The Effects of a 4-week Supplementation With a Ketogenic Nutrient Mix on 24-hour Substrate Metabolism and Muscle Health

This study will investigate the effect of providing a daily ketogenic nutritional supplement in the evening for a prolonged time (4 weeks) to induce a mild ketogenic state during the night in healthy elderly (60-80 years), overweight/obese (BMI: 25-35 kg/m2) individuals with low physical activity, on 24h rhythmicity in energy metabolism as compared to a non-ketogenic, isocaloric control.

Study Overview

• Status: Recruiting
• Conditions: Overweight and Obesity
• Intervention / Treatment: Dietary supplement: ketogenic nutritional Supplement; Dietary supplement: non-ketogenic, isocaloric control

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Merel Timmermans, MSc; Phone Number: 0031 88 3887793; Email: merel.timmermans@maastrichtuniversity.nl
• Study Contact Backup: Name: Joris Hoeks, Dr.

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 60-80 years
• Body mass index (BMI) 25-35 kg/m2
• Sedentary lifestyle (not more than 2 hours of structured physical activity per week in the past 3 months)
• Stable dietary habits (no weight loss or gain > 5 kg in the past 3 months)
• Healthy (as determined by dependent physician based on medical questionnaire)
• Regular sleeping habits (7-9h of daily sleep)

Exclusion Criteria:

• Type 2 diabetes
• Participants with active congestive heart failure and/or severe renal and or liver insufficiency
• Uncontrolled hypertension
• Alcohol consumption of >3 servings per day for men and >2 servings per day for women
• Unstable body weight (weight gain or loss > 5 kg in the last 3 months) or intention to lose weight
• Participants who are on an intermittent fasting diet
• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the investigator which would possibly hamper our study results
• Significant food allergies/intolerance (seriously hampering study meals or study product)
• Participants who do not want to be informed about unexpected medical findings
• Blood donation during or within 2 months prior to the study
• Disturbances in circadian rhythm determined with the follow criteria:
• Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire)
• Heavily varying sleep-wake rhythm
• Night shift work during last 3 months
• Travel across > 1 time zone in the last 3 months
• High daily caffeine intake > 400mg (more than 4 cups of coffee or energy drinks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic nutritional supplement; Daily ketogenic nutritional supplement for 4 weeks	Dietary supplement: ketogenic nutritional Supplement; Daily ketogenic nutritional supplement for 4 weeks
Placebo Comparator: non-ketogenic, isocaloric control; Daily control for 4 weeks	Dietary supplement: non-ketogenic, isocaloric control; Daily control for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta respiratory exchange ratio (from 23:00 till 04:00)	Measured with indirect calorimetry	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal mitochondrial function	Measured in muscle biopsy	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein and gene markers of skeletal muscle metabolism	Measured in muscle biopsy	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Metabolic blood markers	Measured in blood samples	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Interstitial ketone levels	Measured with a continuous ketone monitor	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Interstitial glucose levels	Measured with a continuous glucose monitor	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Whole body substrate utilization	Measured with indirect calorimetry	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Whole body energy expenditure	Measured with indirect calorimetry	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Physical performances	Measured with 6-minute walk test, chair-stand-test, and handgrip strength test	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Cognitive performance	Measured using Cambridge Neuropsychological Test Automated Battery (CANTAB) and cerebral perfusion measured with transcranial doppler ultrasound	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Other perceivable benefits: microvasculature	Measured with retinal images	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Other perceivable benefits: sleep quality	Measured with sleep quality questionnaires	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control
Body composition	Measured with BodPod	Measured after 4 weeks of daily supplementation with a ketogenic nutritional supplement or non-ketogenic, isocaloric control

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Joris Hoeks, Dr., Maastricht University; Principal Investigator: Peter Joris, Dr., Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: September 8, 2025
• First Submitted That Met QC Criteria: February 3, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: NL-009725

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No