NAD+ is a central coenzyme in the metabolic process, found in all living organisms, from bacteria to humans. It's involved in numerous functions, with its highest concentration in mitochondria, the cell organelles that provide energy to the entire cell.

As we age, the amount of NAD+ decreases, inevitably affecting processes including energy production and DNA repair. Fortunately, vitamin B3, also known as niacin, is the primary NAD+ precursor, and it can be taken in supplement form to help raise NAD levels.

In this article, we'll explore the importance of niacin not only for overall health and disease prevention due to deficiency but also for longevity.

Nicotinamide Adenine Dinucleotide (NAD)

What is NAD and Why is it Important for Longevity?

Short for Nicotinamide Adenine Dinucleotide, NAD is a coenzyme found in all living cells that plays a crucial role in many biological processes, particularly those related to energy production and cellular repair, like glycolysis and oxidative phosphorylation (2).

The Basics of NAD

NAD is a coenzyme, meaning it assists enzymes in driving metabolic reactions. It exists in two forms: NAD+ (oxidized) and NADH (reduced). These forms are essential for transferring electrons in the mitochondria, the powerhouse of our cells, where energy (ATP) is produced.

Why NAD+ is Crucial for Longevity

1. Energy Production: NAD+ is essential for converting the food we eat into the energy our cells need to function. Without sufficient NAD+, our cells cannot produce the energy required to survive and function optimally, which can lead to cellular energy depletion and even cell death (2).
2. DNA Repair: NAD+ helps repair damaged DNA. Every day, our DNA is damaged by environmental factors and normal cellular processes. NAD+ activates enzymes called PARPs (poly(ADP-ribose) polymerase), which are responsible for repairing this damage and maintaining genome stability (11).
3. Cell Health and Function: NAD+ is essential for proper mitochondrial function, which is critical to overall cellular health and energy levels. Mitochondrial function declines with age, but maintaining NAD+ levels can help mitigate this effect (12).
4. Activation of Sirtuins: Sirtuins are proteins that play a key role in longevity by regulating cellular health. They require NAD+ to function, and supplements can help activate them. Sirtuins help control inflammation, support DNA repair, and increase metabolic efficiency (3).
5. Stem Cell Function: As we age, the body's renewal and regeneration processes slow down. NAD+ supports the health and function of stem cells, which are essential for tissue regeneration and maintaining healthy organs as we age (13).

The Decline of NAD+ with Age

NAD+ levels decline with age, contributing to cellular dysfunction and age-related diseases (14). This reduction is linked to a variety of age-related health issues, including decreased energy, reduced DNA repair efficiency, and diminished cellular function. 

Researchers believe that by boosting NAD+ levels, we can potentially slow down or even reverse some aspects of the aging process.

There are several ways to maintain or boost NAD+ levels:

• Diet: Foods rich in vitamin B3 (niacin), such as chicken, tuna, and mushrooms can help increase NAD+ levels.
• Supplements: NAD+ precursors like nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and Niacin are popular supplements that have been shown to effectively raise NAD+ levels.
• Exercise: Regular physical activity can help boost NAD+ levels naturally.
• Intermittent Fasting: Some studies suggest that intermittent fasting can increase NAD+ levels and activate sirtuins.

Three Ways That NAD+ Can Be Synthesized

1. De novo from tryptophan;
2. In Salvage pathway from nicotinamide riboside (NR) that turns into nicotinamide mononucleotide (NMN) by enzyme called nicotinamide riboside kinase.
3. Via the Preiss-Handler pathway where nicotinic acid/niacin is transformed through a three-step reaction to NAD+.

Vitamin B3 to Boost NAD+ levels: NMN, NR, NAD, and Niacin Explained

• NMN
• NR
• Niacin

Niacin's Impact on Longevity

Niacin, also known as vitamin B3 or nicotinic acid, is a water-soluble vitamin discovered by biochemist Conrad Elvehjem in 1937 (1). Early studies on niacin focused primarily on its deficiency and the treatment of related disorders, as insufficient niacin intake affects the skin, digestive organs, and nervous system. Very low levels lead to pellagra—a disease characterized by diarrhea, dermatitis, dementia, and, if untreated, death.

