Isoliquiritigenin is a powerful chalcone found in licorice root that provides exceptional sleep-promoting and neuroprotective benefits. This specialized plant compound, distinguished by its unique trihydroxychalcone structure, helps improve sleep quality by inhibiting monoamine oxidase (MAO) and modulating dopamine receptors, reduces inflammation through multiple pathways, provides potent antioxidant protection, demonstrates significant anticancer potential by inhibiting cancer cell proliferation and angiogenesis, offers joint-protective benefits by inhibiting cartilage-degrading enzymes, supports cardiovascular health, shows liver-protective properties, exhibits mood-regulating effects, provides metabolic benefits, and represents one of the most biologically active compounds in licorice while working synergistically with other licorice compounds like liquiritigenin to enhance overall health effects.
Alternative Names: 4,2′,4′-Trihydroxychalcone, ILG, Licorice Chalcone, Licorice Flavonoid
Categories: Flavonoid, Chalcone, Phytochemical, Polyphenol
Primary Longevity Benefits
- Anti-inflammatory
- Antioxidant
- Neuroprotective
- Cellular signaling modulation
Secondary Benefits
- Cardiovascular health
- Metabolic health
- Sleep promotion
- Cognitive function
- Joint health
- Liver protection
- Anti-cancer properties
- Mood regulation
Mechanism of Action
Isoliquiritigenin (ILG) exerts its diverse biological effects through multiple molecular mechanisms. As a potent antioxidant, ILG directly scavenges reactive oxygen species (ROS) and enhances endogenous antioxidant defense systems by activating the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which increases the expression of antioxidant enzymes like glutathione S-transferase and heme oxygenase-1. ILG demonstrates significant anti-inflammatory properties by inhibiting nuclear factor-kappa B (NF-κB) activation, a master regulator of inflammation, thereby reducing the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. It also inhibits cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes, further reducing inflammatory mediator production.
In the nervous system, ILG functions as a potent human monoamine oxidase (hMAO) inhibitor, with competitive inhibition of hMAO-A and mixed inhibition of hMAO-B, which may contribute to its neuroprotective and mood-regulating effects. It also modulates dopamine receptors, acting as an antagonist of the D1 receptor and an agonist of the D3 receptor, while also functioning as an agonist of the vasopressin V1A receptor. ILG crosses the blood-brain barrier and enhances GABA receptor function, which explains its sleep-promoting and anxiolytic effects. For metabolic health, ILG improves insulin sensitivity by activating AMPK (AMP-activated protein kinase) and PPAR-γ (Peroxisome proliferator-activated receptor gamma) pathways, enhances glucose uptake in tissues, and protects pancreatic β-cells from oxidative damage.
It also positively influences lipid profiles by regulating cholesterol metabolism genes and enhancing bile acid excretion. In the cardiovascular system, ILG improves endothelial function by enhancing nitric oxide production, reduces lipid peroxidation, and inhibits platelet aggregation. For joint health, ILG inhibits matrix metalloproteinases (MMPs), particularly MMP-13, which is involved in cartilage degradation in osteoarthritis. It also shows synergistic effects with other compounds like sulforaphane in protecting cartilage.
ILG exhibits anticancer properties through multiple mechanisms, including inhibition of the VEGF/VEGFR-2 signaling pathway (anti-angiogenesis), induction of apoptosis in cancer cells, cell cycle arrest, and inhibition of cancer cell migration and invasion. It also modulates various cell signaling pathways involved in cancer progression, including JAK/STAT, MAPK, PI3K/Akt, and Wnt/β-catenin pathways. In the liver, ILG protects hepatocytes from oxidative damage, enhances detoxification enzymes, and promotes bile production. Additionally, ILG exhibits immunomodulatory effects by regulating the activity of T cells, B cells, macrophages, and natural killer cells, helping to balance immune responses without causing immunosuppression.
Optimal Dosage
Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.
The optimal dosage of isoliquiritigenin (ILG) has not been definitively established in humans due to limited clinical trials. Based on preclinical studies and traditional usage of licorice extracts, a general dosage range of 50-200 mg per day of isolated ILG is commonly suggested. For standardized licorice root extracts containing ILG, dosages typically range from 250-500 mg daily, standardized to contain 1-5% isoliquiritigenin.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Anti-inflammatory support | 100-150 mg of isolated ILG daily, or 300-500 mg of standardized licorice extract | May be divided into 2-3 doses throughout the day for sustained effects due to ILG’s relatively short half-life |
| Sleep promotion | 50-100 mg of ILG | Best taken 30-60 minutes before bedtime; lower doses may be effective when combined with other sleep-promoting compounds |
| Neuroprotection | 100-200 mg daily | Long-term consistent use may be required for optimal neuroprotective effects |
| Joint health | 100-150 mg daily | May be more effective when combined with other anti-inflammatory compounds like curcumin or sulforaphane |
| Metabolic health | 100-200 mg daily | Best taken with meals to enhance absorption and potentially improve postprandial glucose response |
| Liver support | 100-150 mg daily | Should be used cautiously in those with existing liver conditions; monitoring of liver function is recommended |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Adults (18-65 years) | 50-200 mg daily of isolated ILG, or 250-500 mg of standardized extract | Start with lower doses and gradually increase as tolerated |
| Seniors (65+ years) | 50-100 mg daily of isolated ILG, or 250-350 mg of standardized extract | Lower starting doses recommended due to potential changes in metabolism and increased sensitivity; monitor for interactions with medications |
| Children and adolescents (<18 years) | Not recommended | Safety and efficacy not established in pediatric populations |
Dosing Frequency
Due to the relatively short half-life of isoliquiritigenin (approximately 4-6 hours), divided dosing 2-3 times per day is often recommended for sustained effects. For sleep promotion, a single dose before bedtime is typically sufficient.
