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September 02, 2021 5 min read

While growing up and reading whatever I could get my hands on to learn about muscle growth; I could remember all the talk and input from so-called “experts” that you need to confuse a muscle for it to grow!

I bought into this idea and remember the days of altering my training including doing supersets, drop sets, very high-rep sets, etc. etc.

As I got older and started studying this area more formally, I started thinking: 'How do you confuse a muscle? Muscles don’t have brains! Is this idea of manipulating all of these resistance training variables really useful?'  

I knew intensity was important, but it was hard to say if all of these resistance training variables are needed or is it best to utilize a standard progressive resistance training program that takes working sets to positive failure?

Let’s take a look at some recent, very well executed research that digs into this exact question?

Skeletal Muscle

Skeletal muscle tissue plays an important role in maintaining metabolic health, reducing disease risk, and improving athletic performance [1].

An important nonpharmacological stimulus for maintaining or increasing muscle mass is the practice of resistance training. We know that an acute bout of resistance training promotes protein synthesis, which if practiced over time, results in the increase of muscle size [2].  

In order to potentiate muscle size and strength; reputable strength and conditioning guidelines recommend periodic changes in resistance training, especially the more trained a person is [3]. 

These changes involve manipulating common resistance training variables such as exercise load (i.e. intensity), training volume (i.e. total sets/reps), muscle contraction type contractions [e.g. isolated, eccentric (lengthening muscle under tension) or concentric (shortening muscle under tension)] and interset rest intervals.

No one has truly looked at the premise of whether manipulating these variables will enhance muscle hypertrophy (i.e. growth) in resistance-trained individuals.  

Resistance training to failure matters

There is a vast amount of research that shows manipulating one single resistance training variable at a time results in a similar acute post exercise stimulation of protein synthesis and hypertrophy response to resistance training when each exercise set is performed until, or close to, positive failure [4].

Exercising up to, or close to, positive failure seems to promote a substantial increase in protein synthesis and muscle size [5].

Positive failure means that you pushed a resistance training set to failure and you can’t execute another rep by yourself in good form without having a spotter help you.  

There is very little controlled research comparing the protein synthesis response to acute exercise and changes in muscle mass to a systematic manipulation of several resistance training variables throughout training sessions, as opposed to modulating each variable independently.  

The research…

A recent study investigated the impact of methodically manipulating resistance training variables on the individual resistance training-induced muscle growth response when training sessions are performed with high-level effort in resistance-trained participants [6].

To address this question, the investigators measured changes in muscle cross-sectional area in response to an 8-week unilateral resistance training model with all sets performed close to positive failure. The control leg performed a standard progressive resistance training protocol, whereas the opposite leg performed a variable resistance training protocol which changed exercise load, volume, contraction type, and interset rest interval each session. 

Major finding

The major finding was that there is a comparable increase in leg muscle size following an 8 week period that compared standard progressive protocol against a variable resistance training protocol.

The similar increase in both groups occurred despite the greater total training volume in the variable group.

Essentially, there was no greater benefit of participants performing a specific resistance training protocol.

Key points of this study and similar areas of research:

  • This research indicates that a standard progressive resistance training protocol and a resistant training protocol that systematically manipulated training variables (i.e., load, volume, type of contraction, and interset rest interval) produced similar increases in leg muscle cross-sectional area following 8 weeks of training.
  • It seems that there isn’t a requirement to often change training variables in order to prevent a plateau in growth in trained individuals. This is assuming that the training is performed very close to positive failure.
  • Other research that investigated more complex manipulations of different resistance training schemes (e.g., bodybuilding versus powerlifting programs, constant repetition versus varied repetition programs, and crescent pyramid versus drop-set programs reported no difference in the muscle size response between these resistance training protocols. 

Summary and my thoughts

In summary, this research indicates a similar response in muscle size growth when comparing a program that systematically manipulated training variables against a standard progressive resistance program during an 8-week period in resistance-trained young participants. 

It’s important to note that this study was very well done and published in one of the top research journals in physiology.  The premise of “confusing a muscle” by manipulating resistance training variables is not backed by this research over an 8-week period.

The research indicates that utilizing a progressive resistance program is ideal and the most efficient way to train in order to maximize all the benefits that come from resistance training. One caveat is that this study was relatively short at 8-weeks.

I don’t believe we would have seen any differences if the training program was extended to 12 or 16 weeks. I think the bottom line is that muscles grow and get stronger from progressive training and maximum intensity. 



1. Bamman, M.M., B.M. Roberts, and G.R. Adams, Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy. Cold Spring Harb Perspect Med, 2018. 8(6).

2. Damas, F., et al., Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol, 2016. 594(18): p. 5209-22.

3. Garber, C.E., et al., American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc, 2011. 43(7): p. 1334-59.

4. Nobrega, S.R., et al., Effect of Resistance Training to Muscle Failure vs. Volitional Interruption at High- and Low-Intensities on Muscle Mass and Strength. J Strength Cond Res, 2018. 32(1): p. 162-169.

5. Burd, N.A., et al., Enhanced amino acid sensitivity of myofibrillar protein synthesis persists for up to 24 h after resistance exercise in young men. J Nutr, 2011. 141(4): p. 568-73.

6. Damas, F., et al., Myofibrillar protein synthesis and muscle hypertrophy individualized responses to systematically changing resistance training variables in trained young men. J Appl Physiol (1985), 2019. 127(3): p. 806-815.

Dr. Paul Henning

About Dr. Paul

I'm currently an Army officer on active duty with over 15 years of experience and also run my own health and wellness business. The majority of my career in the military has focused on enhancing Warfighter health and performance. I am passionate about helping people enhance all aspects of their lives through health and wellness. Learn more about me