Longitudinal association of dietary spermidine with hepatic function indexes and cardiometabolic traits in older adults with metabolic syndrome

Abstract Purpose: Spermidine administration ameliorates hepatic steatosis and cardiometabolic dysfunction in animal models. However, evidence in humans remains limited. We aimed to explore the 1-year longitudinal associations between changes in dietary spermidine intake and hepatic function indexes and cardiometabolic traits in overweight and obese older adults with metabolic syndrome. Methods: We used baseline and 1-year follow-up data from 2664 participantsfrom the PREDIMED-Plus trial. Dietary spermidine intake was estimated using a semi-quantitative food frequency questionnaire. Time series clustering identified temporal patterns of 1-year change in spermidine intake. Linear mixed-effects models assessed the associations between spermidine intake clusters and changes in hepatic and cardiometabolic markers. Results: Three distinct spermidine intake patterns were identified across baseline, six-months and 1-year follow-up. Cluster 3, characterized by the highest baseline and increased 1-year intake, was associated with mean reductions in fatty liver index (-8.97 [-9.96 to -7.97], p-int < 0.001), hepatic steatosis index (-1.88 [-2.13 to -1.63], p-int < 0.001), alanine aminotransferase (-2.93 [-3.83 to -2.02] U/L, p-int < 0.05), aspartate aminotransferase (-1.11 [-1.76 to -0.45] U/L, p-int < 0.05) and glycated hemoglobin levels (-0.14 [-0.18 to -0.10] %, p-int < 0.01), compared to Cluster 1. Cluster 3 also showed, mean decreases in body mass index (-1.26 [-1.37 to -1.15]), waist (-3.72 [-4.11 to -3.32] cm) and hip circumference (-2.33 [-2.67 to -1.99] cm) (all p-int < 0.001). Conclusion: A 1-year increase in dietary spermidine intake was associated with improvements in hepatic function indexes and cardiometabolic traits in overweight and obese older adults with metabolic syndrome. Clinical Trial: Retrospectively registered at the International Standard Randomized Controlled Trial Registry (89898870) on 24th July 2014