Abstract MP59: Associations of Plasma Inosine With Lipid Profiles in the Bogalusa Heart Study

Abstract

Introduction: Inosine, a naturally occurring purine nucleotide, has been used as a dietary supplement to enhance overall health. An emerging study in a rat model has indicated that inosine holds promise as a potential treatment for atherosclerosis by reducing cholesterol-driven inflammation and improving vascular function, providing a foundational concept for further investigation in humans. Hypothesis: We hypothesize that inosine can improve lipid profiles among humans. Methods: We profiled inosine and 886 known metabolites using plasma samples from 1,261 participants of the Bogalusa Heart Study (BHS) 2013-2016 survey. Linear regression models were used to evaluate the relationship between inosine and four lipid phenotypes, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, while controlling for age, sex, race, education, smoking, drinking, BMI, lipid medication, and total physical activity. Statistically significant findings in the BHS were validated in the Protein and Blood Pressure (ProBP) study, where 80 adults with available stored samples underwent 8-week dietary supplementation of carbohydrate, milk protein, and soy protein in a random order with 2-week washouts. Inosine and lipids were measured at baseline and post-intervention. We tested associations of longitudinal changes of inosine with changes in lipids profile. We also performed formal mediation analyses in the BHS to identify metabolites and metabolic pathways that might mediate inosine’s association with lipids. Results: In the BHS, inosine was significantly associated with HDL cholesterol (β=1.85, 95% CI: 0.72- 2.98) but not with LDL cholesterol, triglycerides, or TC. In the ProBP trial, inosine change was positively associated with HDL cholesterol change during the soy protein intervention (β=2.13, 95% CI: 0.59-3.66). Our mediation analysis identified 74 metabolites that nominally mediated (p<0.05) the inosine-HDL association. After Bonferroni correction for 228 independent metabolite clusters, three metabolites, including PC(18:2(9Z,12Z)/20:4(5Z,8Z,11Z,14Z)), arachidonic acid, and LysoPC(18:2/0:0) were significant mediators (p<0.05/228). The 74 nominally significant metabolites were enriched in the sphingolipid metabolic pathway (False Discovery Rate= 0.00312). Conclusion: Inosine appears to enhance HDL cholesterol, possibly through the sphingolipid metabolic pathway.