DGL and Licorice Root: Forms, Evidence, Dosing, and Safety

DGL and Licorice Root: Forms, Evidence, Dosing, and Safety

Last Updated:

Licorice root, derived from the perennial plant Glycyrrhiza glabra (from the Greek glykos meaning "sweet" and rhiza meaning "root"), has been used in traditional medicine for thousands of years. The earliest documented uses date back to approximately 2500 BCE in Assyrian and Egyptian cultures, where it was employed as an expectorant and digestive remedy [1][2]. By the time of ancient Greek civilization (4th century BCE) and Chinese medicine (documented around 200 BCE), licorice was prescribed for respiratory ailments, sore throats, and gastrointestinal discomfort [2][3].

The major active compound in licorice root is glycyrrhizic acid (also referred to as glycyrrhizin in its natural mineral-bound form), a triterpenoid saponin that provides the root's characteristic intense sweetness — up to 50 times sweeter than sucrose [4][5]. Licorice root powder typically contains 2–15% glycyrrhizic acid, while concentrated licorice root extracts may contain 10–25% [6][7][8]. In the gut, glycyrrhizic acid is partially converted to glycyrrhetinic acid (also called glycyrrhizinic acid). Both compounds inhibit the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which normally converts active cortisol to inactive cortisone and active aldosterone to its inactive metabolite. By blocking this enzyme, licorice effectively increases cortisol and aldosterone levels, causing sodium retention, potassium loss (hypokalemia), fluid retention, and increased blood pressure — a condition known as pseudohyperaldosteronism or acquired mineralocorticoid excess syndrome [4][6][9].

Because of these significant risks, deglycyrrhizinated licorice (DGL) was developed in the 1940s–1950s as a safer alternative. DGL is a processed extract from which the majority of glycyrrhizin has been removed through hydrolysis or other methods, reducing glycyrrhizin content to below 3% (often less than 1%) [4][10][11]. This modification preserves the root's beneficial bioactive compounds — particularly flavonoids (such as glabridin, liquiritigenin, and isoliquiritigenin) and polysaccharides — while minimizing the risk of mineralocorticoid-like adverse effects [10][12].

Beyond glycyrrhizin, licorice root contains hundreds of bioactive compounds. Anethole contributes the characteristic "licorice" flavor and some sweetness (also found in anise and fennel seeds, which do not contain glycyrrhizin and do not carry its health risks) [6]. Glabridin, a prenylated isoflavone, demonstrates anti-inflammatory and antioxidant effects by inhibiting lipid peroxidation and modulating inflammatory pathways [13][14]. Liquiritigenin possesses estrogen-like activity through interaction with estrogen receptors [14]. Isoliquiritigenin, a chalcone derivative, shows antimicrobial activity against various pathogens [14]. Polysaccharides and glycoproteins contribute to mucoprotective effects by promoting mucus secretion and stabilizing the gastric mucosal barrier [14][15].

DGL was first commercialized in the 1950s under the brand Caved-S, which gained traction for ulcer healing in Europe [16]. Its popularity surged in the 2000s as a natural supplement alternative amid growing awareness of long-term proton pump inhibitor (PPI) risks, such as nutrient deficiencies (including magnesium depletion) and increased fracture incidence [17]. Today, DGL is primarily used for gastrointestinal support — particularly heartburn, acid reflux, peptic ulcers, and gastritis — and is available in chewable tablets, powders, and lozenges.

Table of Contents

Overview

Licorice root has a rich history spanning millennia of traditional use, but its modern supplement applications center on two distinct product categories: regular licorice (containing glycyrrhizin) and deglycyrrhizinated licorice (DGL, with glycyrrhizin removed). Understanding the difference is critical for safety.

Regular licorice's primary active compound, glycyrrhizin, inhibits the enzyme that breaks down cortisol and aldosterone. This can increase blood pressure, deplete potassium, and cause fluid retention — effects that are surprisingly easy to trigger through supplements, candy, or tea. Fatal cardiac events have been reported from licorice candy consumption [50].

DGL preserves licorice's beneficial flavonoids (glabridin, liquiritigenin, isoliquiritigenin) and polysaccharides while removing the dangerous glycyrrhizin component. These retained compounds provide anti-inflammatory, antioxidant, and mucosal-protective effects that support gastrointestinal health [10][12][15].

Forms and Bioavailability

Regular Licorice Root

Regular (non-deglycyrrhizinated) licorice products retain their full glycyrrhizin content:

  • Licorice root powder: Contains 2–15% glycyrrhizic acid [7][8]. Available in capsules, loose powder, and as a component of herbal blends.
  • Licorice root extract: More concentrated, containing approximately 10–25% glycyrrhizic acid [6][8]. Standardized extracts specify the glycyrrhizin percentage on the label.
  • Licorice tea: Highly variable glycyrrhizin content. A study of 33 brands found that a 250 mL (approximately 8 oz) cup of licorice tea contained anywhere from 0.5 mg to 112.5 mg of glycyrrhizic acid, with an average of 31.5 mg per cup [18]. This enormous variability makes dosing unpredictable.
  • Licorice candy: Black licorice candy contains glycyrrhizin, though amounts vary widely. One study found that labeled glycyrrhizin amounts were 50% lower than actual measured content, indicating labels may be inaccurate [19]. In the US, manufacturers are not required to list glycyrrhizin amounts, although the FDA states soft candies can contain no more than 3.1% glycyrrhizin by weight [19].

