Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease
Abstract
Objective Failure to mirror the diurnal cortisol profile could contribute to the impaired subjective health status in Addison's disease (AD). Some patients report benefit from the use of various nutritional compounds. The objective of this study was to investigate the impact of licorice and grapefruit juice (GFJ) on the absorption and metabolism of cortisone acetate (CA). Design Patients (n=17) with AD on stable CA replacement therapy were recruited from the outpatient clinic at Haukeland University Hospital, Norway. They were assessed on their ordinary CA medication and following two 3-day periods of co-administration of licorice or GFJ. Methods Time series of glucocorticoids (GCs) in serum and saliva were obtained, and GCs in 24 h urine samples were determined. The main outcome measure was the area under the curve (AUC) for serum cortisol in the first 2.6 h after orally administered CA. Results Compared with the ordinary treatment, the median AUC for serum cortisol increased with licorice (53 783 vs 50 882, P Conclusion Licorice and in particular GFJ increased cortisol available to tissues in the hours following oral CA administration. Both patients and physicians should be aware of these interactions.
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Licorice and grapefruit juice potentiate the mineralocorticoid effect of hydrocortisone.
“Licorice and grapefruit juice potentiate the mineralocorticoid effect of hydrocortisone and should be avoided (109).”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [109]
Cites
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Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1710 · Cited by 1,769 · see citing works
“Licorice and grapefruit juice potentiate the mineralocorticoid effect of hydrocortisone and should be avoided (109).”
BackgroundSelf-citationHusebye, E. S., Allolio, B., Arlt, W., Badenhoop, K., Bensing, S., Betterle, C., Falorni, A., Gan, E. H., Hulting, A. ‐., Kasperlik‐Zaluska, A., et al. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12162 · Cited by 403 · see citing works
Self-citationHusebye, E. S., Pearce, S. H., Krone, N. P., & Kämpe, O. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00136-7 · Cited by 378 · see citing works
Self-citationØksnes, M., Björnsdottir, S., Isaksson, M., Methlie, P., Carlsen, S., Nilsen, R. M., Broman, J.-E., Triebner, K., Kämpe, O., Hulting, A.-L., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4253 · Cited by 134 · see citing works
Self-citationAn Integrative Approach to HPA Axis Dysfunction: From Recognition to Recovery
Ring, M. (2025) · The American Journal of Medicine · doi:10.1016/j.amjmed.2025.05.044 · Cited by 89 · see citing works
Bäcklund, N., Brattsand, G., Israelsson, M., Ragnarsson, O., Burman, P., Edén Engström, B., Høybye, C., Berinder, K., Wahlberg, J., Olsson, T., et al. (2020) · European Journal of Endocrinology · doi:10.1530/eje-19-0872 · Cited by 46 · see citing works
- Authors
- Methlie, P., Husebye, E. E. S., Hustad, S., Lien, E. A., & Løvås, K.
- Affiliations
- University of Bergen (NO)
- Haukeland University Hospital (NO)
- Corresponding author
- Methlie, Paal
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-11
- Volume
- 165
- Issue
- 5
- Pages
- 761-769
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2155468326
- Cited by
- 50
- References
- 5
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Haukeland Universitetssjukehus
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Effects of Natural Compounds
- Keywords
- Addison's disease, grapefruit juice, licorice, cortisone acetate, drug interactions, glucocorticoid metabolism, diurnal cortisol rhythm, tetrahydrocortisone, salivary cortisol
- MeSH terms
- Addison Disease, Adult, Aged, Beverages, Cortisone, Female, Glycyrrhiza, Humans, Hydrocortisone, Male, Middle Aged, Up-Regulation, Food-Drug Interactions, Citrus paradisi
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