Research in the last number of decades has clearly outlined the overall beneficial effects of exercise on human health and performance, but explanations for why some people do not respond favourably to exercise remain poorly characterised. These individual cases of “non-responders” to specific modalities of exercise present an intriguing question: what physiological differences in these individuals underpin this lack of response, compared to say those that experience moderate to strong improvements in health and/or performance indicators? From a statistical perspective, a non-response is the lack of a difference between a control and a treatment condition with respect to a specific variable. A physiological non-response, however, is likely underpinned by an individual’s genetic code and the mechanisms by which it is transcribed, translated and post-translationally modified. In the context of exercise physiology research, a non-response would be quantified as a lack of beneficial health and/or performance adaptations to a specific training intervention, or exercise “resistance”. A more commonplace, but similar analogy to this concept of exercise resistance would be drug resistance in an individual undergoing a pharmacological intervention for a specific disease/condition. Those who do not respond well to an initial drug intervention usually move on to a combination of the previously used treatment with another drug, or a new drug treatment entirely. Interestingly, aspects of such approaches have been applied by exercise physiologists in recent years.
Results from recent randomised controlled trials indicate that substantial individual variability exists in the magnitude of response to continuous endurance training (ET). Data from the HERITAGE study demonstrated a mean increase in maximal oxygen uptake (VO2 max) equal to 400 mL/min, while individual responses ranged from negligible improvements to as great as 1000 mL/min. Non-responses to ET have also been observed for other performance measures including lactate threshold, submaximal exercise heart rate and time-trial performance. Although recent estimates suggest the incidence of non-responders to ET for VO2 max is between 20% and 45%, it is important to note that there are few individuals who do not respond positively to this exercise modality by improving one of the aforementioned measures. The individuals who do elicit such a response, are often termed “global” non-responders, in that no improvement in any pertinent outcome measure is evidenced in response to an exercise intervention.
So what to do with these global non-responders to ET? Well, it has been argued previously that non-responders to exercise simply do not exist, and that by simply altering the exercise modality, intensity, and volume will induce an exercise response. In this regard, recently popularised alternatives to continuous ET such as high-intensity (HIIT) or sprint (SIT) interval training may prove to be useful stimuli. Astorino and Schubert (2014) recently investigated whether a wide range of individual responses to interval exercise exist, similar to ET. As one might expect, non-responders for VO2 max following SIT were observed following chronic (6 training sessions over 2 weeks) SIT protocols. Similar to ET, individual patterns of response across VO2 max and other indices performance indicators were observed in this study. Additionally, Gurd et al. (2016) identified an overall rate of HIIT/SIT non-responders for VO2 max of 22%, while non-response rates of 44% and 50% were observed for time-trial performance and lactate threshold were also identified. Given this information, it’s clear that while interval training regimens may benefit many individuals, non-responses to this training modality exist, similar to ET.
So we know that ET works for some, but not others and that the same can be said for HIIT/SIT protocols. However, with this information we still cannot ascertain if the previously mentioned global non-responders to ET do not respond favourably to interval training regimens. To answer this question, Bonafiglia et al. (2016) used a crossover design to assess the individual response to both chronic (3 weeks) ET and SIT in the same group of subjects. In short, non-responders to both modalities of exercise were identified in various measures of exercise adaptation including VO2 max, lactate threshold and submaximal heart rate. Interestingly, all individuals responded in at least one variable when exposed to both ET and SIT. In other words, any potential global non-responders to ET responded favourably to SIT in at least one variable, and vice versa.
These results suggest that non-responses to exercise training may be mitigated by changing the training stimulus for non-responders to a specific exercise modality. Such findings lend credence to the argument that the existence of true non-responders to exercise training is unlikely and that different training protocols should be considered when optimising individual exercise prescription. As the exercise metabolism field continues to combine the plethora of -omics data with molecular phenotyping of study participants in clinical exercise trials, we will move closer towards shifting the paradigm by allowing exercise prescriptions to be targeted at those most likely to benefit and alternative approaches to treat those who do not.
References & related reading:
- Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. Bouchard C, An P, Rice T, Skinner JS, Wilmore JH, Gagnon J, Pérusse L, Leon AS, Rao DC. J Appl Physiol (1985). 1999 Sep; 87(3):1003-8.
- Volume of exercise and fitness nonresponse in sedentary, postmenopausal women. Sisson SB, Katzmarzyk PT, Earnest CP, Bouchard C, Blair SN, Church TS. Med Sci Sports Exerc. 2009 Mar; 41(3):539-45.
- Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ. J Appl Physiol (1985). 2009 May;106(5):1479-86.
- Differences in adaptations to 1 year of aerobic endurance training: individual patterns of nonresponse. Scharhag-Rosenberger F, Walitzek S, Kindermann W, Meyer T. Scand J Med Sci Sports. 2012 Feb;22(1):113-8.
- Exercise training response heterogeneity: physiological and molecular insights. Sparks LM. Diabetologia. 2017 Dec;60(12):2329-2336.
- Individual Responses to Completion of Short-Term and Chronic Interval Training: A Retrospective Study. Astorino TA, Schubert MM. PLOS One. 2014; 9(5): e97638.
- Incidence of nonresponse and individual patterns of response following sprint interval training. Gurd BJ, Giles MD, Bonafiglia JT, Raleigh JP, Boyd JC, Ma JK, Zelt JG, Scribbans TD. Appl Physiol Nutr Metab. 2016 Mar;41(3):229-34.
- Inter-Individual Variability in the Adaptive Responses to Endurance and Sprint Interval Training: A Randomized Crossover Study. Bonafiglia JT, Rotundo MP, Whittall JP, Scribbans TD, Graham RB, Gurd BJ. PLOS One. 2016; 11(12): e0167790.
Tom Aird is a postgraduate researcher in the Department of Physical Education and Sport Sciences at the University of Limerick. Contact Tom via email at Tom.Aird@ul.ie or view his research profile on Researchgate