ACTivating Fat OXidation Through Capsinoids
Condition: Overweight and Obesity
MeSH terms: Overweight
Study type: Interventional

Summary: 
      Prior evidence suggests that capsinoids ingestion may increase resting energy expenditure
      (EE) and fat oxidation (FATox) in humans, although whether they can modulate those parameters
      during exercise conditions remains poorly understood. Investigators aimed to determine the
      effects of dihydrocapsiate (DHC) ingestion on EE and FATox during an acute bout of aerobic
      exercise at FATmax intensity (the intensity that elicits maximal fat oxidation [MFO] during
      exercise) in overweight/obese men.

      A total of 24 sedentary overweight/obese men participated in this randomized, triple-blinded,
      placebo-controlled, crossover trial. On the first day, participants underwent a submaximal
      exercise test in a cycloergometer to determine their MFO and FATmax intensity during
      exercise. After 72 hours had elapsed, the participants returned in 2 further days (≥ 72 hours
      apart) and performed a 60 min steady-state test (SST, i.e., cycling at their FATmax, constant
      intensity) after ingesting either 12 mg of DHC or placebo; these conditions were randomized.
      Respiratory gas exchange was monitored by indirect calorimetry. Serum markers concentrations
      (glucose, triglycerides, and non-esterified fatty acids), skin temperature, thermal
      perception, heart rate and perceived fatigue were assessed as secondary outcomes.
    

Detailed description: 
      The study protocol and design have been approved by the Human Research Ethics Committee of
      the University of Granada (n°839/CEIH/2019) and the Servicio Andaluz de Salud and adhered to
      the tenets of the Declaration of Helsinki as revised in 2013.

      Participants were asked to confirm having commuted to the research center by car, bus, tram,
      or motorcycle, having slept, as usual, having refrained from stimulant beverages within 24 h,
      and having avoided any moderate or vigorous physical activity within 24 h and 48 h
      (respectively).

      METHODS SUMMARY

      Briefly, in the first visit, sociodemographic and lifestyle data were registered, and medical
      screening was performed, blood samples were collected, and anthropometry and body composition
      measures were taken. On the second visit, the MFO during exercise and cardiorespiratory
      fitness (peak volume of oxygen consumption, VO2 peak) were respectively assessed through a
      submaximal exercise test coupled to a maximal effort test. On visits third and fourth,
      participants performed a 60 min steady-state exercise bout on a cycle ergometer at FATmax
      intensity (i.e., at the intensity at which MFO is elicited) after having ingested either 12
      mg of DHC or placebo. The conditions (DHC or placebo) on visits 3 and 4 were randomized. The
      washout period between visits 3 and 4 was ≥72 h. Of note, all exercise tests took place at a
      strictly controlled temperature of 22-23 ºC, given that environmental temperature largely
      influences EE and FATox.

      EXTENDED METHODS

      MEDICAL SCREENING, SOCIODEMOGRAPHIC DATA COLLECTION, AND ANTHROPOMETRY AND BODY COMPOSITION
      ASSESSMENTS:

      On the first visit, participants arrived at the research center at 08:00 h, in fasting
      conditions (8 h). Participants were informed about the study protocols details and gave their
      oral and written informed consent to participate in the study. Sociodemographic data and data
      related to participants´ dietary habits (including pungent consumption), appetite, physical
      activity levels, sleep, and other lifestyle habits were recorded by questionnaires (some of
      them filled at home). Afterward, a medical doctor conducted an anamnesis to ensure that each
      participant was in suitable physical conditions to participate in the study and to practice
      exercise. Next, participants underwent an electrocardiogram in resting conditions, which was
      conducted by an expert medical doctor. Systolic and diastolic blood pressure were also
      measured with an automatic sphygmomanometer (Omron M2; Omron Healthcare, Kyoto, Japan). These
      measurements were repeated on 3 consecutive occasions and the average systolic and diastolic
      blood pressure were calculated. Only participants presenting a non-risk medical history and
      normal electrocardiogram were allowed to participate in the study. Blood samples were
      collected from the antecubital vein in the morning (8.00-9.00 am), with subjects sitting and
      in resting conditions. Blood samples were collected in serum Vacutainer Tubes® (Vacutainer®
      SST™ II Advance tubes) and centrifuged following the manufacturer's instructions. Afterward,
      serum samples were sent to the hospital lab for the analysis of the analytes of interest.

      Anthropometry and body composition assessments also took place on the first visit. Body
      weight and height were measured (no shoes, light clothing) using a model 799 Seca scale and
      stadiometer (Seca, Hamburg, Germany). Waist circumference was measured twice at the minimum
      perimeter area with a measuring tape (mm precision), and the mean value was calculated. For
      those participants with abdominal obesity, waist circumference was measured just above the
      umbilicus (horizontal plane). Body fat mass and percentage, lean body mass, and visceral
      adipose tissue (VAT) mas were then measured by whole-body dual-energy X-ray absorptiometry
      (HOLOGIC, Discovery Wi, Marlborough, MA). Body mass, lean mass, and fat mass indexes were
      calculated as kg/m2.

