01 — Evidence
Evidence Summary
The evidence for ursolic acid is deep in the laboratory and thin in the clinic: broad, repeated anti-cancer activity in cells and animals, only early-phase human trials of an intravenous formulation, and small, mixed oral trials confined to muscle and metabolic health rather than oncology.
Human
Clinical Record
Early-phase; mostly non-oncology
Human cancer data are limited to early Phase I trials of an intravenous liposomal formulation; oral ursolic acid has been tested only outside oncology, with mixed results.
- A Phase I trial of intravenous liposomal ursolic acid reported stable disease in 60% after two cycles — uncontrolled, not proof of efficacy
- No oral ursolic acid has been tested against a cancer endpoint
- Oral muscle, metabolic and anti-inflammatory trials are small and mixed — some positive, some null
Animal
Preclinical Signal
Broad xenograft outcomes
Ursolic acid slowed tumor growth across many cancer types, often without overt toxicity, and preserved muscle in cancer-cachexia models even during chemotherapy.
- Slowed colorectal, prostate, breast, gastric, ovarian, liver and pancreatic tumor models
- Reduced lung-and-liver metastasis in a transgenic prostate model
- Preserved muscle across five cancer-cachexia models, persisting through chemotherapy
In Vitro
Cell Model Data
Mechanistic; concentration-limited
Across diverse cancer lines ursolic acid suppresses survival signaling and triggers apoptosis and ferroptosis — but the effective concentrations sit above the free-compound levels reached orally in people.
- Suppressed STAT3, Wnt/β-catenin, PI3K–AKT–mTOR and ER-stress signaling
- Triggered mitochondrial apoptosis and iron-dependent ferroptosis; reversed EMT markers
- Effective concentrations sit far above the free-compound levels reached orally
Human
Clinical Record
The human cancer record is limited and early. A completed Phase I trial of intravenous liposomal ursolic acid in patients with advanced solid tumors reported stable disease in 60% after two cycles — an uncontrolled tolerability-and-activity signal, not evidence of efficacy — while oral ursolic acid has been tested only outside oncology, in small trials of muscle, metabolic and inflammatory endpoints with mixed results.[29,30,31,37,52,53]
Continue reading — full research detail+
The oncology-setting human data all come from one group's intravenous liposomal formulation: a single-dose dose-escalation study in 63 subjects established a maximum tolerated dose of 98 mg/m² with hepatotoxicity and diarrhea as dose-limiting toxicities,[53] a pharmacokinetic study characterized dose-proportional exposure,[37] and a multiple-dose Phase I trial reported stable disease in 60% of 21 patients after two cycles with no grade ≥3 adverse events.[52] All used an intravenous pharmaceutical formulation — not the oral supplement — and none was controlled, so none establishes efficacy; the one registered oral oncology trial (prostate cancer) was withdrawn before enrolling.
The oral human evidence, all outside oncology, is genuinely mixed. On the positive side, a randomized trial of 24 adults with metabolic syndrome (150 mg/day, 12 weeks) reported metabolic-syndrome remission in 50% versus placebo,[30] one resistance-training trial reported greater handgrip-strength gain,[29] and one reported lower CRP, IL-6 and TNF-α.[31] On the negative side, a double-blind trial of 400 mg/day in resistance-trained men found no additional effect on muscle mass or strength,[54] and a balanced placebo-controlled trial found no change in TNF-α, IL-6 or IL-10.[55] These are small studies in different populations, doses and co-interventions; they do not jointly establish a validated human host benefit.
Signal maturity: early. Human oncology exposure exists only as an intravenous formulation in uncontrolled Phase I trials; oral supplemental ursolic acid has no controlled cancer data, and the oral host-benefit evidence is small and mixed. Every oncology-relevant mechanism on this page rests on animal or cell-model data.