Titration Recommendations
It is advisable to start with the lower end of the dosage range (approximately 50 mg daily of isolated ILG or 250 mg of standardized extract) and gradually increase over 1-2 weeks as tolerated, monitoring for any adverse effects. This approach helps minimize potential side effects and allows for identification of the minimum effective dose.
Cycling Recommendations
Some practitioners recommend cycling isoliquiritigenin with periods of 4-6 weeks of use followed by 1-2 weeks off to prevent potential adaptation and maintain efficacy. However, this approach is based on clinical experience rather than robust scientific evidence.
Research Limitations
Most dosage recommendations for isoliquiritigenin are extrapolated from preclinical studies and traditional usage patterns rather than controlled human clinical trials. More research is needed to establish optimal dosing regimens for specific conditions in humans.
Bioavailability
Absorption Rate
Isoliquiritigenin (ILG) has relatively poor oral bioavailability (approximately 7-12%) due to its low aqueous solubility, extensive first-pass metabolism, and rapid elimination. The compound is primarily absorbed in the small intestine through passive diffusion and possibly active transport mechanisms.
Enhancement Methods
Liposomal encapsulation: Increases bioavailability by up to 3-4 times by protecting ILG from degradation and enhancing intestinal absorption, Nanoparticle formulations: Zein phosphatidylcholine nanoparticles have shown improved delivery and sustained release of ILG, Deep eutectic solvent formulations: Novel delivery systems that significantly enhance ILG solubility and bioavailability, Co-administration with piperine: Black pepper extract may inhibit ILG metabolism and increase absorption, Phospholipid complexes: Improve lipid solubility and membrane permeability, Cyclodextrin inclusion complexes: Enhance aqueous solubility and stability, Emulsion-based delivery systems: Improve dissolution rate and intestinal absorption
Timing Recommendations
For optimal absorption, isoliquiritigenin is best taken with meals containing some fat content, which can enhance its absorption. Taking divided doses throughout the day rather than a single large dose may improve overall bioavailability due to the compound’s relatively short half-life (approximately 4-6 hours). Evening administration may be beneficial for those using ILG for its sleep-promoting effects.
Metabolism And Elimination
Isoliquiritigenin undergoes extensive phase I and phase II metabolism in the liver. The primary metabolic pathways include glucuronidation, sulfation, and methylation. The compound and its metabolites are primarily excreted through the urine and, to a lesser extent, through bile into feces. The plasma half-life of ILG is relatively short (4-6 hours), necessitating multiple daily dosing for sustained effects.
Blood Brain Barrier Penetration
Studies indicate that isoliquiritigenin can cross the blood-brain barrier to some extent, which explains its neurological effects including neuroprotection, sleep promotion, and mood regulation. The lipophilic nature of the molecule contributes to its ability to penetrate the CNS.
Bioavailability Challenges
The main challenges affecting isoliquiritigenin bioavailability include poor water solubility, chemical instability in gastrointestinal conditions, extensive first-pass metabolism, and rapid elimination. These factors contribute to its overall low oral bioavailability, which has prompted research into various enhanced delivery systems.
Food Interactions
Consuming isoliquiritigenin with high-fat meals may increase its bioavailability by enhancing solubility and lymphatic transport. Certain flavonoids in foods may compete with ILG for metabolic enzymes, potentially affecting its bioavailability. Acidic foods may affect the stability of ILG, as the compound is pH-sensitive and can convert to liquiritigenin under certain pH conditions.
