Oleanolic acid is a pentacyclic triterpene found in olive oil, olive leaves, and many medicinal plants that provides powerful liver protection, anti-inflammatory benefits, and metabolic regulation while supporting cardiovascular and immune health.
Alternative Names: 3β-Hydroxyolean-12-en-28-oic acid, Caryophyllin, OA
Categories: Pentacyclic Triterpene, Phytochemical, Plant Compound
Primary Longevity Benefits
- Hepatoprotective
- Anti-inflammatory
- Antioxidant
- Metabolic regulation
Secondary Benefits
- Cardiovascular support
- Blood glucose regulation
- Immune modulation
- Neuroprotection
- Anti-cancer properties
Mechanism of Action
Oleanolic acid (OA) exerts its diverse biological effects through multiple molecular pathways. As a hepatoprotective agent, OA activates nuclear factor erythroid 2-related factor 2 (Nrf2), which enhances the expression of antioxidant enzymes such as glutathione S-transferase, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase, thereby protecting liver cells from oxidative damage. OA’s anti-inflammatory properties stem from its ability to inhibit nuclear factor-kappa B (NF-κB) signaling, a master regulator of inflammation. By blocking IκB kinase (IKK) activity, OA prevents the translocation of NF-κB to the nucleus and subsequent expression of pro-inflammatory genes, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and various inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).
In metabolic regulation, OA activates AMP-activated protein kinase (AMPK), a key energy sensor that regulates cellular metabolism. This activation leads to improved insulin sensitivity, enhanced glucose uptake in tissues, and reduced lipid accumulation. OA also modulates peroxisome proliferator-activated receptor gamma (PPAR-γ), which further contributes to its beneficial effects on glucose and lipid metabolism. For cardiovascular protection, OA improves endothelial function by enhancing nitric oxide production and reducing oxidative stress in vascular tissues.
It also exhibits anti-hyperlipidemic effects by regulating cholesterol metabolism genes and enhancing bile acid excretion. In the context of neuroprotection, OA crosses the blood-brain barrier and exerts antioxidant and anti-inflammatory effects in neural tissues. It protects neurons from excitotoxicity and oxidative stress-induced damage, potentially benefiting neurodegenerative conditions. OA’s anti-cancer properties involve multiple mechanisms, including the induction of apoptosis in cancer cells through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways.
It inhibits cancer cell proliferation by arresting the cell cycle at various phases and suppresses metastasis by inhibiting matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT). Additionally, OA modulates various signaling pathways involved in cancer progression, including PI3K/Akt, MAPK/ERK, JAK/STAT, and Wnt/β-catenin pathways. In the immune system, OA exhibits immunomodulatory effects by regulating the activity of T cells, B cells, macrophages, and natural killer cells, helping to balance immune responses. Recent research has also identified OA as an activator of DAF-16 (the C.
elegans homolog of FOXO transcription factors in mammals), which may contribute to its longevity-promoting effects observed in model organisms. This activation of stress resistance pathways may translate to enhanced cellular resilience and longevity in humans, though more research is needed to confirm this mechanism in human subjects.
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.
