Why 3 Sets of an Exercise are Better than 1, and Why 5 Sets are (Probably) Better than 3
While still enthusiastically promoted in some circles, single-set weight training routines have repeatedly been shown to produce inferior results to multiple set routines. A recent review of the research by James Krieger, published in the Journal of Strength and Conditioning Research, found that 2 to 3 sets per exercise are associated with 46% greater strength gains than 1 set, in both trained and untrained subjects[1].
The effect of even higher numbers of sets is unclear; 4–6 sets resulted in only 13% greater gains than 2–3 sets, but this figure was derived from limited data[2]. Exercise scientists, like society in general, seem to be enamoured by the number 3 (who ever heard of the Four Stooges, the Four Wise Men, four-day growth, or ménage à quatre?) with most studies comparing single-set protocols with three-set routines. A mere 2 studies included in the review incorporated 4 or more sets per exercise.
Which leaves those of us who’d like to see some bona fide scientific support for higher-set protocols, like the old time-honoured standby 5 x 5 routine, in a bit of a pickle.
So in order to shed further light on this issue, Terzis and colleagues decided to venture down to the molecular level to see if manipulating the number of sets had any impact upon anabolic processes in muscle cells[3].
Resistance exercise evokes acute increases in the activation of a nifty little protein known as the mammalian target of rapamycin (mTOR) and its downstream targets p70S6 kinase (p70S6k) and the ribosomal protein S6, which are thought to regulate initiation of the translation of skeletal muscle protein. Moreover, the acute increase in the phosphorylation of p70S6k following an initial bout of resistance training is closely correlated with the increase in human skeletal muscle mass after a few months of weight training.
For those who just read that last paragraph, scratched their heads, and muttered “what the hell does that mean, Colpo?!”, here’s the simplified translation: Weight training ramps up the activity of mTOR, p70S6k and ribosomal protein S6, which may in turn increase muscle growth and strength. Because most people lift weights to gain muscle and strength, this is a good thing.
So to determine if the number of sets during a workout had any effect on mTOR, p70S6k, ribosomal protein S6 and a bunch of other signalling proteins with hard-to-pronounce names, Terzis and his team convinced eight untrained males to visit their laboratory – not once, but three times. This wasn’t your usual lab – along with test tubes, scalpels, and rodents stressing over their longevity prospects, it was equipped with a leg press machine.
On separate occasions, and in random order, the subjects performed one, three and five sets of 6 repetition maximum (RM) on the leg pres. Muscle biopsies were taken from the vastus lateralis muscle in the thigh both prior to and 30 minutes after each training session.
Now to explain the results, I’m going to have to use some big words again, so bear with me here. Phosphorylation of Akt was not altered significantly after any of the training protocols, whereas that of the mammalian target of rapamycin was enhanced to a similar extent by all three training volumes. The phosphorylation of p70S6k was elevated threefold after 3 x 6 RM and sixfold after 5 x 6 RM, while the phosphorylation of S6 was increased 30- and 55-fold following the 3 x 6 RM and 5 x 6 RM exercises, respectively.
These findings indicate that when resistance exercise is performed, at least in a fasted state as in this study, the increase in phosphorylation of signaling molecules such as p70S6k and the S6 ribosomal protein in human muscle depends on the exercise volume. If these differences in signalling protein activity translate to real life differences in muscle growth, then it could help explain why 3 set routines consistently outperform single-set routines in clinical studies and why 5-set routines such as the classic 5 x 5 have garnered such a loyal following, despite a distinct lack of self-aggrandizing, multi-millionaire, mustachioed magazine publishers or vocal chain-smoking, Ayn Rand-quoting ex-bodybuilding champs to aggressively promote its virtues (just like the Four Stooges, I bet you never heard of the Weider 5 x 5 Principle, huh?).
Practical application: If you’re after maximal muscle and strength development, 3 sets is better than 1, and 5 sets is quite possibly better than 3. Am I a genius at interpreting this stuff, or what?