Animal
Preclinical Signal
Tumor-model outcomes are broad and repeatedly positive across colorectal, prostate, breast, gastric, ovarian, hepatocellular and pancreatic systems, with reduced lung-and-liver metastasis in a transgenic prostate model — though most used injected or high oral doses that a human capsule does not reach.[12,15,16]
Continue reading — full research detail+
Ursolic acid slowed colorectal,[2,12] prostate,[15,19] breast,[13,21] gastric,[16] ovarian,[18] hepatocellular[50] and pancreatic[51] tumor growth in xenograft and syngeneic models, several reporting no overt toxicity, and reduced lung-and-liver metastasis in the TRAMP transgenic prostate model.[15]
A distinct and stronger strand is the cachexia work: dietary ursolic acid preserved muscle mass and strength across five mouse models of cancer cachexia and continued to do so during chemotherapy, without changing food intake or tumor burden,[23] and preserved muscle and cardiac tissue in tumor-bearing mice while lowering MuRF1 and STAT3/NF-κB signaling.[24,25]
Signal maturity: developed preclinically. The animal work is the credible translational signal — but delivered by varied routes and doses that cannot be converted into a human tumor exposure. The muscle-preservation strand is the most mature, drawing a direct line to a defined host benefit.
In Vitro
Cell Model Data
Across diverse cancer lines ursolic acid suppresses proliferation, migration and survival signaling (STAT3, Wnt/β-catenin, PI3K–AKT–mTOR), triggers mitochondrial apoptosis and ferroptosis, and reverses EMT markers. The load-bearing caveat is concentration.[5,10,20]
Continue reading — full research detail+
Reported anticancer concentrations cluster around 5–40 µM — for example cytotoxic IC50 values of 35, 47 and 80 µM across three prostate lines[5] and an ion-channel-target IC50 of 13.85 µM.[46] The mechanistic readouts are consistent: PARP cleavage and caspase-9/3 activation on the death side, GPX4 and system-xc− suppression driving ferroptosis, and Snail/Twist reversal on the invasion side.[5,10,16]
These effective concentrations substantially exceed the sub-micromolar free-compound plasma levels achievable from oral ursolic acid (≈0.15 µM in rat), so in-vitro potency reflects what the molecule can do to a cell, not a concentration the body reproduces orally — the gap quantified in the Pharmacokinetics and Administration section below.[39]
Signal maturity: the in-vitro mechanistic case is deep and consistent, but most targets require concentrations above the free-compound plasma level reached orally — which is why the animal work, not these numbers, carries the translational read. Dominant evidence tier: preclinical.
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02 — Pathways
Pathway Interaction Profile
Ursolic acid has cited pathway-level evidence in every functional role, most of it corroborated in living animals — yet each tumour-directed role is held at a partial rating because the concentrations that drive these mechanisms exceed what oral use achieves in humans, and no human cancer outcome exists.
Animal-corroborated across angiogenesis, invasion and stemness in several cancer types, but rated partial: the effective exposure is not reached by oral use, and no human anti-metastatic outcome has been measured.
Block Seeding & Niche Formation
Research concerning formation of supportive pre-metastatic niches at distant sites.
Angiogenesis / VEGF / HIF-1α
In colorectal xenograft, chick-CAM and endothelial assays ursolic acid reduced intratumoral microvessel density and lowered VEGF-A and bFGF, and in a 4T1 breast model it cut growth and metastasis alongside lower VEGF and HIF-1α.[12,13,14]
NF-κB / IL-6 inflammatory axis
In prostate cells and the TRAMP transgenic model ursolic acid suppressed CXCR4 transcription through NF-κB inhibition and reduced lung and liver metastasis.[15]
Prevent Tumor Cell Shedding
Research concerning invasion and escape from existing lesions (EMT and ECM breach).
EMT & metastatic invasion
In gastric cell lines and a xenograft ursolic acid lowered N-cadherin, vimentin, Snail and Twist through the Axl/NF-κB axis, with parallel Snail/Slug suppression reported in breast lines.[16,17]
Prevent Dormant Reactivation
Research concerning wake-up signalling and reactivation of dormant disseminated tumour cells.
