Disturbances in brain insulin-sensitivity are not only observed in obesity and type 2 diabetes (T2D), but also during brain aging and in dementia. Ketone monoester supplements may improve brain insulin-sensitivity, which can be quantified by measuring the gray-matter cerebral blood flow (CBF) response to intranasally administered insulin. We hypothesize that acute ketone monoester supplementation increases (regional) brain vascular function and insulin-sensitivity thereby improving cognitive performance and appetite control. The primary objective is to evaluate in older men the acute effect of ketone monoester supplementation on (regional) brain vascular function and insulin-sensitivity, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labelling (ASL). The CBF response to intranasal insulin is a robust and sensitive physiological marker of brain insulin-sensitivity. Secondary objectives are to investigate effects on cognitive performance as assessed with a neuropsychological test battery, and appetite control as quantified by functional MRI (fMRI) with visual food cues.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
18
Ketone monoester supplement (395 mg/kg body mass)
The placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water
Maastricht University Medical Center
Maastricht, Limburg, Netherlands
Brain Vascular Function
Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
Time frame: Change from placebo intervention at 30 minutes after supplement intake
Brain Insulin Sensitivity
Cerebral blood flow measurements before and after a nasal insulin spray as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
Time frame: Change from placebo intervention at 60 minutes after supplement intake
Appetite-related brain reward activity
Blood oxygenation level-dependent (BOLD)-functional MRI (fMRI) response to food cues
Time frame: Change from placebo intervention at 40 minutes after supplement intake
Cognitive Performance
Cambridge Neuropsychological Test Automated Battery (CANTAB)
Time frame: Change from placebo intervention at 120 minutes after supplement intake
Brain Perfusion
Transcranial Doppler (TCD) ultrasound will be used to assess the velocity of blood flow through the middle cerebral artery (MCA)
Time frame: Change from placebo intervention at 120 minutes after supplement intake
Blood pressure
Office blood pressure and heart rate
Time frame: Change from placebo intervention at 90 minutes after supplement intake
Ketone metabolism
Circulating beta-hydroxybutyrate concentrations
Time frame: During 120 minutes following supplement intake
Glucose metabolism
Circulating glucose and insulin concentrations
Time frame: During 120 minutes following supplement intake
Markers related to low-grade systemic inflammation
Circulating high-sensitive C-reactive protein concentrations
Time frame: During 120 minutes following supplement intake
Appetite hormones
Circulating ghrelin concentrations
Time frame: During 120 minutes following supplement intake
Perceived hunger and satiety
Visual analogue scale (VAS) questionnaires
Time frame: During 120 minutes following supplement intake
Anthropometric measurements
Weight, length, waist and hip circumference
Time frame: Before supplement intake
Food intake
Food Frequency Questionnaire to assess food intake over the past month
Time frame: Once 120 minutes following supplement intake
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