NAD+ Explained: The Powerful Molecule Shaping Energy and Cellular Health

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Dr. Eric Fete, Founding Physician

Of all the molecules shaping today’s conversation about healthspan and longevity, few are as essential — and as misunderstood — as NAD+.

This coenzyme, found in every living cell, fuels the most fundamental processes of life: turning food into energy, repairing DNA, and supporting resilience against stress and disease. Yet most people hearing about NAD+ in a gym locker room, an IV clinic, or on social media only get fragments of the story. For some, it has become a miracle cure. For others, it’s just another wellness fad.

The truth lies somewhere in between. At ResetOne, we see NAD+ as a powerful building block in longevity — but only when it’s used wisely, clinically, and in context.

The Science of NAD+: Why It Matters

Nicotinamide adenine dinucleotide — better known as NAD+ — is a molecule so essential that every cell in your body depends on it. Without it, life simply couldn’t continue. That’s why it’s central to the conversation about aging and performance.

One of its most important jobs is in energy production. It helps convert the food you eat into usable fuel, and without it, your mitochondria — the powerhouses of your cells — can’t function properly. But energy isn’t the only story. This coenzyme also plays a vital role in DNA repair. Every day, your genetic material is damaged by oxidative stress, sunlight, and even normal metabolism. NAD+ activates the enzymes that patch that damage and keep your DNA intact.

It also fuels sirtuins — the “longevity proteins” that regulate stress responses, inflammation, and metabolism. And in the brain, it supports neurotransmitter balance and nerve protection, helping your mind stay clear and resilient.

Think of it as both the spark plug and the mechanic inside your cells: creating the energy to keep everything running while fixing the wear and tear that builds up over time.

Why NAD+ Declines With Age

By midlife, cellular NAD+ levels can drop to nearly half of what they were in youth. Several forces drive this decline.

Chronic inflammation, oxidative stress, and DNA damage all consume this coenzyme more quickly, leaving less available for essential functions. At the same time, the enzymes that normally build and recycle it become less active with age. Other enzymes, like CD38, actually accelerate its breakdown — and their activity rises as we get older, especially in the presence of inflammation.

Lifestyle factors compound the problem. Poor sleep, overeating, ongoing stress, and a lack of movement all make matters worse, further depleting this crucial molecule.

Together, these changes contribute to hallmark signs of aging: mitochondrial dysfunction, metabolic imbalance, neurodegeneration, and reduced resilience to stress.

Signs Your NAD+ May Be Low

You can’t feel NAD+ directly, but when reserves start to dip, the effects often show up in everyday life. People may notice persistent fatigue or reduced stamina, slower recovery from exercise or illness, or lingering muscle soreness. Cognitive changes are also common — brain fog, memory lapses, or difficulty concentrating. On a metabolic level, low availability can make the body more susceptible to blood sugar issues and weight gain. And overall, the system becomes less resilient, with stress or minor illness hitting harder than it used to.

Of course, these symptoms aren’t unique to NAD+ decline. That’s why at ResetOne, we look at biomarker patterns and context before deciding whether targeted support makes sense.

How Do We Know if You Need NAD+ Support?

Right now, there isn’t a single standardized blood test that accurately reflects NAD+ status in humans. The tests that do exist are still in research and not consistent enough for everyday use.

At ResetOne, we approach this differently. Instead of relying on one imperfect test, we look at patterns across multiple biomarkers: inflammation, oxidative stress, mitochondrial function, and metabolic health, combined with your symptoms and overall health goals.

If your labs show high oxidative stress, signs of insulin resistance, or mitochondrial inefficiency, and you’re also experiencing fatigue, slow recovery, or brain fog, that’s often where additional support makes sense. In other words: we don’t guess, but we also don’t depend on unproven tests. We integrate the whole picture.

Who Should — and Shouldn’t — Use NAD+

While generally considered safe, supplemental support isn’t right for everyone.

Best candidates:

• People looking to support healthy aging
• Those addressing metabolic decline or fatigue
• Athletes seeking improved stamina and recovery
• Patients with evidence of metabolic stress or mitochondrial inefficiency

Not recommended for:

• People with active cancer or high cancer risk (NAD+ may also fuel tumor growth)
• Those with uncontrolled cardiovascular disease, diabetes, or liver disease
• Pregnant or breastfeeding women
• Anyone self-prescribing supplements without guidance

How to Boost NAD+: Food, Lifestyle, and Advanced Interventions

Foods That Support Healthy Levels

It’s no surprise that a healthy diet supports optimal levels, but it’s helpful to know which foods act as precursors and cofactors your body uses to build and recycle NAD+:

• Niacin-rich foods (Vitamin B3) in descending order: tuna, beef liver, turkey, chicken, salmon, peanuts, mushrooms, brown rice.
• Nicotinamide riboside (NR): present in small amounts in milk and dairy products.
• Tryptophan-rich foods: eggs, cheese, oats, soy, nuts, seeds.
• Leafy greens: spinach, kale, broccoli provide folate and polyphenols
• Whole grains and legumes: supply minerals like magnesium and zinc
• Yeast-based foods: nutritional yeast and brewer’s yeast are rich in B vitamins and natural precursors.

