NAD Supplementation Study

Study Overview
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Brief Summary
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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.

Official Title
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The Effects of NAD+-Precursor Supplementation on Energy Metabolism in Physically Compromised Elderly

Conditions
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Aging, Mitochondrial Function

Intervention / Treatment
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* Dietary Supplement: NAD-precursors
* Dietary Supplement: Control


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, dubbel-blind, cross-over trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br> | Dietary Supplement: NAD-precursors<br>* 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.<br>|
| Placebo Comparator: Control<br> | Dietary Supplement: Control<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex vivo mitochondrial respiration | 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. | After 4 weeks of supplementation. | 
| Basal metabolic rate | Basal metabolic rate expressed as kcal/kg/min | After 4 weeks of supplementation. | 
| In vivo mitochondrial capacity | In vivo mitochondrial capacity measured with 31P-MRS. | After 4 weeks of supplementation. | 
| Submaximal exercise energy expenditure | Submaximal exercise energy expenditure expressed as kcal/kg/min | After 4 weeks of supplementation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose tolerance | Glucose tolerance measured by oral glucose tolerance test. | After 4 weeks of supplementation. | 
| Ectopic lipid accumulation | Liver and skeletal muscle lipid accumulation measured with H-MRS in vivo. | After 4 weeks of supplementation. | 
| Acetylcarnitine levels | Skeletal muscle acetylcarnitine levels measured with H-MRS in vivo, before and after exercise stimulation (cycling). | After 4 weeks of supplementation. | 
| Physical function | Measured by Short Physical Performance Battery and Frailty criteria. | After 4 weeks of supplementation. |