What is NAD+ and why is it so important?
08 Nov 2021
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What is NAD+ and why is it so important?
Optimized energy, better aging, more drive, higher metabolism. These vital elements of wellbeing have a huge impact on our short- and long-term health. Yet scientists have shown that much of how we survive and thrive is controlled by just one tiny molecule: NAD+.
Here we’ll cover everything you need to know about why NAD+ is essential to your health, how NAD+ decreases with age, and why boosting NAD+ with NMN might be an optimal choice to keep your body working at its best.
What is NAD+?
NAD+ (nicotinamide adenine dinucleotide) is a naturally occurring molecule found in all living cells. The technical term for NAD+ and molecules like it is ‘coenzyme’ – but an easier way to think of NAD+ is as a ‘helper’ molecule.
- Enzyme = a substance that sparks or speeds up chemical reactions in living things
- Coenzyme (like NAD+) = a ‘helper’ molecule that enables enzymes to go about their business
NAD+ is an essential helper molecule in the chemical reactions in your cells that turn food into energy (otherwise know as metabolism) and powers cellular processes that keep you alive.
Why is NAD+ so important?
NAD+ is one of the most important molecules in the body because of its key role in providing cells with energy.
When you think about energy and the human body, you usually think of large movements that need lots of power – activities like playing sport, running for the bus, jugging kids, or carrying groceries.
But NAD+ helps create energy your body uses for hundreds of other processes you don’t even notice, like repairing damage, fighting infection, combating inflammation, fueling brain function, even warding off the effects of aging itself. There is almost no biological process that doesn’t need NAD+1.
When you think about energy and the human body, you usually think of large movements that need lots of power – activities like playing sport, running for the bus, jugging kids, or carrying groceries.
But NAD+ helps create energy your body uses for hundreds of other processes you don’t even notice, like repairing damage, fighting infection, combating inflammation, fueling brain function, even warding off the effects of aging itself. There is almost no biological process that doesn’t need NAD+1.
NAD+ is a natural battery charger
In its role as a helper molecule, NAD+ activates enzymes that help generate over 90% of your body’s energy. It binds to enzymes and transfers tiny units of energy (electrons) between molecules. By transferring electrons in this way, NAD+ is part of a process that is like recharging a battery.
A battery gets drained when electrons are released to deliver energy. Those electrons need help returning to their starting point so they can create more energy. NAD+ moves electrons back and forth in this process, charging and recharging your cells so they can go about the very important business of keeping your body running2.
A battery gets drained when electrons are released to deliver energy. Those electrons need help returning to their starting point so they can create more energy. NAD+ moves electrons back and forth in this process, charging and recharging your cells so they can go about the very important business of keeping your body running2.
Where do you get NAD+ from?
Your body naturally makes NAD+ from other smaller molecules. These raw ingredients are called precursors.
You absorb precursors mostly from diet (several NAD+ precursors are forms of vitamin B3). Once they enter your body, precursors are put on a biological factory production line called a pathway, which is basically a series of chemical reactions that result in NAD+.
Your body uses two different production lines to create nicotinamide adenine dinucleotide. One creates NAD+ from scratch (called the denovo pathway). The other production line reuses and recycles some of the ingredients used in NAD+ production (called the salvage pathway). Although there are multiple production lines, they all lead to the same product: NAD+3.
NAD+ declines with age
The fact that NAD+ is the most abundant molecule in your body besides water confirms how vital it is to your wellbeing.
But despite its critical importance to your health, levels of NAD+ decline as you get older4. By age 65 you have about half the NAD+ you had at 305.
Scientists believe this rapid decline is driven by two events: a reduction in the amount of NAD+ your body creates as you get older (even if other factors like diet and exercise remain unchanged)6, coupled with a depletion of NAD+ supplies caused by NAD+ consuming enzymes7.
Unfortunately, the more your NAD+ pool is depleted, the less fuel there is to support the hundreds of processes which keep your body running. Declining NAD+ is one of the main drivers of the development of mitochondrial dysfunction, metabolic abnormalities, and age-related diseases4, which all come at a serious cost to your health.
But despite its critical importance to your health, levels of NAD+ decline as you get older4. By age 65 you have about half the NAD+ you had at 305.
Scientists believe this rapid decline is driven by two events: a reduction in the amount of NAD+ your body creates as you get older (even if other factors like diet and exercise remain unchanged)6, coupled with a depletion of NAD+ supplies caused by NAD+ consuming enzymes7.
