Ursolic acid is a pentacyclic triterpene found in apple peels, holy basil, and rosemary that enhances muscle growth and preservation, reduces inflammation, and provides antioxidant protection while supporting metabolic and cardiovascular health.
Alternative Names: 3β-hydroxy-urs-12-en-28-oic acid, Malol, Prunol, UA
Categories: Pentacyclic Triterpene, Phytochemical, Plant Compound
Primary Longevity Benefits
- Anti-inflammatory
- Antioxidant
- Metabolic regulation
- Muscle preservation
Secondary Benefits
- Neuroprotection
- Cardiovascular support
- Blood glucose regulation
- Immune modulation
- Anti-cancer properties
- Skin health
Mechanism of Action
Ursolic acid (UA) exerts its diverse biological effects through multiple molecular pathways and cellular targets. As an anti-inflammatory agent, UA inhibits nuclear factor-kappa B (NF-κB) signaling by preventing the phosphorylation and degradation of IκB, thereby blocking the nuclear translocation of NF-κB and subsequent expression of pro-inflammatory genes. This leads to reduced production of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). UA also inhibits cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), further contributing to its anti-inflammatory effects.
The antioxidant properties of UA stem from both direct and indirect mechanisms. It directly scavenges reactive oxygen species (ROS) and indirectly activates nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of cellular antioxidant responses. Nrf2 activation leads to increased expression of antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutathione S-transferase (GST). In metabolic regulation, UA activates AMP-activated protein kinase (AMPK), a key energy sensor that regulates cellular metabolism.
This activation enhances glucose uptake in skeletal muscle, improves insulin sensitivity, and promotes fatty acid oxidation. UA also modulates peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, which further contributes to its beneficial effects on glucose and lipid metabolism. One of UA’s most distinctive properties is its ability to promote muscle growth and prevent muscle wasting. It inhibits atrophy-related gene expression by blocking the activation of atrogin-1 and MuRF1, key mediators of muscle protein degradation.
UA also enhances insulin-like growth factor-1 (IGF-1) signaling in muscle tissue, promoting protein synthesis and muscle hypertrophy. This mechanism is particularly relevant for its potential applications in sarcopenia and age-related muscle loss. In the context of neuroprotection, UA crosses the blood-brain barrier and exerts multiple beneficial effects. It activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which promotes neuronal survival and inhibits apoptosis.
UA also reduces neuroinflammation through its effects on microglia and astrocytes, and enhances brain-derived neurotrophic factor (BDNF) expression, supporting neuronal health and plasticity. For cardiovascular protection, UA 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. UA’s anti-cancer properties involve multiple mechanisms, including the induction of apoptosis through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways.
It inhibits cancer cell proliferation by arresting the cell cycle at various phases, particularly G1 and G2/M, through modulation of cyclins and cyclin-dependent kinases. UA also suppresses metastasis by inhibiting matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT). Additionally, UA modulates various signaling pathways involved in cancer progression, including PI3K/Akt, MAPK/ERK, JAK/STAT, and Wnt/β-catenin pathways. In the immune system, UA 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 identified UA 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. UA also promotes autophagy, a cellular ‘housekeeping’ process that removes damaged proteins and organelles, which is crucial for cellular health and longevity.
For skin health, UA stimulates collagen synthesis, inhibits collagenase activity, and protects against UV-induced damage, making it valuable for anti-aging skincare applications.
