title: Effects of grapefruit juice on cortisol metabolism in healthy male Chinese subjects.
abstract: Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β-OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200, 400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and following GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from 0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P <0.05) and the ratio of cortisol to cortisone (P <0.005) and reducing 6β-OHC excretion (P <0.05) and the ratio of 6β-OHC to cortisol (P <0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated doses had persistent but no cumulative effects. GFJ significantly reduced the ratio of 6β-OHC to cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism although a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Xiao
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR. Electronic address: btomlinson@cuhk.edu.hk.
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000328:Adult; D001628:Beverages; D032083:Citrus paradisi; D003348:Cortisone / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged
chemical_list: C001380:6 beta-hydroxycortisol; D003348:Cortisone; D006854:Hydrocortisone
keywords: 11β-Hydroxysteroid dehydrogenase 2; 6β-Hydroxycortisol; Cortisol; Cortisone; Cytochrome P450 3A; Grapefruit juice