Effects and Interactions of Liquorice and Grapefruit on Glucocorticoid Replacement Therapy in Addison's Disease
Condition: Addison Disease
MeSH terms: Addison Disease
Study type: Interventional

Summary: 
      Addison's disease is a rare disease, wherein the adrenals can not produce sufficient steroid
      hormones (cortisol and aldosterone). Patients with Addison's disease report impaired
      subjective health status, and they have increased all-cause mortality. Conventional therapy
      is by oral replacement of glucocorticoid and mineralocorticoid hormones, but this strategy
      imperfectly mimic the diurnal cortisol variations, and render the patients both over- and
      under-treated. Anecdotally, some patients with adrenal insufficiency may benefit from the use
      of various nutritional compounds. We hypothesised that liquorice and grapefruit altered the
      metabolism and absorption of cortisone acetate.
    

Detailed description: 
      In the present study, cortisone acetate absorption and metabolism are assessed in subjects
      with Addison's disease on three occasions. On the first occasion, the subjects are on their
      regular diet, but avoid ingestion of grapefruit and liquorice. At the end of the baseline
      assessment the order of the nutritional compounds (liquorice-grapefruit juice or grapefruit
      juice-liquorice) to be investigated in the next two assessments are randomised.

      On the two next occasions, the absorption and metabolism of cortisone acetate is studied when
      study subjects consume liquorice and grapefruit juice. Between the use of grapefruit and
      liquorice there is a wash out period of at least 3 weeks.

      For studies on liquorice effects, the subjects ingest 24-gram liquorice per day (equivalent
      of 150-mg glycyrrhizinic acid per day). For studies on grapefruit juice effects, subjects
      drink 200-ml grapefruit juice three times a day for three days. They maintain their regular
      medication and usual diet.

      Time-series of cortisol and cortisone are obtained in serum and saliva samples on the third
      day of liquorice/grapefruit juice use. 24-hour urine is also collected.

      Measurements of cortisol and metabolites in serum and saliva are used to calculate
      pharmacokinetical parameters. The measurements from samples obtained when using the
      investigated nutritional compounds are compared to the baseline assessment in each subject.
      Metabolites in 24-hour urine are compared similarly to investigate changes in urinary
      excretion, and to estimate the activity of enzymes involved in the metabolism of cortisol
      (5alfa-reductase, 5beta-reductase, cytochrome P450 3A4 system, 11-beta hydroxysteroid
      dehydrogenase).
    

Intervention name(s): Liquorice; Grapefruit Juice
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 24 gram liquorice eq. to 150 mg glycyrrhizinic acid, taken orally, for three days.; 200 ml pink grapefruit juice three times a day, taken orally, for three days.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Addison Disease; Pharmacokinetics; Hormone Replacement Therapy; cortisone acetate; Quality of Life