Numerous health organizations recommend that most adults try to achieve a minimum of 30 minutes of moderate-intensity aerobic exercise on five days each week (or 150 minutes) or vigorous-intensity aerobic exercise for a minimum of 25 minutes on three days each week (or 75 minutes) or an equivalent combination of both [American College of Sports Medicine (ACSM), 2014; American Council on Exercise (ACE), 2014; Haskell et al., 2007]. Paradoxically, there is also emerging evidence that suggests considerable individual variability in exercise-induced changes in common cardiovascular disease risk factors, with some individuals actually experiencing an adverse response (a response in an unfavorable direction) when exposed to regular exercise (Buford, Roberts and Church, 2013; Bouchard et al., 2012).

Given that exercise is considered an effective treatment for many chronic conditions, understanding the factors associated with adverse responses is of growing importance for health and fitness professionals. Exactly what is an adverse response to exercise? Are there exercise training programs or other lifestyle factors predictive of training responsiveness? How can you, as a health and fitness professional, prevent your clients from experiencing an adverse response to exercise? This article explores answers to these intriguing questions.

What are the health benefits of regular exercise?

Physical inactivity is associated with numerous unhealthy conditions, including obesity, hypertension, type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). It also contributes to an estimated 250,000 premature deaths each year (Booth et al., 2000). Conversely, it is widely accepted that regular exercise has positive effects on multiple health outcomes related to cardiovascular morbidity and mortality (Warburton, Nicol and Bredin, 2006). Moreover, regular exercise is linked with reduced risk of certain forms of cancers, improved psychological health and an overall improved quality of life (Garber et al., 2011). In fact, as Robert H. Butler, a highly regarded gasterointerologist once noted, “If exercise could be purchased in a pill, it would be the single most widely prescribed and beneficial medicine in the nation.”

The evidence-base underpinning the widespread benefits of exercise is so overwhelming that multiple organizations, including the American Medical Association, ACSM and ACE advocate for exercise to be included as a standard part of the disease prevention and treatment medical paradigm in the United States. It’s hard to fathom that with all these accolades to its credit that there could possibly be any downside to exercise.

Does everyone benefit from regular exercise?

Responders, Non-responders and Adverse Responders


A favorable change in a physiological parameter (e.g., improved body composition, reduced cholesterol and better blood glucose control) is the anticipated and desired outcome to exercise training. Commonly, this is defined in the scientific literature as a change (Δ>0) in the favorable direction (Sisson et al., 2009). For example, an individual who experiences a reduction in resting heart rate of five beats per minute from three months of aerobic training would be categorized as a responder.


A non-responder is an individual who performs regular exercise training, yet undergoes no change (Δ≤0) in their physiological function. Although it would appear to be intuitive that all previously untrained and sedentary individuals undertaking exercise can expect positive changes to their physiological function and overall health, this is not the case for a segment of the population. For instance, an estimated 20 to 45 percent of people may be considered non-responders to exercise training (Sisson et al., 2009).

Adverse Responders

More recently, research suggests a small (but significant) segment of the population may experience a decline in their cardiometabolic health after starting an exercise program. Individuals who fall within this unwanted category are typically described as adverse responders. An adverse response is defined as an exercise-induced change that worsens cardiometabolic health beyond measurement error and expected day-to-day variation. A recent study that combined data from six exercise intervention studies revealed that adverse responses in individual cardiovascular and metabolic (cardiometabolic) risk factors ranged from 8 to 13 percent in sedentary adults undergoing four to six months of aerobic exercise training (Bouchard et al., 2012).

It has been well established over the last few decades that there is substantial heterogeneity in the physiological adaptations to exercise training. For example, research indicates that individual improvement in cardiorespiratory fitness ranges from negative 5 percent to a positive 58 percent following five to six months of standardized aerobic exercise training (Sisson et al., 2009). Moreover, there is also considerable variability in the exercise traininginduced responses of common cardiovascular and metabolic risk factors (e.g., blood pressure, insulin and cholesterol). The most common explanation for these differences in training responses is genetics. In fact, the HERITAGE Family Study, conducted in the 1990s, reported that nearly half (47 percent) of the variability in cardiorespiratory fitness training adaptations was heritable (Skinner et al., 2000). A number of terms have been used to describe the phenomenon of wide variability in physiological adaptation to uniform training, including responder, non-responder and adverse responder, each of which are defined in the adjacent sidebar.

