Nicotinamide Riboside Protects Heart Function in Dilated Cardiomyopathy: Preclinical Findings

Synopsis

In chronic heart failure, the heart’s energy metabolism is severely impaired. NAD+ is a key molecule that helps cells produce energy and respond to stress, making it an important focus in heart disease research. However, how NAD+ is regulated in failing hearts is not well understood. To investigate this, researchers measured enzymes involved in making NAD+ in human failing hearts and mouse models of heart disease. They found a 30% reduction in NAD+ levels in diseased mouse hearts, along with decreased expression of an enzyme (NAMPT) that recycles nicotinamide, an NAD+ precursor. Meanwhile, another enzyme (NMRK2) that uses a different NAD+ precursor was increased, especially in one model of heart failure. Similar changes were seen in human heart samples. Further studies showed that NMRK2 is activated by energy stress and low NAD+ levels. Supplementing with nicotinamide riboside (NR), a precursor to NAD+, helped restore NAD+ levels and improved heart function in these mice. NR also raised levels of certain metabolites that could serve as markers of treatment. These findings suggest that NR, which efficiently boosts NAD+ production, may be a promising therapy for heart failure, especially for forms with limited treatment options like dilated cardiomyopathy.

Journal

Circulation