What Is NAD+? How To Boost Levels With Supplements

All of us want more energy. But where does energy come from? At the cellular level, it all begins with NAD⁺ (nicotinamide adenine dinucleotide).

Every cell in your body depends on it. At the core of metabolism, NAD⁺ shuttles energy-rich electrons into the mitochondria, where they’re spun into ATP, the universal energy currency of life. Without it, your cells couldn’t power a heartbeat, a muscle contraction, or a thought. NAD⁺ also fuels enzymes that police DNA for damage, coordinate defenses, and help cells switch into repair mode.¹ 

In this sense, NAD⁺ is both the wiring that carries power and the emergency crew that rushes in when something breaks.

The catch is that NAD⁺ doesn’t stay constant. By midlife, levels may sink to half of our youthful peak. As the pool of NAD⁺ shrinks, energy falters and repair systems wane, edging the system toward breakdown.*

It’s no wonder, then, that NAD⁺ has become a focus of aging science. In animals, topping up NAD⁺ has brought tired cells back to life. Could the same be done for us? The answer is more complicated than it looks, and that complexity is where the real story begins.*

What Does NAD⁺ Do In The Body? 

NAD⁺ plays two starring roles in biology: fueling energy and enabling repair.

Every calorie you eat must pass through a gauntlet of steps before it becomes usable energy. At each stage, NAD⁺ grabs high-energy electrons and delivers them to mitochondria, which churn out ATP.² 

NAD⁺ also powers enzymes that help cells adapt to and withstand stress. The most famous are the sirtuins, a family of proteins that act as molecular regulators of resilience. They keep mitochondria efficient, reduce oxidative spillover, and respond to stress by quieting inflammatory signals and activating protective pathways.³ In animal models, dialing up these enzymes has been shown to extend lifespan by up to 16%, as well as preserve youthful muscle and metabolism^.4 

Another NAD⁺-dependent family, the PARPs (poly-ADP ribose polymerases), patrol DNA for damage. Each cell faces thousands of lesions every day, and PARPs use NAD⁺ to build chains that summon the repair crew.⁵ 

Centenarians offer real-world proof of this system’s importance. People who reach 100 years or more show stronger PARP activity than younger controls, hinting at unusually robust DNA repair capacity.⁶ 

But here’s the rub. Every time PARP leaps into action, it burns through NAD⁺ molecules. As DNA damage builds with age, PARP activity drains the pool, leaving less NAD⁺ for sirtuins and for energy metabolism.⁷ That leads to a cellular tug-of-war over a dwindling resource. 

Which brings us to the crux of the problem. 

What Happens To NAD+ As You Get Older?

NAD⁺ levels fall steadily with age, dropping about 4% each year across adulthood. That may not sound like a lot, but it adds up fast. By the time you’re 40, your NAD⁺ may already be down by more than a third, compared to your twenties.⁸ And it only goes downhill from there.

As NAD⁺ slips away, the enzymes that depend on it start to falter. And inside the cell, the toll is clear. 

In aging mice, mitochondria produced only about half the ATP of youth, literally half the energy their cells once had. And this shortfall is tied directly to dwindling NAD⁺ and fading sirtuin activity.⁹ 

Yet the picture isn’t all grim. 

When scientists restored NAD⁺ in these same rodents, their mitochondria bounced back to youthful performance. ATP output rebounded, sirtuin activity strengthened, and the cells effectively recharged their power supply.

So the obvious question is, could we do the same thing in humans?

Can We Just Supplement NAD⁺ Directly?

The solution seems simple: just put NAD⁺ in a pill! But biology, true to form, doesn’t make it that easy.

In the digestive tract, NAD⁺ is dismantled by enzymes before it can reach your bloodstream. What your cells see are fragments, not the intact molecule, and recycling these pieces isn’t very efficient.¹⁰ 

Instead, the body prefers to absorb smaller forms of vitamin B3, then rebuild NAD⁺ in cells through established metabolic pathways. That’s why we focus on these precursors, rather than NAD⁺ itself.

How Does The Body Manufacture NAD⁺?

Because NAD⁺ can’t be taken up whole, cells rely on internal assembly lines to manufacture it. 

Various forms of B3 rely on different biological pathways, in effect taking separate routes that converge on NAD⁺.

Niacin

Niacin feeds into the Preiss–Handler pathway, a specialized expressway into NAD⁺ that runs particularly strongly in the liver, kidneys, and intestines.¹² These organs are the body’s industrial hubs: managing blood sugar, breaking down fats, detoxifying chemicals, and processing nutrients. All of these processes burn through enormous amounts of NAD⁺. 

