Impact of Diet-induced Change in Energy Balance on Metabolism in Endurance Athletes (Carpe DIEM)

Impact of Diet-induced Change in Energy Balance on Metabolism in Endurance Athletes: the Carpe DIEM Study

Recent research has suggested that increasing levels of physical activity are associated with a reduction in the independent components that contribute to total energy expenditure (such as resting metabolic rate and non-exercise movement) - this occurs to conserve energy required for physical activity where energy provision becomes scarce. There are potential deleterious health and performance consequences of a reduced energy supply to fundamental metabolic processes, putting individuals regularly undertaking high levels of physical activity, such as endurance athletes, at risk. However, this association is largely based on observational data in only moderately active populations, and it is currently unclear what role energy balance status and biological sex has on this relationship.

This research intends to address these unknowns by assessing the impact of diet-induced manipulation of energy balance (conditions of energy deficit and energy surplus) in individuals undertaking habitually high levels of physical activity on independent components of total energy expenditure (resting metabolism, exercise and non-exercise movement).

Male and female athletes conducting regular moderate-to-high training volumes will undertake a randomised crossover study with a 7-day state of energy deficit and a 7-day state of energy surplus. Participants will continue to live and train as normal, but their diet will be controlled by specific food provision over the intervention periods in order to facilitate both conditions. Independent components of energy expenditure, markers of health, metabolism and performance will be measured to allow for comparison of conditions.

Study Overview

• Status: Not yet recruiting
• Conditions: Relative Energy Deficiency in Sport; Energy Balance; Energy Deficit; Low Energy Availability
• Intervention / Treatment: Dietary supplement: Controlled energy-deficit diet; Dietary supplement: Habitual diet with surplus snacks

Detailed Description

People with very active lifestyles such as athletes, dancers, and military personnel, need to eat a lot of food to make up for the large amount of energy they burn. If they don't match their food intake to their energy needs, they may enter a state of 'energy deficit'. This means their bodies are burning more calories than they're taking in, which can lower performance, increase the risk of injuries and illnesses, and potentially harm overall health.

Traditional scientific understanding assumes that more doing physically activity leads to burning more calories (the 'additive' model). However, newer studies suggest that the body might have built-in safeguards to limit how many total calories it burns, no matter how much a person exercises. This idea (the 'constrained' model) proposes that when people exercise more, their bodies might compensate by slowing down other metabolic processes to keep overall energy use within a certain range. Although this mechanism could help the body conserve energy, it may also mean that essential functions (like immune system support and reproductive function) can become impaired.

Most research on energy deficit so far has focused on people with normal or moderate levels of physical activity. Because extremely active people experience far higher daily energy demands, the 'constrained' mechanisms could manifest differently or to a greater degree and the negative health and performance consequences might be more severe. There is also limited knowledge about how quickly these changes in energy use begin and how they affect important processes at the cellular level, such as muscle mitochondrial function or immune cell health.

This study aims to fill these gaps by measuring total energy use (and its separate parts) in highly active individuals under two conditions: when participants eat enough to cover their energy demands and when participants are purposely in an energy deficit (intentionally eating less than they need). One of our main goals is to measure changes in resting metabolic rate (RMR), which is the energy the body uses at rest to keep vital functions going. Investigators will also examine cellular changes by looking at indicators like immune cell function to see how these might help us detect early signs of harmful energy shortages.

By understanding whether, and to what extent, the body's energy use is 'constrained', investigators can develop better guidelines to help very active individuals avoid unhealthy energy deficits. Ultimately, this research could improve both performance and long-term health for athletes, military personnel, dancers, and anyone else who regularly exercises at high levels.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joshua J Bakker-Dyos, BSc(Hons) MBChB; Phone Number: +447740191473; Email: jbd28@bath.ac.uk

Study Locations

• United Kingdom
  • Bath, United Kingdom, BA2 7AY
    • University of Bath
    • Contact: Joshua J Bakker-Dyos; Phone Number: +447740191473; Email: jbd28@bath.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Self-identified endurance-trained sport participants
• Training volume: >7 hours per week endurance training
• Training frequency: at least 5 days per week

Exclusion Criteria:

• Diagnosis of Relative Energy Deficiency in Sport (REDs)
• Active eating disorder (EDE-Q)
• Active flare of a chronic disease (e.g. inflammatory bowel disease)
• Type 1 or 2 diabetes mellitus
• Untreated or undergoing active treatment of anaemia (any cause)
• Current injury which precludes undertaking high volume endurance training
• Individuals following a habitual low-carbohydrate, high-fat diet
• Any medical diagnosis which precludes intense exercise (e.g. untreated cardiac arrhythmia)
• Allergy or intolerance to study foods
• Blood donation within preceding 8 weeks of study start date
• Use of medications that affect substrate utilisation (e.g. statins, corticosteroids, thyroxine, HRT)
• For females: current pregnancy, breastfeeding within past 6 months or post-menopausal
• Unable to undertake a treadmill running test
• Participation in any research study in the past 8 weeks
• Participation in a research study within the past year involving more than one DEXA scan
• Unable to provide informed consent due to impaired cognitive capacity or decision-making ability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Energy deficit; Diet-induced 50% energy deficit (based on estimated average total daily energy expenditure) by allocation of pre-made meals and snacks over 7-days	Dietary supplement: Controlled energy-deficit diet; Participants receive a prepared diet providing approximately 50% of their estimated daily energy expenditure to induce a sustained energy deficit; Other Names: Energy deficit
Experimental: Energy surplus; Diet-induced energy surplus (approximately 500-1000kcal/day) achieved by allocation of additional snacks to be consumed on top of habitual free-living diet, to avoid inadvertent energy deficit	Dietary supplement: Habitual diet with surplus snacks; Participants continue their normal diet with the addition of high-calorie snack items to achieve an approximate daily energy surplus; Other Names: Energy surplus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting metabolic rate (RMR) in kcal/day	The effect of a 7-day period of energy expenditure-matched diet-induced energy deficit versus energy surplus on RMR. Measured via indirect calorimetry using the Douglas bag method. Expired gas will be collected in a seated, fasted state under thermoneutral conditions, and oxygen consumption and carbon dioxide production will be used to calculate energy expenditure.	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total energy expenditure (from doubly labelled water) in kcal/day		Measured during both 7-day interventions starting at approximately week 4 and week 9.
Total energy expenditure ( from sum of independent components of energy expenditure) in kcal/day		Measured during both 7-day interventions starting at approximately week 4 and week 9
Peripheral blood mononuclear cell (PBMC) mitochondrial respiration	Assessment of mitochondrial respiratory function in isolated PBMCs using high-resolution respirometry (Oroboros). Measures include basal (routine), leak, oxidative phosphorylation (OXPHOS), and electron transfer system (ETS) capacity states. Data will be used to assess changes in mitochondrial function in response to exercise and nutritional intervention. Units: pmol O₂·s-¹·10⁶ cells-¹ (picomoles of oxygen consumed per second per million PBMCs).	Measured pre- and post-exercise at visits 2/3 (pre- and post-intervention 1) and visits 4/5 (pre- and post-intervention 2), approximately weeks 4-12.
Sub-maximal exercise performance (during steady-state treadmill exercise)	Running economy (oxygen consumption at a fixed submaximal speed, expressed as ml O₂·kg-¹·min-¹)	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Free T3 in pmol/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks.
Interstitial glucose concentration in mmol/l	Continuous glucose monitoring using Dexcom G7 reporting mean daily and daily variability in interstitial glucose concentration.	Measured during both 7-day interventions starting at approximately week 4 and week 9.
Bone mineral density (DEXA)	Bone mineral density will be assessed using dual-energy X-ray absorptiometry (DEXA). DEXA will provide areal BMD (g/cm²).	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Bone mineral density (pQCT)	Bone mineral density will be assessed using peripheral quantitative computed tomography (pQCT) at the tibia. Measures will include volumetric BMD (vBMD) in mg/cm³ in cortical and trabecular compartments.	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Subjective measures of fatigue	Daily subjective fatigue will be assessed using the Hooper Index (fatigue subscale, 5-item 1-5 Likert scale). Higher scores indicate greater perceived fatigue. Units: Hooper Index: total score (5-25)	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Sleep duration in h/night	Accelerometer-dervied using arm-worn Actigraph LEAP device.	Measured during both 7-day interventions starting at approximately week 4 and week 9.
Non-exercise activity thermogenesis (NEAT) (estimated from ActiGraph LEAP device) in kcal/day		Measured during both 7-day interventions starting at approximately week 4 and week 9
Exercise energy expenditure (estimated from ActiGraph LEAP device) in kcal/day		Measured during both 7-day interventions starting at approximately week 4 and week 9
Sub-maximal exercise performance (during steady-state treadmill exercise)	Substrate utilisation (absolute in g·min-¹)	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Sub-maximal exercise performance (during steady-state treadmill exercise)	Substrate utilisation (relative as % total energy expenditure)	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Bone mineral density (pQCT)	Cross-sectional area in mm²	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Bone mineral density (pQCT)	Strength-strain index in mm³	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks
Subjective measures of fatigue	Daily subjective fatigue will be assessed using the Fatigue Assessment Scale (FAS), a 10-item validated questionnaire scored from 10 to 50. Higher scores indicate greater perceived fatigue. Units: total score (10-50).	Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.
Total testosterone in nmol/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Free testosterone in pg/mL		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
cortisol in nmol/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
IGF-1 in ng/mL		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
leptin in ng/mL		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Female-specific hormones: oestradiol in pmol/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Female-specific hormones: FSH in IU/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Female-specific hormones: LH in IU/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Inflammatory markers: interleukin-6 (IL-6) in pg/mL		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
high-sensitivity C-reactive protein (hsCRP) in mg/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
ferritin in µg/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
serum iron in µmol/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
transferrin in g/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
total iron binding capacity (TIBC) in µmol/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
transferrin saturation as a percentage		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
soluble transferrin receptor in mg/L		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
hepcidin in ng/mL		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
Lipid markers: total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in mmol/L; non-esterified fatty acids (NEFA) in mmol/L; and glycerol in µmol/L.		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks
HbA1c will be reported in both % (DCCT-aligned) and mmol/mol (IFCC standard).		Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

Collaborators and Investigators

• Sponsor: University of Bath
• Collaborators: Royal Centre for Defence Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 14, 2025
• First Submitted That Met QC Criteria: August 11, 2025
• First Posted (Actual): August 14, 2025

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: physical activity; energy balance; energy availability; energy deficit
• Additional Relevant MeSH Terms: Mental Disorders; Feeding and Eating Disorders; Relative Energy Deficiency in Sport
• Other Study ID Numbers: 6854-11590; 345572 (Other Identifier: Health Research Authority)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No