Now what? Are non-responders and adverse responders inevitable and something to simply chalk up to bad genes? Or can health and fitness professionals look to parameters of the exercise-training program itself or potential lifestyle factors that may mitigate training unresponsiveness?

What exercise-program attributes influence training adaptations?

The F.I.T.T. principle—frequency, intensity, time (duration) and type of exercise—is a common approach to program design (ACSM, 2014). The overall homeostatic stress of an exercise session is comprised of these components, and in turn, provides the stimulus to initiate adaptive physiological responses. Research suggests that variation in the exercise-training stimulus is at the heart of training responsiveness (Mann, Lamberts and Lambert, 2013). Here are three key features of the exercise program that can substantially influence training adaptations:

  • A greater volume of exercise equates to a greater likelihood of being a responder.

Although most health organizations are in agreement that completing 150 minutes per week of moderate-intensity exercise confers numerous health benefits, research has also attempted to answer the question of whether exceeding this recommendation yields additional benefit in a dose-response manner. In 2009, Sisson and colleagues examined predictors of cardiorespiratory fitness non-response following six months of aerobic exercise training in previously sedentary overweight or obese women. Participants in the study were randomized to one of three exercise training interventions: (1) a group that performed 75 minutes per week of moderate-intensity exercise, (2) a group that performed 150 minutes per week of moderate-intensity exercise, and (3) a group that performed 225 minutes per week of moderate-intensity exercise. Researchers concluded that one of the most important predictors of a positive cardiorespiratory fitness response to exercise training is a greater volume of exercise. A total of 44.9 percent, 23.8 percent and 19.3 percent of the 75 minutes per week, 150 minutes per week and 225 minutes per week exercise intervention groups, respectively, were non-responders. The take-home message: A greater volume of exercise training increases the likelihood of being a responder.

  • Threshold-based training minimizes the occurrence of non-responders.

Exercise intensity is arguably the most critical component of exercise programming. Failure to meet minimal threshold values may result in lack of a training effect, while an exercise intensity that is too high could lead to overtraining and negatively impact adherence to an exercise program. The traditional reference standard for recommending exercise intensity is expressed in terms of percentages of heart rate reserve (%HRR) or oxygen uptake reserve (%VO2R). This is considered the relative percent method. ACSM (2014) recommends an exercise intensity of 40 to 59% of HRR/VO2R for improving and maintaining cardiorespiratory fitness. Nevertheless, despite a large evidence base supporting the ACSM relative-percent concept recommendation for prescribing exercise intensity, there is concern that the approach consists of a very large range of acceptable percentages and fails to take into account individual metabolic responses to exercises (Katch et al., 1978).

Alternatively, it has been suggested that a threshold based model for establishing exercise intensity might better identify the lowest effective training stimulus for all individuals with varying fitness levels. Indeed, ACE (2014) recommends a threshold-based model approach to programming exercise intensity in its three-zone training model. A recently published ACE-sponsored research project compared the effectiveness of two exercise-training programs for improving cardiorespiratory fitness: a threshold based training model vs. the more common, and ACSM-recommended, relative-percent method (i.e., %HRR). It was demonstrated that a threshold-based exercise intensity approach: (1) elicited significantly greater improvements in maximal oxygen uptake (VO2max), and (2) attenuated the individual variation in VO2max training responses when compared to relative percent exercise training. In fact, there was positive improvement in VO2max in 100 percent of the individuals in the threshold-based training group. Conversely, only 67 percent of individuals in the relative percent method group experienced a favorable change in VO2max. The take-home message: Threshold-based training minimizes the occurrence of non-responders.

  • Flexible training is superior to a fixed exercise-training program.

