Aspirin: From High Doses to High Dilutions – A Historical Critical Review and New Proposals

Platelets and vessel walls interact to retain blood flow homeostasis during inflammatory conditions. Rebound effects of anti-thrombotic agents, such as prostanoids and COX inhibitors can lead to thrombosis, infarct and stroke. Aspirin has been prescribed for decades due to its powerful anti-platelet action, but it is also related to withdrawal syndrome peaks, resistance and thrombogenesis. Moreover, other paradoxical effects have also been described. A single high dose of aspirin can generate thrombus eight to ten days later; however, highly diluted aspirin can also produce the same effect in one hour, by unknown pathways, though it is known that high dilutions of aspirin can reduce PGI2 activity. Additionally, aspirin anti-thrombotic effects are also reversed by its high dilutions. Despite the fact that COX-2 selective inhibition and highly diluted aspirin have pro-thrombotic properties, the simultaneous administration of both does not further increase thrombus formation. Metabolic changes in platelets, rebound effect, delayed inhibition of COX-2 and residual endothelial aspirin accumulation are plausible hypotheses, since these patterns lead to the concept of hormesis. However, other fields of investigation, such as the characterization of nanostructures and electronic field properties of high dilutions, have not been studied yet for aspirin. Further studies involving the participation of COX-2 in macrophages, and the description of high dilution physicochemical properties and their putative relationships, are promising areas for follow-up in this subject.

Keywords: Aspirin, high dilutions, experimental models