These foods won’t “flood” your system with NAD+, but they help maintain a steady baseline — ensuring your body has the raw materials for cellular energy.

Lifestyle Habits That Influence Levels

• Exercise: boosts the activity of enzymes that synthesize NAD+, especially endurance and high-intensity training
• Fasting or time-restricted eating: reduces NAD+ consumption
• Sleep and circadian rhythm: NAD+ levels cycle daily; disrupted sleep throws this rhythm off
• Heat and cold exposure: saunas and cold plunges can activate stress pathways linked to NAD+ metabolism
• Stress management: chronic stress increases NAD+ consumption; mindfulness and recovery practices protect it

These habits form the foundation. At ResetOne, they’re always the first step — before layering in advanced therapeutics.

Advanced Therapeutics for NAD+: What Works and What Doesn’t

When it comes to NAD+ support, the medical and supplement worlds are brimming with options — IV drips, nasal sprays, oral precursors, and a wave of new compounds hitting the market. It’s become one of the hottest areas in longevity, but here’s the catch: not all approaches deliver the same impact. Some are overhyped, some are promising but unproven, and a few are genuinely game-changing.

This is where clinical judgment matters. Beyond food and lifestyle, advanced therapeutics can add powerful layers of support — but only when chosen wisely, with an understanding of how they work, who they benefit most, and where the science actually stands.

1. IV drips and injections

These are the most heavily marketed treatments, often billed as a fast, dramatic way to “flood” the body with NAD+. In reality, much of it given intravenously is rapidly broken down before it can be used by cells. The NAD+ molecule itself is too large to be absorbed directly. Some people feel a temporary lift, but the effect is inconsistent and often short-lived. IV drips also come with downsides: they can be uncomfortable (the well-known “NAD burn”), require significant time, and are costly.

They also carry an extra caution: people with poor histamine clearance often don’t tolerate IV or injectable NAD+ well. Rapid delivery can provoke flushing, headaches, nausea, or allergy-like symptoms. For these patients, IV is rarely the right choice. 

2. Nasal sprays

Another emerging way to deliver NAD+ is through nasal sprays. This method bypasses the digestive system, which means more of the compound may stay intact and available for your body to use. Because it’s absorbed through the nasal passages, there’s also potential for it to reach the brain more directly than oral forms.

Early research is still limited, but the results so far are intriguing — especially in the areas of cognitive function and neuroprotection. Some patients describe feeling more mental clarity and focus, though larger studies are needed to confirm these effects. While nasal sprays aren’t yet as common as IVs or oral supplements, they’re an exciting option being studied as part of the next wave of NAD+ support.

3. Oral precursors (NR and NMN)

When people talk about NAD+ supplements, they’re usually referring to precursors — compounds that don’t deliver NAD+ directly, but instead act as raw materials your body can convert into it. The two most widely studied are nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).

In animal studies, both NR and NMN have shown promising effects: better metabolic health, stronger mitochondrial function, and even slower markers of age-related decline. Human trials are smaller but encouraging. Participants have reported improvements in insulin sensitivity, energy metabolism, and fatigue, suggesting these precursors may help the body replenish NAD+ in meaningful ways.

That said, there are some caveats. Supplement quality varies widely — not every product on the market contains what it claims, and purity can be inconsistent. Absorption is another factor: some people respond well, while others see little change in their levels or symptoms. For this reason, it’s important to use clinical-grade formulations and to evaluate whether precursors are actually making a difference based on biomarkers and outcomes.

In short: NR and NMN offer a practical, accessible way to support NAD+, but they’re not one-size-fits-all. When used thoughtfully and in the right context, they can form a steady foundation for NAD+ replenishment.

4. NAD+ protectors (CD38 inhibitors)

Supporting NAD+ isn’t just about making more of it — it’s also about keeping what you already have. One of the main culprits in NAD+ decline is CD38, an enzyme that becomes more active with age and chronic inflammation. Think of it as a leak in your cellular fuel tank: the harder CD38 works, the faster your supply drains away.

Researchers are exploring ways to slow this leak, and some promising candidates are found in plants we already know well. Compounds like apigenin (from parsley, celery, and chamomile) and quercetin (in onions, apples, and capers) may help reduce CD38 activity and preserve existing NAD+ levels. While this area of research is still young, the idea of protecting your reserves — not just trying to refill them — represents another important piece of the longevity puzzle.

5. 5-amino-1MQ

Among the advanced therapeutics, 5-amino-1MQ stands out for its unique mechanism. Unlike precursors such as NMN or NR, which add building blocks, this compound works by blocking NNMT — an enzyme that actively depletes nicotinamide, one of the raw materials needed to sustain NAD+. In other words, it doesn’t just top off the tank; it plugs the leak, helping the body preserve its own reserves more efficiently.

Research points to benefits in metabolism, energy efficiency, and body composition, making 5-amino-1MQ an especially intriguing tool in the cellular optimization toolkit. While it is newer on the market, its targeted approach highlights the evolving sophistication of advanced therapeutics designed to support healthy aging at the cellular level.been linked to improved metabolism, fat loss, and enhanced energy. While still considered experimental, it’s a promising way to support healthy levels more efficiently.

