PB0035 - Intake of the artificial sweetener aspartame aggravates arterial thrombosis in mice through augmenting platelet activation.

Background: Artificial sweeteners are widely used in the food industry to replace sugar and combat health issues related with overweight including diabetes and cardiovascular diseases. Aspartame is a low-calorie synthetic dipeptide and its use as the primary nonnutritive sweetener in carbonated beverages was approved in 1981 by the US and EU regulatory agencies. A few recent studies reported associations between aspartame intake and increased risk of cerebrovascular diseases, but the conclusions have been inconsistent across different studies, and the underlying mechanism remains elusive.

Aims: We sought to determine whether aspartame intake affect mice arterial thrombotic risk and whether platelets play a role mediating this effect.

Methods: Eight weeks old male C57BL/6J mice were administered with 72mg/kg aspartame for 1hr or 4 weeks, before respectively subjected to 7.5% FeCl3 induced carotid arterial thrombosis model or flow cytometric analyses of protease activated receptors 4 activation peptide (PAR4-AP)-induced platelet activation (JON/A binding for αIIbβ3 activation). All animal experimental procedures were approved by the Ethics Committee of Soochow University.

Results: Compared to vehicle control, aspartame administration significantly shortened the occlusion time following mice carotid artery injury (10.9±1.4 versus 12.9±2.5 minutes, P< 0.01; figure 1A). Platelets isolated from aspartame-administrated mice exhibited elevated αIIbβ3 activation (86.9±6.2 versus 77.4±11.3 % positive JON/A binding, P< 0.05; figure 1B) compared to that from control mice when triggered by 40µM PAR4-AP.

Conclusion(s): Our results suggest that intake of the artificial sweetener aspartame augments arterial thrombosis in mice through augmenting platelet activation, which might partly explain the previously reported associations between aspartame intake and cardiovascular diseases.