GRAPEFRUIT JUICE AND ITS FLAVONOIDS INHIBIT 11-BETA-HYDROXYSTEROID DEHYDROGENASE

Introduction: The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta -OHSD) oxidizes cortisol to inactive cortisone. Its congenital absence or inhibition by licorice increases cortisol levels at the mineraloco rticoid receptor, causing mineralocorticoid effects. We tested the hyp othesis 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 cortiso l and nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) and different flavonoids and the oxidati on to cortisone measured with use of HPLC analysis. In addition, healt hy 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 11 beta-OHSD req uiring either NAD or NADP were inhibited in a concentration-dependent manner by the flavonoids in grapefruit juice. Normal men who drank gra pefruit juice had a fall in their urinary cortisone/cortisol ratio, su ggesting in vivo inhibition of the enzyme. Conclusion: Dietary flavono ids can inhibit this enzyme and, at high doses, may cause an apparent mineralocorticoid effect.