NAD+ boosting increases atherosclerotic plaques and inflammation in Apoe knockout mice

High-dose NR supplementation in mice did not decrease but increase both aortic plaque lesions and systemic inflammation. These effects may be mediated by increased CD38 expression in macrophages, with NAD⁺ metabolism shifted from sirtuins towards CD38 and PARP1 pathways. Caution should be applied with presumed NAD⁺ boosters in patients with atherosclerosis.