Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.
Level 5 - mechanism / opinion, no new human data
Bench, in vitro, and animal research with observational human tissue biopsies.
PubMed 29217642 · doi:10.1161/CIRCULATIONAHA.116.026099
What was done
Researchers evaluated NAD+ biosynthetic enzyme expression in human failing heart biopsies compared to nonfailing controls, as well as in mouse models of dilated cardiomyopathy (DCM, via serum response factor depletion) and cardiac hypertrophy (transverse aortic constriction [TAC]). They investigated Nmrk2 pathway regulation in isolated rat cardiomyocytes subjected to energy stress and tested the functional and metabolic effects of dietary nicotinamide riboside (NR) supplementation in the mouse models.
What was found
Failing mouse hearts exhibited a 30% decrease in NAD+ levels, decreased nicotinamide phosphoribosyltransferase (NAMPT) expression, and increased nicotinamide riboside kinase 2 (NMRK2) expression (40-fold increase in DCM, 4-fold increase in TAC), a shift also observed in human failing heart biopsies. In rat cardiomyocytes, NR restored NAD+ synthesis during NAMPT inhibition (FK866) and stimulated glycolysis. In vivo, dietary NR supplementation stabilized myocardial NAD+ levels, elevated three metabolic biomarkers (nicotinic acid adenine dinucleotide, methylnicotinamide, and N1-methyl-4-pyridone-5-carboxamide), and attenuated heart failure progression (robustly in DCM, partially in TAC).
Why it matters
This study identifies a metabolic reprogramming pathway in heart failure where the failing myocardium upregulates NMRK2 to utilize NR for NAD+ synthesis, supporting NR supplementation as a candidate therapeutic approach for cardiomyopathy.
Limits
Interventional findings are limited to rodent models and isolated cell cultures. Exact sample sizes for human tissue samples and animal cohorts, as well as quantitative metrics of in vivo cardiac function improvement, were not reported in the abstract. Clinical efficacy and safety in human heart failure patients were not evaluated.
Cited by
- supports Heart failure, central and peripheral neurodegeneration, and UV sun exposure deplete or disturb NAD system levels in affected tissues.
- supports Nicotinamide cannot boost NAD in heart failure animal models because the failing heart overexpresses NMRK2 and relies on the nucleoside pathway.