Cancer stemness (CD44, ALDH, CD133)
Ursolic acid suppressed ALDH+/CD133+ colon cancer-initiating cells and tumoursphere formation, and reduced the cancer-stem-cell fraction in breast cells via Argonaute-2/PTEN.[1,7]
Ursolic acid suppresses glycolytic metabolism and drives cytotoxic autophagy with ovarian and prostate xenograft support; rated partial for the same exposure ceiling that limits every tumour-directed role.
Glucose Axis Pressure
Research concerning glycolytic ATP production and glycolytic intermediates used by cancer cells.
Aerobic glycolysis (Warburg effect)
Ursolic acid bound KLF5 and blocked PI3K/AKT to suppress glycolysis in ovarian cancer, regulated glucose-6-phosphate and glycolytic flux in a prostate xenograft, and lowered HK2, PKM2, ATP and lactate in breast lines.[18,19,20]
Metabolic Flexibility Suppression
Research concerning metabolic adaptation and switching between fuel sources under pressure.
Autophagy & lysosomal system
Ursolic acid induced cytotoxic autophagy alongside apoptosis via PLK1/AKT-mTOR in a 4T1 breast model, and caspase-independent death with LC3/p62 accumulation through JNK in apoptosis-resistant colorectal cells.[21,22]
Amino Acid / Protein Access Pressure
Research concerning nitrogen availability, amino-acid access, and biomass synthesis.
Amino-acid transport & protein synthesis
In lung-cancer cells, ursolic acid inhibited Na⁺/K⁺-ATPase and thereby blocked amino-acid uptake and cellular protein synthesis, without comparably affecting nucleoside uptake or DNA/RNA synthesis — an in-vitro effect at relatively high concentrations.[57]
The broadest role — STAT3, Wnt/β-catenin, PI3K–AKT–mTOR and ER-stress signalling are suppressed with multiple xenograft confirmations across cancer types — but again capped at partial by achievable human exposure.
Expansion Suppression
Research concerning proliferation, cell-cycle progression, and the capacity of lesions to add durable mass.
JAK/STAT (STAT3)
Ursolic acid inhibited STAT3 phosphorylation and blocked IL-6-induced STAT3 in colon cancer-initiating cells and, by oral treatment, in a hepatocellular carcinoma xenograft.[1,2,50]
Wnt / β-catenin
Wnt/β-catenin was attenuated with tumour selectivity in a colorectal xenograft and inactivated via ↓c-Myc/cyclin D1 and ↑p53 in an osteosarcoma xenograft.[3,4,5]
PI3K–AKT–mTOR
Suppressed through AMPK activation in a drug-resistant breast xenograft and via JNK-driven apoptosis in gemcitabine-resistant pancreatic xenografts.[6,7,51]
Attrition Pressure
Research concerning cellular stress vulnerability and net tumour-cell attrition under sustained conditions.
ER stress & unfolded protein response
Ursolic acid triggered a PERK/CHOP and IRE1-TRAF2-ASK1-JNK cascade driving apoptosis in bladder cells, and PERK/eIF2α/CHOP with apoptosis in ovarian lines.[8,9]
Intrinsic apoptosis and ferroptosis are induced with in-vivo confirmation in colorectal and triple-negative breast models, but at concentrations above achievable oral plasma — a partial rating.
Direct Tumor-Directed Killing
Research concerning regulated tumour-cell death (apoptosis, ferroptosis, necroptosis).
Intrinsic apoptosis (mitochondrial / Bcl-2)
Mitochondrial apoptosis — PARP cleavage, caspase-9/3, ↓Bcl-2/Bcl-XL/Mcl-1 and ↑Bax — was reported across prostate lines and a colorectal xenograft.[5,2]
Ferroptosis (execution)
Ferroptosis was induced via miR-214-3p/STAT3/GPX4 and system xc− suppression in a colorectal xenograft, and via KEAP1 stabilization / NRF2 suppression in a triple-negative breast stem-cell xenograft.[10,11]
Ursolic acid's most distinctive host role is preservation of skeletal muscle; alongside it sits preclinical protection of heart, kidney and normal tissue from chemo- and radiotherapy toxicity. It is rated partial because the muscle and metabolic human data are outside cancer and the cancer-context organ-protection evidence is preclinical.
