What is NAD+?
NAD+, also known as nicotinamide adenine dinucleotide, is an essential coenzyme and plays a role in energy metabolism, DNA repair and epigenetic homeostasis.1,2As we age, our bodies don’t produce as much NAD+ as they used to. Ironically, our bodies actually need more NAD+ than ever as we age, a realisation that has prompted scientists to explore the benefits of supplementation. Replenishing the NAD+ levels through NAD+ precursor vitamins, like Nicotinamide Riboside is currently one of the hottest topics in the science world. 1
Nicotinamide Riboside Chloride (NRC) is a precursor vitamin to NAD+, which basically means (without ‘nerding out’ too much) that it can help increase the levels of NAD+ in our bodies by ‘turning into’ NAD+ once ingested. NR appears to have a plethora of potential health benefits to boast.
Other precursor vitamins exist for NAD+ including NMN (Nicotinamide mononucleotide), and tryptophan, niacin2, resveratrol, pterostilbene and quercetin but NRC is the only NAD+ precursor that can directly cross the cell membrane without active transport. 2 Best of all, NRC does all this without nasty side effects, such as flushing, that have been observed in other NAD+ precursor vitamins, plus, it’s more easily absorbed by the body than these other options.2
Within the cell, NRC is converted to NAD+ through a series of enzymatic reactions. NAD+ is then used in multiple cellular processes and is essential for energy metabolism, DNA repair, and cellular signaling. 2Studies have shown that supplementation with NR can increase NAD+ levels in multiple tissues, increase SIRT activity, improve mitochondrial function, and enhance the regenerative potential of stem cells.2
Here are some potential mechanisms through which NAD+ exerts its actions:
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Mitochondrial function: NAD+ plays a crucial role in cellular energy metabolism, particularly in the mitochondria, which are the powerhouses of cells. Mitochondrial dysfunction has been associated with compromised oocyte quality and impaired embryo development. By supporting mitochondrial function, NAD+ may promote optimal energy production and provide the necessary energy resources for oocyte maturation, fertilization, and early embryonic development. 4
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Oxidative stress and DNA repair: NAD+ is involved in maintaining redox balance within cells and activating enzymes called sirtuins, which have antioxidant properties. Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and antioxidant defenses, can negatively impact fertility by damaging cellular components, including DNA. NAD+ may contribute to the regulation of oxidative stress and DNA repair mechanisms, thereby protecting oocytes, sperm, and embryos from oxidative damage and promoting reproductive health. 4
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Epigenetic regulation: NAD+ is involved in epigenetic processes, which refer to modifications to DNA and associated proteins that can influence gene expression patterns without changing the DNA sequence itself. Epigenetic modifications play a critical role in reproductive processes, including oocyte and sperm development,5 fertilization, and early embryo development. NAD+ dependent enzymes, such as sirtuins and poly (ADP-ribose) polymerases (PARPs), are involved in epigenetic regulation and may contribute to the maintenance of proper gene expression patterns during reproductive events.4
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Cellular signaling and metabolism: NAD+ is an essential cofactor for enzymes involved in cellular signaling pathways and metabolic processes. These pathways can influence reproductive events, including folliculogenesis, ovulation, sperm capacitation, and embryo implantation. By modulating cellular signaling and metabolism, NAD+ may affect key processes involved reproductive success.1
References
1. Bertoldo, Michael J., Dave R. Listijono, Wing-Hong Jonathan Ho, Angelique H. Riepsamen, Dale M. Goss, Dulama Richani, Xing L. Jin et al. "NAD+ repletion rescues female fertility during reproductive aging." Cell reports 30, no. 6 (2020): 1670-1681.
2. Mehmel, Mario, Nina Jovanović, and Urs Spitz. "Nicotinamide riboside—the current state of research and therapeutic uses." Nutrients 12, no. 6 (2020): 1616.
3. Li, Hui, Huan Wang, Jianmin Xu, Xinxin Zeng, Yingpu Sun, and Qingling Yang. "Nicotinamide riboside supplementation ameliorated post-ovulatory oocyte quality decline." Reproduction 165, no. 1 (2023): 103-111.
4. Xie, N., Zhang, L., Gao, W. et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Sig Transduct Target Ther 5, 227 (2020). https://doi.org/10.1038/s41392-020-00311-7
5. Meyer-Ficca, M. L., Zwerdling, A. E., Swanson, C. A., Tucker, A. G., Lopez, S. A., Wandersee, M. K., Warner, G. M., Thompson, K. L., Chini, C. C. S., Chen, H., Chini, E. N., & Meyer, R. G. (2022). Low NAD+Levels Are Associated With a Decline of ********* in Transgenic ANDY and Aging Mice. Frontiers in endocrinology, 13, 896356. https://doi.org/10.3389/fendo.2022.896356
