Hypertrophy: What Type of Training Stimulates Muscle Growth?

Muscle hypertrophy is mediated by muscle damage, metabolic stress, and mechanical tension.

Hypertrophy as defined by the English dictionary is: “the enlargement of an organ or tissue from the increase in size of its cells”. 

No doubt you will have heard the word hypertrophy being “thrown” around the gym. I mean lots of bodybuilders talk about hypertrophy training, yet only a few appear to actually know the science behind it. Sure there is a lot of pseudo and bro science, but I’m talking real tangible science.

In this definitive guide I will be explaining the actual science behind hypertrophy, step-by-step. I will also be answering questions such as:

  • How to Stimulate Hypertrophy?
  • How many reps and sets should I do for hypertrophy?
  • Does 5×5 build muscle mass?
  • What is the difference between hypertrophy vs. hyperplasia?

So if you’re stuck at a plateau, or maybe you are simply having trouble building the muscle and strength that you would like, then this article is for you.

By the end of it you’ll understand the science behind muscle growth and how to leverage a hypertrophy training programme to make the type of gains that you want.

What is muscle hypertrophy?

As you read earlier, the definition of hypertrophy is the growth of various tissues through an increase in size of the cross-sectional area (CSA) of its constituent cells.

The word hyper-trophy is derived from both English and Greek languages. Hyper, meaning “above” or “beyond”, and the Greek trophia meaning “growth”.

Literally any of your tissues can participate in hypertrophy. For example, during your transition from a child into an adult, your body will experience smooth muscle tissue and cardiac hypertrophy.

Muscle hypertrophy on the other hand refers specifically to the growth of your skeletal muscle tissues as a result of an adaptive morphological response to heavy and intense weightlifting.

This is quite literally how you become bigger, faster and stronger!

There are two areas in which your muscles can increase in size, these are:

  1. Sarcoplasmic hypertrophy
  2. Myofibrillar hypertrophy

These two types of muscle hypertrophy are distinctly different.

Skeletal muscle terminology

The unique micro-structure of muscle cells has lead to the development of specialised terminology that is exclusive to the cellular biology of muscle tissue.

Therefore, before I explain the what the difference between the 2 different types of hypertrophy is, for ease of understanding I will first breakdown the scientific jargon into plain English.

Muscle cells are named in biology as myocytes.

Myo is a term used to refer to muscle tissue, while cytology is used to reference either a cell or cells. Thus myocyte = muscle cell, which is an individual muscle fibre.

A myocyte is a long tubular shaped structure that has various different subcomponents. It’s structure is organised in the following hierarchy:

Myocyte -> Myofibril -> Sarcomeres -> Actin & Myosin sliding protein filaments

Collectively, myocytes make up skeletal muscle tissue as a single functioning muscle group.

Myofibrillar hypertrophy Vs sarcoplasmic hypertrophy

Myofibrillar hypertrophy is the increase in myofibrills, whereas sarcoplasmic hypertrophy is the increase in extra-cellular fluid.

Sarcoplasmic hypertrophy

Within the myocyte, each myofibril is surrounded by the sarcoplasmic reticulum (SR); a membrane like structure that forms tubules which store plasma (fluid) containing glycosides and calcium ions that are used in skeletal muscular contractions.

Sarcoplasmic hypertrophy is the increase in volume of non-contractile elements found in the sarcoplasmic fluid. In other words, the muscle cell gets volumised by extra-cellular fluids and glycogen.

Therefore sarcoplasmic hypertrophy is said to increase “lean mass gains” producing fuller looking muscles. It does not however increase the number of contractile actin and myosin muscle proteins, and thus does not yield an increase in strength.

Myofibrillar hypertrophy

Myofibrillar hypertrophy is the increase in skeletal muscle protein mass through a process known as sarcomerogenesis; the creation of new sarcomere units.

The creation of new sarcomere units involves the addition of new sliding protein filaments which are synthesised via muscle protein synthesis (MPS). This process causes an increase in the cross-sectional area (CSA) of the muscle fibres.

