TABLE 2.
The safety and antiaging effects of NMN in human clinical trials
| Registration number | Design | Dose & duration | Indicators | Outcome | Location | References |
|---|---|---|---|---|---|---|
| UMIN000021309 | Nonblinded, nonrandomized, non–placebo-controlled study; 10 healthy men aged 40–60 y | Oral administration: 100, 250 or 500 mg for 5 h | Clinical parameters, ophthalmic parameters, sleep quality score, serum parameters, NMN metabolites levels in plasma | ↑NMN metabolites (2Py and 4Py) in plasma and bilirubin levels; ↓creatinine, chloride, and glucose levels within the normal ranges in serum; No significant changes in ophthalmic examination and sleep quality score; Single oral administration of NMN up to 500 mg is safe and well-tolerated in healthy men without causing any significant deleterious effects |
Japan | [35] |
| jRCTs041200034 | Double-blind, randomized, placebo-controlled study; 30 healthy volunteers aged 20–65 y | Oral administration: 250 mg daily for 12 wk | Adverse events, clinical parameters, blood and urine biochemical parameters, body composition, skeletal muscle mass, bone mineral mass, NAD+, and amino acid metabolome of blood | ↑NAD+ and NAMN levels but not NMN; Pulse rate is strongly correlated with the increase in NAD+ level; No obvious adverse effects, and no significant changes in other indicators; Oral administration of NMN is safe |
Japan | [140] |
| / | Double-blind, block-randomized, placebo-controlled study; 32 overweight or obese adults aged 55–80 y | Oral administration: 1000 mg once daily or twice daily for 14 d | NMN, NAD+, and NAD+ metabolome in blood and urine | 1000 mg once or twice daily regimens were safe and associated with substantial dose-related increases in blood NAD levels and its metabolome | America | [122] |
| NCT03151239 | Double-blind, randomized, placebo-controlled study; 25 postmenopausal and prediabetic women aged 55–75 y | Oral administration: 250 mg daily for 10 wk | NMN metabolites and NAD+ in plasma, PBMCs, and skeletal muscle; body composition and basal metabolic variables; skeletal muscle insulin sensitivity and signaling; skeletal muscle global transcriptome profile | ↑ NAD+ and NMN metabolites in plasma; ↑ NMN metabolites in skeletal muscle but not NMN; ↑muscle insulin sensitivity, insulin signaling |
America | [36] |
| ChiCTR2000035138 | Double-blind, randomized, placebo-controlled study; 48 healthy recreationally trained runners aged 27–50 y | Oral administration: 300, 600 or 1200 mg daily for 6 wk | Body composition and cardiopulmonary function | ↑aerobic capacity, enhanced O2 utilization of skeletal muscle; ↑VT in a dose-dependent manner; No obvious adverse symptoms and abnormal ECG |
China | [145] |
| UMIN000036321 | Double-blind, randomized, placebo-controlled study; 42 healthy old men aged ≥65 y | Oral administration: 250 mg daily for 12 wk | Clinical characteristics, blood and urine biochemical parameters, body composition, skeletal muscle mass, segmental lean | ↑NAD+ and NAD+ metabolite levels in blood, improved muscle strength and performance, and no obvious adverse effects were observed | Japan | [141] |
| UMIN000038097 | Double-blind, randomized, placebo-controlled study; 108 overweight or obese adults aged ≥65 y | Oral administration: 250 mg daily for 12 wk | body composition, muscle mass, bone mass, sleep quality, fatigue, physical performances | NMN intake in the afternoon is more effective in improving lower limb function and reducing drowsiness in older adults | Japan | [118] |
| NCT04228640 | Nonblinded, nonrandomized, non–placebo-controlled study; 8 healthy men aged 45–60 y | Oral administration: 300 mg daily for 30–90 d | The telomere length of the PBMC | ↑ telomere length of PBMC, which may be the potential molecular mechanisms of NMN for extending lifespan | China | [147] |
| NCT04228640 | Double-blind, block-randomized, placebo-controlled study; 66 healthy participants aged 40–65 y | Oral administration: 300 mg NMN/d for 60 d | Blood cellular NAD+/NADH concentration in serum, six minutes walking endurance test, blood pressure, pulse pressure, SF-36 questionnaire, adverse events; blood biochemical parameters, HOMA-IR |
↑NAD+/NADH levels in the serum, SF-36 score, minute walking endurance, and HOMA-IR index; ↓blood pressure, pulse pressure, and blood glucose; All test data did not have any statistically significant changes. However, the increase in NAD+/NADH levels in serum and the improvement in overall health and walking endurance were clinically significant |
China | [146] |
| UMIN000043084 | Double-blind, randomized, placebo-controlled study; 31 healthy participants aged 20–65 y | Oral administration: 1250 mg NMN/d for 4 wk | Safety evaluation of NMN oral administration in healthy adult men and women | Did not cause changes exceeding physiological variations (including anthropometry, hematological, biochemical, urine, and body composition) | Japan | [178] |
2Py, N-methyl-2-pyridine-5-carboxamide; 4Py, N-methyl-4-pyridone-5-carboxamide; ECG, electrocardiogram; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; NAD, nicotinamide adenine dinucleotide; NAMN, nicotinic acid mononucleotide; NMN, nicotinamide mononucleotide; PBMC, peripheral blood mononuclear cell; SF-36, 36-Item Short Form Survey; VT, ventilatory threshold.