Clinical trial NCT05107583: Effects of Pre-exercise Carbohydrate Restriction Relative to Fasting on Metabolism, Appetite, and Energy Intake in Healthy Males.
Official title: Comparing the Effects of a High- and Low-carbohydrate Pre-exercise Meal Relative to Fasting on Exercise Metabolism, Subsequent Appetite, and Energy Intake in Healthy Males.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Metabolic Syndrome
Keywords: Fasted exercise
Low-carbohydrate
High-protein
Appetite
Energy Intake
Metabolism
Lead sponsor: Nottingham Trent University
Sponsor class: OTHER
Collaborators: name: Loughborough University
First posted: 2021-11-04
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study design is a randomised, controlled, crossover design in which participants undertake three exercise conditions in a randomised order with at least a seven day period in between trials.
Primary purpose: BASIC_SCIENCE

Brief summary: This study will compare the metabolic, appetite, energy intake, and perceptual responses to a bout of exercise completed in the evening after after a low-carbohydrate lunch meal (\<10% carbohydrate content / 0.2 g/kg carbohydrate; LO-CHO), with the responses to exercise performed after a lunch meal containing a high carbohydrate content (\~60% carbohydrate content / 2.2 g/kg carbohydrate; HI-CHO), and after skipping lunch and fasting for 8 hours since breakfast (FAST).

Detailed description: Regular exercise is known to be a successful strategy for improving several facets of health and maintaining body weight. However, many people are not engaging in enough exercise, and some may not be achieving maximum benefits from the exercise that they already do. Performing exercise in the overnight fasted state has been shown to reduce energy intake over the course of a single day, without any compensatory reductions in free-living energy expenditure. Despite these promising findings, it is likely that not every member of the population is logistically able to perform exercise in the morning due to various work, family and social commitments, and exercise in the evening may be a logical alternative for these individuals.

Studies have found that exercise performed after an overnight fast may incur superior improvements in insulin sensitivity in lean individuals (Van Proeyen et al., 2010), and individuals with overweight or obesity (Edinburgh et al., 2020), compared to exercising after breakfast. These superior improvements may be mediated, in part, by an increased mobilisation and oxidation of endogenous lipid stores. Additionally, overnight fasted exercise may result in a more negative energy balance than exercising after breakfast (Bachman et al., 2016; Edinburgh et al., 2019). We recently examined whether exercise performed in the evening following an extended period of fasting (7 h) would induce similar responses to overnight fasted exercise regarding substrate oxidation patterns and subsequent energy intake (manuscript in preparation - NCT04742530). This research question was important, as we speculate that a large proportion of the population are likely unable to perform exercise in the morning after an overnight fast due to various logistical barriers. Therefore fasting prior to evening exercise could act as an alternative for these individuals.

We found that compared to consuming a carbohydrate-containing meal 2 h prior, fasting before evening exercise resulted in elevated fat oxidation rates during exercise, but was accompanied by compensatory eating at dinner. Additionally, participants reported that fasting throughout the afternoon was difficult. The long-term efficacy of fasted evening exercise may, therefore, be limited by increased hunger and compensatory energy intake.

Consuming a meal lower in carbohydrate and higher in protein and/or fat can increase rates of fat oxidation during exercise (Rowlands \& Hopkins, 2002; Oliviera et al., 2021). Protein is also the most satiating macronutrient, and high-protein diets are associated with reductions in energy intake. Consuming a high-protein pre-exercise meal compared to a typical high-carbohydrate meal also led to greater exercise-induced elevations in hormones typically associated with increased satiety and reduced hunger: peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1) (Oliviera et al., 2021). Therefore, consuming a meal with a low carbohydrate content and higher protein content before exercise, rather than completely fasting, could be utilised to enhance the metabolic responses to exercise, whilst simultaneously managing appetite and subsequent energy intake. Further research is needed to fully understand the metabolic and appetite-related effects of a low-carbohydrate, higher-protein meal prior to exercise in the evening, compared to a typically consumed higher-carbohydrate meal and complete fasting.

Eligibility criteria: Inclusion Criteria:

1. Non-smokers (due to the well-known impact of smoking on appetite.
2. Not currently on a weight management program or have an unusual eating pattern (i.e., extended fasting periods \>8 h other than overnight).
3. Have maintained a stable weight for 6 months (self-reported).
4. No history of gastric, digestive, cardiovascular or renal disease (self-reported).

Exclusion Criteria:

1. Severe food allergies, dislike or intolerance of study foods or drinks.
2. Currently undergoing a lifestyle intervention (structured diet or exercise).
3. Diagnosis of a condition or currently undergoing treatment therapy known to affect glucose or lipid metabolism (e.g., type-2 diabetes, taking statins), or contraindications to exercise.
4. Use of medication or supplements that may affect hormone concentrations and/or substrate metabolism.
5. Excessive alcohol consumption (\>14 units/week).
6. Intensive training schedule (\>10 hours/week).

