How Does the Body Make NAD+?
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Nicotinamide adenine dinucleotide (NAD+) is one of the most important molecules in the human body, yet most people have never heard of it. Found in every living cell, NAD+ helps convert the food you eat into cellular energy, supports DNA repair, and powers proteins involved in healthy aging. Because NAD+ is constantly being used, your body must continuously produce and recycle it to keep your cells functioning properly.
If you're new to this topic, you may also enjoy our guide to What Is NAD+?, where we explain why this remarkable coenzyme is essential for energy production, DNA repair, and healthy aging.
So, how does the body make NAD+? The answer lies in three remarkable biological pathways that work together to create and recycle this essential coenzyme. In this guide, we'll explore how each pathway works, why NAD+ levels naturally decline with age, and what you can do to support your body's natural NAD+ production.
Understanding the Importance of NAD+
Before exploring how the body produces NAD+, it's helpful to understand why this coenzyme is so essential.
NAD+ plays a central role in cellular respiration, the process that converts carbohydrates, fats, and proteins into adenosine triphosphate (ATP)—the primary source of energy used by every cell in the body. Without adequate NAD+, cells cannot efficiently generate the energy required for normal function.
Beyond cellular energy production, NAD+ is also required by several important groups of enzymes, including sirtuins, PARPs, and CD38. These enzymes help regulate cellular repair, healthy aging, immune function, and the body's response to stress.
Sirtuins help regulate cellular health and support healthy aging, while PARP enzymes repair damaged DNA caused by normal metabolism and environmental stressors. CD38 plays an important role in immune function but also consumes significant amounts of NAD+. Because these enzymes constantly use NAD+, the body must continuously replace its supply through several biosynthetic pathways.
The Three Main Biosynthetic Pathways
Rather than relying on a single process, the human body uses three separate pathways to produce and recycle NAD+. Each pathway begins with different nutrients or precursor molecules and works together to maintain healthy NAD+ levels.
The De Novo Pathway
The De Novo pathway creates NAD+ from scratch using the essential amino acid tryptophan, which is obtained from protein-rich foods such as poultry, eggs, dairy products, fish, and legumes.
Because this pathway requires numerous enzymatic steps before NAD+ is produced, it is considered the least efficient method of NAD+ synthesis. However, it serves as an important backup pathway when other vitamin B3 precursors are limited.
The Preiss-Handler Pathway
The Preiss-Handler pathway begins with nicotinic acid (niacin), one form of vitamin B3 obtained through the diet. After several biochemical conversions, niacin is ultimately transformed into NAD+.
Although this pathway contributes to overall NAD+ production, it generally plays a smaller role than the body's primary recycling system.
The Salvage Pathway
The salvage pathway is the primary source of NAD+ production in most human tissues. Instead of creating NAD+ entirely from scratch, it efficiently recycles molecules that are generated after NAD+ has already been used.
This recycling process conserves energy and allows cells to continuously replenish their NAD+ supply with remarkable efficiency.
One of the most researched NAD+ precursors is nicotinamide riboside (NR), which cells can convert into NAD+ through the body's natural biosynthetic pathways. If you'd like to learn more, check out our guide to What Is Nicotinamide Riboside (NR)?.
A Closer Look at the Salvage Pathway
Because the body consumes large amounts of NAD+ every day for energy production, DNA repair, and cellular maintenance, constantly creating new NAD+ from scratch would be highly inefficient.
Instead, enzymes such as sirtuins, PARPs, and CD38 break down NAD+ during normal cellular activity, producing nicotinamide (NAM) as a byproduct.
Rather than allowing this valuable molecule to go to waste, the salvage pathway recycles it.
An enzyme called nicotinamide phosphoribosyltransferase (NAMPT)—often considered the rate-limiting step of the pathway—converts nicotinamide into nicotinamide mononucleotide (NMN). Another group of enzymes called nicotinamide mononucleotide adenylyltransferases (NMNATs) then converts NMN into fresh, usable NAD+.
