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

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 changes in 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 participants from 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 spermidine 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). 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.