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Volume Threshold in Muscle Building

One Set Compared to Three Sets 

Recent research shows that effort is more important than load in building muscle; fatigue is the major trigger for strength and hypertrophy. A recent study explores another factor in the muscle building equation—volume. Research at McMaster University in Canada suggests that three sets to failure may produce a greater and longer lasting muscle building effect than one set to failure.

Whoa, you say, that’s different from what we’ve heard here before. While the finding is new, the significance and the implemented may surprise you. What’s new is our understanding of the physiological intricacies of resistance training. We don’t know it all by any means, but thanks to the McMaster researchers and others, we are learning more all the time. Knowledge can make the difference between training with the precision of a sledge hammer and doing it with a laser beam.  

Got your interest? I hope so. Let’s look at the study.


Earlier research has focused mainly on high volume resistance training; for example, a study by the same research group found no difference in myofibril* protein synthesis (MPS) when young men performed three sets and six sets. The three extra sets were unproductive; perhaps even counterproductive. “Presumably, there is an exercise volume (i.e. load x repetition) dose-response that ultimately reaches a ceiling where the stimulatory effect of more contractions would diminish,” Nicholas A. Burd and colleagues wrote in The Journal of Physiology (August 15, 2010). Simply put, there is in all probability a point of diminishing returns; more volume becomes a waste of time and effort. To help define the tipping point, the McMaster researchers compared myofibril protein synthesis (MPS) in one set and three sets. (*Myofibrils are the rod-like contractile elements in skeletal muscle.)

As a double check, they also monitored changes in several anabolic signaling molecules—molecules that should be in sync with MPS—and phosphorylation.

They “hypothesized that 3 sets would induce a greater increase in MPS in both amplitude and duration versus one set. [They] also hypothesized that the increase in MPS would be reflected in the extent of anabolic signaling protein phosphorylation.” That’s essentially what happened. The question is what it means.

The details are fascinating. As always, it’s complicated.

Study Design

Subject selection was important, because resistance training can have a continuing effect on muscle physiology. A trained subject is likely to respond differently than someone new to resistance training. Relative training experience would affect the response to an isolated bout of exercise. Eight recreationally trained (males, average age 24, body mass index 25) were selected. All were routinely active and reported engaging in lower body resistance training at least once a week for a year or more.

The subjects were randomly assigned to perform unilateral (one limb) knee extensions at 70% of one repetition maximum until failure for 1 set or 3 sets. Failure was defined as the point at which the exercise could not be completed or the subject’s technique failed. Knee joint flexion and lifting cadence was carefully monitored. Lifting duration was 1s concentric (positive) muscle action, 0s pause, and 1s eccentric (negative) muscle action. Muscle response was also evaluated by electromyography (EMG).

Each subject did 3 sets with one leg and one set with the other leg. Each individual was, therefore, his own control—to insure that changes “were due to these stimuli rather than inter-subject variability (i.e. genetics and motivation).” When doing 3 sets, subject rested 2 minutes between sets. The leg used for 1 or 3 sets was balanced for leg dominance.

Biopsies from the thigh (vastus lateralis) were taken at rest, 5 hours, 24 hours, and 29 hours post exercise. The resting and 24 hour muscle sample were taken in the fasting state; the other samples were in the fed state (20 grams of whey protein). One rep maximum for both legs was determined one week before the trails.

Blood samples were also taken.

The participants reported to the lab after an overnight fast and having refrained from strenuous exercise for three days prior to the trial.

After completion of the exercise, participants consumed a drink containing 20 g of whey protein isolate. “This protein dose had previously been shown to maximally stimulate muscle protein synthesis following resistance exercise,” the researchers explained.

After biopsies were obtained 5 hours after completion of the exercise, subjects were instructed to eat their normal meal at least 10 hours before the biopsies 24 hour post exercise. This insured that the 24 hours biopsies would be taken while fasting. Another protein drink was consumed before the biopsies taken 29 hours post exercise.

There was no difference in load from set to set.

That’s the simplified version, but it’s more than enough for our purposes. It was a well thought out and designed study.

Here's what they found.


First set performance was essentially the same for both groups, 1set and 3 sets. But the repetitions declined from set to set when 3 sets were performed. “The repetitions performed during set 1 of 3 sets were significantly greater than set 2 and 3, and set 2 was significantly greater than set 3,” the researchers reported.

It appears that fatigue increased from set to set, as one would expect for motivated participants. With researchers observing every rep one would expect motivated subjects. That's important, because left to their own devices trainees might be inclined to pace themselves from set to set.

EMG readings also showed that fatigue was taking its toll from set to set.

Now we come to the key findings.

Myofibril protein synthesis (MPS) was increased 5 hours post exercise for both 1 set and 3 sets, but remained up at 29 hours post exercise only for 3 sets.

“MPS was elevated above fasting by 2.3- and 3.1-fold at 5 h post-exercise for 1 set and 3 sets, respectively,” they reported. “However, the response at 5 h post-exercise was significantly greater for 3 sets as compared to 1 set. MPS returned to a mean value not different from fasting in 1 set at 29 h post-exercise. However, MPS remained elevated by 2.3-fold above fasting in 3 sets and was significantly greater than 1 set at the same time point.”