Niacin's roles in the body and potent precursor of NAD+:

• Niacin is a precursor to the coenzymes NAD and NADP (nicotinamide adenine dinucleotide phosphate). These two forms are crucial for cellular metabolism and energy production (2).

• Niacin can potentially impact longevity and overall health span because it's involved in DNA repair mechanisms  (3, 4).

• Niacin can help mitigate oxidative stress and reduce inflammation, meaning it offers support for the cardiovascular system and other systems of the body (5, 6, 10).

• Niacin helps improve body composition by supporting muscle function and muscular health (7).

• Niacin assists in maintaining cognitive function and mental sharpness (8).

• Niacin also supports the gut microbiome and helps to prevent pathogens from invading the body (9).

How NMN and NR Can Work to Increase NAD+ Levels

NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) have gained significant attention in longevity and anti-aging research due to their ability to boost NAD+ levels.

How They Work:

• NR can be directly absorbed by cells without needing prior conversion. Once inside, it’s converted into NMN, which is then turned into NAD+ through enzymatic reactions.
• NMN is first converted into NR before it enters the cells. After entry, NR is converted back into NMN and NAD+ through specific enzymes (15).
• Recent research has identified a transporter called Slc12a8, which allows NMN to be directly taken up by cells, making it an efficient precursor for NAD+ synthesis (16).

Comparing NMN and NR supplementing:

• Efficiency: NR is often considered more efficient due to its simpler conversion pathway and direct cellular uptake.
• Cell Entry: NR can enter cells directly, while NMN may require conversion to NR or specific transporters for entry.
• Regulatory Status: NR is widely available as a dietary supplement and is recognized for its safety. NMN, while effective, is still under investigation by regulatory bodies like the FDA and is less widely available in supplement form.

How Niacin Can Help Raise NAD+ Levels

Using niacin as a precursor for NAD+ production is a well-known method for enhancing longevity and overall health.

How It Works:

• Niacin is first converted into nicotinamide mononucleotide (NAMN) by the enzyme nicotinic acid phosphoribosyltransferase.
• NAMN is a key molecule also produced from L-tryptophan in de novo synthesis, making it a common product in multiple pathways.
• NAMN is then transformed into nicotinic acid-adenine dinucleotide (NaAD) by a group of ATP-dependent enzymes known as nicotinate mononucleotide adenylyltransferase.
• Finally, NaAD is converted into NAD+, thereby increasing NAD+ levels in the body.

Additional Benefits of Increasing NAD+ Levels with Niacin:

• In biochemical reactions, the amount of the final product usually controls the synthesis process. However, in the NAD+ production pathway involving niacin, the synthesis continues as long as niacin is available since the limiting factor is the amount of niacin rather than NAD+ (17).
• Various human tissues, including the brain, heart, kidney, liver, lungs, and skeletal muscles, express the necessary NMNAT enzymes to produce NAD+ from niacin, highlighting the widespread potential of this pathway (18).
• In a study with patients suffering from mitochondrial myopathy, niacin supplementation not only restored NAD+ levels but also improved muscle strength and performance. This suggests that niacin can combat muscle fatigue and weakness associated with aging and certain muscle disorders (7).
• Niacin has also been shown to reduce hepatic and visceral fat, which are associated with metabolic syndrome and other health issues. By decreasing these fat deposits, niacin helps support a healthier metabolic profile (19).

Why Niacin May Be More Effective At Increasing NAD+ levels

Niacin has long been studied for its health benefits and its role in increasing NAD+ levels in the body. While NMN and NR are newer NAD+ precursors that have gained attention for their bioavailability, niacin offers several advantages that make it a compelling option. Here’s a detailed comparison:

Differences and Considerations

Extensive Research and Safety

• Proven Track Record: With over 80 years of research, niacin is well-documented for its safety and effectiveness, making it a trusted choice among healthcare professionals and the public.
• Dramatic NAD+ Increase: Clinical studies show that niacin significantly boosts NAD+ levels in both blood and muscle tissue, with one study noting an 8-fold increase in blood NAD+ levels (19).