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 150-600 mg per day of standardized ursolic 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. Enhanced delivery systems (liposomal, nanoparticle) may allow for lower effective doses.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Muscle preservation/growth | 300-600 mg daily | Higher doses within this range may be more effective for muscle-related benefits; enhanced delivery systems recommended due to poor bioavailability |
| Metabolic syndrome/Type 2 diabetes | 200-450 mg daily | Preliminary research suggests potential benefits for glucose regulation and insulin sensitivity at these doses |
| Inflammatory conditions | 300-500 mg daily | Anti-inflammatory effects appear dose-dependent; should be used under medical supervision for inflammatory conditions |
| Cardiovascular health | 150-300 mg daily | May help support healthy blood pressure and lipid levels as part of a comprehensive approach |
| Neuroprotection | 200-400 mg daily | Limited human data; dosage based on animal studies showing neuroprotective effects |
| Skin health (topical applications) | 0.1-2% concentration in topical formulations | Commonly used in anti-aging skincare products; absorption through skin may bypass first-pass metabolism |
| Longevity/general health | 150-300 mg daily | Lower maintenance doses may be appropriate for general health support and potential longevity benefits |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Adults (18-50) | 150-600 mg daily based on specific health goals | Start with lower doses and increase gradually if needed; enhanced delivery systems recommended |
| Older adults (50+) | 200-450 mg daily | May be particularly beneficial for this age group due to muscle preservation effects; monitor for potential drug interactions |
| Seniors (65+) | 150-300 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: 150 mg daily
Adjustment Protocol: May increase by 150 mg every 2-4 weeks if needed and well-tolerated
Maximum Recommended Dose: 600 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
Formulation Considerations
Standard Formulations: May require higher doses due to poor bioavailability
Enhanced Delivery Systems: Liposomal, nanoparticle, or phospholipid complex formulations may allow for 30-50% lower doses
Combination Products: When combined with synergistic compounds like curcumin or piperine, lower doses may be effective
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 0.5-1% 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, Large molecular size limiting passive diffusion
Enhancement Methods
| Method | Description | Evidence Level |
|---|---|---|
| Liposomal formulations | Encapsulation in phospholipid bilayers can increase bioavailability by up to 10-20 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 showing 5-15 fold increases in bioavailability |
| Phospholipid complexes | Formation of phytosomes with phospholipids improves membrane permeability and absorption | Moderate – animal studies show 3-6 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, with one study showing a 10-fold increase in UA bioavailability | Moderate – demonstrated in animal studies |
| Self-emulsifying drug delivery systems (SEDDS) | Improves solubility in gastrointestinal fluids through spontaneous emulsion formation | Moderate – shown effective in preclinical studies |
| Cyclodextrin complexation | Forms inclusion complexes that enhance water solubility | Limited – primarily in vitro data |
| Co-administration with fatty meals | Dietary fat can enhance absorption of lipophilic compounds like UA | Limited – theoretical benefit based on studies with similar compounds |
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 8-12 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 adipose tissue, muscle, and skin; limited blood-brain barrier penetration though some studies show CNS effects
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
Pharmacokinetic Profile
Absorption Characteristics: Slow and incomplete absorption from the gastrointestinal tract
Peak Plasma Concentration: Typically reached 1.5-3 hours after oral administration of standard formulations
Bioavailability Enhancement Factor: Enhanced delivery systems can improve bioavailability by 5-20 fold depending on the specific formulation
Clinical Implications
Dosing Considerations: Higher doses may be required with standard formulations to achieve therapeutic plasma levels
Formulation Selection: Enhanced delivery systems are strongly recommended for clinical applications
Monitoring Recommendations: Plasma level monitoring may be valuable in research settings but is not typically necessary for supplement use
Safety Profile
Safety Rating
Acute Toxicity
LD50: Oral LD50 in mice >8000 mg/kg body weight
Observations: Demonstrates relatively low acute toxicity in animal studies with a wide safety margin
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 | Seen primarily at very high doses in animal studies; monitor liver function with long-term use |
| Muscle cramps | Mild | Rare | Possibly related to effects on muscle metabolism; typically transient |
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 | Effects in severe liver disease are not well-studied |
| Known hypersensitivity | Avoid if allergic to ursolic acid or plants containing high amounts (apple peel, rosemary, 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 |
| Anabolic steroids | Potentiation | Moderate | May enhance anabolic effects due to complementary mechanisms | Use with caution; monitor for enhanced effects or side effects |
| Hepatotoxic medications | Variable | Moderate | Potential for both protective effects and metabolic interactions | Use with caution; monitor liver function |
Upper Limit
Established UL: No officially established upper limit
Research Observations: Doses up to 600 mg daily appear well-tolerated in limited human studies
Safety Concerns: Doses above 600 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; 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
Clinical Trial Safety Data
Phase 1 Trials: Limited phase 1 trials show good tolerability at doses up to 300 mg daily
Adverse Events: Most reported adverse events were mild and transient
Discontinuation Rates: Low discontinuation rates due to adverse effects in available studies
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 muscle 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 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
- Traditional medicine ingredient
- Ingredient in traditional Chinese medicines
- Traditional uses recognized in TCM context
- Regulated under traditional medicine framework
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, particularly in Tulsi products
- Traditional Ayurvedic uses recognized
- Regulated under AYUSH ministry guidelines
Pharmaceutical Status
Approved Drugs: No approved pharmaceutical products containing ursolic acid as the active ingredient
Clinical Trials: Various phases of clinical trials for muscle preservation, 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: No official monograph specifically for ursolic acid, though present in monographs for certain plants, 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, particularly for muscle preservation claims
Harmonization Efforts: No specific international harmonization efforts for ursolic acid
Future Outlook: Likely to remain available as a dietary ingredient while pharmaceutical applications continue to be explored
Cosmetic Regulations
Us: Permitted in cosmetic products; must be listed in ingredients
Eu: Permitted in cosmetic products; must be listed in INCI name
Claims Limitations: Anti-aging and skin health claims must be substantiated and not cross into drug claim territory
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating | Research Notes |
|---|---|---|---|
| Oleanolic Acid | Structurally similar triterpene that often co-occurs naturally with ursolic 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 ursolic and oleanolic acids provides greater benefits than either compound alone, particularly for liver protection and metabolic regulation. |
| Curcumin | Complementary anti-inflammatory and antioxidant effects through different molecular pathways. Curcumin primarily works through NF-κB inhibition and Nrf2 activation, while ursolic acid has additional effects on muscle metabolism and IGF-1 signaling. | 3 | Recent phase 1 clinical trial demonstrated safety and feasibility of the combination. Preclinical studies suggest enhanced anti-cancer and anti-inflammatory effects when combined. |
| Piperine | Enhances bioavailability of ursolic acid by inhibiting P-glycoprotein efflux and first-pass metabolism in the liver. One study showed approximately 10-fold increase in ursolic acid bioavailability when combined with piperine. | 3 | Animal studies have demonstrated significant enhancement of ursolic acid’s hepatoprotective effects when combined with piperine. |
| Resveratrol | Both compounds activate sirtuin pathways and have complementary effects on inflammation and oxidative stress. Resveratrol may enhance the longevity-promoting effects of ursolic acid. | 2 | Limited but promising preclinical evidence for synergistic effects on cellular aging and metabolic health. |
| Leucine | Leucine activates mTOR signaling to promote protein synthesis, while ursolic acid inhibits protein breakdown pathways. This combination may provide enhanced muscle-building effects. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Creatine | Creatine enhances muscle energy production and hydration, while ursolic acid promotes protein synthesis and inhibits breakdown. Together they may provide enhanced muscle-building effects. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Quercetin | Quercetin enhances the bioavailability of ursolic acid by inhibiting P-glycoprotein efflux and may provide complementary antioxidant effects through different mechanisms. | 2 | In vitro and animal studies show enhanced cellular uptake and efficacy when combined. |
| Vitamin D | Both compounds support muscle health through different mechanisms. Vitamin D regulates calcium homeostasis and muscle protein synthesis, while ursolic acid inhibits muscle protein breakdown. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Omega-3 Fatty Acids | Complementary anti-inflammatory effects through different pathways. Omega-3s primarily affect eicosanoid production, while ursolic acid inhibits NF-κB signaling. | 2 | Theoretical synergy based on complementary mechanisms; limited direct studies on the combination. |
| Berberine | Berberine activates AMPK through different mechanisms than ursolic acid. The combination may provide enhanced metabolic benefits, particularly for glucose regulation and lipid metabolism. | 2 | Preclinical studies suggest the combination may be particularly effective for metabolic syndrome and non-alcoholic fatty liver disease. |
| Phosphatidylcholine | Forms complexes with ursolic acid that enhance membrane permeability and absorption. Also provides complementary benefits for liver health. | 3 | Phytosome formulations of ursolic acid with phosphatidylcholine show significantly enhanced bioavailability. |
| Taurine | Taurine supports muscle function through osmotic regulation and calcium handling, while ursolic acid promotes protein synthesis and inhibits breakdown. May provide enhanced muscle benefits. | 1 | Theoretical synergy based on complementary mechanisms; very limited direct studies on the combination. |
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 |