It is believed that the capacity of force production of a myofibril is denoted by the number of contractile actin and myosin protein filaments (1). According to this axiom, myofibrillar hypertrophy should directly increase both strength and muscle mass.

It is therefore understood that myofibrillar hypertrophy results primarily from the growth of each myocyte, rather than an increase in the number of myocytes.

This is important to note because the number of myocytes is determined by your genetics and so far there is no evidence to suggest that myocyte numbers can increase through exercise-induced hypertrophy.

Rather, weightlifting and bodybuilding can only stimulate an increase in muscle cell growth and volume.

Hypertrophy Vs. Hyperplasia

Hypertrophy is the increase in cross sectional area of the individual muscle cell. Hyperplasia is the increase in number of muscle cells,

Hyperplasia or hypergenesis, is the increase in growth of tissues caused by cell proliferation (cell division).

Although hyperplasia and hypertrophy both result in tissue growth, their mechanisms are distinctly different; hypertrophy is an increase in the cell size, whereas hyperplasia is an increase in the number of cells.

Mechanisms of muscle hypertrophy

Muscle hypertrophy has become a profound area of research, and even today scientists do not fully understand the exact mechanisms of the skeleto-muscular adaptation in response to acute and chronic resistance training stimuli.

So far, research has identified three primary factors of hypertrophy:

  1. Mechanical tension
  2. Metabolic stress
  3. Muscle damage

Each one of these hypertrophy factors although different, are inextricably linked, as you will see.

Mechanical tension

Mechanical tension refers to the tension that is applied to your muscles both from the generation of contractile force in the concentric (lifting) phase, and from the stretching of the muscle fibres on the eccentric (lowering) phase of the exercise.

Generally speaking the greater the mechanical tension, the lesser the degree of metabolic stress, and vice-versa. That is the heavier the load the fewer the repetitions, and the lighter the load the greater the repetitions become.

According to research, mechanical tension associated with weightlifting disrupts the structure of skeletal muscle which is thought to activate dormant satellite cells. Once active these satellite cells proliferate and fuse together or bind with existing muscle cells to create new myofibres (2).

This cascade of events gives rise to a positive shift in protein anabolism which then exceeds protein degradation and thus results in hypertrophy.

It is thought that this mechanically-induced shift in protein balance is also due to the triggering of several different myogenic pathways, including mammalian target of rapamycin (mTOR), Akt and Mitogen-activated protein kinase (MAPK).

Metabolic stress

Metabolic stress occurs as a result of exercise that is powered by energy generated from anaerobic glycolysis. This type of energy metabolism burns glucose in a hypoxic (low oxygen) environment which consequently leads to the build-up of lactate and other metabolites.

Anaerobic glycolysis is a metabolic pathway for energy production that powers brief and intense bouts of exercise, such as weightlifting and sprinting.

Exercise-science theorises that the accumilation of stress-related metabolites induce biological mechanisms that propagate a hypertrophic response.

The brilliant work of renowned hypertrophy coach and researcher Brad Schoenfeld (3), has helped to identify some likely mechanisms through which metabolic stress increases hypertrophy, these are:

  • Acute hormone release
  • Reactive Oxygen Species (ROS)
  • Myokines (local growth factors)
  • Cell swelling
  • Muscle fibre recruitment

Vascular occlusion training

Metabolic stress is the fundamental basis of vascular occlusion training, otherwise known as blood flow restriction training (BFRT).

This is where occlusion cuffs are applied to either your arms or thighs prior to exercise. The pressure applied from the cuffs maintains arterial blood inflow while restricting the outflow of blood.

Low-load resistance training (RT) is then performed, creating a hypoxic (oxygen starved) environment and thus causing temporary muscular acidosis. The artificial spiking of metabolic stress is believed to consequently result in a hypertrophic response (4).

Muscle damage

Muscle damage is another theorised modality of muscle hypertrophy, whereby exercise-induced muscle damage is thought to be responsible for promoting additional muscle growth. Although this is a logical assumption, this theory has provoked criticism by some researchers.

