Not Seeing Results In The Gym? You Might Be A Non-Responder

The idea of a non-responder in the fitness world is paradoxical. Often these people are judged as if they aren’t trying hard enough. Some are even called out for not being dedicated.

The term “non-responder” is a bit misleading, however, since it implies that someone is completely unable to adapt to exercise. It is very rare that someone doesn’t adapt to exercise, rather what happens more often is that they don’t adapt as the average person would.

For example, a study finds that a certain exercise protocol causes a 30% increase in muscle mass compared to a protocol that causes a 15% increase. You would obviously want to use the training regimen that did better between the two. However, what you may not notice is the variation within the groups. Often there are subjects who didn’t respond, or responded very little.

This isn’t a new concept, but it does raise some questions.

Why do some respond when others don’t?

Individual differences in response to training are sometimes beyond statistical error, often thought of as outliers. But they’re still important. These differences may seem like an annoyance to scientists looking for statistical significance, but they reflect the genetic variation that makes people diverse. This diversity is not caused by a specific age, sex, or ethnicity, but does play a major role in response to physical activity.³

Several studies have shown differences in responsiveness to resistance exercise. For example, in one study done by Thalacker-Mercer et al., participants completed 16 weeks of resistance training, 3 days per week. Muscle size was measured across all subjects. This study found that one portion of subjects showed no change (non-responders), one showed moderate change, and one showed an extreme response.

Now, this study was heavily monitored for effort and completion, so everyone had the same relative input. What was the difference? The subject’s molecular profile. Specifically, the profile for the extreme responders had enhanced transcriptional regulation, satellite cell function, and muscle growth signaling, while the non-responders had a profile with increased inflammatory signaling. This indicates that the muscle of the extreme response group was primed for growth. Furthermore, it tells us that the non-responders may have a metabolic disadvantage at the molecular level.⁴

Figure 1. Functional annotation of the basal skeletal muscle gene expression profile associated with resistance training (RT)-induced myofiber hypertrophy.

There is one possible limiting factor with this experiment. It could be that the baseline (before exercise) gene expression in muscle is different among responders and non-responders. However, scientists found that baseline gene expression is not related to pre-training size and strength. Thus, this profile clearly reflects the metabolic and functional adaptations of the muscle to resistance exercise.⁵

One theory driving these differences is myonuclear addition. This is based on the concept of myonuclear domain, which is the amount of cytoplasm in a muscle fiber that is controlled by a single nucleus. This concept has been confirmed by several studies that show changes in muscle fiber size that are paralleled by changes in the number of myonuclei.

They also indicate that the myonuclear domain is controlled by two mechanisms: the gain of myonuclei by fusion of satellite cells during hypertrophy and the loss of myonuclei by apoptosis in atrophying muscle fibers. Importantly, there may be a ceiling on the myonuclear domain (∼2,000 μm2) that is reached before the addition of more nuclei.⁷ Therefore, it's possible that the genetic profile of non-responders is playing a role by limiting the myonculear domain.

Looking at a broader picture of this is important since one can get bogged down in the molecular details. A cohort of 585 subjects, age 18-40, participated in a 12 week training study with unilateral resistance exercise in the elbow flexors. Cross sectional area of the arm was measured using MRI. Importantly, subjects who supplemented their diet with additional protein to build muscle were not included.

From this large study there is an interesting breakdown of training response. Of all the subjects, 232 (39%) showed an increase in muscle fiber size between 15-25%. However, 36 subjects gained less than 5% in muscle size. These subjects were deemed non-responders compared to most of the other subjects, but they still had a physiological response.

Hypertrophy isn’t everything, though. Plenty of people are interested in training for strength and power. In the previous study of 585 subjects, 39% showed an increase in 1RM of 40-60%. This happens to be similar to those who showed the most muscle fiber hypertrophy. However, 12 subjects gained less than 5% in 1RM.⁸ The data isn’t specific enough to show that these were the same people who didn’t hypertrophy, but it would make sense if they were.

Key Takeaways

These results show that there are indeed non-responders to resistance exercise. However, even a non-responder can increase muscle mass or strength by 4-5%. This differential response is most likely due to a genetic difference among individuals.

The important thing to remember is that just because you are a non-responder to resistance exercise does not mean that you won’t respond another type of training. Skeletal muscle is highly adaptable and therefore could respond to endurance exercise in a different way.