What is NAD+

Key Takeaways:

  • NAD+ (Nicotinamide Adenine Dinucleotide) is a vital coenzyme found in every cell of your body, playing a key role in energy production and cellular repair.
  • NAD+ supports cellular metabolism, DNA repair, and the activity of important enzymes like sirtuins and PARPs.
  • NAD+ levels naturally decline with age and exposure to metabolic stress, and low NAD+ is associated with various age-related conditions.
  • Scientific research is exploring ways to boost NAD+ levels, including supplementation with precursors like nicotinamide riboside (NR).

What Is NAD+? A Critical Molecule for Cellular Health and Energy

In recent years, NAD+ has emerged as a buzzword in the health and wellness space, sparking growing interest among researchers, biohackers, and health-conscious individuals alike.

Nicotinamide adenine dinucleotide, or NAD+, is a coenzyme found in all living cells. It plays a fundamental role in cellular energy metabolism by enabling the transfer of electrons, a process essential for converting food into energy. This molecule is so important that life would not be possible without it.1

The human body is composed of trillions of cells,2 each of which depends on NAD+ to fuel metabolic processes and maintain cellular function.3 From converting glucose into cellular energy (in the form of adenosine triphosphate, ATP) in the mitochondria, to regulating circadian rhythms and managing stress responses, NAD+ is involved in nearly every aspect of cellular life. To maintain NAD+ levels, we rely on nutrients from our diet, specifically B3 vitamins, which are found in whole foods, fortified products, and supplements.

However, recent research has shown that NAD+ levels naturally decline over time,4 a reduction that has been linked to various chronic and age-related health conditions. This has sparked growing interest in ways to increase NAD+ levels, from supplementation to lifestyle interventions, to support cellular function and promote overall health.

The Role of NAD+ in Cellular Metabolism

Cells transform nutrients from food into energy through metabolic processes. These processes are broadly classified into two categories:

  • Catabolism: The breakdown of molecules to release energy.
  • Anabolism: The process of building complex molecules from simpler ones, requiring energy input.

Cells need a way to productively manage the energy that is required by anabolic processes or released by catabolic ones.5 Heat energy, like the energy released by a burning flame, is difficult for living things to use and typically dissipates quickly from cells.5 To keep energy in a more useful form, cells use special molecules to store and manage energy as chemical energy.

NAD+ is a particularly important energy management molecule that acts as a coenzyme, or helper molecule, by transferring energy to and from a variety of chemical reactions.3

NAD+, along with the closely related molecule nicotinamide adenine dinucleotide phosphate (NADP+), is involved in more than 500 chemical reactions in the cell.6 While both molecules serve as electron carriers, they have distinct cellular roles: NAD+ primarily drives energy-producing catabolic processes like glycolysis and the citric acid cycle, whereas NADP+ powers anabolic processes such as fatty acid synthesis and provides the reducing power needed for antioxidant defense against cellular damage.7

These two molecules are involved in so many chemical reactions that it is difficult to find a metabolic process that does not involve at least one of them. 

Beyond Energy Metabolism: NAD-Consuming Enzymes

NAD+ doesn’t just shuttle electrons—it also serves as a key substrate for several enzyme families that consume it to perform critical biological functions tied to cellular health, stress responses, and longevity.

  • Sirtuins: NAD-dependent enzymes regulating gene expression, mitochondrial function, metabolism, and cellular stress responses.8 Their activity is linked to longevity and aging processes.
  • PARPs (Poly-ADP Ribose Polymerases): Enzymes that use NAD+ to detect and repair DNA damage. Their repair functions consume NAD+.9
  • CD38 and SARM1: Known as NADases, these enzymes break down large amounts of NAD+ during cellular signaling and stress responses. CD38 hydrolyzes about 100 NAD+ molecules to generate a single calcium signaling molecule, cyclic ADP-ribose.10 SARM1 rapidly depletes NAD+ in neurons during injury, contributing to degeneration.11 

As these enzymes ramp up in activity—especially during aging, inflammation, or metabolic stress—they accelerate NAD+ consumption. Over time, this increased enzymatic demand can outpace the body’s ability to replenish NAD+ levels. Maintaining the balance between NAD+ production and its enzymatic breakdown is considered a key factor in sustaining metabolic and cellular health throughout life.

