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David Cooke

Mechanisms of Hypertrophy


The predominant goal for almost every gym-goer in the world is to ‘gain muscle’ or to ‘tone up’. Both of these require muscular hypertrophy – which is an increase in the cross-sectional area (CSA) of a muscle. 

It is well known that the optimal method to achieve greatest muscular hypertrophy is via resistance training using free-weights or machines, but many are left wondering what is the best way to use this method to achieve maximal gains in muscle size. 


Motor Unit: A combination of a neuron (link to the nervous system and the brain) and all of the muscle fibres which that neuron fires.

Glycogen: Carbohydrates that are stored in the body.

Periodisation: Structuring of training to allow for a physiological response.

There are 3 mechanisms that are essential to any training programme that is geared towards inducing muscular hypertrophy:

Mechanical Tension – This is the effect of force throughout a range of motion. High mechanical tension can be created using very high loads or by utilising full ranges of motion with a significant load. This causes muscle hypertrophy by recruiting a lot of motor units and a large proportion of muscle fibres, particularly the fast twitch type (Type 2A & 2B). 

Metabolic Stress – This is the process of accumulating metabolites in the muscles which include: lactate, hydrogen ion, inorganic phosphate, creatine and others. This is commonly referred to as the ‘burn’ or the ‘pump’. This type of training utilises anaerobic glycolysis (Glycogen breakdown without the presence of oxygen) which means the body becomes more efficient at processing and dealing with metabolites which in turn allows us to train at a greater capacity. This allows us to train more often and with more intensity, which will allow for greater muscle gains. 

Muscle Damage – Muscle damage is a product of resistance training due to inflicting injuries to the muscle architecture (connective tissue e.g. ligaments, tendons and the contractile elements e.g. fibres, muscle protein). This causes inflammation in the area which results in more acute responses in muscle cross sectional area due to an increase in the sarcoplasm (cellular tissue that is not muscle fibre). The process of inflammation promotes recovery and stimulates muscle protein synthesis, growth hormone response and testosterone increase. This can also be localised to certain areas of the muscle to some extent and certain muscle fibre types.

There are many variables which we can manipulate our training in order to create the above listed mechanisms. 

Intensity – This typically refers to load (weight on the bar). So, utilising high loads for relevant rep ranges is typically regarded as the most important training factor. Training with non-challenging loads will not maximise muscle hypertrophy. Higher loads in moderate rep ranges (6-12) have been found to be the most efficient due to high mechanical tension, sufficient metabolic stress and a greater time under tension across muscle fibre types.

Volume – This refers to Reps x Load per set. Higher volume training has been found to be ideal for promoting hypertrophy when compared to low volume methods, however, it is unclear which mechanism is the root of this. 

Exercise Selection – Different joint angles and positions have different muscle recruitment patterns so it is essential to include a mixture of exercises to develop the full muscle structure as opposed to overloading a specific region. Multi-joint exercises, typically referred to as compound movements (Bench Press, Squats, Deadlifts, Pull Ups etc.) have been found to achieve greater muscle fibre and motor unit recruitment than single-joint exercises. However, single-joint exercises are better at isolating particular angles and positions. 

Rest – Manipulating rest periods is essential and there is no agreed optimal rest for maximising hypertrophy. Longer rest periods allow for greater force production and load lifted per set, whereas short rests promote more metabolic stress and promotes capillary and mitochondrial density.

Proximity to Failure – Training to failure activates a greater amount of motor units and promotes maximal exercise-induced metabolic stress. However, training to failure regularly can accelerate overtraining and blunt testosterone and growth hormone response.

Rep Speed – Speed of reps can be manipulated to stimulate different types of response. Higher speed reps result in greater stimulation of higher threshold motor units, whereas slower reps create more time under tension and subsequent muscle damage. Eccentric-orientated training has been found to have the best hypertrophic effect due to working through greater ranges of motion and actually improving joint mobility. 


Despite the large number of variables that must be considered to promote hypertrophy, it is not as complicated as it seems. All variables manipulate the three well known mechanisms of mechanical tension, metabolic stress and muscle damage. Gaining a broad understanding of those concepts will allow you to manipulate all of the variables to suit each individual. 

There is no clear variable or mechanism that stands out from another due to the effect of individual differences. Therefore, when creating a hypertrophy specific training programme it is essential to include a blend of all three mechanisms and regularly rotate or periodise the training variables.

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Picture of David Cooke

David Cooke

David served in the Army for 12 years before transferring to the Army Reserves. As well as tutoring and assessing David runs a successful personal training and sports performance business.