Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction

The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD⁺) and NADH levels. Raising NAD⁺ levels with the NAD⁺ precursor, nicotinamide riboside (NR), may represent a novel HF treatment. In this 30-participant trial of patients with clinically stable HF with reduced ejection fraction, NR, at a dose of 1,000 mg twice daily, appeared to be safe and well tolerated, and approximately doubled whole blood NAD⁺ levels. Intraindividual NAD⁺ increases in response to NR correlated with increases in peripheral blood mononuclear cell basal (R ² = 0.413, P = 0.003) and maximal (R ² = 0.434, P = 0.002) respiration, and with decreased NLRP3 expression (R ² = 0.330, P = 0.020). (Nicotinamide Riboside in Systolic Heart Failure; NCT03423342).