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Ursolic Acid

Ursolic Acid is a molecule found in apple peels, and in the Ayurveda herb known as Holy Basil. No human interventions exist right now, but ursolic acid appears to be a promising body recomposition agent; able to increase muscle mass and decrease fat mass. May be anti-fertility, however.

Our evidence-based analysis on ursolic acid features 64 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Ursolic Acid

1Sources and Structure


Ursolic Acid is a pentacyclic triterpenoid that is very widely distributed in food products and herbs.

Major sources (Food products or common supplements) include:

This thing looks to be as common in herbs as Vitamin C, which is in pretty much everything; a lot of herbs were omitted from this list that are not common supplements or otherwise not exceedingly high in Ursolic Acid content


Glycosides (attached to one or more sugars) of Ursolic Acid include urs-12-en-3β-ol-28-oic acid 3β-D-glucopyranosyl-4'-octadecanoate (a glycoside of ursolic acid from the plant Lantana camara.[16])

Compounds that are structurally related to Ursolic acid and are not glycosides thereof include Corosolic acid,[17] Oleanolic acid,[18] Maslinic Acid,[19] Latanolic Acid,[7] Camarin,[7] and Pomolic Acid.[7] These structures are all pentacyclic triterpenoids due to their five-ringed structures, with seemingly similar effects (although differing from one another in potency).



A study investigating the intestinal uptake of ursolic acid (from an ethanolic extract of Sambucus chinensis) found that a dose contributing 80mg/kg bodyweight ursolic acid had about an 0.6% oral bioavailability based on the compound's AUC.[20] When incubated with Caco-2 cells, basolateral (side of membrane facing away from the lumen) recovery of ursolic acid ranges between 15.9+/-3.2% and 19.0+/-4.2%.[11] There do not appear to be significant difference when comparing Ursolic Acid bioavailability in isolation following oral administration to Ursolic Acid from plant sources (in this study, the spice known as Sage).[11]

Very poor intestinal absorption rates

2.2Serum parameters

In a study using an oral dose of 80mg/kg bodyweight Ursolic Acid in rats it was found that; the half-life was 4.3 hours, the Tmax was 1 hour, the Cmax was 294.8ng/mL (645.5nM) and the AUC to infinity was 1175.3 ng/h/ml.[20] The half-life in this study was replicated in humans given an injection of Ursolic Acid microsomes (3.9+/-2.1 hours), and other parameters attained in this study following injections of an average dose of 98mg/m2 (based on body surface area, average is 1.7m2 for adult males) were a Tmax of 4 hours, Cmax of 3404.6+/-748.8ng/mL, and an AUC0-∞ of 9918.4+/-1215.2ng/h/mL with a Clearance rate of 10.0+/-1.2L/h/m2.[21]

Due to the poor bioavailability, low serum levels appear to be achieved; despite this, a half-life of around four hours exists and oral administration seems to peak one hour after ingestion


Following oral administraiton of 0.2% of the diet to rats over a period of 11 weeks (estimated dose of 40mg/kg), Ursolic Acid can be detected in the kidney plasma (2.83+/-0.47nmol/mg) and the kidney tissue itself (3.51+/-0.57nmol/mg);[22] no other organs were tested, and lower doses (0.05-0.1%) were not detected.


One study that gave rats either Ursolic Acid or Oleanolic Acid (related structure) noted that at the higher doses of both supplements that there was a detectable serum level of the other, suggesting that interconversion between the two exists after oral administration in rats.[22]

3Cardiovascular Health


Concentrations of 10uM and 30uM of ursolic acid in the drinking water of ApoE knockout rats, over 24 weeks, can accelerate atherogenic plaque formation.[23] These results may not be highly extrapolatable, as ApoE knockout mice have screwed lipid profiles already.[24]

Conversely, a low dose of Ursolic Acid (0.2% of the diet) fed to mice with diabetes induced by streptozotocin and lacking an LDL receptor found that ursolic acid was able to reduce by 53% the inherent lesions that occur in the endothelium with diabetes; suggesting a protective but not necessarily rehabilitative effect.[25] This protective effect was more potent than resveratrol at 0.2%. Ursolic acid was also able to reduce monocyte migration to the endothelium, which is seen as an inflammatory response (and thus, ursolic acid in part protects via anti-inflammatory means).[25]

The discord between the two studies above[24][25] has been investigated by a third part.[26] In general, the two cannot be directly compared due to large differences in methodology.