Unfortunately, the more your NAD+ pool is depleted, the less fuel there is to support the hundreds of processes which keep your body running. Declining NAD+ is one of the main drivers of the development of mitochondrial dysfunction, metabolic abnormalities, and age-related diseases4, which all come at a serious cost to your health.
How does NAD+ support health?
Research has shown that maintaining levels of NAD+ throughout your life can have profound effects on your wellbeing.
Heart health
NAD+ has been shown to improve cardiovascular functions in humans. Studies have shown that disturbances in NAD+ in heart muscle are linked to dysfunction in the failing heart.
Research indicates that stabilizing NAD+ levels is a promising strategy for improving cardiac function8, and may be linked to beneficial impacts on heart conditions9.
Research indicates that stabilizing NAD+ levels is a promising strategy for improving cardiac function8, and may be linked to beneficial impacts on heart conditions9.
Muscle repair
Your muscles need NAD+ (and the healthy mitochondria to which NAD+ is essential) to generate the energy they need to contract and relax. Multiple studies have shown that replenishing reduced NAD+ levels can help maintain muscle function10,11.
This is important because after age 30 you begin to lose around 3% to 8% of your muscle mass per decade. The rate of decline accelerates after you hit age 6012. Less muscle means greater weakness and less mobility, reduced strength and exercise capacity, and increased risk of falls and fractures later in life.
This is important because after age 30 you begin to lose around 3% to 8% of your muscle mass per decade. The rate of decline accelerates after you hit age 6012. Less muscle means greater weakness and less mobility, reduced strength and exercise capacity, and increased risk of falls and fractures later in life.
Energy creation
As we mentioned earlier, one of the main roles of NAD+ is energy production. It carries electrons from one place to another, which makes it essential to creating not just the energy that helps you move throughout the day, but also the energy that powers the entire network of systems and organs which keep you alive and well.
The cellular ‘respiration’ process of turning nutrients into energy using NAD+ is the foundation of a healthy metabolism. In other words, NAD+ is the beginning of every energy-driven process that maintains health in your body.
The cellular ‘respiration’ process of turning nutrients into energy using NAD+ is the foundation of a healthy metabolism. In other words, NAD+ is the beginning of every energy-driven process that maintains health in your body.
Inflammation and immunity
As you age your immune system declines. You can get sick more easily, and it becomes harder to bounce back from illnesses. Because NAD+ declines with age, your body’s ability to manage the chronic and low-grade inflammation (called inflammaging; a key driver of many age-related diseases like hypertension, diabetes, atherosclerosis, and cancer13) is lessened.
Multiple studies have demonstrated that regulating NAD+ levels could be an effective strategy to control inflammaging. It has also been shown to help regulate diseases driven by chronic inflammation, such as neurodegenerative diseases and some cancers13,14,15.
Multiple studies have demonstrated that regulating NAD+ levels could be an effective strategy to control inflammaging. It has also been shown to help regulate diseases driven by chronic inflammation, such as neurodegenerative diseases and some cancers13,14,15.
Brain health
NAD+ has been shown to play important roles in metabolic processes in your brain. It has positive effects on brain function such as earning, memory, and transmitting messages between cells16.
As you get older, particularly from middle age onwards, changes can start to occur within the brain that may trigger a gradual decline in mental capabilities. This is known as age-related cognitive decline, and it typically results in people becoming more forgetful and less mentally sharp. In severe instances, it can lead to dementia. By supporting metabolic processes in your brain NAD+ can support vital aspects of robust cognitive health16.
As you get older, particularly from middle age onwards, changes can start to occur within the brain that may trigger a gradual decline in mental capabilities. This is known as age-related cognitive decline, and it typically results in people becoming more forgetful and less mentally sharp. In severe instances, it can lead to dementia. By supporting metabolic processes in your brain NAD+ can support vital aspects of robust cognitive health16.
Insulin sensitivity
Insulin is an important hormone that controls many bodily processes. However, insulin problems are at the heart of many modern health conditions. When your cells stop responding properly to insulin it can disrupt the balance of blood sugar levels. This can lead to the onset of type 2 diabetes, which in turn can result in other complications like heart and blood vessel disease, eye damage, kidney conditions, and more.
Treatment with NMN, a molecule your body uses to create NAD+, has been shown to substantially improve insulin sensitivity in pre-diabetic humans17. It has also been shown to reduce insulin sensitivity in subjects with age-related diabetes18,19. These results highlight NMN as an effective path for correcting declines in the way your body responds to insulin as you get older.
Treatment with NMN, a molecule your body uses to create NAD+, has been shown to substantially improve insulin sensitivity in pre-diabetic humans17. It has also been shown to reduce insulin sensitivity in subjects with age-related diabetes18,19. These results highlight NMN as an effective path for correcting declines in the way your body responds to insulin as you get older.
DNA repair
Encoded within your DNA are numerous processes that detect and repair damage inflicted by environmental and internal forces throughout your life. Yet, as good as your body is at repairs, the fix is not always perfect, and damage accumulates. Over time, repair systems fail to correct all the DNA damage and the result is aging and disease.
NAD+ is essential to DNA repair. The proteins in charge of the process use NAD+ as fuel to perform their vital functions20. When NAD+ is plentiful, it can also prevent the action of some proteins that meddle with your body’s ability to mend damaged DNA21. If NAD+ is not present in cells to stop this harmful interaction or to fuel repair, DNA breaks are not fixed. This can lead to cellular damage which drives the aging process itself.
NAD+ is essential to DNA repair. The proteins in charge of the process use NAD+ as fuel to perform their vital functions20. When NAD+ is plentiful, it can also prevent the action of some proteins that meddle with your body’s ability to mend damaged DNA21. If NAD+ is not present in cells to stop this harmful interaction or to fuel repair, DNA breaks are not fixed. This can lead to cellular damage which drives the aging process itself.
Sleep
NAD+ helps regulate circadian rhythms, keeping important processes that rely on a 24-hour cycle (energy metabolism, hormone regulation, body temperature, even the production of NAD+ itself) in sync and working at their best.
A properly functioning 24-hour body cycle is important because misaligned circadian rhythms lead to sleep deprivation, which in turn can have profound consequences on your physical and mental health.
A properly functioning 24-hour body cycle is important because misaligned circadian rhythms lead to sleep deprivation, which in turn can have profound consequences on your physical and mental health.
Can you take NAD+ as a supplement?
Unfortunately, NAD+ can’t be used as a direct supplement because it is not easily absorbed. It’s too large to freely enter cells and is therefore unavailable to be used by your body in all the processes that benefit your health and aging23.
How to boost NAD+ naturally
Luckily for us, our cells are excellent at using NAD+ precursors (remember the building blocks of NAD+ we mentioned earlier?) to make NAD+ naturally. Adding more of the raw ingredients enables your body to make extra amounts of essential NAD+.
The next best thing to taking NAD+ itself is supplementing with NMN (nicotinamide mononucleotide). Like NAD+, NMN is a natural molecule that occurs in all life forms. Supplementing with NMN increases the amount of material available for your body to create more NAD+.
Nicotinamide mononucleotide is just one small chemical reaction away from being NAD+ itself. It is the final stage on the biological production line your body uses to make NAD+. In numerous studies, NMN supplementation has been shown to increase the amount of NAD+ in the body and to improve age-related inflammation, insulin insensitivity, glucose intolerance, mitochondrial dysfunctions, and more24.
This clinical and preclinical evidence highlights NMN as a promising way to counter age-associated diseases and support the foundations of your health.
The next best thing to taking NAD+ itself is supplementing with NMN (nicotinamide mononucleotide). Like NAD+, NMN is a natural molecule that occurs in all life forms. Supplementing with NMN increases the amount of material available for your body to create more NAD+.
Nicotinamide mononucleotide is just one small chemical reaction away from being NAD+ itself. It is the final stage on the biological production line your body uses to make NAD+. In numerous studies, NMN supplementation has been shown to increase the amount of NAD+ in the body and to improve age-related inflammation, insulin insensitivity, glucose intolerance, mitochondrial dysfunctions, and more24.
This clinical and preclinical evidence highlights NMN as a promising way to counter age-associated diseases and support the foundations of your health.
The future of NAD+
The benefits of NAD+ are many. It’s ability to promote bodywide health, recharge energy, support healthy aging, spark vitality, balance immunity, support vital organ and system function, and nurture better sleep has been well documented.
Scientists continue to research NAD+ and its precursors, searching to unveil even more secrets of this life-giving molecule. Thanks to a rapidly growing number of clinical studies demonstrating its vital role in human health, NAD+ boosting is the go-to solution for people seeking to optimize their wellbeing and live life to the fullest now, and in the years ahead.
Scientists continue to research NAD+ and its precursors, searching to unveil even more secrets of this life-giving molecule. Thanks to a rapidly growing number of clinical studies demonstrating its vital role in human health, NAD+ boosting is the go-to solution for people seeking to optimize their wellbeing and live life to the fullest now, and in the years ahead.
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Elevant supplements deliver far more than what traditional supplements can. Prime and Optima work at a cellular level to nourish the building blocks of your health and support better wellbeing, energy and aging.
