Nad Plus Safety Profile — Clinical Evidence & Research Summary

Preclinical Research Summary

Key Preclinical Studies

Study	Model	Key Findings	Ref
Mills et al. (2016)	C57BL/6N mice — NMN 100–300 mg/kg/day oral × 12 mo	Suppressed weight gain ~10% (p<0.001); increased energy expenditure; improved insulin sensitivity; no obvious toxicity	[17]
Das et al. (2018)	Elderly C57BL/6 mice — NMN 500 mg/kg/day oral × 28d	Capillary density restored to young-mouse levels; endurance improved 80% via SIRT1-dependent vascular rejuvenation	[14]
Hou et al. (2018)	3xTgAD Alzheimer's mice — NMN 100 mg/kg SC × 28d–3mo	Decreased Aβ oligomers; restored spatial memory in water maze tasks	[2]
Zhang et al. (2016)	Aged C57BL/6 mice — NR 400 mg/kg/day oral × ~6mo	Extended median lifespan 5% (p<0.05); enhanced muscle stem cell function; increased grip strength	[9]
Cantó et al. (2012)	HFD mice — NR 400 mg/kg/day oral × 8–12 wk	Prevented weight gain (40% less than controls); increased thermogenesis	[11]
Ying/Won (2007/2012)	Rat ischemia — NAD+ 10–20 mg/kg intranasal × 2h post-injury	Reduced infarct volume (p<0.01); bypasses BBB; profound neuroprotection	[15]
Tarragó et al. (2018)	Aged mice (32 mo) — 78c (CD38 inhibitor) oral	Increased NAD+ in liver/muscle/heart; improved glucose tolerance	[8]

Human Clinical Data: NMN Trials

Trial	Population	Dose/Route	Key Results	Ref
Christen et al. (2025)	n=65 healthy adults	1000 mg NMN vs NR vs NAM × 14d	NMN and NR: NAD+ ↑~2-fold; NAM did NOT increase; gut bacteria convert NMN/NR → NA → NAD+	[4]
Yoshino et al. (2021)	n=25 prediabetic women	250 mg NMN oral × 10 wk	Muscle insulin sensitivity ↑25% (AKT/mTOR phosphorylation); no AEs	[10]
Igarashi et al. (2022)	n=42 men ≥65y	250 mg NMN oral × 12 wk	Improved gait speed, left grip strength; hearing improved; safe	[18]
Liao et al. (2021)	n=48 amateur runners	300/600/1200 mg NMN × 6 wk	Dose-dependent VO₂ improvement (VT1, VT2) at 600/1200 mg	[16]
Yi et al. (2023)	n=80 adults 40–65y	300/600/900 mg NMN × 60d	NAD+ ↑3–6-fold; 6MWT ↑~1.5-fold (600/900 mg); biological age unchanged vs ↑ in placebo	[19]
Pencina et al. (2023)	n=32 overweight 55–80y	MIB-626 1000–2000 mg × 14–28d	NAD+ metabolites ↑200-fold; body weight and diastolic BP decreased	[20]

Human Clinical Data: NR Trials

Trial	Population	Dose/Route	Key Results	Ref
Trammell et al. (2016)	n=12 healthy adults	100–1000 mg NR single dose	Dose-dependent NAD+ ↑; 1000 mg → 2.7-fold increase	[5]
Martens et al. (2018)	n=24 ages 55–79	1000 mg NR oral × 6 wk	PBMC NAD+ ↑~60%; trend toward reduced SBP + aortic stiffness	[21]
Brakedal et al. (2022) — NADPARK	n=30 Parkinson's	1000 mg NR oral × 30d	Increased cerebral NAD+ (MRS-confirmed); mild motor improvement	[12]
Wang et al. (2022)	n=30 HFrEF	2000 mg NR oral × 12 wk	Blood NAD+ doubled; NLRP3 reduced; no cardiac functional improvement	[22]
Wu et al. (2025)	Older adults with MCI	1000 mg NR oral × 8 wk	Reduced plasma pTau217 by 7% (vs 18% ↑ placebo) — Alzheimer's biomarker	[13]
de la Rubia et al. (2019)	n=32 ALS	1200 mg NR + pterostilbene × 16 wk	Improved ALSFRS, pulmonary function, muscle strength vs placebo	[23]

Direct IV NAD+ Data

Trial	Population	Dose/Route	Key Results	Ref
Grant et al. (2019)	n=11 healthy men	750 mg IV NAD+ × 6h	Plasma NAD+ ↑~400%; PBMC intracellular NAD+ did NOT increase → questions IV efficacy for intracellular levels	[24]

Safety Summary

Parameter	Finding
NR Safety	Safe up to 2000 mg/day × 12 weeks — GRAS status; no serious AEs
NMN Safety	Safe up to 1250 mg/day × 4 weeks confirmed; no serious AEs at 250 mg × 12 weeks
Common AEs	Mild: nausea, flushing, GI discomfort, headache (oral); injection site reactions, lightheadedness (IV)
Theoretical Risks	Tumorigenesis (not observed in long-term animal studies); SARM1 axonal degeneration; methylation depletion from excess NAM
Contraindications	Active cancer (theoretical), pregnancy/breastfeeding, serious liver/kidney conditions

The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.

For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.