| Growing market demand | Moderate impact on cost | Increasing interest in muscle preservation and anti-aging applications has increased demand and production |
Cost Per Effective Dose
Standard Formulations: $1.50-$4.00 per day for basic extracts (150-300 mg)
Enhanced Formulations: $4.00-$12.00 per day for bioavailability-enhanced formulations
High Potency Formulations: $5.00-$15.00 per day for high-dose (450-600 mg) formulations
Price Trends
Historical Trend: Gradually decreasing over the past decade as extraction and purification methods improve and production scales increase
Future Projections: Likely to continue moderate decrease as production scales increase and more efficient extraction methods are developed
Market Factors: Growing demand for muscle preservation supplements may offset some price decreases
Cost Comparison
| Comparable Compound | Relative Cost | Efficacy Comparison |
|---|---|---|
| Oleanolic acid | Similar | Similar mechanisms for anti-inflammatory and antioxidant effects; ursolic acid has stronger evidence for muscle preservation |
| Leucine | Lower than ursolic acid | Different mechanism for muscle support; more extensive clinical research but potentially less comprehensive benefits |
| Creatine | Much lower than ursolic acid | Different mechanism for muscle support; more extensive clinical research and established efficacy for muscle performance |
| Resveratrol | Similar for standard extracts; higher for enhanced formulations | Some overlapping benefits; different primary mechanisms |
| HMB (β-hydroxy β-methylbutyrate) | Similar to ursolic acid | Similar application for muscle preservation; more clinical research but potentially less comprehensive benefits |
Value Analysis
Cost Benefit Assessment: Moderate value for general health support; potentially high value for specific applications like muscle preservation in aging
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 older adults seeking muscle preservation benefits, Value increases when used as part of a comprehensive approach to healthy aging
Optimal Value Approaches: Using apple peel extracts or holy basil extracts standardized for ursolic 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
Cost Reduction Strategies: Bulk purchasing can reduce per-dose cost, Dietary sources (apple peels, 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 (apple peels from juice 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
Target Demographic Value
Athletes: Moderate to high value for recovery and performance enhancement
Aging Population: High value for muscle preservation and metabolic health
General Wellness: Moderate value as part of a comprehensive supplement regimen
Specific Health Conditions: Potentially high value for individuals with specific metabolic or inflammatory conditions
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 ursolic 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
Topical Formulations: Excellent compatibility with various cosmetic bases; good stability in properly formulated products
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 ursolic 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
Formulation Stability Considerations
PH Stability Range: Most stable at pH 5-7; avoid strongly acidic or alkaline formulations
Excipient Compatibility: Compatible with most common pharmaceutical excipients; avoid strong oxidizing agents
Solvent Compatibility: Soluble in ethanol, methanol, acetone, and other organic solvents; practically insoluble in water
Sourcing
Synthesis Methods
| Method | Description | Efficiency | Commercial Viability |
|---|---|---|---|
| Semi-synthesis from oleanolic acid | Chemical conversion of oleanolic acid (more abundant in some sources) to ursolic 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 |
|---|---|---|---|
| Apple peel | Malus domestica | 0.3-1.0% in dried peel | One of the richest and most commercially significant sources; concentration is highest in waxy cuticle |
| Cranberry | Vaccinium macrocarpon | 0.3-0.9% in dried fruit | Significant commercial source with high ursolic acid content |
| Holy Basil (Tulsi) | Ocimum sanctum | 0.5-2.0% in dried leaves | Traditional Ayurvedic medicinal plant with high ursolic acid content |
| Rosemary | Rosmarinus officinalis | 0.2-1.0% in dried leaves | Culinary and medicinal herb with significant ursolic acid content |
| Thyme | Thymus vulgaris | 0.1-0.5% in dried leaves | Culinary herb with medicinal properties |
| Oregano | Origanum vulgare | 0.1-0.4% in dried leaves | Culinary herb with medicinal properties |
| Sage | Salvia officinalis | 0.2-0.7% in dried leaves | Culinary and medicinal herb |
| Lavender | Lavandula angustifolia | 0.1-0.3% in dried flowers | Aromatic and medicinal plant |
| Bilberry | Vaccinium myrtillus | 0.1-0.4% in dried fruit | Traditional medicinal berry |
| Peppermint | Mentha piperita | 0.1-0.3% in dried leaves | Culinary and medicinal herb |
| Loquat leaf | Eriobotrya japonica | 0.5-1.5% in dried leaves | Traditional East Asian medicinal plant |
| Bearberry | Arctostaphylos uva-ursi | 0.4-1.2% in dried leaves | Traditional medicinal plant |
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% ursolic acid content
- Similar triterpenes such as oleanolic 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., apple peels from juice production) are more sustainable approaches
Commercial Forms
| Form | Purity | Applications |
|---|---|---|
| Crude extract | 10-40% ursolic acid | Traditional medicine, starting material for further purification |
| Standardized extract | 60-80% ursolic acid | Dietary supplements, functional foods |
| High-purity isolate | 90-98% ursolic acid | Pharmaceutical research, high-quality supplements |
