The Acute Effects of Capsiate During Exercise
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Capsiate is a non-pungent analogue of capsaicin, the component of hot peppers that makes them
      hot or spicy. Unlike capsaicin, capsiate is not spicy or hot. Ingestion of capsiate has been
      shown to increase resting oxygen consumption, body temperature, and the burning of fat. As
      such, capsiate appears to act in a manner similar to that of many other substances that
      energize us, increase our alertness and cause a rushing feeling by affecting a system in our
      body that is responsible for the release of adrenaline. The major difference, however, is
      that capsiate is broken down in the stomach into two components: vanilla and a fatty acid,
      and is not absorbed as capsiate into the blood stream at all. This implies that the way
      capsiate works is likely by acting on the cells in the gut (before it is broken down)rather
      than affecting all other cells in the body as it would do if it ended up in the blood.
      Therefore, the gut cells are thought to be the ones responsible for triggering the full-body
      adrenaline response. In any case, the use of capsiate has been shown to be effective in
      preventing weight gain and as such it may represent a possible therapy for treating obesity.
      Many obesity-related programs not involving medication advocate the use of diet and/or
      exercise. However, one of the biggest problems with weight loss from dieting alone is a
      general decrease in our body's ability to burn the food we eat as energy. This very problem
      is the reason for why people turn to adrenaline-releasing drugs like caffeine and ephedra.
      Unfortunately though, if too much is consumed, there is a high risk of bad side-effects.
      However, low dose caffeine/ephedra compounds (that are within specified FDA limits) have
      recently been reported to be effective. Moreover, these compounds are used with great
      frequency by people attempting to lose weight.

      Given that capsiate increases body temperature, promotes the burning of body fat and has an
      exceptionally great side-effect profile, it looks to be a very effective supplement for use
      in treatment of obesity and overweight. As such, it would be important to test this
      supplement along with exercise. This is because consuming capsiate with exercise may enhance
      its effectiveness in increasing the burning of body fat. The primary purpose of this study is
      to examine the response of young healthy males to a 90 minute bout of moderate intensity
      cycling after having consumed 0 mg, 3 mg, or 10 mg of capsiate.
    

Detailed description: 
      Hypotheses

      Based on the rationale and brief background above we propose the following substantive
      hypotheses:

        1. Ingestion of capsiate 30min prior to exercise will elevate resting and exercising oxygen
           consumption (VO2) in a hierarchical manner: 10>3>0mg

        2. Respiratory exchange ratio will be shifted toward greater lipid oxidation (i.e., toward
           0.7) in a hierarchical manner: 10>3>0mg

      Our secondary hypotheses are:

        -  A greater rise in glycerol and FFA at rest and during exercise in a hierarchical manner:
           10>3>0mg

        -  A greater rise in catecholamine (Epinephrine and Norepinephrine) concentrations in a
           hierarchical manner: 10>3>0mg

      Protocol We will use a double-blind repeated measures study design in which subjects will
      complete 3 trials - 0, 3, and 10mg - of capsiate. Based on acute effects seen in previous
      studies 1, 4 we anticipate that a sample size of 12 subjects (all subjects will be males to
      control for possible sex-based differences in substrate oxidation during exercise) would
      appear to be adequate to see significant effects of capsiate on oxygen consumption and
      substrate oxidation. Randomization will be done on a counterbalanced and blocked basis with 3
      conditions and 6 possible order combinations and with 12 subjects, each subject will be
      randomized in a counterbalanced manner so that 2 subjects complete each trial order.: ABC,
      ACB, BCA, BAC, CAB, CBA, order of treatment and assignment will be performed at random and
      under complete control of the McMaster University Pharmacy. The chief pharmacist - Dr. Gita
      Sobhi - will give the code for each treatment to the PI only after completion of the data
      analysis. We will use a cycling protocol at an intensity of 55% of each subject's individual
      peak VO2 for 90 minutes. Workload to determine 55% of peak VO2 will be according to the
      algorithm detailed by Latin et al. 17 This exercise intensity is adequate to elevate
      lipolysis (i.e., glycerol and FFA), catecholamines, and show a substantial shift in RER
      toward lipid oxidation with increasing exercise duration. The PI has experience with this
      protocol and has measured substrate oxidation previously using the same or very similar
      protocols. 18-20 Moreover, this type of exercise intensity represents an intensity that
      elicits an exercising RER in or around 0.9 and thus where there is a good blend (65:35
      carbohydrate:lipid) of fuels being oxidized, but is also an intensity close to what has been
      referred to as 'fatmax', which is defined as the intensity of exercise at which the maximal
      rate of lipid oxidation occurs. 16, 21-23 Thus, in terms of selecting an exercise intensity
      that will reveal the impact of capsiate on both energy expenditure and substrate oxidation we
      believe that this intensity is an optimal one. We will collect breath (breath-by-breath and
      ensemble averaged into 30s bins) and blood samples for 30min into recovery to assess to what
      degree excess post-exercise oxygen consumption is elevated and whether this is accompanied by
      significant fat oxidation and elevated plasma catecholamines.

