Associations of plasma inosine with lipid parameters in a biracial community cohort

Inosine has been investigated as a dietary supplement for athlete performance, inflammation, and neurological disease. A recent study in a hypercholesterolemic rat model has shown its potential for treating atherosclerosis.

This study aimed to investigate the associations between plasma inosine and lipid parameters, and to discover potential mediating pathways.

We profiled inosine and 886 known metabolites in plasma samples from 1,121 participants of a biracial cohort. Linear regression models assessed inosine's association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), log transformed triglycerides (log-TG), and TC to HDL-C ratio (TC/HDL-C), adjusting for relevant covariates. Significant findings were replicated in 78 adults from the Protein and Blood Pressure (ProBP) study, a cross-over randomized control trial by testing longitudinal associations between inosine changes and lipid changes after dietary supplementation of soy protein, milk protein, and carbohydrates. For a replicated association, we employed two complementary approaches to identify potential mediators for enrichment analysis.

In the discovery cohort, inosine was positively associated with HDL-C (β = 1.77, 95 % confidence interval [CI]: 0.003 to 3.54) and negatively associated with TC/HDL-C (β = -0.24, 95 % CI: -0.41 to -0.08) and log-TG (β = -0.08, 95 % CI: -0.15 to -0.02). These results were replicated in ProBP after soy protein intervention with inosine changes leading to increase of HDL-C (β = 1.82, 95 % CI: 0.36 to 3.27) and decrease of TC/HDL-C (β = -0.14, 95 % CI:-0.28 to -0.002) and TG (β = -12.79, 95 % CI: -21.00 to -4.58). Sex-stratified analyses revealed a more pronounced association in women than men, particularly for HDL-C. Six metabolites and 29 enriched pathways of high confidence were identified.

In humans, inosine is associated with better profiles of HDL-C, TC/HDL-C, and log-TG, with more pronounced effects in women for HDL-C. The ProBP trial was registered at ClinicalTrials.gov as NCT00107744.