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

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03151707

Enrollment

Registered

2017-05-12

Start date

2017-10-01

Completion date

2022-09-30

Last updated

2024-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

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.

Interventions

DRUGNicotinamide Riboside

Nicotinamide riboside 2g/day for a 2 week duration

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to the End of Treatment in Brain NAD+/NADH Ratio	Baseline and after 15 days of supplement use	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.

Secondary

Measure	Time frame	Description
Change From Baseline to the End of Treatment in Brain Phosphocreatine (PCr) to Adenosine Triphosphate (ATP) Ratio (PCr/ATP)	Baseline and after 15 days of supplement use	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
Change From Baseline to the End of Treatment in Brain Creatine Kinase (CK) Enzyme Rate	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Change From Baseline to the End of Treatment in Muscle NAD+/NADH Ratio	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in calf muscle NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy
Change From Baseline to the End of Treatment in Muscle Phosphocreatine (PCr) to Adenosine Triphosphate (ATP) Ratio (PCr/ATP)	Baseline and after 15 days of supplement use	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
Change From Baseline to the End of Treatment in Muscle Creatine Kinase (CK) Enzyme Rate	Baseline and after 15 days of supplement use	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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Nicotinamide Riboside 2g/Day Participants will receive NR at a dose of 2g/day Nicotinamide Riboside: Nicotinamide riboside 2g/day for a 2 week duration	11
Total	11

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	6

Baseline characteristics

Characteristic	Nicotinamide Riboside 2g/Day
Age, Continuous	37.4 years STANDARD_DEVIATION 16.4
NAD+/NADH Ratio	3.75 Ratio STANDARD_DEVIATION 0.47
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	4 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	7 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 11
other Total, other adverse events	3 / 11
serious Total, serious adverse events	0 / 11

Outcome results

Primary

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.