Deglycyrrhizinated Licorice (DGL)

DGL products have had glycyrrhizin removed or substantially reduced. Key forms include:

  • Chewable tablets: The most common form, designed to be chewed thoroughly before swallowing to maximize direct contact with the oral and esophageal mucosa. Typically dosed at 380–760 mg per tablet. Chewing is important because the localized coating action on the esophagus and stomach lining is a key part of DGL's mechanism for reflux and ulcer support [10][20].
  • Powder: Can be mixed with water or other liquids. Allows flexible dosing.
  • Lozenges: Designed to dissolve slowly in the mouth, providing prolonged contact with oral and throat tissues. Particularly used for sore throat and canker sore applications [21].
  • Capsules: Less common for DGL, since bypassing the mouth and esophagus may reduce the localized mucosal coating benefit.

Standardized Extracts

Some DGL products are standardized to specific flavonoid content rather than simply listing total DGL weight:

  • GutGard (by Natural Remedies Private Limited): A flavonoid-rich DGL extract standardized to contain greater than 3.5% glabridin and greater than 10% total flavonoids, with very low glycyrrhizin content (no more than 3% w/w). This is the extract used in most recent clinical trials, including the 2025 GERD trial [22][23]. Typical dose: 75 mg twice daily.
  • Non-standardized DGL: Most DGL products list total DGL weight (e.g., 400 mg DGL per tablet) but do not specify flavonoid content or the exact amount of residual glycyrrhizin. Testing has shown that products listing hundreds of milligrams of DGL per serving may still contain several milligrams of glycyrrhizic acid [6].

Comparison Table

Form Glycyrrhizin Content Primary Uses Key Considerations
Licorice Root Powder 2–15% Traditional medicine, tea High variability; risk of hypertension and hypokalemia with regular use
Licorice Root Extract 10–25% Concentrated supplement Higher potency increases both benefits and risks
DGL Chewable Tablets <3% (often <1%) GERD, heartburn, peptic ulcers Chewing maximizes esophageal coating; preferred form for GI use
DGL Powder <3% GI support, flexible dosing Can be mixed into liquids
DGL Lozenges <3% Sore throat, canker sores Prolonged oral contact for localized effects
GutGard (standardized DGL) <3% GERD, H. pylori, clinical research Standardized flavonoid content; most clinical trial data
Licorice Tea 0.5–112.5 mg/cup Casual consumption Extremely variable; unpredictable dosing
Black Licorice Candy Variable Confectionery Label amounts often inaccurate; not a reliable supplement form

Production and Quality

The deglycyrrhizination process, first patented in 1962, primarily employs acid-alkali treatment: licorice extract is diluted in water, heated to 40–52°C, and acidified to pH 2.0–3.0 using sulfuric acid. This causes glycyrrhizin to hydrolyze into glycyrrhetinic acid and precipitate. The precipitate is removed via centrifugation, and the solution is neutralized, concentrated, and dried to yield DGL powder containing at most 1% residual glycyrrhizin [24]. Alternative methods include ion-exchange chromatography using macroporous resins, which selectively adsorb glycyrrhizin while allowing flavonoid-rich fractions to pass through [25]. The process typically yields 40–60% of the original extract weight as dry DGL powder [24].

Quality control for DGL production involves HPLC analysis to confirm glycyrrhizin content below 3%, testing of raw roots for heavy metals (lead, cadmium, copper) and pesticide residues, and adherence to Good Manufacturing Practice (GMP) standards [24][25][26].

Residual Glycyrrhizin in DGL Products

DGL products are not glycyrrhizin-free. Testing has shown that products listing hundreds of milligrams of DGL per serving still contain several milligrams of glycyrrhizic acid. One product tested contained nearly 2% glycyrrhizic acid (approximately 8 mg per 400 mg of DGL) [6]. The expected maximum is no more than 0.75% of the listed DGL amount as glycyrrhizic acid, yet half of tested DGL products exceeded this threshold [6]. For single daily servings, residual glycyrrhizin is unlikely to be problematic. However, individuals taking multiple servings daily on an ongoing basis should be aware of the potential for cumulative glycyrrhizin exposure [6].

Bioavailability of Active Compounds

In DGL extracts, flavonoids represent a higher relative concentration compared to regular licorice due to the removal of glycyrrhizin (which typically comprises 5–15% of unprocessed root extract). This enrichment may enhance the bioavailability and efficacy of flavonoids for gastrointestinal applications [15]. Glabridin, the primary flavonoid, demonstrates anti-inflammatory effects by inhibiting cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) pathways [27]. The polysaccharide fraction stimulates mucus production in epithelial cells, providing direct mucosal protection [14][15].

Evidence for Benefits

Gastroesophageal Reflux Disease (GERD) and Heartburn

GERD is the condition with the most relevant clinical evidence for DGL. The mechanism involves DGL coating the esophagus and stomach, enhancing mucus secretion, and providing anti-inflammatory protection to the mucosal lining [10][15].

2025 Phase III RCT (GutGard): The most rigorous trial to date is a randomized, double-blind, placebo-controlled study evaluating GutGard, a DGL extract standardized to greater than 3.5% glabridin and greater than 10% total flavonoids, with glycyrrhizin content no more than 3%. Participants (n=120) with GERD took 75 mg of the extract twice daily after meals for 8 weeks. The study found significantly better and faster resolution of GERD symptoms compared to placebo, with meaningful improvement in heartburn severity and regurgitation observed within 2 weeks. However, it did not significantly reduce chest discomfort, sour or acidic taste in the mouth, stomach gurgling, nausea, pain in the throat, bloating, belching, or flatulence. The study was funded by the extract manufacturer (Natural Remedies Private Limited), which should be noted when interpreting results [22][23].

Observational evidence: A small 2017 observational study of 58 participants with GERD reported subjective symptom improvement over two years using a herbal formula containing DGL, but lacked a placebo control and could not isolate DGL's individual effects [28].

Smaller trials: Several small trials (n=50–100) have reported 50–60% reductions in heartburn symptoms, though these generally suffer from methodological limitations including small sample sizes and absence of proper controls [10][23].

Synthesis: DGL may provide modest relief from heartburn and regurgitation when taken around mealtimes, with the best evidence coming from the GutGard extract at 75 mg twice daily. The effects appear limited to certain GERD symptoms (heartburn and regurgitation) rather than providing comprehensive symptom relief. More large-scale, independently funded trials are needed.

Peptic and Duodenal Ulcers

Licorice and DGL have a long history in ulcer treatment, dating back to the 1940s when Dutch physician F.E. Revers first observed that whole licorice preparations could promote ulcer healing — but also caused pseudohyperaldosteronism in patients [29]. This led to the development of DGL in 1952 to retain the ulcer-healing benefits while removing the dangerous side effects [30].

Gastric ulcer trial: A double-blind, placebo-controlled trial demonstrated that 2.28 g of DGL daily (760 mg three times daily) significantly reduced gastric ulcer size compared to placebo over 6 weeks [10][23].

Duodenal ulcer trial (positive): One study showed rapid symptom improvement in duodenal ulcer patients with 3–4.5 g of DGL daily [10].

Duodenal ulcer 12-week trial: A double-blind, placebo-controlled trial involving patients with chronic duodenal ulcers found that four drug regimens including DGL resulted in an overall 91% healing rate after 12 weeks, with no significant difference between groups as confirmed by endoscopic examination [31].

Negative trial: A 1971 double-blind study found no significant difference in healing rates between DGL and placebo for duodenal ulcers [32].

1969 gastric ulcer trial: A clinical trial of DGL in gastric ulcers confirmed efficacy comparable to antacids, with faster healing in smaller lesions and no reported side effects [33].

Mechanism: DGL promotes ulcer healing through multiple pathways: it stimulates prostaglandin synthesis (prostaglandins are cytoprotective compounds that maintain mucosal blood flow and stimulate mucus and bicarbonate secretion), enhances mucus production, promotes proliferation of mucus-producing cells, and increases blood flow to the mucosal lining to aid tissue repair [15][34]. The anti-inflammatory flavonoids suppress COX-2 and NF-κB pathways without affecting constitutive COX-1 activity, which is important because COX-1 is needed for baseline mucosal protection [27].

Historical context: DGL was a mainstream ulcer treatment before the discovery of Helicobacter pylori as the primary cause of most peptic ulcers in the 1980s and the subsequent development of proton pump inhibitors (PPIs) and antibiotic eradication therapy. While DGL is no longer a first-line ulcer treatment, it may still have a role as adjunctive therapy, particularly for individuals seeking to reduce PPI use [17].

Synthesis: Evidence from multiple trials suggests DGL can promote gastric ulcer healing at doses of 760 mg three times daily (2.28 g/day) or higher. Results for duodenal ulcers are mixed. Most studies are older (pre-2000) and used small sample sizes, limiting the strength of conclusions. Modern, well-powered RCTs are needed.

Helicobacter pylori

H. pylori infection is the primary cause of most peptic ulcers and a major risk factor for gastric cancer. DGL flavonoids, particularly liquiritigenin, disrupt H. pylori adhesion to gastric epithelial cells and inhibit biofilm formation [35][36].

2013 RCT (GutGard): A randomized, double-blind, placebo-controlled trial (n=100) evaluated GutGard (150 mg daily for 60 days) for H. pylori eradication. The study found a 56% H. pylori-negative rate via stool antigen test in the DGL group versus just 4% in placebo. Similarly, 48% tested negative via urea breath test compared to 2% in placebo — a 30–50% greater reduction in bacterial markers with DGL compared to placebo [37].

In vitro evidence: Laboratory studies from the 2000s support DGL's inhibitory effects on H. pylori adhesion and growth. The antimicrobial mechanism involves disruption of bacterial attachment to gastric epithelial cells and interference with biofilm community structure, which reduces bacterial persistence in the gastric environment [15][35][36].

Practical note: DGL is not a replacement for standard H. pylori triple or quadruple antibiotic therapy. However, the GutGard trial suggests it may have value as an adjunctive treatment, potentially enhancing eradication rates by 20–40% when used alongside conventional antibiotics [15][37]. More research is needed to confirm this adjunctive role.

Gastritis and Dyspepsia

DGL addresses gastritis and dyspepsia by soothing gastric inflammation and improving digestive comfort through its barrier-enhancing properties. In cases of Helicobacter pylori-associated inflammatory gastritis, DGL supports mucosal integrity to reduce discomfort [10][15]. The anti-inflammatory actions are mediated primarily through glabridin's inhibition of COX-2 and NF-κB pathways, reducing production of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) [27].

Functional dyspepsia RCT (GutGard): A randomized, double-blind, placebo-controlled study evaluated GutGard for functional dyspepsia. The extract alleviated symptoms of functional dyspepsia, providing evidence for DGL's role beyond acid reflux [23].

The phenolic groups in DGL's flavonoids also provide antioxidant activity by scavenging free radicals and preventing lipid peroxidation in gastrointestinal tissues, which helps mitigate oxidative stress-induced damage to the mucosal lining [15][38].

No large, well-controlled clinical trials have specifically evaluated non-standardized DGL for gastritis or functional dyspepsia as primary endpoints. The evidence is partly extrapolated from ulcer and GERD trials, as well as the known pharmacological mechanisms.

Oral Health: Canker Sores and Dental Caries

Canker sores: In a clinical study, a DGL mouthwash (200 mg dissolved in 200 mL warm water, used four times daily) resulted in 75% of patients experiencing 50–75% improvement in canker sore symptoms within one day, with complete healing by day three [39]. The anti-inflammatory and mucosal-coating properties of DGL provide a soothing effect on the oral mucosa, reducing pain and accelerating healing.

Dental health: Emerging evidence suggests antimicrobial activity of DGL compounds against Streptococcus mutans, the primary bacterium responsible for dental caries. Isoliquiritigenin disrupts microbial cell membranes, which may help prevent cavity formation [10][14][40]. However, clinical trials specifically evaluating DGL for dental caries prevention are lacking.

Sore throat: DGL lozenges are commercially available and promoted for soothing irritated throat tissues. The mechanism is similar to the esophageal coating action — DGL forms a protective, anti-inflammatory layer over inflamed mucosa. However, specific clinical trials on DGL lozenges for sore throats remain limited [15].

Adrenal Insufficiency

Regular (non-DGL) licorice was traditionally used to treat adrenal insufficiency (Addison's disease), a condition in which the adrenal glands produce insufficient cortisol. The rationale is that glycyrrhizin blocks the conversion of cortisol to cortisone via 11β-HSD2 inhibition, effectively increasing circulating cortisol levels [4][6].

Clinical evidence: Not all individuals with adrenal insufficiency respond to licorice, and those who initially respond may show reduced benefit as adrenal function continues to decline [41][42]. A study by Methlie (2011) found variable responses among patients [41]. An earlier case report by Cotterill (1973) documented initial improvement followed by diminishing benefit [42].

Important distinction: This use applies to regular licorice containing glycyrrhizin, NOT to DGL. Since DGL has had glycyrrhizin removed, it would not be expected to have meaningful effects on cortisol metabolism. The hormonal effects of licorice are specifically attributable to glycyrrhizin's enzyme-inhibiting properties.

Synthesis: The evidence for licorice in adrenal insufficiency is limited to case reports and small studies with variable results. Modern adrenal insufficiency treatment relies on hormone replacement therapy (hydrocortisone, fludrocortisone), not licorice. Self-treating adrenal insufficiency with licorice is not recommended due to the narrow therapeutic window and significant risk of hypertension and hypokalemia [4][6].

Fatigue and Chronic Fatigue Syndrome

An anecdotal report suggested that licorice may reduce symptoms of fatigue among people with chronic fatigue syndrome by increasing sodium retention and consequently raising blood pressure [43]. The proposed mechanism is that some individuals with chronic fatigue may have mildly low blood pressure, and licorice's aldosterone-like effects could counteract this. However, no clinical studies appear to have been conducted to confirm these results [6][43]. This remains an unproven use with significant safety concerns, as the same mechanism that might boost blood pressure in hypotensive individuals would dangerously elevate it in those with normal or high blood pressure.

Stress, Anxiety, and Depression

Despite evidence from laboratory (in vitro and animal) studies suggesting potential benefits of licorice compounds for stress, anxiety, and depression — including modulation of the hypothalamic-pituitary-adrenal (HPA) axis and effects on neurotransmitter systems — there do not appear to be any published clinical studies evaluating licorice or DGL for these conditions in humans [44]. These remain theoretical applications without clinical validation.

Skin Health (Topical Applications)

Atopic dermatitis: A study evaluated topical licorice gel for atopic dermatitis, with results suggesting anti-inflammatory benefits for skin conditions [45]. However, this involved topical application of licorice compounds rather than oral DGL supplementation.

Glabridin's skin effects: Glabridin has demonstrated anti-inflammatory and antioxidant effects in skin cell studies, including inhibition of lipid peroxidation. Some cosmetic products incorporate licorice root extract (particularly glabridin) for skin brightening and anti-inflammatory effects [13][14]. These topical applications are distinct from oral DGL supplementation and are not reviewed in detail here.

DGL (Deglycyrrhizinated Licorice)

DGL dosing varies by indication and product formulation:

Indication Dose Frequency Duration Form Notes
GERD / heartburn 75 mg standardized extract (GutGard) Twice daily after meals 4–8 weeks Tablets Based on 2025 RCT [22]
GERD / heartburn 380–760 mg DGL 20 min before each meal 4–8 weeks Chewable tablets Traditional dosing; chew thoroughly [20]
Peptic/gastric ulcers 760 mg DGL Three times daily before meals 6–16 weeks Chewable tablets Based on ulcer healing trials [10][31]
Duodenal ulcers 1,000–1,500 mg DGL Three times daily (3–4.5 g/day total) 8–12 weeks Chewable tablets Higher dose range used in some trials [10]
H. pylori (adjunct) 150 mg standardized extract (GutGard) Once daily 60 days Tablets Adjunct to standard antibiotic therapy [37]
Canker sores 200 mg dissolved in 200 mL warm water Four times daily as mouthwash Until healed (typically 1–3 days) Powder dissolved in water Topical oral application [39]
General GI support 380–760 mg DGL Before meals As needed Chewable tablets Maintenance dosing [20]

Key dosing principles: Chew DGL tablets thoroughly before swallowing to maximize direct mucosal contact with the esophagus and stomach lining [10][20]. Take DGL approximately 20–30 minutes before meals for optimal coating and protection [6][20]. For bedtime reflux, an additional dose before bed may be beneficial [6]. The maximum well-studied dose is 4.5 g of DGL daily, maintained for up to 4 months [10][46]. Health Canada authorizes oral use of DGL at 380–1,520 mg three times daily (total 1.14–4.56 g per day) for adults in chewable forms, provided the finished product contains no more than 3% of the original glycyrrhizic acid content [20].

