Mulethi and blood pressure, the one herbal interaction with a textbook mechanism

Most herbal safety writing is hedged, and honestly it has to be, the data is usually animal studies, case reports and plausible mechanisms.

Mulethi is different.

Licorice has a fully worked-out, textbook-level mechanism for raising blood pressure and lowering potassium. It appears in endocrinology teaching as a cause of apparent mineralocorticoid excess. The enzyme is named. The dose-response is measured. The clinical syndrome has a name.

And almost no mulethi product in India carries a blood pressure warning.

We sell products containing mulethi. This article is the warning we think belongs on them, and the mechanism is worth understanding because it also tells you exactly who is at risk and why the duration matters more than the dose.

General information, not medical advice. If you have hypertension, heart failure, kidney disease, low potassium, liver disease, or you are pregnant, mulethi is not for you. The reasons are below.

The mechanism, properly

This is the part that makes licorice unusual, so it is worth following.

Start with cortisol. Cortisol is a glucocorticoid, a stress hormone. But it has a structural resemblance to aldosterone, the mineralocorticoid that tells the kidney to retain sodium and excrete potassium.

And cortisol can actually bind and activate the mineralocorticoid receptor. Circulating cortisol levels are far higher than aldosterone levels, so if nothing prevented it, cortisol would swamp that receptor and the body would retain sodium continuously.

What prevents it: an enzyme in the kidney called 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Its job is to convert cortisol into cortisone, which is inactive at the receptor. It is a local gatekeeper, sitting in the kidney, inactivating cortisol before it can act as a mineralocorticoid.

Now add licorice.

Licorice root contains glycyrrhizin (glycyrrhizic acid), typically 2–25% of the root. In the gut it is converted to glycyrrhetinic acid.

And glycyrrhetinic acid inhibits 11β-HSD2.

So the gatekeeper stops working. Cortisol is no longer inactivated in the kidney. It reaches the mineralocorticoid receptor and activates it.

And the kidney then behaves as though aldosterone levels were high, when they are not.

The consequences follow directly:

Sodium retention → water retention → raised blood pressure and oedema.

Potassium excretion → hypokalaemia.

Hydrogen ion loss → metabolic alkalosis.

And aldosterone itself is suppressed, because the body senses the sodium retention. So blood tests show low renin, low aldosterone, and the picture of mineralocorticoid excess.

That syndrome has a name: apparent mineralocorticoid excess, or pseudohyperaldosteronism. “Apparent” because the hormone is not elevated; the receptor is just being activated by the wrong steroid.

This is taught in medical endocrinology. Licorice is one of the standard examples.

What it looks like clinically

Blood pressure rising, in someone previously normotensive, or escaping control in someone treated.

Oedema, puffy ankles, puffy face, rings tightening, a kilo or two of weight gain that is water.

Hypokalaemia, and this is the dangerous part. Low potassium causes:

Muscle weakness and cramps, typically in the legs. Fatigue. Constipation. Palpitations and cardiac arrhythmias, this is the mechanism by which it becomes serious. And in severe cases, rhabdomyolysis, muscle breakdown, and paralysis.

Headache.

And in reported severe cases, hospitalisation with profound hypokalaemia, arrhythmia and, rarely, cardiac arrest.

These are not hypothetical. Case reports of licorice-induced hypertension and hypokalaemia appear in the medical literature, including from licorice confectionery consumption, which is the striking part, because the dose came from sweets rather than medicine.

Dose and duration, and duration matters more

This is dose-dependent, which is the practical key to using mulethi sensibly.

For context on quantities: regulatory and scientific bodies reviewing licorice have suggested that prolonged daily intake above roughly 100 mg of glycyrrhizin should be avoided, and that effects can be seen in sensitive individuals at lower intakes, figures in the region of 2 mg per kilogram per day have been associated with blood pressure effects.

We are deliberately giving ranges rather than a precise safe number, because the published figures vary, individual sensitivity varies a great deal, and the glycyrrhizin content of a given root or extract varies by an order of magnitude. That last point is the one that makes a precise consumer rule impossible: 2% and 25% glycyrrhizin are both “mulethi”.

What matters practically:

Short use is a different thing from long use. A few days of licorice tea or gargles for a sore throat is not the scenario that produces hypokalaemia.

Daily use for months is. And that is exactly how mulethi gets consumed in India, a daily churna, a daily kadha, a daily piece of root chewed because “it is good for the throat.”

So the rule we put on our own packs: not continuously for more than 4 to 6 weeks.

And individual sensitivity is real and wide. Some people develop effects at intakes others tolerate indefinitely. Women appear in the literature as potentially more sensitive. So “my neighbour takes it daily and is fine” is not information about you.

Who must not take it

These are contraindications, not cautions.

Hypertension. The mechanism directly raises blood pressure. And the people most likely to be taking daily herbal preparations are middle-aged and older, overlapping heavily with the hypertensive population.