Preclinical Research Summary

Key Preclinical Studies

Study	Model	Key Findings	Ref
Mills et al. (2016)	C57BL/6N mice — NMN 100–300 mg/kg/day oral × 12 mo	Suppressed weight gain ~10% (p<0.001); increased energy expenditure; improved insulin sensitivity; no obvious toxicity	[17]
Das et al. (2018)	Elderly C57BL/6 mice — NMN 500 mg/kg/day oral × 28d	Capillary density restored to young-mouse levels; endurance improved 80% via SIRT1-dependent vascular rejuvenation	[14]
Hou et al. (2018)	3xTgAD Alzheimer's mice — NMN 100 mg/kg SC × 28d–3mo	Decreased Aβ oligomers; restored spatial memory in water maze tasks	[2]
Zhang et al. (2016)	Aged C57BL/6 mice — NR 400 mg/kg/day oral × ~6mo	Extended median lifespan 5% (p<0.05); enhanced muscle stem cell function; increased grip strength	[9]
Cantó et al. (2012)	HFD mice — NR 400 mg/kg/day oral × 8–12 wk	Prevented weight gain (40% less than controls); increased thermogenesis	[11]
Ying/Won (2007/2012)	Rat ischemia — NAD+ 10–20 mg/kg intranasal × 2h post-injury	Reduced infarct volume (p<0.01); bypasses BBB; profound neuroprotection	[15]
Tarragó et al. (2018)	Aged mice (32 mo) — 78c (CD38 inhibitor) oral	Increased NAD+ in liver/muscle/heart; improved glucose tolerance	[8]

Human Clinical Data: NMN Trials

Trial	Population	Dose/Route	Key Results	Ref
Christen et al. (2025)	n=65 healthy adults	1000 mg NMN vs NR vs NAM × 14d	NMN and NR: NAD+ ↑~2-fold; NAM did NOT increase; gut bacteria convert NMN/NR → NA → NAD+	[4]
Yoshino et al. (2021)	n=25 prediabetic women	250 mg NMN oral × 10 wk	Muscle insulin sensitivity ↑25% (AKT/mTOR phosphorylation); no AEs	[10]
Igarashi et al. (2022)	n=42 men ≥65y	250 mg NMN oral × 12 wk	Improved gait speed, left grip strength; hearing improved; safe	[18]
Liao et al. (2021)	n=48 amateur runners	300/600/1200 mg NMN × 6 wk	Dose-dependent VO₂ improvement (VT1, VT2) at 600/1200 mg	[16]
Yi et al. (2023)	n=80 adults 40–65y	300/600/900 mg NMN × 60d	NAD+ ↑3–6-fold; 6MWT ↑~1.5-fold (600/900 mg); biological age unchanged vs ↑ in placebo	[19]
Pencina et al. (2023)	n=32 overweight 55–80y	MIB-626 1000–2000 mg × 14–28d	NAD+ metabolites ↑200-fold; body weight and diastolic BP decreased	[20]

Human Clinical Data: NR Trials

Trial	Population	Dose/Route	Key Results	Ref
Trammell et al. (2016)	n=12 healthy adults	100–1000 mg NR single dose	Dose-dependent NAD+ ↑; 1000 mg → 2.7-fold increase	[5]
Martens et al. (2018)	n=24 ages 55–79	1000 mg NR oral × 6 wk	PBMC NAD+ ↑~60%; trend toward reduced SBP + aortic stiffness	[21]
Brakedal et al. (2022) — NADPARK	n=30 Parkinson's	1000 mg NR oral × 30d	Increased cerebral NAD+ (MRS-confirmed); mild motor improvement	[12]
Wang et al. (2022)	n=30 HFrEF	2000 mg NR oral × 12 wk	Blood NAD+ doubled; NLRP3 reduced; no cardiac functional improvement	[22]
Wu et al. (2025)	Older adults with MCI	1000 mg NR oral × 8 wk	Reduced plasma pTau217 by 7% (vs 18% ↑ placebo) — Alzheimer's biomarker	[13]
de la Rubia et al. (2019)	n=32 ALS	1200 mg NR + pterostilbene × 16 wk	Improved ALSFRS, pulmonary function, muscle strength vs placebo	[23]

Direct IV NAD+ Data

Trial	Population	Dose/Route	Key Results	Ref
Grant et al. (2019)	n=11 healthy men	750 mg IV NAD+ × 6h	Plasma NAD+ ↑~400%; PBMC intracellular NAD+ did NOT increase → questions IV efficacy for intracellular levels	[24]

Safety Summary

Parameter	Finding
NR Safety	Safe up to 2000 mg/day × 12 weeks — GRAS status; no serious AEs
NMN Safety	Safe up to 1250 mg/day × 4 weeks confirmed; no serious AEs at 250 mg × 12 weeks
Common AEs	Mild: nausea, flushing, GI discomfort, headache (oral); injection site reactions, lightheadedness (IV)
Theoretical Risks	Tumorigenesis (not observed in long-term animal studies); SARM1 axonal degeneration; methylation depletion from excess NAM
Contraindications	Active cancer (theoretical), pregnancy/breastfeeding, serious liver/kidney conditions

For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.

Product Index

Nad Plus: Safety Profile & Research Summary

Preclinical Research Summary

Key Preclinical Studies

Human Clinical Data: NMN Trials

Human Clinical Data: NR Trials

Direct IV NAD+ Data

Safety Summary

References

Related Research Questions

Nad Plus: Safety Profile & Research Summary

Preclinical Research Summary

Key Preclinical Studies

Human Clinical Data: NMN Trials

Human Clinical Data: NR Trials

Direct IV NAD+ Data

Safety Summary

References

Related Research Questions