Primary outcomes:
measure: Fat Oxidation Rate During Steady-State Exercise.
timeFrame: Throughout the 60-minute steady-state bout of cycling
Secondary outcomes:
measure: Voluntary energy intake (Kilocalories) at a laboratory-based test meal.
timeFrame: 60 minutes following the end of the exercise session.
measure: Visual Analogue Scale for Subjective Ratings of Appetite.
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Acylated ghrelin
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Peptide tyrosine-tyrosine (PYY)
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Glucagon-like peptide-1 (GLP-1)
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Glucose
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Insulin
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Non-esterified fatty-acids (NEFA)
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Glycerol
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 3 hours, 3.5 hours (mid-exercise), 4 hours, 5 hours.
measure: Rating of Perceived Exertion (RPE).
timeFrame: Throughout the 60-minute steady-state bout of cycling.
measure: Pre-exercise Subjective Feelings.
timeFrame: Immediately before the exercise session.
measure: Enjoyment of the Exercise Bout.
timeFrame: Immediately following the end of the exercise session.
measure: Carbohydrate Oxidation Rate During Steady-State Exercise
timeFrame: Throughout the 60-minute steady-state bout of cycling
measure: Rate of Energy Expenditure During Steady-State Exercise
timeFrame: Throughout the 60-minute steady-state bout of cycling
measure: Carbohydrate Oxidation Rate At Rest
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 5 hours
measure: Fat Oxidation Rate At Rest
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 5 hours
measure: Rate of Energy Expenditure At Rest
timeFrame: Baseline, 1 hour, 1.75 hours, 2.75 hours, 5 hours
Other outcomes:
Locations:
city: Loughborough
country: United Kingdom
facility: Loughborough University
state: Leicestershire
city: Nottingham
country: United Kingdom
facility: Nottingham Trent University
state: Nottinghamshire
Study officials:
References:
citation: Edinburgh RM, Bradley HE, Abdullah NF, Robinson SL, Chrzanowski-Smith OJ, Walhin JP, Joanisse S, Manolopoulos KN, Philp A, Hengist A, Chabowski A, Brodsky FM, Koumanov F, Betts JA, Thompson D, Wallis GA, Gonzalez JT. Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese. J Clin Endocrinol Metab. 2020 Mar 1;105(3):660-76. doi: 10.1210/clinem/dgz104.
citation: Van Proeyen K, Szlufcik K, Nielens H, Pelgrim K, Deldicque L, Hesselink M, Van Veldhoven PP, Hespel P. Training in the fasted state improves glucose tolerance during fat-rich diet. J Physiol. 2010 Nov 1;588(Pt 21):4289-302. doi: 10.1113/jphysiol.2010.196493.
citation: Edinburgh RM, Hengist A, Smith HA, Travers RL, Betts JA, Thompson D, Walhin JP, Wallis GA, Hamilton DL, Stevenson EJ, Tipton KD, Gonzalez JT. Skipping Breakfast Before Exercise Creates a More Negative 24-hour Energy Balance: A Randomized Controlled Trial in Healthy Physically Active Young Men. J Nutr. 2019 Aug 1;149(8):1326-1334. doi: 10.1093/jn/nxz018.
citation: Bachman JL, Deitrick RW, Hillman AR. Exercising in the Fasted State Reduced 24-Hour Energy Intake in Active Male Adults. J Nutr Metab. 2016;2016:1984198. doi: 10.1155/2016/1984198. Epub 2016 Sep 21.
citation: Rowlands DS, Hopkins WG. Effects of high-fat and high-carbohydrate diets on metabolism and performance in cycling. Metabolism. 2002 Jun;51(6):678-90. doi: 10.1053/meta.2002.32723.
citation: Oliveira CLP, Boule NG, Berg A, Sharma AM, Elliott SA, Siervo M, Ghosh S, Prado CM. Consumption of a High-Protein Meal Replacement Leads to Higher Fat Oxidation, Suppression of Hunger, and Improved Metabolic Profile After an Exercise Session. Nutrients. 2021 Jan 5;13(1):155. doi: 10.3390/nu13010155.
citation: Kendzierski, D., & DeCarlo, K. J. (1991). Physical Activity Enjoyment Scale: Two Validation Studies. Journal of Sport and Exercise Psychology, 13(1), 50-64. doi:10.1123/jsep.13.1.50.
citation: Rothschild JA, Kilding AE, Broome SC, Stewart T, Cronin JB, Plews DJ. Pre-Exercise Carbohydrate or Protein Ingestion Influences Substrate Oxidation but Not Performance or Hunger Compared with Cycling in the Fasted State. Nutrients. 2021 Apr 14;13(4):1291. doi: 10.3390/nu13041291.