Typical supplemental dosages range from 100-500 mg per day of standardized oleanolic acid, though clinical evidence for optimal human dosing is limited. Most studies showing benefits have been conducted in animal models with doses that would translate to this range in humans.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Liver protection | 100-200 mg daily | Used in China as a hepatoprotective agent at these doses; may be effective for mild liver conditions and as a preventive measure |
| Metabolic syndrome/Type 2 diabetes | 200-400 mg daily | Preliminary research suggests potential benefits for glucose regulation and insulin sensitivity at these doses |
| Inflammatory conditions | 200-500 mg daily | Higher doses may be needed for significant anti-inflammatory effects; should be used under medical supervision |
| Cardiovascular health | 150-300 mg daily | May help support healthy blood pressure and lipid levels as part of a comprehensive approach |
| Antioxidant support | 100-300 mg daily | Lower doses may be sufficient when used as part of an antioxidant regimen |
| Longevity/general health | 100-200 mg daily | Lower maintenance doses may be appropriate for general health support and potential longevity benefits |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Adults (18-65) | 100-500 mg daily based on specific health goals | Start with lower doses and increase gradually if needed |
| Seniors (65+) | 100-300 mg daily | Lower doses recommended initially; monitor for potential drug interactions as polypharmacy is common in this age group |
| Children and adolescents | Not recommended | Insufficient safety data for these age groups; should not be used without medical supervision |
Titration
Starting Dose: 100 mg daily
Adjustment Protocol: May increase by 100 mg every 2-4 weeks if needed and well-tolerated
Maximum Recommended Dose: 500 mg daily for most conditions
Cycling Recommendations
Protocol: Some practitioners recommend 8-12 weeks on, followed by 2-4 weeks off
Rationale: May help prevent tolerance development and allow assessment of effects, though clinical evidence for the necessity of cycling is limited
Special Populations
Pregnancy Lactation: Not recommended due to insufficient safety data
Liver Impairment: Use with caution and at reduced doses; monitor liver function
Kidney Impairment: Limited data; use with caution and at reduced doses
Autoimmune Conditions: Consult healthcare provider due to immunomodulatory effects
Research Limitations
Most dosing recommendations are extrapolated from animal studies and limited human trials. Individual responses may vary significantly. Clinical trials with standardized preparations are needed to establish optimal therapeutic dosages for specific conditions.
Bioavailability
Absorption Rate
Very low, approximately 0.7% for oral administration
Factors Affecting Absorption
Poor water solubility (practically insoluble in water), High lipophilicity, Extensive first-pass metabolism in the liver, P-glycoprotein efflux in the intestinal epithelium, Extensive enterohepatic circulation
Enhancement Methods
| Method | Description | Evidence Level |
|---|---|---|
| Liposomal formulations | Encapsulation in phospholipid bilayers can increase bioavailability by up to 10-15 times compared to standard formulations | Moderate – several animal studies and limited human data |
| Nanoparticle delivery systems | Solid lipid nanoparticles and polymeric nanoparticles can enhance solubility and intestinal permeability | Moderate – primarily animal studies |
| Phospholipid complexes | Formation of phytosomes with phospholipids improves membrane permeability and absorption | Moderate – animal studies show 2-4 fold increase in bioavailability |
| Micronization | Reducing particle size increases surface area and dissolution rate | Moderate – demonstrated in in vitro and animal studies |
| Co-administration with piperine | Piperine inhibits P-glycoprotein efflux and hepatic metabolism | Limited – theoretical benefit based on studies with other compounds |
| Emulsification | Self-emulsifying drug delivery systems improve solubility in gastrointestinal fluids | Moderate – shown effective in preclinical studies |
| Cyclodextrin complexation | Forms inclusion complexes that enhance water solubility | Limited – primarily in vitro data |
Metabolism
Primary Pathways: Primarily metabolized in the liver through phase I (oxidation, hydroxylation) and phase II (glucuronidation, sulfation) reactions
Major Metabolites: Various hydroxylated derivatives and glucuronide/sulfate conjugates
Half Life: Approximately 10-15 hours in humans based on limited pharmacokinetic studies
Distribution
Protein Binding: High (>99%) binding to plasma proteins, primarily albumin
Tissue Distribution: Accumulates primarily in the liver, with lower concentrations in other tissues; limited blood-brain barrier penetration
Excretion
Primary Route: Primarily eliminated through biliary excretion and feces
Secondary Routes: Minor urinary excretion of metabolites
Timing Recommendations
Optimal Timing: Best taken with meals containing some fat to enhance absorption
Frequency: Due to relatively long half-life, once or twice daily dosing is typically sufficient
Special Considerations: Absorption may be reduced when taken with high-fiber meals; spacing from fiber supplements is recommended
Safety Profile
Safety Rating
Acute Toxicity
LD50: Oral LD50 in mice >2000 mg/kg body weight
Observations: Demonstrates relatively low acute toxicity in animal studies
Side Effects
| Effect | Severity | Frequency | Notes |
|---|---|---|---|
| Gastrointestinal discomfort | Mild to moderate | Uncommon | May include nausea, stomach upset, or diarrhea, particularly at higher doses |
| Hypoglycemia | Mild to moderate | Rare | Theoretical risk due to glucose-lowering effects; may be of concern in diabetic individuals on medication |
| Allergic reactions | Mild to severe | Very rare | As with any plant compound, allergic reactions are possible but uncommon |
| Headache | Mild | Rare | Reported occasionally in limited human studies |
| Liver enzyme elevations | Mild to moderate | Very rare | Paradoxical effect given its hepatoprotective properties; seen primarily at very high doses in animal studies |
Contraindications
| Condition | Rationale |
|---|---|
| Pregnancy and lactation | Insufficient safety data; potential hormonal effects |
| Bile duct obstruction | May increase bile production and exacerbate condition |
| Scheduled surgery | Discontinue 2 weeks before surgery due to potential anticoagulant effects |
| Severe liver disease | While hepatoprotective, effects in severe liver disease are not well-studied |
| Known hypersensitivity | Avoid if allergic to oleanolic acid or plants containing high amounts (olive, clove, etc.) |
Drug Interactions
| Drug Class | Interaction Type | Severity | Mechanism | Management |
|---|---|---|---|---|
| Antidiabetic medications | Potentiation | Moderate | May enhance hypoglycemic effects | Monitor blood glucose levels; dose adjustment of diabetes medications may be necessary |
| Anticoagulants/Antiplatelets | Potentiation | Moderate | May enhance anticoagulant effects | Monitor for increased bleeding risk; consider dose adjustments |
| Cytochrome P450 substrates | Inhibition | Moderate | May inhibit CYP3A4 and other CYP enzymes | Monitor for increased effects of drugs metabolized by these pathways |
| P-glycoprotein substrates | Inhibition | Moderate | May inhibit P-gp efflux transporter | Monitor for increased drug levels of P-gp substrates |
| Hepatotoxic medications | Protective/Antagonistic | Variable | May reduce hepatotoxicity of some drugs but could interfere with metabolism | Use with caution; monitor liver function |
Upper Limit
Established UL: No officially established upper limit
Research Observations: Doses up to 500 mg daily appear well-tolerated in limited human studies
Safety Concerns: Doses above 500 mg daily have not been well-studied in humans and should be approached with caution
Long Term Safety
Chronic Toxicity Data: Limited long-term human data; animal studies suggest good tolerability with chronic administration
Bioaccumulation: No evidence of significant bioaccumulation in tissues
Adaptation Effects: No significant tolerance or adaptation effects reported
Special Populations
Pediatric: Not recommended due to insufficient safety data
Geriatric: Start with lower doses; monitor for drug interactions
Hepatic Impairment: Use with caution despite hepatoprotective effects; start with lower doses
Renal Impairment: Limited data; use with caution at reduced doses
Monitoring Recommendations
Suggested Tests: Consider baseline and periodic liver function tests with long-term use
Frequency: Before beginning supplementation and every 6-12 months during long-term use
Warning Signs: Persistent gastrointestinal distress, signs of hypoglycemia, unusual fatigue, or jaundice
Regulatory Status
Fda Status
Classification: Generally recognized as a dietary ingredient in the United States
Approved Claims: No FDA-approved health claims
Structure Function Claims: Limited to general statements about supporting liver health, antioxidant activity, and healthy inflammatory response
Regulatory History: Has not been the subject of significant FDA regulatory actions