| Enhanced delivery formulations | Variable, typically using standardized extract | Bioavailability-enhanced supplements (liposomes, phytosomes, nanoparticles) |
| Topical formulations | 0.1-2% ursolic acid in cosmetic bases | Anti-aging skincare products, dermatological preparations |
Industry Trends
- Increasing use in sports nutrition, anti-aging supplements, and metabolic health products
- Development of high-yield cultivars and extraction from agricultural waste streams
- Growing demand driving increased production and research into enhanced delivery systems
Historical Usage
Traditional Medicine Systems
| System | Applications | Historical Preparations | Historical Period |
|---|---|---|---|
| Traditional Chinese Medicine (TCM) | Treatment of inflammatory conditions, Liver and gallbladder support, Wound healing, Management of diabetes and metabolic disorders | Decoctions of loquat leaf (Eriobotrya japonica), Preparations of Chinese hawthorn (Crataegus pinnatifida), Herbal formulations containing multiple ursolic acid-rich plants | Documented use for over 2,000 years |
| Ayurvedic Medicine | Treatment of inflammatory conditions, Skin disorders, Wound healing, Metabolic balance | Holy Basil (Tulsi) preparations, Herbal oils and pastes containing ursolic acid-rich plants, Decoctions and powders of medicinal herbs | Ancient usage, though not specifically identified as ursolic acid |
| European Traditional Medicine | Treatment of inflammatory conditions, Wound healing, Digestive support, General health maintenance | Infusions and tinctures of rosemary, sage, and thyme, Culinary use of herbs rich in ursolic acid, Topical preparations for skin conditions | Dating back to ancient Greek and Roman civilizations |
| Native American Medicine | Treatment of inflammatory conditions, Wound healing, Fever reduction | Preparations of bearberry (Arctostaphylos uva-ursi), Cranberry preparations, Various herbal infusions | Traditional usage predating European contact |
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: Kunkel SD and Adams CM – Pioneering work on muscle effects, Liu J – Research on hepatoprotective effects, Habtemariam S – Comprehensive work on neuroprotective effects
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 anti-inflammatory and antioxidant properties; early research on metabolic effects
2000s 2010s: Discovery of muscle-preserving effects; expanded research into metabolic, anti-cancer, and neuroprotective properties
2010s Present: Development of enhanced delivery systems; clinical trials; growing use in sports nutrition and anti-aging supplements
Cultural Significance
| Culture | Significance |
|---|---|
| Indian | Holy Basil (Tulsi), rich in ursolic acid, has been revered as a sacred plant with medicinal properties for thousands of years |
| Chinese | Plants containing ursolic acid have been valued in traditional medicine and incorporated into many classical formulations |
| Mediterranean | Culinary herbs rich in ursolic acid (rosemary, sage, thyme) have been central to both cuisine and traditional medicine |
| Native American | Cranberry and bearberry, both rich in ursolic acid, have been used medicinally by various tribes |
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 ursolic acid |
| Charaka Samhita | Ancient Ayurvedic text describing medicinal uses of Tulsi and other plants containing ursolic acid |
| De Materia Medica by Dioscorides | Ancient Greek text describing medicinal uses of rosemary, sage, and other plants containing ursolic acid |
Transition To Modern Use
Scientific Validation: Modern research has validated many traditional uses, particularly for anti-inflammatory and metabolic effects
Pharmaceutical Development: Currently in various stages of pharmaceutical development for multiple applications
Supplement Market Emergence: Increasingly available as a dietary supplement, often as part of apple peel extracts, holy basil extracts, or specialized formulations for muscle preservation
Historical Preparation Methods
Decoctions: Boiling plant materials in water to extract water-soluble components (though ursolic acid itself is poorly water-soluble)
Tinctures: Extraction in alcohol, which more effectively extracts ursolic acid
Infused Oils: Extraction into oils for topical applications
Culinary Use: Incorporation of ursolic acid-rich herbs in cooking, providing small but regular dietary intake
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 ursolic acid interventions due to the heterogeneity of study designs and limited number of clinical trials, Systematic reviews of triterpenes including ursolic acid suggest consistent anti-inflammatory, antioxidant, and metabolic benefits across multiple studies
Ongoing Trials
Clinical evaluation of ursolic acid formulations for muscle preservation in aging (various phases), Investigation of ursolic acid for metabolic syndrome and insulin resistance, Studies on enhanced bioavailability formulations of ursolic acid, Evaluation of ursolic acid as an adjunct therapy in neurodegenerative conditions
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
Muscle Effects: While most studies show anabolic effects, some have failed to demonstrate significant muscle growth in certain models
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 muscle preservation, metabolic health, and neuroprotection
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
Population Specific Evidence
Aging Population: Strongest evidence for potential benefits in age-related muscle loss and metabolic dysfunction
Athletes: Limited but promising evidence for performance enhancement and recovery
Metabolic Disorders: Moderate evidence for benefits in insulin resistance and metabolic syndrome
Neurological Conditions: Emerging evidence for neuroprotective effects in various models of neurodegeneration
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.