Effective NAD+ Restoration

• Direct Conversion: Niacin plays a direct role in NAD+ production, converting efficiently into NAD+ through a series of enzymatic reactions.
• Simplified Pathways: Unlike NR, which requires specific enzymes that vary by tissue, niacin’s NAD+ synthesis pathways are more straightforward and universally applicable across different tissues.

Affordability and Accessibility

• Cost-Effective: Niacin is more affordable and widely available compared to NMN and NR, making it an accessible option for boosting NAD+ levels.
• Easy Availability: Niacin can be easily found in most health stores and pharmacies, simplifying its integration into daily routines.

Comprehensive Benefits

• Broader Health Impact: Beyond boosting NAD+, niacin supports overall metabolic health, reducing visceral fat and improving muscle strength, particularly in those with metabolic disorders.
• Heart Health Benefits: Niacin not only raises NAD+ levels but also offers significant cardiovascular benefits, such as lowering cholesterol and improving heart health, making it a valuable dual-purpose supplement.

Considerations for NMN and NR

• Bioavailability and Conversion: While NMN and NR may offer higher bioavailability, their long-term safety and efficacy are still under investigation. 

What About NAD+ IV Infusions? 

Recent research questions the effectiveness of NAD+ intravenous drips in raising intracellular NAD+ levels, which is where it matters most. 

While NAD+ is vital for energy production, DNA repair, and overall cellular health, delivering it through IVs presents challenges.

A key issue is that NAD+ cannot directly enter cells due to its size and polarity. It must first be broken down into smaller molecules like nicotinamide (NAM) or nicotinamide riboside, which can then be absorbed and converted back into NAD+ inside cells. 

Studies show that much of the NAD+ from IV infusions is rapidly metabolized and excreted, with little direct benefit to intracellular NAD+ levels.

Therefore, while NAD+ IV drips may temporarily boost NAD+ in the bloodstream, they do not provide a sustained increase in the NAD+ levels within cells, limiting their impact on longevity. 

Oral supplementation with NAD+ precursors like niacin, NR, or NMN is often more effective, as these are better absorbed and utilized by the body (20).

NAD+ infusions, typically lasting 4-6 hours in specialized clinics, are costly, time-consuming, and have more pronounced side effects than niacin supplementation. Additionally, NAD+ is less stable than niacin, making this treatment less practical for regular use (21).

Oral supplementation with NAD+ precursors like Niacin, NR, or NMN is often considered a more effective strategy for boosting intracellular NAD+ levels, as these precursors are better absorbed and utilized by the body​​.

Niacin's Impact On Cardiovascular Health

Niacin shows remarkable potential in treating various cardiovascular diseases and promoting overall heart health due to its benefits such as:

Modifying blood lipid profiles:

• How? It effectively lowers levels of LDL cholesterol (commonly referred to as "bad" cholesterol) while simultaneously increasing HDL cholesterol (or "good" cholesterol) (22). 
• Result. Reduction of the risk of atherosclerosis and cardiovascular events such as heart attacks and strokes.

Lowering triglyceride concentrations in the blood: 

• Result. Reduction of cardiovascular risks.

Combating chronic inflammation within blood vessels: 

• How? By reducing levels of pro-inflammatory cytokines such as CRP and TNF-α levels (24).
• Result. Maintenance of vascular health and function.

Helping to decrease damage within arterial walls: 

• How? It neutralizes free radicals that contribute to oxidative stress (5).
• Result. Protection against atherosclerosis and other cardiovascular conditions.

Improving endothelial function:

• How? By augmentation of HDL-C that mitigates vascular oxidative stress (25).
• Result. Healthy endothelial function is critical for maintaining proper blood flow and preventing the development of hypertension and other vascular disorders.

Potential Niacin Side Effects and How to Mitigate Them

While niacin is generally safe, there are some common side effects to be aware of when supplementing with niacin, especially in high dosages. These can include flushing (the feeling of the skin being hot and red), itching, and gastrointestinal discomfort. 

To avoid side effects, start with the prescribed dosage, opt for no-flush niacin (the type found in Jung+'s Longevity Foundation), and consult with a specialist first if you have a known heart condition.

