2.4. Intervention
The intervention started with a standard dinner the evening before the first measurement day (day 0 and day 4; The next morning (measurement day; day 1 and day 5), placebo or verum capsules were administered to the subjects. The target dose in the verum arm of the study was 15 mg of spermidine per day (corresponding to five capsules in the morning and five in the evening). The same number of capsules were administered in the placebo arm. Subsequently, during the following 8 h, blood samples (9 mL of whole blood per sample) and saliva samples (after each blood sample) were taken under standardized dietary conditions. For the next 3 days, the respective capsules (verum or placebo) were self-administered by the participants every morning and evening, with one preprandial sampling in the morning. The second measurement day was on day 5 (similar to day 1). After a wash-out phase of 9 days, the second intervention phase started similarly to the first intervention phase.The water intake during the measurement days was standardized until noon. The participants drank 100 mL of non-carbonated water every full hour, directly after blood and saliva samples were taken. After lunch, they had water ad libitum.The calculation of pharmacokinetics was based on all blood and saliva samples. By contrast, only six samples of blood per subject were analyzed for the NMR metabolomics measurements (day 1 before breakfast, day 1 after snack, and day 5 after snack in both intervention phases; corresponding to samples 1, 11, and 25 or 0 h, 8 h, and 104 h, respectively).