Regular Licorice (Glycyrrhizin-Containing)

Regular licorice use requires extreme caution due to glycyrrhizin's effects on cortisol and aldosterone metabolism.

European Commission Scientific Committee on Food recommendation: Limit glycyrrhizin intake to no more than 100 mg per day for most healthy adults [9]. However, this may be too high for people with high blood pressure, slower digestion, or electrolyte/water homeostasis-related conditions such as kidney disease and Cushing's syndrome [9].

More conservative limit: A group of researchers proposed a daily limit of 10 mg of glycyrrhizic acid as safe for most healthy people, based on one-tenth of the European recommendation [47]. This extremely conservative limit reflects the wide individual variability in sensitivity to glycyrrhizin's hormonal effects.

FDA warning: For adults 40 or older, eating 2 oz of black licorice daily for at least two weeks can cause health problems, although younger people can also be affected [19].

Blood pressure effects in healthy young adults: A study showed that eating just 3.3 g (approximately 0.1 oz) of licorice candy containing 100 mg of glycyrrhizin daily for 2 weeks increased systolic blood pressure by approximately 3 mmHg compared to placebo, with a statistically significant increase of 1.7 mmHg observed as early as five days after starting intake [19].

How to Read a Licorice/DGL Supplement Label

  • "DGL" or "Deglycyrrhizinated licorice": Glycyrrhizin has been removed. Should contain less than 3% glycyrrhizin, though actual amounts are often not disclosed.
  • "Licorice root" or "Glycyrrhiza glabra root": Contains full glycyrrhizin content unless otherwise specified.
  • "Standardized to X% glabridin" or "X% total flavonoids": Indicates a quality-controlled extract with specified active compound levels. GutGard is standardized to greater than 3.5% glabridin and greater than 10% total flavonoids.
  • Glycyrrhizin content: Rarely disclosed on DGL products, despite being the most important safety parameter. Ask manufacturers for third-party testing data if consuming multiple daily servings long-term.

Safety and Side Effects

Regular Licorice (Glycyrrhizin-Containing)

Regular licorice carries significant health risks with doses that are surprisingly easy to reach through supplements, candy, or tea.

Mechanism of harm: Glycyrrhizin and its metabolite glycyrrhetinic acid inhibit 11β-HSD2, the enzyme that normally converts active cortisol to inactive cortisone and active aldosterone to its inactive form. This results in mineralocorticoid excess: sodium retention, potassium excretion, fluid accumulation, and elevated blood pressure [4][6][9].

Reported adverse effects of glycyrrhizin include:

  • Loss of potassium (hypokalemia)
  • Fluid retention (edema)
  • Increased blood pressure (hypertension)
  • Abnormal heart rhythms (arrhythmias)
  • Lethargy and muscle weakness
  • Metabolic alkalosis [4][6][9]

Case reports illustrating severity:

Stroke from licorice supplement: A 68-year-old woman developed dangerously high blood pressure (219/123 mmHg) resulting in a stroke (with difficulty speaking and paralysis on one side) after taking a Chinese herbal supplement providing 800 mg of licorice root daily for just two weeks to treat indigestion. Her physicians noted she could have been consuming 8 times the maximum glycyrrhizin dose recommended by the European Commission [48].

Acquired mineralocorticoid excess syndrome: A 65-year-old woman developed high blood pressure (197/89 mmHg), low potassium, high sodium, metabolic alkalosis, and adrenergic symptoms (agitation, anxiety, tremor) four months after beginning a liver support supplement containing 1,000 mg of dried licorice root extract standardized to at least 200 mg of glycyrrhizic acid (twice the European daily limit). Her symptoms, blood pressure, and electrolytes returned to normal two weeks after stopping the supplement and receiving treatment [49].

Fatal cardiac arrest from licorice candy: A 54-year-old man went into cardiac arrest and died after consuming one to two large packages of licorice-flavored soft candy for three weeks. His doctors determined that glycyrrhizic acid led to low potassium and metabolic changes resulting in a fatal rapid abnormal heart rhythm [50].

Severe hypokalemia from licorice tea: A woman in New York drinking five to six cups daily of a licorice tea was found on routine testing to have blood potassium of just 2.0 mEq/L (normal range: 3.5–5.3 mEq/L) — a dangerously low level that can cause cardiac arrhythmias [51]. An 84-year-old man with controlled hypertension developed extremely high blood pressure, headache, photophobia, chest pain from pulmonary edema, fatigue, and low potassium after two weeks of drinking 1–2 glasses daily of homemade licorice root extract [52]. A 57-year-old man with no cardiovascular history experienced atrial fibrillation, likely caused by low potassium, after consuming four glasses of licorice root syrup daily for one month [53].

Licorice candy safety concerns: An analysis of 219 licorice-containing candies, ice creams, and brewed teas in Denmark found that among high-glycyrrhizin products, eating just 4.3 g (0.15 oz) of candy, 59 g (2 oz) of ice cream, or drinking 83 mL (2.8 fl oz) of tea would exceed the 100 mg/day glycyrrhizin limit. Pure licorice products contained 18 times as much glycyrrhizin as other candies. Ten percent of products did not properly include the required warning label [54].

DGL Safety Profile

DGL is generally well-tolerated, with common side effects being rare and mild [10][46].

Reported adverse reactions: Occasional nausea or allergic responses such as rash and itching, occurring in fewer than 5% of users in clinical observations. Unlike regular licorice, DGL at recommended doses does not cause glycyrrhizin-related hypertension or hypokalemia [10][12][46].

Residual glycyrrhizin concern: Because DGL products still contain small amounts of glycyrrhizin (some tested at nearly 2% glycyrrhizic acid content), consuming multiple daily servings on a long-term basis could result in clinically meaningful glycyrrhizin exposure. Single daily servings are unlikely to be problematic [6].

