NAD+ Molecule Science and the Evidence: Biosynthesis, Precursors and Intravenous Use

In short: NAD+ is a coenzyme and a substrate that several enzyme families consume, and cells make it by four routes. Oral precursors (NR, NMN) raise blood NAD+ metabolites in people, but trials in healthy adults have mostly found no clear functional effect, and the literature on intravenous NAD+ is thin: two small pilots, one of them a preprint, and one retrospective tolerability study. This article describes the molecule and the literature and makes no claim about any product.

This article is for healthcare professionals and licensed suppliers who want the biochemistry and the evidence in one place. We write NAD+ with its plus sign throughout, because the abbreviation without it is ambiguous. NAD+ is the oxidised form of nicotinamide adenine dinucleotide, and NADH is the reduced form.

It summarises published papers and reviews, read in November 2026. It does not recommend any use, dose or product, and it does not say that any condition responds to NAD+. Where a study reports funding or affiliations that bear on how it should be read, we say so.

What NAD+ does in the cell

NAD+ has two roles. As a coenzyme it accepts a hydride ion to become NADH and gives it up again, carrying electrons through the redox reactions of metabolism. As a substrate it is consumed: several enzyme families split NAD+ and release nicotinamide while they transfer a group to a protein or break the molecule down. Because that second role uses the molecule up, cells must keep making it, which is why its biosynthesis has been studied closely (Houtkooper et al., 2010; Cantó et al., 2015).

How cells make NAD+

Reviews describe four routes that converge on a small set of enzymes, the NMN adenylyltransferases that join a nicotinamide or nicotinic acid mononucleotide to ATP-derived adenylate (Houtkooper et al., 2010; Katsyuba and Auwerx, 2017). The routes differ in their starting material.

Reviews describe the salvage of nicotinamide as the main route in most mammalian tissues, so the precursors discussed below enter a network that is already in use. Nicotinic acid, nicotinamide and NR are forms of vitamin B3; NMN is a nucleotide. How NMN enters cells is still debated: one group reported a dedicated transporter, and another reported finding no evidence for it (Grozio et al., 2019; Schmidt and Brenner, 2019), and we take no position on it.

What the claim of decline rests on

It is often said that NAD+ falls with age. The human evidence is thinner than the statement. A 2019 trial report opens by noting that the decline has been reported in preclinical models while human data are sparse (Elhassan et al., 2019). Mouse work ties CD38 activity to the fall in tissue NAD+ (Camacho-Pereira et al., 2016). In people, tissue NAD+ is hard to measure, and the blood measurements that most trials report do not stand in for the content of muscle or liver. Two inferences are therefore left open: that low NAD+ is the cause of any functional change, and that raising a blood marker repairs it.

Oral precursors in human trials

Precursor trials in healthy adults are the most developed part of the literature, and they give a consistent first result: oral NR and NMN raise NAD+ metabolites in blood. What follows from that is less clear.

Three limits apply across the table. The trials are short, most last weeks. The populations are small and mostly male. And the common finding is a change in a biochemical marker rather than in a function that matters to a person. The 2025 meta-analysis leaves room for better designs, since its authors call for work on dose, baseline NAD+ status and combined interventions.

Intravenous NAD+: what has been published

The intravenous literature is much smaller, and we read four reports that bear on it.

• A pilot of plasma and urine metabolites (Grant et al., 2019). Eleven healthy men, eight in the test group and three controls given saline, received a six-hour infusion. NAD+ was rapidly and completely removed from plasma during the first two hours, plasma NAD+ rose significantly only at the end of the infusion, and the metabolite pattern was consistent with NAD+ glycohydrolase and pyrophosphatase activity. Urine contained NAD+ itself and methylnicotinamide. The authors report no adverse events. Tissue NAD+ was not measured, so uptake into tissue is an inference. The authors acknowledge the small number of participants, and their affiliations include commercial NAD+ organisations.
• A randomised pilot posted as a preprint (Hawkins et al., 2024). A double-blind, placebo-controlled pilot compared single intravenous infusions of NR and NAD+ with oral NR and saline in generally healthy adults; data from 37 and 16 participants in two phases were analysed. NR infusions were associated with fewer and less severe infusion-related adverse experiences than NAD+ infusions. The NAD+ group showed a rise in white blood cell and neutrophil counts, which the authors read as suggesting an inflammatory response, and blood NAD+ measured on dried blood spots was higher after NR than after NAD+ at three hours. The report had not been peer reviewed when we read it, and we did not review its funding and competing-interest statements.
• A retrospective comparison in a commercial setting (Reyna et al., 2026). The study reviewed records of clients who received NAD+ or NR by infusion. Reported symptoms differed: gastrointestinal symptoms, a faster pulse and chest pressure with NAD+, and tingling and mild cramping with NR, all resolving at the end of the infusion. There was no randomisation and no untreated group, and the authors describe the findings as preliminary; changes in metabolic markers were variable. The authors' conflict-of-interest statement says that all of them were employed by Restore Hyperwellness, a commercial operator, and the records came from a commercial setting.
• A mouse study (Damgaard et al., 2022). Repeated intravenous NR through a jugular catheter raised skeletal muscle NAD+ in mice but did not change muscle respiratory capacity or insulin sensitivity. The study was funded by a supplier.

What is missing matters as much. In a PubMed search on 2 November 2026 we found no peer-reviewed randomised controlled trial of intravenous NAD+ reporting clinical or functional outcomes in people. A search is not proof of absence, but the practical reading is that the intravenous route rests on two small pilots, one of them a preprint, and one uncontrolled tolerability review.

How to read this literature

• Blood is not tissue. A rise in blood NAD+ metabolites shows that a precursor was absorbed and metabolised. It does not show that a tissue was repleted.
• A marker is not an outcome. Most positive findings are changes in a metabolite, not in a function.
• Check who paid. Several of the trials above were sponsored by suppliers or have authors employed by them. That does not invalidate them. The investigator-initiated Dollerup trial, for example, found no functional change.
• Size and length matter. Studies of a dozen or a few dozen people over weeks cannot settle questions about long-term outcomes.

EFBA's position

This article describes a molecule and the published literature. It makes no claim about any product, use or condition. Further background is in the Knowledge Base entries for NAD+ and NMN. IVIXIR products are not registered with NPRA and are not available in Malaysia; this article is not advertising to the public.