Metabolism of Nicotinamide Adenine Dinucleotide+ in Atherosclerosis: Mechanisms and Nutritional Modulation

This narrative review aims to provide a vascular-oriented and nutrition-relevant synthesis of nicotinamide adenine dinucleotide+ (NAD+) metabolism in atherosclerosis and to clarify how dietary and lifestyle factors may modulate NAD+ homeostasis in vascular disease. Although NAD+ has emerged as a central regulator of vascular redox balance, mitochondrial function, inflammation, and DNA repair, its role in atherosclerosis remains conceptually fragmented and has not yet been fully examined within the context of nutrition-relevant research frameworks. We searched PubMed, Web of Science, Embase, and Google Scholar and synthesized evidence from mechanistic, preclinical, and clinical studies. Current evidence suggests that NAD+ network remodeling in atherosclerosis reflects the interplay of precursor availability, enzymatic consumption, and plaque microenvironment stressors. Nutritional modulation approaches can be broadly grouped into 4 domains: NAD+ precursor supplementation, flavonoid-related conservation strategies, gut microbiota-associated pathways, and lifestyle interventions. Human studies have consistently demonstrated systemic NAD-related metabolite engagement following precursor supplementation; however, convincing evidence for direct antiatherosclerotic benefit remains limited, and circulating NAD+ measures may not adequately represent vascular NAD+ status. By integrating vascular biology with nutrition-based modulation strategies, this review provides a practical conceptual framework for interpreting current evidence and guiding future research. Well-designed trials incorporating vascular-specific biomarkers and clinically meaningful cardiovascular endpoints are needed to determine the therapeutic relevance of NAD+-targeted nutritional interventions.