NAD+ Decline with Aging and Metabolic Stress

Despite being essential for cellular health, NAD+ is not a constant resource. One of the most significant discoveries in NAD+ research is that levels of this crucial molecule naturally decline with age. This reduction correlates with decreased cellular efficiency, increased DNA damage, heightened inflammation, and mitochondrial dysfunction—key hallmarks of the aging process. Studies indicate that NAD+ levels can drop by as much as 65% between the ages of 30 and 70.4,12

However, aging is not the sole cause of NAD+ depletion. Various metabolic stressors can accelerate this decline, including:

  • High-Fat/High-Sugar Diet
  • Excess Alcohol Consumption
  • Sedentary Lifestyle
  • Overtraining
  • Excess Sun Exposure
  • Immune Stress
  • Environmental Factors

These factors increase the demand for NAD+ and stimulate enzymes such as sirtuins and PARPs that consume NAD+, further reducing its availability. When NAD+ levels fall, cells become less capable of producing energy, repairing DNA damage, and responding effectively to stress. This decline may contribute to the onset and progression of age-related conditions, including neurodegenerative diseases, metabolic disorders, and cardiovascular problems.

Consequently, maintaining adequate NAD+ levels is gaining recognition as a vital strategy to support healthy aging and enhance cellular resilience.

How to Increase NAD+ Levels

Given how crucial NAD+ is to maintaining cellular health, it is no surprise that scientists are researching ways to replenish it as we age. Although NAD+ naturally declines with age and due to metabolic stress, multiple strategies have been identified to help increase NAD+ levels in the body.13

1. NAD+ Precursor Supplementation

The most direct way to support NAD+ levels is by providing the body with its building blocks, called NAD+ precursors. These include:

  • Nicotinamide Riboside (NR): The most efficient method of increasing NAD+. A form of vitamin B3 shown in clinical studies to safely increase NAD+ levels and support mitochondrial function.
  • Nicotinamide (NAM) and Niacin (NA): Other vitamin B3 forms that can also be converted into NAD+ in the body, though with slightly different pathways and effects.
  • Nicotinamide Mononucleotide (NMN): Another NAD+ precursor that boosts NAD+ levels, but is less efficient, as it cannot directly enter cells. Additionally, as of November 2022, the United States (U.S) Food and Drug Administration (FDA) stated that NMN is excluded from the definition of a dietary supplement, meaning it cannot be legally marketed as one in the U.S.

2. Healthy Lifestyle Habits

Certain lifestyle choices can naturally support NAD+ production and slow its decline14:

  • Regular Exercise: Moderate physical activity stimulates NAD+ biosynthesis.

  • Caloric Restriction or Intermittent Fasting: Reducing calorie intake (by ~20%) or timing meals can activate cellular pathways that increase NAD+ and promote metabolic health.

  • Dietary Sources: NAD+ precursors can be obtained from foods rich in vitamin B3 (niacin), such as poultry, fish, nuts, mushrooms, and green vegetables. While these dietary sources supply the fundamental components needed for NAD+ synthesis, their contribution is generally smaller compared to targeted supplementation.

Benefits of NAD+ Supplementation: Why It Matters for Your Health

Because NAD+ is so central to cellular function, maintaining its levels has widespread health implications across many systems of the body. Scientific studies—spanning animals, cells, and clinical research—have identified several domains where NAD+ may provide significant benefits.