Safety Profile
Safety Rating
Side Effects
- Mild gastrointestinal discomfort (nausea, stomach upset)
- Headache
- Dizziness
- Potential hormonal effects due to weak estrogenic activity
- Potential hypotensive effects at high doses
- Potential hypoglycemic effects (may enhance insulin sensitivity)
Contraindications
- Pregnancy and breastfeeding due to insufficient safety data and potential hormonal effects
- Hormone-sensitive conditions including certain hormone-dependent cancers due to potential estrogenic activity
- Severe liver disease due to the liver’s role in metabolizing the compound
- Severe kidney disease due to potential effects on electrolyte balance
- Hypertension treated with medication (may cause additive hypotensive effects)
- Diabetes treated with medication (may cause additive hypoglycemic effects)
- Scheduled surgery (discontinue 2 weeks before due to potential effects on blood pressure and blood glucose)
Drug Interactions
- Antihypertensive medications: May enhance blood pressure-lowering effects
- Antidiabetic medications: May enhance blood glucose-lowering effects
- Hormone replacement therapy: May interfere due to estrogenic activity
- MAO inhibitors: Potential additive effects as isoliquiritigenin has MAO inhibitory properties
- Anticoagulants/antiplatelet drugs: May enhance effects due to isoliquiritigenin’s mild antiplatelet properties
- Cytochrome P450 substrate drugs: Potential interactions as isoliquiritigenin may affect certain CYP enzymes
- Diuretics: Potential additive effects on electrolyte balance
Upper Limit
A definitive upper limit has not been established for isoliquiritigenin. Based on available research, doses exceeding 300 mg per day of isolated isoliquiritigenin are not recommended due to limited safety data at higher doses. For standardized licorice extracts containing isoliquiritigenin, upper limits should consider the glycyrrhizin content, which should not exceed 100 mg daily due to potential effects on blood pressure and electrolyte balance.
Long Term Safety
Long-term safety studies specifically on isoliquiritigenin are limited. Most safety data is extrapolated from studies on licorice root extracts, which contain multiple compounds including isoliquiritigenin. Chronic high-dose use of licorice extracts has been associated with pseudoaldosteronism (primarily due to glycyrrhizin content), characterized by hypertension, hypokalemia, and fluid retention. Isoliquiritigenin-specific extracts with reduced glycyrrhizin content may have a better long-term safety profile, but more research is needed.
Special Populations
Pregnant Women: Not recommended due to insufficient safety data and potential hormonal effects
Breastfeeding Women: Not recommended due to insufficient safety data and unknown effects on infants
Children: Not recommended due to lack of safety and efficacy data in pediatric populations
Elderly: Use with caution, starting with lower doses due to potential increased sensitivity and higher risk of drug interactions
Liver Impairment: Use with caution as metabolism primarily occurs in the liver; reduced doses may be necessary
Kidney Impairment: Use with caution due to potential effects on electrolyte balance; monitoring recommended
Allergic Reactions
Allergic reactions to isoliquiritigenin are rare but possible, particularly in individuals with known allergies to plants in the Fabaceae (legume) family, which includes licorice. Symptoms may include skin rash, itching, swelling, severe dizziness, or difficulty breathing.
Toxicity Data
Preclinical toxicity studies suggest isoliquiritigenin has a relatively favorable safety profile. In animal studies, the LD50 (median lethal dose) is relatively high, indicating low acute toxicity. Recent subacute toxicity studies of isoliquiritigenin-zein phosphatidylcholine nanoparticles showed no significant toxicity in rodent models at therapeutic doses. Genotoxicity and carcinogenicity studies are limited but have not raised significant concerns to date.
Monitoring Recommendations
For individuals taking isoliquiritigenin regularly, particularly at higher doses or for extended periods, monitoring of blood pressure, blood glucose, electrolyte levels (particularly potassium), and liver function may be advisable. Those with pre-existing medical conditions or taking medications should consult healthcare providers before use and undergo appropriate monitoring based on individual risk factors.
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating | Research References |
|---|---|---|---|
| Sulforaphane | Isoliquiritigenin and sulforaphane work synergistically to inhibit MMP13 gene expression in chondrocytes, potentially providing enhanced protection against cartilage degradation in osteoarthritis. Both compounds activate complementary anti-inflammatory and antioxidant pathways, with sulforaphane primarily working through Nrf2 activation while isoliquiritigenin has broader effects on multiple inflammatory pathways. | 3 | Davidson RK, et al. (2018). Identifying chondroprotective diet-derived bioactives and investigating their synergism. Scientific Reports, 8(1), 1-13. |
| Berberine | The combination of berberine and isoliquiritigenin synergistically improves adipose inflammation and obesity-induced insulin resistance. Berberine primarily works through AMPK activation and regulation of gut microbiota, while isoliquiritigenin has complementary effects on inflammatory pathways and adipocyte function, resulting in enhanced metabolic benefits when used together. | 3 | Zhang XY, et al. (2024). The combination of berberine and isoliquiritigenin synergistically improved adipose inflammation and obesity-induced insulin resistance. Phytotherapy Research, 38(8), 3839-3855. |
| Liquiritigenin | Isoliquiritigenin and liquiritigenin are isomeric compounds that can interconvert based on pH and temperature conditions. When present together, as they naturally occur in licorice root, they provide complementary biological activities. Liquiritigenin has stronger estrogenic effects through selective ERβ binding, while isoliquiritigenin has broader anti-inflammatory and antioxidant properties. | 2 | Ramalingam M, et al. (2018). Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models. Frontiers in Aging Neuroscience, 10, 348. |