Host Mitochondrial Reserve
Studies evaluating whether host-cell mitochondrial and energy-production capacity is maintained under metabolic pressure.
Skeletal muscle preservation & cancer cachexia
Ursolic acid was first identified from human muscle-atrophy signatures as a compound that reduces atrophy and induces hypertrophy in mice by enhancing insulin/IGF-I signalling, and it lowers catabolic myostatin. In cancer cachexia specifically, dietary ursolic acid preserved muscle across five tumour models and through chemotherapy, and preserved muscle and cardiac tissue in tumour-bearing mice while lowering MuRF1 and p-STAT3/p-NF-κB. Human trials outside cancer report gains in muscle strength, insulin sensitivity and lower inflammation.[23,24,25,26,27,28,29,30,31] Notably, STAT3 and NF-κB signaling appears in both the tumor-directed and the anti-cachexia work — a mechanistic convergence, though whether it translates into a clinically useful dual effect has not been tested.
Other Organ-System Reserve
Research concerning renal, cardiac, pulmonary, and other non-hepatic organ reserve under stress.
Protection from chemo- and radiotherapy toxicity
In treatment-toxicity models — all preclinical — ursolic acid improved cardiac function during doxorubicin exposure via AKT/eNOS, reduced cisplatin nephrotoxicity while restoring antioxidant enzymes, and prolonged survival after whole-body irradiation. A cranial-irradiation study is mixed: it improved acute learning and memory but exacerbated the radiation-induced loss of hippocampal neurogenesis — reported here in both directions.[32,33,34,35]
Hepatic Resilience & Clearance
Human and preclinical research on hepatic enzyme systems, bile-acid handling, and liver-related markers.
Hepatic anti-fibrotic protection
In a carbon-tetrachloride liver-fibrosis model (non-cancer), ursolic acid prevented hepatotoxicity and fibrosis via the Nrf2/ARE antioxidant pathway, lowering oxidative and inflammatory markers.[36]
Block Seeding & Niche Formation
Research concerning formation of supportive pre-metastatic niches at distant sites.
Reduced tumor blood-vessel density and lowered VEGF and HIF-1α in colorectal and breast animal models.
Glucose Axis Pressure
Research concerning glycolytic ATP production and glycolytic intermediates used by cancer cells.
Aerobic glycolysis (Warburg effect)
Lowered glycolytic enzymes and lactate, with ovarian and prostate xenograft support.
Expansion Suppression
Research concerning proliferation, cell-cycle progression, and the capacity of lesions to add durable mass.
Suppressed STAT3 signaling across colorectal and liver tumor models, including by oral dosing.
Direct Tumor-Directed Killing
Research concerning regulated tumour-cell death (apoptosis, ferroptosis, necroptosis).
Triggered iron-dependent death via GPX4 and NRF2 suppression in colorectal and breast xenografts.
Host Mitochondrial Reserve
Studies evaluating whether host-cell mitochondrial and energy-production capacity is maintained under metabolic pressure.
Skeletal muscle preservation & cancer cachexia
Preserved muscle in cancer-cachexia models even during chemotherapy; human muscle and metabolic gains reported outside cancer.
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03 — Pharmacokinetics
Pharmacokinetics and Administration
The defining fact about ursolic acid is that it is hard to get into the body. Plain ursolic acid is poorly absorbed, cleared within about an hour, and reaches only sub-micromolar blood levels — well below its active range — so most translational work targets delivery rather than the molecule.
Absorption
Ursolic acid has low, variable oral bioavailability — poorly soluble and poorly absorbed. Reported oral plasma levels differ severalfold between preparations, and no reliable absolute bioavailability figure has been established.