Kiviniemi and colleagues (2010) concluded that exercise training guided by day-to-day heart-rate variability (i.e., flexible training) elicited significantly greater improvements in cardiorespiratory fitness and maximal workloads when compared to exercise training that followed a predetermined workout schedule (i.e., fixed training). The logic supporting a flexible training approach is that it accounts for individual variation in recovery time between each exercise session. For instance, it would clearly be unwise to expect clients to perform an intense resistance-training workout if they remain fatigued from a previous exercise bout. Kiviniemi and colleagues (2010) demonstrated that heart-rate monitoring is an excellent method for confirming a client’s readiness to train. The take-home message: A one-size-fits-all approach to exercise training is inadvisable. A flexible training strategy, guided by individual training recovery requirements, will decrease the likelihood of adverse and non-responders.

What lifestyle factors influence training adaptations?

While individual variation in recovery time between exercise sessions can clearly influence training adaptations, various lifestyle factors may also impact the individual variation in recovery time. A key preventative step to minimizing training unresponsiveness is to use appropriate pre-participation screening to identify those individuals who may be at an increased risk for non-response or adverse response to exercise training. Let’s look at some of these factors, including sedentary behavior, sleep, stress and nutrition, and how they can negatively impact training responsiveness if not addressed.

  • Sedentary behavior counteracts the benefits of regular exercise.

Sitting has been called the new smoking. In fact, excessive sedentary behavior has been linked with numerous chronic diseases, including type 2 diabetes and cardiovascular disease (Hamilton et al., 2008). Interestingly, this increased risk persists whether individuals exercise regularly or not. Individuals who meet the recommendation to exercise moderately for 150 minutes per week, yet remain sedentary at most other times throughout the week, are referred to as “active couch potatoes.” Research has shown excessive sitting time, independent of exercise, is linked to decreased high-density lipoprotein (HDL) cholesterol levels, increased triglycerides and elevated blood glucose (Hamilton et al., 2008). As such, lack of training responsiveness (e.g., non-responder or adverse responder) may be attributable to sedentary behavior and not a product of the exercise program itself. Therefore, it is worth taking the time to gain insight into the habitual activity/sedentary patterns of clients and, if necessary, make recommendations to reduce sedentary behavior.

  • Stress and sleep mediate adaptations to exercise.

Increased stress and insufficient sleep are both factors that may limit overall training responsiveness. For example, Ruuska and colleagues (2012) found that higher life event stress at baseline resulted in reduced improvements in various power- and strength-related parameters following a resistance-training program. Prolonged sleep debt has been associated with increased susceptibility to infection and overtraining syndrome (Mann, Lamberts and Lambert, 2013). Either of these issues compromise quality exercise training. Moreover, chronic sleep debt has also been linked to increased circulating levels of cortisol, which has been linked to impaired muscle recovery (Mann, Lamberts and Lambert, 2013). Overall, the mechanisms through which elevated stress and inadequate sleep compromise favorable training adaptations include reduced training volume, impaired training recovery and a predisposition to overtraining. Therefore, try to properly educate your clients on the importance of stress management and proper sleep to mitigate the negative impact these stressors can have on training responsiveness.

  • Post-exercise nutrition influences training responsiveness.

It is widely accepted that good nutrition is vital to exercise performance. However, it is also becoming increasingly evident that the timing and composition of dietary intake contributes to training responsiveness. For instance, one study found that post-exercise consumption of a carbohydrate-protein beverage elicits a reduction in muscle protein degradation (Harber et al., 2010). A reduction of protein breakdown contributes to enhanced muscle recovery by creating a positive muscle-protein balance in the skeletal muscle. Similarly, post-exercise carbohydrate consumption has been show to significantly increase the rate of muscle glycogen replenishment. Both a positive muscle-protein balance and increased rate of muscle glycogen replenishment will accelerate the recovery process and decrease the time to return to resting homeostasis following exercise training. Consequently, as has been suggested by Mann, Lamberts and Lambert (2013), an increased “readiness” for the next training session is also likely to have a positive influence on training responsiveness. It is worth reminding clients that successful training outcomes are underscored, in part, by proper post-exercise nutrition.


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