Randomized Crossover Trial

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NEUTRAL: See Quality Criteria Checklist below.

To assess the effects of CHO overfeeding or by prolonged prior heavy exercise bouts on post-absorptive and post-prandial resting energy expenditure and substrate oxidation rates.

• Understand and give written consent
• Not on a special diet
• Not using any medication
• Non-smokers
• Healthy as assessed by a medical questionnaire
• Non-obese (i.e., body fat less than 25% in men and less than 35% in women)
• No diabetes mellitus or thyroid disorders
• Consume less than 20 alcoholic beverages per week
• Indulge in moderate sporting activities (between one and seven hours per week)
• Not on a diet
• Stable weight (i.e., no more than 2.5kg within six months.

• Refusal to consent
• Not meeting inclusion criteria.

Recruitment

Subjects were recruited by posters placed in university buildings and student dormitories. Interested individuals were sent a screening questionnaire that was evaluated by a physician and subjects were selected for participation.

Design

Randomized crossover design.

Statistical Analysis

• Repeated measures (within-subjects) model ANOVA was used to evaluate the effects of the exercise and carbohydrate overloading on the RMR and the thermic effect of food
• Pairwise comparisons were performed between the different treatment 
• Pairwise comparisons were statistically evaluated using the within-person T-test with a two-tailed region of rejection at a confidence level of 95%
• Data are given as mean values±SEM.

Timing of Measurements

• Total study was for 24 days, with two periods of eight days (on experimental diets) with a one-week interval in between (on habitual diets) to prevent carryover effects
• Between days one and five and days 16 and 20, subjects were on a controlled weight maintenance diet
• Between days five and nine and 20 and 24, there was CHO overfeeding
• During the seven days between experimental periods, subjects were on their habitual diet
• Subjects were randomized to exercise on two evenings before the RMR measures were taken in first or second period
• On exercise evenings (7:30 p.m. to 10:30 p.m.) of days four and eight, subjects performed a maximum work capacity test on a cycle ergometer, then cycled at fixed percentages of maximum work capacity for a maximum of two periods of 45 minutes separated by a 15-minute rest period
• On days five, nine, 20 and 24, energy expenditure was measured in the mornings in the fasted and post-prandial state.

Dependent Variables

• Post-absorptive resting energy expenditure: RMR measured in fasting state, and RMR measured 4.5 hours after a breakfast meal of 2mJ or less (approximately 478kcal); the average of the two values was used
• Post-prandial resting energy expenditure: Energy expenditure was measured for 3.5 hours after consumption of test meal (see Dietary):
  • Monitored heart rate?
  • Body temperature?
  • Medications administered: Excluded
  • Resting energy expenditure
  • IC type: Ventilated hood
  • Equipment of Calibration: Yes
  • Coefficient of variation using STD gases: No
  • Rest before measure (state length of time rested if available): 30 minutes
  • Measurement length: 60 minutes
  • Steady state: Movements were registered by means of a load cell, placed under one of the legs of the hospital bed
  • Fasting length: Yes, overnight
  • Exercise restrictions XX hours prior to test? Yes
  • Room temp: 23° to 25°C
  • Number of measures within the measurement period: One
  • Were some measures eliminated? No
  • Were a set of measurements averaged? A.M. and post-prandial afternoon measures were averaged to establish baseline measures
  • Coefficient of variation in subjects measures? No
  • Training of measurer? Not specified but likely
  • Subject training of measuring process? Yes
  • Dietary: Test meal for afternoon measurement of post-prandial REE: Liquid yogurt-based meal containing on average 1.34mJ (approximately 320kcal) (13% protein, 34% fat, 53% CHO).

Independent Variables

CHO overfeeding:

• Occurred between days five and nine and between days 20 and 24
• Started at 15% of the energy intake during the weight-maintenance period and added cumulatively to the diet, starting with 15% on the first day and increasing to 60% on the fourth day
• 70% of the CHO overfeeding was composed of normal foodstuffs, predominantly containing monsaccharides and disaccharides; 30% was given as a commercially available maltodextrins supplement (Fantomalt, Nutricia, Zoetermeer, The Netherlands)
• Experimental diets consisted of normal foodstuffs; subjects were provided with foods to be consumed
• They were allowed one free alcoholic consumption each day or one glass of orange juice
• Coffee, tea (without sugar and milk) and mineral water or water could be consumed ad libitum
• Over the entire experimental period, a four-day rotating menu was given to have a balanced number of consumption of each daily menu; it consisted on average of 14% protein, 35% fat, 51% CHO.

