What Is NAD+? The basics, NAD vs NADH, and everyday ways to support it

What is NAD+: A vital molecule for health and longevity

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The molecule your cells run on—and how to keep it steady as you age

What is NAD+? It’s the coenzyme your cells use to make energy, repair DNA, and stay resilient. This guide explains what is NAD, why levels fall, a plain NAD vs NADH refresher, how to increase NAD levels with habits and precursors, whether NAD IV therapy or NAD injections make sense, and answers “can NAD be harmful?” with real data. A recent review in Nature Aging brings the human evidence together; we translate it here in simple terms.

Most people hear about NAD+ from a gym buddy, a trainer, or a podcast on longevity. Under the buzz is a simple idea: your cells spend NAD+ all day to turn food into energy, repair DNA, and keep stress-response systems online. As the years go by, that pool shrinks. The goal isn’t a quick spike; it’s finding steady ways to support what your cells already do.

In one minute

  • NAD+ powers energy production, DNA repair, and stress-response enzymes. Levels trend down with age. 
  • A rise in CD38, an enzyme that consumes NAD+, is a key reason levels drop; it links aging and inflammation to the coenzymes loss. 
  • Lifestyle nudges help: training supports the salvage pathway (NAMPT), sleep/circadian rhythm matters, diet supplies B3. 
  • For supplements, daily precursors have the most practical human data today; in trials, NR and NMN raise blood NAD+.
  • IV approaches can shift blood markers fast in research settings, but they’re clinic-bound and short-lived; a 2024 pilot found NR IV better tolerated than NAD+ IV in healthy adults.

NAD+ and NADH—quick refresher

If you’ve wondered about NAD vs NADH, here’s the short version: NAD+ accepts electrons and becomes NADH; NADH then donates those electrons to help make ATP. Cells cycle between the two constantly, so NAD vs NADH is really about balance: plenty of NAD+ available to accept electrons, and enough NADH to power energy production

Key read: Acta Physiologica explainer on the NAD+/NADH pair and cellular redox.

What NAD+ does for you

Your day runs on thousands of NAD-dependent reactions:

  • Energy: fuels key mitochondrial steps that generate ATP from the food you eat.
  • DNA care: provides the “currency” PARP enzymes spend during DNA repair.
  • Epigenetics and stress response: sirtuins use it to fine-tune gene activity, protein quality, and mitochondrial function.
NAD+ sits at the crossroads of aging biology. The circle shows how NAD+ augmentation relates to the 12 established hallmarks, grouped as primary (purple: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis), antagonistic (yellow: deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, disabled macroautophagy), and integrative (rose: stem-cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis). The center highlights key NAD+-dependent pathways (e.g., PARPs, sirtuins, mitophagy/PGC-1α, AMPK) reported in cell and animal studies.

How your body makes NAD+

Your cells top up the molecule through three routes. Most tissues rely on the salvage pathway, which is why lifestyle and certain precursors make a visible difference.

Salvage (main route in many tissues)

  • Recycles nicotinamide (NAM) back to NAD+ through NAMPT → NMN, then NMNATs → NAD+.
  • Nicotinamide riboside (NR) joins here: NR → NMN via NR kinases (NRKs), then into NAD+.
  • This route is rate-limited by NAMPT and responds to training and circadian rhythm—one reason exercise and sleep matter.

Preiss–Handler (niacin route)

  • Uses nicotinic acid (NA) → NaMN → NaAD → NAD+ (via NAPRT and NMNATs).
  • Clinically familiar because niacin has a long history as vitamin B3.

De novo (from tryptophan)

  • Converts tryptophan through the kynurenine pathway, then merges into the NA branch.
  • Slower and tightly controlled; useful for whole-body balance but not a quick lever for healthy people.

Why this matters::

In human studies, NR and NMN raise blood NAD+ by feeding the salvage pathway, while NA/NAM act through their respective entries. For dose ranges, evidence tiers, and emerging compounds (NRH, NMNH)

What is NAD pathway graphic: De novo (tryptophan), Preiss–Handler (niacin/NA), Salvage (NR, NMN, NAM) with NAD+-consuming enzymes
Pathways at a glance: De novo (from dietary tryptophan), Preiss–Handler (from niacin/NA), and Salvage (recycling NAM; NR and NMN feed here). NAMPT is the rate-limiting step in salvage. NAD+ is also used by enzymes like CD38 and PARPs.

