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

JACC Basic Transl Sci. 2022 Sep 14;7(12):1183-1196. doi: 10.1016/j.jacbts.2022.06.012. eCollection 2022 Dec.


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).

Keywords: AE, adverse event; E/e′, ratio of the early transmitral flow velocity to the early diastolic tissue velocity; GLS, global longitudinal strain; HF, heart failure; HFrEF; HFrEF, heart failure with reduced rejection fraction; IL, interleukin; LV, left ventricular; NAD+; NAD+, nicotinamide adenine dinucleotide; NLRP3, NOD-like receptor family pyrin domain containing 3; NR; NR, nicotinamide riboside; PBMC, peripheral blood mononuclear cell; TNF, tumor necrosis factor; heart failure with reduced ejection fraction; mitochondrial dysfunction; nicotinamide adenine dinucleotide; nicotinamide riboside; sterile inflammation.

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