Pathway Analysis of Allulose as a Sugar Substitute in Mitigating Thrombotic Risks in Sickle Cell Disease Patients

Long-term consumption of erythritol, a widely used sugar substitute, has been associated with increased risks of thrombosis and cardiometabolic diseases. In this study, we investigated the effects and mechanisms of allulose in mitigating these risks compared to erythritol using the clusterProfiler tool in R (version 4.12.6). Since a high-fat diet (HFD) is known to enhance platelet aggregation, we compared the pathways related to these processes between groups of mice treated with allulose and those treated with erythritol. While erythritol exacerbated HFD-induced increased platelet aggregation, allulose treatment significantly reduced it. Further analysis of platelet gene expression in sickle cell disease (SCD) patients to explore the potential of using sugar substitutes revealed that platelet coagulation mechanisms could be exacerbated by HFD. Additionally, the top up- and downregulated pathways in SCD were significantly reduced in the allulose-treated group compared to the erythritol group. Specific mechanisms related to this include the mitochondrial complex I and mitochondrial translational process as potential pathological factors in platelet coagulation related to SCD. Therefore, this study demonstrates that allulose may offer a safer alternative to erythritol in dietary applications, especially in individuals susceptible to thrombotic events, by modulating critical pathways associated with platelet function and mitochondrial activity.