2.1. Study Design
The study was designed as a randomized, placebo-controlled, triple-blinded, two-armed crossover trial with a washout phase of 9 days between the two intervention phases (The subjects were recruited through the University of Luebeck’s email distribution list. Both supplementation and blood/saliva sampling were performed at the Institute of Nutritional Medicine. Randomization, blinding, and the production of the placebo and verum preparations were provided by the Center of Drug Absorption and Transport (C_DAT) of the University of Greifswald, Germany. Randomization was performed using random numbers generated in Microsoft Excel. With the command = random number(), a random number between 0 and 1 was generated for each subject. Subsequently, a comparison was made in blocks of two to determine which subject had the higher random number. Those with the higher random number started with the verum arm, while subjects with the lower random number started with the placebo arm. This procedure ensured an equal distribution (balance) of the two possible orders (V-P or P-V) among the 12 subjects. Thus, 6 subjects each start with verum or placebo. The capsules taken (verum or placebo) were provided by staff in Greifswald on the basis of the generated sequence for weeks 1 and 2, specifically for the subject-specific random number. Externally, verum and placebo are indistinguishable due to color-matched filling powder and capsules of the same size and color. For more information about products and capsules, see To detect possible dietary changes in the course of the study that might have influenced the results, the participants documented their meals throughout the study period in a validated nutritional log. Throughout the study course, subjects were advised to refrain from extraordinary physical work, dietary changes, and alcohol consumption of more than two standard glasses per day. In addition, the participants were advised to follow their usual activity and dietary habits.As this study was designed as an exploratory pharmacokinetic trial, case number calculation was not possible due to a lack of data. A sample size of 12 was considered appropriate as it is established in phase 1 clinical trials. Moreover, the robustness of the data was improved by the cross-over design with placebo control.The study was registered in the German Clinical Trials Register (DRKS) (DRKS00029397).