Aging, Mitochondrial Function
Conditions
Brief summary
This research project aims to determine whether supplementing with a mixture of the NAD+-precursors NA, NAM, and tryptophan can stimulate skeletal muscle mitochondrial function in physically compromised, elderly humans. Outcomes are related to mitochondrial function, energy metabolism, and physical function will be investigated.
Interventions
DIETARY_SUPPLEMENTNAD-precursors
Intervention product containing the NAD+-precursors nicotinic acid, nicotinamide, and tryptophan (total of 204 NE per serving) in a whey protein source for 31 days.
DIETARY_SUPPLEMENTControl
Control product containing amino-acid mixture resembling whey-protein not containing the NAD+-precursors nicotinic acid, nicotinamide, and tryptophan. To be taken for 31 days.
Sponsors
Maastricht University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, dubbel-blind, cross-over trial
Eligibility
Sex/Gender
ALL
Age
65 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females * Age ≥ 65 ≤ 75 years; * BMI ≥ 20 kg/m2 ≤ 30 kg/m2; * Normal physical activity levels: maximum of 1 hour per week engagement in a structured exercise session; * SPPB score 4-9 and (pre-)frail; * Subject should be in sufficient health to participate in the experiments, to be judged by the responsible physician based on the subject's medical history.
Exclusion criteria
* Not meeting all inclusion criteria; * Smoking; * Excessive alcohol use and/or drug abuse; * Subjects with diabetes mellitus type 2; * Significant food allergies or intolerances concerning the study products; * Participation in another biomedical study within 1 month before the first study visit, possibly interfering with the study results; * Medication use known to hamper subject's safety during the study procedures; * Subjects who use selective serotonin re-uptake inhibitors (SSRI), or selective norepinephrin re-uptake inhibitors (SNRI), or monoamino oxidase inhibitors (MAO-inhibitors), or clomipramine, or St. John's wort (Hypericum perforatum); * Subjects with contra-indications for MRI; * Subjects who do not want to be informed about unexpected medical findings; * Subjects who do not want that their treating physician to be informed; * Co-morbidities to which the intervention or program the may pose as a complicating factor; * Inability to participate and/or complete the required measurements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ex vivo mitochondrial respiration | After 4 weeks of supplementation. | Ex vivo mitochondrial function in skeletal muscle measured by oxygen consumption in muscle fibres (muscle biopsy vastus lateralis) on lipid-derived and carbohydrate-derived substrates. |
| Basal metabolic rate | After 4 weeks of supplementation. | Basal metabolic rate expressed as kcal/kg/min |
| In vivo mitochondrial capacity | After 4 weeks of supplementation. | In vivo mitochondrial capacity measured with 31P-MRS. |
| Submaximal exercise energy expenditure | After 4 weeks of supplementation. | Submaximal exercise energy expenditure expressed as kcal/kg/min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose tolerance | After 4 weeks of supplementation. | Glucose tolerance measured by oral glucose tolerance test. |
| Ectopic lipid accumulation | After 4 weeks of supplementation. | Liver and skeletal muscle lipid accumulation measured with H-MRS in vivo. |
| Acetylcarnitine levels | After 4 weeks of supplementation. | Skeletal muscle acetylcarnitine levels measured with H-MRS in vivo, before and after exercise stimulation (cycling). |
| Physical function | After 4 weeks of supplementation. | Measured by Short Physical Performance Battery and Frailty criteria. |
Countries
Netherlands
Outcome results
None listed