Beyond Silver Bullet Solutions: A Multi-factor approach to increase NAD+ Levels

Our Longevity Foundation features not only niacin but also other synergistic ingredients that can help boost longevity mechanisms:

Apigenin provides powerful NAD+ synergy by modulating the activity of enzymes like CD38 and NAMPT, which are involved in NAD+ metabolism. 

Studies suggest that apigenin can increase NAD+ levels and activate the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). Activation of SIRT1 by apigenin can impact cellular metabolism, DNA repair, and other NAD+-dependent pathways, contributing to aging and longevity (26).

Pterostilbene is a sirtuin activator. While it does not directly increase NAD+ levels, activating sirtuins enhances the cellular processes that NAD+ supports, potentially offering health and longevity benefits (27).

Why We Made Longevity Foundation

Jung+'s primary goal was to create formulas that combine only scientifically proven ingredients, each with the ability to target the complex biological mechanisms underlying aging. 

Additionally, we aim to ensure that each component enhances the effectiveness of the others, providing comprehensive support against the multifaceted nature of aging.

Each of our formulas addresses the 12 major hallmarks of aging, which of course includes energy disturbances. In our search for the most effective ingredients, we included niacin in our formula to help:

• Boost mechanisms of longevity.
• Support healthy NAD+ levels and improve energy metabolism on a cellular level. 
• Support heart and vessels.
• Support mental function, clarity, focus and restful sleep. 
• Protects and enhances skin resilience from the inside out. 

Longevity supplements, such as those offered by Longevity Foundation, are scientifically proven to target the biological mechanisms of aging. They help promote cellular health, improve DNA repair, and prevent age-related diseases. However, the key to true health lies not only in taking supplements but also in maintaining a balanced lifestyle.

Combining high-quality supplements with a nutritious diet, regular exercise, stress management, and adequate sleep creates a comprehensive strategy for a longer, healthier life. 

1. Further studies on the concentration of the antipellagra factor (1937). Journal of Biological Chemistry. 
2. NAD+ and Vitamin B3: From Metabolism to Therapies (2008). Journal of Pharmacology and Experimental Therapeutics.
3. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling (2013). Cell.
4. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging (2017). Science.
5. Niacin and Oxidative Stress: A Mini-Review (2016). Journal of Nutritional Medicine and Diet Care.
6. Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2015). Cell Metabolism.
7. Niacin Cures Systemic NAD(+) Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy (2020). Cell Metabolism. 
8. An Update of Biological Aspects and Clinical Applications (2019). International Journal of Molecular Sciences.
9. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes (2015). Frontiers in Genetics. 
10. NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease (2023). Journal of Biological Chemistry.
11. The NAD+ precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation (2017). DNA Repair.
12. NAD⁺ content and its role in mitochondria (2015). Methods in Molecular Biology.
13. NAD+ metabolism, stemness, the immune response, and cancer (2021). Signal Transduction and Targeted Therapy.
14. Age-related NAD+ decline (2021). Experimental Gerontology.
15. The Science Behind NMN–A Stable, Reliable NAD+Activator and Anti-Aging Molecule (2020). Integrative Medicine.
16. The elusive NMN transporter is found (2019). Nature Metabolism.
17. NMNAT: It’s an NAD+ synthase… It’s a chaperone… It’s a neuroprotector (2017). Current Opinion in Genetics & Development.
18. Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells (2007). Journal of Biological Chemistry.
19. Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention (2019). Scientific Reports.
20. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+ (2019). Frontiers in Aging Neuroscience.
21. Nicotinamide adenine dinucleotide: Summary Report (2021). Source: http://hdl.handle.net/10713/15463 
22. Mechanism of action of niacin on lipoprotein metabolism (2000). Current Atherosclerosis Reports. 
23. New Perspectives on the Use of Niacin in the Treatment of Lipid Disorders (2004). JAMA Internal Medicine.
24. The effect of niacin on inflammatory markers and adipokines: a systematic review and meta-analysis of interventional studies (2024). European Journal of Nutrition.
25. Effect of niacin on endothelial function: A systematic review and meta-analysis of randomized controlled trials (2014). Vascular Medicine.
26. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome (2013). Diabetes.
27. Dietary supplementation with NAD+-boosting compounds in humans: Current knowledge and future directions (2023). The Journals of Gerontology: Series A.