• Final N: Five males, five females
• Age: Mean age (±SD), 23±0.08 years; range, 20 to 29 years (two women were using oral contraceptives).
• Anthropometrics: Body weight did not show significant changes during the course of the experiment

Men and Women
	Mean(±SEM)	Range
Weight (kg)	51.8±3.6	51.8 to 81.4
BMI (kg/m2)	22.3 (0.6)	19.5 to 25.9
Body fat (percent) 17.4±1.5	17.4±1.5	8.8 to 25.1

• Location: The Netherlands.

 

 

Men and Women
Maximum work capacity, W
Before CHO	235±13.7
After CHO	238±13.9
Average workload, W
Before CHO	137.9±6.3
After CHO	149/3±11.9
Average exercise duration, minute
Before CHO	80.3±3.5
After CHO	83±3.1

At the start of the CHO period, subjects cycled on average for 80 minutes at 59% of work capacity. At the end of the CHO supplementation period, subjects exercised on average for 83 minutes at 63% of maximum work capacity. In total, subjects cycled in both exercise tests on averaged for more than 100 minutes.

Indirect Calomitry Results and RQs 

Post-absorptive RMR and RQs at Different Periods in the Study

	Control	CHO	Exercise	Exercise + CHO
RMR (kJ per minute) (mean+SEM)	4.56±0.2	4.50±0.28	5.10±0.25	4.82±0.17
RQ	0.83±0.01	0.91±0.01	0.78±0.01	0.87±0.01

 

• Morning RMRs did not differ significantly from afternoon RMRs (P>0.05)
• Glycogen-depleting exercise the day before significantly increased RMR (F-ratio = 8.56, P=0.02) on average by 9.5%. The effect of exercise on RMR was smaller (7.1%) when subjects did receive additional CHO.
• The group mean (±SEM) RMR on the morning after glycogen-depleting exercise completed the night before from 10:00 p.m. to 10:30 p.m.) was 1.219kcal±0.060kcal per minute (Range: 0.958kcal to 1.530kcal per minute)
• No systematic effect of CHO supplementation on the RMR was observed (F-ratio=2.52, P=0.15), nor of the interaction of exercise and carbohydrate overfeeding (P=0.30)
• Both treatments had a significant main effect on fasting RQs, but no significant interaction effect was observed
• Post-absorptive RQs were, on average, 10% higher at the end of the carbohydrate sub-population period compared with the start
• RQs were, on average, 12% lower after exercise, compared with the RQs measured in the non-exercise state. Not all subjects showed the same relative magnitude in response of the RMR to exercise.
• The individual fasting RQ range in weight maintenance phase was 0.80 to 0.86
• Carbohydrate sub-population (OR) exercise and carbohydrate overfeeding had a significant main effect on post-absorptive RQs, but no significant interaction effect was observed
• Post-absorptive RQs were, on average, 10% higher at the end of the CHO supplementation period, compared with the RQs observed at the start of the supplementation period
• The individual fasting RQ range at the end of CHO overfeeding was 0.81 to 0.99
• In contrast, RQs were, on average, 12% lower after exercise compared with the RQs measured in the non-exercise state
• The individual post-absorptive RQ range following glycogen depleting exercise was 0.75 to 0.83
• The individual post-absorptive RQ range following CHO overfeeding and glycogen-depleting exercise the night before was 0.83 to 0.97
• Exercise and carbohydrate supplementation affected post-prandial RQs in much the same way as they influenced the post-absorptive RQs
• The individual post-prandial RQ range in weight maintenance phase was 0.83 to 0.92
• The individual post-prandial RQ range after carbohydrate supplementation was 0.89 to 0.99
• The individual post-prandial RQ range after glycogen-depleting exercise the night before 0.76 to 0.82
• The individual post-prandial RQ range after glycogen-depleting exercise the night before and carbohydrate overfeeding was 0.86 to 0.96
• There was a significant effect of carbohydrate overfeeding on DIT (F-ratio = 11.30, P=0.008), on average of 39% [100 · (153 + 177)/(102 + 135)]
• The effect of carbohydrate overfeeding on DIT was smaller: 31% [100 · (177/135)] when subjects had prior glycogen-depleting exercise. However, the rate of post-prandial energy expenditure had not yet returned to the pre-meal baseline level after 3.5 hours in the CHO/exercise treatment.
• Glycogen-depleting exercise had an effect on DIT of an average 22% [100 · (177 + 135)/(153+102)]. This effect was of borderline significance (F-ratio = 3.77, P=0.08).
• DIT values were significantly increased by 32% (P=0.035) in response to exercise only when subjects did not receive extra carbohydrates
• There was no interaction effect of carbohydrate overfeeding and exercise on DIT
• DIT values expressed as a percentage of the ingested energy content were:
  • Control: 7.6%±0.9%
  • CHO: 11.5%±1.2%
  • Exercise: 10.1%±0.8%
  • CHO and exercise: 13.2%±1.4%.
• Time course of the post-prandial increase in energy expenditure:
  • The highest response was observed in the time interval between 30 and 120 minutes of the post-prandial period
  • After 210 minutes, the thermic effect of food was negligible for all treatments, except for the CHO/exercise treatment.

