NAD (Nicotinamide Adenine Dinucleotide): Benefits & How It Works

NAD (Nicotinamide Adenine Dinucleotide) Benefits & How It Works (1)

NAD+ (nicotinamide adenine dinucleotide) is vital to metabolism and creating energy in the body due to biological processes. Recently, NAD supplements have grown in popularity — especially for anti-aging enthusiasts. Let’s discuss what NAD+ does, how it’s produced in the body, as well as the many NAD+ benefits.

Looking for NAD+ therapy in the Denver area? PrimeHealth offers NAD+ IVs and injections to support energy production and address a number of conditions that may be affected by declining NAD levels.

What is NAD, and what does it do?

NAD is a coenzyme that comes in 2 forms: NAD+ and NADH. NAD+ is responsible for generating cellular energy and maintaining cellular function. NADH is the reduced form of NAD+, essentially the post-reaction version of NAD.

Where can NAD be found in the body? NAD is found in every living cell in your body. NAD+ is an oxidizing metabolite instrumental in the transfer of electrons to carry out intracellular redox reactions.

Despite NAD’s central role in creating energy (ATP), your body has a limited supply. NAD levels decrease with age. This correlation leads some to take NAD supplements to slow the aging process.

Without sufficient NAD levels, our bodies wouldn’t generate enough energy to survive. NAD levels also regulate cellular immune processes, DNA repair, and the sleep/wake cycle (AKA circadian rhythm).

Are NAD and niacin the same? NAD and niacin are not the same. Niacin is a term that refers to multiple vitamin B compounds (like vitamin B3) which are used in your body to synthesize NAD. Niacin is not the only substance that can produce NAD, and niacin has other purposes besides NAD synthesis.

Your Body Makes NAD: Here’s How It Works

How is NAD made? Our bodies make NAD in 3 known metabolic pathways: the kynurenine (de novo) pathway, the Preiss-Handler pathway, and the salvage pathway.

  • The kynurenine (de novo) pathway converts tryptophan to NAD in mammalian cells’ aqueous cytosol, separate from the cellular organelles.
  • The Preiss-Handler pathway converts nicotinic acid to NAD through 3 steps: the enzyme NAPRT converts nicotinic acid to nicotinic acid mononucleotide (NAMN), then the enzyme NMNAT converts NAMN to nicotinic acid adenine dinucleotide (NAAD), then NAD synthetase (NADS) converts NAAD to NAD.
  • The salvage pathway converts vitamin B3-related compounds (nicotinamide/NAM, nicotinamide mononucleotide, nicotinamide riboside) into NAD through the actions of multiple enzymes.

These 3 pathways demonstrate that tryptophan, nicotinic acid, and various B3 compounds are “NAD+ precursors.” Typically, consuming these NAD+ precursors promotes NAD production in the body.

When Your Body Makes Less NAD

As we get older, NAD levels decline. This means that mitochondrial function is reduced, the body produces less energy, DNA damage accumulates, and age-related diseases become more likely.

Reduced NAD levels may increase your risk for low metabolism, chronic fatigue, obesity, diabetes, and high blood pressure (hypertension).

High blood pressure may impact the brain and lead to cognitive impairment. Diabetes and obesity increase your chances of fatal health problems. Low NAD levels are a serious problem.

Slowing or preventing the decrease in NAD levels may combat metabolic disorders and age-related diseases. Keeping NAD levels high as you age may result in improved cellular stress response, reduced DNA damage, and more consistent energy generation.

Benefits of NAD Supplementation (IV, Intramuscular Therapy, and Dietary)

NAD+ precursor supplements (or simply “NAD supplements”) may benefit your mental health, heart health, muscular function, and brain health. They are known for anti-aging and anti-inflammatory benefits. They’re also a recent research topic in the treatment of long COVID.

NAD precursors include vitamin B3-related compounds and tryptophan, the elements needed to produce NAD in the body.

NAD supplements may significantly increase NAD levels in your body. Targeting lower NAD levels with effective supplements may protect against metabolic disorders and age-associated diseases.

What are the side effects of NAD? The potential side effects of NAD therapy include nausea, headache, and brain fog. NAD+ IV therapy is more likely to result in these short-term side effects than oral supplementation with NAD precursors.

1. Mental Health

Getting more NAD via IV, intramuscular therapy, or dietary supplements may help with mental health issues. People with low levels of NAD are at a higher risk of addiction, depression, anxiety, and other mental health disorders.

Recent research shows that infusions of NAD are safe, effective standalone treatments for substance use disorder. For the millions who experience addictive tendencies, especially genetic dispositions, NAD may help reduce addictive cravings and decrease the chance of overdose.

