The Risk and Reward of NAD+: Unlocking Longevity Potential

03/08/2025 | Energetic Media |
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We are living in an age of unprecedented breakthroughs, with longevity and health optimization becoming central themes for both science and personal well-being. Among the advancements sparking curiosity, NAD+ and its related supplements—like NMN, NR, niacin, quercetin, and even direct NAD+ injections—are receiving significant attention. But when considering these trendy supplements, the question remains: Do they hold real promise, or are they just another ripple in an endless wave of fleeting health trends?

I suppose the answer depends on how you approach it. From my experience, viewing these supplements through a risk-reward lens—similar to how I’d weigh an investment—has helped me stay grounded in decisions about experimental health interventions. This way of thinking encourages me to remain skeptical of the hype while still considering the potential benefits. The result is a more measured approach, rooted in evidence, analysis, and common sense.

What Exactly is NAD+?

To unravel why NAD+ is causing a stir, we must first understand what it is. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every cell in your body. It’s involved in critical processes like energy metabolism, DNA repair, and cell communication. Imagine it as the silent workhorse, constantly laboring at the molecular level to keep our engines running efficiently.

However, NAD+ is not invincible. Scientific studies reveal that NAD+ levels decline as we age. This drop has been linked to conditions like neurodegeneration, cardiovascular disease, immune decline, and even metabolic dysfunction.1 And so naturally, the idea of replenishing NAD+ to reverse—or at least slow down—the effects of aging has captivated researchers and enthusiasts alike.

But therein lies the problem. The science supporting NAD+ interventions is still in its infancy. It’s one thing to raise NAD+ levels in mice or even humans; it’s another to categorically tie these increases to better longevity or specific health outcomes.

The NAD+ Supplement Landscape

Here’s where things get interesting. Because pure NAD+ struggles to enter cells due to its instability, many supplements rely on precursors like NMN and NR, which help the body produce NAD+. Additionally, other compounds such as quercetin and apigenin are used to prevent NAD+ breakdown, offering an indirect pathway to raising levels.

Animal studies show promising benefits regarding mitochondrial function, insulin sensitivity, and slowing aging2,3—but you are not a mouse. Most human research so far confirms we can indeed boost NAD+ levels with these supplements, though direct evidence of broader health rewards remains elusive.4

The Lifestyle Connection

Here’s a personal confession that might add a different perspective to this conversation. Before I jump into the latest “magic pill,” I always ask myself this critical question:

“Is it possible to achieve the same result naturally?”

For NAD+—the answer seems to lean toward “yes.” Decades of evidence support the effectiveness of healthful practices to optimize NAD+ production naturally. Some of these strategies may already play a role in your daily life:

  • Nutrition: Consuming high-quality whole foods naturally rich in NAD+ precursors (think proteins and foods containing vitamin B3) supports your body’s ability to produce NAD+.5
  • Ketogenic Diets: Though further research is needed, preliminary studies suggest that low-carb, high-fat diets may help enhance NAD+ levels by promoting more efficient cellular energy production.6
  • Exercise: Want a proven method to boost NAD+? Look no further than aerobic and resistance training, particularly as we age.7
  • Sleep: NAD+ levels are closely linked to our circadian rhythms.8 Maintaining good sleep hygiene can ensure the body doesn’t short-circuit its own NAD+ production processes.

If we focus on these sustainable practices first, we’re not just raising NAD+ levels—we’re creating a foundation for well-rounded health. Supplements can then be considered as an add-on rather than a first resort.

Balancing Risks and Rewards

That being said, NAD+ supplements are intriguing. We know how crucial NAD+ is for cellular function, and we’ve seen its decline tied directly to the aging process. But while the potential upside is incredibly appealing, it’s essential to acknowledge the risks and unknowns.

Here’s what gives me pause as I assess this emerging field:

  1. Lack of Long-Term Data: Safety studies for NAD+ boosters (like NMN and NR) generally show minimal short-term risks, but we lack insights into what happens with prolonged use in humans.9 The truth? No one knows what decades of supplementation might do.
  2. Cancer Concerns: On one hand, NAD+ appears to support healthy cells. Yet, studies suggest that it may also assist cancer cells by giving them the same energy boost.10-12 Does this make NAD+ supplementation risky for those with pre-existing vulnerabilities? Scientific consensus isn’t there yet, but the concern is real.
  3. Disrupting Natural Feedback Loops: The human body is a complex, resource-efficient system. Supplementing NAD+ externally could send signals telling your body to slow—or even stop—natural NAD+ production. This is conjecture, not fact, but the analogy of testosterone injections impairing natural production is difficult to ignore.

