The Dark Side of NAD: Nicotinamide Riboside (NR), one of the precursors to Nicotinamide Adenine Dinucleotide (NAD+), has recently been making headlines as a miracle cure for various symptoms and a biohacking tool to optimize health. It has been sold to boost energy, recover faster, improve cardiovascular health, and improve metabolism—but is NR supplementation the answer? New studies suggest a dark side to NR you may not have considered.

What is Nicotinamide Riboside?

Nicotinamide Riboside (NR) is a form of vitamin B3 and is well known because it acts as a precursor to nicotinamide adenine dinucleotide, also known as NAD+. A desire to increase NAD+ levels has become popular due to the various studies linking it to anti-aging effects like cognitive sharpness and maintaining muscle.^1-2 Since NAD+ levels drop with age, many people focus on increasing their levels as a longevity “hack”.³ NR has risen in popularity recently since many people have found their NAD+ levels increasing the supplementation of NR.⁴

The Dark Side of NAD: NR is Not A Miracle Cure

When something becomes popular in the holistic health space, it often spreads like wildfire. Everyone is looking for a secret supplement to help expand longevity, look more youthful, or improve performance. NAD+ and NR have become popular supplements, making headlines as a miracle cure to all.⁵  NAD+ became especially popular as an IV therapy in the biohacking realm, reaching mainstream health clinics across America.

There is much science to support the beneficial use of NR and NAD+ in various areas of health, including neurological, metabolic, and cardiovascular health.^6-7  New research, however, suggests there may also be a dark side to NR and that the miracle cure supplement may, in fact, cause harm to certain people.⁸

The study discovered that high levels of Nicotinamide Riboside (the precursor to NAD+) could increase someone’s risk of developing triple-negative breast cancer and cause cancer to metastasize or spread to the brain.⁸

This complicates things since one of NR’s widespread uses is to mitigate the side effects of pharmaceutical treatments for cancer. But could the very thing use to minimize the side effects of one illness cause the spread of the disease itself? It appears so.⁸

What are the Alternatives?

Many of the things people use NR for are great goals to have. Caring for your nervous system, cardiovascular system, or metabolism is worth prioritizing, but it’s important not to take a cookie-cutter approach. There are many ways to raise NAD+ naturally, including ^9-14

• Exercise
• A low-carb diet
• Intermittent fasting
• Sauna sessions
• Optimizing your circadian rhythm
• Avoid alcohol

That being said, the use of supplementation can have a tremendous impact on achieving your goals. Of course, there are no two paths alike, but there are many different ways to achieve your goal using other supplements, foods, and lifestyle choices. Here are some simple swaps for some of the various objectives associated with increasing levels of NAD+.^15-18

• For building muscle, try essential amino acids
• For cardiovascular health, try EPA and DHA
• For a cognitive boost, try exogenous ketones 
• For improved energy levels, try ATP-boosting vitamins and minerals

The Dark Side of NAD: Summary

Although Nicotinamide Riboside has skyrocketed in popularity recently due to its ability to increase NAD+ levels in the body, there is no one-size-fits-all approach to achieving any goal. New studies show that NR may also drive the development and spread of certain cancers, highlighting the need for bio-individual approaches to health. Although many goals people pursue that drive the supplementation of NR may be fantastic goals, there are always many different ways to get there.

References

1. Gong, Bing et al. “Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models.” Neurobiology of aging vol. 34,6 (2013): 1581-8. doi:10.1016/j.neurobiolaging.2012.12.005
2. Frederick, David W et al. “Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle.” Cell metabolism vol. 24,2 (2016): 269-82. doi:10.1016/j.cmet.2016.07.005
3. Massudi, Hassina et al. “Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.” PloS one vol. 7,7 (2012): e42357. doi:10.1371/journal.pone.0042357
4. “NAD Benefits.” About NAD, www.aboutnad.com/nad-benefits.
5. Okabe, K., Yaku, K., Tobe, K. et al. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci 26, 34 (2019). https://doi.org/10.1186/s12929-019-0527-8
6. Lautrup, Sofie et al. “NAD+ in Brain Aging and Neurodegenerative Disorders.” Cell metabolism vol. 30,4 (2019): 630-655. doi:10.1016/j.cmet.2019.09.001
7. 7 Braidy, Nady, and Yue Liu. “Can Nicotinamide Riboside Protect against Cognitive Impairment?” Current Opinion in Clinical Nutrition & Metabolic Care, vol. 23, no. 6, 2020, pp. 413–420., doi:10.1097/mco.0000000000000691.
8. 8 Maric, Tamara, et al. “A Bioluminescent-Based Probe for in Vivo Non-Invasive Monitoring of Nicotinamide Riboside Uptake Reveals a Link between Metastasis and NAD+ Metabolism.” Biosensors and Bioelectronics, vol. 220, 2022, p. 114826., doi:10.1016/j.bios.2022.114826.
9. 9 Cantó, Carles et al. “Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle.” Cell metabolism vol. 11,3 (2010): 213-9. doi:10.1016/j.cmet.2010.02.006
10. 10 Elamin, Marwa et al. “Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?.” Frontiers in molecular neurosciencevol. 10 377. 14 Nov. 2017, doi:10.3389/fnmol.2017.00377
11. 11 Houtkooper, Riekelt H., and Johan Auwerx. “Exploring the Therapeutic Space around NAD+.” Journal of Cell Biology, vol. 199, no. 2, 2012, pp. 205–209., doi:10.1083/jcb.201207019.
12. 12 Raynes, Rachel Rene. “SIRT1 Regulation of The Heat Shock Response in an HSF1-Dependent Manner and the Impact of Caloric Restriction.” Digital Commons at University of South Florida, scholarcommons.usf.edu/etd/4567/.
13. 13 Ramsey, Kathryn Moynihan et al. “Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.” Science (New York, N.Y.) vol. 324,5927 (2009): 651-4. doi:10.1126/science.1171641
14. 14 Cederbaum, Arthur I. “Alcohol metabolism.” Clinics in liver disease vol. 16,4 (2012): 667-85. doi:10.1016/j.cld.2012.08.002
15. 15 Børsheim, Elisabet et al. “Effect of amino acid supplementation on muscle mass, strength and physical function in elderly.” Clinical nutrition (Edinburgh, Scotland) vol. 27,2 (2008): 189-95. doi:10.1016/j.clnu.2008.01.001
16. 16 Innes, Jacqueline K, and Philip C Calder. “Marine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020.” International journal of molecular sciences vol. 21,4 1362. 18 Feb. 2020, doi:10.3390/ijms21041362
17. 17 Jensen, Nicole Jacqueline et al. “Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases.” International journal of molecular sciences vol. 21,22 8767. 20 Nov. 2020, doi:10.3390/ijms21228767
18. 18 Dunn, Jacob, and Michael H Grider. “Physiology, Adenosine Triphosphate.” National Library of Medicine , NCBI, www.ncbi.nlm.nih.gov/books/NBK553175/.