New Dietary Ingredient Status: Not formally submitted as a New Dietary Ingredient (NDI) notification for standalone use, though present in many traditional foods and herbs
International Status
Eu
- Not approved as a Novel Food ingredient in isolated form
- Present in traditional foods and botanicals with a history of use
- No approved health claims under European Food Safety Authority (EFSA) regulations
- May be used in food supplements when derived from traditional food sources with a history of use
Canada
- Natural Health Product (NHP) ingredient
- Ingredient in licensed Natural Health Products
- Limited to traditional claims for liver support and general health
- Must comply with Natural Health Products Regulations
Australia
- Complementary medicine ingredient
- Ingredient in listed complementary medicines
- Limited to general health maintenance claims
- Regulated by the Therapeutic Goods Administration (TGA)
China
- Approved drug and traditional medicine ingredient
- Registered drug for liver protection; ingredient in traditional Chinese medicines
- Approved for treatment of hepatitis and liver protection as a pharmaceutical
- Has achieved pharmaceutical status for specific indications
Japan
- Existing food ingredient
- Present in traditional foods and Kampo medicines
- No specific approved health claims
- Not specifically regulated as a functional food ingredient
India
- Ayurvedic ingredient
- Present in traditional Ayurvedic formulations
- Traditional Ayurvedic uses recognized
- Regulated under AYUSH ministry guidelines
Pharmaceutical Status
Approved Drugs: Approved as a hepatoprotective drug in China
Clinical Trials: Various phases of clinical trials for liver disorders, metabolic conditions, and as an adjunct therapy for certain cancers
Orphan Drug Status: No orphan drug designations
Investigational Status: Under investigation for multiple conditions but not designated as an Investigational New Drug (IND) in the US
Quality Standards
Pharmacopeial Monographs: Official monograph with quality standards, No official United States Pharmacopeia monograph, No official European Pharmacopoeia monograph
Industry Standards: Various industry specifications exist for commercial products, typically requiring 60-98% purity depending on intended use
Labeling Requirements
Us: Must be listed as an ingredient; no specific warnings required
Eu: Must be listed as an ingredient; no specific warnings required
Other Regions: Variable requirements; may need traditional use statements in some jurisdictions
Import Export Regulations
Restrictions: No specific restrictions on import/export in most countries
Documentation: Standard documentation for botanical ingredients typically required
Tariff Classifications: Typically classified under botanical extracts or natural products
Regulatory Trends
Increasing Scrutiny: Growing interest from regulatory bodies as research expands
Harmonization Efforts: No specific international harmonization efforts for oleanolic acid
Future Outlook: Likely to remain available as a dietary ingredient while pharmaceutical applications continue to be explored
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating | Research Notes |
|---|---|---|---|
| Ursolic Acid | Structurally similar triterpene that often co-occurs naturally with oleanolic acid. Both compounds share similar molecular targets but may have complementary effects on different pathways. Together they may provide enhanced anti-inflammatory, antioxidant, and metabolic benefits. | 4 | Multiple studies have shown that the combination of oleanolic and ursolic acids provides greater benefits than either compound alone, particularly for liver protection and metabolic regulation. |
| Berberine | Berberine activates AMPK through different mechanisms than oleanolic acid. The combination may provide enhanced metabolic benefits, particularly for glucose regulation and lipid metabolism. | 3 | Preclinical studies suggest the combination may be particularly effective for metabolic syndrome and non-alcoholic fatty liver disease. |
| Quercetin | Quercetin enhances the bioavailability of oleanolic acid by inhibiting P-glycoprotein efflux and may provide complementary antioxidant effects through different mechanisms. | 3 | In vitro and animal studies show enhanced cellular uptake and efficacy when combined. |
| Resveratrol | Both compounds activate sirtuin pathways and have complementary effects on inflammation and oxidative stress. Resveratrol may enhance the longevity-promoting effects of oleanolic acid. | 2 | Limited but promising preclinical evidence for synergistic effects on cellular aging and metabolic health. |
