Everything You Wish you Knew About NAD+

NAD+

What Is NAD+ and Why Is It Important?

People have been trying to find the fountain of youth and prevent aging throughout the entire human history. And even though we never hit that anti-aging jackpot that will let us stay young forever, we now understand a lot about our body’s aging process.

NAD+ is one of the molecules that play a vital role in all of this. So, read on to find out what NAD+ is exactly, how it helps us feel younger, and the best ways you can boost your NAD+ levels.

What Is Nicotinamide Adenine Dinucleotide (NAD+)?

Nicotinamide adenine dinucleotide is a coenzyme that consists of adenine and nicotinamide, and it plays a vital role in the energy metabolism of our cells. You remember the most popular definition in biology – mitochondria is the powerhouse of the cell? Well, NAD+ is crucial for redox reactions in mitochondria where electrons are carried from one molecule to the other, ultimately resulting in the production of energy (ATP).

Nicotinamide adenine dinucleotide exists in two forms, oxidized NAD+ and reduced NADH, and both are vital for the energy processes in mitochondria.

NAD+ exists in the cells of all living things, including ours. Interestingly, we have high NAD+ levels during our youth, and they slowly decrease with age. But luckily, there are ways to slow down this decline and boost your NAD+ levels naturally.

Potential Benefits of Maintaining Healthy NAD+ Levels

Low NAD+ levels have been linked with some health problems like fatigue[1], weight gain[2], decreased brain function[3], sunburn and skin damage[4], an accelerated rate of aging[5], and more.

Maintaining normal NAD+ levels could be crucial for healthy aging and a few other health benefits.

Increasing Longevity

Besides playing an important role in redox reactions, NAD+ also acts as a cosubstrate for other enzymes like sirtuins, poly-ADP-ribose polymerases, and CD38/157[6]. All these enzymes play a vital role in our longevity, and their activity depends on healthy NAD+ levels.

NAD+ increases the activation of SIRT1, a specific sirtuin protein linked with longevity. There are seven sirtuin protein species in mammalian species with different targets in our cells, and they all play important roles in apoptosis, senescence, cell differentiation, and aging[7].

Studies in mice show that NAD+ levels decrease with age, which is associated with lower SIRT1 activity and DNA damage[8]. Interestingly, restoration of healthy NAD+ levels in old animals could bring several health benefits and extend lifespan[9].

Healthy Aging

A longer lifespan doesn’t mean anything if you are affected by other health problems. Luckily, NAD+ activated sirtuins are also known as guardians of the genome, as they protect us against oxidative stress, deterioration, and diseases.

When we are under stress, our body sends signals that it needs help defending itself. Sirtuins are one of the enzymes that come to the rescue, and they promote DNA repair and protect genome integrity. But, they need NAD+ to work. Together, these molecules could improve organ function, disease resistance, inflammatory status, metabolic disorders, and physical endurance[10].

Interestingly, NAD+ decreases with age, but its decrease also leads to the accelerated process of aging. That’s why NAD+ repletion could bring many benefits.

Muscle Function

NAD+ plays a crucial role in redox reactions in mitochondria, and it is responsible for steady energy output. That has a significant impact on our physical performance and fitness levels. Research confirms this association between higher NAD+ levels and improved muscle health[11].

In fact, studies show that NAD+ precursor supplementation improves muscle metabolism and aerobic performance[12]. It also increases physical performance in older individuals[13]

Besides improving mitochondrial health, NAD+ also reduces age-related amyloid protein aggregates in the muscles[14]. Simply put, older adults who have higher levels of NAD+ often exhibit better exercise capacity and outperform their peers.

Metabolic Disorders

Obesity is one of the most common disorders in modern society, affecting 42.4% of US adults[15]. Obesity is a substantial risk factor for many conditions and metabolic disorders, which is why experts are concerned about its increasing prevalence[16].

Decreased levels of NAD+ are linked with obesity and metabolic disorders like diabetes and fatty liver disease[17]. It appears that appropriate supplementation could battle this NAD+ decrease and alleviate diet and age-associated weight gain and accompanying metabolic conditions.

Fertility

There is some evidence that NAD+ repletion could help female fertility during aging[18]. We know that reproductive aging is an inevitable and irreversible process that affects the oocytes. However, this study shows that treatment interventions with NAD+ precursors such as nicotinamide mononucleotide (NMN) increase oocyte quality in aged animals and improve fertility markers.

Brain Health and Prevention of Age-Related Memory Loss

The brain accounts for 20% of the total energy use of our body, which is why neurons contain a lot of mitochondria. Disruption of mitochondria could lead to mental health impairments and increase the risk of neurodegenerative diseases.

Supplementation with NAD+ precursor, nicotinamide riboside (NR), improves cognitive function and synaptic plasticity in mice with Alzheimer’s disease[19]. Similar findings were observed with NADH oral supplementation[20]. It appears that NAD+ enhances DNA repair, which decreases oxidative stress in neurons. That translates to better cognitive performance and slower mental decline.

NADH has also been used as a part of treatment for Parkison’s disease, and it has exhibited tremendous potential for improving the symptoms of this condition[21,22].

In addition, intranasal NAD+ administration could be beneficial for alleviating the effects of brain injury due to deprivation of blood and oxygen in the brain[23]. NAD+ could decrease the scope of brain damage and delay the accompanying neurological deficits, which is vital for certain conditions such as stroke.