One particular criticism of this theory comes in the form of the repeated bout effect (RBE) (5), which consistently demonstrates that muscles become increasingly less susceptible to damage and myotrauma following repeated bouts of exercise.  

Nevertheless, hypertrophy is achieved through consistent and repeated bouts of exercise, which therefore suggests that muscle damage may not contribute to exercise-induced muscle hypertrophy.

But that’s not all, the evidence becomes even more unclear as to whether muscle damage does stimulate hypertrophy. This is because exercise-induced muscle damage still persists in experienced athletes.

The bottom line

The human body responds and adapts to physical workload; resistance training (RT) is known to increase hypertrophy. However, it’s the “bits” inbetween that exercise-science still lacks a full and proper understanding of.

How adaptation takes place and through what physiological mechanisms currently requires more research.

What we do know is that muscle hypertrophy is a very complex and multifaceted process that is influenced and mediated by a whole manner of different factors including satellite cells, immune system responses, cytokines, metabolite accumulation, cortisol, testosterone, insulin and other growth factor proteins (IGF, FGF, HGF, HGH) etc.

How to stimulate muscle hypertrophy

Hypertrophy training can be utilised by female athletes

Muscle hypertrophy is caused by adaptation to regular and progressive workloads that supersede the pre-existing capability of your muscle fibres. You literally have to force your muscles to grow. Muscle growth doesn’t just happen by its own accord; you have to work for it, and work hard for it.

Furthermore, you must also combine progressive overload training with adequate rest and a varied and balanced diet rich in quality proteins.

You can do all the grunting, groaning and teeth-clenching in the world, but without the necessary nutrition, your efforts will be made in vain. Protein is one of the most important rate-limiting factors in muscle hypertrophy, make sure you get enough of it.


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What is progressive overload training?

Progressive overload training is the principle of applying repeated and varying amounts of mechanical tension to skeletal muscles, thereby creating a stimulus for adaptation by triggering a hypertrophic response.

For example, improving your personal best bench-press, progressing from 6 repetitions of 100 kilos to 6 repetitions of 110 kilos, causes muscular overload and leads to adaptation.

That said, it is important that your progression is a product of controlled exercise form and proper movement patterns. This is fundamental to any hypertrophy training programme.


Any progression or increase in load attributed to swinging, jerking or improper movement will do little in the way of stimulating hypertrophy.


Thus adaptation and hypertrophy are inextricably linked; hypertrophy increases the number of actin and myosin sliding filaments resulting in an increase in the size of the individual muscle fibres and consequently their capacity to generate force (6).

Are heavy weights or light weights best for hypertrophy?

Exercise-science generally recognises that different repetition ranges elicit different effects upon muscular adaptations.

In fact various studies provide us with good evidence to support the claim that heavy loads promote the greatest increases in strength while light loads are optimal for muscular endurance (7, 8, 9).

As a practical guideline these are:

1-5 repetitions (Heavy load) = optimum range for increasing strength

6-12 repetitions (Moderate/heavy load) = optimum range for increasing hypertrophy

13+ repetitions (Light load) = optimum range for muscular endurance

That said, these “boundaries” aren’t completely hard and fast. For example, performing 5 all out repetitions using a heavy weight won’t just increase your strength; it will also stimulate hypertrophy. Conversely, hitting 10 repetitions, although primarily aimed at hypertrophy, will also yield an increase in strength.

Strength Vs hypertrophy rep range

You can think of hypertrophy and strength as being interconnected yet different by degree.

The further you move down the scale of the 1-12 rep range, the more you stimulate your strength capacity to increase. Conversely, the further you move up the scale of the 1-12 rep range, muscular adaptations shift more toward hypertrophy.

Nevertheless, training in a specific rep range is no guarantee of increasing your strength or stimulating muscular hypertrophy.