Interestingly, signaling protein activity only partially confirmed the MPS findings.

“[One anabolic signaling protein] demonstrated a coordinated increase with MPS at 5 h and 29 h post-exercise such that the extent…was related to the MPS response. [Two other anabolic signaling proteins were] similar for 1 set and three sets at 24 h fast and 29 h fed, respectively. However, 3 sets induced a greater activation of [two other signaling proteins] at 5 h fed.”

“It is important to recognize that we have limited knowledge on the necessity of activating particular anabolic signaling molecules to stimulate muscle protein synthesis,” the researchers explained. (As noted earlier, there is still a lot we don’t know about the muscle building process.)

“These data suggest that 3 sets of resistance exercise is more anabolic than 1 set and may lead to greater increases in myofibril protein accretion over time,” Burd et al concluded. (Emphasis mine)

As you’ll see, we’ve broken new ground, but are well short of a conclusive finding.

“Our study is the first…to show a dose-response relationship between exercise volume and the response of myofibril protein synthesis (MPS),” Burd et al wrote in the Discussion portion of their report. 

Burd et al also observed that the second protein drink consumed before the biopsies taken 29 hours post exercise had no stimulatory effect after one set of exercise. “It is now apparent that the lack of a stimulatory effect of feeding on MPS following 1 set of resistance exercise at 24-29 h post-exercise suggests that a certain threshold volume of contractile activity is necessary to sensitize the muscle to subsequent feeding.”

The Burd team ended with some limitations on their findings. “From a practical perspective it is important to recognize that scientific studies are performed under highly controlled conditions…Clearly a training study is required to delineate the superiority of 1 set or 3 sets for inducing hypertrophy.” (Emphasis mine)

My Take

As acknowledged by the Burd team, the sets controversy can’t be settled based on a single bout of exercise for one part of a single leg. That’s one of the reasons why the researchers used words such as may and suggest. They steered clear of language connoting finality. And for good reason.

No evidence was cited to show that greater or longer duration MPS with multiple sets results in more strength gains or muscle hypertrophy. It seems logical that it would, but we really don’t know one way or the other. Perhaps the optimal stimulus for hypertrophy is well below the elevations reported in this study. The burden of proof is on the claimant and I am told that there are no studies showing a correlation or cause and effect relationship between MPS (single versus multiple sets) and muscle hypertrophy or strength gains.

A double blind—or at least a single blind—study would be required to provide definitive proof. Double blind means that neither the subjects nor the investigators know which treatment is being administered. The purpose of such a study is to eliminate the risk of prejudgment by the participants. As a practical matter, that will be almost impossible. (I do not mean to in any way challenge the credibility of the McMaster research group. I hold them in the highest regard.) 

The truth is that the sets controversy may never be settled. It may come down to a matter of personal preference.

Stuart M. Phillips, PhD, lead researcher with Dr. Burd in the above study, and my friend Dr. Richard Winett, Director of the Center for Research in Health Behavior at Virginia Tech in Blacksburg, VA, have a middle-ground solution that is likely to have wide appeal.

The Phillips-Winett solution is simple and, I believe, sound. They favor dropping “sets per exercise” as a measure of volume, and suggest adoption of “sets per muscle group” as a more meaningful measure of workload. “Multi-joint exercises affect multiple muscle groups” and often make single joint exercises redundant, they explain. For example, the chest press and shoulder press both work the triceps, making a specific triceps exercise unnecessary and, perhaps counterproductive.

This is a way to have your cake and eat it too. It allows you to do three sets for a body part without doing multiple sets of any one exercise. That’s what I’ve been doing for decades. The key is to focus on exercises that engage more than one joint. Here are some examples.

A routine with the chest press, shoulder press, and dips works the chest, shoulders and triceps two or more times. A pulling example would be the pullover, pulldown, and row. All three movements work the upper back from different angles, making it unnecessary to repeat any one exercise. If you count one or two warm-up sets for each exercise, you have substantial volume.

An example of the same thing for the chest would be the chest press, incline press, and upright pulley crossover (for the lower chest). Again, warm-up plus one hard set of each exercise works chest quite effectively—along with the shoulders and triceps.

The squat, leg press, and deadlift do the same thing for the muscles of the lower back, hips, and thighs. One hard set of each of those compound movements will leave you spent. (I rarely do these exercises together, but it is an option for those concerned about not doing enough sets.)

I can tell you from personal experience that a hard run through any of these three-exercise combinations will not leave you eager for more. You’ll be one and done.

In my opinion, the following quote from Dr. Ralph Carpinelli in my book Challenge Yourself still applies: “The lack of scientific evidence that multiple sets…produce a greater increase in strength or size, in itself, provides a rationale for following a single set protocol.”

Adopt the Phillips-Winett “sets per body part” approach and you won’t go wrong.

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