What is the current evidence for the health benefits of NAD+ (Nicotinamide adenine dinucleotide) IV therapy?

NAD+ IV Therapy: Current Evidence for Health Benefits

There is no credible clinical evidence supporting the use of intravenous NAD+ therapy for any medical condition, and this route of administration is not recommended by any major medical society or guideline. 1, 2, 3

Guideline-Based Recommendations

What Medical Societies Actually Recommend

• The American Society for Parenteral and Enteral Nutrition recommends oral niacin (40 mg/day parenterally only when GI tract is non-functional), NOT intravenous NAD+, for therapeutic purposes in humans 1

• The American College of Nutrition establishes standard oral niacin intake at 16 mg/day for adult males and 14 mg/day for adult females—these are NAD+ precursors, not direct NAD+ administration 2, 3

• For patients requiring parenteral nutrition, the established dosing is niacin 40 mg/day (not NAD+) 2, 3

Regulatory Status

• FDA labeling for intravenous NAD+ lists exclusively cosmetic applications, with no therapeutic medical indications 1

• There are no FDA-approved injectable NAD+ products for clinical use in the United States 2

• No published randomized controlled trials exist for NAD+ infusions in humans in medical databases 1

Safety Concerns with IV NAD+

Direct Risks of Injectable Administration

• Injectable NAD+ bypasses normal protective barriers and introduces significant risks including infection from improper sterile technique, hypersensitivity reactions, and unknown pharmacokinetics when administered parenterally 2, 3

• No standardized dosing protocols exist for injectable NAD+ administration 2

• Injectable administration of unapproved substances falls outside standard medical practice 2

Pharmacokinetic Evidence Against IV Use

• A 2019 pilot study demonstrated that at an infusion rate of 3 μmol/min, NAD+ is rapidly and completely removed from plasma for at least the first 2 hours, with no change in plasma NAD+ or metabolites observed until after 2 hours 4

• The metabolite profile is consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity, meaning the infused NAD+ is immediately broken down rather than utilized intact 4

• Urinary excretion products include NAD+ itself and methylnicotinamide but not nicotinamide, suggesting inefficient conversion to usable forms 4

Potential Long-Term Risks

• NAD(P)H oxidase activity has been implicated in anthracycline-induced cardiotoxicity, raising theoretical concerns about NAD supplementation in certain clinical contexts 2, 3

• High doses of nicotinic acid can cause flushing, nausea, vomiting, hepatotoxicity, blurred vision, and impaired glucose tolerance 1

Evidence for Oral NAD+ Precursors (Not IV NAD+)

What Actually Has Some Evidence

• A 2024 systematic review of oral NADH and precursors (not IV NAD+) in 489 participants showed these were well-tolerated with improvements in quality of life, decreased anxiety, and reduced maximum heart rate after stress testing 5

• Oral nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have been shown safe and significantly increase NAD+ levels in humans, though efficacy is lower than expected from preclinical studies 6

• Most common side effects with oral NAD+ precursors include muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches—none presenting serious health risks 5

Critical Limitation

• The efficacy of oral NAD+ precursors in humans is substantially lower than predicted from animal studies, and clinical trial outcomes have been disappointing compared to preclinical data 6

Clinical Algorithm for Patient Requests

Step 1: Recommend Dietary Sources First

• Prioritize fortified packaged foods, meat and poultry, red fish (tuna and salmon), nuts, legumes, and seeds 1, 3

Step 2: Assess for True Deficiency

• Measure blood or tissue NAD+ levels only if pellagra symptoms present (diarrhea, dermatitis, dementia) 1
• Monitor niacin status through urinary metabolites (N-methyl-nicotinamide and N-methyl-2-pyridone-carboxamide) if clinical suspicion exists 3

Step 3: Treat Confirmed Deficiency with Oral Niacin

• Use oral nicotinic acid (15-20 mg/day) or nicotinamide (300 mg/day) for pellagra treatment 1
• Do not exceed upper limits: 10 mg/day for free nicotinic acid (based on flushing effects) and 900 mg/day for nicotinamide in adults 1, 2, 3

Step 4: Avoid IV NAD+ Entirely

• Avoid NAD+ infusions for therapeutic purposes outside of research protocols due to lack of guideline support, poor pharmacokinetics, and absence of proven clinical benefit 1, 2, 3

Common Pitfalls to Avoid

• Do not confuse oral NAD+ precursor supplementation (which has limited evidence) with IV NAD+ administration (which has no credible evidence) 5, 6

• Do not assume that because NAD+ levels decline with age (correlation coefficient of -0.706 in men and -0.537 in women) that IV supplementation is therefore beneficial or safe 3

• Recognize that preclinical animal studies showing benefit from "supraphysiological" doses do not translate to human IV injection efficacy 3

• The American Academy of Physical Medicine and Rehabilitation does not recommend NAD+ patches due to lack of clinical evidence, reflecting general skepticism toward direct NAD+ delivery methods 1