Product description
What is NAD+?
NAD+ (nicotinamide adenine dinucleotide, oxidized form) is a key coenzyme found in all living cells, essential for fundamental metabolic processes and cellular signaling. This molecule was discovered in 1906 by Arthur Harden and William Young during research on yeast fermentation, which brought them the Nobel Prize in Chemistry in 1929.
Structurally, NAD+ consists of two nucleotides linked by phosphate groups — the adenosine nucleotide and the nicotinamide nucleotide. Its molecular formula is C₂₁H₂₇N₇O₁₄P₂, and its molecular weight is 663.43 Da. NAD+ exists in two forms — oxidized (NAD+) and reduced (NADH) — which are interconverted during redox reactions, serving as an electron carrier in cellular metabolism.
In the body, NAD+ is synthesized de novo from tryptophan or through salvage pathways from precursors such as nicotinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). The key enzyme in salvage synthesis is nicotinamide phosphoribosyltransferase (NAMPT), whose activity is subject to circadian regulation.
One of the most significant discoveries of recent decades is the observation that NAD+ levels decline dramatically with age — by as much as 50% between youth and old age in mammals. This age-related decline in NAD+ correlates with many hallmarks of aging, including mitochondrial dysfunction, genomic instability, and impaired intercellular communication, which has made NAD+ supplementation a subject of intensive longevity research.
Mechanism of action
Coenzyme in redox reactions — NAD+ plays a fundamental role as an electron acceptor in oxidation reactions, being reduced to NADH. This process is central to glycolysis, the Krebs cycle, and β-oxidation of fatty acids. NADH is then oxidized in the mitochondrial respiratory chain, driving ATP synthesis.
Activation of sirtuins — NAD+ is an essential substrate for the family of NAD+-dependent deacetylase enzymes called sirtuins (SIRT1-7). Sirtuins regulate key processes related to aging, including DNA repair, mitochondrial function, metabolism, inflammatory response, and cellular homeostasis. Sirtuin activity depends directly on NAD+ availability, linking cellular energy status with epigenetic regulation.
Substrate for poly(ADP-ribose) polymerase — NAD+ is consumed by PARP enzymes (PARP-1, PARP-2), which are involved in DNA damage repair. In response to extensive DNA damage, PARP hyperactivation can lead to depletion of NAD+ stores, which disrupts energy metabolism and contributes to mitochondrial dysfunction.
Signaling via CD38 — The ectoenzyme CD38 and related CD157 hydrolyze NAD+ in the production of cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), which act as second messengers in calcium signaling. CD38 activity increases with age and is a major factor in the decline of NAD+.
Circadian rhythm regulation — NAD+ biosynthesis is controlled by the biological clock through regulation of NAMPT expression by the BMAL1/CLOCK complex. In turn, NAD+ through activation of SIRT1 modulates the transcriptional activity of this complex, creating a feedback loop linking metabolism with circadian rhythm.
Scientific research directions
Research on NAD+ and its precursors focuses on their potential impact on aging, cognitive function, metabolism, and neurodegenerative diseases.
Aging and longevity
Studies have shown that restoring NAD+ levels through precursor supplementation (NMN, NR) can significantly improve age-related functional defects in rodents, counteracting many aging diseases, including neurodegeneration. In a study of adults aged 45-60, supplementation with 300 mg NMN daily for 90 days resulted in a significant increase in telomere length in white blood cells. Studies in human cells have shown that NAD+ can slow natural aging and protect against UV-induced aging by improving mitochondrial function and activating sirtuins.
Cognitive function and neuroprotection
In a 2025 study, NMN was shown to reverse D-galactose-induced neurodegeneration and improve the intestinal barrier in mice through activation of the SIRT1 pathway. Clinical studies in patients with Alzheimer's disease have shown that a cocktail of compounds containing the NAD+ precursor (NR) reversed neurodegeneration and improved mitochondrial function. In patients with Cockayne’s syndrome, a disease characterized by NAD+ deficiency, supplementation showed promising results.
Metabolism and metabolic diseases
A 2024 study showed that NMN may increase glucose uptake through several mechanisms, including increasing levels of the mitochondrial protein UCP1, which converts glucose into heat. NMN may also increase ketone body production and improve insulin sensitivity. In a study of 30 middle-aged and older overweight and obese individuals, taking 500 mg NMN twice daily for 28 days significantly reduced LDL cholesterol, body weight, and diastolic blood pressure.