This substance use disorder study also showed that NAD significantly reduced depression and anxiety in subjects.

This 2022 animal study also supports the efficacy of NAD supplements for depression. NAD+ is another in a long line of novel depression treatments.

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2. Aging

NAD supplementation may promote anti-aging benefits due to NAD’s role in both energy generation and sirtuin activation.

Sirtuin proteins (such as SIRT1, SIRT2, and SIRT3) protect living organisms from disease and deterioration. Sirtuins naturally sustain genome integrity, promote DNA repair, and may even increase lifespan by slowing the aging process.

NAD fuels sirtuins. Raising your body’s NAD+ levels activates sirtuins, which may slow or reverse aging. Studies show that NAD supplementation increases lifespan in yeast, worms, and mice. Researchers are still examining how these results could translate to human studies.

3. Inflammation

Nicotinamide riboside, a NAD precursor, can reduce inflammation. The anti-inflammatory effects are “more robust” in the elderly and disease populations.

Because inflammation contributes to many disorders, NAD IVs and other forms of supplementation may be great for your immune system and overall health.

Inflammation is a contributing factor in the following conditions

Supplementing with NAD+, whether by IV, intramuscular injection, or dietary supplements, may generally help produce a better immune response and improve inflammatory conditions.

4. Heart Function

NAD supplements are anti-inflammatory, which may improve your heart function, and NAD plays several roles in preventing cardiovascular disease.

This recent study states, “NAD+ protects against metabolic syndrome, heart failure…arrhythmia, and hypertension” (high blood pressure).

In the US, a person dies from cardiovascular disease every 33 seconds, according to the CDC. This leading cause of death requires multiple interventions to prevent, and NAD supplementation seems to be an effective aid to heart health.

5. Neurodegeneration

According to a small 2021 study, NAD IV therapy improved cognitive function in healthy males.

Neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are terrible burdens on the patient, their loved ones, and society. Although the FDA has never approved a significantly effective drug for these conditions, NAD supplementation via IV, IM, or dietary supplements may help reduce the risk of degeneration.

One recent study concludes, “supplementation with NAD+ precursors appeared to be an effective and safe anti-Alzheimer’s disease strategy.”

Other researchers have found NAD precursors as a potential avenue for Parkinson’s prevention. A 2020 case study found that NAD+ IV injections alleviated tremor symptoms in a male patient with Parkinson’s disease.

By 2050, 2.1 billion people will be older than 60 years, according to the WHO. Neurodegenerative diseases are a growing problem that NAD may be able to help with.

Read Next: Benefits of NAC (N-Acetyl-Cysteine) & How To Use 

6. Muscle Function

Mitochondrial function is critical to muscle development and function and exercise performance. NAD supplements help maintain healthy mitochondria and generate consistent energy in your body.

Exercise requires higher cellular NAD production than when you’re resting. Aging leads to a reduction in NAD biosynthesis. NAD supplementation may improve biosynthesis by increasing the bioavailability of NAD precursors.

NAD supplementation “may benefit patients with muscular dystrophies or other neuromuscular degenerative conditions,” according to this animal study.

It is essential to maintain a strong level of NAD in skeletal muscle via supplementation and lifestyle changes. This should keep your quality of life high, even as you age or experience a health condition.

7. Metabolic Disorders

Obesity and diabetes are the two most common metabolic disorders, but many others exist. Not only have NAD precursors successfully increased NAD levels in living organisms, but some studies also report that NAD supplementation may reverse symptoms of some metabolic disorders.

NAD boosters may be useful in preventing diabetes, though certain researchers caution against high doses until the safety is clarified.

Animal studies show that NAD may slow weight gain and prevent adipose tissue formation, helping combat obesity.

Metabolic process dysfunction impacts billions across the globe. Emerging science seems to be pointing towards NAD as a way to help improve people’s metabolism at the cellular level.

8. Long COVID

NAD is a mitochondrial cofactor, which should help with low-energy problems associated with long COVID. These long-lasting symptoms seem most prevalent in females aged 35-69 years old, but many throughout the globe are impacted. Those affected are desperate for a solution.

Post-acute sequelae of COVID-19 (also called long COVID) may include hundreds of symptoms that last long after the initial COVID infection. The most common long COVID symptoms include:

  • Chronic fatigue
  • Insomnia
  • Persistent cough
  • Difficult breathing
  • Abdominal pain
  • Chest pain
  • Heart palpitations
  • Difficulty concentrating
  • Cognitive impairment
  • Memory loss
  • Erectile dysfunction
  • Irregular menstruation

NAD+ IV therapy may resolve low energy levels due to long COVID and inflammation-related conditions. Although NAD is not a solution to all long COVID symptoms, it should help with the most common long COVID symptom: fatigue that won’t go away. 

