Licorice is, more than most confectionery, a product whose flavour and physiological effects are dominated by two specific chemical compounds. The first is glycyrrhizin, a triterpene saponin found in the roots of Glycyrrhiza glabra, which supplies the sweet character of the candy and which, at sustained heavy intake, has documented cardiovascular effects. The second, present in salted Dutch and Finnish licorice but absent from the wider European tradition, is ammonium chloride (salmiak), an inorganic salt that produces the dry, ammoniacal finish characteristic of the northern European salted-licorice tradition. This entry treats both compounds: their structures, their flavour mechanisms, the regulatory framework around their use in confectionery, and the medical concerns at habitual high intake.
The pharmacology of glycyrrhizin is the more medically significant of the two and is the subject of substantial published clinical literature. The chemistry of ammonium chloride in confectionery is less well-studied but is, in flavour-science terms, more interesting: the compound activates a combination of taste-receptor and trigeminal-nerve responses that produce a sensation with no clean parallel elsewhere in the human food vocabulary. Both compounds are essential reading for any serious consumer of Dutch licorice, and both inform the regulatory thresholds discussed throughout the rest of this encyclopedia.
Glycyrrhizin: structure and source
Glycyrrhizin is a triterpene saponin, a class of plant-derived compounds characterised by a steroid-like aglycone backbone (in this case, 18β-glycyrrhetic acid) attached to a sugar portion (a disaccharide of two glucuronic acid units). The molecular formula is C42H62O16, with a molecular weight of approximately 822 g/mol. The compound is highly water-soluble at ambient temperature and is the principal component of licorice extract, accounting for between 6% and 14% of the dry mass of Glycyrrhiza glabra roots depending on growing conditions, plant age, and the specific subspecies.
Glycyrrhizin is approximately 50 times sweeter than sucrose by weight, but with a substantially different temporal profile: where sucrose registers sweetness rapidly (within 1–2 seconds of contact with the tongue) and decays over perhaps 30 seconds, glycyrrhizin registers slowly (peak at 10–15 seconds), persists for substantially longer (perhaps 2–5 minutes of perceptible sweetness), and tapers with a faintly bitter aftertaste. This temporal profile is one of the principal reasons licorice extract is not used as a general-purpose sweetener: it would dominate any product into which it was incorporated and would persist long after the rest of the flavour profile had decayed.
The species used principally in commercial licorice production is Glycyrrhiza glabra, which grows wild across western Asia and the Mediterranean basin. The principal commercial source regions are Iran, Turkey, Uzbekistan, Afghanistan, and southern Italy (specifically Calabria, where the indigenous population of G. glabra is regarded as producing the highest-grade extract). A related species, G. uralensis, is the principal source for Chinese and Japanese licorice products and has a slightly different glycyrrhizin content and flavour profile; the two species are not generally interchanged in the European confectionery industry.
Glycyrrhizin: the cortisol mechanism
The principal pharmacological action of glycyrrhizin in humans is the inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme normally converts cortisol — the active glucocorticoid — into cortisone, the inactive form. The conversion is particularly important in the kidney, where it prevents cortisol from binding to mineralocorticoid receptors and triggering aldosterone-like effects (sodium retention, potassium loss, increased blood volume). When 11β-HSD2 is inhibited, cortisol accumulates in tissues that would normally be protected from it and produces effects similar to those of excess aldosterone — a syndrome called pseudo-hyperaldosteronism or apparent mineralocorticoid excess.
The clinical consequences of pseudo-hyperaldosteronism include hypertension, hypokalaemia (low blood potassium), oedema, and in severe cases cardiac arrhythmia, muscle weakness, and renal damage. The condition is fully reversible on cessation of glycyrrhizin intake, with normal cortisol metabolism resuming over a period of approximately 2–4 weeks once intake stops. The principal at-risk groups are individuals with pre-existing hypertension, individuals with cardiac arrhythmia or congestive heart failure, and individuals on potassium-depleting medications (most notably diuretics).