I mean you could do 5×5 every week, but if you aren’t pushing yourself and resort to lifting a weight that you are easily comfortable with, you probably won’t be successful in stimulating hypertrophy. But if you follow a 5×5 style workout and put everything you have into your sets week in week out, you will attain improvement because you are forcing your muscles to adapt.

Does 5×5 make you bigger?

Although a 5×5 routine is geared more toward increasing strength, if you push yourself you will absolutely stimulate hypertrophy. In fact in my experience 5×5 is a very effective rep range and volume for building a combination of both strength and size.

Pro Tip

I would suggest training in the 6-12 rep range, but also mix it up a little and from time to time utilise a multi-varied approach, training across a wide spectrum of rep ranges.

You will absolutely stimulate hypertrophy and also reap the benefit from various types of mechanistic adaptations including an increase in tendon and ligament strength and hypertrophy.

How many reps and sets should I do for hypertrophy?

Training volume refers to the total number of reps and sets combined. One huge set of 100 reps obviously accounts for more in terms of pure numeric volume than 5 sets of 5 reps. However a single set of 100 reps means little to nothing for muscle hypertrophy.

As a general rule of thumb perform your sets in the hypertrophy rep range, and then if needed add more sets rather than reps to increase your volume.

Number of sets is actually an important consideration for your hypertrophy training programme, and if you are not covering enough volume you may fall short on stimulating maximum hypertrophy.

The results of a recent study also indicate the same (10). In fact, the researchers concluded that:


Muscle hypertrophy follows a dose-response relationship, with increasingly greater gains achieved with higher training volumes.”


In my current 25 years training and 20 years experience as a hypertrophy coach, my empirical observation for the optimal training volume is not a one size fits all, but dependant on various factors including, the individual, their goals and how experienced a lifter they are.


Although volume is important, there is a law of diminishing return. Spend too long in the gym doing too much volume and your workout could end up lacking in intensity and fail to stimulate hypertrophy. 1-1.5 hours should be ample time to complete your workout.


How frequently should you train a muscle group?

Every time you perform an intense workout, protein synthesis is stimulated. Thus it is argued that training as frequently as possible is best for hypertrophy. That is the more often you workout, the more often you can spike protein synthesis.

While in theory this axiom may seem plausible, in practise it isn’t quite as simple. The reality of finding an optimal training frequency is that you have to achieve a balance between stimulation and recovery.

Don’t think just in terms of recovery per muscle group, rather, have a holistic approach and take into consideration other recovery factors. For example, eccentric loading causes the delayed onset of muscle soreness (DOMS), but it is also thought to be more taxing on your central nervous system (CNS) than concentric loading (11).

Training frequency depends on various different factors, the ones that I focus on are:

  • Volume
  • Experience
  • Goals
  • Age

VEGA hypertrophy frequency method

Volume

There are all manner of different hypertrophy programmes and the amount of volume you are working through will significantly affect how frequently you train each muscle group. As a general rule of thumb; the more volume you cover in each of your workouts, the less frequently you can perform them.

Volume is usually dependant on the type of training regime you follow; full body workouts generally involve less volume per muscle group, whereas a more specialised bodybuilding training split covers significantly more volume (exercises, sets and reps) per muscle group.

Needless to say, training frequency for full body workouts allows each muscle group to worked more frequently than that of a specialised bodybuilding split.

The same is also true for intensity; if you increase your training intensity by training to failure, adding force reps, rest pauses, super sets etc, you will find that you are forced to decrease your training volume.

Your body’s capacity to exercise is limited and so is its ability to recover. Thus the more you exert yourself in one way or another, the greater your recovery time will be.

Experience

This one is easy, the longer you have been lifting and the more experienced you are, the more accustomed your muscles will have become to moving heavy loads and intense training. Experienced lifters, under the age of 40 and who have been consistently training hard for years can generally train more frequently.

Goal

If you are a bodybuilder and your goal is to build as much muscle as possible, then of course training as frequently as possible is a must. However if you are only concerned with maintaining your muscles, then you can train less frequently.

