Oxalate as an Emerging Contributor to Cardiovascular Disease: Links to Inflammation, Immunity, and Oxidative Stress

Cardiovascular disease (CVD) is the world's leading cause of death and continues to rise in prevalence, contributing to healthcare and economic costs. Following diagnosis, patients are advised to adopt medication regimens, increase physical activity, and modify dietary intake to reduce disease progression and prevent additional comorbidities. Oxalate is a small molecule in plant-derived foods such as spinach, potatoes, almonds, and peanuts and is also produced endogenously. Although oxalate is traditionally studied in the context of kidney stone disease, recent evidence suggests that it may be a dietary contributor to inflammation and oxidative stress in CVD. Elevated systemic oxalate levels promote reactive oxygen species (ROS) generation and activate inflammatory pathways such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and the NLRP3 inflammasome, which are key players in CVD. In this narrative review, we discuss the current literature describing the role of inflammation in CVD and evaluate emerging evidence that dietary oxalate may influence immune, oxidative, and vascular mechanisms contributing to CVD development and progression. In addition, we highlight populations that may be most vulnerable to oxalate-mediated vascular effects. We conclude by describing existing gaps in knowledge and potential future directions for the field. Understanding these mechanisms further may guide dietary recommendations and delineate oxalate's potential role as a modifiable risk factor for CVD.