Who Stands to Benefit Most?

For someone young, active, and overall healthy, the risk-reward ratio just doesn’t feel worth it yet. Many of the benefits NAD+ enthusiasts tout might already be accessible through a balanced lifestyle. Why layer in unnecessary uncertainty?

For elderly individuals or those with specific health challenges linked to aging, however, NAD+ supplementation becomes an entirely different conversation. Here, the benefits might outweigh the risks, offering tangible improvements in quality of life. But even for this group, the targeted use of supplements should be driven by measurements—testing NAD+ levels first—and should supplement, not replace, lifestyle changes.

The Value of Metrics

One lesson I’ve learned time and time again is this—measurements guide action. We don’t start solving problems until we know they exist. The same is true here. If you suspect your NAD+ levels are low, get tests done. Understand why they’re low, and explore gentle interventions first. Relying on metrics ensures we supplement only based on need, rather than theoretical benefits.

My Closing Reflection

NAD+ supplements are undoubtedly exciting. But so are countless other scientific frontiers that have, with time, proven disappointing. That’s not to say I’m pessimistic. If anything, I feel optimistic that the ongoing research in this space has the potential to revolutionize how we think about aging.

For now, I remain grounded in what is certain. Nature has already equipped our bodies with the tools to thrive—provided we meet it halfway. Proper nutrition, intentional movement, restorative sleep, and meaningful choices are the fundamentals that will elevate anyone’s baseline health.

You can always go back to the fancy stuff later.

If you’ve found this insight helpful—or want to share your thoughts—don’t hesitate to reach out. I’m always thrilled to learn what others have discovered on this shared quest for lasting vitality. And rest assured—if new data tips the scale in any direction, I’ll be the first to shine a light on it.

References

  1. Covarrubias, A.J., Perrone, R., Grozio, A. et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 22, 119–141 (2021). https://doi.org/10.1038/s41580-020-00313-x
  2. Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., Schoonjans, K., Menzies, K. J., & Auwerx, J. (2016). NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (New York, N.Y.), 352(6292), 1436–1443.
  3. Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., Yoshino, J., & Imai, S. I. (2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell metabolism, 24(6), 795–806.
  4. Freeberg, K. A., Udovich, C. C., Martens, C. R., Seals, D. R., & Craighead, D. H. (2023). Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions. The journals of gerontology. Series A, Biological sciences and medical sciences, 78(12), 2435–2448.
  5. Bogan, K. L., & Brenner, C. (2008). Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annual review of nutrition, 28, 115–130. https://doi.org/10.1146/annurev.nutr.28.061807.155443
  6. Elamin, M., Ruskin, D. N., Masino, S. A., & Sacchetti, P. (2017). Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?. Frontiers in molecular neuroscience, 10, 377. https://doi.org/10.3389/fnmol.2017.00377
  7. de Guia, R. M., Agerholm, M., Nielsen, T. S., Consitt, L. A., Søgaard, D., Helge, J. W., Larsen, S., Brandauer, J., Houmard, J. A., & Treebak, J. T. (2019). Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiological reports, 7(12), e14139.
  8. Chen, Q., Xiao, J., Lin, Z., Xu, X., & Chen, J. (2024). NAD+ supplement relieved chronic sleep restriction (CSR)-induced microglial proinflammation in vivo and in vitro. Journal of neuroimmunology, 397, 578469. https://doi.org/10.1016/j.jneuroim.2024.578469
  9. Poljšak, B., Kovač, V., & Milisav, I. (2022). Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies. Antioxidants (Basel, Switzerland), 11(9), 1637. https://doi.org/10.3390/antiox11091637
  10. Palmer RD, Vaccarezza M. Nicotinamide adenine dinucleotide and the sirtuins caution: Pro-cancer functions. Aging Med (Milton). 2021 Nov 30;4(4):337-344. doi: 10.1002/agm2.12184. PMID: 34964015; PMCID: PMC8711221.
  11. Kennedy, B. E., Sharif, T., Martell, E., Dai, C., Kim, Y., Lee, P. W., & Gujar, S. A. (2016). NAD+ salvage pathway in cancer metabolism and therapy. Pharmacological research, 114, 274–283. https://doi.org/10.1016/j.phrs.2016.10.027
  12. Garten, A., Schuster, S., Penke, M., Gorski, T., de Giorgis, T., & Kiess, W. (2015). Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nature reviews. Endocrinology, 11(9), 535–546. https://doi.org/10.1038/nrendo.2015.117