By Nicholas Robinson
The Rise of Anti-Aging and Regenerative Medicine
The field of anti-aging and regenerative medicine is growing fast. As time goes on, people are beginning to live longer. Unfortunately, developing disease or illness seems to be an inevitable part of the aging process. It is important to investigate alternative medicines that allow us to “turn back the clock” and live at peak performance for longer as our population lifespan increases.
With the rise in the popularity of anti-aging and longevity, topics like platelet-rich plasma (PRP), Nicotinamide MonoNucleotide (NMN), glutathione, and Nicotinamide Adenine Dinucleotide (NAD+) have been put in the spotlight. But, for our purposes, we’ll specifically be looking at NAD+.
Discovery and Importance of NAD+
NAD+ was discovered over a century ago as a fermentation stimulant for yeast. Since then, NAD+ has been further researched and found to be an important compound in the body. NAD+ stands for nicotinamide adenine dinucleotide, which is a long name for a specialized coenzyme within the body (Shade, 2020). The term “coenzyme” is a molecule that binds to sites that have enzymes and helps with catalyzing reactions in the body.
NAD+ specifically is a coenzyme for redox reactions (or a reaction that involves a transfer of electrons between two species). This makes NAD+ a key component of energy metabolism and plays a large role in cellular function. As we age, our levels of NAD+ naturally decline between 10–65%. According to a 2020 paper, by middle age, NAD+ levels may only be half the level of what they are in younger years. This decline is associated with age-related diseases such as cognitive decline, cancer, sarcopenia, and others.
It is important to note that the range and rate of decline depends upon genetics and age. This makes an important point—NAD+ could be beneficial for longevity as a factor that could contribute to decreasing age-related diseases and enhancing human health. Simply put, NAD+ declines with age but could be restored with the supplementation of its precursors according to a 2014 study.
It is thought that DNA damage through aging can lead to some of the negative health outcomes associated with aging. With NAD+ replenishment, a 2017 study suggested that this DNA damage can be slowed, and DNA repair improved among cells in the body. The use of NMN as a precursor to NAD+ has also shown some promise in improving NAD+ levels. David Sinclair, a noted Harvard researcher studying NMN, takes it and has provided anecdotal evidence that his lipid profiles resemble that of someone half his age.
NAD+ Precursors and Their Role
NAD+ cannot be taken in its pure form. However, there are precursors for NAD+, two of the most common ones are Nicotinamide Riboside (NR) and Nicotinamide MonoNucleotide (NMN). These two supplements show promise for increasing the levels of NAD+ in the body.
Many current studies have focused on the role NAD+ precursors (NR and NMN) may have in extending lifespan. NMN has been suggested to help various organs in the body and improve vascularity. NAD+ has been suggested to help with things like energy metabolism, DNA repair, inflammation, and stress resistance in a 2020 study. It was also suggested that a deficiency in NAD+ could lead to metabolic diseases, cancer, age-related diseases, and neurodegenerative disorders.
The research has also suggested that energy stressors (like fasting and exercise) can help increase intracellular NAD+ levels. This provides a practical method for improving NAD+ levels or at least limiting its decline by focusing on exercise and caloric restriction. There are also some specific foods that contain levels of NAD+ precursors.
A 2017 paper suggested some of the precursors are known to be nicotinamide (NAM), nicotinic acid (NA), tryptophan (Trp), nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and niacin. Some of the foods that contain these precursors are eggs, fish, meat, dairy, vegetables, and whole grains.
Why NAD+ Supplements Use Precursors
Because you cannot take NAD+ itself as a supplement, you take the precursors to NAD+ in a supplemental form which can then improve NAD+ levels in the body. This is similar to how Vitamin-A supplementation may require the precursor beta-carotene to be converted into Vitamin-A within the body.
You can’t take NAD+ on its own because it is a large molecule. It is so large that it cannot be readily absorbed by the body. However, several studies reviewed in 2021 suggested that the use of NAD+ precursors had positive outcomes in the elderly or people who already had a history of disease or a negative health outcome.
Current Research and Future Directions
So far with NAD+ research, studies in humans are less advanced and still in the developmental stage. There have been some clinical trials that suggested NMN, and NR are safe and effective for increasing NAD+. However, because this is still a new area of study, future research needs to be completed on humans to determine standardization for dosages and protocols for use.
There are very few studies on the long-term effects of NAD+ and precursor supplementation. Future research would need to determine exactly which precursors are most effective for improving NAD+ levels for individuals with various health concerns. Research on this matter is still in its infancy and there may be other significant roles NAD+ plays in the body of which we are not aware.
The present research on NAD+ and its precursors is promising and shows there could be benefits for its use. Future clinical trials will build on the practical and mainstream use of NAD+ as a viable anti-aging medicine.
References
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017). NAD+ in aging: Molecular mechanisms and translational implications. Trends in Molecular Medicine, 23(10), 899–916. https://doi.org/10.1016/j.molmed.2017.08.001
Imai, S., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology, 24(8), 464–471. https://doi.org/10.1016/j.tcb.2014.04.002
Shade C. (2020). The science behind NMN-A stable, reliable NAD+Activator and anti-aging molecule. Integrative medicine (Encinitas, Calif.), 19(1), 12–14.
She, J., Sheng, R., & Qin, Z. H. (2021). Pharmacology and potential implications of nicotinamide adenine dinucleotide precursors. Aging and disease, 12(8), 1879–1897. https://doi.org/10.14336/AD.2021.0523
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
