Dehydroacetic acid induces heart failure by inhibiting succinate dehydrogenase

Here, we found that the approved food additive sodium dehydroacetate (DHA-S) could induce heart failure through disturbing normal metabolism. DHA-S decreases heart rate, exercise capacity, and respiratory capacity in zebrafish. The inhibitory effects of DHA-S on succinate dehydrogenase reduce absorption of glucose and biosynthesis of amino acids. Moreover, DHA-S disturbs mitochondrial energy production and induces (i) the accumulation of large amounts of ROS and (ii) high Ca2+ influx into mitochondria, further deteriorating cell physiology. Blockade of Ca2+ channels with phenytoin sodium could partially prevent these side effects. These data reveal the underlying mechanism of DHA-S-induced heart failure and highlight the effects of Ca2+ regulation on energy metabolism.