Long-term safety: DGL is considered safe for use up to 4 months at recommended doses of up to 4.5 g daily, with no significant adverse events reported in clinical studies. Prolonged use beyond 4–6 weeks should ideally be supervised by a healthcare professional [10][46].

Populations Who Should Avoid All Forms of Licorice (Including DGL)

Many experts caution that licorice in any form should be avoided by [4][6][55]:

  • People with high blood pressure — even the small residual glycyrrhizin in DGL could potentially worsen hypertension in sensitive individuals
  • People with heart disease or heart failure — the risk of fluid retention and potassium depletion
  • People with kidney disease — impaired ability to excrete sodium and maintain potassium balance
  • Pregnant women — licorice during pregnancy has been linked to preterm birth; although licorice is sometimes promoted to help with milk production, research suggests it may actually decrease prolactin, which could reduce milk production [55]
  • Nursing women — insufficient safety data [55]
  • People with hormone-sensitive conditions (e.g., breast cancer, endometriosis) — licorice flavonoids, particularly liquiritigenin, possess phytoestrogenic activity that may influence hormonal balance [10][14][46]
  • People with Cushing's syndrome or other conditions affecting cortisol/aldosterone metabolism [9]

Onset and resolution: Blood pressure effects from glycyrrhizin can manifest within days. A study in healthy young adults showed a statistically significant 1.7 mmHg increase in systolic blood pressure as early as five days after starting licorice intake of 100 mg glycyrrhizin daily [19]. In case reports, symptoms typically developed within 2–4 weeks of daily use and generally resolved within 1–2 weeks after discontinuation [48][49].

Drug Interactions

Regular Licorice (Glycyrrhizin-Containing) — Significant Interactions

Drug/Drug Class Interaction Clinical Significance
Corticosteroids (prednisone, hydrocortisone) Glycyrrhizin potentiates corticosteroid effects by inhibiting cortisol breakdown May increase steroid side effects; dose adjustment may be needed [4][6]
Diuretics (furosemide, thiazides) Both cause potassium loss; additive hypokalemia risk Dangerous combination; can cause severe hypokalemia with cardiac consequences [4][9]
Digoxin Hypokalemia from licorice increases sensitivity to digoxin toxicity Potentially fatal interaction; arrhythmia risk [4][56]
Antihypertensives Licorice raises blood pressure, counteracting antihypertensive drugs Can cause treatment failure; patients may need higher drug doses or develop resistant hypertension [4][6]
Warfarin/anticoagulants Glycyrrhizin may affect drug metabolism via CYP450 pathways Monitor INR more frequently if combining [4]
Oral contraceptives/HRT Estrogen-containing medications may potentiate licorice's hypertensive and potassium-lowering effects Additive risk; some case reports of severe hypokalemia in women on oral contraceptives who consumed licorice [4][6]
Spironolactone Licorice may counteract the potassium-sparing effects of spironolactone Can negate the therapeutic benefit; avoid combination [4][9]
MAO inhibitors Theoretical interaction based on licorice's effects on neurotransmitter metabolism Limited data; use with caution [4]
Insulin/oral hypoglycemics Cortisol excess from licorice can raise blood glucose May worsen glycemic control in diabetic patients [4][6]
Laxatives Additive potassium depletion Chronic laxative use plus licorice significantly increases hypokalemia risk [4]

DGL — Minimal Interactions

Due to the low glycyrrhizin content in DGL products, drug interactions are substantially reduced compared to regular licorice [10][46][56]:

  • Risk of enhancing digoxin effects is negligible at standard DGL doses
  • Risk of potentiating diuretics is negligible
  • However, monitoring may be prudent in sensitive individuals, particularly those already on multiple potassium-lowering medications
  • Healthcare providers should consider monitoring potassium levels if any concerns arise [10][46][56]

Important caveat: As noted in the Safety section, some DGL products contain more residual glycyrrhizin than expected. Individuals taking medications with significant interaction potential (particularly digoxin, diuretics, or antihypertensives) should exercise extra caution even with DGL products, especially at higher doses or with long-term use.

Dietary Sources

Licorice root is not a typical dietary component in Western diets but appears in various food products and beverages:

Source Typical Glycyrrhizin Content Notes
Black licorice candy Variable (up to 3.1% by weight in US) Pure licorice candies contain dramatically more than mixed candies [54]
Licorice tea 0.5–112.5 mg per 250 mL cup (average 31.5 mg) Extremely variable between brands [18]
Licorice root (raw/dried) 2–15% of root weight Chewed or brewed in traditional medicine [7][8]
Licorice-flavored products Often zero (anise-flavored) Many "licorice" flavored foods use anise or fennel, which do not contain glycyrrhizin [6]
Throat Coat tea and similar herbal teas Variable Often contain licorice root as a soothing ingredient; amounts rarely specified [51]
Chinese herbal medicine formulations Variable Licorice root (Gan Cao) is one of the most commonly used herbs in traditional Chinese medicine [2][57]
European licorice confections Often higher than US products EU requires warning labels on high-glycyrrhizin products, though compliance is incomplete [9][54]

Important Distinctions

  • Anise, fennel, and star anise all contain anethole, which provides a "licorice-like" flavor, but they do NOT contain glycyrrhizin and do not carry the same health risks [6]. Most licorice-flavored candies and foods in the US use anise flavoring rather than actual licorice root.
  • "Red licorice" (e.g., Twizzlers) typically contains no actual licorice root or glycyrrhizin — it is flavored with strawberry or cherry.
  • Licorice root in herbal teas can be a hidden source of glycyrrhizin. Check ingredient lists for Glycyrrhiza glabra or "licorice root" if avoiding glycyrrhizin.

