An Ingredient for Healthy Aging: Nicotinamide mononucleotide (NMN)

Photo © AdobeStock.com/ mizina

Everyone would like to experience “healthy aging”: the ability to remain healthy and retain elements of youthfulness while aging—perhaps even to age more slowly. The dietary supplement industry is certainly rife with nutraceutical promises to help users achieve these goals. But are any of those promises true?

Unfortunately, only time will tell if these interventions work. That is, after all, the nature of aging. Nevertheless, it has been interesting to follow the various healthy aging trends to see what seems to have significant potential. One very interesting possibility is nicotinamide adenine dinucleotide (NAD) promoters.

What Is NAD?

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor in all living cells that is involved in fundamental biological processes. Mounting evidence indicates that NAD+ levels decline with age in multiple types of tissues. NAD+ depletion has been associated with hallmarks of aging and may underlie a wide range of age-related diseases, such as metabolic disorders, cancer, and neurodegenerative diseases.

Emerging evidence suggests that elevating NAD+ levels may help slow or even reverse the aspects of aging and also delay the progression of age-related diseases.¹ Furthermore, treatments that replenish intracellular NAD+ may help delay memory loss and extend lifespan in animal models.²

Sounds cool, right? So, how does one go about elevating NAD+ levels? Enter NMN.

NMN, an NAD Precursor

Nicotinamide mononucleotide (NMN) is an NAD+ intermediate. It is synthesized from niacinamide, a form of water-soluble vitamin B3.¹ NMN has been extensively studied and has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions.³

It is a physically stable natural compound that serves as an efficient NAD+ precursor. Furthermore, an animal model⁴ demonstrated that supplementation with NMN substantially mitigated inflammation, improved cellular metabolism, and promoted survival following hemorrhagic shock.

NMN and Prediabetes

Since both obesity and aging impair NAD+ synthesis in rodents, which contributes to metabolic dysfunction, a 10-week, randomized, placebo-controlled, double-blind trial⁵ sought to evaluate the effect of NMN supplementation (250 mg/day) on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Results showed that NMN supplementation increased muscle insulin sensitivity, insulin signaling, and remodeling in this population of women with prediabetes.

NMN and Cardiovascular Fitness

A six-week, randomized, double-blind, placebo-controlled, four-arm clinical trial⁶ including 48 young and middle-aged recreationally trained runners was conducted to investigate the effects of a combination of exercise training and supplementation with NMN on cardiovascular fitness in healthy amateur runners. The participants were randomized into four groups: the 300 mg/day NMN group, the 600 mg/day NMN group, the 1200 mg/day NMN group, and the control group (placebo).

Results showed that the oxygen uptake (VO₂), percentages of maximum oxygen uptake (VO₂max), power at first ventilatory threshold, and power at second ventilatory threshold increased to a higher degree in the 600-mg and 1200-mg groups compared with the control group. In conclusion, NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O₂ utilization of the skeletal muscle.

NMN Increases NAD

Another randomized, double-blind, placebo-controlled, parallel-group trial⁷ investigated the safety of orally administered NNM and its efficacy in increasing NAD+ levels in 30 healthy subjects who received 250 mg/day of NMN (n = 15, administered as 125 mg in the morning and evening) or placebo (n = 15) for 12 weeks. Physiological and laboratory tests were performed during this period.

The researchers found that oral supplementation of NMN for 12 weeks caused no abnormalities in physiological and laboratory tests, and no obvious adverse effects, but significantly increased whole-blood NAD+ levels after NMN administration. It was interesting that the increased amount of NAD+ was strongly correlated with pulse rate before the administration of NMN—suggesting that NMN might best be taken prior to exercise. In conclusion, NMN was found to be a safe and practical strategy to boost NAD+ levels in humans.

More NMN Safety Testing

Speaking of safety, another clinical trial⁸ was conducted to investigate the safety of a single dose of oral NMN (100, 250, and 500 mg) in 10 healthy men. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites, were investigated for five hours after each intervention. Researchers found that there were no safety issues associated with any of the doses of NMN.

Conclusion

NAD+ depletion has been associated with hallmarks of aging and age-related diseases. Elevating NAD+ levels may slow or even reverse the aspects of aging and also delay the progression of age-related diseases. Supplementation with NMN has been shown to increase NAD levels, improve insulin sensitivity, and improve cardiovascular fitness—all with a demonstrated safety profile. NMN appears to be a good healthy aging supplement.

About the author:

Gene Bruno, MS, MHS, RH (AHG), is a certified nutritionist and registered herbalist with 42 years of dietary supplement industry experience. With a master’s degree in nutrition and a second master’s degree in herbal medicine, he has a proven track record of formulating innovative, evidence-based dietary supplements. Mr. Bruno currently serves as both the vice president of scientific and regulatory affairs at NutraScience Labs and professor of nutraceutical science at Huntington University of Health Sciences.

References

1. Aman Y et al. “Therapeutic potential of boosting NAD+ in aging and age-related diseases.” Translational Medicine of Aging, vol. 2 (January 2018): 30-37
2. Fang EF et al. “NAD + replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair.” Cell Metabolism, vol. 24, no. 4 (October 11, 2016): 566-581
3. Yoshino J et al. “NAD + intermediates: The biology and therapeutic potential of NMN and NR.” Cell Metabolism, vol. 27, no. 3 (March 6, 2018): 513-528
4. Sims CA et al. “Nicotinamide mononucleotide preserves mitochondrial function and increases survival in hemorrhagic shock.” Journal of Clinical Investigation Insight, vol. 3, no. 17 (September 6, 2018): e120182
5. Yoshino M et al. “Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.” Science. Published online April 22, 2021.
6. Liao B et al. “Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: A randomized, double-blind study.” Journal of the International Society of Sports Nutrition, vol. 18, no. 1 (July 2021): 54
7. Okabe K et al. “Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood nicotinamide adenine dinucleotide levels in healthy subjects.” Frontiers in Nutrition. Published online April 11, 2022.
8. Irie J et al. “Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men.” Endocrine Journal, vol. 67, no. 2 (February 28, 2020): 153-160