Let’s set the record straight… The idea that metabolic stress (the “burn” you feel during high-rep training) is a major driver of hypertrophy has been widely popularized—but recent evidence-based research suggests it plays only a secondary or indirect role, if any at all.

Why is that?

Mechanical tension is the dominant stimulus or key driver for hypertrophy. It is consistently shown the be the most potent stimulus for hypertrophy, again & again through evidence based research. Here is an article explaining  what mechanical tension is & why it is important: https://www.cptlij.com/blog?id=67c9164f15cd4e7a11afb4ba

Research has also show that high mechanical tension activates mechanosensors in muscle fibers, triggering intracellular pathways (like mTOR) responsible for muscle protein synthesis.

Metabolic stress occurs from byproducts like lactate, hydrogen ions, and inorganic phosphate during high-rep or occlusion training. These can contribute to cell swelling and muscle pump—but without sufficient mechanical tension, this stress alone doesn’t lead to significant growth.

Schoenfeld et al. (2015) showed that low-load, high-rep training (which causes more metabolic stress) only produced similar hypertrophy as high-load training when taken to failure, indicating that mechanical tension from full motor unit recruitment is still the key factor. https://pubmed.ncbi.nlm.nih.gov/28834797/

While metabolic stress correlates with hypertrophy in some studies, it doesn't have a direct causal mechanism. The hypertrophic response is likely due to the fatigue-induced increase in tension rather than the metabolites themselves.

Schoenfeld (2010) – "The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training": While metabolic stress is listed as a potential contributor, the paper emphasizes that mechanical tension is the primary driver. https://pubmed.ncbi.nlm.nih.gov/20847704/

Haun et al. (2019) – "A Critical Evaluation of the Biological Construct Skeletal Muscle Hypertrophy": Concludes that metabolic stress has not been shown to induce hypertrophy without mechanical tension. https://pmc.ncbi.nlm.nih.gov/articles/PMC6423469/

Krzysztofik et al. (2019) – Review notes that metabolic stress may enhance hypertrophy but not independently drive it. https://pmc.ncbi.nlm.nih.gov/articles/PMC6423469/

This recent study explores how local metabolic stress from resistance exercise influences muscle adaptations. It concludes that while metabolic stress can facilitate improvements in muscle strength and endurance, its role in hypertrophy is secondary to mechanical tension.

https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1549609/abstract