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Grapefruit juice and its flavonoids inhibit 11β‐hydroxysteroid dehydrogenase
Author(s) -
Lee Yil Seob,
Lorenzo Beverly J.,
Koufis Theo,
Reidenberg Marcus M.
Publication year - 1996
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(96)90025-9
Subject(s) - cortisone , grapefruit juice , chemistry , mineralocorticoid , nicotinamide adenine dinucleotide , dehydrogenase , enzyme assay , enzyme , endocrinology , nad+ kinase , in vivo , medicine , pharmacology , biochemistry , biology , receptor , pharmacokinetics , microbiology and biotechnology
The enzyme 11β‐hydroxysteroid dehydrogenase (11β‐OHSD) oxidizes cortisol to inactive cortisone. Its congenital absence or inhibition by licorice increases cortisol levels at the mineralocorticoid receptor, causing mineralocorticoid effects. We tested the hypothesis that flavonoids found in grapefruit juice inhibit this enzyme in vitro and that grapefruit juice itself inhibits it in vivo. Methods Microsomes from guinea pig kidney cortex were incubated with cortisol and nicotinamide adenine dinucleotide (NAD) or nicotinamide adenie dinucleotide phosphate (NADP) and different flavonoids and the oxidation to cortisone measured with use of HPLC analysis. In addition, healthy human volunteers drank grapefruit juice, and the ratio of cortisone to cortisol in their urine was measured by HPLC and used as an index of endogenous enzyme activity. Results Both forms of 11β‐OHSD requiring either NAD or NADP were inhibited in a concentration‐dependent manner by the flavonoids in grapefruit juice. Normal men who drank grapefruit juice had a fall in their urinary cortisone/cortisol ratio, suggesting in vivo inhibition of the enzyme. Conclusion Dietary flavonoids can inhibit this enzyme and, at high doses, may cause an apparent mineralocorticoid effect. Clinical Pharmacology & Therapeutics (1996) 59 , 62–71; doi: