Effects of Short-term Adaptation to Ketogenic Diet on Endurance Trained Athletes

NCT07838818 | Active Not Recruiting

• 1 other identifier: GLYCO-LAB
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Skeletal muscle glycogen is a major endogenous carbohydrate store and an important substrate for ATP resynthesis during exercise. Its utilization increases with exercise intensity and duration, and low muscle glycogen availability has long been associated with impaired endurance exercise capacity. Beyond its role as a metabolic substrate, glycogen availability may influence excitation-contraction coupling and Ca²⁺ handling, providing multiple mechanisms through which carbohydrate availability can affect contractile function and fatigue. Ketogenic diets (KD), characterized by severe carbohydrate restriction (\<5% of energy intake), induce a profound redistribution of exercise metabolism. Reduced carbohydrate availability markedly increases fat oxidation while decreasing reliance on carbohydrate and muscle glycogen during exercise. This adaptation has frequently been interpreted as a glycogen-sparing mechanism that could extend endogenous carbohydrate availability during prolonged exercise. However, reduced glycogen utilization does not necessarily imply glycogen preservation, particularly when exercise begins with substantially lower muscle glycogen stores. Direct evidence quantifying muscle glycogen before and after a standardized exercise bout during ketogenic adaptation remains limited. The marked shift toward lipid oxidation may also have consequences for exercise energetics. Fat oxidation provides less ATP per unit of oxygen consumed than carbohydrate oxidation, thereby increasing the oxygen requirement for a given rate of oxidative ATP resynthesis. This may become particularly relevant as exercise intensity and ATP demand increase, when carbohydrate-derived energy provision becomes progressively more important. Thus, ketogenic adaptation may reduce glycogen utilization while simultaneously increasing the oxygen cost of exercise and limiting the capacity to sustain higher exercise intensities. Nutritional ketosis may additionally influence exercise responses beyond skeletal muscle metabolism. KD markedly increases circulating β-hydroxybutyrate (βHB), which can be utilized as an oxidative substrate by peripheral tissues and crosses the blood-brain barrier, contributing to cerebral oxidative metabolism. Whether increased ketone availability modifies the cerebral response to exercise, and whether this relates to perceptual or exercise responses during carbohydrate restriction, remains unclear. Accordingly, the specific aims are:

1. 1.To determine the effects of 10 days of ketogenic adaptation on skeletal muscle glycogen availability and utilization during standardized prolonged exercise. It is hypothesized that KD reduces resting muscle glycogen and attenuates exercise-induced glycogen utilization without preserving post-exercise glycogen availability.
2. 2.To determine the effects of ketogenic adaptation on substrate oxidation, exercise energetics, and exercise capacity. It is hypothesized that the shift toward greater lipid oxidation increases the oxygen cost of standardized submaximal exercise and impairs both prolonged exercise tolerance and subsequent high-intensity endurance capacity.
3. 3.To explore circulating substrate, perceptual, and cerebral responses to exercise during nutritional ketosis. Glucose, lactate, and βHB responses, together with prefrontal cortical oxygenation assessed by functional near-infrared spectroscopy (fNIRS), are examined to determine whether the pronounced peripheral metabolic adaptations are accompanied by detectable alterations in cerebral hemodynamic or perceptual responses.

Conditions

Ketogenic Diet; Control Condition

Outcome Measures

Primary Outcomes (3)

• Skeletal muscle glycogen

  Resting Skeletal muscle glycogen and skeletal muscle utilization during exercise

  10 days

• Endurance performance

  Overall exercise tolerance will be quantified as total exercise duration (min), defined as the combined duration of the 2-h submaximal exercise bout and the subsequent TTE. Subsequent high-intensity endurance capacity will be quantified separately as TTE duration (min) .

  10 days

• Pre-frontal cortex hemodynamics and perceived fatigability during endurance exercise

  Functional near-infrared spectroscopy (fNIRS) was used to evaluate prefrontal cortex hemodynamics during exercise + questionnaire ( ROF, Feeiling scale)

  10 days

Study Arms (2)

KETOGENIC DIET (KD)

EXPERIMENTAL

will follow ketogenic diet during the intervention

Other: Ketogenic diet

CONTROL DIET

ACTIVE COMPARATOR

will follow control diet (55% carbohydrate) during the intervention

Other: Control Diet

Interventions

Ketogenic diet OTHER

KD (5% CHO, 2.0 g/kg/day protein)

KETOGENIC DIET (KD)

Control Diet OTHER

Control diet: 55% CHO, 2.0 g/kg/day protein

CONTROL DIET

Eligibility Criteria

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

You may qualify if:

• Male
• Age 18-40 yr,
• BMI: 18-25 kg/m\^2,
• At least two years of endurance training experience
• a cycling volume of at least 150 km·week
• habitual consumption of a carbohydrate-based diet (\>50% of total daily energy intake from carbohydrates)

You may not qualify if:

• Chronic diseases
• Acute inflammatory states
• Psychiatric disorders
• Recent (within 3 months) treatment with anabolic steroids or systemic corticosteroids

Sponsors & Collaborators

• University of Padova: lead
• University of Bologna: collaborator

Study Sites (1)

Department of Biomedical Sciences, University of Padus

Padova, Italy, 10034, Italy

Location

MeSH Terms

Interventions

Diet, Ketogenic

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 24, 2026
• Study Start: November 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: September 30, 2026
• Last Updated: September 29, 2026

Record last verified: 2025-09

Locations

IT (1)