Muscular Hypertrophy – Using The Science of Set-Rep Schemes

By Gareth Sapstead BSc (Hons)

The purpose of this article is to explore some of the science behind set-rep schemes aimed at inducing muscular hypertrophy, with the aim of providing the reader with the knowledge of how to manipulate these training variables to achieve the best results.

Basically I’m going to tell you how you can get jacked quicker, by choosing the best set-rep combinations for your training needs.

Hypertrophy 101

In short, muscular hypertrophy is an increase in muscle fibre size, a.k.a. muscle growth. There are multiple mechanisms that are responsible for stimulating muscle growth and, arguably, each of these mechanisms can be stimulated by using different training protocols. These mechanisms are:

  • Increased muscle tension or mechanical stress on the muscle tissue, and
  • Intramuscular energy depletion due to metabolic demands (9)

This leads into a cascade of events, or what has been termed ‘upstream signalling’, that causes ‘downstream’ effects (7).This cascade of events includes the following:

  • Mechanical and metabolic stress leading to structural damage (micro-trauma)
  • Signalling from mechanical stress on muscle fibres
  • Hormonal response (testosterone, hGH, MGF, IGF-1, cortisol), and inflammatory response
  • Protein synthesis leading to muscle hypertrophy

By manipulating the number of sets and repetitions conducted within a training session:

  • Mechanical and metabolic stress may be enhanced
  • Anabolic hormonal response (testosterone, hGH, IGF-1, MGF) may be increased
  • Muscle catabolism may be reduced

This cascade of events allows the body to adapt by rebuilding itself bigger and stronger than before. By manipulating sets and repetitions whilst using the necessary loads required for that repetition number, we may also manipulate the way in which we grow, along with the strength we may gain with our additional muscle size, or may not gain as I will explain further.

Current scientific literature points at the following two types of muscle hypertrophy: Non-functional, or sarcoplasmic hypertrophy (i.e. growth in the sarcoplasm and no direct growth of the contractile proteins), and functional hypertrophy, or myofibrillar hypertrophy (i.e. increased amount of myofibrils per muscle fibre and therefore an increase in sarcomeres in parallel (9).

Why should we care? Well, functional hypertrophy brings about an increase in strength or a capacity to increase in strength, whereas non-functional hypertrophy does not (8). There is also the question of the muscle fibres that are being targeting for growth through training.

Bodybuilders have a preferential hypertrophy of type I and type IIa fibres, where as weightlifters and powerlifters have a preferential hypertrophy of type IIx fibres (1), which we know is advantageous for strength and power. Therefore both training methods have developed extra muscle mass, however in a differing manner.

Hypertrophy with strength (functional hypertrophy)

Trainees will often only perform 4 x 3 or 3 x 4 during periods of maximal strength training. Obviously such parameters fall short of the necessary volume required for hypertrophy. By simply increasing the number of sets and reducing the rest intervals so that your 3 x 4 becomes 8 x 4, an immediate hypertrophic effect will be produced.

A minimal load of 85% of your one repetition maximum (or 6RM) is required to recruit the high-threshold motor units as well as elicit gains in strength (4), and these type of set-rep protocols provide this. In addition, its widely accepted among sport and exercise scientists that as intensity (percentage of one repetition maximum) increases, as does the rate at which muscle protein degradates (9), thereby providing a potent stimulus for growth.

However, based on this fact the best number of repetitions for hypertrophy would be one repetition. This is not the case, as although the rate of degradation is at its highest, the total time under tension per set of exercise would be too low, and therefore an absolute minimum of three repetitions per set would be required.

Low repetition sets for the pursuit of muscular size are also made effective through their anabolic hormonal response, particularly testosterone. Kraemer et al (3) reported an inverse relationship between subject testosterone levels and the total number of repetitions performed within a set (i.e. as the intensity increased and the number of repetitions decreased, higher testosterone was observed).

