Hermetica Superfood Encyclopedia
The Short Answer
Isoliquiritigenin is a chalcone-type flavonoid found primarily in licorice root (Glycyrrhiza species) that exerts anti-inflammatory and metabolic effects largely through inhibition of NF-κB signaling and modulation of AMPK pathways. Its broad bioactivity spans glycemic regulation, lipid metabolism, and inflammatory cytokine suppression, supported by both in vitro mechanistic data and early-stage human trials.
CategoryNamed Bioactive Compounds
GroupCompound
Evidence LevelModerate
Primary Keywordisoliquiritigenin benefits
Synergy Pairings3
Isoliquiritigenin — botanical close-up
Health Benefits
Origin & History
Natural habitat
Isoliquiritigenin (ILTG) is a naturally occurring chalcone flavonoid (C15H12O4) primarily sourced from the roots of Glycyrrhiza glabra (licorice) and related Glycyrrhiza species, where it occurs as a minor component alongside liquiritigenin and other chalcones. Extraction typically involves ethanol or methanol solvent extraction of licorice root, followed by chromatographic purification to isolate the yellow crystalline powder.
“Isoliquiritigenin is a marker compound in Glycyrrhiza glabra root, used in Traditional Chinese Medicine as 'gan cao' for over 2,000 years to harmonize formulas and treat cough, gastric ulcers, and inflammation. In Ayurveda ('yashtimadhu') and Japanese Kampo ('kanzo'), licorice preparations have addressed respiratory and digestive issues for centuries, though isolation of ILTG itself is a 20th-century development.”Traditional Medicine
Scientific Research
Human clinical evidence for isoliquiritigenin is limited, with only one small RCT (n=60) testing a licorice flavonoid extract containing ~1.5% ILTG at 150 mg/day for metabolic syndrome (PMID: 23380324), and one pilot study (n=15) using 100 mg/day pure ILTG for anti-inflammatory effects (PMID: 28494188). No high-quality RCTs exist for cancer, neurodegeneration, or skin conditions, with most evidence derived from preclinical studies (PMID: 34684391).
Preparation & Dosage
Traditional preparation
Clinically studied doses include 2.25 mg ILTG daily as part of standardized licorice extract (150 mg containing 1.5% ILTG) for 8 weeks, or 100 mg/day pure ILTG powder in divided doses for 4 weeks. Commercial supplements typically provide 5-20 mg pure ILTG in capsules. Consult a healthcare provider before starting any new supplement.
Nutritional Profile
Isoliquiritigenin (ISL) is a chalcone-type flavonoid (C₁₅H₁₂O₄, MW 256.25 g/mol) primarily found in licorice root (Glycyrrhiza glabra/uralensis), at concentrations of approximately 0.05–0.3% of dry root weight. It is not a macronutrient or micronutrient source; its value is entirely as a bioactive polyphenolic compound. ISL is lipophilic with moderate water solubility (~0.1 mg/mL). Oral bioavailability in humans is estimated at 5–15% due to extensive Phase II metabolism (glucuronidation and sulfation in the intestine and liver, primarily via UGT1A1 and SULT1A1). Peak plasma concentrations following a 100 mg oral dose are estimated at 0.2–0.8 µM, with a Tmax of 1–3 hours. Enterohepatic recycling may produce a secondary plasma peak. ISL is a potent activator of the Nrf2/ARE/HO-1 antioxidant pathway, an inhibitor of NF-κB and NLRP3 inflammasome signaling, and a modulator of aldose reductase and PPARγ. It also functions as a phytoestrogen with selective estrogen receptor β (ERβ) affinity (IC₅₀ ~1–5 µM). Co-administration with a lipid-based carrier or piperine (5–10 mg) may improve bioavailability by 30–60%.
How It Works
Mechanism of Action
Isoliquiritigenin inhibits the NF-κB signaling cascade by blocking IκB kinase (IKK) phosphorylation, thereby suppressing downstream transcription of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β. It activates AMP-activated protein kinase (AMPK), which enhances fatty acid oxidation and improves insulin receptor substrate-1 (IRS-1) signaling, contributing to its insulin-sensitizing effects. Additionally, isoliquiritigenin acts as a partial agonist at PPARγ receptors and inhibits aromatase (CYP19A1), influencing both lipid homeostasis and estrogen biosynthesis.
Clinical Evidence
A randomized controlled trial in postmenopausal women with metabolic syndrome (n=60) demonstrated a 15% reduction in serum triglycerides and a 12% improvement in HOMA-IR after supplementation, providing moderate-quality evidence for metabolic benefit (PMID: 23380324). A preliminary study in healthy volunteers reported a 20% reduction in C-reactive protein, though the small sample size and short duration limit conclusions. The majority of mechanistic evidence derives from in vitro cell culture studies and rodent models, where doses of 10–50 mg/kg/day consistently reduced inflammatory markers and improved lipid profiles. Robust phase II or III human clinical trials are currently lacking, meaning evidence strength for most claimed benefits remains preliminary to moderate.
Safety & Interactions
Isoliquiritigenin shares structural similarities with phytoestrogens and may interact with estrogen receptor signaling, making use in hormone-sensitive conditions such as estrogen receptor-positive breast cancer, uterine fibroids, or endometriosis potentially contraindicated. Because it inhibits CYP19A1 (aromatase) and may affect CYP3A4 activity, co-administration with estrogen therapies, tamoxifen, or drugs with narrow therapeutic windows metabolized by CYP3A4 warrants caution. High doses in animal models have shown mild hepatotoxic signals, though human data on liver safety at supplemental doses are insufficient. Pregnancy and breastfeeding safety has not been established, and use should be avoided in these populations pending further study.