But there’s a problem. At higher doses, niacin causes uncomfortable flushing and other side effects,¹³ making it tough to rely on niacin alone for sustaining NAD⁺. 

Niacinamide

Niacinamide (NAM) works through the salvage pathway, the body’s main recycling route for NAD⁺. Every time NAD⁺ is used, it leaves behind niacinamide.¹⁴ Rather than letting it go to waste, cells reclaim it and run it back through the salvage route to make fresh NAD⁺. 

This pathway is the backbone of NAD⁺ metabolism throughout the body. It runs especially hot in high-demand tissues like skeletal muscle, the brain, and the immune system — where NAD⁺ turnover is relentless to power movement, cognition, and defense.¹⁵ 

Yet again, there’s a tradeoff. With high intake, excess niacinamide has to be cleared. The body does this by methylating it, i.e., attaching methyl groups borrowed from nutrients like folate or SAMe.¹⁶ That clearance can sap molecular resources needed for other jobs, such as DNA repair and neurotransmitter production. 

Nicotinamide Riboside (NR)

Nicotinamide riboside (NR) is a late addition to the B3 family, first identified in 2004.¹⁷ What makes it stand out is that it has its own dedicated enzymes, the NR kinases, which act as a custom gate into NAD⁺, plugging it directly into the salvage pathway. Remarkably, this specialized machinery has been conserved from yeast to humans, as if biology stamped this pathway as “too important to lose.”

That efficiency shows up in people. Among all the NAD⁺ precursors, NR has built the strongest human track record for safety and effectiveness, and it can significantly boost NAD⁺ at comparatively low doses. In a 2019 clinical trial, a daily dose of just 300 mg raised whole-blood NAD⁺ by about 50% in a matter of eight weeks.¹⁸* 

Each of these precursors tells a different part of the story of NAD⁺. None is perfect in isolation, but together they reveal a strategy for sustaining NAD⁺. 

Here’s how to put that into action.

How Should We Think About Supporting NAD⁺?

1. Leverage Biology’s Backup Systems

NAD⁺ precursors don’t all travel the same route or reach the same destinations with equal efficiency. 

• Niacin feeds into a pathway that is most active in metabolic centers like the gut.¹² 
• Niacinamide works through the salvage pathway, especially important in high-turnover tissues like the immune system and brain.¹⁵
• Nicotinamide riboside also feeds into the salvage pathway, but it relies on its own enzymes (NRK), which are especially active in liver, kidney, and muscle.^19,20 

This “division of labor” implies that moderate doses of more than one precursor may better mirror biology’s own design, spreading the workload rather than overtaxing a single pathway.

Key takeaway: Use a mix of NAD⁺ precursors, like niacin, niacinamide, and NR, for broader support.

2. Balance the Methylation Burden

Excess niacinamide (and to a lesser extent, other B3s) has to be cleared. The body does this by attaching methyl groups, which are also used for DNA repair, neurotransmitters, and detoxification. Over time, high doses can strain this system.

Key takeaway: Pair any NAD⁺ precursors with methyl donors, such as methylfolate, vitamin B12, and betaine (or choline), to stay in balance.*

3. Tune the Salvage System

Supplying precursors isn’t the whole story. Equally important is how well the body recycles NAD⁺ once it’s been used. That recycling job depends on an enzyme called NAMPT (nicotinamide phosphoribosyltransferase).¹⁴ The more active NAMPT is, the more efficiently cells can stretch every molecule of NAD⁺. 

Certain plant compounds can help tilt the balance. When plants are stressed, like by pests or harsh sunlight, they generate protective compounds that, when we consume them, act as gentle stress signals for our own cells.²¹

Resveratrol is a prominent example. At low-to-moderate doses, it sparks mitochondria to work more efficiently and activates NAMPT, potentially boosting the efficiency of NAD⁺ recycling.^22,23*

Grape seed proanthocyanidins present another intriguing candidate for this role. In animal experiments, they’ve been shown to dial up NAMPT and boost NAD⁺ in specific tissues.^24,25 

These plant signals act like subtle biochemical nudges, helping you get more mileage out of every molecule of NAD⁺.

Key Takeaway: Stack NAD⁺ precursors with plant-derived boosters, like resveratrol or grape seed proanthocyanidins.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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