NAD.

Nicotinamide riboside is phosphorylated by NRK1 and NRK2 to NMN and then adenylylated to NAD+, so it feeds the pool directly. It is one of the standard routes by which oral dosing raises tissue NAD+.

NMN is converted to NAD+ by nicotinamide mononucleotide adenylyltransferase in a single step. It sits at the last junction of the salvage pathway before the cofactor itself.

Nicotinic acid enters through the Preiss-Handler route via nicotinic acid mononucleotide and nicotinic acid adenine dinucleotide to reach NAD+. This is the long-recognised dietary route for building the cofactor.

Excess nicotinamide is cleared by nicotinamide N-methyltransferase, a reaction that spends S-adenosylmethionine methyl groups. Trimethylglycine donates a methyl group back to homocysteine to regenerate methionine, which is the stated reason it is formulated alongside NAD precursors, though the size of the methyl draw in people taking these doses is still being measured.

Nicotinamide enters the NAD pool through NAMPT in the salvage pathway, and it is also the by-product released whenever a sirtuin or PARP consumes NAD, which feeds back to slow those enzymes.

Nicotinic acid is converted to nicotinic acid mononucleotide and then to NAD through the three-step Preiss-Handler route. It reaches the same pool as the salvage precursors by different chemistry.

Tryptophan is converted to NAD through the kynurenine pathway, the only route that builds the pyridine ring from scratch. It is the reason NAD status tracks protein intake as well as B3 intake.

Kynureninase is a pyridoxal-phosphate enzyme, and it is the step that channels tryptophan toward NAD rather than away from it. Low B6 shifts that traffic off the NAD route.

Kynurenine 3-monooxygenase is FAD-dependent, so riboflavin status gates the tryptophan-to-NAD route. Riboflavin also drives the flavoprotein reactions that reoxidise NADH.

3-hydroxyanthranilate 3,4-dioxygenase in the tryptophan-to-NAD route is a non-heme iron enzyme. Iron status therefore affects how much NAD is built de novo.

Pterostilbene raises sirtuin activity, and every sirtuin deacetylation reaction spends one NAD. Supplying both matches the demand created to the supply available.

Quercetin inhibits CD38, the main ectoenzyme that hydrolyses NAD and its precursors at the cell surface. Slowing that breakdown preserves more of the pool.

Complex I strips electrons from NADH and hands them to ubiquinone, so the two carriers sit back to back in the respiratory chain. Neither turns over without the other being available in the right redox state.

Dihydrolipoamide dehydrogenase reoxidises lipoamide by handing its electrons to NAD, which is how the pyruvate and alpha-ketoglutarate dehydrogenase complexes reset each cycle. NAD is the compulsory acceptor for lipoate chemistry.

Glutathione reductase uses NADPH, made from NADP, to return oxidised glutathione to its active form. The size and redox state of the NAD and NADP pool sets how fast glutathione is recycled.

Methylene blue accepts electrons from NADH and passes them further down the chain, which shifts the NAD to NADH ratio toward the oxidised form. It acts on NAD redox rather than on pool size.

Surplus nicotinamide is methylated by nicotinamide N-methyltransferase using S-adenosylmethionine, and methylfolate helps regenerate that methyl donor. Raising NAD precursor intake raises the methyl demand.

Ribose-5-phosphate feeds the PRPP pool that supplies the ribose-phosphate half of every NAD molecule made through the salvage and Preiss-Handler routes. Ribose availability is part of what limits nucleotide assembly.

NAD synthesis runs through ATP-dependent steps catalysed by nicotinamide mononucleotide adenylyltransferase and NAD synthetase, and every ATP-dependent step needs magnesium as the Mg-ATP complex. NAD kinase, which makes NADP from NAD, is magnesium dependent as well. The relationship is textbook enzymology rather than a supplementation trial.

Human alcohol and retinol dehydrogenases are zinc metalloenzymes and they cannot run their NAD-dependent oxidation without the catalytic zinc in place. Zinc status therefore sits upstream of one whole branch of NAD-dependent metabolism. This is settled enzymology, not a claim that adding zinc raises NAD.

Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase both require thiamine pyrophosphate as a cofactor and both transfer electrons onto NAD+. Without thiamine the reaction stalls and NAD+ is not reduced at that step. The dependency runs one way, from thiamine to the reaction, and is standard biochemistry.

Coenzyme A is built from pantothenic acid and it accepts the acetyl group in the same pyruvate dehydrogenase reaction that reduces NAD+. The two cofactors are structural partners in that complex. Read it as pathway architecture rather than as a dosing recommendation.

Glutamine is the nitrogen donor for the glutamine-dependent NAD synthetase step that converts nicotinic acid adenine dinucleotide into NAD. Separately, glutamine-derived glutamate is oxidised by glutamate dehydrogenase using NAD as the electron acceptor. Both connections are settled biochemistry.

NAC supplies cysteine for glutathione synthesis, and returning oxidised glutathione to its reduced form runs on glutathione reductase using NADPH, which comes from NAD via NAD kinase and the pentose phosphate pathway. The two nutrients sit on either side of the same redox ledger. This is mechanism, not a measured co-supplementation result.

CD38 hydrolyses NAD and its activity rises with age in animal work. Apigenin inhibits CD38 in cell and rodent studies, which is the reason formulators pair it with NAD precursors. Human data on the pairing is not there yet, so this is a preclinical mechanism.

Luteolin has been reported to inhibit CD38 in enzyme and cell assays, which would slow NAD consumption rather than raise its synthesis. The work is preclinical. Regard it as a mechanistic rationale for a pairing, not as a human result.

Sirtuins are NAD-dependent deacetylases, so their activity is limited by NAD availability. Resveratrol has been studied as a sirtuin activator, putting the two on the same axis from opposite sides, substrate and enzyme. Human evidence for the combination raising sirtuin output is not settled.

CD38 converts NAD into cyclic ADP-ribose, which releases calcium from intracellular stores through ryanodine receptors. That places NAD upstream of a normal calcium signalling route. The link is biochemistry and does not imply that taking calcium changes NAD levels.

Urolithin A promotes mitophagy in preclinical work, clearing damaged mitochondria, while NAD availability supports the redox reactions running in the ones that remain. Formulators combine them for that reason. The pairing has not been measured together in people.

Spermidine induces autophagy in cell and animal models. NAD-dependent sirtuins are also linked to autophagy regulation, so the two converge in the literature. The overlap is preclinical and the combination has not been tested in humans.

Malate dehydrogenase oxidises malate to oxaloacetate and reduces NAD+ to NADH, both in the citric acid cycle and in the malate-aspartate shuttle that moves reducing equivalents into mitochondria. Malate is therefore a direct partner of the NAD+ pool in energy metabolism. This is standard pathway biochemistry.