Age

Simply put, the older you become the more degeneration your body will encounter and thus your ability to recover from intense physical exercise is lessened. Having worked with clients in their sixties, I can genuinely say that age related recovery is an important consideration in training frequency.


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What exercises are the best for hypertrophy?

Heavy Loads are best for hypertrophy

Aside from rep ranges, volume and frequency, the exercises that you perform also play an important part in stimulating your muscles to grow.

For example, let’s look at cable cross-over’s Vs decline bench-presses.

A couple of heavy sets of 6 reps of decline bench-press is significantly more effective at stimulating pectoral hypertrophy than the equivalent sets and reps of cable cross-over’s. The latter certainly wouldn’t do much for your before and after transformation pictures!

This is because decline bench-press is a compound (multi joint) exercise and utilises more than one muscle group. Compound movements enable you to add more of a load and apply more mechanical tension to your muscles. Whereas cable cross-over’s are an isolation (single joint) exercise, which are biomechanically weaker movements.

This is why it is fundamentally important to include a variety of compound exercises into your hypertrophy programme. Be sure to utilise compound exercises for both your lower body and upper body.

Squats for example work your legs (quadriceps & hamstrings), glutes, and to a lesser degree, back and calf.

Here are some compound exercises that I recommend incorporating into your workouts:

  • Dead lifts
  • Squats
  • Decline bench-press
  • Overhead shoulder press
  • Barbell rows
  • Close-grip bench-press
  • Leg press

Can supplements increase hypertrophy?

Amino-XS fermented plant based BCAA and EAA supplement

Muscle protein synthesis (MPS) and hypertrophy are synonymous. Skeletal muscle responds and adapts to exercise-induced stimuli by synthesising new actin and myosin sliding protein filaments.

The growth of new protein structures is a result of muscle protein synthesis (MPS). Therefore any supplement that can trigger MPS can be used to help increase muscle hypertrophy.

Whey Protein and Amino Acids.

To date, science teaches us that one of the most effective substance known to increase MPS is the branched chain amino acid (BCAA) Leucine. Various studies indicate that Leucine, and to a lesser degree, all 3 BCAAs, trigger an anabolic pathway known as mammalian target of rapamycin (mTOR).

mTOR is an important signalling pathway responsible for regulating multiple biological functions including cell proliferation, cell growth and autophagy. With regard to hypertrophy mTOR is the powerhouse that drives the synthesis of new muscle tissue.

Whey protein is rich in leucine and BCAAs and it is well-documented that whey protein triggers mTOR (12, 13). Therefore it can be consumed post workout (I’d suggest consuming it directly after) to aid in recovery and to increase hypertrophy.

You can also go one step further by consuming Leucine and BCAAs either pre or intra workout. Because BCAAs are pre digested proteins, they readily enter your bloodstream, trigger MPS (14, 15) and kick-start anabolism while you are working out.


Because weight training increases targeted muscular blood flow through hyperaemia, drinking amino acids during your workout essentially force feeds your muscles with these anabolic building blocks.


This was one of the premises behind the formulation of plant-based Amino-XS which contains all 3 BCAAs; leucine, valine and isoleucine. It also includes a compliment of other essential amino acids (EAAs) to trigger and further facilitate muscle protein synthesis (MPS).

Myostatin-related muscular hypertrophy

Muscle hypertrophy is not only triggered by resistance training but can also be caused by a genetic mutation that signals a myogenic pathway (myo= muscle, gen = to produce).

Myostatin-related muscular hypertrophy is a relatively rare (the incidence is not currently known) genetic condition that is characterised by an unusually large skeletal muscle mass and low body fat percentage (16).


Individuals with Myostatin-related muscular hypertrophy can look like bodybuilders, yet may not even workout.


The MSTN gene encodes a protein called myostatin which is almost exclusively found in skeletal muscle tissues where it is understood to limit muscle growth.

Mutations in the MSTN gene cause a reduction in production of the myostatin protein, resulting in an abnormally large skeletal muscle mass. It isn’t a serious medical condition and individuals who have it don’t usually experience any health related problems.

