Are Some People Exercise Non-Responders?


Are Some People Exercise Non-Responders?

Some people derive more benefits from exercise than others. That’s not surprising, is it? You’ve probably seen people who get into shape very quickly while it takes months for equally motivated people to get returns from an exercise program. We’re all a little different from a genetic and a lifestyle standpoint. Plus, we have varying levels of motivation and differ with respect to physical factors like body weight and body composition. Surprisingly, a small number of people get little or no apparent fitness benefits from a structured exercise program. When they do aerobic exercise, their aerobic capacity, or body’s ability to carry oxygen, doesn’t increase to an appreciable degree. Are some people exercise non-responders?

The Mystery of Exercise Non-Responders

In recent years, scientists have coined the term “exercise non-responders” to describe people who either respond very little or not at all to an exercise program. Keep in mind, it takes time to develop a higher level of fitness, several weeks to several months. So, training for a few weeks without seeing results doesn’t mean you’re a non-responder. Non-responders are individuals who work out consistently for a few months and fail to experience a boost in their aerobic capacity.

Studies that have looked at the response to an exercise program show there’s a wide variation in how individuals respond to exercise training. Some people see dramatic results in a short period of time while others show fitness improvements slowly or to a lesser degree. But, in this case, we’re talking about the small percentage of people who experience no apparent improvements in aerobic capacity with training.

Some experts have questioned whether exercise non-response is a real entity or simply due to inadequate training or the wrong kind of workout for that particular individual. For example, some people may respond to high-intensity workouts but derive little benefit from moderate-intensity training. Some non-responders may simply need to train harder or more often. This seems to be borne out by at least one study. In this study, researchers asked exercise non-responders to increase the number of workouts they did on a weekly basis from one workout per week to three. They also asked non-responders who were exercising three times a week to boost their workout frequency to five days a week. With these changes, all experienced improvements in cardiovascular fitness.

The Role of Selenoprotein-P

Despite this, there is evidence that exercise non-response is a real entity and scientists now have a better idea of why it might happen. Recently, researchers at Kanazawa University in Japan discovered, using cultured human muscle cells as well as mice, that a particular protein, called selenoprotein P, produced by the liver, interferes with the response to aerobic exercise. Mice that were deficient in selenoprotein experienced 2X the improvement in exercise capacity in response to aerobic training compared to mice with higher levels of this protein. Plus, they exhibited greater improvements in insulin sensitivity, one of the many health benefits of exercise.

Does the same hold true in humans? In another study, healthy, untrained women took part in an 8-week aerobic training program to improve their aerobic capacity. Unfortunately, those who had high levels of selenoprotein P in their blood didn’t experience the same increase in exercise capacity as those with lower levels of this protein.

How can you explain this? What scientists have discovered is selenoprotein P binds to a receptor on muscles called LRP1*4 and this reduces the phosphorylation, or activation, of AMPK. You can think of AMPK as a cell’s energy sensor, as AMPK goes up as a cell’s energy stores go down. Aerobic exercise, itself, activates AMPK and is believed to explain some of the health benefits of exercise, including improvements in insulin sensitivity. If selenoprotein P blocks phosphorylation of AMPK, it can potentially interfere with adaptations to exercise. Link Between Selenoprotein P and Metabolic Health

Who is more likely to have higher levels of selenoprotein P? People with type 2 diabetes, pre-diabetes, fatty liver, and older people have higher levels than healthy, younger folks. In fact, research shows that high levels of selenoprotein P are associated with an increased risk of cardiovascular disease, insulin resistance, and inflammation. So, people who have poor metabolic health may get less health and fitness benefits from exercise relative to healthier people due to higher quantities of selenoprotein P.

Keep in mind, that these studies are preliminary. No one knows for sure why some people don’t respond to exercise and others do. Plus, some experts believe that everyone responds to exercise, regardless of genetics and metabolic health, it’s just a question of finding the right type of exercise and prescribing it in the appropriate dose. One person may need only 2 or 3 days of exercise a week to get physically fit while someone else may need 4 or 5 sessions a week. Likewise, moderate-intensity exercise may work for some people while others may need high-intensity training. Still, the selenoprotein-P link is a compelling one.

If selenoprotein P is a driver of exercise non-responsiveness and its higher in people who aren’t healthy metabolically, improvements in metabolic health would be expected to enhance the fitness adaptations to a workout. For example, if a person with type 2 diabetes lost weight and improved their blood sugar level, their selenoprotein P level might drop, and they might become more exercise responsive. The link between exercise non-responsiveness and poor metabolic health seems to be real. The authors of a study published in the Journal of Clinical Endocrinology and Metabolism point out that up to one in five people with type 2 diabetes are low or non-responders to exercise.

The Bottom Line

We each all respond to exercise a bit differently based on factors like genetics. Plus, the type of training and the intensity of that training influences the extent of adaptations and how quickly they appear. A small sub-segment of the population seems not to respond to the same degree, possibly due to higher selenoprotein P levels. The question is whether lowering this protein, through improving metabolic health, will unlock the capacity to respond. Nevertheless, exercise offers health benefits that go beyond improving aerobic capacity. Exercise helps preserve muscle tissue and bone mass and it’s an excellent stress reliever. The list of reasons to exercise just keeps growing even for exercise non-responders.


References: “Why Does the Same Exercise Exert Effects on Individuals Differently?
Biochem J. 2009 Mar 1; 418(2): 261–275.doi: 10.1042/BJ20082055.
J Clin Endocrinol Metab. 2011 Aug;96(8):E1325-9. doi: 10.1210/jc.2011-0620. Epub 2011 Jun 15.
Diabetes in Control. “Are There Really Exercise Non-Responders”
J Clin Endocrinol Metab 2014 Nov 20:jc20142545. [Epub ahead of print]


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