Does Nicotinamide adenine dinucleotide (NAD) supplementation cause cancer?

Does NAD Supplementation Cause Cancer?

Based on the available evidence, there is no direct evidence that NAD supplementation causes cancer in humans. In fact, some research suggests NAD intermediates may have protective effects against certain types of cancer 1.

Understanding NAD and Its Role in the Body

NAD (Nicotinamide adenine dinucleotide) is a coenzyme that plays essential roles in:

• Energy metabolism
• DNA repair
• Gene expression
• Stress response

NAD exists in the body in two forms:

• NAD+ (oxidized form)
• NADH (reduced form)

NAD is obtained through several pathways:

• De novo synthesis from tryptophan
• Salvage pathway from nicotinamide
• Conversion from other NAD precursors (nicotinamide riboside, nicotinamide mononucleotide)

NAD and Cancer: The Evidence

Cancer Cell Metabolism

• Cancer cells often have altered metabolism with increased NAD requirements 2
• Increased NAD levels can enhance glycolysis (Warburg effect) in cancer cells 2
• The enzyme NAMPT (nicotinamide phosphoribosyltransferase), which is rate-limiting for NAD synthesis, is frequently amplified in several cancer cells 2

Therapeutic Approaches

• Some cancer treatments actually aim to deplete NAD in cancer cells 3
• NAMPT inhibitors that deplete NAD levels can suppress cancer cell proliferation 4
• This suggests that while cancer cells may require elevated NAD, supplementation doesn't necessarily promote cancer development

Protective Effects

• Oral nicotinamide (NAM), an NAD precursor, has been shown to decrease the incidence of keratinocyte carcinoma in high-risk skin cancer patients 1
• NAD is necessary for DNA repair, which helps prevent potentially oncogenic mutations 1
• Nicotinamide riboside (NR) supplementation has been shown to suppress hepatocellular cancer progression in mice 5

Clinical Guidelines and Recommendations

Current clinical guidelines do not indicate that NAD supplementation causes cancer:

• ESPEN micronutrient guidelines (2022) discuss niacin (which forms NAD) requirements but do not mention cancer risk 6
• Guidelines for basal cell carcinoma management (2018) mention that oral nicotinamide may actually reduce the risk of subsequent keratinocyte carcinoma, though evidence is still developing 6
• Guidelines on nonnutritive sweeteners (2019) and various ESPEN nutrition guidelines do not identify NAD supplementation as a cancer risk 6

Practical Considerations

When considering NAD supplementation:

1. Appropriate Dosing:

   • Follow recommended dosages for niacin/nicotinamide (14-18 mg/day for adults) 6
   • Higher therapeutic doses should be medically supervised

2. Monitoring:

   • No special monitoring is required for standard doses 6
   • At higher doses, side effects like flushing may occur with nicotinic acid form

3. Special Populations:

   • Those with a history of cancer should discuss supplementation with their healthcare provider
   • Patients with multiple acyl-CoA dehydrogenase deficiency (MADD) may require higher doses (50-200 mg/day) 6

Conclusion

While cancer cells may have altered NAD metabolism and increased NAD requirements, there is no evidence that NAD supplementation causes cancer in humans. Some research even suggests potential protective effects against certain cancers. As with any supplement, NAD precursors should be taken at appropriate doses and under medical supervision when used for therapeutic purposes.