| Vitamin E (Mixed Tocopherols) | Vitamin E provides complementary antioxidant protection through direct radical scavenging, while oleanolic acid works primarily through Nrf2 activation and enzyme induction. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Milk Thistle (Silymarin) | Both compounds have hepatoprotective effects through different mechanisms. Silymarin enhances glutathione production and membrane stability, while oleanolic acid activates Nrf2 and inhibits inflammatory pathways. | 3 | Several studies suggest enhanced liver protection when combined, particularly against toxin-induced damage. |
| Curcumin | Curcumin provides complementary anti-inflammatory effects through inhibition of different inflammatory mediators. May also enhance bioavailability through effects on intestinal transporters. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Piperine | Enhances bioavailability of oleanolic acid by inhibiting P-glycoprotein efflux and first-pass metabolism in the liver. | 2 | Demonstrated to enhance bioavailability of many compounds with similar absorption limitations; specific studies with oleanolic acid are limited. |
| EGCG (from Green Tea) | Complementary effects on metabolic pathways and antioxidant systems. EGCG may enhance the cellular uptake of oleanolic acid. | 2 | In vitro studies suggest synergistic effects on cancer cells and in metabolic regulation. |
| Omega-3 Fatty Acids | Complementary anti-inflammatory effects through different pathways. Omega-3s primarily affect eicosanoid production, while oleanolic acid inhibits NF-κB signaling. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Maslinic Acid | Structurally similar triterpene often found alongside oleanolic acid in olive products. Has complementary effects on glucose metabolism and inflammation. | 3 | Natural co-occurrence suggests evolutionary synergy; several studies on olive extracts containing both compounds show enhanced benefits. |
| Phosphatidylcholine | Forms complexes with oleanolic acid that enhance membrane permeability and absorption. Also provides complementary benefits for liver health. | 3 | Phytosome formulations of oleanolic acid with phosphatidylcholine show significantly enhanced bioavailability. |
Antagonistic Compounds
Cost Efficiency
Relative Cost
Medium to high
Cost Factors
| Factor | Impact | Description |
|---|---|---|
| Extraction complexity | Moderate to high impact on cost | Requires multi-step extraction and purification processes to achieve high purity |
| Source material availability | Moderate impact on cost | Available from multiple plant sources, but concentration is relatively low requiring large amounts of raw material |
| Purification requirements | High impact on cost | Achieving pharmaceutical-grade purity requires sophisticated purification techniques |
| Formulation complexity | High impact on cost for enhanced formulations | Bioavailability-enhanced formulations (liposomes, nanoparticles) add significant cost |
| Scale of production | Moderate impact on cost | Currently produced at relatively small scale compared to mass-market supplements |
Cost Per Effective Dose
Standard Formulations: $1.00-$3.00 per day for basic extracts (100-200 mg)
Enhanced Formulations: $3.00-$10.00 per day for bioavailability-enhanced formulations
Pharmaceutical Grade: $5.00-$15.00 per day for high-purity pharmaceutical preparations
Price Trends
Historical Trend: Gradually decreasing over the past decade as extraction and purification methods improve
Future Projections: Likely to continue moderate decrease as production scales increase and more efficient extraction methods are developed
Market Factors: Growing demand for natural products may offset some price decreases
Cost Comparison
| Comparable Compound | Relative Cost | Efficacy Comparison |
|---|---|---|
| Ursolic acid | Similar | Similar mechanisms and benefits; often used interchangeably |
| Milk thistle extract (silymarin) | Lower than oleanolic acid | Similar hepatoprotective effects through different mechanisms; more extensive clinical research |
| Curcumin | Similar for standard extracts; higher for enhanced formulations | Similar anti-inflammatory effects through different mechanisms; more extensive clinical research |
| Resveratrol | Higher than oleanolic acid | Some overlapping benefits; different primary mechanisms |
| Berberine | Lower than oleanolic acid | Similar metabolic benefits through different mechanisms; more extensive clinical research |
Value Analysis
Cost Benefit Assessment: Moderate value for general health support; potentially high value for specific conditions like liver protection