      We will use recreationally active subjects (peak VO2 > 40 ml/kg/min) so that we're assured
      they will be able to complete the protocol. Subjects will be screened using a standard health
      questionnaire (see attached consent form) and a maximal exercise test. Subjects will be
      healthy non-smokers between the ages of 18-30 and will be recruited from the local McMaster
      University campus or surrounding community. Exercise trials will take place in the overnight
      fasted state (last meal at 2000h) after having consumed a standardized diet on the day prior
      to the exercise trial. Having subjects in the fasted state does not present a risk or barrier
      to the subjects completing the trial as based on past experience with this protocol. It is
      emphasized that being in the fasted state is also the easiest state in which to interpret the
      data from the standpoint of substrate oxidation. The pre-trial day diet will consist of
      energy estimated for each subject based on the Harris-Benedict equation 24 with an activity
      factor of 40%. The diet will be 50:30:20 in terms of percent energy from
      carbohydrate:fat:protein. Subjects will consume the same diet on the days prior to each
      exercise trial to control for pre-study calorie and carbohydrate/fat intake, which could
      affect substrate oxidation. Subjects will refrain from consumption of alcohol and caffeine on
      the day of the trial. Trials will take place at least 5d (but no more than 7d) apart and will
      commence at a time between ~7-10am and will proceed according to the schematic timeline shown
      in figure 1. The testing time for subjects will remain consistent throughout the study. We
      also believe that it is prudent for subjects to consume a fixed and constant volume of water
      (1000ml) during all trials to prevent dehydration and to allow subjects to complete the ride
      in safe manner.

      All data will be analyzed using a repeated measures two-way analysis of variance with time as
      a within factor and dose as a between factor. Significant ANOVA effects will be further
      scrutinized using Tukey's test as a post-hoc procedure. Where significant correlation of one
      variable with another exists an analysis of covariance may also be performed. Significance
      will be accepted at P<0.05.

      Analysis VO2 and RER for energy expenditure and substrate use - standard equations using
      revised non-protein RER as described by Jeukendrup and Wallis. 26 HR - using Polar™
      monitoring and on-line collection via the AEI metabolic cart BP - using Finapres™ blood
      pressure monitoring. Blood glucose, glycerol, lactate - fluorometric methods as detailed in
      Passoneau and Lowry 27 and as performed previously by the PI. 18, 20, 28 Free fatty acids -
      colorimetric micro-assay method from WAKO diagnostics
      (http://www.wakodiagnostics.com/r_nefa.html) Catecholamines - using reverse phase HPLC and
      electrochemical detection as described previously. 18, 20
    

Intervention name(s): Acute consumption of Capsiate Natura; Acute consumption of Capsiate Natura; Acute ingestion of identical placebo capsules
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 10 capsules = 3 mg total capsiate. Consumed ONCE orally as capsules 30 minutes before starting to exercise. 3 active capsules containing 1 mg capsiate each and 7 placebo capsules.; 10 capsules = 10 mg total capsiate. Consumed ONCE orally as capsules 30 minutes before starting to exercise. Each capsule contains 1 mg capsiate.; 10 mg placebo = 0 mg total capsiate. Consumed ONCE orally as capsules 30 minutes before starting to exercise. Each capsule contains 1 mg capsiate.
Other intervention name(s): Brand: Capsiate Natura, Capsinoid; Brand: Capsiate Natura
Intervention MeSH terms: Capsaicin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Acute Exercise protocol; Crossover design; Oxygen consumption (VO2); Respiratory Exchange Ratio (RER); Adrenergic System Agonism; Capsiate Natura; Young; Male