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

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

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.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Nicotinamide Riboside

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age: 18-80 year-old
2. Male or female
3. Without psychiatric diagnosis according to a structured psychiatric interview (Structured Clinical Interview for DSM-V Axis I Disorders (SCID))
4. Without history of a psychotic disorder and/or mood disorder among parents, siblings, or children, as obtained via self-report only.

Exclusion Criteria:

1. Significant medical or neurological illness.
2. 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.
3. Taking any other medications, including over the counter supplements with the exception of oral contraceptives for women
4. Pregnancy. Females of child-bearing age must be using an effective contraceptive method.
5. History of smoking, substance abuse or dependence.
6. 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)
7. Medical condition that would prevent blood draws, including current anti-coagulant or anti-aggregant therapy, tendency for abnormal scarring (e.g. keloids).
8. Difficulty in swallowing capsules.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide riboside 2g/day; Participants will receive NR at a dose of 2g/day	Drug: Nicotinamide Riboside; Nicotinamide riboside 2g/day for a 2 week duration

What is the study measuring?

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 The NAD+/NADH ratio is calculated by first quantifying NAD+ and NADH separately in the data and then obtaining a simple ratio. There is a normative NAD+/NADH ratio range in healthy brain and deviations from this level in either direction can be a sign of pathology.	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

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Dost Ongur, MD PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: May 4, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 2017P000006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes