What is NAD+, and why would anyone inject it? NAD+ — nicotinamide adenine dinucleotide — is a coenzyme found in every living cell, and its central job is turning the food you eat into energy your cells can spend. NAD+ injections deliver that same molecule as a compounded prescription medication, and interest in them has grown alongside research connecting falling NAD+ levels to the way cells age. This guide covers what NAD+ does in the body, why levels decline, how injections differ from oral supplements such as NMN and NR, what human studies have and have not shown, and how to bring the question to a licensed provider.
What does NAD+ do in the body?
NAD+ is a coenzyme that carries electrons during metabolism. Inside mitochondria it cycles between an oxidized form (NAD+) and a reduced form (NADH), feeding electrons into the machinery that produces ATP — the molecule cells spend on nearly everything they do. It also fuels enzymes that repair DNA and regulate metabolism, including sirtuins and PARPs.
ATP is often called the universal currency of cellular energy. It powers muscle contraction, nerve signaling, metabolism, and tissue repair, and mitochondria produce most of it by breaking down nutrients. NAD+ sits at the center of that process: the constant cycling between NAD+ and NADH is what moves electrons through the mitochondrial electron transport chain and keeps ATP production running without excessive leakage of reactive byproducts.
The same molecule does a second job. Sirtuins — enzymes involved in DNA repair and metabolic regulation — cannot function without NAD+ as a cofactor. PARPs, another enzyme family, consume NAD+ while responding to DNA damage, and under heavy genotoxic stress they become a major drain on the cellular NAD+ pool (Chini et al., 2024). Because energy production and cellular repair draw on the same limited supply, researchers treat NAD+ availability as a meaningful variable in how cells hold up over time. Two widely cited reviews — Verdin (2015) in Science and Katsyuba and Auwerx (2017) in The EMBO Journal — frame NAD+ as a central node in aging, metabolism, and neurodegeneration research, and describe the push to translate that biology "from bench to bedside."
Mitochondria, ATP, and the energy cost of aging
Mitochondria convert nutrients into ATP by passing electrons down the electron transport chain. That process inevitably produces reactive oxygen species (ROS): in small amounts they act as adaptive signals, while in excess — a pattern more common in aged cells — they cause oxidative damage. Mitochondrial function declines with age and stress, a recognized hallmark of aging.
Mitochondria are more than power plants. They help orchestrate cell survival, programmed cell death (apoptosis), and redox balance — the ongoing equilibrium between oxidation, which accompanies energy production and stress, and reduction, which accompanies repair and recovery. When electrons flow through the transport chain, a fraction escapes and forms ROS. Cells are built to handle a baseline of this: modest ROS exposure triggers adaptive, protective responses, a phenomenon sometimes called mitohormesis. The trouble starts when production outpaces the cell's antioxidant defenses.
With age, this system loses efficiency. Reviews describe the pattern in general terms — slower recovery from exertion, reduced metabolic efficiency, accumulating oxidative wear — rather than as a single universal number. It is worth being direct about that gap: the research literature this article draws on documents mitochondrial and NAD+ decline qualitatively, and does not settle on a specific figure for how much NAD+ a person loses by a given age. Any page quoting one precise universal percentage is going beyond what the reviews support.
Why NAD+ declines — and what that does to cells
NAD+ falls with age for two connected reasons: cells make less of it, and other processes consume more of it. A 2024 review in Aging Cell by Chini and colleagues identifies CD38 — an NAD+-consuming enzyme that becomes more abundant in aging tissues — as a major driver of depletion, and links low NAD+ to cellular senescence.
Senescence is the state in which a cell stops dividing but stays metabolically active, often secreting inflammatory signals. The Chini review connects NAD+ decline to senescence through two routes: accumulating DNA damage (which activates NAD+-consuming repair enzymes) and mitochondrial dysfunction (which undermines the energy supply repair depends on). Falling NAD+ and cellular aging can therefore feed each other.
