The Impact of NAD+ on Mitochondria

If you’ve ever wondered why we slow down as we get older and become more prone to illness and injury, it’s time to consider NAD+ and what it can do for you. Nicotinamide adenine dinucleotide (NAD+) is a vitally important molecule that hundreds of chemical reactions and processes within each cell rely on to work correctly. NAD+ works as a coenzyme, directly and indirectly affecting metabolism, DNA health and repair, cellular aging, and the proper functioning of the immune system.

As we age, NAD+ production declines steeply, causing the cellular repair systems that rely on it to accumulate damage that doesn’t get fixed correctly, if at all. As this deep cellular damage builds up, our cells become increasingly less able to rejuvenate themselves. Basic chemical reactions that produce energy inside our tissues also slow down when NAD++ supplies drop off.

How Does NAD+ Work?

NAD+ works by enabling the chemical and biological processes that regulate hundreds of functions in each cell. It’s found in most of the cells in the body, located within the interior fluids of cells (cytoplasm), the storage site of cellular genetic material (the nucleus), and the mitochondria, each cell’s center of energy production.

NAD+ is required by the mitochondria of every cell to produce and use adenosine triphosphate (ATP), the most basic fuel needed by each cell of the body. Inadequate amounts of NAD+ cause cells to become sluggish, inefficient, and in cases of severe NAD+ deficiency, to die prematurely, accelerating the aging process. Without ATP, all life functions of every cell in your body would halt within minutes, but it’s important to recognize that ATP production is not all that NAD+ does.

NAD+ as a Cofactor

NAD+ is a coenzyme, a type of cofactor. Cofactors help enzymes work by turning them off or on and modulating how rapidly they work. Cofactors like NAD+ aren’t part of the chemical reactions themselves; instead, they control when and how the reactions take place. Without NAD+, many biological processes would either not work at all or would work at the wrong speed. Its extreme versatility makes NAD+ one of the most important cofactors in the body, responsible for controlling over 500 biological functions, including cell aging, cellular metabolism, tissue repair, and DNA repair.

Low NAD+ is associated with numerous illnesses and health issues, such as type II diabetes, chronic inflammation, chronic fatigue, insulin resistance, degenerative disorders of the brain, and many diseases and conditions associated with aging. Low NAD+ is also partially responsible for the loss of elasticity in facial tissues, wrinkles, and aged-looking skin.

The Roles of NAD+

NAD+ does many things. Here are some of the highlights:

Activates Sirtuins 

Sirtuins are proteins that manage cellular aging, repair DNA, regulate the creation of mitochondria, regulate glucose metabolism within the cells, and inhibit inflammation. Sirtuins control how long cells live and how active they are during their lifespans, which has led researchers to focus on them as major factors in human aging. Plentiful NAD+ is a requirement for activating all of the sirtuins. Put simply, without NAD+, sirtuins won’t work at all and all the functions that rely on them will fail.

Supports Brain Tissue Health

Brain tissue demands more of the body’s energy and nutrients than any other organ in the body but making use of those nutrients calls for plentiful amounts of NAD+. A lack of healthy levels of NAD+ reduces the activity of brain cells and makes them less able to send and receive signals from each other. In fact, poor NAD+ levels are associated with brain fog, poor concentration, impaired memory, and poor mental focus. Low NAD+ is also correlated with several neurodegenerative disorders and dementia, such as Alzheimer’s.

Getting enough NAD+ is also required for the production of dopamine, serotonin, and norepinephrine, the neurotransmitters that are necessary for a stable mood, our ability to feel pleasure and manage pain, and for creating and retrieving memories. These neurotransmitters also control our circadian rhythm (sleep-wake cycle), our ability to focus and concentrate, as well as dozens of other critical body functions.

Boosts Immune System Health

NAD+ can modulate the functioning of the immune system by controlling inflammation and prompting the activation of sirtuins, particularly SIRT6. NAD+ also helps improve the immune system’s effectiveness by increasing the number of T-cells during illness. T-cells also fight infections and attack cancer cells.

Supports Muscle Health

NAD+ helps muscle cells regenerate after exercising, allowing muscle tissue to grow stronger. This same process allows muscles to heal after injuries. Because muscles use a great deal of energy during exercise or vigorous activity, they must have large amounts of NAD+ to properly use glucose and other nutrients to contract and lengthen correctly.

Improves Weight Loss

Healthy levels of NAD+ help cells produce energy. Inadequate levels of NAD+ cause a person’s metabolism to slow down dramatically. Because NAD+ is necessary for cells to break down and use glucose, not getting enough NAD+ causes blood sugar levels to rise, causing system inflammation, while dramatically slowing metabolism. By restoring NAD+ levels to their optimum level, it becomes easier to lose weight.