Concentration Gap
Active in cells at ~5–40 µM, but oral ursolic acid reaches much lower, highly variable plasma levels — and plasma is an imperfect proxy for tumor-tissue exposure.
Clinical Dose Context
Oral human trials outside oncology used hundreds of mg/day; the intravenous oncology trials reached a maximum tolerated dose of 98 mg/m². No validated oral anti-cancer dose exists.
Formulation Effects
Phospholipid complexes, coamorphous piperine forms, nanocrystals and solid dispersions raise oral exposure ~2.6–19× over plain ursolic acid in animals.
Metabolism
Metabolized by CYP3A4 and CYP2C9 and handled by several drug transporters; disposition is incompletely characterized, and low oral exposure reflects poor solubility, permeability and presystemic metabolism together.
Co-Dosing
A substrate of drug-metabolizing enzymes and transporters, and an in-vitro CYP inhibitor; the clinical size of any interaction from oral supplements is unquantified.
Absorption
Plain ursolic acid is poorly absorbed orally — classified BCS Class IV (low solubility, low permeability). In rats, free oral ursolic acid reached a plasma Cmax of only 68.26 µg/L (≈0.15 µM) in one study,[39] though other oral preparations reach severalfold higher levels with longer half-lives — an herbal-extract preparation, for example, gave a Cmax near 294.8 ng/mL and a ~4.3-hour half-life[58] — so elimination is rapid but formulation- and matrix-dependent rather than a fixed sub-hour value. No robust absolute oral bioavailability (F%) for plain ursolic acid was identified in the literature reviewed here; most studies report only relative improvement from formulation, and a systematic review likewise concludes its pharmacokinetics remain incompletely characterized, complicated by poor solubility, tissue tropism and gut-microbiota interactions.[40,45,60]
Concentration Gap
This is the load-bearing honesty of the profile — though it is a translational gap, not a single precise number. Ursolic acid's anticancer mechanisms operate in cell culture at roughly 5–40 µM (a representative ion-channel-target IC50 is 13.85 µM; prostate cytotoxic IC50s span 35–80 µM). Against that, oral ursolic acid reaches far lower and highly variable plasma levels: one rat study of free ursolic acid reported a Cmax near 0.15 µM,[39] while an oral herbal-extract preparation reached ~294.8 ng/mL[58] — so exposure depends heavily on formulation and matrix, and no human oral study has demonstrated levels comparable to the concentrations used in most cell experiments. Two caveats keep this from being a clean fold-calculation: plasma concentration is an imperfect proxy for tumor-tissue exposure (several oral animal studies report anti-tumor effects despite low plasma levels), and the free unbound fraction is not established. The one human exposure that does reach the low micromolar range came from an intravenous liposomal formulation (peak ~3457 ng/mL, ≈7.6 µM), which then fell roughly ten-fold within two hours — and that is neither oral nor plain ursolic acid.[39,58,46,5,37]
Clinical Dose Context
Human oral dosing has been used only outside oncology, generally at hundreds of milligrams per day (150 mg/day for metabolic syndrome; 400–450 mg/day in muscle and resistance-training trials).[30,29,54] The intravenous liposomal oncology trials escalated to a maximum tolerated dose of 98 mg/m².[52,53] No validated oral anti-cancer dose exists — oral oncology dose-finding has not been done.