At this moment in time, it appears Ursolic Acid is not a significant concern for cardiovascular health and may be protective; more studies to iron out the differences would be needed


One study noted that, in vitro, in human umbilical vein endothelial cells (HUVECs) as well as cells taken from humans, ursolic acid was able to prevent cell differentiation and induce cell death in both cell cultures potently at 12.5uM, and in isolated cells at 6.25uM. Lower doses did not have any influence on cell death, and 3.125uM has a non-significant increase in cell differentation relative to controls in isolated cells.[23]

4Interactions with Glucose Metabolism


Ursolic acid acts as a inhibitor of the PTP1B enzyme[27][28] with studies looking at its IC50 value (concentration required to inhibit half of the active enzyme) in the range of 3.6+/-0.2μM,[29] 3.08μM,[27] and 3.9μM;[30] repeatedly demonstrated potency. The PTP1B enzyme in a negative regulator of the insulin receptor (suppressing its effects[31]) and is a therapeutic target for the treatment of high blood glucose in Type II Diabetes.[32] The inhibition of Ursolic acid on PTP1B extends to related enzymes T-cell protein tyrosine phosphatase (TCPTP), and src homology phosphatase-2 (SHP2) at similar potencies with no effect on LARD1, PTPα, or PTPε.[27] Ursolic acid is about twice as potent as its similarly structured and commonly co-existing molecule, Corosolic Acid (IC50 7.2+/-0.8μM).[28]

At concentrations of 50-100μM, Ursolic acid may act as an insulin mimetic and act upon the receptor with no inherent effect at 10μM.[33] One of the only studies to note acute blood glucose reductions with Ursolic Acid was done with injections of 200mg/kg, which likely was in this range to act on the insulin receptor.[34]

Concentrations as low as 1mcg/mL Ursolic Acid (0.45uM) can increase the efficacy of biologically relevant concentrations of insulin,[33] where insulin alone reaches maximum stimulation of its receptor within 5 minutes yet with 10mcg/mL ursolic acid maximal stimulation is increased up to 15 minutes with more overall post-receptor actions of insulin, measured by Akt and ERK phosphorylation as well as GLUT4 translocation, where 1nM insulin with 10mcg/mL ursolic acid reached a level of GLUT4 translocation seen with 100nM insulin.[33]

Beneficially influences actions on the insulin receptor, although it is more likely that it works on the PTP1B enzyme and augments insulin's actions on the receptor as the concentration for it to act on the receptor itself is rather high


Ursolic acid, similar to structurally related pentacyclic triterpenoids, appears to inhibit α-amylase activity although to a greater potency than Corosolic acid or Lupeol.[35]


Ursolic Acid appears to beneficially influence parameters of Diabetes when used as combination therapy alongside Rosiglitazone (anti-diabetic drug) in mice given both concurrently.[36] 

In streptozotocin-induced diabetic mice, Ursolic acid as monotherapy note that 0.05% of the diet (approximately 10mg/kg) can reduce blood glucose by 12.3% relative to control in 4 weeks[37] with another study using fourfold this dose (0.2%) over a period of 11 weeks decreased blood glucose to 53% of high-fat fed diabetic control (although still twice that of healthy control).[25] Ursolic acid tends to decrease blood glucose in a dose dependent manner (as some studies have tested graded intakes of Ursolic acid within this range of 0.05-0.2%[22]) with similar potency to Oleanolic Acid.[22]

Ursolic Acid appears to be beneficial either by itself or in conjunction with anti-diabetic agents for reducing serum glucose over an experimental period

Decreases in HbA1c have been noted with 0.05% of the diet as Ursolic Acid in diabetic mice (9.5%), with 0.1% (19%) and 0.2% (34%; all values relative to diabetic control) over 10 weeks, which coexisted with a reduction in urinary glycosylated proteins and Ursolic acid being nonsignificantly less effective than Oleanolic acid.[22] 

A decrease of Aldose Reductase activity has been noted in vivo with oral Ursolic Acid in a dose dependent manner, which at 0.2% reached 67% of diabetic control (still 59% higher than nondiabetic control, and was not absolute protection),[22] which validates previous in vitro studies noting Aldose Reductase inhibition with Ursolic Acid in a noncompetitive manner.[38] The in vivo study also noted minor beneficial trends in the activities of sorbitol dehydrogenase and glyoxalase I,[22] and anti-glycative properties have been noted to occur in hepatic tissue as well,[37] where a beneficial trend of glucose regulatory enzymes (suppressing glucose-6-phosphatase and upregulating glucokinase) occurs with 0.05% of the feed .[37]