Healthy Aging

Research has shown that NAD+ levels decline markedly with age across multiple tissues—including the skin, brain, and skeletal muscle4,12,15—compromising cellular resilience and potentially accelerating age-related dysfunction. This decline is accompanied by an increase in oxidative stress and heightened activity of enzymes like PARPs,4 which consume NAD+ in response to DNA damage. These changes are closely tied to several of the biological mechanisms identified as the Hallmarks of Aging, including mitochondrial dysfunction, genomic instability, and impaired intercellular communication—each contributing to the progressive decline in cellular function over time.16

Encouragingly, studies have shown that replenishing NAD+ levels can support mitochondrial health, enhance cellular energy production, reduce oxidative stress, and improve overall cellular function.1,17–19 By restoring NAD+ availability, these interventions may help counteract age-related cellular decline and support healthier aging at the molecular level.

Cellular Energy Production & Repair

NAD+ is essential for two of the most fundamental processes that keep cells alive and functioning: generating energy and repairing damage.1 As a key coenzyme in cellular metabolism, NAD+ facilitates the generation of ATP by supporting critical biochemical reactions in glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. Simultaneously, NAD+ powers essential repair mechanisms that protect the genome, such as PARPs, which detect and repair DNA damage, and sirtuins, which regulate cellular stress responses and maintain mitochondrial health.

Without sufficient NAD+, cells struggle to meet their energy demands and repair the everyday damage caused by metabolism and environmental stressors, which may contribute to aging and disease over time.

Brain Health

The brain is a highly metabolically active organ, requiring constant energy to function. Despite making up only 2% of the body’s weight, the brain consumes about 20% of the body’s total energy.20 This energy is produced by mitochondria, making mitochondrial performance a key factor in brain health.

Researchers have increasingly linked brain function to mitochondrial efficiency, and age-related declines in NAD+ levels within the human brain have been documented,15,21 underscoring the importance of restoring these levels. Studies have shown that supplementing NAD+ can raise cerebral NAD+ concentrations22,23 and influence the brain’s metabolic profile. By supporting efficient energy metabolism in brain cells, NAD+ may help maintain brain health over time. 

Muscle Health

Skeletal muscles—the muscles responsible for voluntary movement—depend on both healthy mitochondria and adequate levels of NAD+ to generate the energy required for contraction and relaxation.24,25 Research has demonstrated that elevating NAD+ levels can increase mitochondrial biogenesis in skeletal muscle, effectively increasing the number of mitochondria within muscle tissue, supporting muscle health.26 

Additionally, increased NAD+ availability has been associated with modest improvements in body composition as seen through an increase in lean mass and a decrease in fat mass.27 Notably, higher NAD+ levels have also led to a significant rise in acetylcarnitine concentrations within skeletal muscle—a molecule that helps bring fuel into the mitochondria. 

Cardiovascular Health

Like the brain, the heart is one of the most energy-demanding organs in the body and contains more mitochondria per cell than any other tissue.28 As a result, its function is highly dependent on both mitochondrial activity and the availability of NAD+. Research has shown that elevating NAD+ levels is associated with favorable trends, including reductions in systolic blood pressure and arterial stiffness18—two key markers of cardiovascular health.

NAD+ As a Cornerstone of Longevity and Wellbeing

As the science of NAD+ continues to unfold, it’s becoming increasingly clear that this vital molecule plays a foundational role in supporting healthy aging. Far from being a miracle cure, NAD+ should be viewed as a crucial cofactor that helps maintain cellular function and resilience over time. Age-related declines in NAD+ have been observed across multiple tissues—including the brain, skin, and muscle—and have been linked to key mechanisms described by the Hallmarks of Aging, such as mitochondrial dysfunction, genomic instability, and impaired cellular communication.

While research in animals has generated significant excitement by demonstrating that replenishing NAD+ can reverse certain aspects of age-related decline, the human story is still being written. Early clinical studies are beginning to show promise, especially in areas like cardiovascular and cognitive health, but larger and longer-term trials are needed to fully understand the benefits and boundaries of NAD+ restoration in people.

Ultimately, NAD+ is not about chasing longevity at any cost—it is about investing in healthspan: the years lived in good health, with energy, resilience, and function intact. As we age and our ability to adapt to cellular stress diminishes, supporting NAD+ levels through lifestyle and nutritional strategies may offer a scientifically grounded way to promote healthier aging—not defying aging, but thriving at every age. 


References

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