NAD+ and intravenous administration: what the research shows and does not show

In short: NAD+ is a coenzyme and a consumed substrate, and cells make it by several routes. Oral precursors raise blood measurements of NAD+ metabolites in people, but the trials that looked for functional change in healthy adults mostly did not find one. For intravenous NAD+ in healthy people the published record is one small metabolite pilot, one preprint pilot and one retrospective tolerability review. This article describes the molecule and the studies 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 oxidized form of nicotinamide adenine dinucleotide, and NADH is the reduced form.

It summarizes published papers that we read, with identifiers checked in PubMed on November 3, 2026. It recommends no use, dose or product, and says nothing about any condition responding to NAD+. Where author affiliations or grants bear on how a study should be read, we say so.

Two questions that are easily mixed up

Most public statements about NAD+ run two questions together. The first asks whether a route of administration raises NAD+ or its metabolites in blood or in a tissue. The second asks whether that rise changes anything that matters to a person. The first can be answered by a small study that measures metabolites. The second needs functional outcomes, adequate numbers and enough time. The published human work mostly answers the first and says little about the second.

What the molecule 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 chemical group or break the molecule down. Because the second role uses the molecule up, cells must keep making it, which is why its biosynthesis has been studied so closely (Houtkooper et al., 2010; Cantó et al., 2015).

How cells make NAD+

Reviews describe four routes to NAD+. Cells can build it from the amino acid tryptophan, from nicotinic acid by the Preiss-Handler pathway, and from nicotinamide by a salvage pathway that recycles what the consuming enzymes release. A fourth route starts from nicotinamide riboside (NR). A 2004 paper showed that NR is a nutrient for yeast and human cells and identified the NRK genes that convert it, establishing a route that does not depend on the Preiss-Handler pathway (Bieganowski and Brenner, 2004). Nicotinamide mononucleotide (NMN) is an intermediate between NR and NAD+ (Katsyuba and Auwerx, 2017).

Whether NMN enters cells whole is disputed: one group proposed a transporter for it (Grozio et al., 2019), and a published reply argued that the evidence for it was absent (Schmidt and Brenner, 2019). A precursor in blood therefore does not show how, or whether, it reaches the inside of a given cell.

Where the idea of an age-related fall comes from

Popular writing presents a fall in NAD+ with age as settled. The primary literature is more careful. A 2019 trial in older men begins by noting that the fall has been reported in preclinical models while human data are sparse (Elhassan et al., 2019), and the most cited mechanistic work is in mice, where CD38 activity was linked to lower tissue NAD+ (Camacho-Pereira et al., 2016). In people, tissue NAD+ is hard to measure, and the blood values that most trials report say little about the content of muscle or any other tissue. That leaves two inferences unproven: that a low value causes any change in function, and that raising a blood marker corrects it.

What the oral precursor trials measured

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

The same limits run through the table. The trials are short, mostly a matter of weeks, with small and largely male groups, and their usual finding is a movement in a biochemical marker and not in a function that matters to a person. For older adults the 2025 meta-analysis is the most complete summary of the functional question, and its pooled results are null on the measures listed.

Intravenous NAD+: what has been published

The intravenous literature in healthy people is much smaller. We read four reports that bear on it.

A metabolite pilot (Grant et al., 2019). Eleven healthy men aged 30 to 55, eight in the test group and three controls given saline, received a six-hour infusion. The authors report that plasma NAD+ and its measured metabolites did not change until after the second hour, that NAD+ was rapidly and completely removed from plasma over that period, and that the metabolite pattern was consistent with NAD+ glycohydrolase and pyrophosphatase activity. Urine contained NAD+ itself and methylnicotinamide. No adverse events were observed. Tissue NAD+ was not measured, so uptake into tissue is an inference. The affiliations include a commercial NAD+ company.

A randomized 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, and analyzed data from 37 and 16 participants in two phases. NR infusions were associated with fewer and less severe adverse experiences during the infusion than NAD+ infusions, and no attributable adverse events were reported through 14 days of follow-up. White blood cell and neutrophil counts rose in the NAD+ group, which the authors read as suggesting an inflammatory response. Blood NAD+ measured on dried blood spots was higher after NR infusion than after NAD+ infusion or oral NR at three hours. The report was not peer reviewed when we read it, and the product tested is a commercial NR formulation named in its title.

A retrospective review in a commercial setting (Reyna et al., 2026). The authors reviewed the records of clients who received repeated daily infusions of NAD+ or NR. Reported symptoms differed. NAD+ was associated with moderate to severe gastrointestinal symptoms, a faster pulse and chest pressure, and NR with tingling and mild cramping, all of which resolved when the infusion ended. Most routine blood safety markers showed no significant change, one enzyme marker fell in the NAD+ group only and stayed within its reference range, and exploratory metabolic markers moved variably. There was no randomization and no untreated group, and the authors are affiliated with a commercial operator that provides such infusions.

A mouse study (Damgaard et al., 2022). Repeated intravenous NR given through a jugular catheter raised skeletal muscle NAD+ in mice but did not change muscle respiratory capacity or insulin sensitivity. One co-author is affiliated with an NR supplier.

The gaps need stating too. On November 3, 2026 we searched PubMed for human trials of intravenous NAD+ and for randomized trials that mention infusion of NAD+. In healthy people we found no randomized trial that reports clinical or functional outcomes. The search did return one single-center randomized trial reported in 2026 in hospital patients with a specific diagnosis. This article does not discuss disease settings, so we do not summarize it, and it cannot be read as evidence about healthy people or about any product. A search is not proof of absence, but in healthy people the intravenous route rests on two small pilots, one a preprint, and one uncontrolled review.

How to read this literature

• Blood describes blood. A rise in blood NAD+ metabolites shows that a precursor was absorbed and metabolized. It does not show that any tissue received it. For intravenous NAD+ itself, the Grant pilot found rapid removal from plasma, which fits breakdown of the infused molecule outside cells.
• A metabolite is not a result for a person. Most positive findings are movements in a measurement, not in a function.
• Read the affiliations and grants. Several of the studies above list an author affiliated with a company that sells the compound tested, or a grant from one. That does not invalidate them. The investigator-initiated Dollerup trial, funded by a foundation, found no functional change.
• Numbers and duration. A dozen or a few dozen people followed for weeks cannot settle questions about longer-term outcomes.
• Route and compound differ. Each route and compound needs its own evidence.

What this article does and does not say

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. In the Philippines a medicinal product that contains NAD+ is subject to the same licensing and registration framework described in our article on the License to Operate and Certificate of Product Registration.