Metabolic Flexibility and Ketone Production During Energy Deficit

NCT07429058 | Completed

• 1 other identifier: MetaFlex
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, interventional study examines the effects of short-term carbohydrate restriction, with and without caloric restriction, on indices of metabolic flexibility in healthy adults. Participants are randomly assigned to either a low-carbohydrate diet or a standard diet under energy balance, followed by the same diet under controlled caloric restriction. Primary outcomes include measures of carbon dioxide production, breath ketones and interstitial glucose. Secondary outcomes include blood and urinary ketones, body weight, body composition, and selected metabolic biomarkers.

Conditions

Dietary Carbohydrate Restriction, Energy Deficit

Keywords

Metabolic Flexibility; Ketone Production; Caloric Restriction; Low Carbohydrate Diet; Continuous Glucose Monitoring

Outcome Measures

Primary Outcomes (2)

• Carbon dioxide production and breath acetone concentration

  Carbon dioxide production and breath acetone concentration are assessed using portable breath analysis devices during standardized daily measurements and timepoints.

  Baseline, during the energy-deficit intervention period, and post-intervention (over approximately 3 weeks)

• Interstitial glucose concentration assessed by continuous glucose monitoring

  Continuous glucose monitoring is used to assess interstitial glucose concentration, including average glucose levels, glucose variability, and time in glycemic ranges.

  Continuously assessed throughout the study period (approximately 3 weeks)

Secondary Outcomes (12)

• Urinary ketone concentration

  Daily during the study period (approximately 3 weeks)

• Capillary blood ketone concentration

  Daily during the study period (approximately 3 weeks)

• Fasting capillary blood glucose concentration

  Daily during the study period (approximately 3 weeks)

• Body weight

  Daily during the study period (approximately 3 weeks)

• Fat Mass

  Baseline (Day 1), mid-intervention (approximately Day 14), and post-intervention (approximately Day 21)

Study Arms (2)

Low-Carbohydrate Diet

EXPERIMENTAL

Participants assigned to this arm follow a low-carbohydrate diet. Daily carbohydrate intake is reduced to approximately 75-125 g per day (about 15% of total energy intake), with remaining energy derived primarily from fat (\~70%) and protein (\~15%). Diets are individually tailored to meet estimated energy and micronutrient requirements. Participants are instructed to maintain their habitual physical activity throughout the study.

Other: Low-Carbohydrate Diet

Standard Diet

ACTIVE COMPARATOR

Participants assigned to this arm follow a standard mixed diet combined. The diet consists of approximately 50-55% carbohydrates, 25-35% fat, and 15% protein. Diets are individually tailored to meet estimated energy and micronutrient requirements. Participants are instructed to maintain their habitual physical activity throughout the study.

Other: Standard Diet With Caloric Restriction

Interventions

Low-Carbohydrate Diet OTHER

Participants receive a low-carbohydrate diet. All meals are provided and individually tailored based on estimated energy requirements. Carbohydrate intake is restricted to 75-125 g per day, with the remaining energy intake derived from fat and protein. The intervention is administered for 14 days.

Low-Carbohydrate Diet

Standard Diet With Caloric Restriction OTHER

Participants receive a standard mixed diet. All meals are provided and individually tailored based on estimated energy requirements. The macronutrient distribution consists of approximately 50-55% carbohydrates, 25-35% fat, and 15% protein. The intervention is administered for 14 days.

Standard Diet

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-40 years
• Body mass index (BMI) 18.5-27 kg/m²
• Regular exercise or vigorous physical activity at least once per week
• Willing and able to comply with the dietary intervention and study procedures
• For female participants: non-pregnant and using hormonal contraception

You may not qualify if:

• Acute or chronic illness
• Use of medications known to interfere with study outcomes
• Intolerance or allergy to components of the study diets
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Technical University of Munich: lead
• Metaflow Ltd.: collaborator

Study Sites (1)

Technical University of Munich

München, Bavaria, 80809, Germany

Location

MeSH Terms

Interventions

Diet, Carbohydrate-Restricted; Caloric Restriction

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Energy Intake

Study Officials

• Karsten Köhler, Prof. Dr.

  Professorship for Exercise, Nutrition and Health, Technical University of Munich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Karsten Köhler

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: February 24, 2026
• Study Start: November 24, 2023
• Primary Completion: March 11, 2024
• Study Completion: April 26, 2024
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

DE (1)