Why levels fall with age (CD38 and more)

As we get older, CD38 activity rises in several tissues. CD38 breaks down NAD+ and even degrades NMN, trimming the pool that cells rely on. In mouse and tissue studies, higher CD38 is linked to its decline and mitochondrial dysfunction; blocking or deleting CD38 preserved NAD+ and improved metabolic readouts. Human adipose data point the same way: CD38 expression is higher with age. 

Inflammation plays into this story. Senescent cells and inflammatory signals push macrophages toward a CD38-high state, which speeds NAD+ use. This is one reason lifestyle and body composition influence NAD+ biology.

Read more: understanding inflammation and aging

Why do NAD levels decline with age?

Habits that speed the decline

None of this is about blame; it’s about knowing the levers.

  • Low activity: less stimulus for NAMPT, the rate-limiting enzyme in the main salvage pathway. 
  • Chronic inflammation: extra CD38 activity from immune cells drains NAD+. 
  • Circadian disruption and short sleep: the NAD+ system is tied to the body clock; erratic sleep patterns can throw it off. 
  • Excess alcohol: ethanol metabolism pushes the NADH/NAD+ redox balance the wrong way and burdens liver metabolism.  

Each of these acts like a small leak in the tank. Patch a few leaks and the whole system runs better.

“The loss of NAD as we age, and the resulting decline in sirtuin activity, is thought to be a primary reason our bodies develop diseases when we are old but not when we are young.”

– David A. Sinclair, Lifespan: Why We Age—and Why We Don’t Have To

How to increase nad+ levels naturally

Readers ask “how to increase NAD levels?” more than anything else. Start with the basics:


Quick note:

Training supports the salvage pathway through NAMPT, the rate-limiting step in NAD+ recycling. That’s one reason exercise and sleep show up over and over in NAD+ research.

Training

Regular exercise is a reliable way to support the salvage pathway. Human work shows higher muscle NAMPT in trained people, and programs in previously sedentary adults move NAMPT in the right direction over weeks. Start where you are and build. Get started with the best exercises for longevity.

Fasting and meal timing


Short fasting windows and time-restricted eating line up with the clock that drives daily NAD+ swings. Lab and human data show that fasting nudges NAMPT and related pathways. Keep it sustainable and watch total protein and micronutrient intake. Learn more about intermittent fasting here.

Dietary B3 (niacin/niacinamide)

Foods that supply vitamin B3 feed the coenzyme production. See our guide to foods that contain NAD/NAD precursors.

Sleep

Aim for a consistent sleep window. Sirtuins and NAD+ follow daily rhythms; regular timing supports those cycles. Learn more about the importance of sleep on longevity

If you’re mapping how to increase NAD levels naturally, pair training with consistent sleep and a B3-rich diet.

Supplements in context (in short)

  • Vitamins NA and NAM raise NAD+ via established routes. Niacin flush is common at higher doses; very high, long-term nicotinamide can work against sirtuin-linked goals.
  • Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are the newer precursors with the strongest human evidence for raising blood NAD+. Multiple NR trials report sustained increases; an NMN RCT in postmenopausal women with prediabetes showed gains in muscle insulin sensitivity alongside higher levels.

Want the full comparison, including emerging compounds (NRH, NMNH) and where tryptophan fits?

NAD+ Precursors: what they are, how they work, and which ones have human data

Tip:

Read also this human study from Andrea Maier and colleagues, which reports remarkable results on NMN supplementation’s effects on NAD+ levels and healthy aging

NAD IV therapy and injections: what studies say

Clinics offer NAD+ IV therapy and, more recently, NR IV. Early human pilots show that IV routes can shift blood NAD+ quickly, but comfort varies and the effect is short-lived unless you keep returning to the clinic. Emerging data suggest NR IV is better tolerated than NAD+ IV therapy in healthy adults under controlled conditions. For everyday life, most people who want support choose oral precursors with published human data.

Our position is consistent with the comparison study: oral NAD+ itself isn’t the practical choice (low absorption), while NR and NMN have clearer evidence for raising the molecule levels in people.

Can NAD be harmful? Safety snapshot

Most clinical studies so far run for weeks to months and focus on specific groups.

  • NR: repeat-dose trials in middle-aged and older adults show sustained rises in whole-blood NAD+ with good tolerability.
  • NMN: in a 10-week RCT, postmenopausal women with prediabetes improved muscle insulin sensitivity; safety looked acceptable in that timeframe. Larger and longer trials are in progress.
  • NA/NAM: long clinical history as vitamin B3 forms. Expect flushing with niacin; keep nicotinamide within standard vitamin ranges unless guided by a clinician.

Also interesting: Top 11 longevity hacks backed by science

Where our products fit

If you want a simple, daily option, our NAD+ Booster Capsules combine NR with standard-dose NAM, feeding the main salvage pathway that most tissues use.