Heart failure. Sodium and water retention is precisely what you are trying to avoid.

Kidney disease. Potassium handling is already impaired, and this adds a potassium-wasting mechanism to a system that cannot compensate.

Existing low potassium, from any cause.

Liver cirrhosis or cholestasis, glycyrrhetinic acid handling is altered, and these patients are already prone to electrolyte problems.

Pregnancy. And this deserves its own note: epidemiological research, notably from Finland where licorice consumption is high, has associated heavy licorice intake in pregnancy with shorter gestation and preterm birth, and follow-up work has raised questions about neurodevelopmental outcomes in the children. The proposed mechanism is plausible, glycyrrhizin inhibits the placental enzyme that protects the fetus from maternal cortisol. So: avoid in pregnancy.

Breastfeeding, avoid therapeutic doses.

And hormone-sensitive conditions, weak oestrogenic activity has been reported, so ask.

The drug interactions

And these follow mechanically from the potassium effect, which makes them predictable rather than mysterious.

Diuretics, thiazides and loop diuretics (furosemide, torsemide) also cause potassium loss. The effects add, and this is the combination most likely to produce clinically significant hypokalaemia.

Digoxin. Critical. Low potassium increases digoxin toxicity, this is standard pharmacology. A patient on digoxin who takes daily licorice is at risk of digoxin toxicity without changing their digoxin dose at all.

Corticosteroids, glycyrrhetinic acid also inhibits the enzyme that inactivates cortisol more broadly, so licorice potentiates corticosteroid effects.

Antihypertensives of all classes, licorice opposes them. Blood pressure escaping previously good control, with no other explanation, is a reason to ask what someone is taking.

ACE inhibitors, ARBs, spironolactone, these raise potassium, so the interaction is in the opposite direction, and the point is that the electrolyte balance becomes unpredictable, which is its own problem.

Insulin and diabetes medication, monitoring.

Warfarin, reported interaction.

Stimulant laxatives, additive potassium loss.

And a general one worth stating: mulethi is in an enormous number of herbal formulations, cough preparations, digestive churnas, throat lozenges, kadha mixes, Ayurvedic compound medicines. Someone can be taking it from three sources without ever deciding to take licorice. That cumulative, invisible exposure is the most common way this happens in practice.

DGL, the form that solves it

And this is a genuinely useful piece of information.

DGL, deglycyrrhizinated licorice, is licorice with the glycyrrhizin removed.

Which means the blood pressure and potassium mechanism is removed with it, because that mechanism is entirely attributable to glycyrrhizin and its metabolite.

And the demulcent, soothing properties largely remain, the physical coating effect that makes licorice useful for the throat and the stomach does not depend on glycyrrhizin.

So for gastrointestinal use, DGL is the sensible form, and it is what most of the gastrointestinal research uses.

Our position: where the purpose is demulcent, throat or stomach, and especially for anything intended for repeated or longer-term use, DGL is the better choice, and the fact that it is less widely sold in India is a gap rather than a reason.

What a label should say

Glycyrrhizin content, ideally. Because 2% and 25% root are both sold as mulethi, and the difference is more than tenfold. Almost nobody declares this, and it is the number that would actually let a consumer judge the risk.

Whether it is DGL or whole licorice.

“Do not use continuously for more than 4–6 weeks.”

“Not for use if you have high blood pressure, heart disease, kidney disease, low potassium or liver disease.”

“Not for use in pregnancy.”

And a line for anyone on diuretics, digoxin, steroids or blood pressure medication.

We put these on our packs. Almost nothing else on the shelf does, and this is not a difficult or expensive thing to print.

And the honest balance

We should not leave this sounding as though mulethi were dangerous in ordinary use.

It is not. A few days of licorice tea or gargles for a sore throat, or mulethi as a minor component of a formulation taken briefly, is a reasonable thing to do, and licorice has a long, genuine traditional use for the throat. It works, by a mechanism we can describe, it coats the irritated surface and reduces friction.

What makes it unusual is that it is one of the very few herbs where the harm is fully mechanistically understood, measurable in a blood test, and entirely predictable from the dose and duration.

So this is not a vague “consult your doctor” caution. It is a specific, checkable one: potassium and blood pressure, in someone taking licorice daily for months.

And that specificity is the reason the warning should be printed. A risk this well characterised has no excuse for being invisible.

What we will and will not say

Sayable: the botanical name (Glycyrrhiza glabra) and part used (root); a traditional-use statement framed as traditional use, including the classical kanthya designation described as a classical designation; the glycyrrhizin content or DGL status; the quantity; and authorised claims for any vitamins or minerals present.

And the governing fact: there is no authorised health claim for licorice.

