Deglycyrrhizinated Licorice (DGL) Root Extract
Mechanism of Action +
### The Biochemistry of Licorice and the Necessity of Deglycyrrhizination
To understand the mechanism of Deglycyrrhizinated Licorice (DGL), one must first understand the pharmacology of standard *Glycyrrhiza glabra* (licorice root). Raw licorice root contains a potent triterpenoid saponin known as glycyrrhizin (or glycyrrhizic acid), which typically comprises 0.3% to 8.3% of the root's dry weight. Upon ingestion, glycyrrhizin is hydrolyzed by intestinal flora into glycyrrhetinic acid.
Glycyrrhetinic acid is a potent inhibitor of the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). In the human body, 11β-HSD2 is highly expressed in aldosterone-selective tissues, such as the distal convoluted tubules and collecting ducts of the kidneys. Its primary physiological role is to convert active cortisol into inactive cortisone. Because cortisol binds to the mineralocorticoid receptor (MR) with equal affinity as aldosterone, but circulates at concentrations 100 to 1,000 times higher, the rapid inactivation of cortisol by 11β-HSD2 is crucial to prevent illicit activation of the MR.
When glycyrrhetinic acid inhibits 11β-HSD2, local concentrations of cortisol in the kidneys skyrocket, leading to massive activation of the mineralocorticoid receptors. This induces a state of apparent mineralocorticoid excess (AME), characterized by severe sodium retention, profound hypokalemia (potassium loss), metabolic alkalosis, and a dangerous, sometimes fatal, increase in blood pressure. Examine.com data highlights this with a Grade F (Moderate Detriment) for blood pressure across 5 studies involving 137 participants.
Deglycyrrhizination is the specific extraction process utilized to remove glycyrrhizin to levels below 0.5% (often below detectable limits). This process yields DGL, a fraction that retains the therapeutic bioactive flavonoids and chalcones of the root while completely bypassing the 11β-HSD2 inhibition pathway, rendering it safe for cardiovascular health.
### Mucosal Defense and Gastrointestinal Pharmacology
The primary therapeutic targets of DGL are the gastric and esophageal mucosa. Unlike proton pump inhibitors (PPIs) or H2-receptor antagonists that suppress gastric acid secretion, DGL does not significantly alter the pH of the stomach. Instead, it enhances the mucosal barrier.
DGL achieves this through several distinct pathways: 1. **Upregulation of Mucin Production:** DGL stimulates the proliferation of mucin-secreting goblet cells and enhances the synthesis and secretion of gastric mucin. Mucin is a highly glycosylated protein that forms a viscous, gel-like layer over the gastric epithelium, providing a physical barrier against hydrochloric acid and pepsin. 2. **Enhanced Mucosal Blood Flow:** The flavonoids in DGL promote local vasodilation in the gastric mucosa. Increased microcirculation ensures a steady supply of oxygen and nutrients to the epithelial cells, accelerating cellular turnover and the healing of micro-ulcerations. 3. **Prostaglandin E2 (PGE2) Modulation:** DGL mildly stimulates the local release of protective prostaglandins (like PGE2) in the gut lining. PGE2 is critical for maintaining mucosal integrity, stimulating bicarbonate secretion (which neutralizes acid at the epithelial surface), and reducing local inflammation.
### Antioxidant and Anti-Inflammatory Flavonoids
With the glycyrrhizin removed, the pharmacological profile of DGL is dominated by its rich flavonoid content, most notably glabridin, licochalcone A, liquiritin, and isoliquiritigenin.
**Glabridin:** This is the most abundant isoflavan in licorice root. Glabridin exhibits potent antioxidant properties. Clinical data from Examine.com notes a Grade C (Moderate Improvement) in reducing LDL oxidation. Glabridin achieves this by incorporating itself into the LDL particle and protecting the lipid core from reactive oxygen species (ROS) and macrophage-mediated oxidative stress. Furthermore, glabridin downregulates the expression of pro-inflammatory cytokines (such as TNF-alpha and IL-6) by inhibiting the NF-κB signaling pathway.