Many of our patients at PrimeHealth have improved their post-COVID symptoms of chronic fatigue by use of weekly IM (intramuscular) NAD+ injections for a few subsequent weeks.

Dealing with long COVID and live in Colorado? Get NAD+ injections from PrimeHealth to regain your energy!

Skin Health and Anti-Aging

Collagen is the protein that provides structure and strength to our skin. As we age, collagen levels deplete, leading to sagging skin, wrinkles and premature aging. NAD+ helps to bolster the production of this vital protein by supporting cellular health and promoting efficient enzyme activity. This reinforcement of collagen can help keep your skin firm and supple.

Moreover, the NAD+ benefits in promoting skin elasticity can’t be overstated. Elasticity is what keeps our skin looking youthful and bouncy. By boosting cellular metabolism and improving mitochondrial function, NAD+ aids in maintaining this essential skin quality. Enhanced elasticity means your skin can stretch and snap back into place more easily, preventing the formation of fine lines and wrinkles.

Energy and Performance Enhancement

Mitochondria, often called the cell’s powerhouse, produce the energy our cells need. NAD+ (Nicotinamide Adenine Dinucleotide) is key to this process. Think of NAD+ as a helper molecule that aids in various chemical reactions, especially those involved in energy metabolism. When there’s plenty of NAD+, it boosts mitochondrial function, helping our cells efficiently turn nutrients into energy.

For athletes or anyone looking to up their physical game, this is huge. Better mitochondrial function means more energy for your muscles during workouts, leading to longer endurance and quicker recovery. Imagine easily running that extra mile or lifting heavier weights—that’s the potential of having optimal NAD+ levels. Adding NAD+ boosters or supplements can seriously improve your exercise performance.

Detoxification and Cellular Cleansing

NAD+ plays a crucial role in keeping our cells clean and healthy through a process called cellular detoxification and autophagy. Think of autophagy as the cell’s own version of a cleaning crew. It’s a natural process where cells break down and recycle their own components, essentially getting rid of the junk that accumulates over time. This trash removal is vital for cell rejuvenation while maintaining cellular health and function.

NAD+ is a key player in this process. It helps to fuel the enzymes that drive autophagy, ensuring that cells can efficiently remove toxins and waste products. When cells have ample NAD+, they can better handle oxidative stress and damage, which is important because a build-up of cellular waste can lead to various health issues, including inflammation and aging.

Combating Neurological Disorders

NAD+’s potential as a therapeutic intervention for neurological disorders like Alzheimer’s and Parkinson’s disease is truly fascinating.

Alzheimer’s and Parkinson’s diseases are notorious for their devastating impact on the brain, leading to memory loss, decline in mental clarity, and motor dysfunction. At the core of these disorders is a gradual loss of neurons, caused by oxidative stress, inflammation, and impaired mitochondrial function. This is where NAD+ comes into play. NAD+ helps promote cellular energy production and repair, which is crucial for maintaining healthy brain function.

One of the key mechanisms behind NAD+’s neuroprotective effects is its role in supporting efficient mitochondrial function. Mitochondria, as the powerhouse of the cell, are extremely important in neurons, which need a constant supply of energy. By boosting mitochondrial efficiency, NAD+ ensures that neurons have the energy required to survive and function, even under stress. This can help slow down the neuronal loss seen in Alzheimer’s and Parkinson’s diseases.

Potential Therapeutic Applications

NAD+ is more than just an anti-aging hero; its therapeutic potential spans a wide range of health concerns, making it a fascinating topic in contemporary medical research and human clinical trials.

One of the most promising areas of NAD+ research is its role in tackling metabolic disorders. Conditions like obesity, diabetes, and metabolic syndrome wreak havoc on the body’s metabolism, leading to issues like insulin resistance, high blood sugar, and increased fat storage. NAD+ is integral to maintaining metabolic balance by supporting the enzymes involved in energy production and glucose metabolism.

Also, when it comes to heart health, NAD+ is no slouch either. Cardiovascular diseases, including hypertension, heart disease, and stroke, are often driven by oxidative stress and endothelial dysfunction.

NAD+ contributes to the repair mechanisms in blood vessels and helps regulate blood pressure. By enhancing mitochondrial function, NAD+ ensures heart cells have the energy they need to perform optimally.

Overall, the scope of NAD+ research is expanding rapidly, with numerous clinical trials exploring its therapeutic potential.

How To Increase Your NAD Levels

There are natural ways to increase your NAD levels. These dietary and lifestyle adjustments may improve your overall health and reduce your risk of various systemic diseases.

