The Secrets of NMN: A Gateway to Healthier Ageing?

The pursuit of longevity and maintaining health into later years has raised the question of the importance of nicotinamide mononucleotide (NMN). This molecule, essential for our cellular functions, is linked to ageing, suggesting a profound potential to impact how we age gracefully. Investigating NMN reveals exciting possibilities for enhancing health span, promising a future where ageing is accompanied by vitality rather than decline. 

What is Nicotinamide Mononucleotide (NMN)?

NMN is not merely a dietary supplement; it's a crucial component of cellular health¹, acting as a precursor to NAD+, a molecule vital for energy metabolism and cellular functions. Found naturally in the body, NMN's role is to support the production of NAD+, thereby influencing various processes, including DNA repair, metabolic activities, and energy production. Its presence is akin to providing the raw materials necessary for the intricate machinery of our cells to function optimally.

Within our cells, NMN contributes to the synthesis of NAD+, directly affecting our cellular energy and the maintenance of healthy physiological functions. As we age, NMN levels decrease, leading to reduced NAD+ production and the onset of age-related decline. Supplementation with NMN² can potentially replenish NAD+ levels, supporting cellular health and longevity.

How does Nicotinamide Mononucleotide (NMN) Work?

NMN aids in bolstering NAD+ levels within our bodies, combating the natural decline associated with ageing. By rejuvenating NAD+ availability, NMN facilitates the enhancement of energy metabolism, DNA repair, and cell survival mechanisms, thereby potentially slowing ageing markers.

By supporting the production of NAD+, NMN plays a pivotal role in regulating key cellular functions such as energy metabolism, DNA repair, gene expression, and cellular stress responses. The decline in NMN levels as we age can lead to a corresponding decrease in NAD+, contributing to the physiological manifestations of ageing. However, supplementation with NMN has been shown to improve insulin sensitivity, enhance heart function, and reduce fatigue3, underscoring its potential as a powerful ally in the fight against ageing. It is important, however, to consult with a healthcare professional before beginning NMN supplementation to ensure it aligns with your individual health needs.

What Can NMN Be Used For?

Leveraging NMN encompasses addressing age-associated energy decline, enhancing metabolic health, and possibly supporting cognitive functions. NMN's promising effects extend across various aspects of health, from improving metabolic markers like insulin sensitivity to enhancing cardiovascular health and reducing fatigue. These insights, based on emerging research, suggest NMN's role in combatting the multifaceted nature of ageing, making it a focal point for interventions aimed at improving the quality of life in the elderly.

The Benefits of Nicotinamide Mononucleotide (NMN)

Research illuminates NMN’s capacity to improve insulin sensitivity, boost physical energy, and fortify cellular health. These attributes spotlight NMN as a cornerstone in age defiance and healthspan extension.

Clinical and preclinical studies⁴ have highlighted NMN's potential in a wide array of health benefits, including its role in energy metabolism, DNA repair, and cellular defence mechanisms. NMN supplementation has been observed to offer promising outcomes in improving heart function, enhancing physical energy, and possibly supporting cognitive functions, reflecting its versatility in promoting health and well-being.

The Limitations and Side Effects of Nicotinamide Mononucleotide (NMN)

Given its natural presence in the body and the food we consume, NMN is considered safe, with minimal reported side effects. One study in 2021⁵, did observe side effects in patients given 250 milligrams of NMN daily for 12 weeks. Side effects included abdominal pain, diarrhoea, gas and upper respiratory health issues. This study did have limited participants however, with only 15 participants taking the NMN. 

While NMN has been tested and is considered safe, it is important to remember that long-term studies are limited and starting any new supplementation should always be done under the supervision of your health care professional. 

FDA Concerns

The U.S. Food and Drug Administration (FDA) made a significant decision in 2022 regarding NMN being used as dietary supplements. Initially, the FDA allowed one company, SyncoZymes⁶, to market NMN as a dietary supplement. Prior to 2022, several manufacturers had submitted notifications for NMN, but none received FDA approval until May 16, 2022, when SyncoZymes' notification was accepted, granting them permission to market NMN in the United States.

Seeking to capitalise on this opportunity, Inner Mongolia Kingdomway Pharmaceutical Limited submitted an NDI notification⁷ for NMN on July 28, 2022, with plans to market their NMN-containing supplement in the U.S., similar to SyncoZymes. However, on October 11, 2022, Kingdomway encountered a significant obstacle. The FDA responded to their notification, stating that NMN is currently being investigated as a new drug⁸  and hence cannot be marketed as a dietary supplement in the U.S. This denial was based on a provision in the Federal Food, Drug, and Cosmetic Act, which safeguards the interests of pharmaceutical companies developing new drugs and prevents circumvention of the drug approval process. The FDA cited the submission of an Investigational New Drug (IND) application for NMN by another pharmaceutical company as the reason for the NDI denial.

Essentially, since the FDA has determined that NMN is currently under investigation as a new drug, it therefore cannot be marketed as a dietary supplement. The FDA's decision to restrict NMN as a dietary supplement is based on the understanding that NMN is being evaluated for its potential use as a pharmaceutical drug, which is subject to more stringent regulations compared to dietary supplements. The FDA aims to ensure that proper scientific evidence, safety considerations, and quality control measures are in place before endorsing any health-related claims or allowing the marketing of NMN as a dietary supplement.

