Metabolic Flexibility and Ketone Production During Energy Deficit

Technical University of Munich30 enrolled

Overview

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.

This is a monocentric, randomized, open-label nutrition intervention conducted in healthy adults aged 18 to 40 years. The study investigates the effects of short-term carbohydrate and caloric restriction on indices of metabolic flexibility. After screening and baseline assessments, participants undergo an initial period of energy balance with a standardized diet, followed by a 2-week intervention phase. Participants are randomly assigned in a 1:1 ratio to either a low-carbohydrate diet or a standard mixed diet. Participants are instructed to maintain their habitual physical activity throughout the study. During the first week of the intervention period, energy intake is equivalent to estimated energy requirements. During the second week, energy intake is reduced by \~500 kcal/d. Metabolic outcomes are assessed using repeated laboratory and remote measurements. Primary outcomes include breath-based measures of carbon dioxide and acetone production, as well as continuous glucose monitoring. Secondary outcomes include urinary and capillary blood ketones, body weight, body composition, resting metabolic rate, plasma glucose and selected biomarkers (leptin, insulin, triiodothyronine, GLP-1, HbA1c). Data are collected at baseline, during the intervention, and post-intervention. The total participation time per participant is approximately three weeks. The study aims to characterize short-term metabolic responses to dietary carbohydrate manipulation and energy deficit under controlled conditions.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

Conditions

Dietary Carbohydrate Restriction, Energy Deficit

Interventions

Low-Carbohydrate DietOTHER

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.

Standard Diet With Caloric RestrictionOTHER

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * Acute or chronic illness * Metabolic disorders or conditions associated with altered glucose or lipid metabolism (exclusion of pre-diabetes and diabetes via HbA1c measurement) * Use of medications known to interfere with study outcomes * Intolerance or allergy to components of the study diets * Pregnancy or breastfeeding

Locations (1)

Technical University of Munich

München, Bavaria, Germany

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Continuously assessed throughout the study period (approximately 3 weeks)

Secondary Outcomes

Urinary ketone concentration

Urinary ketone concentration is assessed once daily using reagent test strips and self-reported by participants.

Time frame: Daily during the study period (approximately 3 weeks)

Capillary blood ketone concentration

Capillary blood ketone concentration is measured once daily in the fasting state using a handheld ketone meter.

Time frame: Daily during the study period (approximately 3 weeks)

Fasting capillary blood glucose concentration

Fasting blood glucose concentration is measured once daily using a capillary blood glucose meter.

Time frame: Daily during the study period (approximately 3 weeks)

Body weight

Body weight is measured daily using a Bluetooth-enabled electronic scale.

Time frame: Daily during the study period (approximately 3 weeks)

Data from ClinicalTrials.gov

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