NAD+: Research Outcomes and What Studies Report

What Is NAD+?

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme present in all living cells that functions as an essential electron carrier in cellular redox reactions and as a cosubstrate for a range of non-redox signaling enzymes. A 2018 review published in Advances in Food and Nutrition Research described it as indispensable for cellular metabolism and respiration, and noted its additional role as a substrate for enzymes involved in DNA repair and cell signaling. The compound exists in oxidized (NAD+) and reduced (NADH) forms; this interconversion is central to how cells generate and transfer energy. One critical distinction for interpreting the research: the majority of supplementation literature studies NAD+ precursors — specifically NMN (nicotinamide mononucleotide) or NR (nicotinamide riboside) — rather than NAD+ itself. Results from NMN or NR studies cannot be attributed to NAD+ directly and are not the basis of the claims in this article.

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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 Metabolism and Redox Homeostasis — A 2018 preclinical study published in Antioxidants & Redox Signaling developed extraction and quantitation methods for NAD+, NADH, NADP+, and NADPH from biological samples, establishing that accurate measurement of these cofactors is necessary to understand cellular redox balance across tissue types.

2. Age-Related Osteoarthritis — A 2025 animal study published in ACS Nano reported that NAD+-loaded hydrogel microspheres injected into a rodent model of age-related osteoarthritis reduced chondrocyte senescence, attenuated synovial inflammation, and improved joint lubrication simultaneously.

3. Cellular Senescence Attenuation — A 2025 animal study published in ACS Nano reported that a nanoparticle delivery system designed to recycle intracellular NAD+ reduced markers of cellular senescence in preclinical models, addressing the compound's known instability and poor cellular uptake when administered directly.

4. Skin Aging and CD38 Interaction — A 2024 observational study examined the pharmacological activity of exogenous NAD+ in the context of skin aging, finding that CD38 — an NAD+-consuming enzyme upregulated with age — substantially limits the efficacy of topical or supplemented NAD+ and that CD38 inhibition may be necessary for meaningful intracellular delivery.

5. Erythrocyte NAD+ Levels and Physical Activity — A 2024 human observational study enrolled trained athletes and sedentary controls, finding that systematic sports participation was associated with higher erythrocyte NAD+ concentrations, suggesting that exercise may modulate NAD+ status through mechanisms independent of dietary precursor intake.

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How Does NAD+ Work?

NAD+ operates through two distinct biochemical roles. In its redox role, it accepts electrons during glycolysis and the citric acid cycle, becoming NADH, which then donates those electrons to the mitochondrial electron transport chain for ATP synthesis. The 2018 review in Advances in Food and Nutrition Research detailed this function as foundational to cellular respiration.

In its non-redox role, NAD+ is consumed — not recycled — as a cosubstrate by enzymes including sirtuins, PARPs (poly-ADP-ribose polymerases), and CD38. Sirtuins use NAD+ to regulate gene expression, mitochondrial biogenesis, and stress responses. PARPs consume large amounts of it during DNA repair. CD38, an ectoenzyme that hydrolyzes NAD+, becomes increasingly active with age and is a focus of research on why tissue NAD+ levels decline over the lifespan. The 2024 observational study by Kang et al. identified CD38 overexpression as a primary barrier to maintaining intracellular NAD+ levels in aging skin tissue, positioning CD38 inhibition as a potential adjunct rather than an alternative to NAD+ supplementation.

Delivery is a recognized technical challenge. A 2025 ACS Nano animal study noted that NAD+ cannot be directly absorbed by most cell types in its intact form, is chemically unstable outside the cell, and lacks targeting specificity when administered systemically — problems that nanoparticle encapsulation strategies are now attempting to address.

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What Does Animal Research Show?

Two 2025 preclinical studies provide the most mechanistically detailed animal data available in this pool.

The first, by Lin et al. in ACS Nano, engineered lubricated hydrogel microspheres loaded with NAD+ for intra-articular injection in a rodent model of age-related osteoarthritis. The study reported a three-pronged effect: the NAD+ payload reduced chondrocyte senescence markers, the hydrogel matrix physically improved joint lubrication, and the overall formulation attenuated synovitis. No equivalent data in human joints yet exists from this delivery format.

