Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental coenzyme found in all living cells, essential for energy production, DNA repair, and cellular homeostasis. Yet, as we age, our levels of NAD⁺ naturally decline a process now recognised as a major contributor to the molecular hallmarks of aging, including mitochondrial dysfunction, genomic instability, cellular senescence, and chronic inflammation (Verdin, 2015; Covarrubias et al., 2020).

Why NAD⁺ Decline Matters

The aging process is accompanied by a progressive reduction in cellular NAD⁺ concentrations, which compromises the activity of NAD⁺-dependent enzymes such as sirtuins and PARPs. These enzymes are critical for DNA repair, chromatin remodelling, and the regulation of oxidative stress (Conlon, 2021; Christiano et al., 2023). As NAD⁺ levels drop, the efficiency of these protective mechanisms diminishes, accelerating the accumulation of DNA damage, promoting genomic instability, and increasing susceptibility to age-related diseases (Lautrup et al., 2023).

In addition, NAD⁺ plays a vital role in epigenetic regulation. Sirtuins NAD⁺-dependent deacetylases control gene expression through histone modification, impacting inflammation, metabolic balance, and cellular differentiation (Covarrubias et al., 2020). Low NAD⁺ levels contribute to the dysregulation of these pathways, triggering chronic inflammation and phenotypic drift, both of which are linked to degenerative diseases and functional decline (Campbell, 2022).

Mitochondrial Health and Cellular Energy

Mitochondria rely on NAD⁺ for oxidative phosphorylation and ATP production. A deficiency in NAD⁺ reduces the efficiency of the electron transport chain, resulting in energy deficits and increased oxidative stress in metabolically demanding tissues such as the brain, heart, and skeletal muscle (Prolla and Denu, 2014; Srivastava, 2016). This energetic shortfall contributes to fatigue, cognitive decline, and physical frailty associated with aging (Lautrup et al., 2019).

Moreover, NAD⁺ is central to regulating cellular senescence. Declining levels impair the cell’s ability to maintain homeostasis, leading to the accumulation of senescent cells that release pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). This chronic inflammatory state damages surrounding tissues and accelerates systemic aging (Chini et al., 2019; Christiano et al., 2023).

Why Injectable NAD⁺?

While oral NAD⁺ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have demonstrated some efficacy, their bioavailability is limited by first-pass metabolism in the liver (Iqbal and Nakagawa, 2024). Intramuscular (IM) NAD⁺ injections bypass the gastrointestinal tract and deliver the coenzyme directly into systemic circulation, ensuring rapid uptake and more consistent therapeutic outcomes (Conlon, 2021; Song et al., 2023).

NAD⁺ injection therapy has been shown to restore intracellular NAD⁺ levels, reactivating sirtuins and PARPs, improving mitochondrial function, enhancing cellular repair mechanisms, and reducing the burden of senescence. This positions injectable NAD⁺ as a promising intervention in regenerative and preventative medicine, particularly in clinical protocols aimed at preserving cognitive function, cardiovascular resilience, and skin and tissue health (Campbell, 2022; Verdin, 2015).

Medical-Only Administration: Safety First

Given the complexity of NAD⁺ biochemistry and the systemic effects of NAD⁺ restoration, this therapy should be administered only by qualified healthcare professionals in a controlled clinic environment. IM injections require appropriate dosage assessment, patient monitoring, and clinical oversight to ensure optimal safety and efficacy.

Adverse effects such as flushing, nausea, or hypotension—although rare—can occur if NAD⁺ is administered too rapidly or at excessive doses. Trained medical professionals are equipped to manage these risks and tailor protocols based on individual patient physiology, medication history, and treatment goals (Song et al., 2023).

Conclusion: NAD⁺iD Injections and the Future of Regenerative Health

As research continues to uncover the profound systemic effects of NAD⁺ on aging, metabolism, and mitochondrial function, injectable NAD⁺ therapy is emerging as a transformative option in aesthetic and functional medicine. By restoring this vital molecule, patients can experience improved energy, cognitive clarity, tissue resilience, and a more youthful biological profile. At our clinic, NAD⁺iD injections are administered exclusively by medical professionals, ensuring both the science and the safety are honoured.

References

Campbell, J.M. (2022). Supplementation with NAD⁺ and its precursors to prevent cognitive decline across disease contexts. Nutrients, 14(15), 3231. https://doi.org/10.3390/nu14153231

Chini, C., Hogan, K.A., Warner, G.M., Tarragó, M.G., Peclat, T.R., Tchkonia, T., Kirkland, J.L., & Chini, E.N. (2019). The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD⁺ decline. Biochemical and Biophysical Research Communications, 513(2), 486–493. https://doi.org/10.1016/j.bbrc.2019.03.199

Christiano, C., Cordeiro, H.S., Tran, N., & Chini, E.N. (2023). NAD metabolism: Role in senescence regulation and aging. Aging Cell. https://doi.org/10.1111/acel.13920

Conlon, N.J. (2021). The role of NAD⁺ in regenerative medicine. Plastic & Reconstructive Surgery, 150(2S), 41S–48S. https://doi.org/10.1097/PRS.0000000000009673

Covarrubias, A.J., Perrone, R., Grozio, A., & Verdin, E. (2020). NAD⁺ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x

Iqbal, T., & Nakagawa, T. (2024). The therapeutic perspective of NAD⁺ precursors in age-related diseases. Biochemical and Biophysical Research Communications, 702, 149590. https://doi.org/10.1016/j.bbrc.2024.149590

Lautrup, S., Hou, Y., Fang, E.F., & Bohr, V.A. (2023). Roles of NAD⁺ in health and aging. Cold Spring Harbor Perspectives in Medicine, 14(1), a041193. https://doi.org/10.1101/cshperspect.a041193

Lautrup, S., Sinclair, D.A., Mattson, M.P., & Fang, E.F. (2019). NAD⁺ in brain aging and neurodegenerative disorders. Cell Metabolism, 30(4), 630–655. https://doi.org/10.1016/j.cmet.2019.09.001

Prolla, T.A., & Denu, J.M. (2014). NAD⁺ deficiency in age-related mitochondrial dysfunction. Cell Metabolism, 19(2), 178–180. https://doi.org/10.1016/j.cmet.2014.01.005

Song, Q., Zhou, X., Xu, K., Liu, S., Zhu, X., & Yang, J. (2023). The safety and anti-ageing effects of nicotinamide mononucleotide in human clinical trials: An update. Advances in Nutrition, 14(6). https://doi.org/10.1016/j.advnut.2023.08.008

Srivastava, S. (2016). Emerging therapeutic roles for NAD⁺ metabolism in mitochondrial and age-related disorders. Clinical and Translational Medicine, 5, 25. https://doi.org/10.1186/s40169-016-0104-7

Verdin, E. (2015). NAD⁺ in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208–1213. https://doi.org/10.1126/science.aac4854