      SUBMAXIMAL AND MAXIMAL EXERCISE TESTS:

      On the second visit, individuals arrived at the research center normally between 15:30 and
      19:00. Participants confirmed having met the above-stated pre-experimental conditions, as
      well as arriving in fasting conditions (5-6 h) and having followed a standardized diet that
      participants were instructed to follow during the previous day. Then, participants urinated,
      dressed as above, and entered a quiet, warm (22-23 °C) room. A submaximal-graded exercise
      test was performed (to determine the MFO) coupled to a maximum effort test (used to determine
      the VO2peak) employing an Ergoselect 200 cycle ergometer (Ergoline GmbH, Lindenstrasse,
      Germany). More in detail, the submaximal exercise protocol coupled to indirect calorimetry
      started with a 3 min stage at 20 watts (W) as a warm-up, followed by increments of 20 W every
      3 min, until resting exchange ratio (RER) was ≥1 at least for 30 s (as determined by indirect
      calorimetry). At this point, the maximal exercise protocol started (with no interruptions),
      and increments of 20 W took place every 1 min until volitional exhaustion was reached, or
      participants had to stop because of peripherical fatigue. Of note, the cycling power values
      (W) at which MFO happened for each individual were used as the target exercise intensity
      (i.e. FATmax) for the subsequent steady-state tests. Through the exercise test, participants'
      perceived fatigue was assessed using a rating of the reported perceived exertion (RPE) scale,
      and heart rate was measured using a Polar RS800 heart-rate monitor (Polar Electro Inc.,
      Woodbury, NY, USA). Respiratory gas exchange was monitored with a CPX Ultima CardioO2 system
      (Medical Graphics Corp., St Paul, MN) with a facemask model 7400 (Hans Rudolph Inc., Kansas
      City, MO), and a preVent™ metabolic flow sensor (Medical Graphics Corp.). Oxygen consumption
      (VO2) was measured using a galvanic fuel cell and carbon dioxide production (VCO2) was
      assessed using a non-dispersive infrared sensor. According to the manufacturer's
      recommendations, the gas analyzer was calibrated using standard gas concentrations
      immediately before each test.

      STEADY-STATE EXERCISE TESTS:

      On the third visit (≥72 h after the second day), and again on the fourth visit (≥72 h later
      to avoid carry-out effects), participants came to the laboratory and underwent the
      steady-state tests after the ingestion of DHC or placebo, in a randomized order. Participants
      arrived at the same time as on the second visit and confirmed having met exactly the same
      pre-experimental conditions. Participants urinated, dressed in standard clothing, and entered
      a quiet, warm (22-23 °C) room. A Polar RS800 heart-rate monitor was placed on their chest
      using a chest wrap band. Then, a set of 16 DS-1922 L Button TM wireless thermometers
      (Thermochron, Dallas, TX, USA) were attached to the subject's skin in different places to
      monitor skin temperature changes through the experiment. They were put on the forehead, left
      pectoralis, left elbow region, left index fingertip, left forearm, rear neck central area,
      right clavicula, right deltoid, right shinbone, right sub-clavicular area, right
      supra-clavicular area, right thigh, and upper breastbone. Afterward, participants sat and
      stay relaxed for 10 min (resting period, timepoint -20´), and were instructed not to move nor
      cross their arms and legs, and their baseline skin temperature and heart rate measures were
      taken. The first intravenous blood sample was collected 10 min before starting the
      steady-state test (timepoint -10'). Immediately 3 min after the first blood collection
      (timepoint -7'), participants ingested either 12 mg of DHC (4 pills 3 mg each one) or
      placebo. Then participants sat in the cycle ergometer where the steady-state tests would be
      performed, and a gas mask was put on for the gases exchange measurement. The same metabolic
      cart as on the second visit was used. The gas collection started 1 min before the beginning
      of the steady-state test (timepoint -1') with the participants sitting in the cycle ergometer
      without pedaling. After 1 min of gases recording in resting conditions, the steady-state test
      at FATmax intensity started and continued until min 60, the moment at which the test was
      ended. Gases exchange and heart rate were continuously monitored. At time points 15', 30',
      45', and 60', blood samples were collected.

      TEST SUBSTANCES: DIHYDROCAPSIATE AND PLACEBO:

      Investigators employed Capsiate Gold™ soft-gel capsules from Ajinomoto®. These capsules
      consisted of 3 mg of purified DHC vehiculated with canola oil, modified corn starch,
      vegetable glycerin, carrageenan, water, disodium hydrogen phosphate, and soy lecithin.
      Hemicellulose powder was used as a placebo. Both DHC and hemicellulose were encapsulated by
      independent manufacturers and put in different containers by an independent researcher (not
      involved in the current study). Each container was labeled with a different code (0 or 1) so
      that evaluators were not aware of the administered substance - therefore preventing bias. Of
      note, both DHC and placebo capsules looked exactly similar to unable the identification of
      the content by either researchers or participants.
    

Intervention name(s): Capsinoids + Exercise; Placebo + Exercise
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 60 minutes of aerobic exercise (cycle-ergometer) at FATmax intensity + supplementation with 12 mg of dihydrocapsiate (7 min before starting the aerobic exercise); 60 minutes of aerobic exercise (cycle-ergometer) at FATmax intensity + placebo pills (7 min before starting the aerobic exercise)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: capsinoids; dihydrocapsiate; FATmax; MFO; aerobic exercise; nutraceuticals; food ingredients