What are the side effects of Nicotinamide Mononucleotide (NMN) supplementation?

Side Effects of Nicotinamide Mononucleotide (NMN)

NMN supplementation appears to be generally safe at recommended doses, but may cause gastrointestinal symptoms in some individuals and has potential for drug interactions, particularly with medications metabolized through cytochrome P450 enzymes.

Safety Profile of NMN

• NMN is a precursor to nicotinamide adenine dinucleotide (NAD+), a coenzyme involved in over 400 enzymatic reactions in the body that helps convert nutrients into energy, create cholesterol and fats, repair DNA, and exert antioxidant effects 1

• Clinical trials have shown that oral NMN supplementation at doses of 250 mg/day for 12 weeks produced no abnormalities in physiological and laboratory tests and no obvious adverse effects in healthy subjects 2

• The European Food Safety Authority (EFSA) has established an upper intake level (UL) for nicotinamide (a related compound) at 12.5 mg/kg body weight/day or approximately 900 mg/day for adults 1

Potential Side Effects

• Unlike nicotinic acid (another form of niacin), NMN does not typically cause flushing, which is a common side effect seen with nicotinic acid supplementation 1

• Gastrointestinal effects may occur with NMN supplementation, similar to those reported with other NAD+ precursors, including:

  • Nausea
  • Vomiting
  • Diarrhea
  • Anorexia 1

• Individual responses to NMN supplementation vary widely, with some people experiencing more pronounced effects than others 3

Safety Data from Animal Studies

• Toxicity studies in rats have established a No-Observed-Adverse-Effect-Level (NOAEL) for high-purity NMN at:

  • 1,000 mg/kg/day in female rats
  • 500 mg/kg/day in male rats 4

• Another study determined the NOAEL for NMN to be ≥1500 mg/kg/day in rats with no toxic effects observed on body weight, food and water consumption, biochemical parameters, or organ histology 5

• At extremely high doses (2000 mg/kg/day), adverse effects in animal studies included reduced body weight, reductions in body weight gains, and diminished food consumption 4

Metabolic Effects and Considerations

• NMN supplementation has been shown to increase plasma NMN and NAD+ levels in humans 2, 3

• Some studies have reported that NMN supplementation may increase postprandial serum insulin levels, which could be relevant for individuals with diabetes or insulin resistance 3

• The elevation levels of NMN and insulin vary widely among individuals, suggesting personalized responses to supplementation 3

Drug Interactions

• While specific data on NMN drug interactions is limited, caution should be exercised with medications that interact with the cytochrome P450 enzyme system, as other NAD+ precursors have shown interactions 1

• Particular attention should be paid when combining NMN with:

  • Warfarin (potential interaction similar to other NAD+ precursors)
  • Medications for diabetes (due to potential effects on insulin levels) 1, 3

Special Populations

• There is insufficient evidence regarding the safety of NMN supplementation during pregnancy and lactation 1

• The safety profile in individuals with liver or kidney disease has not been well established, and these populations may be at higher risk for adverse effects due to altered metabolism or excretion 1

Monitoring Recommendations

• Monitoring of urinary metabolites (N-methyl-nicotinamide and N-methyl-2-pyridone-carboxamide) can be used to assess niacin status and potentially monitor for excessive intake 1

• For individuals taking NMN supplements, regular monitoring of metabolic parameters may be advisable, particularly if they have pre-existing conditions like diabetes 3

Conclusion

While current evidence suggests that NMN supplementation is generally safe at recommended doses, long-term safety data in humans remains limited. Most human studies have been relatively short-term (12 weeks or less), and more research is needed to establish the long-term safety profile of NMN supplementation 2, 6.