Extreme Exercise and Energy Expenditure (4E) Study
Condition: Cardiovascular Diseases; Obesity, Visceral; Liver Fat; Metabolic Syndrome; Lifestyle
MeSH terms: Cardiovascular Diseases; Metabolic Syndrome; Obesity, Abdominal
Study type: Interventional

Summary: 
      The goal of this clinical trial is to provide evidence, through an extreme exercise
      prescription (1,144 km of road cycling on seven consecutive days), that weight loss is not
      the appropriate outcome to evaluate the effects of exercise on abdominal adiposity and
      ectopic fat depots (e.g. liver fat and epi/pericardial fat) in eleven recreational
      middle-aged male cyclists (aged 50 to 66 years) without symptoms of cardiovascular disease.
      The main questions it aims to answer are:

        -  If energy intake is substantially increased to compensate energy expenditure and prevent
           weight loss following an extreme exercise prescription, will significant changes in body
           composition and body fat distribution be observed?

        -  Will these changes translate into improvements in the cardiometabolic health profile
           even in the absence of weight loss?

      Participants will be asked to partake in several evaluations: fasting plasma
      lipoprotein-lipid profile and inflammation markers, glycated hemoglobin, cardiorespiratory
      fitness, submaximal exercise test including measurement of energy expenditure, resting and
      exercise blood pressure and heart rate, evaluation of regional adiposity, liver fat content,
      epi/pericardial fat, nutritional quality, and level of physical activity. After baseline
      evaluations, participants will be asked to alternately bike 208 km and 104 km per day on a
      pre-specified course for seven consecutive days. They will be accompanied during each of the
      seven bike rides by research professionals in a recreational vehicle. Participants' weight,
      body composition and waist circumference will be measured under standardized conditions in
      the morning after an overnight fast and after the exercise. Their heart rate will be
      continuously monitored, and participants will wear accelerometers to estimate their daily
      exercise-related energy expenditure. Foods and fluids will be provided to participants and
      recorded. At the end of the 1,144 km/ 7-days bike ride, baseline evaluations will be repeated
      with the exception of the maximal exercise treadmill test, nutritional quality, and level of
      physical activity. To facilitate the conduct of the protocol, the eleven participants will be
      evaluated and followed in two distinct groups.
    

Detailed description: 
      Although there is robust evidence that a physically active lifestyle including regular
      leisure time physical activity and exercise (>150 min per week of moderate to vigorous
      exercise per week) is associated with a reduced mortality risk and improved cardiometabolic
      health, some scientists have promoted the notion (which has certainly been taken up by the
      lay press) that if one wants to lose weight, focus should be placed on caloric restriction
      rather than on exercise. Several academic debates have been held on this issue which have
      left some health professionals and the public confused and perplexed.

      The investigators' research group has been active in this area on several fronts. First, the
      investigators have pioneered the notion that in cardiovascular and "metabolic" medicine, the
      health risk of overweight and obesity was not appropriately assessed by an index based on
      body weight (body mass index, which is expressed in kg/m^2). For instance, using imaging
      technology (computed tomography), the investigators were among the first, more than 30 years
      ago, to begin to extensively study regional body fat distribution, showing that excess
      visceral adipose tissue accumulation was more closely related to an atherogenic and
      diabetogenic cardiometabolic risk profile than excess body weight or total body fat. As
      sedentary individuals with a diet of poor nutritional value (rich in processed fat and added
      sugar - promoting preferential visceral fat deposition) are also often characterized by a
      lower muscle mass and by high levels of abdominal visceral fat, several lifestyle
      intervention studies that the investigators and others have conducted in sedentary males with
      visceral obesity have shown that with regular exercise, one could lose visceral adipose
      tissue while gaining muscle mass, which would lead to trivial or sometimes no changes in body
      weight. Thus, if body composition is altered by an energy deficit produced by regular
      exercise, the investigators have proposed that weight loss may sometime be misleading as an
      outcome as it may not always reflect favorable changes in body composition (muscle mass
      increasing) and in visceral adiposity and levels of ectopic fat (decreasing). On that basis,
      the investigators have proposed that changes in waist circumference could be more useful than
      body weight loss in the evaluation of the benefits of a lifestyle modification program
      involving regular endurance exercise such as brisk walking, jogging, or biking. For instance,
      the investigators have previously reported that waist circumference was rather sensitive to
      lifestyle changes involving regular physical activity/exercise. Accordingly, lifestyle
      intervention studies have shown that a reduction of 4 cm in waist girth was predictive of a
      58% reduction in the risk of developing type 2 diabetes among individuals who were initially
      characterized by abdominal obesity and glucose intolerance.