Here are the best ways to naturally boost your NAD levels:

  • NAD+ IV therapy or intramuscular (IM) injections — Intravenous or IM treatment delivers concentrated NAD directly into your bloodstream, raising NAD levels rapidly and efficiently, and thereby promoting whole-body wellness in all of the above ways. Getting NAD+ via IV or IM injection is the most bioavailable way to increase your NAD levels.
  • A diet rich in NAD precursors — Since vitamin B3 compounds and tryptophan are precursor nutrients to NAD biosynthesis, eating more vitamin B3 or tryptophan should increase your body’s capability to produce NAD. These include animal products (red meat, fish, poultry, cheese, egg whites, and milk), brown rice, nuts, seeds (especially sunflower and pumpkin seeds), legumes, and bananas.
  • Movement and exercise — Physical exercise depletes NAD+ but requires your body to synthesize more. Activity and exercise are good for your overall physical and mental health and train your body to produce NAD+ at higher rates. As you age, aerobic exercise has been shown to slow how levels of NAD+ decline.
  • Avoiding long sun exposureSun exposure may result in ultraviolet (UV) damage to your DNA. Your body uses NAD+ to repair DNA damage, therefore lowering NAD levels. Avoid exposure to UV light, such as from the sun, to avoid NAD depletion.
  • Supplements — NAD precursor supplements raise NAD levels, which results in various health benefits. Other vitamins and supplements can reduce stress, lowering your body’s requirements for NAD utilization and depletion.

The Future of NAD

For nearly 100 years, NAD+ and NADH have proved to be critical in our understanding of human metabolism and aging. NAD has enormous potential in future research — some hope it will eventually unlock the cure to obesity or even aging.

NAD has been called the “miracle molecule” for its ability to restore and maintain cellular health, even in aging patients. Recent animal studies conclude that NAD may prove beneficial in treating age-related conditions, chronic fatigue, heart disease, diabetes, Alzheimer’s disease, and obesity.

However, successful animal studies do not always translate to successful human studies. The next step is for scientists to confirm the safety and effectiveness of NAD in large-scale populations.

You may have noticed that most of the science cited in this article is from 2022 or 2023. NAD’s true potential has only recently been unlocked in research studies. We’re only at the beginning of studying the NAD+ benefits.

This 2022 study encourages future NAD studies to explore the long-term adverse effects of NAD precursor supplements and negative interactions with drugs and other supplements — neither of which has been well-explored in large-scale clinical trials.

Is NAD right for you?

NAD supplements and NAD IV and IM therapy are well-tolerated by most people. Its evidence-based NAD+ benefits may slow the aging process and increase anyone’s holistic health — mind and body.

Discuss any dietary and/or supplement routine changes with your healthcare provider. It may interact with pharmaceuticals or dietary supplements you take, and these interactions aren’t clearly defined yet. 

NAD+ benefits seem like exciting scientific breakthroughs, but this substance is not an FDA-approved medication and should not be used to prevent or treat any disease.

PrimeHealth is an integrative health clinic in Denver, Colorado. Our healthcare providers understand the right combination of supplements, dietary, and lifestyle changes that can give you back control over your health. Schedule a free phone consultation today.