Animal work supplies the classic mechanistic picture. In mice, Gomes and colleagues (2013, Cell) showed that declining NAD+ induces a pseudohypoxic state — the cell behaves as if starved of oxygen even when oxygen is present — which disrupts communication between the nucleus and the mitochondria. That is a mouse finding, not a human outcome, but it is one of the foundational results behind the field's interest in restoring NAD+.
What this biology does not yet deliver is a settled human therapy. Recent human trials of NAD+-raising strategies have produced modest or mixed results, and researchers describe clinical translation as still maturing. The sections below look at that human evidence directly.
NAD+ is not a peptide — and why the label matters
NAD+ is a dinucleotide: two nucleotide units joined through their phosphate groups. It is not a peptide, which is a chain of amino acids. The distinction matters because "NAD+ peptide" marketing blurs which evidence applies — studies of NAD+ biology and its oral precursors say nothing about an engineered peptide that raises NAD+.
You will sometimes see NAD+ sold alongside peptide therapies, and some websites go further and describe "NAD+ peptides" as a product category. No such compound class exists in the peer-reviewed literature. Pages that use the phrase typically cite studies of NR or NMN — small-molecule precursor supplements — and let the reader assume the results carry over to whatever is being sold.
The practical takeaway for a patient is a reading habit: whenever you encounter an NAD+ claim, check which substance was studied (NAD+ itself, NR, or NMN), how it was given (oral or injected), and in whom. Promise prescribes NAD+ itself — the coenzyme, as an injectable compounded medication. It often appears on the same menu as peptides because both are compounded injectables, not because it is one.
NAD+ injections vs oral precursors (NMN and NR)
NAD+ injections deliver the coenzyme itself under a prescription. NMN and NR are oral precursors, sold as dietary supplements, that the body converts into NAD+ through its own enzymatic pathways. Most published human trials tested the oral precursors, so the controlled-trial evidence base for injected NAD+ specifically is much thinner.
| NAD+ injections | NR (nicotinamide riboside) | NMN (nicotinamide mononucleotide) | |
|---|---|---|---|
| What it is | The NAD+ coenzyme itself (a dinucleotide) | An oral precursor the body converts into NAD+ | An oral precursor the body converts into NAD+ |
| How it is taken | Injection, prescription-only | Capsule, sold as a dietary supplement | Capsule, sold as a dietary supplement |
| Regulatory status | Compounded medication — not FDA-approved | Dietary supplement — not FDA-approved to prevent or treat any disease | Dietary supplement — not FDA-approved to prevent or treat any disease |
| Human trial base | Limited; few controlled trials of the injected form | The most-studied precursor, including randomized trials and small pilots | Meta-analyzed in older adults; no significant muscle benefits found |
The rows of that table are not interchangeable. A finding from an oral NR trial in one patient population cannot be assumed to apply to NMN, to injections, or to a different population — the molecule, the route, and the people all differ. That is not a technicality; it is the main reason this guide keeps repeating which study population each number came from.
What human studies of NAD+ precursors show
Human results are mixed. A 2025 systematic review and meta-analysis of randomized trials in adults with mean ages of 60.9 to 83 found no significant effect of NMN on muscle mass, strength, or gait speed — and its authors concluded that current evidence does not support NMN or NR supplementation for preserving muscle mass and function in older adults.
The details of that meta-analysis (Prokopidis et al., 2025, Journal of Cachexia, Sarcopenia and Muscle) are worth having. Pooled across randomized trials in older adults, NMN showed a mean difference in skeletal muscle index of −0.42 (95% CI −0.99 to 0.14, p = 0.14) — not statistically significant — and no significant changes in handgrip strength or gait speed. Secondary findings cut both ways: NR was associated with a longer six-minute-walk distance in patients with peripheral artery disease, but with worse scores on the short physical performance battery and five-times-chair-stand test in people with mild cognitive impairment.
A separate 2025 pilot deserves careful framing because it is often summarized generously. Szarvas and colleagues (Journal of Pharmacology and Experimental Therapeutics) gave oral NR to 8 older adults with peripheral artery disease for 4 weeks in an open-label design — no placebo group, and both patients and investigators knew who was being treated. The team reported positive trends in endothelial function and cognitive performance. The frequently quoted oxidative-stress and mitochondrial findings from this study came from an in-vitro arm: cultured brain-microvascular endothelial cells exposed to participants' serum in the laboratory, not measurements made in the patients themselves. An 8-person uncontrolled pilot generates hypotheses; it does not establish effects.