Synergy Stack
Hermetica Formulation Heuristic
Also Known As
ILTG4,2',4'-trihydroxychalconeliquiritigenin chalconegan cao compoundyashtimadhu flavonoidkanzo chalconelicorice chalconeGlycyrrhiza chalcone
Frequently Asked Questions
What is isoliquiritigenin and what foods contain it?
Isoliquiritigenin is a chalcone flavonoid found predominantly in the roots and rhizomes of licorice species, particularly Glycyrrhiza uralensis, Glycyrrhiza glabra, and Glycyrrhiza inflata. It is also present in smaller quantities in shallots (Allium ascalonicum), legumes such as soybeans, and certain traditional herbal preparations. Licorice root extract typically contains isoliquiritigenin at concentrations of 0.05–0.5% by dry weight depending on species and processing method.
How does isoliquiritigenin affect blood sugar and insulin sensitivity?
Isoliquiritigenin activates AMPK in skeletal muscle and liver tissue, which promotes GLUT4 translocation to the cell membrane and enhances glucose uptake independent of insulin signaling. In the clinical trial published as PMID 23380324, postmenopausal women with metabolic syndrome showed a 12% improvement in HOMA-IR scores, a validated surrogate marker of insulin resistance, over the study period. Animal studies using 20–50 mg/kg/day in high-fat diet rodent models have consistently replicated improved fasting glucose and insulin tolerance test outcomes, though direct human dose translation remains unconfirmed.
Does isoliquiritigenin have estrogen-like effects?
Yes, isoliquiritigenin exhibits selective estrogen receptor modulator (SERM)-like activity, binding ERα and ERβ with moderate affinity and producing tissue-dependent agonist or antagonist effects. It also potently inhibits aromatase (CYP19A1) with an IC50 in the range of 0.5–2 µM in cell-free assay systems, meaning it can simultaneously reduce endogenous estrogen biosynthesis while directly activating estrogen receptors at certain tissues. This dual activity makes it a subject of interest in menopause research but also raises concern for individuals with hormone-sensitive cancers or those taking hormonal therapies.
What is the typical dosage of isoliquiritigenin used in studies?
Human clinical research on isoliquiritigenin is limited, and no standardized therapeutic dosage has been formally established for any indication. The metabolic syndrome trial (PMID 23380324) used a standardized licorice flavonoid extract rather than pure isoliquiritigenin, complicating direct dose extrapolation. In preclinical rodent studies, effective doses have ranged from 10 to 100 mg/kg/day; applying standard allometric scaling to humans suggests a rough equivalent of approximately 80–800 mg/day for a 70 kg adult, though this range has not been validated for safety or efficacy in human trials.
Can isoliquiritigenin interact with cancer medications?
Isoliquiritigenin inhibits CYP3A4 and CYP1A2 enzymatic activity in vitro, which could theoretically alter plasma concentrations of chemotherapeutic agents metabolized by these enzymes, including certain taxanes, vinca alkaloids, and tyrosine kinase inhibitors. Its aromatase-inhibiting properties may also antagonize the mechanism of aromatase inhibitor drugs such as anastrozole or letrozole used in hormone receptor-positive breast cancer treatment. Until dedicated drug interaction pharmacokinetic studies in humans are conducted, co-use with any oncology medication should only occur under direct physician supervision.
What is the bioavailability of isoliquiritigenin and how is it affected by food?
Isoliquiritigenin has relatively low oral bioavailability due to extensive first-pass metabolism and poor intestinal absorption, though consuming it with dietary fats may enhance absorption slightly. Licorice root extracts standardized for isoliquiritigenin content generally show better bioavailability than isolated forms, as other compounds in the extract may support uptake. Taking isoliquiritigenin with meals containing fat sources is recommended to optimize absorption potential.
Who would benefit most from isoliquiritigenin supplementation based on current evidence?
Individuals with metabolic syndrome, elevated triglycerides, or insulin resistance appear to benefit most from isoliquiritigenin, particularly postmenopausal women showing significant improvements in metabolic markers. Those with elevated inflammatory markers (high C-reactive protein) may also see modest benefits from its anti-inflammatory effects. People seeking antioxidant support through Nrf2 pathway activation represent another potential beneficiary population, though more research is needed to confirm optimal candidacy.
How does isoliquiritigenin compare to other licorice-derived compounds for metabolic support?
Isoliquiritigenin is one of the more potent bioactive compounds in licorice root for triglyceride reduction and insulin sensitivity improvement, though it typically works synergistically with other licorice flavonoids like liquiritigenin and glabridin rather than in isolation. Unlike glycyrrhizin (the sweet compound in licorice), isoliquiritigenin does not cause sodium retention or hypertension, making it a safer choice for those concerned about blood pressure effects. Standardized licorice extracts containing multiple active compounds may provide broader metabolic benefits than isoliquiritigenin alone.
Explore the Full Encyclopedia
7,400+ ingredients researched, verified, and formulated for optimal synergy.
Browse IngredientsThese statements have not been evaluated by the Food and Drug Administration. This content is for informational purposes only and is not intended to diagnose, treat, cure, or prevent any disease.
hermetica-encyclopedia-canary-zzqv9k4w isoliquiritigenin curated by Hermetica Superfoods at ingredients.hermeticasuperfoods.com and licensed CC BY-NC-SA 4.0 (non-commercial share-alike, attribution required)
