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Introduction

Muscle growth has never lacked opinions. In gyms and online, hypertrophy is often attributed to hormone spikes, the burn, the pump, or metabolic stress. But muscle tissue does not respond to trends, it responds to biology.

A comprehensive 2026 review published in the Journal of Sport and Health Science systematically examined the mechanisms behind load-induced hypertrophy. Instead of reinforcing gym folklore, the authors evaluated human mechanistic data, tracer studies, and controlled resistance training experiments to answer a central question: What actually drives skeletal muscle growth at the cellular level?

• Type of paper: Mechanistic review

• Focus: Load-induced hypertrophy in humans

• Domains analyzed: Mechanical tension, hormonal fluctuations, metabolic stress, cell swelling, sarcoplasmic hypertrophy, and physiological limits

• Core conclusion: Mechanical tension is the primary stimulus initiating hypertrophy

Rather than relying on single experiments, this review integrates decades of human resistance training data to evaluate which mechanisms hold up under scrutiny, and which do not.

What the Research Showed

Across multiple experimental models, the evidence converges on a consistent pattern:

• Acute post-exercise increases in testosterone, growth hormone, and IGF-1 do not correlate with muscle protein synthesis or long-term hypertrophy.

• Artificially elevating lactate does not increase mTOR activation or muscle protein synthesis.

• Adding blood flow restriction to heavy training does not produce additional hypertrophy when mechanical tension is matched.

• Increases in muscle fiber size are predominantly associated with myofibrillar protein accretion.

• Hypertrophy follows a diminishing-return curve over time.

These findings are not drawn from a single isolated trial, they emerge repeatedly across unilateral training studies, hormone-manipulation designs, tracer methodology, and imaging-based structural analyses.

Mechanisms & Physiology

Mechanical Tension & Mechanotransduction

Mechanical tension refers to the force generated within muscle fibers during contraction or stretch. That force is sensed by molecular structures, including integrins, focal adhesion complexes, and titin, which convert mechanical load into biochemical signals. This process is known as mechanotransduction.

These signals converge on pathways such as mTORC1 and associated regulators of protein translation. The result: increased myofibrillar protein synthesis and fiber cross-sectional area expansion.

Importantly, hypertrophy can occur across a wide load range. Light loads performed close to failure and heavy loads performed with high force output both generate sufficient mechanical tension to stimulate these pathways. The muscle appears to respond to tension magnitude and fiber recruitment, not to load labels like “light” or “heavy.”

Hormones: Correlation vs. Causation

The review closely examines studies that directly tested whether acute hormonal elevations drive hypertrophy.

In unilateral training models, only the trained limb hypertrophied, despite identical systemic hormone exposure. In experiments designed to create 4–5× higher post-exercise hormone concentrations, no differences in muscle protein synthesis or hypertrophy were observed between high-hormone and low-hormone conditions.

Sex-based data strengthens this conclusion. Despite 10–20× higher testosterone levels in males, relative hypertrophy rates between males and females are similar when training variables are matched.

The distinction is critical: physiological hormonal fluctuations differ entirely from supraphysiological anabolic steroid exposure. Pharmacological testosterone dramatically increases fat-free mass. Natural post-workout spikes do not.

Metabolic Stress & Lactate: What the Evidence Actually Tests

Metabolic stress theory suggests that lactate, hydrogen ions, and inorganic phosphate stimulate growth directly. However, infusion studies that elevated lactate systemically failed to increase mTOR activation or muscle protein synthesis.

Even blood flow restriction (BFR), which amplifies metabolite accumulation, does not produce additional hypertrophy when mechanical tension is equated. What BFR likely alters is fiber recruitment timing, not anabolic signaling per se.

In other words, metabolic stress may influence how fibers are recruited during fatigue. But the downstream hypertrophic stimulus still appears to be mechanical loading of those fibers.

Sarcoplasmic vs. Myofibrillar Hypertrophy

Sarcoplasmic hypertrophy refers to disproportionate expansion of non-contractile components (fluid, glycogen, enzymes) relative to myofibrillar proteins.

Some short-term high-volume studies suggested possible sarcoplasmic expansion. However, many of these findings carry statistical limitations or small sample sizes. More robust tracer studies show that resistance training primarily elevates myofibrillar protein synthesis, not sarcoplasmic protein synthesis.

Recent imaging evidence indicates that radial fiber growth is largely driven by myofibrillogenesis, the addition of contractile proteins, rather than volumetric expansion of non-contractile space.

Sarcoplasmic expansion, if it occurs, appears minor or potentially transient compared to contractile growth.

Physiological Limits of Muscle Growth

A meta-analysis cited in the review examined 111 resistance training studies. The average gain in fat-free mass across ~10 weeks was approximately 1.53 kg. High responders gained around 3 kg; low responders gained less than 0.5 kg.

Growth is fastest in early training phases and progressively slows. Long-term natural fat-free mass index (FFMI) ceilings appear constrained. In contrast, anabolic steroid use produces dramatically greater increases.

Muscle hypertrophy is therefore:

• Progressive

• Mechanically driven

• Genetically influenced

• Subject to diminishing returns

It is not limitless.

Practical Application

From a physiological standpoint, the implications are straightforward:

• Prioritize progressive mechanical tension.

• Load selection can vary, effort and fiber recruitment matter more.

• Volume shows a dose-response relationship, but more is not infinitely better.

• Programming should not revolve around chasing hormone spikes or the pump.

• Expect growth to slow as training age increases.

The muscle adapts structurally to repeated strain. Consistency and progressive overload remain central.

The Bottom Line

When examined at the cellular level, hypertrophy appears to be a structural adaptation to mechanical tension and intracellular signaling cascades, not a response to transient systemic spikes or gym sensations. The biology of muscle growth is far more grounded in force transmission and protein accretion than in metabolic hype.

Reference

Van Every DW, Lees MJ, Wilson B, Nippard J, Phillips SM.
Load-induced human skeletal muscle hypertrophy: Mechanisms, myths, and misconceptions.
Journal of Sport and Health Science. 2026;15:101104.
DOI: 10.1016/j.jshs.2025.101104