The Effects of Boosting NAD+ on Atherosclerosis and Inflammation: Preclinical Findings

Synopsis

NAD+ is a key molecule that activates sirtuins, which are linked to benefits like lifespan extension and improved metabolism in mice. Supplements like nicotinamide riboside (NR) are used to boost NAD+, but they compete with other enzymes like PARP1 and CD38. This study tested whether NR protects against atherosclerosis in mice. ApoE knockout mice were fed a high-cholesterol diet with low, medium, or high NR doses, and macrophages were treated with NR and oxidized LDL. High-dose NR increased aortic plaque, inflammation markers (TNFα, IL-6), and LDL cholesterol, while liver and blood NAD+ stayed the same but the metabolite 4PY rose. SIRT1 and liver lipoprotein receptors decreased, CD38 increased, and PARP1 activity was reduced. In macrophages, high NR raised CD38 and inflammatory markers. Overall, high NR worsened plaque and inflammation, likely by shifting NAD+ use from sirtuins to CD38 and PARP1, suggesting caution when using NAD+ boosters in atherosclerosis.

Journal

Atherosclerosis