Appears to have anti-glycative effects, and may attenuate the side-effects of diabetes associated with high blood glucose

Beyond anti-glycative protective effects, low doses of Ursolic Acid (0.01% of rat feed) have been noted to attenuate the rate of developing diabetic nephropathy possibly secondary to anti-inflammatory properties[39] and less atherosclerotic lesions have been noted with Ursolic Acid, which were slightly more protective than an equal dose (0.2% of the diet) resveratrol.[40]

Low to moderate doses of Ursolic Acid also appear to protect rats from immune-system related side effects of diabetes, and may offer putative protective effects

5Fat Mass and Obesity


Upregulation of c-Cbl associated protein (aka. CAP) protein content and mRNA has been noted in adipocytes treated with 4-20uM Ursolic Acid.[41]

Ursolic acid at 4-20uM appears to augment Rosiglitazone-induced glucose uptake into insulin resistance fat cells in vitro, although combination treatment was associated with less adipocyte differentiation than Rosiglitazone alone.[41]

Ursolic acid appears to increase lipolysis in vitro via Protein Kinase A activation, and downstream of that Hormone Sensitive Lipase (HSL) and Perilipin A activity.[42] Upregulation of Adipose Tissue Lipase (ATGL) has been noted in adipocytes independent of PKA.[42] 


100mg/kg Ursolic Acid in rats appears to attenuate the increase in triglycerides in response to a fatty meal, which was thought to be through inhibiting pancreatic lipase;[43][44] an estimated human equivalent dosage is 16mg/kg.


10mg/kg (rat dose) Ursolic acid over 15 weeks to otherwise healthy rats fed a high-fat diet is able to attenuate a 24% increase in body weight to 10.7%, which is not significantly different than the active control of 10mg/kg Sibutramine.[45] This study noted that the high-fat induced alterations in adipokines (Ghrelin, Leptin) and liver histology were otherwise normalized in both intervention groups, and that Ursolic acid was associated with an increase in insulin levels relative to high fat control and reduced glucose levels relative to all groups including normal chow control.[45]

6Skeletal Muscle and Performance


Irisin is a myokine (although it can be secreted from other tissues such as the brain, heart, and adipose[46]) that is known to in part be correlated with IGF-1 kinetics, although its overall role in skeletal muscle physiology and exercise is still being elucidated.[47][48]

Supplementation of 150mg ursolic acid three times daily with meals (totalling 450mg daily for eight weeks) in otherwise healthy men subject to resistance training appears to be effective in increasing serum irisin by 12% relative to placebo.[49] This observation occurred alongside a 22.8% increase in IGF-1 relative to baseline despite no change occurring in the placebo group given resistance training, although eight weeks was insufficient to alter lean or fat mass significantly.[49]

Supplementation of ursolic acid is thought to increase circulating levels if Irisin, a peptide secreted from a few organs (including skeletal muscle) that browns adipose tissue and may have antiobese effects. More research is needed to confirm this function of ursolic acid


Ursolic acid is implicated as being an agent to counter genetic responses of fasting that mediate muscle breakdown.[34] When fed to mice at 0.14% and 0.27% of the diet by weight (overall intake unknown) it was able to prevent muscle breakdown via genetic signalling that is the opposite of those that mediate muscle breakdown from fasting, and it was able to increase skeletal muscle accrual by increasing anabolic gene transcription, most notably that of IGF-1.[34] It did not seem to increase IGF-1 expression in adipose tissue, suggesting that this activity is specific to skeletal muscles. This anabolic effect has been replicated in vitro showing protein accrual and increasing muscle cells size, but does not influence muscle cell differentiation.[50]

Injections of 200mg/kg bodyweight, twice a day for 7 days, was shown in rats to reduce muscle protein loss associated with fasting.[34]

Increases in muscle protein synthesis are seen at 1uM, but become statistically significant at 10uM.[50] It is fairly dose-dependent of a response in increasing protein accrual, but concentrations exceeding 25uM induce loss of protein from cells and myotoxicity.[50] The growth was only seen in vitro with growth medium rather than differentiation medium or serum-free medium, the difference being GM using 10% fetal bovine serum albumin and DM 2% horse serum. These results suggest that ursolic acid may augment amino acid accrual from serum amino acids, or food.[50]