Formulation Effects
Because plain ursolic acid is so poorly absorbed, most translational effort targets delivery. Every figure below is animal and relative to plain ursolic acid — none is a human anti-cancer result.
| Formulation | Relative oral exposure | What it adds |
|---|---|---|
| Phospholipid complex | ~4–8.5× | Also extends half-life (0.69 → 8.28 h)[39,40] |
| Coamorphous + piperine | ~5.8× | Bioavailability vs plain crystalline UA; piperine also inhibits CYP3A4[41] |
| Nanocrystals | ~2.6× | Smaller particles dissolve and absorb faster[42] |
| Amorphous solid dispersion | ~19× | ~19× in this rat study; lower Caco-2 efflux[43] |
Metabolism
Ursolic acid's disposition is incompletely characterized. Experimental human recombinant-enzyme work implicates both CYP2C9 and CYP3A4 in its oxidative metabolism, alongside the ABC transporters P-glycoprotein, BCRP and MRP2,[56] with Phase II conjugation also contributing. Its low and variable oral exposure reflects poor solubility, poor permeability and presystemic metabolism together — not any single mechanism, and a short elimination half-life (how fast the drug leaves the circulation once it is there) should not be conflated with first-pass loss (how much reaches the circulation at all). Consistent with a metabolic bottleneck, lung microsomes clear ursolic acid far more slowly than liver microsomes, so non-oral routes bypass much of the first-pass loss — pulmonary delivery raised exposure ~80× over oral in rats.[45,56]
Co-Dosing Considerations
Ursolic acid interacts with drug-metabolizing enzymes and transporters in laboratory systems, but no controlled human interaction study of isolated oral ursolic acid exists — so the flags below reflect mechanistic potential, not a measured clinical effect. Each row is flagged by the most cautious guidance its cited evidence supports.
Discuss whether to combine, separate, or avoid ursolic acid and a medication with your treating oncology team or physician.
| Flag | Interaction |
|---|---|
| Caution | Drugs cleared by CYP enzymes. Ursolic acid isolated from cranberry inhibited intestinal CYP3A potently in vitro (IC50 <10 µM) and may have contributed to a cranberry-juice–midazolam interaction — but that clinical effect was shown for cranberry juice, not isolated ursolic acid. Its hepatic inhibition in human liver microsomes is weak and high-concentration (e.g. CYP2C19 IC50 ~120 µM). The clinical size of any interaction from an oral ursolic acid supplement is unquantified.[47,48,59] |
| Caution | Ursolic acid is itself a substrate of CYP3A4/CYP2C9 and of the transporters P-glycoprotein, BCRP and MRP2, so its own (already low) exposure can shift when combined with drugs that inhibit or induce these enzymes and transporters.[41,56] |
| Monitor | In cell systems, ursolic acid can blunt drug-induced CYP3A4/CYP2B6 expression by antagonizing the PXR and CAR nuclear receptors; whether this alters co-dosed drug levels in people is unknown.[49] |
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04 — Onset & Washout
Onset and Washout
Ursolic acid runs on two timescales: a short pharmacologic one set by its sub-hour half-life, and a slow host one — the muscle and metabolic effects seen in people took weeks of daily dosing.
Immediate Onset
Plasma ursolic acid rises and falls within hours in animal studies, but the half-life is formulation-dependent, and no study has measured how quickly any effect begins or fades in people — onset is not established.
Steady State
A 14-day study of the intravenous liposomal formulation found no drug accumulation; this has not been characterized for oral ursolic acid.
Accumulated Effect
Human oral muscle and metabolic trials assessed their endpoints after 8–12 weeks of daily dosing; when any effect begins was not measured.
Dosing Pattern in Studies
Human trials used continuous daily dosing for 8–12 weeks. This describes how ursolic acid was studied, not a recommended regimen.
Washout
No validated washout period is established for ursolic acid.
Because ursolic acid can inhibit intestinal CYP3A4, any interaction concern should be raised with the care team as soon as the compound is started, not deferred to a washout window. Its short half-life means the compound itself leaves the blood quickly, but that is not an assurance of safety when combining it with other medication.
Two Distinct Clocks
Ursolic acid plausibly acts on two separable timescales, though neither has been directly measured for a defined effect. The direct-pharmacology clock (Clock A) would track plasma exposure — for plain ursolic acid a rapid but formulation-dependent decline, on the order of hours in animal studies. The accumulated-host clock (Clock B) is where the muscle and metabolic endpoints were assessed in people, after weeks of continuous dosing. No study has measured how quickly any pharmacodynamic effect actually begins or fades, so onset and offset for a given endpoint are not established — the "weeks" figure describes when endpoints were measured, not when an effect started.
