What Is NAD+ Studied For?

What Is NAD+?

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells that functions as an electron carrier in redox reactions and as a substrate for enzymes that regulate metabolism, DNA repair, and aging-related processes. A 2018 review published in Advances in Food and Nutrition Research described it as essential to cellular metabolism and respiration, and noted its additional role as a cosubstrate for enzymatic transformations including ADP-ribosylation. It is not a peptide.

One distinction is critical for understanding the research landscape: the majority of human supplementation studies investigate NAD+ precursors — nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) — rather than the compound itself. NMN and NR are chemically distinct molecules that the body converts into NAD+. Results from NMN or NR studies cannot be attributed directly to exogenous NAD+, and this article maintains that boundary throughout.

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What Is NAD+ Studied For?

Research on NAD+ goes back to 2018 — 8 years — with studies continuing through 2025.

1. Cellular Redox Metabolism and Energy Pathways — A 2018 human observational review in Advances in Food and Nutrition Research documented that NAD+ and its phosphorylated form NADP are indispensable cofactors for the majority of cellular oxidation-reduction reactions, establishing their foundational role in energy metabolism.

2. Cellular Senescence and Age-Related Decline — A 2025 preclinical study published in ACS Nano examined a nanoparticle delivery strategy for intracellular NAD+ recycling in aged rodent models, reporting attenuation of senescence-associated phenotypes including reduced inflammatory marker expression and improved mitochondrial function.

3. Osteoarthritis and Joint Tissue Degradation — A 2025 preclinical study also published in ACS Nano loaded NAD+ into lubricated hydrogel microspheres and tested them in a rodent model of age-related osteoarthritis, reporting reductions in chondrocyte senescence, synovial inflammation, and cartilage degradation markers.

4. Skin Aging Biology — A 2024 observational study in Cells examined how exogenous NAD+ interacts with CD38, an enzyme that degrades it, finding that synergistic suppression of CD38 expression amplified the pharmacological effects of applied NAD+ in the context of skin aging models.

5. Exercise Physiology and Erythrocyte NAD+ Levels — A 2024 human observational study in BMC Sports Science, Medicine & Rehabilitation measured erythrocyte NAD+ and NADP+ concentrations across athlete and non-athlete populations, finding that systematic sports participation was associated with higher erythrocyte NAD+ concentrations, though the study design did not permit causal conclusions.

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How Does NAD+ Work?

NAD+ operates through two distinct biochemical roles. As an electron carrier, it cycles between its oxidized form (NAD+) and reduced form (NADH), shuttling electrons through metabolic pathways including glycolysis and the citric acid cycle. A 2022 review in Current Medicinal Chemistry described this carrier function as central to cellular energy homeostasis.

The second role is enzymatic. NAD+ serves as a substrate — meaning it is consumed rather than recycled — for a class of enzymes that include sirtuins, PARPs (poly-ADP-ribose polymerases), and CD38. A 2018 review in Advances in Food and Nutrition Research identified this substrate activity as why intracellular NAD+ levels matter beyond simple redox cycling: each enzymatic reaction depletes the pool. Sirtuins use NAD+ to regulate gene expression and stress responses; PARPs consume it during DNA damage repair; CD38 degrades it as part of calcium signaling. The 2024 Cells study focused specifically on CD38's degradative activity, arguing that controlling CD38 expression is a lever for sustaining intracellular NAD+ availability when exogenous NAD+ is introduced.

A recurring challenge in the research is delivery. The 2025 ACS Nano senescence study noted that exogenous NAD+ cannot be directly absorbed by cells in its intact form and is unstable outside the cell, which has driven the engineering of nanocarrier systems designed to protect and deliver it intracellularly.

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What Does Animal Research Show About NAD+?

Two 2025 preclinical studies — both published in ACS Nano — represent the most targeted animal research specifically on exogenous NAD+ delivery rather than precursor supplementation.

The first, by Lin and colleagues, engineered hydrogel microspheres loaded with NAD+ and coated to provide joint lubrication. In a rodent model of age-related osteoarthritis, intra-articular injection of these microspheres addressed three simultaneous disease mechanisms: chondrocyte senescence, synovial inflammation, and insufficient lubrication. The study reported that the three-pronged approach reduced cartilage degradation markers and inflammatory cytokine expression. The delivery vehicle was a meaningful part of the intervention — plain NAD+ injection without the carrier was not separately reported as an equivalent comparator.