Benefits of NAD+ (What NMN Helps Your Body Produce)

Elevating NAD+ levels via NMN supplementation could play a critical role in ageing and wellness. High NAD+ levels have been associated with increased activation of sirtuins, proteins involved in DNA repair and longevity. Furthermore, enhanced NAD+ levels⁹  may offer protective benefits against neurodegenerative diseases, cardiovascular issues, and even certain cancers, underscoring the potential of NMN in supporting broad health domains.

Does NMN Supplementation Work?

Emerging studies exhibit promising outcomes regarding NMN’s efficacy in elevating NAD+ levels, suggesting a potential for mitigating ageing effects.  The effectiveness of NMN supplementation in humans is supported by a growing body of research¹⁰, indicating improvements in markers of metabolic health, exercise performance, and possibly even sleep quality. However, the landscape of NMN research is still evolving, with ongoing studies aimed at validating these benefits across larger populations and diverse health outcomes.

Natural Sources of NMN

To boost NMN levels naturally, incorporating NMN-rich foods into your diet can be beneficial. Avocados, broccoli, cabbage, tomatoes, and raw beef are excellent sources of NMN, offering a dietary approach to support your body's NAD+ production.

What are its Anti-Ageing Properties?

NMN stands out for its anti-ageing potential, demonstrated through its ability to mimic aspects of caloric restriction, enhance DNA repair mechanisms, and support mitochondrial function. These actions collectively contribute to the slowing of the ageing process, positioning NMN as a key molecule in the pursuit of longevity. NMN’s role in DNA repair, sirtuin activation, and mitochondrial biogenesis¹¹ positions it as a vanguard against ageing. These mechanisms collectively endeavour to sustain cellular integrity and function over time.

NMN represents a promising frontier in longevity science, with implications for healthy aging that align with the broader quest for enhancing life quality. As we delve deeper into NMN's effects and mechanisms, the vision of aging with health and vitality becomes increasingly attainable, offering hope for a future where we not only live longer but live well.

References 

1. ww.nmn.com. (n.d.). The Science Behind NMN. [online] Available at: https://www.nmn.com/news/the-science-behind-nmm  (Accessed: 14 March 2024). 

2. Shade, C. (2020). The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integrative medicine (Encinitas, Calif.), [online] 19(1), pp.12–14. 

3. Song, Q., Zhou, X., Xu, K., Liu, S., Zhu, X. and Yang, J. (2023). The Safety and Anti-Ageing Effects of Nicotinamide Mononucleotide in Human Clinical Trials: An Update. Advances in Nutrition. [online] doi:https://doi.org/10.1016/j.advnut.2023.08.008.

4. Ur Rahman, S., Qadeer, A. and Wu, Z. (2023). Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging. Aging and Disease. [online] doi:https://doi.org/10.14336/AD.2023.0519-1.

5. Okabe, K., Yaku, K., Uchida, Y., Fukamizu, Y., Sato, T., Sakurai, T., Tobe, K. and Nakagawa, T. (2022). Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects. Frontiers in Nutrition, [online] 9. doi:https://doi.org/10.3389/fnut.2022.868640.

6. Drake, K. (2024). FDA Bans NMN as a Dietary Supplement: Why and What Happened? [online] HealthNews. Available at: https://healthnews.com/longevity/longevity-supplements/fda-b-nmn-can-no-longer-be-sold-as-a-dietary-supplement-in-the-us/. (Accessed: 14 March 2024). 

7. Letter, F. (2022). FDA Letter States that β-Nicotinamide Mononucleotide is Not Lawful Dietary Supplement. [online] Lexology. Available at: https://www.lexology.com/library/detail.aspx?g=824d29bd-aa83-41a2-bade-a95f22d9866e (Accessed: 14 March 2024). 

8. www.nmn.com. (n.d.). The FDA Prolongs Its Inaction Regarding NMN. [online] Available at: https://www.nmn.com/news/the-fda-prolongs-its-inaction-regarding-nmn (Accessed: 14 March 2024). 

9. Lautrup, S., Sinclair, D.A., Mattson, M.P. and Fang, E.F. (2019). NAD+ in Brain Aging and Neurodegenerative Disorders. Cell Metabolism, [online] 30(4), pp.630–655. doi:https://doi.org/10.1016/j.cmet.2019.09.001.

10. Nadeeshani, H., Li, J., Ying, T., Zhang, B. and Lu, J. (2022). Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns. Journal of Advanced Research, [online] 37(37), pp.267–278. doi:https://doi.org/10.1016/j.jare.2021.08.003.

11. Wang, Y.-J., Paneni, F., Stein, S. and Matter, C.M. (2021). Modulating Sirtuin Biology and Nicotinamide Adenine Diphosphate Metabolism in Cardiovascular Disease—From Bench to Bedside. Frontiers in Physiology, 12. doi:https://doi.org/10.3389/fphys.2021.755060.