What are the clinical uses and recommended dosing of NAD (nicotinamide adenine dinucleotide) in practice?

Clinical Uses of NAD (Nicotinamide Adenine Dinucleotide)

NAD should not be administered as direct intravenous or intramuscular injections for therapeutic purposes, as there is no guideline support, no FDA approval for medical indications, and no published randomized controlled trials demonstrating clinical benefit. 1, 2

Established Clinical Applications

Niacin Supplementation (NAD Precursors)

The clinically appropriate approach is to use niacin precursors (nicotinic acid, nicotinamide, nicotinamide riboside) rather than direct NAD administration:

Daily Requirements:

• Adult males (>14 years): 16 mg/day 3
• Adult females (>14 years): 14 mg/day 3
• Pregnant women: 18 mg/day 3
• Lactating women: 16 mg/day 3

Enteral Nutrition:

• Provide at least 1.2 mg per day of riboflavin in 1500 kcal (Grade A) 3
• Use oral/enteral route whenever the gastrointestinal tract is functional 1, 2

Parenteral Nutrition:

• Provide 40 mg niacin per day when GI tract is non-functional (Grade B) 3, 1
• This is standard niacin, not injectable NAD+ 2

Treatment of Niacin Deficiency (Pellagra)

When to Suspect Deficiency:

• Clinical triad: diarrhea, dermatitis, dementia 1, 2
• Risk factors: corn-based diet, malnutrition, chronic alcoholism, malabsorptive states 1, 2

Treatment Dosing:

• Oral nicotinic acid: 15-20 mg/day 1, 2
• Nicotinamide: 300 mg/day 1, 4
• Nicotinamide is preferred as it does not cause flushing 4

Specialized Clinical Applications

Dermatologic Use:

• Nicotinamide 1000 mg/day has been studied for reducing actinic keratoses and keratinocyte carcinomas in high-risk patients 4

Multiple Acyl-CoA Dehydrogenase Deficiency (MADD):

• Riboflavin (which supports NAD metabolism) can be given at 50-200 mg/day 3

Safety Considerations and Upper Limits

Nicotinic Acid:

• Upper limit: 10 mg/day for free nicotinic acid 3, 1
• Causes flushing at doses as low as 30 mg/day 3, 4
• High doses (3 g/day used for hypercholesterolemia) can cause nausea, vomiting, liver toxicity, blurred vision, impaired glucose tolerance 1, 2
• Monitor hepatic transaminases (ALT, AST) at baseline and every 6 months when using therapeutic doses 4
• Discontinue if transaminases exceed 2-3 times upper limit of normal 4

Nicotinamide:

• Upper limit: 12.5 mg/kg body weight/day (approximately 900 mg/day for adults) 3, 1
• No flushing effects 3, 4
• No adverse effects observed at doses up to 25 mg/kg body weight/day in prolonged studies 3
• More favorable safety profile than nicotinic acid 4

Critical Pitfalls to Avoid

Do Not Use Direct NAD+ Injections:

• No published randomized controlled trials exist for NAD+ infusions in humans 1, 2
• FDA labeling lists only cosmetic uses, not therapeutic medical indications 1, 2
• NAD+ is a large, charged molecule with poor bioavailability and stability when injected 2
• The American Academy of Physical Medicine and Rehabilitation does not recommend NAD+ patches due to lack of clinical evidence 1, 2

Do Not Confuse Forms:

• Niacin precursors (oral) have established safety and efficacy data 1, 2
• Direct NAD+ administration lacks regulatory approval for therapeutic use 2
• Injectable NAD+ is not superior to oral precursors—no evidence supports this claim 2

Monitor for Adverse Effects:

• Common side effects of NAD precursors: gastrointestinal symptoms (nausea, vomiting, diarrhea), muscle pain, nervous disorders, fatigue, sleep disturbance, headaches 2, 5
• Potential risks of raising NAD+ levels: accumulation of toxic metabolites, tumorigenesis, promotion of cellular senescence 6
• NAD(P)H oxidase activity implicated in anthracycline-induced cardiotoxicity 1

Clinical Algorithm for Patient Requests

Step 1 - Dietary Optimization:

• Recommend niacin-rich foods: fortified packaged foods, meat, poultry, red fish (tuna, salmon), nuts, legumes, seeds 3, 1, 2

Step 2 - Assess for Deficiency:

• Measure urinary metabolites (N-methyl-nicotinamide, N-methyl-2-pyridone-carboxamide) if clinical suspicion exists 3, 4
• Blood or tissue NAD+ levels can be measured if pellagra symptoms present 1, 2

Step 3 - Treat Confirmed Deficiency:

• Use oral nicotinamide 300 mg/day or nicotinic acid 15-20 mg/day 1, 2
• Reserve parenteral niacin (40 mg/day) for non-functional GI tract 1, 2

Step 4 - Avoid Unproven Therapies:

• Do not recommend NAD+ infusions outside research protocols 1, 2
• Lack of guideline support, poor pharmacokinetics, and absent proven clinical benefit 1, 2

Monitoring Parameters

Baseline Assessment:

• Hepatic transaminases (ALT, AST) before therapeutic doses 4
• Fasting glucose or hemoglobin A1c to monitor metabolic effects 4

Ongoing Monitoring:

• Repeat hepatic transaminases every 6 months during therapeutic dosing 4
• No standardized monitoring protocols exist for NAD+ supplementation 4