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 cell signaling. This molecule was discovered in 1906 by Arthur Harden and William Young while researching yeast fermentation, which earned them the Nobel Prize in Chemistry in 1929.
Structurally, NAD+ consists of two nucleotides connected by phosphate groups - an adenine nucleotide and a nicotinamide nucleotide. The molecular formula is C₂₁H₂₇N₇O₁₄P₂ and the molecular weight is 663.43 Da. NAD+ exists in two forms - oxidized (NAD+) and reduced (NADH) - which are converted into each other during redox reactions, acting 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 the rescue synthesis is nicotinamide phosphoribosyltransferase (NAMPT), whose activity is regulated daily.
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 features of aging, including mitochondrial dysfunction, genomic instability, and impaired intercellular communication, which has made NAD+ supplementation the subject of intense 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 fatty acid β-oxidation. NADH is then oxidized in the mitochondrial respiratory chain, driving ATP synthesis.
SirtuIn Activation - NAD+ is an essential substrate for a family of NAD+-dependent deacetylase enzymes called sirtuins (SIRT1-7). Sirtuins regulate key aging-related processes, including DNA repair, mitochondrial function, metabolism, inflammatory response, and cellular homeostasis. The activity of sirtuIn directly depends on the availability of NAD+, linking the energy status of the cell with epigenetic regulation.
Substrate for poly(ADP-ribose) polymerase - NAD+ is consumed by PARP enzymes (PARP-1, PARP-2), which participate in the repair of DNA damage. In response to extensive DNA damage, PARP hyperactivation may lead to NAD+ depletion, which disrupts energy metabolism and contributes to mitochondrial dysfunction.
CD38 Signaling - The ectoenzyme CD38 and the related CD157 hydrolyze NAD+ to produce cyclic ADP-ribose (cADPR) and nicotinic adenine dinucleotide phosphate (NAADP), which act as secondary messengers in calcium signaling. CD38 activity increases with age and is the main factor in the decline in 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+, by activating SIRT1, modulates the transcriptional activity of this complex, creating a feedback loop linking metabolism with the circadian rhythm.
Directions of scientific research
Research on NAD+ and its precursors focuses on the potential impact on aging, cognitive functions, metabolism and neurodegenerative diseases.
Aging and longevity
Research has 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 on adults aged 45-60, supplementation with 300 mg of 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 down natural aging and protect against UV-induced aging by improving mitochondrial function and activating sirtuIn.
Cognition and neuroprotection
A 2025 study showed that NMN reverses D-galactose-induced neurodegeneration and improves the intestinal barrier in mice by activating the SIRT1 pathway. Clinical trials in Alzheimer's disease patients showed that a cocktail of compounds containing the NAD+ precursor (NR) reversed neurodegeneration and improved mitochondrial function. In patients with Cockayne syndrome, a disease characterized by NAD+ deficiency, supplementation has shown promising results.
Metabolism and metabolic diseases
A 2024 study found that NMN can increase glucose uptake through several mechanisms, including increasing levels of the mitochondrial protein UCP1, which converts glucose into heat. NMN may also increase the production of ketone bodies and improve insulin sensitivity. In a study of 30 overweight and obese middle-aged and older people, taking 500 mg of 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 exercise. Research shows that NMN supplementation can improve aerobic capacity and mitochondrial function in skeletal muscle. The NAMPT-NAD+-SIRT pathway regulates metabolic adaptations to physical 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 life - revolutionized the understanding of the molecular mechanisms of aging.
The main NAD+ precursors used in supplementation include:
- NMN (nicotinamide mononucleotide) - direct precursor of NAD+, 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) - 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. NMN and NR supplementation has shown the ability to increase tissue NAD+ levels in humans, although optimal dosage and long-term effects remain under investigation.
In 2024, researchers proposed a combinatorial approach to activating sirtuIn by combining NAD+ precursors with sirtuIn activators (STACs), such as resveratrol or SRT2104, as a potential anti-aging intervention.
Research safety profile
General tolerance - NAD+ and its precursors (NMN, NR) show a good safety profile in clinical trials. Numerous human studies indicate that supplementation offers benefits with minimal or no side effects, although some studies show no observable benefits.
NMN/NR side effects - Occasionally observed symptoms include: mild gastrointestinal symptoms (nausea, discomfort), skin redness at high doses, occasional headaches.
Interactions - Theoretical concerns include the potential impact of high NAD+ levels on PARP activation in the presence of extensive DNA damage. Supplementation is not recommended for 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, designating it as an investigational drug, although this decision is controversial. NR (Niagen) remains available as a supplement.
Dosage in studies - Clinical studies used doses of NMN 250-500 mg daily and NR 300-1000 mg daily. The optimal long-term dosage remains undetermined.
Bibliography - latest scientific research
- 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 aging 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