Factors Affecting Value: Poor bioavailability of standard formulations reduces cost-effectiveness, Enhanced formulations offer better value despite higher cost due to improved absorption, Value increases for individuals with specific health concerns addressed by oleanolic acid’s mechanisms
Optimal Value Approaches: Using olive leaf extracts standardized for oleanolic acid content may provide better value than isolated compound, Combination products leveraging synergistic compounds may offer better overall value, Enhanced delivery systems significantly improve value despite higher cost
Economic Accessibility
Affordability Assessment: Moderately accessible for regular use in developed countries; may be cost-prohibitive in developing regions
Insurance Coverage: Generally not covered by health insurance except in China where pharmaceutical forms are approved drugs
Cost Reduction Strategies: Bulk purchasing can reduce per-dose cost, Dietary sources (olive products, culinary herbs) provide small amounts at lower cost, Seasonal purchasing when raw material harvests reduce extraction costs
Sustainability Economics
Environmental Cost Factors: Moderate environmental footprint from extraction processes and solvent use
Sustainable Sourcing Impact: Use of agricultural by-products (olive leaves from olive oil production) improves economic and environmental sustainability
Long Term Economic Outlook: Likely to become more economically viable as production scales increase and more efficient extraction methods are developed
Stability Information
Shelf Life
Pure Compound: 3-5 years when stored properly
Standardized Extracts: 2-3 years when stored properly
Formulated Products: 1-3 years depending on formulation and packaging
Storage Recommendations
Temperature: Store at room temperature (15-25°C); avoid exposure to high temperatures
Light: Protect from direct light; amber or opaque containers recommended
Humidity: Store in a dry place; avoid exposure to high humidity
Packaging: Airtight containers preferred; nitrogen-flushed packaging may extend shelf life
Degradation Factors
| Factor | Impact | Prevention |
|---|---|---|
| Oxidation | Moderate susceptibility; can lead to formation of oxidation products at the C-3 hydroxyl group and C-12 double bond | Use of antioxidants (e.g., vitamin E, rosemary extract) in formulations; oxygen-barrier packaging |
| Heat | Relatively stable at normal temperatures; significant degradation occurs above 80°C | Avoid exposure to high temperatures during processing and storage |
| Light | Moderate photosensitivity; prolonged exposure to UV light can cause degradation | Opaque or amber containers; storage away from direct light |
| pH extremes | Stable in mildly acidic to neutral conditions; degradation accelerates in strongly acidic or alkaline environments | Buffer formulations to maintain optimal pH range (5-7) |
| Microbial contamination | Susceptible to microbial degradation in liquid formulations or high-humidity conditions | Appropriate preservatives in liquid formulations; proper drying and storage of plant materials |
| Enzymatic degradation | Plant enzymes can degrade oleanolic acid in crude extracts | Heat inactivation of enzymes during extraction; proper drying of plant materials |
Compatibility With Delivery Systems
Capsules: High compatibility with vegetable or gelatin capsules
Tablets: Moderate compatibility; may require appropriate excipients for proper disintegration
Liquid Formulations: Poor solubility in aqueous systems; requires solubilizers or emulsifiers
Liposomes: Good compatibility; enhances stability and bioavailability
Nanoparticles: Good compatibility with various nanoparticle systems; may enhance stability
Stability Enhancing Additives
| Additive | Mechanism | Typical Concentration |
|---|---|---|
| Vitamin E (mixed tocopherols) | Antioxidant protection | 0.1-0.5% |
| Ascorbyl palmitate | Antioxidant protection | 0.1-0.3% |
| Rosemary extract | Natural antioxidant protection | 0.2-0.5% |
| Phospholipids | Formation of protective complexes | 10-30% relative to oleanolic acid |
| Medium-chain triglycerides | Protective matrix in lipid formulations | Variable based on formulation |
Stability Testing Methods
Accelerated stability testing (elevated temperature and humidity), Real-time stability testing under recommended storage conditions, Photostability testing according to ICH guidelines, HPLC analysis for quantification and detection of degradation products, Dissolution testing for solid dosage forms
Special Handling Considerations
Manufacturing: Minimize exposure to heat during processing; consider inert gas protection for sensitive operations
Transportation: Maintain temperature control; avoid extreme conditions
Reconstitution: For powdered formulations, reconstitute immediately before use in appropriate vehicles