Sources

  1. Blum, K., Han, D., Baron, D., Kazmi, S., Elman, I., Gomez, L. L., … & Badgaiyan, R. D. (2022). Nicotinamide Adenine Dinucleotide (NAD+) and Enkephalinase Inhibition (IV1114589NAD) Infusions Significantly Attenuate Psychiatric Burden Sequalae in Substance Use Disorder (SUD) in Fifty Cases. Current Psychiatry Research and Reviews Formerly: Current Psychiatry Reviews, 18(2), 125-143.
  2. Wang, J., Sun, R., Xia, L., Zhu, X., Zhang, Q., & Ye, Y. (2022). Potential Therapeutic Effects of NAMPT-Mediated NAD Biosynthesis in Depression In Vivo. Brain Sciences, 12(12), 1699.
  3. 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.
  4. Conlon, N. J. (2022). The Role of NAD+ in Regenerative Medicine. Plastic and Reconstructive Surgery, 150, 41S-48S.
  5. Kwon, J., Idoine, R., Ishtiaq, Y., Nkrumah-Elie, Y., Rosene, M., & Shao, A. (2022). The Clinical Effects of Nicotinamide Riboside on Inflammatory Parameters. Current Developments in Nutrition, 6(Supplement_1), 987-987.
  6. Idoine, R., Kwon, J., Ishtiaq, Y., Rosene, M., Shao, A., & Nkrumah-Elie, Y. (2022). Impact of Boosting NAD on Immune Function: Results From NR Preclinical Studies. Current Developments in Nutrition, 6(Supplement_1), 983-983.
  7. Navarro, M. N., Gomez de las Heras, M. M., & Mittelbrunn, M. (2022). Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing. British Journal of Pharmacology, 179(9), 1839-1856.
  8. Katayoshi, T., Uehata, S., Nakashima, N., Nakajo, T., Kitajima, N., Kageyama, M., & Tsuji-Naito, K. (2023). Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Scientific Reports, 13(1), 2786.
  9. Lin, Q., Zuo, W., Liu, Y., Wu, K., & Liu, Q. (2021). NAD+ and cardiovascular diseases. Clinica Chimica Acta, 515, 104-110.
  10. Zhang, X., Zhang, Y., Sun, A., & Ge, J. (2022). The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential. Genes & Diseases, 9(4), 959-972.
  11. Gibson, S. B., Mestayer, R., Berg, J., Grant, R., & Dyess, G. (2021). Intravenous Administration of Nicotinamide Adenine Dinucleotide Improves Cognitive Performance in Human Subjects: Implications for Clinical Populations. Archives of Physical Medicine and Rehabilitation, 102(10), e42.
  12. Wang, X., He, H. J., Xiong, X., Zhou, S., Wang, W. W., Feng, L., … & Xie, C. L. (2021). NAD+ in Alzheimer’s disease: molecular mechanisms and systematic therapeutic evidence obtained in vivo. Frontiers in Cell and Developmental Biology, 9, 668491.
  13. Brakedal, B., Dölle, C., Riemer, F., Ma, Y., Nido, G. S., Skeie, G. O., … & Tzoulis, C. (2022). The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell metabolism, 34(3), 396-407.
  14. Rutherford, L., Gadol, E., Broom, S. L., Olds, T., Mestayer, R. F., & Mestayer, P. (2020). Intravenous administration of nicotinamide adenine dinucleotide alleviates tremors associated with Parkinson’s disease: a case report. J Gerontol Geriatr Med, 6, 046.
  15. Ji, L. L., & Yeo, D. (2022). Maintenance of NAD+ homeostasis in skeletal muscle during aging and exercise. Cells, 11(4), 710.
  16. Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A., Mouchiroud, L., … & Auwerx, J. (2016). NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Science translational medicine, 8(361), 361ra139-361ra139.
  17. Goody, M. F., & Henry, C. A. (2018). A need for NAD+ in muscle development, homeostasis, and aging. Skeletal Muscle, 8(1), 1-14.
  18. Okabe, K., Yaku, K., Tobe, K., & Nakagawa, T. (2019). Implications of altered NAD metabolism in metabolic disorders. Journal of biomedical science, 26(1), 1-13.
  19. Fan, L., Cacicedo, J. M., & Ido, Y. (2020). Impaired nicotinamide adenine dinucleotide (NAD+) metabolism in diabetes and diabetic tissues: Implications for nicotinamide‐related compound treatment. Journal of Diabetes Investigation, 11(6), 1403-1419.
  20. Roh, E., Myoung Kang, G., Young Gil, S., Hee Lee, C., Kim, S., Hong, D., … & Kim, M. S. (2018). Effects of chronic NAD supplementation on energy metabolism and diurnal rhythm in obese mice. Obesity, 26(9), 1448-1456.
  21. Davis, H. E., McCorkell, L., Vogel, J. M., & Topol, E. J. (2023). Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology, 1-14.
  22. Block, T., & Kuo, J. (2022). Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome. Clinical Pathology, 15, 2632010X221106986.
  23. Zheng, M., Schultz, M. B., & Sinclair, D. A. (2022). NAD+ in COVID-19 and viral infections. Trends in Immunology.
  24. Poljsak, B., Kovač, V., & Milisav, I. (2020). Healthy lifestyle recommendations: Do the beneficial effects originate from NAD+ amount at the cellular level?. Oxidative medicine and cellular longevity, 2020.
  25. de Guia, R. M., Agerholm, M., Nielsen, T. S., Consitt, L. A., Søgaard, D., Helge, J. W., … & 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.
  26. Okabe, K., Yaku, K., Uchida, Y., Fukamizu, Y., Sato, T., Sakurai, T., … & Nakagawa, T. (2022). Oral administration of nicotinamide mononucleotide is safe and efficiently increases blood nicotinamide adenine dinucleotide levels in healthy subjects. Frontiers in Nutrition, 9.
  27. Poljšak, B., Kovač, V., & Milisav, I. (2022). Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies.Antioxidants, 11(9), 1637.