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Commentary to Accompany

Exercise Nonresponders: Genetic Curse, Poor Compliance, or Improper Prescription?

Tanaka, Hirofumi

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Exercise and Sport Sciences Reviews: July 2018 - Volume 46 - Issue 3 - p 137
doi: 10.1249/JES.0000000000000156
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V˙O2max needs no definition for the readers of Exercise and Sport Sciences Reviews (ESSR) because it is a, if not the, most frequently used abbreviation in exercise physiology. It is a measure of cardiorespiratory fitness for exercise professionals, a gauge for endurance capacity and potential for coaches and athletes, and an index of cardiovascular disease risk for clinical scientists. When V˙O2max is used as a measure of exercise training response, considerable variabilities exist in the individual responses. Some subjects respond with substantial improvements whereas gains are either minimal or nonexistent in others. This latter group has been labeled as exercise nonresponders. Much of this variability has been attributed to a variety of factors including a poor compliance/adherence to exercise program and a genetic predisposition to a specific type of exercise training stimuli. In the current issue of ESSR, Joyner and Lundby (1) argue that trainability depends largely on the dose of exercise training and that genetic predispositions may not be as important as we previously thought. Would the notion of nonresponders that we excuse some individuals as a “genetic curse” be a misnomer or a phenomenon that depends on the context

Arguably, one of the most strenuous exercise training studies to date was conducted by Hickson et al. (2) back in 1970s. The participants, mainly graduate students and postdocs, ran continuously as fast as possible for 30 min or longer 3 d a week (equivalent to running 5- to 10-km races every other day) and cycled six 5-min-long intervals at the intensity to reach V˙O2max in 5 min (equivalent to performing six V˙O2max tests in row) on alternate days. One open day (i.e., nontraining day) of the week was devoted for V˙O2max tests resulting in no rest day in a week. The average increase in V˙O2max after 10 wk was approximately 40%. There was no nonresponder because even the lowest responder achieved an 18% increase in V˙O2max. Several studies since then have demonstrated that increasing exercise intensity or dose abolished nonresponders in previously sedentary adults (1). Would individuals who failed to respond to one type of exercise training be able to obtain sufficient gains when a different type of training was prescribed? In a recent randomized crossover exercise intervention study (3), all the participants responded to exercise when they were exposed to both endurance and sprint interval training protocols. More interestingly, improvements in V˙O2max, or a lack thereof, for a specific individual after endurance training did not predict the improvements in V˙O2max after sprint interval training.

These results suggest that the vast majority, if not all, of exercise participants may be able to gain the benefits from exercise training protocols as long as the exercise stimuli are appropriate and sufficient. Clearly, there is no single exercise training routine that works for everyone. As a number of exercise guidelines remind us, exercise prescription needs to be diversified (as in cross-training) and individually tailored to optimally improve function and maximize adaptations. The concept of nonresponders to medical treatments is highly prevalent in the clinical literature because “resistance hypertension” and “vaccine failure” are a few examples to designate small groups of patients who are resistant to the treatments. Exercise training is unique and distinct in that the dose of the treatment strategies can be increased and altered without much regard to toxicities, adverse effects, and complications. Even if V˙O2max is unresponsive to exercise training in some populations, other benefits from regular exercise are innumerable. Even breaking up sitting or sedentary time confers cardiometabolic benefits (4). Exercise is clearly medicine!


1. Joyner MJ, Lundby C. Concepts about VO2max and trainability are context dependent. Ex. Sport Sci. Rev. 2018; 46:138–43.
2. Hickson RC, Bomze HA, Holloszy JO. Linear increase in aerobic power induced by a strenuous program of endurance exercise. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 1977; 42:372–6.
3. Bonafiglia JT, Rotundo MP, Whittall JP, Scribbans TD, Graham RB, Gurd BJ. Inter-individual variability in the adaptive responses to endurance and sprint interval training: a randomized crossover study. PLoS One. 2016; 11:e0167790.
4. Benatti FB, Ried-Larsen M. The effects of breaking up prolonged sitting time: a review of experimental studies. Med. Sci. Sports Exerc. 2015; 47:2053–61.
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