      Thus, there is a need to propose a paradigm shift among health professionals to evaluate the
      impact of lifestyle intervention programs involving physical activity/exercise in high-risk
      overweight obese individuals with visceral obesity: Weight loss is no longer the optimal or
      most clinically relevant outcome - losses of visceral adiposity and ectopic fat may be more
      relevant clinically.

      In 2015, a member of the investigators' team was asked to write an editorial on a spectacular
      study which provided very relevant data to the debate about diet vs. exercise and weight
      loss. In that impressive exercise study, recreational middle-aged cyclists were required to
      bike 2,700 km over 14 days and asked to try to match their energy intake to their very large
      energy expenditure, the objective being not to lose weight over the course of the
      intervention. Thus, the daily exercise "prescription" was huge as the authors wanted to test
      the ability of these elderly and fit recreational cyclists to match their energy intake to
      their energy expenditure. The most striking and important finding of this unusual study is
      that despite the huge energy expenditure associated with the 2,700 km bike expedition,
      participants did not lose weight. However, such lack of change in body weight was completely
      misleading in terms of energy balance and changes in body composition. Indeed, the cyclists
      lost 2.2 kg of body fat while gaining 2.5 kg of fat-free mass, a remarkable finding
      considering that such changes were observed over a period of only two weeks.

      Results of this study provide additional evidence that body weight is a poor outcome to
      assess the effect of a physical activity/exercise program. In the investigators' previously
      published exercise training studies, a common observation has been the disconnect between
      changes in body weight and changes in body composition, the latter being sometime observed
      even in the absence of weight loss. As weight poorly tracks changes in body composition
      induced by exercise, no wonder why exercise is indeed perceived as not being helpful to lose
      weight by some health professionals. The investigators propose that body weight is a
      misleading outcome when comes the time to evaluate the clinical benefits of exercise in
      individuals with overweight/obese.

      One remaining and clinically important issue remains to be addressed regarding the effects of
      a large volume of exercise not inducing weight loss: to what extent substantial changes in
      visceral/ectopic fat could have been observed had imaging data been available? In addition,
      it would have been interesting for the 2,700 km bike intervention study to report changes in
      waist circumference, this metric being more sensitive to regular exercise than body weight.
      In the investigators' previous intervention studies, it has been their experience to find
      participants losing quite a bit of visceral fat and dropping their waistline by several
      centimeters, while not losing any body weight.

      Thus, on the basis of the above observations, the investigators put forward the hypotheses
      that:

        1. a very large volume of exercise (1,144 km of bicycle performed for 7 consecutive days)
           will induce major changes in body composition and in levels of visceral adipose
           tissue/ectopic fat in a sample of middle-aged recreational cyclists who will be asked to
           match their energy intake to their very large energy expenditure during the course of
           the one-week extreme exercise intervention. Thus, in a study where, by design, no weight
           loss is planned nor wanted, the investigators expect to see major changes in body
           composition (slight increase in muscle mass and substantial reductions in the size of
           visceral adipose tissue and ectopic fat depots);

        2. changes in levels of visceral adipose tissue and ectopic fat will be better reflected by
           changes in waist circumference - which should decrease in the absence of body weight
           loss.

      The investigators recognize that this is an extreme exercise prescription that has little
      relevance to public health. However, results of this study will be very important in shedding
      light on the importance of shifting our attention from body weight loss to other, more
      clinically relevant fat depots. Thus, the purpose of the study is to provide evidence,
      through an extreme exercise prescription, that weight loss is not the appropriate outcome to
      evaluate the effects of exercise on visceral adiposity and ectopic fat depots (e.g. liver fat
      and epi/pericardial fat) which will likely be mobilized to a very significant extent in only
      one week.
    

Intervention name(s): High-volume road cycling
Intervention type(s): Behavioral
Intervention description(s): 1,144 km of road cycling performed on seven consecutive days with an increase in energy intake to maintain a stable body weight
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: cardiac fat; cardiometabolic health; cardiorespiratory fitness; ectopic fat; energy balance; exercise; liver fat; obesity; physical activity; visceral adipose tissue