Sourcing
Synthesis Methods
| Method | Description | Efficiency | Commercial Viability |
|---|---|---|---|
| Semi-synthesis from betulin | Chemical conversion of betulin (abundant in birch bark) to oleanolic acid | Moderate; multi-step process | Limited commercial application due to complexity and cost |
| Total chemical synthesis | Complete chemical synthesis from basic precursors | Low; complex multi-step process | Not commercially viable due to complexity and cost |
| Biotransformation | Microbial or enzymatic conversion of related triterpenes | Variable depending on specific process | Emerging technology with potential for future commercial application |
Natural Sources
| Source | Scientific Name | Concentration | Notes |
|---|---|---|---|
| Olive leaves and olive oil | Olea europaea | 0.4-1.0% in olive leaves; trace amounts in extra virgin olive oil | One of the richest and most commercially significant sources |
| Clove | Syzygium aromaticum | 0.3-0.8% in dried flower buds | Traditional medicinal plant with significant oleanolic acid content |
| Apple fruit peel | Malus domestica | 0.1-0.3% in dried peel | Concentrated in the waxy cuticle of the fruit skin |
| Jujube | Ziziphus jujuba | 0.2-0.5% in dried fruit | Traditional Chinese medicinal plant |
| Forsythia fruit | Forsythia suspensa | 0.2-0.7% in dried fruit | Used in traditional Chinese medicine |
| Sage | Salvia officinalis | 0.1-0.4% in dried leaves | Culinary and medicinal herb |
| Rosemary | Rosmarinus officinalis | 0.1-0.3% in dried leaves | Culinary and medicinal herb |
| Oregano | Origanum vulgare | 0.1-0.2% in dried leaves | Culinary herb with medicinal properties |
| Thyme | Thymus vulgaris | 0.05-0.2% in dried leaves | Culinary herb with medicinal properties |
| Lavender | Lavandula angustifolia | 0.05-0.15% in dried flowers | Aromatic and medicinal plant |
| Privet fruit | Ligustrum lucidum | 0.3-0.6% in dried fruit | Used in traditional Chinese medicine |
Extraction Methods
Solvent extraction
Supercritical CO2 extraction
Alkaline hydrolysis followed by acid precipitation
Ultrasound-assisted extraction
Microwave-assisted extraction
Quality Considerations
- Commercial supplements typically standardized to 60-98% oleanolic acid content
- Similar triterpenes such as ursolic acid (not harmful but affects standardization); synthetic analogues
- HPLC, LC-MS, and NMR are standard methods for identity and purity confirmation
- Wild harvesting of some source plants may raise sustainability issues; cultivation and use of agricultural by-products (e.g., olive leaves from olive oil production) are more sustainable approaches
Commercial Forms
| Form | Purity | Applications |
|---|---|---|
| Crude extract | 10-40% oleanolic acid | Traditional medicine, starting material for further purification |
| Standardized extract | 60-80% oleanolic acid | Dietary supplements, functional foods |
| High-purity isolate | 90-98% oleanolic acid | Pharmaceutical research, high-quality supplements |
| Enhanced delivery formulations | Variable, typically using standardized extract | Bioavailability-enhanced supplements (liposomes, phytosomes, nanoparticles) |
Historical Usage
Traditional Medicine Systems
| System | Applications | Historical Preparations | Historical Period |
|---|---|---|---|
| Traditional Chinese Medicine (TCM) | Liver protection and treatment of hepatitis, Treatment of inflammatory conditions, Management of diabetes and metabolic disorders, Cardiovascular support | Decoctions of plants rich in oleanolic acid such as Ligustrum lucidum fruit, Forsythia suspensa fruit preparations, Herbal formulations containing multiple oleanolic acid-rich plants | Documented use for over 2,000 years |
| Ayurvedic Medicine | Treatment of inflammatory conditions, Liver support, Skin conditions | Herbal oils and pastes containing oleanolic acid-rich plants, Decoctions and powders of medicinal herbs | Ancient usage, though not specifically identified as oleanolic acid |
| Mediterranean Traditional Medicine | Olive leaf preparations for fever and infections, Olive oil for general health maintenance, Herbal preparations for inflammatory conditions | Olive leaf teas and extracts, Culinary use of herbs rich in oleanolic acid (rosemary, sage, oregano), Olive oil as both food and medicine | Dating back to ancient Greek and Roman civilizations |
Modern Discovery
Isolation: First isolated and characterized in the early 20th century
Identification In Traditional Remedies: Recognized as an active component in many traditional medicinal plants in the mid-20th century
Pharmacological Characterization: Systematic investigation of biological activities began in the 1970s-1980s
