Acute and Sub-Chronic Exposure to Artificial Sweeteners at the Highest Environmentally Relevant Concentration Induce Less Cardiovascular Physiology Alterations in Zebrafish Larvae

SIMPLE SUMMARY: The usage of artificial sweetener has been increased from year to year as the result of pursuing healthy lifestyle. However, ironically, several studies suggest that the consumption of artificial sweeteners cause sugar-related adverse effects (e.g., obesity, type 2 diabetes and cardiovascular disease). In this study, we explore the potential cardiovascular adverse effect of several artificial sweeteners using zebrafish as animal model. We found that artificial sweetener at the highest concentration found in nature only slightly alter the cardiovascular performance of zebrafish larvae. Furthermore, no alteration of cardiac performance showed after longer incubation which support the safety of artificial sweeteners. ABSTRACT: Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn helps prevent lifestyle diseases such as obesity. However, as their popularity has increased, the release of artificial sweetener to the aquatic environment has also increased at a tremendous rate. Thus, our study aims to systematically explore the potential cardiovascular physiology alterations caused by eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharine and sucralose, at the highest environmentally relevant concentration on cardiovascular performance using zebrafish (Danio rerio) as a model system. Embryonic zebrafish were exposed to the eight artificial sweeteners at 100 ppb and their cardiovascular performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output, heartbeat variability, and blood flow velocity) was measured and compared. Overall, our finding supports the safety of artificial sweetener exposure. However, several finding like a significant increase in the heart rate and heart rate variability after incubation in several artificial sweeteners are noteworthy. Biomarker testing also revealed that saccharine significantly increase the dopamine level in zebrafish larvae, which is might be the reason for the cardiac physiology changes observed after saccharine exposure.