| Glycyrrhizin | While glycyrrhizin is often removed from isoliquiritigenin-focused extracts due to potential side effects at high doses, low levels of glycyrrhizin may work synergistically with isoliquiritigenin for certain anti-inflammatory and antiviral effects. Glycyrrhizin primarily works through inhibition of HMGB1 and viral entry mechanisms, while isoliquiritigenin has complementary effects on inflammatory signaling pathways. | 2 | Wahab S, et al. (2021). Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology. Plants, 10(12), 2751. |
| Artemisinin | Isoliquiritigenin has shown synergistic antimalarial effects when combined with artemisinin derivatives. Isoliquiritigenin appears to enhance the oxidative stress induced by artemisinin in Plasmodium parasites while also providing complementary anti-inflammatory effects that may help manage malaria symptoms. | 2 | Kumar S, et al. (2024). Isoliquiritigenin from licorice root: A multi-stage anti-malarial with synergistic impact on multidrug-resistant P. falciparum. Pharmacological Research – Modern Chinese Medicine, 10, 100396. |
| Curcumin | Isoliquiritigenin and curcumin have complementary anti-inflammatory and antioxidant mechanisms. Both compounds inhibit NF-κB activation through slightly different mechanisms, and when combined, they provide more comprehensive inhibition of inflammatory pathways. They also show synergistic effects in cancer cell models, with enhanced induction of apoptosis and inhibition of proliferation. | 2 | Lin SR, et al. (2020). Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. British Journal of Pharmacology, 177(6), 1409-1423. |
| EGCG (Epigallocatechin gallate) | Isoliquiritigenin and EGCG from green tea show synergistic antioxidant and anti-inflammatory effects. EGCG primarily works through hydrogen atom transfer mechanisms for antioxidant effects, while isoliquiritigenin employs single electron transfer, providing complementary antioxidant protection. They also target overlapping but distinct inflammatory pathways. | 2 | Zhou J, et al. (2014). Research progress on synergistic anti-tumor mechanisms of compounds in Traditional Chinese Medicine. Journal of Traditional Chinese Medicine, 34(1), 100-105. |
| Resveratrol | Isoliquiritigenin and resveratrol show synergistic effects in activating SIRT1 and AMPK pathways, which are important for metabolic health and longevity. They also provide complementary antioxidant protection through different chemical structures and reaction mechanisms. | 2 | Aliper A, et al. (2017). Towards natural mimetics of metformin and rapamycin. Aging, 9(11), 2245-2268. |
| Piperine | Piperine from black pepper enhances the bioavailability of isoliquiritigenin by inhibiting certain metabolic enzymes responsible for its breakdown and elimination. This is not a therapeutic synergy but rather a pharmacokinetic enhancement that can increase the effectiveness of isoliquiritigenin supplementation. | 2 | Hu Y, et al. (2023). Exploring the mechanism of solubilization and release of isoliquiritigenin in deep eutectic solvents. International Journal of Pharmaceutics, 644, 123298. |
Antagonistic Compounds
| Compound | Interaction Type | Evidence Rating | Recommendations |
|---|---|---|---|
| Iron supplements | Isoliquiritigenin, like many polyphenols, can chelate iron and potentially reduce its absorption when taken simultaneously. This interaction is primarily of concern with supplemental iron rather than dietary iron sources. | 2 | Separate the intake of isoliquiritigenin and iron supplements by at least 2 hours. |
| Certain CYP450 substrate medications | Isoliquiritigenin may inhibit certain cytochrome P450 enzymes, particularly CYP3A4, potentially affecting the metabolism of drugs that are substrates for these enzymes. This could lead to increased blood levels and potential toxicity of these medications. | 2 | Consult with a healthcare provider before combining isoliquiritigenin with medications known to be metabolized by CYP450 enzymes, particularly CYP3A4 substrates. |
| Tamoxifen and other selective estrogen receptor modulators | Due to its weak phytoestrogenic activity, isoliquiritigenin may potentially interfere with the therapeutic effects of selective estrogen receptor modulators used in hormone-sensitive conditions. | 2 | Individuals using tamoxifen or other SERMs should consult with their healthcare provider before using isoliquiritigenin supplements. |
| MAO inhibitor medications | Since isoliquiritigenin has been shown to have MAO inhibitory properties, combining it with pharmaceutical MAO inhibitors could potentially lead to additive effects and increased risk of side effects, including hypertensive crisis if combined with tyramine-rich foods. | 2 | Avoid combining isoliquiritigenin with pharmaceutical MAO inhibitors unless under direct medical supervision. |
| Anticoagulant and antiplatelet medications | Isoliquiritigenin has mild antiplatelet properties that could potentially enhance the effects of anticoagulant and antiplatelet medications, increasing bleeding risk. | 2 | Use with caution in combination with anticoagulant or antiplatelet medications; medical monitoring may be necessary. |
| Antihypertensive medications | Isoliquiritigenin may have hypotensive effects that could potentially enhance the blood pressure-lowering effects of antihypertensive medications, leading to excessive blood pressure reduction. | 2 | Monitor blood pressure when combining isoliquiritigenin with antihypertensive medications; dose adjustments may be necessary. |
| Antidiabetic medications | Isoliquiritigenin may enhance insulin sensitivity and glucose uptake, potentially leading to additive hypoglycemic effects when combined with antidiabetic medications. | 2 | Monitor blood glucose levels when combining isoliquiritigenin with antidiabetic medications; dose adjustments may be necessary. |
| High-dose vitamin C | High doses of vitamin C may potentially interfere with the antioxidant mechanisms of isoliquiritigenin through redox cycling, potentially reducing its effectiveness. | 1 | Consider separating the intake of high-dose vitamin C and isoliquiritigenin by several hours. |
| Calcium supplements | Similar to iron, isoliquiritigenin may chelate calcium and potentially reduce its absorption when taken simultaneously. | 1 | Consider separating the intake of isoliquiritigenin and calcium supplements by at least 2 hours. |
Cost Efficiency
Relative Cost
Medium to High
Cost Per Effective Dose
Pure Isoliquiritigenin: Pure isoliquiritigenin (95%+ purity) typically costs $200-500 per gram for research-grade material. For a typical effective dose of 50-200 mg per day, this translates to approximately $10-100 per month for pure isoliquiritigenin supplementation.
