Nicotinamide Riboside–Mediated Cardioprotection Depends on Insulin Signaling and Glycolytic Metabolism: Preclinical Findings

Synopsis

Low levels of nicotinamide adenine dinucleotide (NAD+) contribute to heart diseases, aging, and ischemia-reperfusion injury (IRI)—the tissue damage that occurs when blood supply returns to the heart after blockage. Nicotinamide riboside (NR), a vitamin B3–derived NAD+ precursor, has shown strong protective effects against IRI, but the underlying mechanism was unclear. Using isolated mouse hearts, researchers tested how NR influences heart metabolism during IRI under different energy conditions. NR supplementation increased NAD+ levels in all cases but only protected the heart when glycolysis (glucose breakdown) was moderately active. NR enhanced glycolytic intermediates such as phosphoenolpyruvate (PEP) and boosted energy metabolism, reducing heart injury. However, when glycolysis was blocked or already maximized by insulin, NR lost its protective effects. These findings suggest that NR’s cardioprotective power depends on its ability to activate glycolysis, providing metabolic flexibility during stress. In contrast, high insulin levels—which already stimulate glycolysis—eliminate NR’s benefit, revealing how NAD+ metabolism and glucose utilization work together to influence heart protection.

Journal

Basic Research in Cardiology