Can NAD⁺ (nicotinamide) supplementation induce remission in melanoma, and what dose is recommended?

NAD⁺ Supplementation Does Not Induce Melanoma Remission and Is Not Recommended for This Purpose

No evidence supports the use of NAD⁺ or its precursors (nicotinamide) to induce remission in melanoma patients. The available research demonstrates that nicotinamide may have chemopreventive properties against keratinocyte cancers but does not treat established melanoma, and current guidelines do not recommend NAD⁺ supplementation for cancer treatment 1, 2.

Evidence Against Therapeutic Use in Melanoma

Lack of Treatment Efficacy

• A 2023 meta-analysis found no significant reduction in non-melanoma skin cancers with nicotinamide supplementation (RR 0.82,95% CI 0.61-1.12), and this study did not even evaluate melanoma treatment outcomes 3
• The only melanoma-specific research (2020) examined nicotinamide's effects on melanoma cells in vitro and found that physiologically achievable concentrations (50 μM) did not affect melanoma cell viability, proliferation, or invasiveness 4
• Nicotinamide at 50 μM had no anti-tumor effects on four different human melanoma cell lines, indicating it cannot induce remission 4

Potential Safety Concerns in Melanoma

• Melanoma cells actively release extracellular NAMPT (the enzyme that produces NAD⁺), which promotes tumor progression through MAPK, AKT, and NF-κB pathway activation 5
• NAMPT is a direct target of the BRAF oncogenic signaling pathway in metastatic melanoma, and melanoma cells require increased NAD⁺ for metabolic reprogramming that supports proliferation and survival 6, 7
• Supplementing NAD⁺ precursors could theoretically fuel melanoma metabolism rather than suppress it, though the 2020 study found no enhancement of melanoma growth at physiologic doses 6, 4

Guideline-Based Recommendations for NAD⁺ Use

Approved Indications

• NAD⁺ precursors (niacin/nicotinamide) are recommended only for preventing niacin deficiency (pellagra) and, in some contexts, for chemoprevention of actinic keratoses and keratinocyte cancers in high-risk patients 1, 8, 2
• Standard dosing for deficiency prevention: 16 mg/day for adult males, 14 mg/day for adult females 8, 2
• For pellagra treatment: 300 mg/day of nicotinamide 8

Routes Not Recommended

• Injectable NAD⁺ has no FDA approval for therapeutic medical indications, only cosmetic applications 1, 2
• No published randomized controlled trials exist for NAD⁺ infusions in humans 1
• NAD⁺ is a large, charged molecule with poor bioavailability when injected, making oral precursors the preferred route when the GI tract is functional 1, 8

Clinical Algorithm for Melanoma Patients Inquiring About NAD⁺

First-Line Response

• Explain that NAD⁺ supplementation has no proven benefit for treating or inducing remission in melanoma 4, 3
• Redirect focus to evidence-based melanoma treatments (surgery, immunotherapy, targeted therapy for BRAF mutations) rather than unproven metabolic interventions 6

If Patient Has Documented Niacin Deficiency

• Assess for pellagra symptoms: diarrhea, dermatitis, dementia 1, 2
• Risk factors include corn-based diet, malnutrition, chronic alcoholism, malabsorptive states 1, 2
• Treat with oral nicotinamide 300 mg/day, not injectable NAD⁺ 8

Safety Monitoring If Patient Insists on High-Dose Nicotinamide

• Upper safety limit for nicotinamide is approximately 900 mg/day for adults 1, 8
• Monitor hepatic transaminases (ALT, AST) at baseline and every 6 months if doses approach 1000 mg/daily 8
• Discontinue if transaminases exceed 2-3 times upper limit of normal 8
• Common side effects at high doses include gastrointestinal symptoms (nausea, vomiting, diarrhea) 8

Key Clinical Pitfalls to Avoid

• Do not confuse chemoprevention with treatment: nicotinamide may reduce new keratinocyte cancers in high-risk patients but does not treat established melanoma 4, 3
• Do not recommend injectable NAD⁺ based on marketing claims about "boosting cellular energy"—these lack regulatory approval and clinical evidence 1, 2
• Do not assume that because melanoma cells require NAD⁺ for metabolism, supplementation will help patients—it may theoretically support tumor growth 6, 5
• Nicotinic acid (different from nicotinamide) causes flushing at doses as low as 30 mg and has a much lower upper safety limit (10 mg/day) 1, 8, 2

Nuanced Consideration: Potential Future Research Direction

• One 2020 study found that melanomas arising in patients taking nicotinamide had significantly increased peritumoral and tumor-infiltrating CD4+ and CD8+ lymphocytes compared to placebo, suggesting possible immune modulation 4
• However, this observation was from a secondary analysis of a chemoprevention trial, not a melanoma treatment study, and does not justify clinical use for remission induction 4
• The authors concluded that clinical trials of nicotinamide for melanoma chemoprevention (not treatment) may be warranted, but no such trials have been published 4