Metabolic Flexibility and Ketone Production During Energy Deficit

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.

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