p70S6K, 4E-BP1, Pax7, myogenic gene expression, leg extension, young men
- MeSH terms
- Gene Expression Regulation, Humans, Male, Muscle Proteins, Phenylalanine, RNA, Messenger, Signal Transduction, Exercise, Weight-Bearing, Myogenic Regulatory Factors, Muscle Fibers, Skeletal, Intracellular Space, PAX7 Transcription Factor, Resistance Training, Young Adult
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