Overview of β-Nicotinamide Mononucleotide (β-NMN)

β-Nicotinamide mononucleotide (β-NMN) is a direct precursor to nicotinamide adenine dinucleotide (NAD+), a vital coenzyme involved in cellular metabolism, DNA repair, and aging processes. NMN supplementation has been shown to increase NAD+ levels, which are known to decline with age and are associated with various age-related diseases and metabolic disorders(Fukamizu et al., 2022; Zheng et al., 2024; Su et al., 2024; Yi et al., 2022).

Pharmaceutical Applications

Healthspan and Disease Amelioration

NMN has demonstrated potential in extending healthspan and alleviating age-related conditions in preclinical models. Recent clinical trials in humans have shown that oral NMN supplementation significantly increases blood NAD+ concentrations, improves physical performance, and is well tolerated without significant adverse effects(Pencina et al., 2022; Fukamizu et al., 2022; Su et al., 2024; Yi et al., 2022). These findings support NMN's promise as a therapeutic agent for age-related diseases and metabolic dysfunctions.

Safety and Tolerability

Multiple clinical studies have confirmed the safety of β-NMN at doses up to 1250 mg daily for several weeks, with no severe adverse events or clinically significant changes in physiological parameters observed in healthy adults(Fukamizu et al., 2022; Su et al., 2024; Yi et al., 2022). This safety profile is crucial for its consideration in pharmaceutical and nutraceutical products.

Industrial Production and Biotechnological Advances

The pharmaceutical industry benefits from advances in NMN biosynthesis, which enable cost-effective and scalable production. Engineered microbial strains, such as Escherichia coli and Bacillus subtilis, have been optimized to produce high yields of NMN from inexpensive substrates like glucose, nicotinamide, and xylose(Liu & Yu, 2021; Shoji et al., 2020; Su et al., 2024; Mao et al., 2024; Tan et al., 2024). Innovations in enzyme engineering and whole-cell biocatalysis have further improved production efficiency, stability, and scalability, making NMN more accessible for pharmaceutical applications(He et al., 2022; Mao et al., 2024; Tan et al., 2024).

Broader Industry Use

Beyond pharmaceuticals, NMN is also utilized in the food and cosmetics industries due to its role in promoting healthy aging and maintaining metabolic balance(Zheng et al., 2024). However, its primary pharmaceutical interest lies in its potential to support NAD+ replenishment therapies for aging and metabolic diseases.

Summary Table: Key Aspects of β-NMN in the Pharmaceutical Industry

Conclusion

β-Nicotinamide mononucleotide is a promising compound in the pharmaceutical industry, valued for its ability to boost NAD+ levels, its safety in human use, and the recent advances in its efficient, large-scale biosynthesis. These attributes support its growing role in therapies targeting aging and metabolic health.

References

Pencina, K., Lavu, S., Santos, M., Beleva, Y., Cheng, M., Livingston, D., & Bhasin, S. (2022). MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-aged and Older Adults.. The journals of gerontology. Series A, Biological sciences and medical sciences. https://doi.org/10.1093/gerona/glac049

Fukamizu, Y., Uchida, Y., Shigekawa, A., Sato, T., Kosaka, H., & Sakurai, T. (2022). Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports, 12. https://doi.org/10.1038/s41598-022-18272-y

Liu, Y., & Yu, B. (2021). Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide. Microbial Biotechnology, 14, 2581 - 2591. https://doi.org/10.1111/1751-7915.13901

He, Z., Yang, X., Tian, X., Li, L., & Liu, M. (2022). Yeast Cell Surface Engineering of a Nicotinamide Riboside Kinase for the Production of β-Nicotinamide Mononucleotide via Whole-Cell Catalysis.. ACS synthetic biology. https://doi.org/10.1021/acssynbio.2c00350

Zheng, C., Li, Y., Wu, X., Gao, L., & Chen, X. (2024). Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide. Nutrients, 16. https://doi.org/10.3390/nu16142354

Shoji, S., Yamaji, T., Makino, H., Ishii, J., & Kondo, A. (2020). Metabolic design for selective production of nicotinamide mononucleotide from glucose and nicotinamide.. Metabolic engineering. https://doi.org/10.1016/j.ymben.2020.11.008

Su, C., Cheng, L., Gong, J., Li, H., Xu, Z., & Shi, J. (2024). Systematic engineering for efficient production of nicotinamide mononucleotide from d-xylose and nicotinamide in Escherichia coli. Food Bioscience. https://doi.org/10.1016/j.fbio.2024.103859

Yi, L., Maier, A., Tao, R., Lin, Z., Vaidya, A., Pendse, S., Thasma, S., Andhalkar, N., Avhad, G., & Kumbhar, V. (2022). The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience, 45, 29 - 43. https://doi.org/10.1007/s11357-022-00705-1

Mao, X., Zhang, P., Gong, J., Marshall, G., Su, C., Qin, Z., Li, H., Xu, G., Xu, Z., & Shi, J. (2024). Protein Engineering of Nicotinamide Riboside Kinase Based on a Combinatorial Semirational Design Strategy for Efficient Biocatalytic Synthesis of Nicotinamide Mononucleotides.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.4c05520

Tan, Z., Yang, Y., Wu, Y., Yan, J., Zhang, B., Hou, Y., & Jia, S. (2024). Biosynthesis of β-nicotinamide mononucleotide from glucose via a new pathway in Bacillus subtilis. Frontiers in Microbiology, 15. https://doi.org/10.3389/fmicb.2024.1405736