Because of its speed and efficiency, the salvage pathway accounts for the majority of NAD+ production in mammalian cells.
Why Do NAD+ Levels Decline With Age?
One of the most common questions researchers have explored is why NAD+ levels naturally decrease as we get older.
Several factors appear to contribute to this decline. As we age, the activity of NAMPT—the key enzyme involved in the salvage pathway—gradually decreases, making it more difficult for cells to recycle NAD+ efficiently.
At the same time, the body experiences greater oxidative stress, accumulated DNA damage, and chronic low-grade inflammation. These changes increase the activity of NAD+-consuming enzymes such as PARPs and CD38, causing cells to use NAD+ more rapidly than it can be replaced.
Although this decline is considered a normal part of aging, it has become an important area of research because of NAD+'s central role in cellular energy and healthy aging.
Factors That Can Deplete NAD+ Levels
In addition to aging, several lifestyle and environmental factors may increase the body's demand for NAD+.
Chronic Inflammation: Ongoing inflammation can increase the activity of CD38, an enzyme that consumes significant amounts of NAD+.
DNA Damage: Exposure to ultraviolet radiation, pollution, smoking, and other environmental stressors increases DNA repair activity, causing PARP enzymes to consume additional NAD+.
Poor Metabolic Health: Excess calorie intake, obesity, and sedentary lifestyles place greater metabolic demands on cells and may increase NAD+ utilization.
Sleep and Circadian Disruption: Poor sleep habits and disrupted circadian rhythms may influence the activity of genes involved in NAD+ production and cellular metabolism.
Lifestyle Strategies to Support Natural NAD+ Production
While aging cannot be stopped, healthy lifestyle habits may help support the body's natural ability to produce and recycle NAD+.
Regular cardiovascular and resistance exercise has been shown to increase NAMPT activity in skeletal muscle, helping support the body's primary NAD+ recycling pathway.
A balanced diet that provides adequate vitamin B3 and sufficient protein supplies important building blocks used in NAD+ synthesis. Foods containing niacin, nicotinamide, and tryptophan all contribute to the body's natural production pathways.
Maintaining healthy sleep habits, managing chronic stress, and supporting overall metabolic health may also help preserve healthy NAD+ levels over time.
In addition to dietary sources of vitamin B3, some people choose supplements containing NAD+ precursors such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN). These compounds provide building blocks that cells can use to produce NAD+ through the body's natural biosynthetic pathways. If you're comparing the two, our article Nicotinamide Riboside vs. NMN: What's the Difference? explains how they work, how they differ, and what current research says about each.
Frequently Asked Questions
Can your body make NAD+ naturally?
Yes. Every cell in the human body continuously produces and recycles NAD+ through several biological pathways using nutrients obtained from food and molecules generated during normal cellular processes.
Can you get NAD+ from food?
Foods do not provide significant amounts of usable NAD+, but they do supply important nutrients such as vitamin B3 and tryptophan that help your body produce NAD+ naturally.
What vitamin helps make NAD+?
Vitamin B3 is the primary vitamin involved in NAD+ production. Different forms—including niacin, nicotinamide, and nicotinamide riboside—can all contribute to the body's natural NAD+ biosynthetic pathways.
Conclusion
Every second of every day, your body is producing, using, and recycling NAD+ to power the essential functions that keep your cells alive. Through the De Novo, Preiss-Handler, and Salvage pathways, your cells work continuously to maintain healthy NAD+ levels despite the constant demands of energy production, DNA repair, and cellular maintenance.
To continue learning about cellular health, explore these related guides:
What Is Nicotinamide Riboside (NR)?
Nicotinamide Riboside vs. NMN: What's the Difference?
Why Do NAD+ Levels Decline With Age?
While aging and lifestyle factors can gradually reduce NAD+ availability, understanding how these pathways work highlights the importance of supporting overall cellular health through regular exercise, balanced nutrition, quality sleep, and other healthy habits. As research into NAD+ continues to grow, so does our understanding of the vital role this remarkable coenzyme plays in lifelong wellness.