Key Researchers: Liu J. – Pioneering work on hepatoprotective effects, Honda T. and Rounds B.V. – Development of synthetic derivatives, Pollier J. and Goossens A. – Elucidation of biosynthetic pathways
Evolution Of Usage
Pre 1950: Used primarily in traditional medicine without knowledge of active compounds
1950s 1970s: Identification as active component in traditional remedies; early pharmacological studies
1980s 1990s: Recognition of hepatoprotective properties; development as a drug for liver disorders in China
2000s Present: Expanded research into metabolic, anti-inflammatory, and anti-cancer properties; development of enhanced formulations to overcome bioavailability limitations
Cultural Significance
| Culture | Significance |
|---|---|
| Chinese | Plants containing oleanolic acid have been valued in traditional medicine and incorporated into many classical formulations |
| Mediterranean | Olive and its derivatives, rich in oleanolic acid, have been central to diet, medicine, and cultural practices |
| European herbalism | Many European medicinal herbs containing oleanolic acid (sage, rosemary) have been used for centuries for various ailments |
Historical Safety Record
Traditional Use Safety: Generally considered safe based on centuries of traditional use
Documented Adverse Effects: Few historical reports of adverse effects when used in traditional preparations
Historical Contraindications: Limited documentation of specific contraindications in traditional texts
Key Historical Texts
| Text | Relevance |
|---|---|
| Shennong Ben Cao Jing (Divine Farmer’s Materia Medica) | Early Chinese pharmacopeia describing several plants now known to contain oleanolic acid |
| De Materia Medica by Dioscorides | Ancient Greek text describing medicinal uses of olive and other plants containing oleanolic acid |
| Chinese Pharmacopoeia | Modern official recognition of oleanolic acid as a hepatoprotective agent |
Transition To Modern Use
Scientific Validation: Modern research has validated many traditional uses, particularly for liver protection and anti-inflammatory effects
Pharmaceutical Development: Developed as a drug for liver disorders in China; ongoing research for other applications
Supplement Market Emergence: Increasingly available as a dietary supplement, often as part of olive leaf extracts or specialized formulations
Scientific Evidence
Evidence Rating
Rating Rationale: Moderate evidence from numerous preclinical studies and limited human trials. Strong mechanistic understanding but lacks large-scale clinical trials for most applications.
Key Studies
Meta Analyses
Limited formal meta-analyses exist specifically for oleanolic acid interventions due to the heterogeneity of study designs and limited number of clinical trials, Systematic reviews of triterpenes including oleanolic acid suggest consistent anti-inflammatory and hepatoprotective effects across multiple studies
Ongoing Trials
Clinical evaluation of oleanolic acid formulations for metabolic syndrome (various phases), Investigation of oleanolic acid-enriched olive extracts for cardiovascular health, Studies on enhanced bioavailability formulations of oleanolic acid, Evaluation of oleanolic acid as an adjunct therapy in non-alcoholic fatty liver disease
Research Gaps
Clinical Validation: Large-scale, well-designed clinical trials are needed to validate preclinical findings
Bioavailability: Further research on enhancing bioavailability in humans is critical
Long Term Effects: Studies on long-term safety and efficacy are lacking
Dosing Optimization: Optimal dosing regimens for specific conditions need to be established
Drug Interactions: More comprehensive evaluation of potential drug interactions is needed
Contradictory Findings
Liver Effects: While generally hepatoprotective, some studies suggest potential hepatotoxicity at very high doses
Cancer Effects: Complex effects on cancer pathways with both pro- and anti-cancer effects reported depending on context and cancer type
Bioavailability Impact: Disagreement on the clinical relevance of poor bioavailability, with some researchers suggesting local gastrointestinal effects may be beneficial regardless of systemic absorption
Expert Opinions
Consensus View: Generally recognized as a promising natural compound with multiple health benefits, particularly for liver health and metabolic conditions
Areas Of Disagreement: Optimal formulations, dosing, and specific clinical applications remain subjects of debate
Future Directions: Focus on enhanced delivery systems and targeted clinical trials is recommended by most experts
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.