What happens when you take licorice tea with digoxin?
Licorice root (Glycyrrhiza glabra) contains glycyrrhizin (also called glycyrrhizic acid), a sweet-tasting saponin that the body hydrolyzes into glycyrrhetinic acid. Glycyrrhetinic acid potently inhibits the renal enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), whose job is to convert active cortisol into inactive cortisone in cells that express the mineralocorticoid receptor. When that enzyme is blocked, cortisol accumulates locally and activates the mineralocorticoid receptor in the same way that aldosterone would, producing a syndrome called apparent mineralocorticoid excess: sodium and water retention, high blood pressure, and significant loss of potassium and magnesium in the urine. The result is hypokalemia and sometimes hypomagnesemia.
Digoxin is a cardiac glycoside used in heart failure and to control ventricular rate in atrial fibrillation. It works by inhibiting the sodium-potassium ATPase on cardiac myocytes, raising intracellular sodium and indirectly increasing intracellular calcium, which strengthens cardiac contraction. Digoxin's binding to that pump is competitively reduced by potassium. When serum potassium falls, the digoxin binding site is more available, and the effective potency of any given digoxin dose increases.
This is the heart of the problem. Licorice-induced hypokalemia is exactly the kind of electrolyte disturbance that turns a therapeutic digoxin level into a toxic one. There are published case reports of digoxin toxicity caused by licorice consumption.
Why is this important?
Digoxin has one of the narrowest therapeutic windows in medicine. Plasma levels of 0.5 to 0.9 ng/mL are usually targeted in heart failure; levels above 2 ng/mL are associated with toxicity. Toxic effects include serious cardiac arrhythmias (premature ventricular contractions, bidirectional ventricular tachycardia, atrial fibrillation with slow ventricular response, complete heart block), nausea and vomiting, fatigue, confusion, and characteristic yellow-green visual disturbances.
Because licorice can drop serum potassium silently over weeks of regular use, a patient on a previously stable digoxin dose can drift into the toxic zone without any change in the prescription. The first manifestation is sometimes a serious arrhythmia, with no preceding nausea or vision changes.
The dose of licorice that causes mineralocorticoid effects is lower than people often assume. Daily intake of as little as 100 to 200 mg of glycyrrhizin (which can be reached with a few cups of strong licorice tea, two or three pieces of European-style black licorice candy, or some chewable digestive products containing licorice) can cause measurable potassium loss in susceptible people. Older adults, women, people with low body weight, and people with kidney disease are more vulnerable.
What should you do?
If you take digoxin, treat licorice as a contraindication. Do not drink licorice tea daily, do not eat real black licorice candy regularly, and read labels on digestive teas and "throat coat" style herbal blends, which often contain licorice root.
If you have been consuming licorice and are on digoxin, stop the licorice and contact your clinician. Request a basic metabolic panel (potassium, magnesium, sodium, kidney function) and a digoxin level. Recovery of potassium can take days to weeks because the mineralocorticoid effect persists after the licorice is stopped.
Seek urgent care for any of the following while on digoxin: new palpitations, irregular pulse, marked slowing of the pulse (below 50 beats per minute at rest), severe fatigue or confusion, persistent nausea or vomiting, loss of appetite, or visual changes such as yellow or green halos around lights.
Be aware that the risk extends beyond digoxin to any drug whose effects are amplified by low potassium, including QT-prolonging medications (many antibiotics, antiarrhythmics, and antipsychotics), and loop or thiazide diuretics, which already cause potassium loss.
The interaction does not apply to deglycyrrhizinated licorice (DGL), a form of licorice used for gastritis and reflux from which the offending glycyrrhizin has been removed. DGL is generally considered safe with digoxin, but read the label carefully and confirm with a pharmacist that the product is truly deglycyrrhizinated.
Which specific products are affected?
The drug side of the interaction is digoxin (Lanoxin, Digox) and the related glycoside digitoxin. The mechanism (potassium loss) also affects sensitivity to other cardiac glycosides and increases arrhythmia risk in patients on diuretics, amiodarone, sotalol, dofetilide, methadone, and many psychiatric medications.
On the licorice side, the relevant products include licorice root tea, licorice spice blends, traditional black licorice candy (Twizzlers in the U.S. are not real licorice, but Dutch drop, Australian licorice, and European Panda or Halva-style licorice typically are), licorice extracts and lozenges, herbal cough syrups, throat coat teas, many traditional Chinese herbal formulas (where gan cao is a near-universal ingredient), and combination digestive teas. Star anise tea is sometimes confused with licorice but does not contain glycyrrhizin.
The bottom line
Licorice tea can cause hypokalemia, and low potassium dramatically increases the risk of digoxin toxicity, including dangerous arrhythmias. The combination is one of the few herbal interactions that should be treated as a near-contraindication: do not drink licorice tea or eat real black licorice while taking digoxin. If you have been doing so, stop and ask your clinician to check your potassium and digoxin level. Deglycyrrhizinated licorice (DGL) does not carry the same risk.