Spermidine and spermine in elderly patients with coronary artery disease: a cross-sectional study of dietary intake and plasma and skeletal muscle concentrations

BACKGROUND AND AIMS: Spermidine, a polyamine abundant in plant-based and fermented foods, has been associated with reduced cardiovascular and all-cause mortality. However, whether dietary spermidine intake is reflected in circulating and skeletal muscle concentrations remains unclear, and tissue data are scarce. We therefore investigated the associations between dietary spermidine intake and spermidine concentrations in plasma and skeletal muscle in elderly patients with coronary artery disease. METHODS: We examined dietary spermidine and spermine intake using a food frequency questionnaire, and plasma and skeletal muscle concentrations by targeted LC-MS/MS. Associations between intake, plasma and skeletal muscle concentrations were assessed using multivariable linear regression models adjusted for age, sex, body mass index, educational level, total daily energy intake, serum creatinine, medical treatment and comorbidities. RESULTS: A total of 192 patients with coronary artery disease were included (age 72 years [68-76] and 80% male). Median dietary spermidine intake was 11.5 mg/day [9.5-14.3] (n = 184). Median spermidine concentrations were 21.0 ng/mL [16.2-27.1] in plasma (n = 188) and 7120 ng/g [6200-8500] in skeletal muscle (n = 101). Higher dietary spermidine intake was modestly associated with higher plasma spermidine concentrations, corresponding to an 18% higher plasma concentration per doubling of intake in the unadjusted model (p = 0.02). The association remained robust after adjustment for covariates (p < 0.05). Skeletal muscle spermidine concentrations were not associated with intake or plasma concentrations (p > 0.05). Skeletal muscle contained markedly higher polyamine concentrations than plasma, and skeletal muscle spermine exceeded spermidine 6.7-fold. Women exhibited higher energy-adjusted spermidine intake (p = 0.02) and higher skeletal muscle spermidine concentrations than men (p < 0.01). Participants with higher educational attainment had higher dietary spermidine intake and plasma spermidine concentrations (p < 0.05). CONCLUSIONS: These findings suggest that plasma spermidine reflects habitual dietary exposure to a limited extent, whereas skeletal muscle polyamine pools appear to be maintained by strong intracellular regulation. Potential sex-related differences in polyamine metabolism or tissue distribution warrant further investigation. Randomised controlled trials are required to establish causality and determine clinical relevance. TRIAL REGISTRATION: NCT06186102, registered at ClinicalTrials.gov on 7 December 2023 by the authors. TRIAL PROTOCOL: POLYCAD trial protocol, Trials, 2025.