**Licochalcone A:** This chalcone has demonstrated significant antibacterial properties, particularly against *Helicobacter pylori*, the primary bacterial pathogen responsible for peptic ulcer disease and chronic gastritis. Licochalcone A disrupts the bacterial cell membrane and inhibits bacterial energy metabolism, providing a synergistic effect when DGL is used alongside traditional eradication therapies.
### Pharmacokinetics and Delivery Mechanisms
The pharmacokinetics of DGL are unique because its primary mechanism of action for gastrointestinal distress is topical rather than systemic. When DGL is swallowed as a whole capsule, it bypasses the esophagus and much of the upper stomach before dispersing. However, when DGL is chewed or taken as a lozenge, the active flavonoids mix with saliva.
Salivary epidermal growth factor (EGF) is a potent stimulator of mucosal healing. The act of chewing DGL stimulates salivary flow, mixing the DGL flavonoids with endogenous EGF. This viscous, flavonoid-rich salivary mixture then coats the esophagus and the stomach lining as it is swallowed, providing immediate, localized anti-inflammatory and mucin-stimulating effects. This is why clinical applications overwhelmingly favor chewable DGL tablets taken 20-30 minutes before meals.
What is DGL supplement good for? +
Is licorice good for adrenal fatigue? +
Who should not take DGL supplements? +
Does licorice help with hyperpigmentation? +
What medications should not be taken with licorice? +
What not to mix with licorice extract? +
Can DGL affect blood pressure? +
Should I take DGL before bed? +
How long does it take for DGL licorice to work? +
Can you take DGL licorice with omeprazole? +
What is the best DGL dosage for GERD? +
What is the best DGL dosage for gastritis? +
Are there side effects of DGL licorice? +
Why are DGL supplements often chewable? +
Does DGL interact with blood thinners? +
Can I take DGL on an empty stomach? +
Everything About Deglycyrrhizinated Licorice (DGL) Root Extract Article
## The Definitive Guide to Deglycyrrhizinated Licorice (DGL) Root Extract
Licorice root (*Glycyrrhiza glabra*) is one of the oldest and most widely used botanicals in traditional medicine, with a history spanning ancient Egyptian, Greek, Roman, and Chinese dynasties. While traditionally revered for its ability to soothe the stomach and respiratory tract, modern clinical science uncovered a significant flaw in raw licorice: it causes severe spikes in blood pressure.
Enter Deglycyrrhizinated Licorice (DGL)—a triumph of botanical processing. By removing the specific compound responsible for cardiovascular side effects, DGL delivers the profound gut-healing, anti-inflammatory, and antioxidant benefits of licorice root safely and effectively.
### The Glycyrrhizin Dilemma: Why DGL is Essential
To understand DGL, you must understand what was removed from it. Raw licorice root contains a saponin called **glycyrrhizin**. When consumed, glycyrrhizin is metabolized into glycyrrhetinic acid, which acts as a potent inhibitor of the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2).
In the human body, 11β-HSD2 acts as a gatekeeper in the kidneys. Its job is to deactivate cortisol so that it doesn't bind to mineralocorticoid receptors. When glycyrrhizin inhibits this enzyme, cortisol floods these receptors, acting like the hormone aldosterone. The result? The body aggressively retains sodium and excretes potassium. This leads to a dangerous condition known as apparent mineralocorticoid excess (AME), resulting in water retention, severe hypokalemia, and dangerous spikes in blood pressure. In fact, Examine.com data assigns standard licorice a Grade F (Moderate Detriment) for blood pressure based on multiple clinical trials.
**Deglycyrrhizination** is the extraction process that removes glycyrrhizin down to trace, biologically insignificant levels (typically below 0.5%). What remains is DGL: a potent complex of licorice flavonoids that provides all the gastrointestinal benefits without the cardiovascular risks.
### How DGL Heals the Gut
Unlike over-the-counter antacids or proton pump inhibitors (PPIs) that completely shut down stomach acid production—which can lead to malabsorption of nutrients and bacterial overgrowth—DGL works by enhancing the body's natural defense mechanisms.
#### 1. Mucin Stimulation and Mucosal Coating The stomach protects itself from its own highly acidic environment by secreting a thick layer of mucus (mucin). DGL actively stimulates the goblet cells in the gastric lining to increase mucin production. This creates a thicker, more robust physical barrier between the delicate stomach tissue and harsh gastric juices (hydrochloric acid and pepsin).