References
1. Hong W, Mo F, Zhang Z, Huang M, Wei X. Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism. Front Cell Dev Biol. 2020;8:246
2. Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53
3. Xie, N., Zhang, L., Gao, W. et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Sig Transduct Target Ther 5, 227 (2020)
4. Chini CCS, Tarragó MG, Chini EN. NAD and the aging process: Role in life, death and everything in between. Mol Cell Endocrinol. 2017 Nov 5;455:62-74
5. Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It's Destroyed. Cell Metab. 2016;23(6):965-966
6. Yoshino J, Mills KF, Yoon MJ & Imai S Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528–536
7. Camacho-Pereira J et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 23, 1127–1139
8. Walker MA, Tian R. Raising NAD in Heart Failure: Time to Translate?. Circulation. 2018;137(21):2274-2277
9. Vignier N, Chatzifrangkeskou M, Morales Rodriguez B, et al. Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2018 Nov 15;27(22):3870-3880
10. Romani M, Sorrentino V, Oh CM, et al. NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle. Cell Rep. 2021;34(3):108660
11. Ryu D, Zhang H, Ropelle ER, et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci Transl Med. 2016;8(361):361ra139
12. Volpi E, Nazemi R, Fujita S. Muscle tissue changes with aging. Curr Opin Clin Nutr Metab Care. 2004;7(4):405-410
13. Covarrubias AJ, Kale A, Perrone R, et al. Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nat Metab. 2020;2(11):1265-1283
14. Minhas PS, Liu L, Moon PK, et al. Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation. Nat Immunol. 2019;20(1):50-63
15. Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports. 2019;28(7):1717-1728.e6
16. Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem. 2006 Aug 4;281(31):21745-21754
17. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. Published online April 22, 2021
18. Basu R, Breda E, Oberg AL, et al. Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes. 2003;52(7):1738-1748
19. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536
20. Wilk, A., Hayat, F., Cunningham, R. et al. Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. Sci Rep 10, 651 (2020)
21. Jun Li, Michael S. Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A. Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. SCIENCE24 MAR 2017 : 1312-1317
22. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141
2. Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53
3. Xie, N., Zhang, L., Gao, W. et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Sig Transduct Target Ther 5, 227 (2020)
4. Chini CCS, Tarragó MG, Chini EN. NAD and the aging process: Role in life, death and everything in between. Mol Cell Endocrinol. 2017 Nov 5;455:62-74
5. Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It's Destroyed. Cell Metab. 2016;23(6):965-966
6. Yoshino J, Mills KF, Yoon MJ & Imai S Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528–536
7. Camacho-Pereira J et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 23, 1127–1139
8. Walker MA, Tian R. Raising NAD in Heart Failure: Time to Translate?. Circulation. 2018;137(21):2274-2277
9. Vignier N, Chatzifrangkeskou M, Morales Rodriguez B, et al. Rescue of biosynthesis of nicotinamide adenine dinucleotide protects the heart in cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2018 Nov 15;27(22):3870-3880
10. Romani M, Sorrentino V, Oh CM, et al. NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle. Cell Rep. 2021;34(3):108660
11. Ryu D, Zhang H, Ropelle ER, et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci Transl Med. 2016;8(361):361ra139
12. Volpi E, Nazemi R, Fujita S. Muscle tissue changes with aging. Curr Opin Clin Nutr Metab Care. 2004;7(4):405-410
13. Covarrubias AJ, Kale A, Perrone R, et al. Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nat Metab. 2020;2(11):1265-1283
14. Minhas PS, Liu L, Moon PK, et al. Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation. Nat Immunol. 2019;20(1):50-63
15. Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports. 2019;28(7):1717-1728.e6
16. Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem. 2006 Aug 4;281(31):21745-21754
17. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. Published online April 22, 2021
18. Basu R, Breda E, Oberg AL, et al. Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes. 2003;52(7):1738-1748
19. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536
20. Wilk, A., Hayat, F., Cunningham, R. et al. Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. Sci Rep 10, 651 (2020)
21. Jun Li, Michael S. Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A. Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. SCIENCE24 MAR 2017 : 1312-1317
22. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141
23. Naoko KIMURA, Tsutomu FUKUWATARI, Ryuzo SASAKI, Katsumi SHIBATA, Comparison of Metabolic Fates of Nicotinamide, NAD+ and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH, Journal of Nutritional Science and Vitaminology, 2006, Volume 52, Issue 2, Pages 142-148, Released June 15, 2007, Online ISSN 1881-7742, Print ISSN 0301-4800
24. Shade C. The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integr Med (Encinitas). 2020;19(1):12-14
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