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NCT Number: NCT07122778

Impact of Diet-induced Change in Energy Balance on Metabolism in Endurance Athletes

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.

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Key information

Age range

18 year–49 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Controlled energy-deficit diet

Dietary Supplement

Participants receive a prepared diet providing approximately 50% of their estimated daily energy expenditure to induce a sustained energy deficit

Other names: Energy deficit

Habitual diet with surplus snacks

Dietary Supplement

Participants continue their normal diet with the addition of high-calorie snack items to achieve an approximate daily energy surplus

Other names: Energy surplus

Primary outcomes

  1. Resting metabolic rate (RMR) in kcal/day

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

    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.

Secondary outcomes

  1. Total energy expenditure (from doubly labelled water) in kcal/day

    Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9.

  2. Total energy expenditure ( from sum of independent components of energy expenditure) in kcal/day

    Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9

  3. Peripheral blood mononuclear cell (PBMC) mitochondrial respiration

    Time frame: 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.

    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).

  4. Sub-maximal exercise performance (during steady-state treadmill exercise)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

    Running economy (oxygen consumption at a fixed submaximal speed, expressed as ml O₂·kg-¹·min-¹)

  5. Free T3 in pmol/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks.

  6. Interstitial glucose concentration in mmol/l

    Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9.

    Continuous glucose monitoring using Dexcom G7 reporting mean daily and daily variability in interstitial glucose concentration.

  7. Bone mineral density (DEXA)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

    Bone mineral density will be assessed using dual-energy X-ray absorptiometry (DEXA). DEXA will provide areal BMD (g/cm²).

  8. Bone mineral density (pQCT)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

    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.

  9. Subjective measures of fatigue

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

    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)

  10. Sleep duration in h/night

    Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9.

    Accelerometer-dervied using arm-worn Actigraph LEAP device.

  11. Non-exercise activity thermogenesis (NEAT) (estimated from ActiGraph LEAP device) in kcal/day

    Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9

  12. Exercise energy expenditure (estimated from ActiGraph LEAP device) in kcal/day

    Time frame: Measured during both 7-day interventions starting at approximately week 4 and week 9

  13. Sub-maximal exercise performance (during steady-state treadmill exercise)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks

    Substrate utilisation (absolute in g·min-¹)

  14. Sub-maximal exercise performance (during steady-state treadmill exercise)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks

    Substrate utilisation (relative as % total energy expenditure)

  15. Bone mineral density (pQCT)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks

    Cross-sectional area in mm²

  16. Bone mineral density (pQCT)

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks

    Strength-strain index in mm³

  17. Subjective measures of fatigue

    Time frame: Measured at lab visits 1-5 (baseline and pre- and post-interventions) from 0 to 12 weeks.

    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).

  18. Total testosterone in nmol/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  19. Free testosterone in pg/mL

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  20. cortisol in nmol/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  21. IGF-1 in ng/mL

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  22. leptin in ng/mL

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  23. Female-specific hormones: oestradiol in pmol/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  24. Female-specific hormones: FSH in IU/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  25. Female-specific hormones: LH in IU/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  26. Inflammatory markers: interleukin-6 (IL-6) in pg/mL

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  27. high-sensitivity C-reactive protein (hsCRP) in mg/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  28. ferritin in µg/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  29. serum iron in µmol/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  30. transferrin in g/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  31. total iron binding capacity (TIBC) in µmol/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  32. transferrin saturation as a percentage

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  33. soluble transferrin receptor in mg/L

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  34. hepcidin in ng/mL

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  35. 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.

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

  36. HbA1c will be reported in both % (DCCT-aligned) and mmol/mol (IFCC standard).

    Time frame: Measured at lab visits 2-5 (pre- and post-interventions) from 4 to 12 weeks

Study contacts

Contact information is provided by the study sponsor or research team.

Joshua J Bakker-Dyos, BSc(Hons) MBChB

CONTACT

[email protected]

+447740191473

Sponsors and collaborators

Lead sponsor

University of Bath

Other

Collaborators

  • Royal Centre for Defence Medicine

Registry information

Official study title

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

Acronym: Carpe DIEM

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Aug 14, 2025
Registry last updated
Aug 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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