Muscular Hypertrophy

When it comes to maximising muscular hypertrophy, two things are needed: mechanical tension and metabolic stress. Ok, mechanical tension alone might be sufficient to induce the hypertrophic response, but if you want the best gains possible, then you can’t forget about metabolic stress. It’s a nice powerful addition to the muscle building process! So, if your goal is to develop maximum muscle mass, then your training should be arranged in such a way to promote both optimal levels of mechanical tension and metabolic stress. With both, you can’t fail.

Short Vs. Long Rest Periods

Although I have talked about the importance of training volume, intensity and frequency (the big three) in the development of muscle size, one thing that I haven’t mentioned is inter-set rest times. In other words, how much time you take to rest between each exercise set. In my opinion, inter-set rest times seem to be pretty overlooked when it comes to optimal training programming for size and strength. Most of the focus seems to be on the big three. Well, inter-set rest times are important because they can have a huge influence on the level of fatigue you experience during your training, the extent of recovery, how long your training sessions lasts and, your training goal. All of which have a significant impact on whether or not you achieve your size and strength goals.

What we do know at the moment is that it’s not exactly clear what the best inter-set rest times are for inducing maximum muscular hypertrophy. There are a lot of mixed opinions on the subject! Some say shorter rest times are better, others say higher rest times are better, and some even say a mixture is probably the best option. What further complicates matters is whether training status (trained vs. untrained) has a significant impact on hypertrophy responses due to different rest times.

Overall, there is a lot of uncertainty at present. But, a few things have popped up in the scientific literature which have begun to shed some light on the topic.

The Non-Overly Sciencey Verdict On Set Times

It’s likely that the best tactic to maximise muscular hypertrophy is to utilise a range of short and long inter-set rest times. Why? More mechanical tension AND metabolic stress!

Training with longer inter-set rest times might potentially allow for higher training volumes. These higher training volumes allow for greater levels of protein synthesis increasing the hypertrophic response. If you are a more advanced lifter, then you will need more volume anyways to keep progressing. Thus, longer inter-set rest times might be better still for all you more advanced lifters out there. Long inter-set rest times also allow for heavier weights to be lifted (working near your 1 RM). Heavier weights allow for greater levels of force production and motor recruitment which are also really important factors in muscular size increases. It is also worth mentioning that due to the greater levels of fatigue and demands placed by multijoint exercises (e.g. your compounds), longer inter-set rest times might be needed in order to preserve higher levels of performance. Ultimately, what we are saying is that these longer rest times are probably great for increasing mechanical tension (the initial driver for muscular hypertrophy).

Training with shorter inter-set rest times might also be hugely beneficial for increasing muscle size. Essentially, shorter rest times prevent your muscles from fully recovering between exercise sets, thus increasing their levels of fatigue during training. This allows all sorts of great stuff to occur in terms of increased metabolic stress within the muscles (also a driver of hypertrophy!). This will include an increase in muscle fiber recruitment, increases in cellular swelling, an accumulation of lactic acid, acute elevations in hormones and lots of other hypertrophic-influencing effects. Overall, once a certain level of mechanical tension is generated, these metabolic stresses may play an additive role in the hypertrophic response. Unlike compound exercises, single-joint (isolation-type) exercises are much less fatiguing and demanding, thus don’t require longer inter-set rest periods.

It’s likely then that in your training, incorporating shorter inter-set rest times when it comes to your isolation exercises might be a nice way of ensuring you are able to general significant amounts of metabolic stress in order to maximise the hypertrophic response. Overall, short inter-set rest times are also probably good to include in your training if you are looking for maximum muscle size.

Interested in the science behind this? Then keep reading below!

The Science:

•Study 1•

In 2016, Schoenfeld et al investigated the effects of short and long inter-set rest times on muscle thickness of the elbow flexors, triceps brachii and quadriceps femoris muscles via ultrasound imaging. 21 young resistance trained men performed either a resistance training program with 1 minute inter-set rest or 3 minute inter-set rest intervals. The study lasted 8 weeks and participants performed 3 full body workouts per week, with 8-12 RM and with 7 different exercises per session.

