Earlier this year, I wrote a column on the “minimal effective dose” of strength training. Remarkably, newbie lifters can make gains with as little as one set of six to 15 reps per week—on average, at least. But average results don’t tell the full story. Some people will gain more than average; others will gain less. If you’re a typical endurance-focused Sweat Science reader, there’s a good chance you’re in the second category. What does it take to put on muscle for those who don’t respond to the minimum?

　　A new study in the Journal of Applied Physiology, from researchers at the University of Sao Paulo and other institutions in Brazil as well as the University of Alabama at Birmingham, fills in some details about this question. By assigning volunteers to do different lifting routines with each leg, they eliminate a bunch of the individual variations that usually cloud the results of strength training studies. The results offer hope for those who might initially be classed as “non-responders” to resistance training, and suggest that the best way to turn on muscle-building adaptations is straightforward: add more sets.

　　To start, it’s worth unpacking this idea of “non-responders.” Starting in the 1980s and 1990s, a series of studies explored the role of genetics in exercise response. Give a bunch of people the same training program, and their genes will explain about half of the variance in how much their fitness improves, the studies found. Some people, it turned out, didn’t seem to get fitter at all, even after several months of training. This idea of exercise non-responders got a lot of enthusiastic attention (“So that’s why I’m not as fit as I want to be!”)—and some pushback. Later studies tended to show that if you took the non-responders from a study and had them train harder or at higher volumes, they would indeed get fitter.

　　The studies above focused on aerobic exercise, but you’d expect similar results with resistance training. The new study, which was led by Hamilton Roschel of the University of Sao Paulo, was designed to see whether adding extra sets would turn non-responders into responders. They recruited 85 volunteers (41 men, 44 women), all over the age of 60 and not currently doing any strength training; older adults are generally less responsive to the anabolic stimulus of strength training, making non-response more likely. The exercise program involved two workouts per week for ten weeks, consisting of sets of between 8 and 15 reps of single-leg knee extensions with the weight chosen to reach failure in each set. Each volunteer did one set per workout with one leg, and four sets per workout with the other leg.

　　Muscle size was measured by MRI, and as expected, the one-set routine produced plenty of non-responders. Sixty percent of the subjects failed to gain more than 3.3 percent in the cross-section of their quadriceps (a minimum threshold for statistically significant improvement based on the repeatability of the MRI measurement). With four sets, the proportion of non-responders dropped to 19 percent, and those who responded to one set had bigger responses to four sets. The conclusion: doing more sets leads to greater muscle gain, even among those who don’t seem to gain initially.

　　This may seem painfully obvious, but the same isn’t true for strength as measured by one-rep max. Doing four reps didn’t produce notably bigger strength gains than one set, which seems both surprising and unfair. This result is consistent with previous studies, though; in fact, I wrote about a study from Brad Schoenfeld’s group back in 2018 that found exactly the same thing in young experienced lifters: five sets was better than three sets, which in turn was better than one set for muscle size; but all three options were basically the same for bench press strength. Strength is a function of muscle size and of the complex signaling process between brain and muscle. The two don’t always go hand in hand.

　　In fact, there are more nuances in the individual (rather than average) data from Roschel’s study. Among those who responded to one set, only 51 percent got significantly bigger muscle-size results from four sets, and 15 percent actually did worse on four sets. Normally when I see results like that, I’d assume that those 15 percent had some other life stress going on during the four-set part of the study that tanked their results. But in this case, the one-set and four-set parts of the study were taking place simultaneously in different legs. That suggests that, while four sets are better than one for some people, they really are worse for others.

　　So the superficial takeaway from this study is that you can get away with fairly minimal one-set training if your main goal is to get stronger, but you’ll probably benefit from more sets if—like many aging athletes—you’re more concerned with gaining or simply maintaining muscle mass. That echoes the earlier results from Schoenfeld and others. The deeper and more interesting takeaway, though, is that this rule isn’t true for everyone. The resulting uncertainty is inconvenient and a bit annoying, but it means we have to fall back on a simpler rule: if what you’re doing isn’t working, even if it follows the latest research, try changing it.

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