Dietary spermidine intake and skeletal muscle spermine/spermidine ratio are associated with peak oxygen consumption and whole-body composition in patients with coronary artery disease

Background

Spermidine and spermine are naturally occurring polyamines essential for cellular homeostasis, promoting cell growth, proliferation, autophagy, muscle stem cell activation, and immune regulation. Higher dietary spermidine intake has been associated with reduced cardiovascular and all-cause mortality, and a low blood spermine/spermidine ratio has been suggested as a potential indicator of sarcopenia risk. However, the physiological effects of spermidine intake and tissue polyamine concentrations in patients with coronary artery disease (CAD) remain poorly defined.

Purpose

To investigate the associations of dietary spermidine intake and the skeletal muscle spermine/spermidine ratio with peak oxygen uptake per kilogram body weight (peakVO₂/kg) and appendicular lean mass indexed to body mass index (ALM/BMI).

Methods

We conducted a cross-sectional analysis of baseline data from an ongoing randomised controlled trial including older adults (age ≥ 65 years) with coronary artery disease (previous coronary artery revascularization or myocardial infarction). Dietary spermidine intake was assessed using a validated food frequency questionnaire, and spermidine and spermine concentrations in plasma and skeletal muscle were quantified by targeted liquid chromatography-tandem mass spectrometry. Outcomes included peak VO₂/kg by cardiopulmonary exercise test, whole-body composition assessed by dual-energy X-ray absorptiometry, fasting lipid profile, and high-sensitivity C-reactive protein (hs-CRP). Linear regression models were adjusted for age and sex. Dietary spermidine intake data was log-transformed due to skewed distribution.

Results

In 180 elderly patients with coronary artery disease (80% men; median age 72 years [range 65-88]), higher dietary spermidine intake was associated with higher peakVO₂/kg (β=3.3 mL·kg⁻¹·min⁻¹; p<0.01), higher peak workload (β=30 W; p<0.01), higher ALM/BMI (β=0.15; p<0.001), lower body fat percentage (β=−4.0%; p<0.01), lower triglycerides (β=−0.32 mmol/L; p=0.03), and higher HDL cholesterol (β=0.24 mmol/L; p<0.01).

In skeletal muscle (n = 101), higher spermine/spermidine ratio was associated with higher peakVO₂/kg (β = 1.26 mL·kg⁻¹·min⁻¹; p < 0.001), higher peak workload (β = 7.8 W; p < 0.01), higher ALM/BMI (β = 0.02; p = 0.03), lower body fat percentage (β = −1.0%; p < 0.01), higher HDL cholesterol (β = 0.06 mmol/L; p < 0.01), and lower high-sensitivity C-reactive protein (β = −0.78 mg/L; p = 0.02).

Conclusion

In older CAD patients, dietary spermidine intake and the intramuscular spermine/spermidine ratio were associated with higher peak VO2/kg, higher ALM/BMI and lower body fat percentage. The causal nature of this association remains to be determined by a randomised controlled trial.