How to Maintain Healthy NAD+ Levels

Knowing all the benefits of NAD+, there are several ways you can maintain your NAD+ at healthy levels. Interestingly, taking NAD+ supplements may not be the best way to do so, as NAD+ is a large molecule. So, when you ingest it, your cells take it apart and use those building blocks for various purposes in the body, including synthesizing new NAD+ molecules.

Taking NAD+ precursors could be the better approach, and there are also several lifestyle changes with positive effects, such as:

  • Caloric restriction
  • Fasting
  • Exercising
  • Ketogenic diet
  • Heat shock therapy

Caloric restriction is one of the best ways to extend longevity. It affects many signaling pathways, reduces inflammation, regulates insulin sensitivity, and it can also increase levels of NAD+ in our bodies[24]. Caloric restriction activates nicotinamide phosphoribosyltransferase (NAMPT), triggering a salvage biosynthesis pathway that transforms NAM into NAD+.

However, significantly cutting your calories for prolonged periods is not feasible or advisable for most people. A significant drop such as 20-30% of your average caloric intake could have several health benefits. Still, you should always do it in consultation with a health practitioner to make sure you are not depriving your body of essential nutrients.

Some types of fasting, such as intermittent fasting, could bring the same benefits and are easier to maintain in the long run. However, more studies are needed to confirm these claims. Overall, intermittent fasting is an excellent way to enter a fat-burning state called ketosis, which affects the bioavailability of NAD+[25]. If you are not a big fan of fasting, you can try the ketogenic diet, which focuses on limiting carb consumption and getting most of your calories from fats and proteins.

Physical activity has many positive outcomes on our overall health. Exercise stimulates NAMPT, which boosts the production of NAD+ and the activation of SIRT1[26]. Studies in both mice and human subjects have shown that physical activity is essential for maintaining higher NAD+ levels during aging. It appears that aerobic training and high-intensity interval training (HIIT) could be the best types of workouts for this purpose.

Lastly, heat shock therapy or heat, in general, could trigger the increased production of NAD+. Hot tubs, heated pools, saunas, and other heat sources cause your heart to pump faster, requiring more energy to cool your body down. That’s why it produces more NAD+ to meet the increased energy demand[27].

If you are interested in the molecular mechanisms behind any of the mentioned lifestyle recommendations, head over to the Journal of Oxidative Medicine and Cellular Longevity’s review from December 2020.

Additional Preventive Measures to Maintain Healthy NAD+ Levels

Besides caloric restriction, exercise, and other lifestyle adjustments, certain things don’t increase your NAD+ levels, but they help maintain them. For instance, UV rays damage your skin cells, and NAD+ is one of the things important for the repair. That’s why using sunscreen and wearing protective clothing can minimize this UV-induced damage and preserve NAD+. 

In addition, a healthy diet based on whole foods and regular activity can boost your overall well-being and mitochondrial health, which could help your body use NAD+ more efficiently.

Best Ways to Positively Impact Your NAD+ Levels

There are several quick ways to impact your NAD+ levels, including:

  • NAD+ IV Therapy – This therapy is done in a few series, and intravenous infusion ensures that you get the most out of NAD+.
  • NAD+ SubQ Shots – These quick injections bring a small dose of NAD+ under your skin and allow slow absorption over several hours.
  • NAD+ precursors like NR – The supplementation with these building blocks can increase the production of NAD+.
  • NAD+ boosters like Fisetin and Apigenin (28)

Dr. Paulvin offers all of those therapy and supplementation options at his Manhattan office. He also provides remote consults for all people looking to learn more about NAD+ or try boosting their NAD+ levels at home.

Scientific Sources:

  1. https://pubmed.ncbi.nlm.nih.gov/10071523/ 
  2. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(12)00192-1 
  3. https://pubmed.ncbi.nlm.nih.gov/15134388/ 
  4. https://pubmed.ncbi.nlm.nih.gov/19149600/ 
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088772/ 
  6. https://pubmed.ncbi.nlm.nih.gov/24786309/ 
  7. https://www.cell.com/cell-metabolism/pdf/S1550-4131(14)00265-4.pdf
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082551/ 
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/ 
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107309/ 
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840929/ 
  12. https://pubmed.ncbi.nlm.nih.gov/31494696/
  13. https://pubmed.ncbi.nlm.nih.gov/30725213/ 
  14. https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31649-1
  15. https://www.cdc.gov/obesity/data/adult.html 
  16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386197/ 
  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511662/ 
  18. https://www.sciencedirect.com/science/article/pii/S2211124720300838 
  19. https://pubmed.ncbi.nlm.nih.gov/23312803/ 
  20. https://pubmed.ncbi.nlm.nih.gov/15134388/ 
  21. https://pubmed.ncbi.nlm.nih.gov/8101414/ 
  22. https://pubmed.ncbi.nlm.nih.gov/9013405/ 
  23. https://pubmed.ncbi.nlm.nih.gov/17127275/ 
  24. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12273 
  25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683958/ 
  26. https://www.sciencedirect.com/science/article/abs/pii/S0047637409001523 
https://www.researchgate.net/figure/HS-induces-an-increase-in-the-NAD-NADH-ratio-A-NAD-and-B-NADH-concentrations-were_fig7_235372219

Medical Disclaimer:

The Information in this guide is designed to complement, not replace, the relationship between a patient and his/her own physician and is for informational purposes only. The information is not intended to be medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you saw or read on my website.

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