Muscle function and physical performance
NAD+ levels decline in skeletal muscle with age and physical exertion. Studies show that NMN supplementation may improve aerobic capacity and mitochondrial function in skeletal muscle. The NAMPT-NAD+-SIRT pathway regulates metabolic adaptations to exercise and caloric restriction.
Scientific context
NAD+ is at the center of scientific research on aging as a molecule linking energy metabolism with epigenetic regulation and DNA repair. The discovery of the link between NAD+ and sirtuins in the 1990s — when the SIR2 gene in yeast was shown to extend replicative lifespan — revolutionized the understanding of the molecular mechanisms of aging.
Among the main NAD+ precursors used in supplementation are:
- NMN (nicotinamide mononucleotide) — direct NAD+ precursor, actively studied in the context of aging
- NR (nicotinamide riboside) — another precursor, commercially available as Niagen
- Nicotinamide (NAM) — a form of vitamin B3, although high doses may inhibit sirtuins
- Nicotinic acid (niacin) — the classic vitamin B3, but causes characteristic “flushing”
NAD+ differs from classic vitamin supplements in that it acts not only as a coenzyme, but also as a substrate for signaling enzymes. Supplementation with NMN and NR has been shown to raise NAD+ levels in tissues in humans, although optimal dosing and long-term effects remain under investigation.
In 2024, researchers proposed a combination approach to sirtuin activation by combining NAD+ precursors with sirtuin activators (STACs), such as resveratrol or SRT2104, as a potential anti-aging intervention.
Safety profile in studies
General tolerance — NAD+ and its precursors (NMN, NR) show a good safety profile in clinical studies. Numerous human studies indicate that supplementation offers benefits with minimal or no side effects, although some studies show no observable benefits.
NMN/NR adverse effects — Sporadically observed symptoms include: mild gastrointestinal complaints (nausea, discomfort), skin flushing at high doses, occasional headaches.
Interactions — Theoretical concerns relate to the potential impact of high NAD+ levels on PARP activation in extensive DNA damage. Supplementation is not recommended in people with active cancer without medical consultation, due to the role of NAD+ in cell proliferation.
Regulatory status — NMN and NR are available as dietary supplements in many countries. In 2022, the FDA excluded NMN from the dietary supplement category in the US, recognizing it as an investigational drug, although this decision is controversial. NR (Niagen) remains available as a supplement.
Dosing in studies — In clinical studies, NMN doses of 250-500 mg daily and NR 300-1000 mg daily have been used. The optimal long-term dosing remains undefined.
Bibliography – latest scientific studies
- Lin Y et al. NMN reverses D-galactose-induced neurodegeneration and enhances the intestinal barrier of mice by activating the Sirt1 pathway. Front Pharmacol. 2025;16:1545585. PubMed
- Elmorsy EA et al. E1231/NMN protects against experimental metabolic syndrome: The central role of SIRT1 in modulating AKT/Nrf2/NFκB signaling. Front Pharmacol. 2025;16:1558709. PubMed
- Sah P et al. Sirtuin activators as an anti-aging intervention for longevity. Explor Drug Sci. 2025;3:100881. PDF
- Vinten C et al. Promising Results With NAD Supplementation in Rare Diseases With Premature Aging and DNA Damage. Aging Cell. 2025;24(1):e14350. PMC
- Pospieszna B et al. Erythrocyte nicotinamide adenine dinucleotide concentration is enhanced by systematic sports participation. BMC Sports Sci Med Rehabil. 2024;16(1):216. PubMed
- Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. PubMed
- Sinclair DA, Guarente L. Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016;17(10):679-690. PubMed
- Imai S. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2:16017. PubMed
- McReynolds MR et al. NAD+ flux is maintained in aged mice despite lower tissue concentrations. Cell Syst. 2021;12(12):1160-1172. PubMed
- Kane AE, Sinclair DA. Sirtuins and NAD+ in the Development and Treatment of Metabolic and Cardiovascular Diseases. Circ Res. 2018;123(7):868-885. PMC