Pre-prandial and Post-prandial Substrate Utilization Rates

Preprandial and Postprandial Substrate Utilization Rates at Different Periods in the Study

 

	Pre-prandial				Post-prandial
	Control	CHO	Exercise	CHO+Ex.	Control	CHO	Exercise	CHO/Ex.
Protein (mg per minute)	46±4	37±3	51±4	45±4	46±4	37±3	51±4	45±4
Fat (mg per minute)	49±4	22±6	79±6	37±4	37±4	13±5	84±6	30±4
Glucose (mg per minute)	100±6	165±12	58±7	143±11	169±11	237±15	93±8	223±16
Lipogenesis (mg per minute)	0	0	0	0	1.1±0.9	6.2±1.8	0	2.8±0.8

• Protein oxidation rates were significantly reduced by CHO feeding
• Fat oxidation rates, both pre-prandially and post-prandially, were systematically decreased by CHO supplementation
• Glucose oxidation rates were significantly increased after CHO overloading
• Exercise had a significant impact on pre-prandial and post-prandial glucose and fat oxidation rates
• Post-prandial glucose and fat balances were significantly affected by both exercise and CHO over-feeding
• Post-prandial fat balances were:
  • Control: 5.2g±1.0g
  • CHO: 9.9g±1.1g
  • Exercise: -4.5g±1.2g
  • CHO and exercise: 6.4g±0.9g.
• Pre-prandial glucose balances were:
  • Control: 8.2±2.1g
  • CHO: 22.9±1.6g
  • Exercise: -8.0±1.6g
  • CHO and exercise: -4.8±3.6g.
• There were no significant interaction effects of CHO overfeeding and exercise on substrate utilization rates and nutrient balances. 

Post-prandial RQs (Average RQ over 3.5 Hours After Eating)

Diet-induced Thermogeneisis and Postprandial RQs at Different Periods in the Study

	Control	CHO	Exercise	Exercise+CHO
DIT (kJ)	102±12	153±16	135±10	177±18
RQ	0.87±0.01	0.94±0.01	0.79±0.01	0.90±0.01

 

As stated by the author in the body of report:

• The results of the present study show an increased RMR in response to prior glycogen-depleting exercise, but not in response to CHO overloading.   . .  . the impact of exercise on diet-induced thermogenesis was less pronounced, in particular, when subjects did receive additional CHO. 
• Exercise had an effect on RMR but was smaller in combination with CHO overloading
• Other studies have not identified a significant after-effect on RMR of prior exercise . . . the reasons are considerable variation in type, intensity and duration of applied exercise tests. It is likely that only prolonged strenuous glycogen-depleting exercise affects the body‘s energy economy sufficiently well to cause an enhanced thermogenesis in the post-exercise period.
• Prior exercise increases energy expenditure both in post-absorptive and post-prandial phase. In assessing the thermic response to food control of prior exercise may be warranted.
• Intense prolonged prior exercise increases energy expenditure both in the post-absorptive and the post-prandial phase. Short-term CHO overfeeding enhances the thermic response to food considerably, but does not increase RMR. The results indicated that in assessing the thermic response to food control over prior exercise may be warranted. The results also underscore the role of the antecedent diet in determining an individual's thermic response to food.

University/Hospital:

Wageningen Agricultural University

Strengths

Systematically explained IC measure and how they established exercise intensity and duration.

Generalizability/Weaknesses

• Generalizable to non-obese young adults who already have weekly exercising habits
• Questionable validity of indirect calorimeter
• Small N
• These are important variables on REE measurement accuracy. Did not achieve a 12-hour fasting measure; however, gave supporting diet-induced data (from pilot testing) on that rationale. Gave a “yes” for IC measure quality due to repeat measures and aggressive adherence to measurement protocol.
• [Analyst note: The baseline RMR measure did not identify if there were exercise restrictions prior to baseline measure. Because this exercise represents glycogen-depleting, endurance exercise that could only be completed by trained endurance athletes, this study did not appropriately answer the evidence analysis question and was not used in the Conclusion Statement].