Still choosing between formats? Read What is NMN? and NR benefits & side effects.

Tip:

unsure what suits you? Try a two-month A/B at home—month 1 Liposomal NMN, month 2 NAD+ Booster (NR + NAM), and track sleep, afternoon energy, and recovery. People vary; a short self-trial beats guesswork.

FAQ


Is NAD+ the same as NADH?


No. That’s the core of NAD vs NADH: NAD+ accepts electrons to become NADH; NADH donates them to help make ATP.


Do oral NAD+ pills work better than precursors?


No. Direct oral NAD+ isn’t the route with the best human evidence. Studies today more clearly support NR and NMN for raising blood Nicotinamide Adenine Dinucleotide.



How to increase
NAD+ levels?



Train regularly, keep sleep/circadian habits steady, eat a B3-rich diet, and consider studied precursors like NR or NMN.



Are NAD injections or IV therapy better options?


IV routes can move blood markers fast in a clinic setting, but the effect is brief and sessions take time. For daily use, people usually prefer oral precursors with practical dosing and human data.


Can NAD be harmful?


At standard vitamin ranges, serious issues are uncommon. Niacin flush is common at higher doses; very high chronic nicotinamide may not match sirtuin-linked goals. Ask a clinician if you have a condition or take medications.

References
  1. Zhang J, Wang H-L, Lautrup S, et al. Emerging strategies, applications and challenges of targeting Nicotinamide Adenine Dinucleotide in the clinic. Nature Aging (2025). https://doi.org/10.1038/s43587-025-00947-6
  2. Dellinger RW, Santos SR, Morris M, et al. Repeat dose NRPT (nicotinamide riboside + pterostilbene) increases NAD+ in humans: randomized, double-blind, placebo-controlled. npj Aging and Mechanisms of Disease (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6577427/
  3. Yi L, Maier AB, Tao R, et al. β-Nicotinamide mononucleotide supplementation in healthy middle-aged adults: randomized, double-blind, placebo-controlled, dose-dependent trial. GeroScience (2022). https://pubmed.ncbi.nlm.nih.gov/36482258/
  4. Camacho-Pereira J, Tarragó MG, Chini EN, et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction. Nature Medicine (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933983/
  5. Katsyuba E, Auwerx J. Modulating Nicotinamide Adenine Dinucleotide metabolism, from bench to bedside. Nature Metabolism (2018) and related reviews. Open-access overview: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558103/
  6. Canto C, Auwerx J. Nicotinamide Adenine Dinucleotide and sirtuins in the circadian clock and metabolism. Trends in Endocrinology & Metabolism (2018). https://www.sciencedirect.com/science/article/pii/S2468501118300063
  7. Kunz WS. The NAD+/NADH redox couple in bioenergetics. Acta Physiologica (2013). https://onlinelibrary.wiley.com/doi/full/10.1111/apha.13921
  8. Yoshino J, Mills KF, Yoon MJ, Imai S-I, et al. NMN improves muscle insulin sensitivity in women with prediabetes (trial report). Science (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747183/
  9. Ma L, et al. Fasting and the salvage pathway in humans (NAMPT response to short-term fasting). Am J Physiol Endocrinol Metab (2010). https://pubmed.ncbi.nlm.nih.gov/20148352/
  10. Synthesis on IV routes (NAD+ IV vs NR IV) and tolerability from early pilot work; overviewed in clinical reviews on Nicotinamide Adenine Dinucleotide targeting. See the Nature Aging review (Ref. 1) and recent clinical summaries: https://pmc.ncbi.nlm.nih.gov/articles/PMC9170600/

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Prof. Dr. Andrea Maier

Prof. Dr. Andrea Maier is an internist and professor of aging (“ longevity medicine ”) at the Vrije Universiteit in Amsterdam and the University of Melbourne, Australia. She studies the aging body and searches for anti-aging treatments. She heads the Center for Healthy Longevity in Singapore.
Why do we gradually decline during our average life of more than 80 years? Can we stop that process? Or maybe even turn around? And to what extent should we really want that? Maier gives practical tips on how we can extend our lifespan while also staying healthy.

Topics Andrea Maier talks about

  • Health
  • Aging and rejuvenation
  • Interventions to reverse aging
  • Gerontology
  • Innovation in medicine
  • Medicine


Background Andrea Maier

Andrea Maier graduated in Medicine from the University of Lübeck in 2003. She specialized in internal medicine at the Leiden University Medical Center and subsequently chose the subspecialty of Geriatric Medicine. This is where she started her research into aging.

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