NAD+ 500 mg

Nicotinamide adenine dinucleotide is not a peptide. It is a dinucleotide: two ribonucleotides, one bearing a nicotinamide base and one bearing adenine, joined tail to tail through their 5'-phosphate groups by a pyrophosphate bridge. The nicotinamide is attached to its ribose in the beta configuration at the anomeric carbon, and the pyridine nitrogen of that ring is quaternary. That quaternary nitrogen is what the plus sign in NAD+ denotes; it is a formal charge on the ring, not a salt. Reduction places a hydride on carbon 4 of the nicotinamide ring to give NADH, and the molecule cycles between the two states without being consumed.

Two molecular weights circulate for the same substance and both are defensible. PubChem (CID 5892), Merck/Sigma-Aldrich (product 124542) and Cayman Chemical (item 16077) all record the neutral inner-salt formula C21H27N7O14P2, with Sigma-Aldrich stating 663.43 g/mol and the other two stating 663.4; that value is also what the formula returns when recomputed from standard atomic weights, and it is the figure on file for this item. Wikipedia's chembox instead draws the oxidised form as the cation C21H28N7O14P2+ and gives 664.4 g/mol. The difference is one proton and a drawing convention, not a disagreement about what the compound is. CAS 53-84-9 refers to the free acid; salt forms of NAD carry their own separate registry numbers, so a certificate of analysis quoting a different CAS is describing a different salt, not necessarily a different molecule.

The compound was first inferred in 1906 by Arthur Harden and William Young, who observed that yeast juice lost fermentative activity on dialysis and recovered it when the dialysate was returned. They called the missing factor a coferment; the name cozymase came into use afterwards. Von Euler-Chelpin and Myrback purified cozymase in 1923 and identified it as a nucleoside sugar phosphate, and in 1936 Otto Warburg showed the coenzyme's role in hydride transfer and identified the nicotinamide portion as the site of the redox chemistry. In living cells NAD+ is assembled by three routes: de novo from tryptophan via the kynurenine pathway, from nicotinic acid via the Preiss-Handler pathway, and by salvage of nicotinamide through the enzymes NAMPT and NMNAT (Canto, Menzies and Auwerx, 2015). Because the molecule contains no amino acids, it is not produced by the solid-phase peptide synthesis used for most items in a peptide catalogue. Analytically, both oxidation states absorb near 260 nm through the adenine ring, but only the reduced form has a second absorbance peak near 339 to 340 nm, with a molar extinction coefficient of 6220 M-1 cm-1. That single spectroscopic difference is the basis of a large fraction of spectrophotometric enzyme assays in biochemistry, since the appearance or disappearance of absorbance at 340 nm tracks turnover directly.

The literature on this compound splits into two very unequal halves, and conflating them is the most common error in material written about it. The body of work on NAD+ as an intracellular redox cofactor and enzyme co-substrate is enormous and more than a century old. The body of work on administering intact NAD+ to a living organism is far smaller. Most of the human clinical literature commonly attributed to NAD+ was in fact run on its precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which are different molecules with different transport and metabolism. The paragraphs below keep the two apart.

Two published human studies have administered intact NAD+ intravenously. Grant et al. (2019) infused NAD+ at 3 micromol per minute over six hours and sampled plasma and urine throughout. They reported no measurable change in plasma NAD+, nor in the metabolites nicotinamide, methylnicotinamide, ADP-ribose or NMN, until after two hours, and interpreted this as rapid and essentially complete removal of NAD+ from plasma over that period. At six hours they detected increased urinary excretion of NAD+ and of methylnicotinamide, with no significant rise in urinary nicotinamide, and described the metabolite profile as consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity. The authors present the work explicitly as a pilot study.

Yu et al. (2026) subsequently reported a single-centre, prospective, randomised, placebo-controlled trial in 180 adults with heart failure due to ischaemic cardiomyopathy (left ventricular ejection fraction of 45 percent or below, NYHA class II to III), assigning intravenous NAD+ at 10 mg per day or matched placebo for seven days alongside guideline-directed medical therapy (registration ChiCTR2200059169). The pre-specified primary endpoint, change in ejection fraction at one month, favoured the NAD+ arm (45.44 plus or minus 8.55 percent versus 42.44 plus or minus 9.09 percent, p = 0.024). The secondary endpoints did not reach statistical significance and were reported by the authors as trends only: NT-proBNP at day 7 (p = 0.102), the six-month composite of major adverse cardiac and cerebrovascular events (14.6 percent versus 24.7 percent, p = 0.089), and improvement in NYHA class at one month (p = 0.088). No differences were observed in structural parameters. The authors state that the finding warrants validation in larger multicentre trials with clinical endpoints.

The precursor trials are better powered and are what most quantitative statements in this field actually rest on. Martens et al. (2018) ran a 2 x 6-week randomised, double-blind, placebo-controlled crossover trial in healthy middle-aged and older adults using nicotinamide riboside chloride at 500 mg twice daily; they measured a rise of approximately 60 percent in NAD+ in peripheral blood mononuclear cells relative to placebo, and reported the regimen as well tolerated. Elhassan et al. (2019) supplemented 12 aged men with 1 g of NR per day for 21 days in a placebo-controlled crossover design and used targeted metabolomics on muscle biopsies: the muscle NAD+ metabolome was elevated, evidenced by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products, while mitochondrial bioenergetics were unchanged. That study also recorded lower levels of circulating inflammatory cytokines.

For NMN, Yoshino et al. (2021) conducted a 10-week randomised, placebo-controlled, double-blind trial in 25 postmenopausal women with prediabetes who were overweight or obese, at 250 mg per day (trial registration NCT03151239). Insulin-stimulated glucose disposal measured by hyperinsulinaemic-euglycaemic clamp increased after NMN and did not change after placebo, alongside increased phosphorylation of AKT and mTOR in skeletal muscle. PubMed lists four published Comment-in responses to that paper, which is worth noting when the result is cited without qualification. On the preclinical side, Camacho-Pereira et al. (2016), working in rodents, reported that expression and activity of the NADase CD38 rise with age, that CD38 is required for the age-related fall in NAD+ and the accompanying mitochondrial dysfunction through a pathway involving SIRT3, and that CD38 is the principal enzyme degrading NMN in vivo. Broader reviews (Canto et al., 2015; Rajman, Chwalek and Sinclair, 2018) survey NAD+ biosynthesis and its consumption by sirtuins, PARPs and CD38/CD157. Rajman et al. are direct about the limits of the evidence: it is dominated by rodent work and by short human studies reporting biomarker rather than clinical endpoints. Anyone using this material as a laboratory reagent should read the human precursor literature as adjacent to, not a substitute for, data on the intact dinucleotide.