Not sayable: treats sore throat infection, treats cough, treats ulcers, boosts immunity, treats adrenal fatigue, and that last one deserves naming, because “adrenal fatigue” is not a recognised diagnosis, and licorice is sold for it on the basis of its cortisol-related mechanism. Using a cortisol-prolonging compound for a condition that does not exist, in people who may well have an undiagnosed real condition, is the worst version of this ingredient’s marketing.

And the most honest summary:

Glycyrrhizin inhibits the kidney enzyme that inactivates cortisol. Cortisol then activates the mineralocorticoid receptor. The kidney retains sodium and dumps potassium. Blood pressure rises and potassium falls.

It is dose- and duration-dependent, so a few days for a sore throat is fine and daily use for months is not.

Hypertension, heart failure, kidney disease, low potassium, liver disease and pregnancy are contraindications, not cautions.

Digoxin plus licorice is the combination to be most careful about, because low potassium makes digoxin toxic.

And DGL removes the entire problem while keeping what makes licorice useful.

When to see a doctor

Do not take mulethi at all if you have: hypertension; heart failure or heart disease; kidney disease; low potassium; liver cirrhosis or cholestasis; or if you are pregnant. Avoid therapeutic doses while breastfeeding.

Ask your doctor first if you take: diuretics (furosemide, torsemide, thiazides); digoxin, this one matters most; corticosteroids; any blood pressure medication; ACE inhibitors, ARBs or spironolactone; insulin or diabetes medication; warfarin; stimulant laxatives; or if you have a hormone-sensitive condition.

And tell your doctor if you are taking several herbal formulations, because mulethi is a component of a great many of them and the exposure adds up invisibly.

Stop and get medical advice if you develop: swelling of the ankles, legs or face; a rise in blood pressure; muscle weakness or cramps; palpitations or an irregular heartbeat; unusual fatigue; headache; constipation; or rapid weight gain that looks like fluid. Ask for potassium and blood pressure to be checked, and say that you have been taking licorice, because the diagnosis is straightforward once someone knows to look, and invisible until then.

Emergency: marked muscle weakness or inability to move the limbs; palpitations with dizziness or fainting; chest pain; severe breathlessness.

The short version

1. Licorice has a textbook mechanism for raising blood pressure, not a vague caution
2. It appears in endocrinology teaching as a cause of apparent mineralocorticoid excess
3. Cortisol can activate the mineralocorticoid receptor
4. Normally the kidney enzyme 11β-HSD2 inactivates cortisol first
5. Licorice root contains glycyrrhizin, 2–25% of the root
6. Gut bacteria convert it to glycyrrhetinic acid
7. Glycyrrhetinic acid inhibits 11β-HSD2
8. So cortisol reaches the receptor and the kidney behaves as if aldosterone were high
9. Sodium and water retained; potassium excreted; hydrogen ions lost
10. Result: raised blood pressure, oedema, hypokalaemia, metabolic alkalosis
11. Renin and aldosterone test low, hence “apparent” excess
12. Clinically: rising BP, puffiness, muscle weakness, cramps, fatigue, constipation
13. Hypokalaemia can cause arrhythmias, this is how it becomes serious
14. Severe cases include rhabdomyolysis and paralysis
15. Case reports exist, including from licorice confectionery
16. Prolonged intake above roughly 100 mg glycyrrhizin daily should be avoided
17. Effects have been associated with intakes around 2 mg/kg/day in sensitive people
18. A precise consumer rule is impossible because root glycyrrhizin varies tenfold
19. Duration matters more than dose, days are fine, months are not
20. Daily churna, kadha or chewed root for the throat is exactly the risky pattern
21. Our rule: not continuously for more than 4 to 6 weeks
22. Individual sensitivity varies widely, someone else’s tolerance tells you nothing
23. Contraindicated: hypertension, heart failure, kidney disease, low potassium, liver disease
24. Avoid in pregnancy, heavy intake is associated with preterm birth in epidemiological work
25. Glycyrrhizin inhibits the placental enzyme shielding the fetus from maternal cortisol
26. Diuretics add potassium loss, the most likely combination to cause trouble
27. Digoxin is the critical one: low potassium makes digoxin toxic
28. Licorice potentiates corticosteroids
29. It opposes all antihypertensives, unexplained loss of BP control is a clue
30. Mulethi is in a huge number of formulations, so exposure accumulates invisibly
31. DGL has the glycyrrhizin removed, which removes the mechanism
32. And the demulcent effect does not depend on glycyrrhizin, so DGL keeps it
33. For repeated or longer-term demulcent use, DGL is the better choice
34. Labels should declare glycyrrhizin content or DGL status, almost none do
35. “Adrenal fatigue” is not a recognised diagnosis and is the worst use of this herb
36. There is no authorised health claim for licorice

Ingredient detail: mulethi. Our products: Panch Tulsi Drops, Immunity Drops. Related reading: मुलेठी के फ़ायदे गले के लिए, mulethi for skin brightening, and label compliance.