Healthy
Conditions
Keywords
nicotinamide adenine dinucleotide, NAD, NAD+, pharmacokinetics, nicotinamide riboside, nicotinamide mononucleotide, brain kinetics
Brief summary
The objective of the NAD-brain study is to determine the blood and brain pharmacokinetics of NAD replenishment therapy (NRT) using Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN).
Detailed description
The NAD-brain study will perform a parallel assessment of NAD replenishment therapy (NRT) pharmacokinetics in the blood and brain of healthy human subjects. A total of 6 healthy individuals (3 men and 3 women) will undergo repeated blood sampling and 31P-MRS brain scans during two 20-day periods, each of which will start with 8 days of daily intake of Nicotinamide Riboside (NR) 600mg x 2, or Nicotinamide Mononucleotide (NMN) 600mg x 2. The two 20-day periods will be 14 days apart to allow for washout of the previous compound. Moreover, a total of 6 healthy individuals (3 men and 3 women) and 6 individuals with Parkinson's disease (3 men and 3 women) will receive NR 1200 mg daily (600 mg x 2) for 4 weeks, with a total measurement/assessment period of 7 weeks, and undergo repeated blood sampling and 31P-MRS brain scans once per week during this time. Blood will be analyzed for NAD-metabolites. The simultaneous change in NAD-metabolism over time in blood and brain will be assessed and blood and brain pharmacokinetics for NRT in humans will be established.
Interventions
DIETARY_SUPPLEMENTNicotinamide Riboside (NR)
The NAD-brain study will perform a parallel assessment of NAD replenishment therapy (NRT) pharmacokinetics in the blood and brain of healthy human subjects . A total of 6 healthy individuals (3 men and 3 women) will undergo repeated blood sampling and 31P-MRS brain scans during two 20-day periods, each of which will start with 8 days of daily intake of Nicotinamide Riboside (NR) 600mg x 2, or Nicotinamide Mononucleotide (NMN) 600mg x 2. The two 20-day periods will be 14 days apart to allow for washout of the previous compound. Blood will be analyzed for NAD-metabolites using spectroscopic assays. By this approach we will measure the simultaneous change in NAD-metabolism over time in blood and brain and establish blood and brain pharmacokinetics for NRT in humans.
DIETARY_SUPPLEMENTnicotinamide mononucleotide
The NAD-brain study will perform a parallel assessment of NAD replenishment therapy (NRT) pharmacokinetics in the blood and brain of healthy human subjects. A total of 6 healthy individuals (3 men and 3 women) will undergo repeated blood sampling and 31P-MRS brain scans during two 20-day periods, each of which will start with 8 days of daily intake of Nicotinamide Riboside (NR) 600mg x 2, or Nicotinamide Mononucleotide (NMN) 600mg x 2. The two 20-day periods will be 14 days apart to allow for washout of the previous compound. Blood will be analyzed for NAD-metabolites using spectroscopic assays. By this approach we will measure the simultaneous change in NAD-metabolism over time in blood and brain and establish blood and brain pharmacokinetics for NRT in humans.
Sponsors
Haukeland University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 30-85 years at the time of enrollment. * Neurologically healthy at the time of enrollment.
Exclusion criteria
* History of acute or chronic neurological disorder affecting the central nervous system (CNS). Migraine, cluster headache, and tension headache are allowed, but not on the day of the study visits. * Impaired renal function. * Impaired hepatic function. * Severe hematological disease. * Any psychiatric disorder that would interfere with compliance in the study. * Any severe somatic illness that would make the individual unable to comply and participate in the study. * Mitochondrial disease. * Use of high dose vitamin B3 supplementation within 30 days of enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NAD metabolism | For Stage-1: 20 days for NR and 20 days for NMN comprising 8 days treatment, and 11 days washout. For Stage-2 (NR): 7 weeks comprising 4 weeks of treatment and 3 weeks washout | The change of cerebral NAD levels (measured by 31P-MRS) and of blood NAD-metabolites (measured by HPLC-MS), over time (20 days), after the administration of oral NRT with the following NAD precursors: NR 600mg x 2 daily, NMN 600mg x 2 daily. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interindividual differences | For Stage-1: 20 days for NR and 20 days for NMN comprising 8 days treatment, and 11 days washout. For Stage-2 (NR): 7 weeks comprising 4 weeks of treatment and 3 weeks washout | Descriptive analyses of interindividual differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT. |
| Between-sex differences | For Stage-1: 20 days for NR and 20 days for NMN comprising 8 days treatment, and 11 days washout. For Stage-2 (NR): 7 weeks comprising 4 weeks of treatment and 3 weeks washout | Between-sex differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT. |
Countries
Norway
Outcome results
None listed