NRH

NRH is the reduced form of nicotinamide riboside, and it is the most potent NAD-raising molecule in this batch by a wide margin. Every number supporting that statement comes from cultured cells or from mice.

The interest is mechanistic and genuine. NR has to be phosphorylated by nicotinamide riboside kinases, NRK1 and NRK2, and that step is rate-limiting. NRH bypasses it. Two independent groups published in 2019 that NRH uses a different, NRK1-independent route to NAD, via an ATP-dependent kinase activity that converts it to NMNH, which means the reduced precursors constitute a separate branch of NAD biosynthesis rather than a slightly better version of the same one.

In cells, NRH raised NAD 2.5 to 10-fold over control within as little as an hour, and beat NR and NMN at every equivalent concentration tested. In C57BL/6J mice it raised tissue NAD after intraperitoneal injection, and a second group showed it is orally bioavailable in mice and prevented cisplatin-induced acute kidney injury.

Against that: there is no published human pharmacokinetic study, no published human safety study, and no published human trial of any kind. NRH is nonetheless sold online as a supplement, usually on copy that cites the cell-culture fold-change as if it were a human result.

There is also a reason for caution that is specific to this family. The closest relative, NMNH, is a more potent NAD enhancer than NMN and in the same experiments inhibited glycolysis and the TCA cycle, induced cell cycle arrest and suppressed cell growth. Raising NAD harder and faster is not self-evidently better, and nobody has established what the reduced precursors do to a human.

There is no human evidence for NRH of any kind. No pharmacokinetic study, no safety study, no trial. That is the entire human record and it is why this page has no human evidence section.

What exists is two independent 2019 papers, in cells and mice, agreeing that NRH raises NAD faster and higher than NR or NMN and does it through a different enzymatic route. Independent replication of a mechanism by two groups in the same year is a real thing and worth stating plainly. It is also a statement about biochemistry, not about people.

The gap between those two facts is where the product is sold. Vendor copy for NRH routinely quotes the 2.5 to 10-fold figure without saying it is a cell-culture number, and describes oral bioavailability without saying it was measured in mice.

There is a specific reason not to assume that more potent is better here. NRH's immediate metabolite NMNH, studied by a third group, raised NAD more than NMN and simultaneously suppressed glycolysis, the TCA cycle and cell growth, and induced cell cycle arrest in vitro. A compound that shifts the NAD to NADH ratio strongly is doing something to central carbon metabolism, and in the one experiment that looked, what it did was slow it down. Whether that is harmful, neutral or therapeutic in a human is unknown because nobody has looked.

Three claim types get collapsed into one in almost all consumer writing about this pathway, and keeping them apart is most of the work. A biomarker claim is that a compound raises blood NAD. That is easy to demonstrate and for several of these compounds it is simply true. A surrogate claim is that it moves something sitting between a biomarker and a symptom, such as arterial stiffness or an acylcarnitine profile. A clinical claim is that a person walks further, remembers more, gets fewer cancers or lives longer. A compound can be firmly established at the first level and have nothing at all at the third, and that is the actual position of most of the NAD pathway. There is no published human trial of any NAD precursor with a hard clinical endpoint that reported a benefit, with one exception on this list, and that exception is nicotinamide in skin cancer, which works through DNA repair in sun-damaged skin rather than through anything to do with ageing.