The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update

The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update

Article Summary: Exploring the Potential of NMN Supplementation for Anti-Aging Effects


  • Nicotinamide adenine dinucleotide (NAD+) is vital for human physiology.
  • NAD+ levels decline with age in various body parts.
  • Increasing NAD+ status may affect the aging process and associated metabolic issues.
  • Nicotinamide mononucleotide (NMN) is a precursor to NAD+.
  • NMN supplementation increases NAD+ levels and may address aging-related disorders.
  • The use of NMN as an anti-aging health supplement is gaining popularity.
  • The safety and physiological effects of NMN supplementation in humans need clarification.
  • Multiple human clinical trials with NMN are currently ongoing.
  • This review summarizes the progress of these trials and the biology of NMN/NAD+.
  • Future research directions are discussed.

The Significance of NMN Supplementation in Anti-Aging:

  • The global demand for anti-aging products is increasing due to a growing population over the age of 60.
  • NMN has become a popular anti-aging product used as a supplement and in cosmetics.
  • The global NMN market was valued at $252.7 million in 2020 and is projected to reach $385.7 million by 2027.
  • The US FDA has prohibited β-NMN as a health supplement, causing concerns among manufacturers and consumers.
  • NAD+ depletion is linked to aging and age-related diseases, making the maintenance of NAD+ levels crucial for health.
  • Caloric restriction and NAD+ precursors like NMN can raise NAD+ concentrations and potentially have anti-aging effects.
  • Animal studies show promising results with NMN supplementation, but human research is still needed to establish safety and anti-aging effects.

Understanding NMN and NAD+:

  • NAD+ exists in oxidized (NAD+) and reduced (NADH) forms.
  • NAD+ is crucial for energy metabolism and redox reactions.
  • Maintaining normal NAD+ levels is essential for healthy aging and tissue homeostasis.
  • Aging is associated with a gradual decline in NAD+ concentration across human tissues.
  • Reduced NAD+ levels can lead to decreased energy production and contribute to aging and age-related disorders.
  • Strategies to increase NAD+ levels have shown positive outcomes in preclinical studies, including improved organ functions and cognitive protection.
  • NMN is a direct precursor to NAD+ and has been shown to increase NAD+ levels in human trials.
  • NMN supplementation has exhibited safety and potential anti-aging effects, such as improved aerobic capacity, muscle strength, and cognitive function.
  • NMN is available as a dietary supplement and is often combined with other anti-aging agents.
  • NMN can be synthesized through chemical, microbial, or enzymatic methods.
  • More comprehensive clinical trials are needed to evaluate the safety and efficacy of NMN in humans.

Safety and Efficacy of NMN Supplementation:

  • Several published human clinical trials have been conducted on NMN supplementation.
  • Short-term studies on healthy men showed no significant clinical symptoms, harmful effects, or vital sign changes.
  • Oral administration of various NMN doses (250 mg-1000 mg) has been found to be safe and well-tolerated.
  • However, the number of participants in the conducted trials has been limited.
  • Further research is needed to determine the long-term oral administration safety and dietary reference intake of NMN in different age groups.
  • NMN supplementation has shown potential in improving sleep quality, physical activity, and physical performance.
  • It did not significantly affect ophthalmic parameters or overall cognitive function.
  • NMN supplementation improved insulin sensitivity and telomere length in certain population groups.
  • Completed but unpublished and ongoing clinical trials are investigating the safety, anti-aging effects, and therapeutic potential of NMN.

Future Research Directions and Conclusion:

  • Longer, larger, and better-designed trials are needed to determine safe dosages, tolerance, and frequency of NMN supplementation in the long term.
  • Studies should include larger and more diverse populations to observe potential adverse effects and understand if NMN benefits specific groups.
  • More comprehensive research is necessary to fully comprehend the beneficial effects and underlying mechanisms of NMN.
  • Mechanistic toxicological studies should be conducted to evaluate absorption, metabolic enzyme effects, and the role of gut microbiota.
  • The effects of NMN on different tissues and organs should be studied.
  • Establishing clear standards and baseline NAD+ measurements in populations is essential.
  • The excessive hype surrounding NMN in the market should be addressed, and efficacy in humans, particularly for skin aging, should be further investigated.
  • Appropriate clinical trials are necessary to evaluate the effects and safety of NMN supplements.


  • Human clinical trials suggest that NMN supplementation is generally safe and may have potential as an anti-aging agent.
  • More extensive research is needed to determine safe dosages, long-term effects, and potential adverse reactions.
  • NMN supplementation has exhibited positive outcomes in improving various health parameters.
  • The authors are grateful to anonymous reviewers and editors for their valuable input, which has improved the manuscript's quality.
  • The supplementary data for this article can be found online.

Title of paper: The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update

Author(s): Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J.

Year published: 2023

Published in: Adv Nutr

Original article can be found here.

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