Mechanisms of Carrageenan-Induced Immune Inflammation and Thrombosis: A Narrative Review

This review summarizes carrageenan (CGN)-induced immune inflammation and thrombosis, route-dependent effects, and studies conducted in animal models, distinguishing experimental conditions from human dietary exposure. PubMed, Web of Science, and CNKI were searched, and studies were stratified by subtype, dose, route, and model. Toll-like receptor 4 (TLR4) is central to CGN-mediated immune activation, but the CGN-TLR4/MD-2 co-crystal structure remains undetermined. MyD88 mediates TNF-α, and TRIF-dependent NLRP3 contributes to IL-1β maturation, but this dual-branch pathway has been confirmed in mouse peritoneal macrophages only and does not activate IRF3/IFN-β. Route determines outcomes: intravenous CGN activates FXII/CLEC-2, causing rapid thrombosis; intraperitoneal CGN triggers macrophage TNF-α/IL-1β release, initiating the inflammation-endothelial injury-coagulation cascade; and oral CGN has been shown under specific experimental model conditions to be degraded by gut microbiota into low-molecular-weight fragments, which may potentially induce colitis. These outcomes have not been confirmed to be the consequences of typical human dietary exposure. These findings were primarily derived from non-oral, high-dose, degraded-product, or in vitro studies and cannot be directly extrapolated to human dietary exposure. Food-grade CGN, low-molecular-weight/degraded CGN, and poligeenan differ fundamentally in metabolism and toxicology. Under conditions of an intact barrier and normal dietary exposure, the current evidence does not indicate a consistent pro-inflammatory or pro-thrombotic risk of food-grade CGN; however, this does not exclude all potential effects, as microbiota degradation efficiency, fragment exposure, and special-population susceptibility have not been fully investigated. Future studies should determine the CGN-TLR4/MD-2 structure, validate the dual-branch pathway independently, and conduct human metabolic tracing and special-population studies.