Ursolic Acid

(3β)-3-hydroxyurs-12-en-28-oic acid
Evidence Level
Limited
3 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Pentacyclic triterpenoid found in apple peel, holy basil, oregano, rosemary, loquat, and many medicinal plants. Generated enormous interest from preclinical mouse studies showing muscle anabolism and brown fat induction. HUMAN trials have largely been NEGATIVE for muscle/strength outcomes — a notable preclinical-to-clinical translation failure.

Studied Dose MUSCLE/STRENGTH: 400-450 mg/day divided (Bang 2014: 450 mg POSITIVE; Pereira 2020: 400 mg NEGATIVE). LOQUAT: 500 mg/day → 50 mg UA NEGATIVE. <1% bioavailability — phytosomal preferred.
Active Compound Ursolic acid (UA) — pentacyclic triterpenoid carboxylic acid (C30H48O3, MW 456.7). Also called urson, prunol, or malol

Benefits

Single small positive RT trial (n=16) showed strength benefit

Bang 2014 (, Korean J Physiol Pharmacol) randomized 16 healthy men to resistance training (RT) alone (n=7) or RT + ursolic acid 450 mg/day (n=9) for 8 weeks. UA group showed greater strength gains and elevated serum irisin (myokine that activates browning of white fat). Limited by very small sample. Single positive trial frequently cited but with substantial selection/multiple comparison concerns.

Larger trials FAILED to confirm muscle/strength benefits

Cho 2016 (, Pusan University) RCT in 54 healthy adults given 500 mg/day loquat leaf extract (delivering 50.94 mg UA) for 12 weeks: NO differences in muscle strength, muscle mass, or physical performance vs placebo. Pereira 2020 (, Clin Nutr) RCT in 22 active men on high-protein diet + RT given 400 mg/day UA: NO additional effect on muscle strength or mass beyond what RT + protein achieved. Net: rigorous trials show NO meaningful effect on muscle outcomes.

Mouse data showed dramatic effects (poor translation to humans)

Kunkel 2012 (PLoS One) showed UA decreased adiposity, glucose intolerance, and fatty liver disease while increasing skeletal muscle mass and brown fat in diet-induced obese mice. Striking results drove massive clinical interest — but human translation has been disappointing. Possible reasons: poor oral bioavailability in humans, dose-effect mismatches, species-specific muscle anabolism mechanisms. Important reminder of preclinical-clinical translation gap.

Anti-inflammatory and antioxidant effects (modest)

UA inhibits NF-κB, reduces TNF-α, IL-6, and COX-2 expression in vitro and animal models. Antioxidant via Nrf2 pathway activation. These mechanisms may underlie some claimed benefits in skin aging, cardiovascular health, and metabolic syndrome — though again, human RCT data are limited and mostly small.

Theoretical metabolic benefits (animal studies)

In animals, UA increased uncoupling protein 1 (UCP1) expression, brown fat mass, and energy expenditure — promising for obesity. systematic review reviewed 17 eligible studies on UA and adipose/muscle tissue, concluding mechanistic effects are clear but human clinical translation is limited and inconsistent.

Mechanism of action

1

IGF-1/Akt/mTOR pathway activation (mouse muscle)

In mouse muscle, UA promotes hypertrophy via IGF-1 receptor signaling → Akt phosphorylation → mTORC1 activation → S6K1 → protein synthesis. Also suppresses atrophy genes (atrogin-1, MuRF-1). This was the headline finding in Kunkel 2011 Cell Metabolism that drove enormous clinical interest. The pathway is real in mice; translation to humans appears blunted or absent at clinically achievable doses.

2

Brown fat induction via UCP1 (mouse)

UA increases brown adipose tissue (BAT) markers including uncoupling protein 1 (UCP1), triggering thermogenesis. Combined with skeletal muscle hypertrophy effect, drove obesity-prevention enthusiasm in animal models. Human BAT response to oral UA has not been demonstrated.

3

Irisin elevation (small human evidence)

Bang 2014 showed UA + RT increased serum irisin levels — irisin is a myokine that promotes browning of subcutaneous white fat. The mechanistic chain UA → irisin → BAT browning is the most plausible link between mouse and human data, though replicate human studies are needed.

4

Anti-inflammatory: NF-κB inhibition

UA blocks IκB phosphorylation and degradation, preventing NF-κB nuclear translocation. Reduces TNF-α, IL-1β, IL-6 production. Mechanism comparable to many other anti-inflammatory triterpenes (boswellic acids, betulinic acid). Effects observable at concentrations achievable in inflamed tissues.

Clinical trials

1
Bang 2014 — UA + Resistance Training in Men (Small Positive)
PubMed

Randomized controlled trial (Bang HS, Seo DY, Chung YM, Oh KM, Park JJ, Arturo F, Jeong SH, Kim N, Han J 2014, Korean J Physiol Pharmacol 18(5):441-446, doi:10.4196/kjpp.2014.18.5.441, PMID 25352765).

16 healthy male participants (mean age 29.4 years, BMI 27.1) randomly assigned to resistance training alone (RT n=7) or RT + UA (RT+UA n=9) for 8 weeks. UA dose 450 mg/day (3x150 mg).

RT+UA group showed greater strength gains, body fat reduction, and serum irisin elevation compared to RT-only group. Authors concluded UA + RT augments muscle strength via irisin pathway. SIGNIFICANT LIMITATIONS: very small sample (n=16 total, 7 vs 9), short duration, single-center, no published replication. Frequently cited as the 'positive UA trial' but the evidence base is fragile.