Standardized Extracts: Standardized licorice extracts containing 1-5% isoliquiritigenin typically cost $20-60 for a one-month supply, depending on the standardization level, additional processing to reduce glycyrrhizin content, and brand positioning.
Enhanced Formulations: Specialized delivery systems like liposomal isoliquiritigenin or nanoparticle formulations typically command premium prices, ranging from $40-120 for a one-month supply, though these may offer improved bioavailability.
Value Analysis
Cost Effectiveness Rating: Moderate
Cost Vs Benefit Assessment: The cost-effectiveness of isoliquiritigenin supplementation varies depending on the specific health application and individual response. For general antioxidant and anti-inflammatory support, standardized licorice extracts offer reasonable value. For specific therapeutic applications requiring higher doses or enhanced bioavailability, the cost-benefit ratio becomes less favorable due to the higher cost of pure isoliquiritigenin or specialized formulations. The limited human clinical evidence for many proposed benefits also impacts the overall value assessment.
Alternatives Comparison: For many of isoliquiritigenin’s proposed benefits, more well-studied and potentially more cost-effective alternatives exist. For anti-inflammatory effects, curcumin supplements are generally less expensive and have more robust clinical evidence. For antioxidant benefits, quercetin or mixed flavonoid supplements may offer better value. For sleep promotion, melatonin is significantly less expensive. However, isoliquiritigenin’s unique combination of effects across multiple biological pathways may justify its higher cost for certain individuals seeking its specific benefits profile.
Market Factors
Supply Chain Considerations: The cost of isoliquiritigenin is influenced by several supply chain factors, including the availability and quality of licorice root, extraction efficiency, purification processes, and demand fluctuations. Licorice is cultivated in several regions globally, with China being a major producer, making the supply chain vulnerable to regional agricultural conditions and trade policies.
Production Scale: Current production of high-purity isoliquiritigenin is relatively small-scale compared to more common supplements, contributing to higher costs. As research interest and consumer demand increase, economies of scale may gradually reduce production costs.
Market Trends: The market for isoliquiritigenin and standardized licorice extracts has been growing steadily as research on their health benefits expands. Increasing consumer interest in natural compounds with multiple health benefits is likely to drive continued market growth and potentially more competitive pricing over time.
Cost Reduction Strategies
Dosage Optimization: Finding the minimum effective dose through careful titration can significantly improve cost-efficiency. Many users may achieve desired benefits at lower doses than those used in some research studies.
Formulation Selection: For many applications, standardized licorice extracts offer better value than pure isoliquiritigenin, particularly when the synergistic effects of other licorice compounds are beneficial.
Combination Approaches: Using isoliquiritigenin in combination with synergistic compounds may allow for lower effective doses. For example, combining smaller amounts of isoliquiritigenin with sulforaphane for joint health or with berberine for metabolic health may provide cost-effective synergistic benefits.
Timing Strategies: Cyclical usage patterns (e.g., 4-6 weeks on, 1-2 weeks off) may help maintain effectiveness while reducing overall consumption and cost.
Insurance Coverage
Prescription Status: Isoliquiritigenin is not available as a prescription medication and is therefore not covered by prescription drug insurance in any major market.
Health Savings Accounts: In the United States, isoliquiritigenin supplements may be eligible for purchase using Health Savings Account (HSA) or Flexible Spending Account (FSA) funds if prescribed by a healthcare provider for a specific medical condition, though policies vary by plan administrator.
International Coverage: In most countries, dietary supplements including isoliquiritigenin are not covered by national health insurance programs or private health insurance.
Cost Effectiveness By Application
| Application | Cost Effectiveness | Notes |
|---|---|---|
| Anti-inflammatory support | Moderate | Standardized licorice extracts offer reasonable value, though other anti-inflammatory supplements like curcumin may provide better cost-effectiveness for general inflammation management. |
| Sleep promotion | Low to Moderate | More cost-effective alternatives like melatonin exist, though isoliquiritigenin may offer additional benefits beyond sleep promotion. |
| Neuroprotection | Moderate | Limited clinical evidence makes value assessment difficult, but the potential long-term benefits for brain health may justify the cost for some individuals. |
| Joint health | Moderate | May offer good value when used in combination with other joint-supporting compounds like glucosamine or sulforaphane. |
| Metabolic health | Moderate | May offer reasonable value, particularly when combined with lifestyle modifications and potentially other supplements like berberine. |
Stability Information
Shelf Life
Pure isoliquiritigenin powder typically has a shelf life of 1-2 years when stored under optimal conditions. Standardized extracts containing isoliquiritigenin generally have a shelf life of 2-3 years. Formulated products like capsules or tablets typically have a shelf life of 1-3 years, depending on the specific formulation and packaging.
