What is Nicotinamide and What is it Used For?
Nicotinamide (also called niacinamide) is the water-soluble amide form of vitamin B3 that serves as the primary precursor to NAD+, a coenzyme required by over 400 enzymes in the body for energy production, DNA repair, and cellular metabolism. 1
Chemical Identity and Metabolic Function
Nicotinamide differs from nicotinic acid (niacin) in both structure and side effect profile, though both are collectively termed "niacin." 1 The body converts all absorbed niacin into NAD+ (nicotinamide adenine dinucleotide), which is essential for:
- Converting nutrients into energy through ATP production 1, 2
- Creating and repairing DNA 1, 3
- Synthesizing cholesterol and fats 1
- Exerting antioxidant effects 1
NAD+ serves as the sole substrate for PARP-1 (poly-ADP-ribose polymerase-1), a nuclear enzyme critical for DNA repair and genomic stability. 3
Established Clinical Uses
Skin Cancer Prevention in High-Risk Patients
The National Institute of Dermatology recommends 1000 mg/day of nicotinamide for reducing actinic keratoses and keratinocyte carcinomas in high-risk patients. 4 This dose has been validated in Phase III clinical trials and works by:
- Enhancing DNA repair mechanisms 2, 3
- Preventing UV-induced immunosuppression 2
- Supporting energy-dependent cellular repair processes 2
The 1000 mg/day dose exceeds the standard upper limit of 900 mg/day for adults, but has proven safe in clinical trials for this specific indication. 5 However, nicotinamide must be combined with comprehensive sun protection (SPF ≥15 sunscreen, protective clothing, sun avoidance 10 AM-4 PM) as it does not substitute for UV protection. 5
Treatment of Niacin Deficiency (Pellagra)
Clinical Nutrition guidelines recommend 300 mg/day of nicotinamide for treating pellagra, a niacin deficiency disease characterized by diarrhea, dermatitis, and dementia. 4 Risk factors include corn-based diets, malnutrition, chronic alcoholism, and malabsorption states. 6
FDA-Approved Dietary Supplement
Nicotinamide is FDA-approved as a prescription dietary supplement at 750 mg per tablet for patients with unique nutritional needs requiring increased nicotinamide levels. 7 The FDA labeling indicates use for patients who are deficient or at risk for deficiency. 7
Dermatological Applications
Nicotinamide has demonstrated efficacy in treating multiple skin conditions including:
Recommended Intake Levels
Standard Daily Requirements
The American College of Nutrition establishes age- and sex-specific recommendations: 1, 4
- Adult males (>14 years): 16 mg/day
- Adult females (>14 years): 14 mg/day
- Pregnant women: 18 mg/day
- Lactating women: 16 mg/day
- Parenteral nutrition dosing: 40 mg/day 1, 4
Upper Safety Limits
The European Food Safety Authority sets the upper limit for nicotinamide at 12.5 mg/kg body weight/day, approximately 900 mg/day for adults. 1, 4 This is substantially higher than the 10 mg/day limit for free nicotinic acid due to nicotinamide's superior safety profile. 1
No adverse effects were observed at doses up to 25 mg/kg body weight/day (approximately 1750 mg/day for a 70 kg adult) in prolonged studies of diabetic subjects. 1
Critical Safety Distinction: Nicotinamide vs. Nicotinic Acid
Nicotinamide does NOT cause flushing, whereas nicotinic acid commonly causes facial, arm, and chest flushing within 30 minutes at doses as low as 30 mg. 4, 6 This fundamental difference makes nicotinamide far more tolerable for therapeutic use. 4
The upper safety limit for nicotinic acid is only 10 mg/day due to flushing effects and potential transient hypotensive episodes in elderly patients. 1 Clinical doses of nicotinic acid for hypercholesterolemia treatment (3 g/day) are 300-fold higher than this safety limit. 1
Dietary Sources
Niacin is obtained from fortified packaged foods, meat and poultry, red fish (tuna and salmon), and lesser amounts in nuts, legumes, and seeds. 1, 4, 6 The body can also synthesize niacin from the amino acid tryptophan in the liver (1 mg nicotinamide = 1 niacin equivalent). 1
Monitoring at Therapeutic Doses
When using therapeutic doses approaching or exceeding 1000 mg daily, the American College of Cardiology recommends monitoring hepatic transaminases (ALT, AST) at baseline and every 6 months due to risk of liver enzyme elevations. 4 Additionally, baseline fasting glucose or hemoglobin A1c should be monitored for metabolic effects. 4
Discontinue immediately if hepatic transaminases exceed 2-3 times the upper limit of normal. 4
Common Side Effects
The most common side effects of nicotinamide supplementation are gastrointestinal symptoms including:
These effects are generally mild and dose-dependent. 5
Key Clinical Pitfalls to Avoid
Do not confuse nicotinamide with nicotinic acid—they have vastly different side effect profiles, with nicotinic acid causing flushing at low doses while nicotinamide does not. 4, 6
Do not use injectable NAD+ instead of oral nicotinamide—no published randomized controlled trials exist for NAD+ infusions in humans, and guidelines recommend oral precursors whenever the GI tract is functional. 6 The American Society for Parenteral and Enteral Nutrition recommends standard niacin at 40 mg/day for parenteral nutrition, not injectable NAD+. 6
For immunosuppressed organ transplant recipients requiring skin cancer prevention, consider alternative chemopreventive strategies such as systemic retinoids or capecitabine instead of nicotinamide. 5