Metabolome response to glycemic load in a randomized, controlled, crossover feeding trial in humans

Abstract

<bold>Background: </bold>Observational studies show habitual dietary patterns with low glycemic load (LGL), compared to high glycemic load (HGL), are protective against chronic conditions such as cancer, cardiovascular disease and obesity. <bold>Objective:</bold> To investigate the metabolomes' response to glycemic load as measured in plasma and urine. We expected to differentiate between diets and see a shift in energy usage with reduced beta-oxidation and reduced inflammation after LGL. <bold>Design:</bold> A subset of 20 participants from a previously completed controlled crossover feeding trial had metabolomics conducted on12hr fasting blood draw and 24hr urine collection from the last day of the HGL and LGL interventions. Plasma analysis was done using LC/MS, urine using LC/MS and GC/MS. Student's paired t-test, cluster and pathway analysis were conducted. <bold>Results:</bold> 12 plasma metabolites significantly altered between the diets, only kynurenate remained significant after FDR. 70 urine metabolites differed significantly after FDR. In both samples amino acids represented largest portion of altered metabolites. Biomarkers suggest tendency for increased depression and reduced energy after HGL, reflecting subjective measurements of mood and fatigue. <bold>Conclusion:</bold> Clear separation is detected in plasma and urine after diets of differing GL; however no clear pathway or trend identified to suggest protective effect of LGL diet. Biomarkers and subjective measures suggest HGL results in more depressive symptoms and reduced energy while LGL reduces fatigue.