Storage Recommendations
Temperature: Store at room temperature (15-25°C or 59-77°F). For long-term storage of pure isoliquiritigenin, refrigeration (2-8°C or 36-46°F) is recommended.
Humidity: Keep in a dry environment with relative humidity below 60% to prevent moisture absorption and hydrolysis.
Light: Store in light-resistant, opaque containers as isoliquiritigenin is photosensitive and can degrade when exposed to light, particularly UV radiation.
Oxygen: Minimize exposure to oxygen by using containers with minimal headspace and consider oxygen absorbers or nitrogen flushing for bulk storage of pure compound.
Packaging: Amber glass bottles, opaque HDPE containers, or aluminum foil pouches with moisture barriers are recommended. Blister packs may be suitable for tablet formulations.
Degradation Factors
| Factor | Mechanism | Prevention |
|---|---|---|
| Oxidation | Isoliquiritigenin contains multiple hydroxyl groups that are susceptible to oxidation, particularly in the presence of oxygen, metal ions, or oxidizing agents. | Use of antioxidants (e.g., vitamin E, ascorbyl palmitate), oxygen scavengers in packaging, and storage in sealed containers with minimal headspace. |
| Photodegradation | UV and visible light can catalyze oxidation reactions and structural changes in isoliquiritigenin’s conjugated system. | Use of opaque or amber containers, storage away from direct light, and addition of UV stabilizers in formulations. |
| pH instability | Isoliquiritigenin is pH-sensitive and can undergo isomerization to liquiritigenin under alkaline conditions. The chalcone structure is generally more stable in acidic environments. | Maintaining appropriate pH in liquid formulations (slightly acidic is preferable), use of buffering agents, and avoiding strongly alkaline excipients. |
| Thermal degradation | High temperatures accelerate oxidation and isomerization reactions, as well as potential hydrolysis of the chalcone structure. | Storage at controlled room temperature or refrigeration, avoiding exposure to heat during processing and storage. |
| Enzymatic degradation | In natural extracts, residual enzymes like chalcone isomerase can catalyze the conversion of isoliquiritigenin to liquiritigenin. | Proper extraction and processing techniques to inactivate enzymes, including heat treatment or addition of enzyme inhibitors. |
| Moisture | Water can facilitate hydrolysis reactions and provide a medium for microbial growth, which can further degrade isoliquiritigenin. | Use of desiccants in packaging, moisture-resistant barriers, and storage in low-humidity environments. |
Stability Enhancing Additives
| Additive | Mechanism | Typical Concentration |
|---|---|---|
| Vitamin E (tocopherols) | Acts as an antioxidant to prevent oxidative degradation | 0.1-0.5% in formulations |
| Ascorbyl palmitate | Synergistic antioxidant that can regenerate other antioxidants like vitamin E | 0.05-0.2% in formulations |
| Citric acid | Chelates metal ions that can catalyze oxidation, also helps maintain acidic pH | 0.1-0.3% in formulations |
| Butylated hydroxytoluene (BHT) or Butylated hydroxyanisole (BHA) | Synthetic antioxidants that prevent oxidative degradation | 0.02-0.1% in formulations (use is regulated in some regions) |
| Cyclodextrins | Form inclusion complexes with isoliquiritigenin, protecting it from environmental factors | 5-15% in formulations |
Stability Testing Methods
| Method | Description | Parameters Measured |
|---|---|---|
| Accelerated stability testing | Exposing the product to elevated temperatures (40°C) and humidity (75% RH) to predict long-term stability | Physical appearance, color, odor, assay content, degradation products |
| Photostability testing | Exposing the product to defined light sources (UV and visible) to assess light sensitivity | Color changes, assay content, formation of degradation products |
| Real-time stability testing | Storing the product under recommended conditions and testing at defined intervals | Physical appearance, assay content, microbial limits, dissolution (for solid dosage forms) |
| HPLC analysis | Quantitative determination of isoliquiritigenin content and detection of degradation products | Assay content, purity, degradation products |
Formulation Stability
Solid Forms: Isoliquiritigenin is generally more stable in solid dosage forms (capsules, tablets) than in liquid formulations. Microencapsulation or matrix entrapment can further enhance stability in solid forms.
Liquid Forms: Liquid formulations are more challenging for stability. Solutions should be slightly acidic (pH 4-6) and contain appropriate antioxidants and chelating agents. Suspensions may offer better stability than solutions.
Liposomal Formulations: Liposomal encapsulation can significantly improve stability by protecting isoliquiritigenin from environmental factors, though these formulations may have their own stability challenges.