Fights Fatigue

Because NAD+ is required for cells to produce energy correctly, it makes sense that low amounts of NAD+ lead to fatigue.

Where Do We Get NAD+?

Some foods can increase your NAD+ supplies. They include:

• Mushrooms
• Green vegetables
• Whole grains
• Foods made from yeast
• Fish (sardines, tuna, salmon)

Other ways to increase your NAD+ include fasting and exercise, which are healthy habits. However, fasting and exercise take time to start delivering benefits. The most rapid and convenient way to experience the vast benefits of improved NAD+ levels that you need is through supplementation, which can be in the form of oral supplements or IV therapy.

Not only is NAD+ supplementation the most convenient way to increase your NAD+, but it delivers higher levels of NAD+ than diet, exercise, or fasting can.

Resources

• Berry, J. (n.d.). Neurotransmitters: What they are, functions, and psychology. Medical News Today. Retrieved July 26, 2022, from https://www.medicalnewstoday.com/articles/326649#types
• Dali-Youcef, N. (2009, July 8). Sirtuins: The 'magnificent seven', function, metabolism and longevity. Annals of medicine. Retrieved July 26, 2022, from https://pubmed.ncbi.nlm.nih.gov/17701476/
• Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). 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
• Cuenoud, B., Ipek, Ö., & Shevlyakova, M. (2021, September 16). Brain Nad is associated with ATP energy production and membrane phospholipid turnover in humans. Frontiers in Aging Neuroscience. Retrieved July 26, 2022, from https://www.frontiersin.org/articles/10.3389/fnagi.2020.609517/full
• Dopamine: What it is, Function & Symptoms. Cleveland Clinic. (n.d.). Retrieved July 26, 2022, from https://my.clevelandclinic.org/health/articles/22581-dopamine
• Grabowska, W., Sikora, E., & Bielak-Zmijewska, A. (2017). Sirtuins, a promising target in slowing down the ageing process. Biogerontology, 18(4), 447–476. https://doi.org/10.1007/s10522-017-9685-9
• Grahnert A, Grahnert A, Klein C, Schilling E, Wehrhahn J, Hauschildt S. Review: NAD +: a modulator of immune functions. Innate Immun. 2011;17(2):212-233. https://journals.sagepub.com/doi/pdf/10.1177/1753425910361989
• Goody, M. F., & Henry, C. A. (2018). A need for NAD+ in muscle development, homeostasis, and aging. Skeletal muscle, 8(1), 9. https://doi.org/10.1186/s13395-018-0154-1
• Kane, Alice, & Sinclair, D. (2018, September 13). Sirtuins and NAD+ in the development and treatment of metabolic and cardiovascular diseases. Circulation Research. Retrieved July 26, 2022, from https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.118.312498
• Lautrup, S., Sinclair, D., Mattson, M., & Fang, E. (2019, October 1). NAD+ in Brain Aging and Neurodegenerative Disorders. Cell metabolism. Retrieved July 26, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787556/
• Li W, Sauve AA. NAD+⁺ content and its role in mitochondria. Methods Mol Biol. 2015;1241:39-48. doi:10.1007/978-1-4939-1875-1_4
• Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. https://pubmed.ncbi.nlm.nih.gov/22848760/
• Miranda, D. (n.d.). Mayo Clinic Finds Potent NAD+ Booster Promotes Inflammatory Response. NAD+ Aging and Science. Retrieved July 26, 2022, from https://www.nad.com/news/nad-precursor-nrh-inflammation-macrophage-immune-cells
• Mehmel, M., Jovanović, N., & Spitz, U. (2020). Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients, 12(6), 1616. https://www.mdpi.com/2072-6643/12/6/1616/htm
• Montemayor-Quellenberg, M. (2014, October 14). New discovery in regulating autoimmune diseases. New Discovery in Regulating Autoimmune Diseases | Harvard Medical School. Retrieved July 26, 2022, from https://hms.harvard.edu/news/new-discovery-regulating-autoimmune-diseases
• Rappou E, Jukarainen S, Rinnankoski-Tuikka R, et al. Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue. J Clin Endocrinol Metab. 2016;101(3):1263-1273. doi:10.1210/jc.2015-3054
• What is NAD+? What is NAD+? | Nicotinamide Adenine Dinucleotide. (n.d.). Retrieved July 26, 2022, from https://NAD+.com/what-is-NAD+
• Yaku, K., Okabe, K., Gulshan, M. et al. Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD). Sci Rep 9, 13102 (2019). https://doi.org/10.1038/s41598-019-49547-6
• Ying W. NAD++ and NAD+H in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888. Published 2007 Jan 1. https://europepmc.org/article/MED/17127427
• Zhao, Y., Zhang, J., Zheng, Y. et al. NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation 18, 207 (2021). https://doi.org/10.11