What are the uses and safety of Nicotinamide adenine dinucleotide (NAD) injections?

NAD Injections: Clinical Evidence and Recommendations

Primary Recommendation

NAD injections are not recommended for therapeutic medical use due to lack of clinical guideline support, absence of proven clinical benefit, and poor pharmacokinetic profile—patients should be directed toward oral NAD precursors (nicotinamide or nicotinamide riboside) when supplementation is indicated. 1

Current Guideline Position

• No established clinical guidelines recommend NAD injections for any medical condition 1, 2
• The American Academy of Physical Medicine and Rehabilitation explicitly does not recommend NAD delivery systems (including patches and by extension, injections) due to lack of clinical evidence 1, 2
• FDA labeling for intravenous NAD lists only cosmetic uses, not therapeutic medical indications 1

Established Safe Alternatives

Oral NAD Precursors (Preferred Route)

When NAD supplementation is clinically indicated, oral administration of precursors is the evidence-based approach:

• Nicotinamide (NAM): Upper limit is 900 mg/day for adults (12.5 mg/kg body weight/day), with no flushing effects and proven safety at doses up to 25 mg/kg/day in prolonged studies 1, 3
• Nicotinic acid: Daily dietary reference intake is 16 mg/day for males and 14 mg/day for females, though clinical doses for hypercholesterolemia can reach 3 g/day 3
• Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN): Demonstrated safe oral administration with significant NAD+ level increases in humans, though efficacy is lower than preclinical studies suggested 4

Parenteral Nutrition Context Only

• Parenteral nutrition should provide at least 40 mg of niacin per day (Grade B recommendation) 1, 3
• This represents the only guideline-supported context for intravenous NAD precursor administration, specifically in patients unable to use the gastrointestinal tract 1

Safety Concerns with High-Dose NAD Administration

Direct Toxicity Risks

• Hepatotoxicity: High doses of nicotinic acid can cause liver toxicity 1, 2
• Metabolic effects: Impaired glucose tolerance, nausea, vomiting, and blurred vision 1, 2
• Cardiovascular concerns: NAD(P)H oxidase activity has been implicated in anthracycline-induced cardiotoxicity, raising concerns about NAD supplementation in certain clinical contexts 1

Theoretical Long-Term Risks

• Tumorigenesis: Potential risk with chronic NAD+ elevation 5
• Cellular senescence promotion: Possible acceleration of aging processes 5
• Epigenetic alterations: High-dose NAM alters cellular methyl metabolism, affecting DNA and protein methylation, leading to changes in cellular transcriptome and proteome 6
• PARP inhibition: NAM itself inhibits poly(ADP-ribose) polymerases, which protect genome integrity 6

Clinical Algorithm for Patient Inquiries

Step 1: Assess for True Deficiency

• Measure for pellagra symptoms (diarrhea, dermatitis, dementia) if deficiency suspected 1
• Identify risk factors: corn-based diet, malnutrition, chronic alcoholism, malabsorptive states 1
• Consider urinary metabolites (N-methyl-nicotinamide and N-methyl-2-pyridone-carboxamide) to assess niacin status 3

Step 2: First-Line Dietary Approach

• Recommend dietary sources: meat, poultry, fish (especially red fish like tuna and salmon), nuts, legumes, seeds, and fortified packaged foods 1, 3

Step 3: If Supplementation Needed

• For confirmed pellagra: Oral nicotinic acid 15-20 mg/day or nicotinamide 300 mg/day 1
• For general supplementation: Nicotinamide up to 900 mg/day or nicotinamide riboside per emerging evidence 3, 4
• Avoid injections: No clinical benefit demonstrated, poor pharmacokinetics, and lack of guideline support 1

Step 4: Special Populations

• Pregnant women: 18 mg/day 3
• Lactating women: 16 mg/day 3
• Parenteral nutrition patients only: 40 mg/day intravenously 1, 3

Evidence Quality Assessment

The most recent and highest-quality evidence comes from 2025 Clinical Nutrition guidelines synthesized in Praxis Medical Insights, which provide clear Grade A and B recommendations for oral/enteral routes while offering no support for injection therapy 1. Clinical trials of oral NAD precursors (NR and NMN) demonstrate safety and NAD+ elevation in humans, though efficacy remains lower than preclinical studies suggested 4. The systematic review by multiple sources confirms limited acute toxicity but emphasizes that long-term human clinical trials remain nascent 5, 7.

Critical Pitfalls to Avoid

• Do not prescribe NAD injections for anti-aging or wellness purposes—no clinical evidence supports this practice and theoretical risks exist 1, 5
• Do not assume injection superiority over oral routes—the gastrointestinal tract should be used whenever functional 1
• Do not ignore upper intake limits—nicotinic acid flushing occurs at just 10 mg/day upper limit, while nicotinamide is safer at 900 mg/day 1, 3
• Do not use in patients with liver disease without careful monitoring—hepatotoxicity risk with high doses 1, 2