This study explores whether spermidine supplementation improves the metabolic, neurological-cognitive and cardiovascular response to structured exercise training in patients with heart failure with preserved ejection fraction. The investigators aim to show that a faster adaptation to exercise may improve long term adherence to a more active lifestyle.

Heart failure with preserved ejection fraction is the largest unmet need in medicine. Exercise training is a pivotal lifestyle intervention which has been shown to have beneficial effects with regards to metabolic, neurological-cognitive and cardiovascular outcomes in these patients. Yet, not every patients responds equally fast to an exercise training intervention. This trial explores whether the supplementation of spermidine can increase the response to a structured aerobic exercise training. The investigators will recruit 30 patients who will either receive a spermidine supplement or a placebo. The study participants are invited for a first follow-up visit after four weeks. The exercise intervention starts at week 5 and continues for 12 weeks. Hence, overall there are three visits (baseline, week four and week twelve).

Inclusion Criteria:

• diastolic heart failure (E/e' > 8, left ventricular ejection fraction (LVEF) => 50 %, dyspnea)

Exclusion Criteria:

• nutritional supplements with polyamines
• acute myo-, endo- or pericarditis
• aortic valve stenosis (2nd degree)
• cardiomyopathy or severe left ventricular hypertrophy (Interventricular septal end diastolic thickness or posterior wall thickness > 17 mm)
• AV block (second degree)
• pulmonary hypertension
• thromboembolic event in the last six months
• anemia
• infection (with fever) within the last four weeks
• cancer

Our ethics approval does not allow to share IPD for this trial.