Sourcing
Synthesis Methods
| Method | Starting Materials | Advantages | Disadvantages |
|---|---|---|---|
| Claisen-Schmidt condensation | 2,4-dihydroxyacetophenone and 4-hydroxybenzaldehyde | Well-established synthetic route, moderate yield | Multiple steps, purification challenges |
| Enzymatic synthesis | Liquiritigenin as precursor with chalcone isomerase | Environmentally friendly, high stereoselectivity | Higher cost, limited scale-up potential |
| Green chemistry approaches | Various eco-friendly catalysts and starting materials | Reduced environmental impact, fewer toxic reagents | Still in development, variable yields |
Natural Sources
| Source | Concentration | Notes |
|---|---|---|
| Licorice root (Glycyrrhiza glabra) | Primary natural source, containing approximately 0.5-1.5% isoliquiritigenin by dry weight | The most commercially significant source for isoliquiritigenin extraction |
| Glycyrrhiza uralensis (Chinese licorice) | Contains approximately 0.3-1.2% isoliquiritigenin by dry weight | Commonly used in Traditional Chinese Medicine |
| Glycyrrhiza inflata | Contains approximately 0.2-1.0% isoliquiritigenin by dry weight | Another species of licorice used in traditional medicine |
| Dalbergia odorifera (Jiangxiang) | Contains trace amounts of isoliquiritigenin | Used in Traditional Chinese Medicine |
| Sinofranchetia chinensis | Contains trace amounts of isoliquiritigenin | Less common source |
| Allium species (including shallots) | Contains very small amounts of isoliquiritigenin | Not commercially viable for extraction |
Extraction Methods
| Method | Efficiency | Advantages | Disadvantages |
|---|---|---|---|
| Ethanol extraction | Moderate to high efficiency (60-80% recovery) | Relatively simple process, food-grade solvent | Co-extracts other compounds requiring further purification |
| Methanol extraction | High efficiency (70-90% recovery) | Higher extraction efficiency than ethanol | Toxic solvent requiring complete removal, not suitable for food-grade products |
| Supercritical CO2 extraction | Moderate efficiency (50-70% recovery) | Clean extraction without toxic solvents, selective for certain compounds | Expensive equipment, may require co-solvents for optimal extraction |
| Ultrasound-assisted extraction | Enhanced efficiency (70-85% recovery) | Reduced extraction time, lower solvent consumption | Requires specialized equipment |
| Microwave-assisted extraction | Enhanced efficiency (65-85% recovery) | Rapid extraction, reduced solvent use | Potential thermal degradation if not carefully controlled |
Quality Considerations
- High-quality isoliquiritigenin extracts should be standardized to contain at least 95% pure isoliquiritigenin for research purposes, or at least 80% for dietary supplements. For standardized licorice extracts, isoliquiritigenin content should be clearly specified (typically 1-5%).
- Common contaminants to test for include heavy metals (lead, arsenic, cadmium, mercury), pesticide residues, microbial contamination, and mycotoxins. Glycyrrhizin content should also be monitored and specified, as high levels can cause side effects.
- Isoliquiritigenin is sensitive to oxidation, light exposure, and pH changes. Quality products should include appropriate stabilizers and be packaged in light-resistant containers with minimal headspace to prevent oxidation.
- Look for products with third-party testing certificates, GMP (Good Manufacturing Practice) certification, and detailed specification sheets showing purity levels and testing for contaminants.
Sustainable Sourcing
- Licorice is a perennial plant that can be sustainably cultivated with proper agricultural practices. Wild harvesting should be avoided as it can lead to habitat destruction and species depletion.
- Licorice cultivation can have positive environmental impacts when properly managed, as the plant can help prevent soil erosion and can grow in marginal lands not suitable for food crops.
- Fair trade practices should be considered when sourcing licorice, particularly from regions where labor practices may be questionable.
- Look for products with organic certification, sustainable harvesting certifications, or fair trade certifications when available.
Commercial Forms
- Typically available as a yellow crystalline powder with ≥95% purity for research purposes
- Standardized licorice extracts containing specified levels of isoliquiritigenin (typically 1-5%)
- Capsules, tablets, and liquid formulations containing either pure isoliquiritigenin or standardized licorice extracts
Historical Usage
Traditional Medicine Systems
Traditional Chinese Medicine
- Tonifying spleen and qi deficiency
- Moistening the lungs and resolving phlegm
- Clearing heat and detoxifying
- Moderating the effects of other herbs in formulations
- Treating cough, sore throat, and respiratory conditions
- Supporting digestive health
Ayurvedic Medicine
- Respiratory conditions
- Voice disorders
- Digestive complaints
- Skin conditions
- Anti-inflammatory applications
Western Herbal Medicine
- Soothing sore throats and coughs
- Supporting digestive health
- Treating ulcers
- Adrenal support
- Anti-inflammatory applications
Modern Discovery
Isolation: Isoliquiritigenin was first isolated from licorice root in the early 20th century, but detailed characterization and structure elucidation occurred primarily in the 1950s and 1960s.
