Intramuscular NAD+ Injections: Limited Evidence and No Established Clinical Role
There is no high-quality evidence supporting the use of intramuscular NAD+ injections in generally healthy adults, and no established dosing protocols exist for this route of administration. The available clinical evidence focuses exclusively on oral NAD+ precursors (nicotinamide mononucleotide, nicotinamide riboside, NADH), not intramuscular formulations.
Evidence Base for NAD+ Supplementation
Oral NAD+ Precursors Show Modest Benefits
The only clinically studied routes for NAD+ augmentation involve oral supplementation with NAD+ precursors:
Nicotinamide mononucleotide (NMN) at 1000 mg daily (500 mg twice daily) for 28 days in overweight/obese middle-aged adults significantly reduced total cholesterol by 26.89 mg/dL, LDL cholesterol by 18.73 mg/dL, body weight by 1.9 kg, and diastolic blood pressure by 7.01 mmHg 1
NMN at 250 mg daily for 6-12 weeks in older men safely elevated blood NAD+ levels and showed nominally significant improvements in gait speed and grip strength, though these findings require validation in larger studies 2
Oral NADH at 20 mg daily for 2 months in chronic fatigue syndrome patients decreased anxiety scores and maximum heart rate after stress testing, but did not improve overall functional performance or fatigue intensity 3, 4
Safety Profile of Oral Supplementation
Oral NAD+ precursors demonstrate acceptable safety:
Common side effects include muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches, but no serious adverse events have been reported 4
The upper limit for nicotinamide (the primary NAD+ precursor in diet) is 12.5 mg/kg body weight daily (approximately 900 mg/day for adults), with no adverse effects observed at doses up to 25 mg/kg/day in prolonged studies 5
Why Intramuscular Route Lacks Evidence
No Clinical Trials for IM NAD+ Administration
The systematic review of NAD+ safety and effectiveness across 489 participants in 10 randomized trials found zero studies evaluating intramuscular NAD+ injections 4. All interventions used oral formulations of NADH or NAD+ precursors.
Intramuscular Injections Have Known Drawbacks
Clinical guidelines consistently discourage intramuscular injections when oral alternatives exist:
Intramuscular vitamin A injections in preterm infants, while effective, were noted to be painful and prompted research into intravenous alternatives 5
Pain management guidelines explicitly state that "intramuscular injections are painful and have no pharmacokinetic advantage" over intravenous routes 5
Physiologic Rationale Favors Oral Route
NAD+ functions as an intracellular coenzyme required by over 400 enzymes for energy metabolism, DNA repair, and antioxidant effects 5. Oral NAD+ precursors effectively elevate blood NAD+ levels and tissue concentrations 2, 1, making invasive intramuscular administration unnecessary.
Recommended Approach for NAD+ Augmentation
If Considering NAD+ Supplementation
For patients interested in NAD+ augmentation based on the limited available evidence:
Use oral nicotinamide mononucleotide (NMN) 1000 mg daily (500 mg twice daily) if targeting cardiometabolic outcomes in overweight/obese middle-aged adults 1
Use oral NMN 250 mg daily if targeting age-related muscle function in older adults 2
Use oral NADH 20 mg daily only for anxiety reduction in chronic fatigue syndrome, recognizing limited efficacy for other outcomes 3
Critical Caveats
The evidence base remains very limited with small sample sizes and short treatment durations (28 days to 12 weeks) 4, 2, 1
No studies have evaluated long-term safety beyond 12 weeks 4
Claims about intramuscular NAD+ injections lack any peer-reviewed clinical trial support and should be viewed with extreme skepticism 4
Patients should be counseled that NAD+ supplementation remains investigational, with the strongest evidence supporting modest improvements in cholesterol, blood pressure, and body weight in overweight middle-aged adults 1