The active metabolite responsible for the inhibition is glycyrrhetic acid, the aglycone formed by hydrolysis of glycyrrhizin in the gut. The hydrolysis is performed by intestinal bacterial β-glucuronidases, with the resulting glycyrrhetic acid absorbed and circulated. The metabolite has a relatively long elimination half-life (approximately 10 hours), which means that habitual daily intake produces sustained tissue concentrations even at moderate single doses.
The EFSA daily limit
The European Food Safety Authority has set a tentative upper limit of 100 mg of glycyrrhizin per day as a regular consumption guideline for adults, based on a 2003 review by the EU Scientific Committee on Food and reaffirmed in subsequent EFSA opinions. This limit is intended to be protective for healthy adults consuming licorice routinely; it is not a strict toxicological threshold (the dose at which acute effects appear is substantially higher) but a guideline for chronic intake. For comparison: typical Dutch sweet drop contains approximately 0.5–0.8% glycyrrhizin by weight; salted drop contains 0.8–1.5%; dubbelzout contains up to 2.2%. The 100 mg daily limit therefore corresponds to approximately:
| Variety | Glycyrrhizin % | Daily limit (g of candy) |
|---|---|---|
| Sweet drop (zoete) | ~0.5% | ~20 g (perhaps 8–10 lozenges) |
| Salted drop (zoute) | ~1.0% | ~10 g (perhaps 4–5 lozenges) |
| Dubbelzout | ~2.0% | ~5 g (perhaps 2–3 lozenges) |
| Specialist black-stripe | ~3.0% | ~3 g (perhaps 1–2 lozenges) |
It is worth being precise: the 100 mg limit is a guideline for regular daily intake, not for occasional consumption. A single 250-gram bag of dubbelzout consumed in one sitting at a party is unlikely to produce significant pharmacological effects, although it may cause acute gastrointestinal discomfort. The medical concern arises with sustained consumption — perhaps multiple bags per week, week after week, for several weeks — and is most acute in individuals already at cardiovascular risk.
Documented case reports
Cases of severe pseudo-hyperaldosteronism from licorice overconsumption appear in the medical literature with some regularity. The Dutch journal Nederlands Tijdschrift voor Geneeskunde has published multiple case reports over the past four decades, almost all involving sustained heavy consumption (typically 100g or more per day, often substantially more) over periods of weeks to months. The patient profile is consistent: middle-aged or older adults, often with pre-existing hypertension, who have substantially increased their licorice intake — usually for dietary or recreational reasons — and have presented with hypertension, hypokalaemia, oedema, or in some cases more severe cardiac symptoms.
The most cited single case is a 2012 report from Erasmus MC in Rotterdam concerning a 60-year-old man who developed severe hypertension (220/130 mmHg) and hypokalaemia (potassium 2.1 mmol/L) after eating approximately 300g of dubbelzout per day for three months. The patient's symptoms resolved completely within four weeks of stopping licorice consumption. Similar cases have been reported in the Finnish, Swedish, and German medical literature, with patient profiles consistent with the Dutch pattern.
The documented cases are, it should be emphasised, exceptional rather than typical. The Dutch national average drop consumption — perhaps 5g per day for an adult who eats drop daily — is well below the threshold at which pharmacological effects appear, and the substantial majority of habitual Dutch drop eaters never approach the EFSA guideline. The warning labels on dubbelzout packaging are intended for the small minority who do not stop, not for the typical consumer.
Ammonium chloride: structure and dissociation
Ammonium chloride (NH4Cl) is a simple inorganic salt with a molecular weight of 53.5 g/mol. The compound is highly water-soluble (about 372 g/L at 20°C) and dissociates fully in aqueous solution into ammonium (NH4+) and chloride (Cl−) ions. The compound is very slightly acidic in solution (a 1% solution has pH approximately 5.0–5.2), and the dissolution process is endothermic — the compound absorbs heat as it dissolves, producing a slight cooling sensation that can be detected on the tongue.
