Table 3 Human clinical trials of NAD precursors, NMN and NR

NR

Study for PK and safety in healty volunteer.

Randomized, double-blind, crossover study. Healthy volunteers (n = 12), Age from 33 to 55, BMI from 18.5 to 29.9

Oral administration. Single administration at 100, 300, and 1000 mg

Increased NAD and NAAD levels in PBMC. No seriouse adverse side effects. Two individuals self-reported flushing at the 300 mg dose.

[97] (NCT02191462)

NR

Study for PK and safety in healty volunteer.

Non-randomized, open-label, non-placebo controlled study. Healthy volunteers (n = 8), Age from 21 to 50

Oral administration. Dose-escalation at 250 mg (Day 1, 2), 500 mg (Day 3, 4), 1000 mg (Day 5, 6), and 2000 mg (Day 7, 8)

Approximately 100% Increase in NAD level in whole blood with a potisitve colleration of NR level. No seriouse adverse side effects.

[98] (NCT02689882)

NR

Study for safety and efficacy against physical activities in elderly people.

Non-randomized, open-label, crossover study. Healthy volunteers (n = 30), Age from 55 to 79, BMI =24 ± 4

Oral administration. Crossover of placebo for 6 weeks and NR 500 mg twice daily for 6 weeks

Increased NAD and NAAD levels in PBMC. Well torelated and no seriouse adverse side effects. Lowered systolic blood pressure and arterial stiffness in NR treated group.

[99] (NCT02921659)

NR

Study for kinetics and efficacy against exercise performance in elderly people.

Randomized, double-blind, crossover study. Healthy young (n = 12, 22.9 ± 1.0 years) and elderly (n = 12, 71.5 ± 1.0 years) volunteers

Single oral administration. Crossover of placebo and NR 500 mg

Increased NADH and NADPH levels in RBCs. Regarding exercise performance, Isometric peak torque and fatigue index is improved in NR treated old group.

[100] N/A

NR

Study for safety and efficacy against insulin sensitivity in obese men

Randomized, placebo-controlled, double-blinded study. Healthy, sedentary, obese men (n = 40), Age from 40 to 70, BMI > 30

Oral administration. Placebo or NR 1000 mg twice daily for 12 weeks.

Increased urinary NR, NAM, MeNAM in NR treasted group. Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved Resting energy expenditure or body composition was not affected. No serious adverse side effects.

[101] (NCT02303483)

NRPT (NR and pterostilbene)

Study for safety and efficacy against NAD sustainability in elderly people

Randomized, placebo-controlled, double-blinded study. Healthy volunteers (n = 120), Age from 60 to 80

Oral administration. Placebo, 1XNRPT (250 mg NR and 50 mg PT), or 2XNRPT (500 mg NR and 100 mg PT) daily for 8 weeks.

Increased NAD level in whole blood with a dose-dependent manner. Total and LDL cholesterol levels were increased in NPRT treated group. No lserious adverse side effects.

[102] (NCT02678611)

NMN

Study for efficacy against in insulin sensitivity and β-cell functions in female elderly people.

Randomized, placebo-controlled, double-blinded study. Postmenopausal women 55–75 years old, BMI 25.0–44.9, and pre-diabetic.

Oral administration. Placebo or NMN 250 mg daily for 8 weeks.

N/A

(NCT03151239)

NMN

Study for PK and safety in healty volunteer.

Non-randomized, open-label, non-placebo controlled study. Male healthy volunteers (n = 10), Age from 40 to 60

Oral administration. Single administration. Dose is not described.

N/A

[103] (UMIN000021309)

NMN

Study for PK, safety, and effects on hormones in healty volunteer.

Randomized, dose comparison, double-blinded study. Healthy volunteers (n = 20), Age from 50 to 70

Oral administration. Single administration in dose of 100 mg or 200 mg of NMN.

N/A

(UMIN000025739)

NMN

Study for PK and safety in healty volunteer.

Non-randomized, open-label, non-placebo controlled study. Male healthy volunteers (n = 10), Age from 40 to 60

Oral administration. Long-term NMN administration for 8 weeks. Dose is not described.

N/A

[104] (UMIN000030609)