Research Milestones:
| Period | Developments |
|---|---|
| 1950s-1960s | Structure elucidation and basic chemical characterization of isoliquiritigenin |
| 1970s-1980s | Initial studies on biological activities, particularly anti-inflammatory properties |
| 1990s-2000s | Expanded research into antioxidant, anticancer, and cardioprotective properties; improved extraction and analytical methods |
| 2000s-2010s | Detailed molecular mechanism studies; identification of specific receptor interactions; development of enhanced delivery systems |
| 2010s-Present | Advanced research into neuroprotective effects, sleep promotion, metabolic benefits; synergistic interactions with other compounds; clinical potential exploration |
Cultural Significance
Culinary Uses: Licorice, which contains isoliquiritigenin, has been used as a flavoring agent in confectionery, beverages, and various cuisines across cultures. It is particularly prominent in Northern European, Middle Eastern, and East Asian culinary traditions.
Non Medicinal Applications: Licorice extracts have been used in tobacco products, as a foaming agent in beverages, and in cosmetic formulations. The sweet flavor of licorice (primarily due to glycyrrhizin rather than isoliquiritigenin) made it valuable as a natural sweetener before the widespread availability of sugar.
Evolution Of Usage
Traditional To Modern Transition: While licorice root has been used holistically in traditional medicine systems for millennia, modern research has focused on isolating and studying specific bioactive compounds like isoliquiritigenin. This represents a shift from whole-plant medicine to targeted compound applications based on scientific understanding of mechanisms of action.
Changing Applications: Traditional uses focused primarily on respiratory, digestive, and inflammatory conditions. Modern research has expanded potential applications to include metabolic disorders, neurodegenerative conditions, cancer prevention, and cardiovascular health, based on improved understanding of isoliquiritigenin’s molecular targets and signaling pathway effects.
Historical Safety Observations
Traditional Cautions: Traditional Chinese Medicine texts noted that licorice should be used with caution in cases of fluid retention, hypertension, and certain kidney conditions. These empirical observations align with modern understanding of potential side effects related to glycyrrhizin content (though less applicable to isoliquiritigenin-specific extracts).
Dosage Evolution: Traditional preparations typically used moderate amounts of licorice as part of complex formulations, while modern isoliquiritigenin supplements often provide concentrated amounts that exceed what would be obtained from traditional preparations. This shift in dosing paradigms necessitates careful safety evaluation.
Scientific Evidence
Evidence Rating
Key Studies
Meta Analyses
Limited formal meta-analyses specifically on isoliquiritigenin exist due to the relatively early stage of clinical research on this compound. Most reviews focus on broader categories like licorice flavonoids or chalcones.
Ongoing Trials
Several preclinical studies are investigating isoliquiritigenin’s potential in metabolic disorders, neurodegenerative conditions, and as an adjuvant in cancer therapy, Early-phase clinical trials exploring standardized licorice extracts containing isoliquiritigenin for inflammatory conditions and metabolic health
Research Gaps
Clinical Trials: There is a significant lack of well-designed human clinical trials specifically evaluating isoliquiritigenin’s efficacy and safety across various health conditions. Most evidence comes from preclinical studies.
Bioavailability: More research is needed on enhancing the bioavailability of isoliquiritigenin in humans and determining optimal delivery systems.
Long Term Effects: Studies on long-term safety and efficacy of isoliquiritigenin supplementation in humans are lacking.
Dosage Optimization: Research to establish optimal dosing regimens for specific health conditions is needed.
Drug Interactions: Comprehensive studies on potential interactions with medications are limited.
Evidence By Benefit
Anti Inflammatory
- Moderate
- Strong preclinical evidence from in vitro and animal studies demonstrating inhibition of inflammatory pathways, but limited human clinical data.
Antioxidant
- Moderate
- Well-established antioxidant properties in laboratory studies, with mechanisms including direct ROS scavenging and Nrf2 pathway activation, but limited human clinical data.
Neuroprotective
- Moderate
- Promising preclinical evidence for MAO inhibition, dopamine receptor modulation, and GABA receptor effects, but limited human clinical data.
Sleep Promotion
- Moderate
- Good evidence from animal studies showing effects on sleep architecture through GABAA receptor modulation, but limited human clinical data.
Joint Health
- Moderate
- In vitro studies show inhibition of matrix metalloproteinases and synergistic effects with other compounds for cartilage protection, but limited in vivo and human clinical data.
Metabolic Health
- Moderate
- Animal studies demonstrate improvements in insulin sensitivity and glucose metabolism, but limited human clinical data.
Anticancer
- Moderate
- Extensive in vitro and some animal studies showing multiple anticancer mechanisms, but limited human clinical data.
Expert Opinions
Consensus: Experts generally view isoliquiritigenin as a promising bioactive compound with multiple potential health benefits, particularly for inflammatory conditions, metabolic health, and neuroprotection. However, most emphasize the need for more rigorous human clinical trials before making definitive health claims.
Controversies: Some debate exists regarding the optimal extraction and standardization methods for isoliquiritigenin from natural sources, as well as the relative importance of isoliquiritigenin compared to other licorice compounds in contributing to the plant’s traditional medicinal effects.
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.