In confectionery applications, ammonium chloride is added either to the candy paste during the blending stage (treated under how drop is made) or as a surface coating after the candy has set. The choice of method affects the eating experience: paste-incorporated salmiak releases gradually as the candy dissolves in the mouth, producing a sustained ammoniated finish; surface-coated salmiak hits the tongue immediately on first contact, producing a sharp initial impression that fades as the coating dissolves. The classical salmiak-coated schoolkrijt is the principal example of the surface-coating method.
Ammonium chloride: the flavour mechanism
The flavour of ammonium chloride is not produced by any single sensory pathway. The compound activates at least three distinct mechanisms simultaneously, producing the complex sensation that defines salmiakdrop:
- The chloride ion contributes to perceived saltiness through the same epithelial sodium channels that detect sodium chloride. The signal is similar to that produced by table salt, although the magnitude is somewhat lower per unit of salt concentration.
- The ammonium ion activates several bitter-taste receptors in the TAS2R family, particularly TAS2R7 and TAS2R10, producing the characteristic bitter-metallic component that distinguishes salmiak from ordinary salt.
- The local pH change produced by dissolution (slightly acidic) activates trigeminal nerve receptors, particularly the TRPV1 receptor (the same receptor that registers capsaicin from chilli peppers and the cooling effect of menthol). This trigeminal activation is responsible for the dry, sharp, almost burning sensation that Dutch eaters describe as scherp ("sharp").
The trigeminal involvement is what makes salmiak a culturally acquired taste in a literal sense. Trigeminal responses are partly defensive reflexes — the body's signal that something potentially harmful is in contact with sensitive tissue — and the perception of these signals is plastic, shifting from unpleasant to pleasurable through habituation. Habitual salmiak eaters experience the same physiological signal as habitual chilli eaters experience the capsaicin response: as a positive, even pleasurable sensation rather than as a defensive warning. Non-habitual eaters experience the same signal as alarming, which is the predictable response of an unhabituated trigeminal system.
Ammonium chloride: regulatory framework
Ammonium chloride (E 510) is approved for use as a food additive in the European Union under EU Regulation 1333/2008 and is generally regarded as safe at customary intake levels by both the EU FSA and the US FDA. The Dutch NVWA does not formally limit the concentration in confectionery, but requires explicit warning labels on products exceeding specific thresholds:
- Above 2.0% NH4Cl by weight: the package must carry the "rich in liquorice" notice, indicating that consumption should be moderate.
- Above 4.49% NH4Cl by weight: the package must carry the explicit "consume in moderation; do not consume if suffering from hypertension" warning.
- Products approaching or exceeding 7.99% are typically restricted to specialist channels and may carry additional warnings about cardiovascular risk.
The 4.49% threshold corresponds to the boundary between standard salted (zoute) and double-salted (dubbelzout) licorice. The 7.99% threshold corresponds to the boundary between dubbelzout and the specialist black-stripe (zwartestrook) products that are sold only through specialist confectioners. The Finnish regulatory framework is similar but with somewhat higher thresholds, reflecting the higher tolerance of the Finnish market.
Acute toxicity and the LD50 question
The acute toxicity of both glycyrrhizin and ammonium chloride at any plausible dietary intake is essentially nil. The lethal dose of ammonium chloride in humans is in the range of 1.5–3 grams per kilogram of body weight, which for a 70-kilogram adult corresponds to approximately 100–200 grams of pure ammonium chloride — an amount that would require eating perhaps 2–4 kilograms of the strongest commercial dubbelzout in a single sitting. Glycyrrhizin acute toxicity is similarly remote, with the LD50 in animal studies corresponding to perhaps 800 mg/kg, well above any plausible single-meal intake.
The medical concerns described in this entry are, accordingly, all chronic-intake concerns rather than acute-toxicity concerns. The warning labels on Dutch dubbelzout packaging are about sustained habitual consumption, not about single doses, and the populations at meaningful risk are those with pre-existing cardiovascular conditions consuming licorice routinely at amounts substantially above the EFSA guideline. For healthy adults eating drop occasionally, even at relatively high salt grades, the candy is essentially without medical concern.