#### 2. The Importance of the Chewable Format If you look at the market, almost all effective DGL supplements are chewable tablets or lozenges. This is not just for flavor; it is a pharmacokinetic necessity. When you chew DGL, the active flavonoids mix with your saliva. Saliva contains Epidermal Growth Factor (EGF), a polypeptide that stimulates cell growth and tissue repair. The viscous mixture of DGL and saliva coats the esophagus as you swallow, delivering targeted, topical relief to inflamed esophageal tissue—making it highly effective for acid reflux and GERD.
#### 3. Anti-H. pylori Activity *Helicobacter pylori* is a resilient bacterium that burrows into the stomach lining, causing chronic inflammation, gastritis, and peptic ulcers. DGL contains a specific chalcone called **licochalcone A**, which has demonstrated significant antibacterial properties against *H. pylori*. By disrupting the bacterial cell membrane, DGL helps manage bacterial loads and supports the healing of ulcerated tissue.
### Beyond the Gut: Antioxidant and Anti-Inflammatory Power
While DGL is primarily known as a digestive aid, the flavonoids left behind after deglycyrrhizination are potent systemic antioxidants.
**Glabridin**, the most abundant isoflavan in DGL, has been shown to protect lipids from oxidative damage. According to Examine.com, licorice extract provides a Grade C (Moderate Improvement) in reducing the oxidation of Low-Density Lipoprotein (LDL). Oxidized LDL is a primary driver of atherosclerosis (plaque buildup in the arteries). By incorporating itself into the LDL particle, glabridin shields it from reactive oxygen species.
Furthermore, DGL exerts anti-inflammatory effects by inhibiting the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, reducing the production of pro-inflammatory prostaglandins and leukotrienes throughout the body.
### Synergies: Stacking DGL for Maximum Efficacy
Clinical data and traditional practices suggest that DGL works exceptionally well when combined with other specific nutrients: * **DGL + Lycopene:** Examine.com notes that licorice and lycopene work synergistically to prevent LDL oxidation, offering a powerful one-two punch for cardiovascular health. * **DGL + Cranberry Extract:** This combination confers synergistic anti-inflammatory and antibacterial effects, particularly useful for managing unwanted bacterial adhesion in the gut and urinary tract. * **DGL + Slippery Elm & Marshmallow Root:** In sports nutrition and wellness formulations, DGL is frequently stacked with these mucilaginous herbs to create a comprehensive "gut-soothing" matrix that coats the entire GI tract.
### Dosage, Timing, and Real-World Application
For optimal results, timing is everything with DGL.
* **Standard Dose:** The clinical standard for DGL extract is typically 400mg to 800mg per dose. (Note: Examine.com cites 1-15g daily for raw root equivalents, but modern DGL extracts are highly concentrated). * **Timing:** DGL should be taken **20 to 30 minutes before meals**. This allows the DGL-saliva mixture to coat the esophagus and stomach lining, prepping the gastrointestinal tract for the influx of food and stomach acid. * **Format:** Always opt for chewable tablets or powders. Swallowing a DGL capsule whole bypasses the esophagus and misses out on the salivary EGF activation, significantly reducing its efficacy for acid reflux.
### Safety Profile and Label Literacy
Thanks to the deglycyrrhizination process, DGL is incredibly safe for long-term use. However, label literacy is crucial. When purchasing a licorice supplement, you must ensure the label explicitly states "DGL" or "Deglycyrrhizinated." If the product is just labeled "Licorice Root Extract" without specifying the glycyrrhizin content (which should be <0.5%), you risk severe blood pressure elevations with daily use.
While DGL is safe for the vast majority of people, those with severe renal impairment or pregnant women should consult a healthcare provider before use, as even trace amounts of active compounds can interact with sensitive physiological states.
### Conclusion
Deglycyrrhizinated Licorice (DGL) is a masterclass in botanical refinement. By stripping away the harmful glycyrrhizin, science has unlocked the pure, gut-healing potential of licorice root. Whether you are an athlete dealing with stress-induced gastritis, or simply someone looking for natural relief from post-meal acid reflux, DGL offers a scientifically backed, highly effective solution that works *with* your body's natural defenses rather than against them.