Steady State
The intravenous 14-day Phase I study found no drug accumulation, with steady-state trough concentrations remaining low (7.31 ng/mL) — the pharmacokinetics on the last day resembled the first. This is consistent with rapid clearance rather than tissue build-up, and means "steady state" for the intravenous formulation is a low, quickly-turning-over level rather than a rising reservoir; oral steady-state behavior has not been characterized.[37]
Dosing Pattern in Studies
The human trials that showed muscle and metabolic effects used continuous daily oral dosing for 8–12 weeks. This describes how ursolic acid was studied, not a recommended regimen, and no comparable schedule has been tested for a cancer endpoint.[30,29]
Washout
No validated washout period exists. The relevant caution is not clearance time but enzyme interaction: because ursolic acid inhibits intestinal CYP3A4, the potential to alter co-dosed drug levels begins as soon as it is taken, so that risk should be raised with the treating team at the start rather than managed by a washout interval. The decision to start, combine, or stop ursolic acid belongs to the reader's medical team.[47]
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05 — Safety
Safety Profile
Human adverse-effect data for ursolic acid is limited to one Phase I study of an intravenous formulation and a handful of oral muscle/metabolic trials; the notable signal is a dose-limiting liver-enzyme elevation at the top intravenous dose.
Gastrointestinal effects — nausea, diarrhea and abdominal distention were the most frequent adverse events, mostly mild to moderate.
Hepatotoxicity was dose-limiting — across the intravenous dose-escalation trials, hepatotoxicity and diarrhea were the dose-limiting toxicities; the maximum tolerated dose was 98 mg/m².
Mostly mild otherwise — other events were largely grade 1–2 (nausea, abdominal distention, transient hematuria, mild rash); the multiple-dose trial reported no grade ≥3 events.
All from an IV formulation — this record is for intravenous liposomal ursolic acid, not oral supplements, and there is no ursolic-acid-specific liver-injury monograph.
Adverse Effects in Human Trials
Human adverse-effect data come from one group's intravenous liposomal formulation, across three studies. A single-dose dose-escalation study in 63 subjects established a maximum tolerated dose of 98 mg/m², with hepatotoxicity and diarrhea as the dose-limiting toxicities at 74–130 mg/m²; other events were mostly grade 1–2 (nausea, abdominal distention, microscopic hematuria, a transient sodium rise, mild rash).[53] A pharmacokinetic study reported similar tolerability — including a grade-3 transaminase elevation — with no drug accumulation over 14 days,[37] and the multiple-dose Phase I trial reported no grade ≥3 adverse events over repeated 14-day cycles.[52] All of this concerns an intravenous pharmaceutical formulation, not oral supplemental ursolic acid, which has not undergone comparable safety characterization.
Liver-safety context
There is no ursolic-acid-specific drug-induced-liver-injury monograph, so the consistent human hepatic signal is the dose-limiting liver-enzyme elevation seen across the intravenous dose-escalation trials above. Notably, ursolic acid's own action on the liver in animal models is protective (anti-fibrotic) — that host benefit is described under Protect, not read here as a safety reassurance. Drug and herb interactions are handled once in the Pharmacokinetics and Administration section; they are not restated here.
06 — Sourcing
Sourcing Guide
Ursolic acid is sold as a standalone supplement and within rosemary, holy basil and loquat-leaf extracts. Because plain ursolic acid is so poorly absorbed, the meaningful distinction between products is delivery — enhanced-absorption formulations versus plain powder — rather than the compound itself. A botanical extract that merely contains ursolic acid is also not pharmacokinetically equivalent to a standardized, enhanced-absorption dose of the isolated compound.
Ursolic Acid Sourcing Guide07 — Literature
References
Last reviewed: August 2026