IntroductionThe 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.MethodsMicrosomes 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.ResultsBoth 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.ConclusionDietary flavonoids can inhibit this enzyme and, at high doses, may cause an apparent mineralocorticoid effect.Clinical Pharmacology&Therapeutics(1996)59,