3.2. Safety and Compliance to the Intervention
6-PN
Participant compliance to the IP was good with only 17% and 13% of participants who were non-compliant in the HE and placebo groups respectively. Similarly, compliance of the CaD supplements was good with only 11% and 4% of participants consuming <80% or >120% of the supplements in the HE and placebo group, respectively. Both HE and placebo capsules were well tolerated.Analysis of the prenylflavonoids concentrations in urine and plasma confirmed the good adherence to the treatment. Indeed, X, IX, 6-PN, 8-PN, and their metabolites (glucuronide and sulfated forms) were present after 48 weeks in both urine and plasma of the HE group, while absent or negligible in the placebo group. In urine samples from the HE group, total 8-PN was detected in 94% of the participants with a mean concentration of 13.96 ± 19.11 ng/mL; total 8-PN was detected in 76% of participant plasma samples of the HE group at a mean concentration of 1.09 ± 0.92 ng/mL (Regarding safety, there were a total of 127 TEAEs reported during the trial, of which 55 were noted in the HE group and 77 in the placebo group (