In addition Pullinen et al (5) used ten sets of six repetitions (10 x 6) of half-squat variations with only a 50% one repetition maximum load, and reported an 18% increase in testosterone levels following training. Others such as Raastad et al (6) have reported as much as a 100% increase in testosterone levels using 3-6 repetition maximum loads for squats, front squats and leg extensions.

Parameters such as; 8 x 4, 10 x 3, 5 x 5, 5 x 6 and so on using around 60-90 seconds rest between sets, therefore all work extremely well to increase both muscular hypertrophy and maximal strength.

Hypertrophy without an emphasis on strength (Non-functional Hypertrophy)

Sometimes we don’t care how we get big or how strong we are, we just want to look the part.

Most trainees have heard that for hypertrophy sets of 8-12 repetitions is best, and as long as you don’t care about how strong you are, of how functional your muscle is, then that repetition bracket is the one for you (and by the way, by ‘functional’ I don’t mean being able to squat on a stability ball, nor will I ever: I’m talking about muscle that is as strong as it looks!).

It has been suggested that the optimal ‘trade-off’ between the rate of muscle protein degradation (as we talked about earlier where it is at its highest at 1RM loads) and time under tension is at around ten repetitions per set (9), where a greater overall amount of micro-trauma may occur, and therefore growth.

Higher repetition sets are mostly so effective, however through the prevention of blood and oxygen from entering the muscle during a set, which stimulates hypertrophy via an increase in the production of systematic and local growth factors (IGF-1, MGF and hGH). Need more convincing? Gotshalk et al (2) simulated a whole training session using eight exercises all performed using 3 x 10 at 10RM loads. The authors reported a 700% increase in hGH, and a 32% increase in testosterone within the post exercise period.

With all of that said it’s no wonder why set-rep schemes such as 4 x 8, 4 x 10, 3 x 12 all work extremely well for good old fashioned non-functional, bodybuilder style hypertrophy.

Something to consider!

A little while ago I had a thought: If you think about it the most common tried and tested (both scientifically and from experience) set-rep combinations for muscle growth all fall between the numbers 24 and 40, for example 5 x 5 = 25, 3 x 8 = 24, 8 x 3 = 24, 4 x 10 = 40, 3 x 12 = 36 and so on.

Below 24 and the volume ends up being too low, and to optimally train for hypertrophy total volume per body part or per exercise needs to be fairly high. Too high (i.e. over 40 total repetitions per exercise) and you either start to train endurance type fibres, which are less susceptible to growth, or your ability to recover from such protocols will be severely impaired, and training would be sub-optimal for muscular growth.

The ‘trick’ to gaining size is to train with as much volume per body part as possible, without exceeding your own ability to recover. The ‘magic’ numbers 24 and 40 may provide a ‘framework’ for use in hypertrophy-style training in order to allow the control of exercise volume, thereby optimising training session effectiveness.


There are a wide variety of set-rep combinations out there, which ones you use in your hypertrophy-style training depend on your needs. Try using a mixture of set-rep combinations within your own muscle building workouts, and not just one loading parameter. This will help to allow the development of both functional and non-functional hypertrophy by ‘knocking out’ a variety of different motor units within the same training session, and thereby optimising muscular growth.

Here’s an example of a chest and triceps session using basic exercises and a variety of hypertrophy set-rep schemes, to be performed once every 5-7 days:

  • A1) Flat Barbell Bench Press, 5 x 5 (use a 4 second eccentric tempo), 90 seconds rest between sets
  • B1) 45° Incline Dumbbell Bench Press, 4 x 8, superset with B2
  • B2) 45° Incline Dumbbell Flies, 4 x 10, 90-120 seconds rest before returning to B1
  • C1) Cable Cross-Over, 3 x 12-15, 60 seconds rest between sets
  • D1) Parallel Bar Triceps Dips, 4 x 8-10, superset with D2
  • D2) Rope Triceps Push-Downs, 4 x 10-12, 90-120 seconds rest before returning to D1
Gareth is a strength coach and fitness specialist studying for his masters (MSc) in strength and conditioning.
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