Geographic and Cultural Context

Glycyrrhiza glabra is native to the Mediterranean region, including southern Europe, western Asia, and North Africa. Major cultivation occurs in Turkey, Greece, and China, which accounts for approximately 70% of worldwide production [3][58]. The plant thrives in temperate to subtropical climates, preferring deep, well-drained, loamy soils, and can grow up to 1–2 meters in height with extensive root systems [3]. Licorice roots are typically harvested after 3–4 years of growth [58]. In traditional Chinese medicine, licorice root (Gan Cao) is one of the most frequently prescribed herbs, used as a "harmonizing" agent in complex herbal formulas [2][57]. In Western herbalism, DGL has become the preferred form for gastrointestinal applications due to its safety profile [15][17].

Sustainability Considerations

Due to overexploitation, particularly in wild populations across Central Asia and the Mediterranean, sustainable harvesting practices are increasingly important. Cultivation in controlled fields and limits on extraction rates help preserve natural habitats while supporting supply stability [58][59].

References

    1. National Center for Complementary and Integrative Health (NCCIH). "Licorice Root." https://www.nccih.nih.gov/health/licorice-root

    2. Wang L, et al. "Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology." Phytomedicine. 2020. doi: 10.1016/j.phymed.2020.153282

    3. Pastorino G, Cornara L, Soares S, et al. "Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review." Phytother Res. 2018;32(12):2323-2339. doi: 10.1002/ptr.6178

    4. Omar HR, et al. "Licorice abuse: time to send a warning message." Ther Adv Endocrinol Metab. 2012;3(4):125-138. doi: 10.1177/2042018812454322

    5. Isbrucker RA, Burdock GA. "Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin." Regul Toxicol Pharmacol. 2006;46(3):167-192. doi: 10.1016/j.yrtph.2006.06.002

    6. ConsumerLab. "DGL and Licorice Root Supplement Review." Accessed 2026. https://www.consumerlab.com/reviews/dgl-licorice-root-supplement-tea-candy/licorice/

    7. Fry JC. "Licorice flavoring." In: Natural Food Additives, Ingredients and Flavourings. 2012.

    8. Sohail M, et al. "Chemical analysis of glycyrrhizic acid in licorice." J Food Biochem. 2017. doi: 10.1111/jfbc.12376

    9. European Scientific Committee on Food. "Opinion on glycyrrhizinic acid and its ammonium salt." 2003. https://ec.europa.eu/food/safety/sci-com/scf/

    10. Grokipedia. "Deglycyrrhizinated licorice." https://grokipedia.com/page/Deglycyrrhizinated_licorice

    11. NIH NCCIH. "Licorice Root: Overview." 2020. https://www.nccih.nih.gov/health/licorice-root

    12. Raveendra KR, et al. "DGL for acid reflux: Supplement efficacy and clinical safety." Alternative Medicine Review. 2012.

    13. Simmler C, Pauli GF, Chen SN. "Phytochemistry and biological properties of glabridin." Fitoterapia. 2013;90:160-184. doi: 10.1016/j.fitote.2013.07.003

    14. Aly AM, Al-Alousi L, Salem HA. "Licorice: a possible anti-inflammatory and anti-ulcer drug." AAPS PharmSciTech. 2005;6(1):E74-E82. doi: 10.1208/pt060113

    15. Glycyrrhiza glabra monograph. Alternative Medicine Review. 2005;10(3):230-237. https://altmedrev.com/wp-content/uploads/2019/02/v10-3-230.pdf

    16. Turpie AG, et al. "Clinical trial of deglycyrrhizinized liquorice in gastric ulcer." Gut. 1969;10(4):299-302. doi: 10.1136/gut.10.4.299

    17. Life Extension. "Nutritional Dangers of Acid Reflux Medications." Life Extension Magazine. June 2013.

    18. Allcock E, et al. "Licorice tea consumption and hypokalemia." BMJ Case Reports. 2015. doi: 10.1136/bcr-2015-209942

    19. Geijerstam A, et al. "Effects of licorice candy on blood pressure in healthy young adults." Am J Clin Nutr. 2024. doi: 10.1016/j.ajcnut.2024.03.013

    20. Health Canada. "Natural Health Product Monograph: Deglycyrrhizinated Licorice." https://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=77

    21. Das SK, et al. "Deglycyrrhizinated liquorice in aphthous ulcers." J Assoc Physicians India. 1989;37(10):647. PMID: 2632490

    22. Raj A, et al. "Efficacy of GutGard in the management of gastroesophageal reflux disease." Complement Med Res. 2025. doi: 10.1159/000536529

    23. Raveendra KR, et al. "An extract of Glycyrrhiza glabra (GutGard) alleviates symptoms of functional dyspepsia: a randomized, double-blind, placebo-controlled study." Evid Based Complement Alternat Med. 2012;2012:216970. doi: 10.1155/2012/216970

    24. US Patent 3,046,195. "Process for deglycyrrhizinating licorice." 1962.

    25. Dong Y, et al. "Separation of glycyrrhizic acid from licorice root extract using macroporous resins." J Chromatogr A. 2015. doi: 10.1016/j.chroma.2015.01.077

    26. HPLC quantification methods for glycyrrhizin and flavonoids in licorice extracts.

    27. Chandrasekaran CV, et al. "Dual inhibitory effect of Glycyrrhiza glabra (GutGard) on COX and LOX products." Phytomedicine. 2011;18(4):278-284. doi: 10.1016/j.phymed.2010.08.001

    28. Yeh AM, Golianu B. "Integrative treatment of reflux and functional dyspepsia in children." Children (Basel). 2014;1(2):119-133. doi: 10.3390/children1020119

    29. Revers FE. "De behandeling van het ulcus ventriculi met succus liquiritiae." Ned Tijdschr Geneeskd. 1946;90:135-137.

    30. Revers FE. "Heeft succus liquiritiae een genezende werking op de maagzweer?" Ned Tijdschr Geneeskd. 1952;96:2598-2602.

