What is the recommended dosing for injectable Nicotinamide Adenine Dinucleotide (NAD) via Intramuscular (IM) or Subcutaneous (SQ) injection?

Injectable NAD+ Dosing: Evidence-Based Recommendations

Direct Answer

There is no established, evidence-based dosing regimen for injectable NAD+ via intramuscular (IM) or subcutaneous (SQ) routes, and this practice lacks FDA approval or guideline support. 1, 2

Critical Evidence Gaps

No medical guidelines or regulatory bodies provide recommendations for direct NAD+ injection. The available evidence addresses only oral NAD+ precursors (nicotinamide riboside, nicotinamide mononucleotide, nicotinic acid), not injectable NAD+ itself. 1, 3, 4

Why Injectable NAD+ Is Problematic

• NAD+ is a large, charged molecule with poor bioavailability and questionable stability when injected intramuscularly or subcutaneously. 1
• All established safety data and dosing guidelines apply exclusively to oral NAD+ precursors, not direct NAD+ injection. 2, 3, 4
• Parenteral nutrition protocols use niacin (a precursor) at 40 mg/day, not NAD+ directly. 1, 2

Evidence-Based Alternative: Oral NAD+ Precursors

The only clinically validated approach is oral supplementation with NAD+ precursors, which have established safety profiles and proven efficacy in raising NAD+ levels. 2, 3, 4

Established Dosing for NAD+ Precursors (Oral Only)

Nicotinamide (Niacinamide):

• Maximum safe dose: 12.5 mg/kg/day (approximately 900 mg/day for adults). 1, 2
• No adverse effects observed up to 25 mg/kg/day in diabetic subjects. 2
• Does not cause flushing, unlike nicotinic acid. 2

Nicotinic Acid:

• Upper limit for free nicotinic acid: 10 mg/day (based on flushing threshold of 30 mg/day). 1, 2
• Clinical therapeutic doses for hypercholesterolemia: 3 g/day (oral). 1, 2
• Significant vasodilation and flushing risk at doses ≥30 mg/day. 1

Nicotinamide Mononucleotide (NMN):

• Clinical trial dosing: 1000 mg/day (500 mg twice daily) for 28 days safely increased NAD+ levels and improved cardiometabolic parameters. 5
• Well-tolerated with significant reductions in body weight, LDL cholesterol, and blood pressure. 5

Nicotinamide Riboside (NR):

• Commonly studied doses range from 250-1000 mg/day in clinical trials. 3
• Safe and effective at raising NAD+ levels in multiple tissues. 3

Safety Considerations

Common side effects of NAD+ precursor supplementation include:

• Gastrointestinal symptoms: nausea, vomiting, diarrhea. 1, 4
• Muscle pain, nervous disorders, fatigue, sleep disturbance, headaches. 4
• All adverse events in clinical trials were non-serious and well-tolerated. 4, 5

Clinical Recommendation

If NAD+ augmentation is desired, use oral NAD+ precursors with established safety data:

1. First-line: Nicotinamide mononucleotide (NMN) 500-1000 mg/day orally for adults with metabolic risk factors. 5

2. Alternative: Nicotinamide riboside (NR) 250-1000 mg/day orally for general NAD+ augmentation. 3

3. Avoid injectable NAD+ entirely due to lack of safety data, efficacy evidence, and potential for poor bioavailability. 1, 2

Important Caveats

• Injectable NAD+ formulations available through compounding pharmacies are not FDA-approved and lack quality control standards. 1
• No standardized monitoring protocols exist for NAD+ supplementation. 2
• Urinary metabolites (N-methyl-nicotinamide and N-methyl-2-pyridone-carboxamide) can assess niacin status if deficiency is suspected. 2
• Blood NAD+ levels can be measured, but clinical correlation with symptoms is more important than absolute values. 2