NAD+

1. 01Bloodstream

   In the blood, infused NAD+ is quickly cleared and partly broken down

   When NAD+ is put straight into a vein, blood and cell surfaces have enzymes that can chop it up. In the one small test in healthy volunteers, the NAD+ vanished from the blood for the first 2 hours, either taken into tissues or broken down. Only later in the 6-hour drip did levels in the blood rise. Scientists still do not know how much whole NAD+ gets into cells.

   For experts

   In a human pilot of intravenous NAD+ (Grant et al., 2019), plasma NAD+ was rapidly and completely removed for at least the first 2 hours (attributed by the authors to tissue uptake and/or metabolism); by the end of the 6-hour infusion plasma NAD+, nicotinamide, ADP-ribose and methylnicotinamide had risen about 4-fold, with NMN raised 2 hours later; the pattern fit NAD+ glycohydrolase and pyrophosphatase activity. The pilot had 8 infused participants and 3 saline controls. Mechanistic cell work shows extracellular NMN must be converted to nicotinamide riboside before cellular uptake via NRK1 (Ratajczak et al., 2016). Some intact NAD uptake has been reported in two cultured cell types at low concentrations (Billington et al., 2008), so uptake of intact NAD+ in vivo is unresolved. Human data: pilot only; cell data: in vitro.[src][src][src]

2. 02Liver

   The body makes its own supply, and the liver is a key source

   You do not need to swallow NAD+ to have it. Cells build it from vitamin B3 and from an amino acid called tryptophan. In mice, the liver builds NAD+ from tryptophan and sends a B3 form out into the blood for other organs to reuse.

   For experts

   NAD+ is synthesised de novo from tryptophan, from nicotinic acid via the Preiss-Handler pathway, and by salvage from nicotinamide, NR and NMN. Isotope-tracer work in mice showed NAD is made from tryptophan selectively in the liver, which then excretes nicotinamide; tissues differ widely in NAD flux (high in small intestine and spleen, low in skeletal muscle); intravenous NR or NMN delivered intact molecules to tissues, whereas the same agents given orally were metabolised to nicotinamide in the liver (Liu et al., 2018). These are animal and cell tracer data; they describe precursor handling, not NAD+ infusions in humans.[src][src]

3. 03Muscle

   Inside cells, NAD+ carries electrons that make energy

   In muscle and every other tissue, NAD+ works like a rechargeable battery pack. It picks up electrons when food is broken down, becoming NADH, and hands them to the cell's power stations, the mitochondria. That job is the reason cells cannot live without it.

   For experts

   NAD+/NADH is the principal electron-carrier pair in glycolysis, the TCA cycle and fatty-acid oxidation, feeding complex I of the respiratory chain. The NAD+/NADH ratio links energy status to adaptive signalling, including mitochondrial stress responses (Cantó et al., 2015; Verdin, 2015). This is established biochemistry in humans and other species; it does not by itself show that adding NAD+ from outside raises this activity.[src][src]

4. 04Elsewhere

   NAD+ is also used up by repair and control enzymes

   Besides carrying energy, NAD+ is a fuel that certain enzymes burn. Some help repair damaged DNA. Others switch genes on and off. Because they consume NAD+, heavy demand for repair can lower the cell's supply.

   For experts

   NAD+ is a co-substrate for sirtuin deacylases (SIRT1-7), PARPs (DNA-damage response and chromatin remodelling) and the NADases CD38 and CD157, which regulate metabolism, DNA repair, cellular senescence and immune function (Covarrubias et al., 2021; Verdin, 2015). Consumption by PARPs and sirtuins accounted for most NAD turnover in cell lines (Liu et al., 2018). Evidence is mostly from cells and rodents; human causal links between NAD+ levels and disease are not established.[src][src][src]

5. 05Immune system

   CD38 and the 'NAD+ falls with age' idea

   An enzyme called CD38, found on immune cells and other tissues, breaks down NAD+. In older mice it becomes more active and NAD+ falls. In people, a large 2026 study found that NAD+ in whole blood does not fall with age, so the idea is less settled than it sounds.

   For experts

   In mice, CD38 expression and NADase activity rise with age and are required for the age-related NAD decline and mitochondrial dysfunction; CD38 is also the main enzyme degrading NMN in vivo (Camacho-Pereira et al., 2016). Reviews describe tissue NAD+ decline with ageing in rodents and humans (Covarrubias et al., 2021), but a 2026 analysis of seven independent human cohorts found whole-blood NAD+ stable with age and across lifestyle interventions, while changing, as expected, with NR supplementation (Trętowicz et al., 2026). Tissue-level human ageing data remain limited.[src][src][src]

6. 06Heart

   Heart: a placebo-controlled human trial of infused NAD+

   Researchers in China gave 180 people with heart failure either an NAD+ drip or a placebo drip for 7 days, on top of usual care. A month later the pumping measure was slightly better with NAD+. Later hospital and event numbers leaned the same way but were not clear enough to count. One trial in one hospital is a first hint, not proof.

   For experts

   In a single-centre, randomised, placebo-controlled trial of 180 adults with ischaemic cardiomyopathy (LVEF <=45%, NYHA II-III), 7 days of intravenous NAD+ added to guideline-directed therapy gave a higher LVEF at 1 month than placebo (45.44 +/- 8.55% vs 42.44 +/- 9.09%, p=0.024). NT-proBNP at day 7 (p=0.102), 6-month MACCE (14.6% vs 24.7%, p=0.089) and NYHA improvement (p=0.088 at 1 month) did not reach significance, and structural echo parameters did not differ. The authors cite sirtuin-mediated mitochondrial effects as the rationale and note limited power for clinical events (ChiCTR2200059169). The study drug and a research grant came from the manufacturer; the paper states the funders had no role in the study or analysis. This is human evidence, but small, from one centre, and awaiting replication.[src][src]

7. 07Brain

   Brain: evidence so far is for precursors, not NAD+ drips

   In a small trial in people with early Parkinson's disease, the vitamin-B3 form nicotinamide riboside, taken by mouth, raised NAD in the brain. That is a different molecule from NAD+ and a different route, so it says little about NAD+ drips.

   For experts

   NADPARK, a randomised phase I trial (30 newly diagnosed, treatment-naive people with Parkinson's disease, 30 days of oral NR vs placebo), reported a significant but variable rise in cerebral NAD measured by 31P-MRS, and altered cerebral metabolism with mild clinical improvement in those with increased brain NAD (Brakedal et al., 2022). Oral NR also raises blood NAD+ metabolites in humans (Trammell et al., 2016; Martens et al., 2018). These findings concern an oral precursor and are not evidence that intravenous NAD+ reaches the brain.[src][src][src]

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