Due to a scarcity of longitudinal trials directly measuring changes in muscle girth, previous recommendations for inter-set rest intervals in resistance training programs designed to stimulate muscular hypertrophy were primarily based on the post-exercise endocrinological response and other mechanisms theoretically related to muscle growth. New research regarding the effects of inter-set rest interval manipulation on resistance training-induced muscular hypertrophy is reviewed here to evaluate current practices and provide directions for future research. Of the studies measuring long-term muscle hypertrophy in groups employing different rest intervals, none have found superior muscle growth in the shorter compared with the longer rest interval group and one study has found the opposite. Rest intervals less than 1 minute can result in acute increases in serum growth hormone levels and these rest intervals also decrease the serum testosterone to cortisol ratio. Long-term adaptations may abate the post-exercise endocrinological response and the relationship between the transient change in hormonal production and chronic muscular hypertrophy is highly contentious and appears to be weak. The relationship between the rest interval-mediated effect on immune system response, muscle damage, metabolic stress, or energy production capacity and muscle hypertrophy is still ambiguous and largely theoretical. In conclusion, the literature does not support the hypothesis that training for muscle hypertrophy requires shorter rest intervals than training for strength development or that predetermined rest intervals are preferable to auto-regulated rest periods in this regard.
Alex’s Notes: A critical aspect of weight training prescription is the amount of rest taken between sets, and the review at hand aims to review the current research pertaining to the effect of inter-set rest intervals on muscular hypertrophy. Moreover, it was co-authored by Brad Schoenfeld, one of the leading experts in the field of critical thinking, common sense, and of course, the mechanisms behind resistance training induced muscle growth.
Inter-set rest time can effect long-term muscle growth via three potential mechanisms: hormonal response, metabolic stress, and muscle damage. The first two provide arguments for shorter rest periods and are very close-knit because the hormonal responses are the result of increased metabolic stress. Shorter rest times does not allow the body sufficient time to clear out metabolite build-up, and the hormonal argument for shorter rest intervals is primarily based on the acute elevation in growth hormone. Testosterone may also be elevated via lactate accumulation, and cortisol also is greatly elevated. Overall, the growth hormone response requires 30-60 second rest periods, while anything under two minutes will elevate cortisol levels. A review of the hormonal response concluded that if the elevation of certain hormones is indeed a part of the hypertrophic response, the overall magnitude is likely small. Another interesting fact that people seem to overlook is that growth hormone has never been found to have direct anabolic properties on skeletal muscle, only connective tissue.
It is more likely that the hormonal changes from exercise programming are merely the body’s way of “dealing” with the different types of exercise prescription. Regardless, there is evidence in metabolic stress for promoting hypertrophy outside of the hormonal response it elicits. This is best demonstrated in studies using blood-flow restriction, which produce robust hypertrophic responses without the muscle damage common of traditional weight-training.
But muscle damage is still – arguably – the most important component of muscle hypertrophy via its upregulation of local IGF-1 and satellite cell recruitment. Of course there is a threshold where too much damage is detrimental, but ignoring this, rest interval length may not be ideal because it does not allow for a higher total amount of work relative to longer rest intervals. In one of the most comprehensive studies on rest interval length to date, there were no differences between 2 vs. 5 minutes of rest in muscle growth. Granted 2 minutes isn’t really considered “short”.
Anyways, Schoenfeld’s concluding remarks on the matter of inter-set rest time summarize things extremely well.
“More generally, the literature as a whole suggests that rest interval manipulation has minor effects on muscle hypertrophy compared with other training parameters such as work volume, which suffers when inter-set rest is insufficient even in trainees accustomed to this type of training [6, 12, 13]. Given that the positive effects of full recovery between sets on strength and power are well-documented and that Buresh et al.  found increased muscular hypertrophy but not strength in the higher rest interval group compared with the shorter rest interval group, the literature does not support the theory that training for maximum muscle hypertrophy requires shorter rest intervals than training for strength.”
The required time for rest is dependent on more important programming variables such as intensity, the magnitude of the load lifted, exercise order, and so on. Additionally, the person’s goals are critical, as someone training for pure strength will need more rest than someone looking to get a pump. In fact, it is likely that the body knows best, and this type of rest interval auto-regulation where physiological “readiness” determines the rest time has been demonstrated successfully with both compound and isolation exercises.
Bottom line: More research is needed on the topic, but it is unlikely that rest interval length has a substantial effect on muscle growth.