    31. Morgan AG, et al. "Comparison of cimetidine, antacid, DGL, and placebo in duodenal ulcer." Gut. 1982. PMID: 3891678

    32. Engqvist A, et al. "A trial of deglycyrrhizinated liquorice in the treatment of duodenal ulcer." Gut. 1973;14:711-715. doi: 10.1136/gut.14.9.711

    33. Turpie AG, et al. "Clinical trial of deglycyrrhizinized liquorice in gastric ulcer." Gut. 1969;10:299-302. doi: 10.1136/gut.10.4.299

    34. Van Marle J, et al. "Deglycyrrhizinised liquorice (DGL) and the renewal of rat stomach epithelium." Eur J Pharmacol. 1981;72(2-3):219-225. doi: 10.1016/0014-2999(81)90279-x

    35. Wittschier N, et al. "The antimicrobial effects of deglycyrrhizinated licorice root extract on Helicobacter pylori." J Ethnopharmacol. 2009. doi: 10.1016/j.jep.2009.02.039

    36. Asha MK, et al. "Pharmacological effects and underlying mechanisms of licorice-derived flavonoids on H. pylori." J Nat Med. 2013. doi: 10.1007/s11418-012-0644-7

    37. Puram S, et al. "Effect of GutGard in the management of Helicobacter pylori: a randomized double blind placebo controlled study." Evid Based Complement Alternat Med. 2013;2013:263805. doi: 10.1155/2013/263805

    38. Yang R, et al. "Aqueous extracts and polysaccharides from Liquorice roots: antioxidant and mucosal protective activity." Food Chem. 2018. doi: 10.1016/j.foodchem.2018.05.109

    39. Das SK, et al. "Deglycyrrhizinated liquorice in aphthous ulcers." J Assoc Physicians India. 1989;37:647. PMID: 2632490

    40. Ajagannanavar SL, et al. "The Power of Licorice (Radix glycyrrhizae) to Improve Oral Health." Int J Pharm Sci Res. 2014. doi: 10.13040/IJPSR.0975-8232.5(2).40-44

    41. Methlie P, et al. "The effects of licorice on cortisol metabolism and adrenal insufficiency." Eur J Endocrinol. 2011;165(5):761-769. doi: 10.1530/EJE-11-0525

    42. Cotterill JA. "Licorice and Addison's disease." Lancet. 1973;1(7796):294-295.

    43. Baschetti R. "Chronic fatigue syndrome and liquorice." N Z Med J. 1995;108(1003):300.

    44. Wang J, et al. "Potential benefits of licorice for stress, anxiety and depression: a systematic review." Heliyon. 2023. doi: 10.1016/j.heliyon.2023.e17506

    45. Saeedi M, Morteza-Semnani K, Ghoreishi MR. "The treatment of atopic dermatitis with licorice gel." J Dermatolog Treat. 2003;14(3):153-157. doi: 10.1080/09546630310014369

    46. Drugs.com. "Licorice Uses, Benefits & Dosage." https://www.drugs.com/npc/licorice.html

    47. Stormer FC, et al. "Glycyrrhizic acid in liquorice — evaluation of health hazard." Food Chem Toxicol. 1993;31(4):303-312. doi: 10.1016/0278-6915(93)90080-i

    48. Shin IS, et al. "Licorice-induced stroke." Neurohospitalist. 2019;9(1):45-47. doi: 10.1177/1941874418765333

    49. Szendrey S, et al. "A case of acquired mineralocorticoid excess syndrome from a licorice-containing supplement." J Med Case Rep. 2024;18:84. doi: 10.1186/s13256-024-04404-1

    50. Edelman ER, et al. "Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest." N Engl J Med. 2020;383:1263-1275. doi: 10.1056/NEJMcpc2002420

    51. Saha A, et al. "Severe hypokalemia from excessive licorice tea consumption." Cureus. 2025. doi: 10.7759/cureus.57219

    52. Falet JP, et al. "Hypokalemia and hypertension from licorice root extract consumption." CMAJ. 2019;191(21):E581. doi: 10.1503/cmaj.181360

    53. Erkus ME, et al. "Licorice root syrup consumption-induced atrial fibrillation." Turk Kardiyol Dern Ars. 2016;44(6):517-519. doi: 10.5543/tkda.2016.25044

    54. Ballin NZ, et al. "Glycyrrhizin in licorice-containing candies, ice cream, and tea in Denmark." Food Control. 2022;141:109152. doi: 10.1016/j.foodcont.2022.109152

    55. LactMed. "Licorice." National Library of Medicine. 2021. https://www.ncbi.nlm.nih.gov/books/NBK501922/

    56. Drugs.com. "Digoxin and licorice interactions." https://www.drugs.com/interactions-check.php?drug_list=920-0,4115-0

    57. Chinese Pharmacopoeia Commission. "Pharmacopoeia of the People's Republic of China." 2020 edition.

    58. Shu G, et al. "Glycyrrhiza glabra: Botany, cultivation, and sustainable use." In: Medicinal Plants and Fungi. 2019.

    59. Eisenman SW. "Need for Sustainable Utilization and Conservation of Glycyrrhiza Species." Medicinal Plant Conservation. 2017.

Related Posts

Back to blog