•The results?•
It was found that the muscle thickness of the anterior thigh, elbow flexors and triceps brachii were significantly greater for the 3 minute group in comparison to the 1 minute group.

•The conclusion?•
The study suggested that longer inter-set rest times likely promote greater increases in muscular hypertrophy over shorter inter-set rest times in young resistance trained men.


Schoenfeld et al (2016). Figure shows the changes in muscle thickness after (post) LONG and SHORT inter-set rest times. 

•Study 2•

In 2016, McKendry et al looked at the influence of different inter-set rest times on levels of myofibrillar protein synthesis (MPS). In this study, 16 trained male participants completed 4 sets of bilateral leg-press and knee-extension exercises at an intensity of 75% of 1RM. The inter-set rest times between each set were 1 minute or 5 minutes. Muscle biopsies were taken at 0, 4, 24 and 28 hours post-exercise. Continuous infusion of L-C6 phenylalanine was conducted to observe the resulting changes in post-exercise MPS following the resistance training protocols.

•The Result?•
It was found that MPS was increased 0 to 4 hours post exercise for both the 1 minute and 5 minutes inter-set rest time groups. However, increases in MPS 0-4 hours post-exercise were significantly greater for the 5 minute rest-time group. At 24-28 hours post exercise, MPS rates were the similar between both groups.

Furthermore, this coincided with reduced extents of post-exercise phosphorylation of p70S6K and rpS6 for the 1 minute group in comparison to the 5 minute group. Moreover, extents of phosphorylation for eEF2, TSC2, AMPK and REDD1 proteins were greater for the 1 minute group.

•The Conclusion?•
Longer inter-set rest times allow for potentially higher levels of early post-exercise MPS. This is likely to occur through changes in the levels of phosphorylation of key intracellular signalling proteins necessary for this post-exercise MPS. The pattern of phosphorylation changes caused by the 5 minute group likely led to an optimisation of this intracellular signalling environment resulting in higher levels of early post-exercise MPS in comparison to the 1 minute group.

Important to note: changes in muscle thickness were not monitored in this study, only the post-exercise MPS responses. However, this study lends nice support to the results of the Schoenfeld et al (2016) study. Why? It is possible that the greater changes in muscle thickness observed by Schoenfeld et al as a result of longer inter-set rest times, might be due to the changes in early post-exercise MPS.


McKendry et al (2016). Figure shows the increase in early post-exercise MPS 0-4 hours after exercise. The increase in early post-exercise MPS is significantly greater with 5 minute inter-set rest times in comparison with 1 minute inter-set rest times. 


Is There A Benefit To Short Inter-Set Rest Times?

Although these studies point towards longer inter-set rest times (3-5 minutes) being potentially superior than shorter inter-set rest times (<1 minute) for increasing muscular hypertrophy (due to allowing adequate levels of mechanical tension to be generated), it is likely that shorter rest times do play a potential additive role in the muscle building process. Don’t neglect shorter rest periods just yet! As pointed out by Grgic et al (2017), shorter inter-set rest times are going to reduce the ability of the muscle to re-establish homeostasis and as such will likely lead to a range of processes occurring that all signal a level of metabolic stress in the muscle. Given that metabolic stress has been shown to play a role in the hypertrophy process, short inter-set rest times might also have an important place in your training program.

As shown by Grgic et al (2017), combining both shorter and longer inter-set rest times might provide the best way of enabling your training to generate both high levels of metabolic stress and mechanical tension needed to maximise muscle size gains.


Grgic et al (2017). Figure shows the possible benefits of combining both short and longer inter-set rest times to maximise muscle hypertrophy. The aim is to incorporate both in order to achieve optimal levels of mechanical tension and metabolic stress.

Any questions, ask away!