The second, by Liu et al., also in ACS Nano, developed a nanoparticle system intended to both deliver NAD+ directly into senescent cells and recycle it intracellularly to sustain elevated levels. Preclinical results showed reduced expression of senescence-associated secretory phenotype (SASP) components — inflammatory cytokines that senescent cells release and that accelerate tissue degeneration. The authors identified three barriers their system was designed to overcome: poor cellular uptake, chemical instability, and lack of tissue targeting. These barriers remain relevant to any discussion of exogenous NAD+ administration.

A third animal study, by Tsurho et al. in Developmental Biology (2025), used a zebrafish model to examine what happens when NAD+ biosynthesis is genetically disrupted during development. Embryos with biallelic pathogenic variants in NAD+ synthesis pathway genes exhibited cardiac, renal, vertebral, and limb anomalies consistent with congenital NAD deficiency disorder (CNDD). This model does not test supplementation effects but establishes that adequate NAD+ biosynthesis is developmentally essential.

A 2018 preclinical study in Antioxidants & Redox Signaling by Lu et al. addressed measurement methodology rather than therapeutic outcomes, validating extraction protocols for NAD+, NADH, NADP+, and NADPH across multiple tissue types. This methodological groundwork underpins the quantitative claims made in other studies in this pool.

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What Does Human Research Show?

Human data on NAD+ itself — as opposed to its precursors NMN or NR — is sparse in this study pool.

A 2024 human observational study (Pospieszna et al., BMC Sports Science, Medicine & Rehabilitation) measured erythrocyte NAD+, NADP+, NADH, and NADPH concentrations across groups categorized by long-term athletic training status and age. Athletes showed higher erythrocyte NAD+ concentrations than sedentary controls, and the study examined age-related trends within those groups. The design was observational, with no control over diet or supplementation, and the study does not establish that elevated NAD+ caused any performance outcome — only that the association exists.

An open-label safety pilot (Yamaguchi et al., Endocrine Journal, 2024) with three healthy, middle-aged Japanese men examined long-term NMN supplementation and tracked blood NAD+ biosynthesis as an outcome measure. Whole-blood NAD+ concentrations rose with NMN supplementation. This study is attributed to NMN, not NAD+, and is included here only because it measured NAD+ as an endpoint — not because it tests the effects of exogenous NAD+ administration. The sample size of three makes any efficacy inference premature.

The 2024 observational work by Kang et al. in Cells reviewed evidence for exogenous NAD+ in skin aging contexts. It identified CD38 — which is upregulated in aging tissue — as the primary obstacle to pharmacological efficacy, finding that the enzyme degrades supplemented NAD+ before it can reach intracellular targets. The study design was observational and did not report outcomes from a controlled human trial.

Two of the eight primary studies in this pool were published in ACS Nano, both in 2025, and both are animal preclinical work.

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What Is Still Unknown About NAD+?

Several fundamental questions remain open. Human clinical trials directly testing exogenous NAD+ administration — rather than NMN or NR precursors — are limited to small, preliminary designs. No large randomized controlled trial has assessed NAD+ supplementation outcomes in humans.

The delivery problem identified in animal research has no established human solution. Nanoparticle and hydrogel approaches reported in the 2025 ACS Nano studies are preclinical only. Whether these formulations translate to human pharmacokinetics, safety, and tissue penetration is untested.

The CD38 problem — enzymatic degradation of circulating NAD+ before it reaches intracellular targets — is documented in observational and in vitro work but not resolved by any intervention in this study pool. Whether CD38 inhibition is safe and effective as a co-treatment in humans remains an open research question.

The zebrafish congenital deficiency model (Tsurho et al., 2025) raises questions about critical windows during development, but extrapolating zebrafish developmental biology to human developmental medicine requires substantial additional study.

The 2018 review (Kirkland & Meyer-Ficca) noted that niacin-derived NAD+ biosynthesis supports DNA repair through PARP activation, but the clinical significance of supplementing NAD+ specifically — versus its dietary precursors — for DNA repair outcomes in humans has not been established by the studies in this pool.

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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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