Study summary · research use only
Nicotinic acid riboside maintains NAD(+) homeostasis and ameliorates aging-associated NAD(+) decline
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, the authors examined how liver-derived nicotinamide feeds systemic NAD+ synthesis, using liver-specific nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) knockout mice (LKO). Despite blunted hepatic NAD+ and nicotinamide production in LKO mice, circulating nicotinamide and NAD+ in other organs were reported to be unaffected. Metabolomics identified accumulation of nicotinic acid riboside (NaR) in LKO liver, with cytosolic 5'-nucleotidase II (NT5C2) identified as the NaR-producing enzyme. The authors report that the liver releases NaR to the bloodstream and kidneys take up NaR to synthesize NAD+ via nicotinamide riboside kinase 1 (NRK1). Serum NaR was reported to decline with aging, while oral NaR supplementation in aged mice was associated with increased serum nicotinamide and multi-organ NAD+, including kidneys, and with reduced kidney inflammation and albuminuria.
Abstract
Liver-derived circulating nicotinamide from nicotinamide adenine dinucleotide (NAD+) catabolism primarily feeds systemic organs for NAD+ synthesis. We surprisingly found that, despite blunted hepatic NAD+ and nicotinamide production in liver-specific nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion mice (liver-specific knockout [LKO]), circulating nicotinamide and extra-hepatic organs' NAD+ are unaffected. Metabolomics reveals a massive accumulation of a novel molecule in the LKO liver, which we identify as nicotinic acid riboside (NaR). We further demonstrate cytosolic 5'-nucleotidase II (NT5C2) as the NaR-producing enzyme. The liver releases NaR to the bloodstream, and kidneys take up NaR to synthesize NAD+ through nicotinamide riboside kinase 1 (NRK1) and replenish circulating nicotinamide. Serum NaR levels decline with aging, whereas oral NaR supplementation in aged mice boosts serum nicotinamide and multi-organ NAD+, including kidneys, and reduces kidney inflammation and albuminuria. Thus, the liver-kidney axis maintains systemic NAD+ homeostasis via circulating NaR, and NaR supplement ameliorates aging-associated NAD+ decline and kidney dysfunction.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.