The second, by Liu and colleagues, developed a nanoparticle system designed to target senescent cells and recycle intracellular NAD+. In aged rodent models, the system was reported to attenuate senescence-associated secretory phenotype (SASP) markers, reduce mitochondrial dysfunction signals, and improve cellular function. The researchers emphasized the targeting specificity as essential — the goal was to concentrate NAD+ recycling activity in senescent cells specifically rather than raising systemic NAD+ broadly.

A 2023 preclinical study in FEBS Letters by Kim and colleagues examined what happens to NMN — an NAD+ precursor — when it passes through the gut microbiome before conversion. The study found that gut microbial enzymes deamidate NMN via pathways not present in mammalian hosts, producing alternative metabolites. This is relevant to NAD+ research because it clarifies that orally administered precursors may not follow the assumed conversion pathway cleanly, complicating the interpretation of oral NMN studies. This finding belongs to NMN biology, not to NAD+ directly, but it informs how researchers design delivery systems for NAD+ and its precursors.

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What Does Human Research Show About NAD+?

Human research directly studying exogenous NAD+ administration remains limited. Most human trial data in the broader field investigates precursors, and those results cannot be attributed to NAD+ itself.

Two human observational studies in this pool examine NAD+ in human contexts without administering it as an intervention. A 2024 observational study in BMC Sports Science, Medicine & Rehabilitation measured erythrocyte NAD+ and NADP+ concentrations in athletes versus non-athletes across age groups. The study found that systematic sports participation was associated with elevated erythrocyte NAD+ concentrations, and that age-related declines in NAD+ were observable in the non-athlete cohort. The design did not involve intervention or randomization, so it documents associations rather than causation.

A 2024 paper in Cells reviewed the pharmacology of exogenous NAD+ in the context of skin aging. It examined CD38 as the primary enzymatic barrier to NAD+ supplementation efficacy — CD38 degrades exogenous NAD+ before it reaches intracellular targets — and proposed that combining NAD+ with CD38 inhibitors could amplify effect. The study design was observational and mechanistic rather than a controlled trial.

Two studies appearing in ACS Nano — the 2025 osteoarthritis and senescence papers noted above — are both preclinical. Human clinical data from controlled trials directly testing NAD+ administration was not represented in the primary study pool for this article.

One open-label safety pilot by Yamaguchi and colleagues, published in Endocrine Journal in 2024, enrolled three healthy middle-aged Japanese men and assessed long-term NMN supplementation on metabolism, sleep, and NAD+ biosynthesis. The study reported that NMN supplementation raised blood NAD+ levels and was well tolerated over the observation period. This finding is attributable to NMN, not to exogenous NAD+. It is reported here solely to illustrate how NMN research is distinct: NMN raises endogenous NAD+, but that is not the same as administering NAD+ directly.

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What Is Still Unknown About NAD+?

Several substantive gaps remain. Direct human clinical trial data on exogenous NAD+ administration — its bioavailability, effective dose range, and clinical outcomes — is largely absent from the published record. The preclinical delivery innovations in the 2025 ACS Nano studies address known barriers (cellular impermeability, instability, lack of tissue targeting), but neither study has been replicated in human models.

The relationship between circulating or erythrocyte NAD+ levels and functional outcomes in humans remains correlational. The 2024 sports observational study established an association between athletic activity and higher erythrocyte NAD+, but whether raising NAD+ levels pharmacologically would produce comparable functional benefits has not been tested in controlled human trials represented in this study pool.

The CD38 degradation problem identified in the 2024 Cells paper also has no resolved clinical answer. Combining NAD+ with CD38 inhibitors is a proposed strategy, but no human trial data on that combination is available here. The microbiome-mediated deamidation finding from the 2023 FEBS Letters NMN study adds further complexity to oral delivery strategies for the entire NAD+ precursor class.

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Where Can I Buy NAD+?

NAD+ is available for purchase from BioMax Research at biomaxresearch.com. BioMax Research is a highly regarded source for research peptides, with every product third-party lab tested and backed by a verifiable certificate of analysis (COA).

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