Licorice (glycyrrhizin) — interactions

The interaction almost nobody knows about, and it hospitalises people. Glycyrrhizin inhibits 11β-HSD2, so cortisol acts on the mineralocorticoid receptor: sodium and water retained, potassium lost, blood pressure up. Reported at intakes as low as ~100 mg glycyrrhizin per day sustained.

Also known as: liquorice, Glycyrrhiza glabra, glycyrrhizin, glycyrrhizic acid, mulethi. Category: seasoning.

What it does, mechanism by mechanism

11β-HSD2 inhibition (pseudohyperaldosteronism) — inhibits, strong

Blocks the enzyme that inactivates cortisol in the kidney, so cortisol acts on the mineralocorticoid receptor. Produces the picture of excess aldosterone with low aldosterone: sodium retention, potassium loss, hypertension.

Produces hypokalaemia, metabolic alkalosis, oedema and hypertension — pseudohyperaldosteronism, with aldosterone SUPPRESSED. Case reports include rhabdomyolysis, hypokalaemic paralysis and cardiac arrhythmia. It resolves on withdrawal, but slowly (weeks).

Sources: Størmer FC 1993, Omar HR 2012, Farese RV Jr 1991 · more on 11β-HSD2 inhibition (pseudohyperaldosteronism)

Flagged on its own

Moderate Licorice (glycyrrhizin) — pseudohyperaldosteronism on its own, before any other substance is involved

Mechanism: 11β-HSD2 inhibition (pseudohyperaldosteronism)

Glycyrrhizin inhibits 11β-hydroxysteroid dehydrogenase type 2, the enzyme that converts cortisol to inactive cortisone inside the kidney. Cortisol then reaches the mineralocorticoid receptor, and the body behaves as if aldosterone were high while aldosterone is actually suppressed: sodium and water retained, potassium excreted, blood pressure up.

What to watch for. Rising blood pressure, swelling, muscle weakness or cramps, and on a blood test low potassium with metabolic alkalosis. Reported at sustained intakes around 100 mg glycyrrhizin per day; severe cases have included hypokalaemic paralysis, rhabdomyolysis and arrhythmia. It resolves on stopping, but over weeks rather than days.

Sources: Størmer FC 1993, Omar HR 2012, Farese RV Jr 1991

What it reaches in this dataset

Via 11β-HSD2 inhibition (pseudohyperaldosteronism)

This list is what is IN the table. It is not the set of substances this interacts with — that set is larger and partly unknown, and the mechanism is the thing to carry to a substance we have not listed.

Specific combinations

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.

72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Størmer FC, Reistad R, Alexander J (1993). Glycyrrhizic acid in liquorice—Evaluation of health hazard. Food and Chemical Toxicology. doi:10.1016/0278-6915(93)90080-I
  2. Omar HR, Komarova I, El-Ghonemi M, et al. (2012). Licorice abuse: time to send a warning message. Therapeutic Advances in Endocrinology and Metabolism. doi:10.1177/2042018812454322
  3. Farese RV Jr, Biglieri EG, Shackleton CHL, Irony I, Gomez-Fontes R (1991). Licorice-Induced Hypermineralocorticoidism. New England Journal of Medicine. doi:10.1056/NEJM199110243251706

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.