NAD+ side effects and results in studies
In the human trials, oral NAD+ precursors (NR and NMN) were well tolerated: adverse events were similar to placebo, and one 12-week NMN trial reported none. A systematic review of NADH and precursor trials listed muscle pain, nervous disorders, fatigue, sleep disturbance and headache as the most common side effects, none serious; no record here studies NAD+ given by injection.
Adverse events reported
| Event | As reported | Source |
|---|---|---|
| Overall adverse events (oral NMN, 28 days) | Similar between the NMN and placebo groups (n=30) | Pencina KM et al. |
| Adverse events (oral NMN 250 mg/day, 12 weeks) | Well tolerated; no adverse events reported (n=36) | Katayoshi T et al. |
| Tolerability (oral NR 1,000 mg, 30 days) | Well tolerated in newly diagnosed Parkinson's disease (n=30) | Brakedal B et al. |
| Tolerability (oral NR, 2 × 6 weeks) | Well tolerated in healthy middle-aged and older adults | Martens CR et al. |
| Muscle pain, nervous disorders, fatigue, sleep disturbance, headache | Most common side effects across 10 trials (489 participants) of NADH and precursors; none presented a serious risk | PMID 37971292 |
| Flushing, lower phospholipids, higher bilirubin | Seen with niacin (nicotinic acid) in a one-day study of combined metabolic activators; described as potentially risky | PMID 37271226 |
Outcomes measured
| Outcome | Result as reported | Source |
|---|---|---|
| Circulating NAD+ (NR vs NMN vs nicotinamide) | NR and NMN, but not nicotinamide, comparably raised circulating NAD+ over 14 days | Christen S et al. |
| Body weight, blood pressure, lipids (oral NMN) | Body weight −1.9 kg, diastolic blood pressure −7.0 mmHg, total cholesterol −26.9 mg/dL versus placebo | Pencina KM et al. |
| Muscle strength, aerobic capacity, insulin sensitivity (oral NMN) | No significant difference from placebo | Pencina KM et al. |
| Brain NAD and inflammation (oral NR, Parkinson's) | Significant but variable rise in cerebral NAD; lower cytokines in serum and CSF; mild clinical improvement in those whose brain NAD rose | Brakedal B et al. |
| Muscle NAD+ metabolome (oral NR, aged men) | Raised; mitochondrial bioenergetics unchanged; circulating inflammatory cytokines lower | Elhassan YS et al. |
| Neuronal-origin vesicle markers (oral NR) | NAD+ higher; Aβ42, pJNK and pERK1/2 lower | Vreones M et al. |
| Arterial stiffness (oral NMN) | Pulse wave velocity tended to fall; not significantly different from placebo | Katayoshi T et al. |
| Fatigue and quality of life (oral NADH + CoQ10, ME/CFS) | Cognitive fatigue and FIS-40 score fell and SF-36 improved from baseline within the treatment group | Castro-Marrero J et al. |
What the studies don't show
These results come from oral precursors and oral NADH, not from NAD+ itself in solution, and none of the records studies injected or infused NAD+. The trials are small and last from 14 days to 12 weeks, so they say nothing about long-term safety, and several of the positive results are biomarkers or within-group changes rather than differences from placebo.