Two gaps matter for anyone considering NAD+ injections. First, these are precursor studies — controlled trials of injected NAD+ itself are scarce. Second, the populations studied are specific: older adults, and patient groups such as peripheral artery disease. Healthy younger and middle-aged adults — often the people this kind of therapy is marketed to — are underrepresented in the trial literature.
What researchers measure in NAD+ studies
Typical study endpoints include blood NAD+ concentration and the NAD+/NADH ratio, mitochondrial mass and activity, oxidative-stress markers such as ROS production and glutathione levels, sirtuin activation and DNA-repair markers, and recovery after a physical stressor. NAD+ testing remains mostly a research tool rather than part of routine clinical bloodwork.
Researchers also vary their models deliberately: neural tissue for questions about cognition, musculoskeletal tissue for healing and repair, and metabolic cell models for glucose and lipid handling. Knowing this list has a practical use — if a clinic advertises that it will "measure and restore" your NAD+ level, it is fair to ask which assay it uses and what reference range it is comparing you against, because methods differ between laboratories and are not standardized for clinical care.
Where NAD+ research is heading
Forward-looking directions include blocking CD38 to slow NAD+ consumption in aging tissues, combining NAD+ support with antioxidants or metabolic regulators, personalized bioenergetic profiling, modulating redox enzymes such as superoxide dismutase and catalase, and mapping how NAD+ interacts with autophagy — including mitophagy, the clearance of dysfunctional mitochondria — and hormone signaling. All of it is early-stage research, not available therapy.
NAD+ is also one entry point into a wider field. Researchers interested in cellular energy study other compounds in the same neighborhood — among them MOTS-c, a peptide investigated in metabolic and mitochondrial research, and SS-31, another mitochondria-focused compound under study. Each has its own distinct evidence base, and none of the NAD+ findings above transfer to them; Promise groups them with NAD+ under Energy & Focus.
References
Peer-reviewed sources cited in this guide, with PubMed listings.
- Verdin E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208–1213. PubMed
- Katsyuba E, Auwerx J. (2017). Modulating NAD+ metabolism, from bench to bedside. The EMBO Journal, 36(18), 2670–2683. PubMed
- Gomes AP, et al. (2013). Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624–1638. PubMed
- Chini CCS, Cordeiro HS, Tran NLK, Chini EN. (2024). NAD metabolism: Role in senescence regulation and aging. Aging Cell, 23(1), e13920. PubMed
- Szarvas Z, et al. (2025). Effects of NAD+ supplementation with oral nicotinamide riboside on vascular health and cognitive function in older adults with peripheral artery disease: Results from a pilot 4-week open-label clinical trial. Journal of Pharmacology and Experimental Therapeutics, 392(7), 103607. PubMed
- Prokopidis K, et al. (2025). The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. Journal of Cachexia, Sarcopenia and Muscle, 16(3), e13799. PubMed
Talking to a provider about NAD+
NAD+ injections are available only by prescription. A licensed provider reviews every request and decides whether NAD+ is medically appropriate for you — not everyone qualifies, and the provider may decline. When it is prescribed through Promise, NAD+ is compounded by a licensed U.S. pharmacy and shipped as part of your treatment plan.
Come to that conversation with three things. First, what you are hoping to address — low energy, focus, recovery — described concretely, because it shapes whether NAD+ is even the right conversation. Second, your full medication and health history, which is what the clinical review runs on. Third, calibrated expectations: as this guide has laid out, the strongest human data concerns oral precursors in older and clinically specific populations, with mixed results, and the injected form has a thinner controlled-trial record. A good outcome of the visit is a decision you understand — including, sometimes, a no.
This article is for educational purposes only and is not medical advice. Talk with a licensed healthcare provider about your individual health questions and before starting or stopping any treatment.