The Effects of Nicotinamide Riboside Supplementation on Brain NAD+/NADH Ratio and Bioenergetics

Study Overview
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Brief Summary
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The primary aim of this study is to investigate the effects of exogenously administered nicotinamide riboside (NR) on brain NAD+/NADH ratio and bioenergetics functions in healthy individuals using phosphorus magnetic resonance spectroscopy (31P MRS) imaging. The secondary aims are to investigate the change in brain PCr/ATP and creatine kinase enzyme rate after NR use. In addition, NAD+/NADH ratio, PCr/ATP and CK enzyme rate will be measured in the calf muscle, as secondary outcome measures.

Official Title
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The Effects of Nicotinamide Riboside Supplementation on Nicotinamide Adenine Dinucleotide (NAD+/NADH) Ratio and Bioenergetics

Conditions
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Healthy

Intervention / Treatment
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* Drug: Nicotinamide Riboside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-80 year-old Male or female Without psychiatric diagnosis according to a structured psychiatric interview (Structured Clinical Interview for DSM-V Axis I Disorders (SCID)) Without history of a psychotic disorder and/or mood disorder among parents, siblings, or children, as obtained via self-report only. Exclusion Criteria: Significant medical or neurological illness. Diagnosis diabetes mellitus (DM), uncontrolled hypertension (HTN), severe hypotension, coronary artery disease (CAD), metabolic syndrome, glaucoma, liver impairment, decreased renal function, respiratory disorders, uncontrolled peptic ulcer disease. Taking any other medications, including over the counter supplements with the exception of oral contraceptives for women Pregnancy. Females of child-bearing age must be using an effective contraceptive method. History of smoking, substance abuse or dependence. Contraindication to MR scan (claustrophobia, cardiac pacemakers, metal clips and stents on blood vessels, artificial heart valves, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal- containing intrauterine devices) Medical condition that would prevent blood draws, including current anti-coagulant or anti-aggregant therapy, tendency for abnormal scarring (e.g. keloids). Difficulty in swallowing capsules.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinamide riboside 2g/day<br>Participants will receive NR at a dose of 2g/day | Drug: Nicotinamide Riboside<br>* Nicotinamide riboside 2g/day for a 2 week duration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the end of treatment in brain NAD+/NADH ratio | Change from baseline to the end of treatment in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy | Baseline and after 15 days of supplement use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the end of treatment in brain phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio (PCr/ATP) | Change from baseline to the end of treatment in brain phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio (PCr/ATP) as measured by in vivo 31P magnetic resonance spectroscopy | Baseline and after 15 days of supplement use | 
| Change from baseline to the end of treatment in brain creatine kinase (CK) enzyme rate | Change from baseline to the end of treatment in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy | Baseline and after 15 days of supplement use | 
| Change from baseline to the end of treatment in muscle NAD+/NADH ratio | Change from baseline to the end of treatment in calf muscle NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy | Baseline and after 15 days of supplement use | 
| Change from baseline to the end of treatment in muscle phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio (PCr/ATP) | Change from baseline to the end of treatment in calf muscle phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio (PCr/ATP) as measured by in vivo 31P magnetic resonance spectroscopy | Baseline and after 15 days of supplement use | 
| Change from baseline to the end of treatment in muscle creatine kinase (CK) enzyme rate | Change from baseline to the end of treatment in calf muscle creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy | Baseline and after 15 days of supplement use |