Addressing Individual Variability in Response to Exercise
Addressing Individual Variability in Response to Exercise
In this proposal, the investigators challenge the assumption that following the physical
 activity guidelines implies benefit for ALL adults, and that if benefit is not achieved in
 response to first line therapy, it will be by simply exercising more. Thus, for improving
 cardiorespiratory fitness and cardiometabolic risk factors, unanswered questions include: 1)
 To what extent, regardless of exercise amount or intensity, is exercise not associated with
 benefit? Demonstration of a resistance to benefit through exercise in a substantial number of
 adults would be a novel and important finding, would counter the assumptions of many if not
 most health care practitioners, and could have immediate and direct application in all health
 care settings. 2) To what extent will non-responders to first line therapy (150 min/wk) be
 required to increase exercise amount or intensity to achieve benefit? 3) To what extent will
 failure to improve CRF segregate (be associate with) with cardiometabolic risk factors? The
 investigators propose that adults who remain exercise resistant for improvement in CRF and
 cardiometabolic risk despite increasing amount or intensity are at high risk of metabolic
 disease and consequently, are candidates for alternative treatment strategies. 4) To what
 extent is biological sex and/or phenotype a determinant of response or non-response to
 exercise?
The trial has three objectives:

 Primary objective: Determine whether alterations in exercise amount and intensity improves
 the rate of clinically meaningful improvements in aerobic exercise capacity as measured by
 cardiorespiratory fitness (CRF, VO2peak) among adults.

 Secondary objective: Determine whether common cardiometabolic risk factors segregate with
 respect to variation in CRF to first line therapy in adults, and, whether clinically
 meaningful improvements in cardiometabolic risk factors segregate with associated improvement
 in CRF.

 Tertiary objective: Identify whether biological sex and/or phenotype are determinants of
 variation in CRF and cardiometabolic risk factors in response to first line therapy, and,
 whether they predict variability in CRF response to alterations in exercise dose.
Inclusion Criteria:

 -  Sedentary lifestyle (planned physical activity for one day per week or less).

 -  Weight stable (± 2 kg) for 6 months prior to the beginning of the study.

 -  BMI between 20 and 40 kg/m2.

 Exclusion Criteria:

 -  Physical impairment which would make the intervention very difficult or unsafe
 according to doctor's advice.

 -  Diabetes, current smokers.

 -  Plan to move from the area in next 8 months.