6. 1-Methylnicotinamide (1-MNA)

Another promising therapeutic is 1-Methylnicotinamide (1-MNA), a compound naturally produced in small amounts in the liver and muscles during exercise. What makes 1-MNA stand out is its ability to block NNMT, the same enzyme that accelerates NAD+ decline. By doing so, it helps maintain balance in the system while also offering benefits that extend beyond NAD+ preservation.

Studies highlight its anti-inflammatory and vascular-protective properties, along with positive effects on energy metabolism, recovery, and fatigue — including in post-viral and high-stress states. Early evidence also points to potential advantages for cardiovascular resilience and metabolic efficiency, positioning 1-MNA as an exciting new option in the landscape of cellular health support.

The medical perspective:

I tend to favor 1-MNA and short, strategic courses of NMN or NR. These provide a reliable foundation the body can use to naturally rebuild its NAD+ pool. When layered with the right lifestyle strategies — and, in select cases, nasal delivery — the results are typically more consistent and sustainable than what we see with IV drips. While IV has its place, it’s rarely my first choice and can pose challenges, especially for patients with histamine sensitivity.

In some situations, we may also incorporate advanced options like 5-amino-1MQ, which helps reduce NAD+ depletion by targeting it at the enzymatic level. Ultimately, the key is tailoring every intervention to a patient’s unique biomarkers, health status, and long-term goals.

NAD+ and How it Affects Fitness + Performance

By Emily Hoffman, Head of Fitness

Because it’s central to ATP (energy) production, NAD+ directly impacts stamina, endurance, and recovery capacity. When depleted or low, muscles fatigue more quickly, mitochondria struggle to keep up with energy demand, and recovery from training slows down.

Optimizing levels can shift that balance in several key ways:

• Improved stamina and endurance: Mitochondria generate more ATP, which translates into greater energy availability during workouts.
• Faster recovery between sessions: Adequate levels support muscle repair and reduces oxidative stress after intense training.
• Enhanced resilience to fatigue: By fueling sirtuins and DNA repair enzymes, it helps muscles adapt to stress, so you can train harder with less wear and tear.
• Metabolic efficiency: Higher availability improves insulin sensitivity and glucose uptake, giving muscles a more stable energy supply during exercise.

I notice that those who add NAD+ support to their regimen often notice subtle but meaningful improvements rather than dramatic overnight changes. In workouts, this shows up as steadier energy throughout a session and fewer mid-workout crashes. Recovery also tends to feel smoother — muscle soreness resolves more quickly, and fatigue doesn’t linger as long between training days. Many describe it as being able to train with greater consistency, stringing strong workouts together without the usual dips or setbacks. It’s not a stimulant or a quick fix; instead, it provides a steady foundation that makes exercise and recovery feel more efficient, sustainable, and rewarding over time.

Think of it as premium-grade fuel for the engine you’re already building in the gym.

I also see improvements in fitness gains because patients are supported in a 360 degree way, from better sleep to better focus.

NAD+ in Everyday Life: Beyond the Gym  

NAD+ is central to much more than just energy and exercise. It quietly supports multiple daily functions:

Sleep & Circadian Rhythm

• NAD+ levels rise and fall in a daily rhythm that interacts with circadian clock genes.
• This cycle helps regulate when we feel alert vs. sleepy.
• Low levels can disrupt circadian alignment, leading to poor-quality sleep and daytime fatigue.

Cognitive Function & Focus

• Supports neurotransmitter balance and neuronal repair.
• Fuels sirtuins in the brain, which protect against neurodegeneration.
• Patients often describe extra support as giving them clearer thinking and better memory.

Stress Resilience

• NAD+ helps regulate the body’s stress response by supporting sirtuins and mitochondrial efficiency.
• This translates into a better ability to “bounce back” from both physical and mental stress.

Metabolism & Weight Regulation

• NAD+ plays a key role in insulin sensitivity and glucose metabolism.
• Helps muscles use energy more efficiently and reduces metabolic strain.

Cellular Repair & Longevity

• Beyond energy, it is essential for DNA repair and maintaining genomic stability.
• This isn’t something people feel day to day, but it’s one of the reasons it is considered a cornerstone of healthy aging.

NAD+ in Context: Your Longevity Reset

NAD+ isn’t just another wellness trend. It’s a molecule at the center of life itself — one that every cell relies on to create energy, repair damage, and stay resilient under stress. Supporting it wisely can mean more than just a temporary lift; it can help build the cellular foundation for sharper thinking, steadier energy, stronger performance, and healthier aging.

But the approach matters. Chasing quick fixes or overhyped fads rarely delivers lasting results. The real power lies in combining daily habits that sustain NAD+ naturally — movement, nutrition, quality sleep, stress resilience — with advanced therapeutics chosen and timed based on your unique biomarkers. That’s where science moves from theory into practice.

At ResetOne, we bring these pieces together into one integrated system, so you’re not left experimenting on your own or guessing what might work. Instead, you gain a strategy — personalized, physician-guided, and designed to extend not just your years, but the quality within them.

Long live longevity.^™