If Darwin’s theory of evolution and “natural selection” is true, the MSTN gene must be an anomaly; retarding muscle mass is contrary to survival of the fittest.

Conclusion

Muscle hypertrophy is the increase in size of your muscle cells and can be stimulated by progressive overload resistance training. In order to maintain continued muscle growth, you must regularly partake in exercise and train intensely using heavy loads.

Hypertrophy training has far reaching implications; just about every athlete on the planet can benefit from increasing their strength and building extra muscle. Moreover, hypertrophy training isn’t just for bodybuilders.

Although the world of biochemical processes that govern hypertrophy are incredibly complex, your approach to building muscle should remain relatively simple. Train hard, eat well, sleep well, be consistent, be patient, apply the principles outlined in this blog including my VEGA hypertrophy frequency method, and you will build muscle.

A wealth of other health benefits are also associated with increasing your muscle mass. Skeletal muscle plays an integral role in immune system function and metabolism, and therefore is fundamental in maintaining your health.

Furthermore, performing regular hypertrophy workouts can help fend off age related muscular atrophy (sarcopenia) and thus promote healthy ageing. Even Public Health England recommend resistance training for older adults.

So now it’s your turn, leave a comment and tell me about your favourite hypertrophy training techniques.

Scientific reference data:

1. Muscle structure and theories of contraction
https://www.sciencedirect.com/science/article/abs/pii/S0096417418301288?via%3Dihub

2. The mechanisms of muscle hypertrophy and their application to resistance training.
https://www.ncbi.nlm.nih.gov/pubmed/20847704

3. Potential mechanisms for a role of metabolic stress in hypertrophic adaptations to resistance training.
https://www.ncbi.nlm.nih.gov/pubmed/23338987

4. Role of metabolic stress for enhancing muscle adaptations: Practical applications
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489423/

5. Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise.
https://www.ncbi.nlm.nih.gov/pubmed/12641640

6. Form follows function: how muscle shape is regulated by work.
https://www.ncbi.nlm.nih.gov/pubmed/10710412

7. Muscular adaptations in response to three different resistance-training regimens: specificity of repetition maximum training zones.
https://www.ncbi.nlm.nih.gov/pubmed/12436270

8. Effects of Low- vs. High-Load Resistance Training on Muscle Strength and Hypertrophy in Well-Trained Men.
https://www.ncbi.nlm.nih.gov/pubmed/25853914

9. Strength/endurance effects from three resistance training protocols with women.
https://journals.lww.com/nsca-jscr/pages/articleviewer.aspx?year=1994&issue=11000&article=00005&type=abstract

10. Resistance Training Volume Enhances Muscle Hypertrophy but Not Strength in Trained Men.
https://www.ncbi.nlm.nih.gov/pubmed/30153194

11. Eccentric Muscle Contractions: Risks and Benefits
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510035/

12. Whey protein ingestion activates mTOR-dependent signalling after resistance exercise in young men: a double-blinded randomized controlled trial.
https://www.ncbi.nlm.nih.gov/pubmed/22253983

13. Whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in human skeletal muscle.
https://www.ncbi.nlm.nih.gov/pubmed/24384983

14. Leucine-Enriched Nutrients and the Regulation of mTOR Signalling and Human Skeletal Muscle Protein Synthesis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096790/

15. The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141572/

16. Myostatin-Related Muscle Hypertrophy
https://www.ncbi.nlm.nih.gov/books/NBK1498/

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PJ
PJ

Paul Jenkins MSc applied chemistry, founder of DNA Lean®, is an ex junior national level sprinter, national level bodybuilder, sports coach and nutritionist. Paul has almost 20 years experience coaching athletes of various disciplines and is an expert in optimising body composition; he specialises in fat loss, hypertrophy and competition prep. Paul is also an advocate of food-based medicine and firmly believes that natural ingredients from plants and herbs can be used to help to improve athletic performance. Featured on

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