2
Cho 2016 — Loquat UA in Healthy Adults (Negative)
PubMed

Randomized double-blind placebo-controlled trial (Cho YH, Lee SY, Kim CM, Kim ND, Choe S, Lee CH, Shin JH 2016, Evid Based Complement Altern Med 2016:4374940, doi:10.1155/2016/4374940). NCT02401113.

54 healthy adults randomized to 500 mg/day loquat leaf extract (delivering 50.94 mg ursolic acid) or placebo for 12 weeks. Outcomes: peak torque/body weight at 60° knee extension, handgrip strength, skeletal muscle mass, physical performance, metabolic parameters at baseline, 4 weeks, 12 weeks.

NO DIFFERENCES in muscle strength, muscle mass, or physical performance between UA and placebo groups at any time point. Authors noted the dose may have been too low to observe effect. Counters small positive trials and is the largest, longest, most rigorous human UA trial to date with negative outcome on the primary muscle endpoints.

3
Pereira 2020 — UA + High-Protein Diet + RT in Men (Negative)
PubMed

Double-blind placebo-controlled trial (Pereira RM, Botezelli JD, da Cruz Rodrigues KC, Mekary RA, Cintra DE, Pauli JR, da Silva ASR, Ropelle ER, Pimentel GD 2020, Clin Nutr 39(11):3325-3332, doi:10.1016/j.clnu.2020.02.030, PMID 32593524).

22 young men randomized to control + RT (CON, n=12, 400 mg/day placebo) or UA + RT (UA, n=10, 400 mg/day UA) for 8 weeks. Both groups consumed ~1.6 g/kg protein and performed identical RT program.

Both groups showed significant increases in body weight and BMI from training/diet effect. NO ADDITIONAL effect of UA on muscle strength or mass beyond what RT + high-protein diet alone achieved. Conclusion: 'Ursolic acid has no additional effect on muscle strength and mass in active men undergoing a high-protein diet and resistance training.' Most well-controlled trial with directly relevant population (RT + adequate protein) and clearly negative result.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated at doses studied; no serious adverse events reported in clinical trials.
Mild GI upset (nausea, abdominal discomfort) at high doses or empty stomach.
Hepatotoxicity at very high doses in animals — clinical relevance unknown.
Possible drug interactions via CYP modulation at high doses.
Pregnancy/lactation: no safety data; avoid.

Important Drug interactions

CYP1A2/3A4 substrates: UA may modulate at high doses; clinical relevance unclear.
Statins: theoretical interaction; minimal clinical evidence.
Anti-diabetic drugs: animal data suggest UA may have mild glucose-lowering effects; monitor.
Anticoagulants: theoretical mild antiplatelet effect (rare).
Most medications: no significant documented interactions at typical supplement doses.

Frequently asked questions about Ursolic Acid

What is Ursolic Acid?

Pentacyclic triterpenoid found in apple peel, holy basil, oregano, rosemary, loquat, and many medicinal plants.

What does Ursolic Acid do?

In mouse muscle, UA promotes hypertrophy via IGF-1 receptor signaling → Akt phosphorylation → mTORC1 activation → S6K1 → protein synthesis. Also suppresses atrophy genes (atrogin-1, MuRF-1). In clinical research, Ursolic Acid has been studied for single small positive rt trial (n=16) showed strength benefit, larger trials failed to confirm muscle/strength benefits, mouse data showed dramatic effects (poor translation to humans).

Who should take Ursolic Acid?

Ursolic Acid may be most relevant for people interested in athletic performance, muscle & recovery, anti-inflammatory. It has been clinically studied for single small positive rt trial (n=16) showed strength benefit, larger trials failed to confirm muscle/strength benefits, mouse data showed dramatic effects (poor translation to humans). As with any supplement, consult your healthcare provider before starting, especially if you have medical conditions or take prescription medications.

How long does Ursolic Acid take to work?

Most clinical trial effects appear over weeks of consistent use; individual response varies. Acute or same-day effects (where applicable) typically appear within hours, but most cumulative benefits — particularly those affecting biomarkers, mood, sleep quality, or chronic symptoms — require 4-12 weeks of regular use to fully assess. If you don't notice benefit after 12 weeks at the appropriate dose, it may not be your responder.

When is the best time to take Ursolic Acid?

For performance or energy goals, Ursolic Acid is typically taken 30-60 minutes before exercise or in the morning. Some people take it with food to reduce GI sensitivity; others prefer empty-stomach timing for faster absorption. Always check product labeling and follow personalized guidance from your healthcare provider.

Is Ursolic Acid worth taking?

Ursolic Acid has limited clinical evidence (Evidence Level 2/5 on NutraSmarts) — preliminary research suggests potential benefit, but more rigorous trials are needed. Whether it's worth taking depends on your specific goals, what you've already tried, your budget, and your overall supplement strategy. The honest framing: no supplement is essential for most people, and lifestyle factors (sleep, exercise, diet, stress management) typically produce larger effects than any single supplement. Ursolic Acid is most worth trying if its evidence-supported uses align with your specific goals.

What is the recommended dosage of Ursolic Acid?

The clinically studied dose for Ursolic Acid is MUSCLE/STRENGTH: 400-450 mg/day divided (Bang 2014: 450 mg POSITIVE; Pereira 2020: 400 mg NEGATIVE). LOQUAT: 500 mg/day → 50 mg UA NEGATIVE. <1% bioavailability — phytosomal preferred.. Always follow product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Ursolic Acid used for?

Ursolic Acid is studied for single small positive rt trial (n=16) showed strength benefit, larger trials failed to confirm muscle/strength benefits, mouse data showed dramatic effects (poor translation to humans). Bang 2014 (, Korean J Physiol Pharmacol) randomized 16 healthy men to resistance training (RT) alone (n=7) or RT + ursolic acid 450 mg/day (n=9) for 8 weeks.