Ursolic acid's influence on muscle cells appears to not influence ribosomal content nor satellite cells, as evidence by no changes in RNA content of muscle cells incubated with ursolic acid and no myocyte differentation.[50]

Ursolic acid can also increase insulin-induced phosphorylation of Akt (an intermediate in muscle protein synthesis), which is linked to muscle protein synthesis.[51] Another intermediate downstream of Akt and phosphorylated by S6K1/S6K2, rpS6, is only increased under good growth conditions in vitro but can be upregulated 1.8-fold.[50]

In rats subject to resistance training, an infusion of ursolic acid appears to sustain the exercise-induced activation of p70S6K (downstream of mTOR) for a more prolonged period of time than control exercise.[52]

Low dosages appear to beneficially influence skeletal muscle, but higher dosages have been implicated in preserving muscle mass during fasting. These higher dosages may not be feasible due to low oral bioavailability, but lower dosages are definitely possible. Many of the effects seen are related to the insulin-signalling pathway of muscle anabolism.

7Inflammation and Immunology


Ursolic acid does not appear to inhibit the 5-Lipoxygenase enzyme.[53]

8Interactions with Hormones


Ursolic acid-like compounds (11-ketoursolic acid and 3-acetyl,11-ketoursolic acid) have been implicated in inhibiting the 11β-Hydroxysteroid Dehydrogenase type 1 enzyme (11βHSD1), which converts cortisone to active cortisol, with IC50 values of 2.06 and 1.35uM respectively.[54] Corosolic Acid was more effective than other compounds tested at 0.81uM, and Ursolic acid itself had an IC50 of 1.9uM.[54] At least at the concentrations tested, none of the above pentacyclic triterpenoids inhibited the 11βHSD2 enzyme, which catalyzes the conversion of cortisone to cortisol.

Should theoretically reduce cortisol, but this has not yet been tested in a living system


One study noted a decrease in circulating leptin levels associated with 0.14% ursolic acid in rat feed,[34] but these results may be influenced by weight loss. When there are no significant changes in weight, leptin does not appear to change significantly.[37]


Ursolic acid appears to have weak activity as an aromatase inhibitor, although this may be irrelevant due to the potency and the bioavailability of ursolic acid.[55][56] Derivatives of ursolic acid appear to be fairly useless in inhibiting the aromatase enzyme.[56] The IC50 of ursolic acid was 32uM, thrice less potent than Apigenin (10uM).[56]

8.4Growth Hormones

One human study which gave healthy participants 150mg ursolic acid three times a day with meals (totalling 450mg each day) for eight weeks alongside resistance training noted that supplementation was able to increase circulating IGF-1 concentrations by 22.8% relative to placebo (also given resistance training).[49]

9Interactions with Organ Systems


A rat model of benign prostatic hyperplasia using 5mg/kg Ursolic acid oral administration alongside testosterone injections noted suppression of prostatic growth to a similar degree as the active control (10mg/kg Finasteride) and a suppression of both testosterone and DHT rivalling Finasteride in magnitude; Finasteride was more effective in reducing serum levels of prostate specific antigen (PSA).[57] The authors hypothesized a 5α-reductase inhibiting effect, although it was not established in vitro in this study (this study was responded to,[58] which merely discussed the need more research and product standardization).


In studies measuring liver enzymes, there is no increase following 5mg/kg oral ingestion for 4 weeks.[57]

10Interactions with Cancer Metabolism


Ursolic acid (as well as related compounds maslinic acid and oleanolic acid[59]) is known as an angiogenesis inhibitor, preventing the formation of new blood vessels from larger ones. In blood vessel cells, ursolic acid seems to act via inhibiting the PI3K-Akt pathway and Nitric Oxide induction, which suppresses cellular changes preceding angiogenesis.[59][60] These results have been seen in vivo with nontoxic dosages of ursolic acid, and ursolic acid also inhibits expression of MMP2 and MMP9 (intermediates required for the final stages of angiogenesis into new tissue)[61]

This inhibition of vascularization is currently under investigation for its anti-cancer therapeutic potential, as new tumor cells require blood flow and need angiogenesis to occur for them to survive.[62] The previous study that tested rats with ursolic acid noted that the experimental group having ursolic acid at 4.25mcg/kg (50umol/kg) for 5 days had 42.03% as much vascularization in melanoma tumors as control (untreated).

11Safety and Toxicity

11.1Male fertility

Ursolic acid, when fed to rats at 5mg/kg bodyweight, was able to cause infertility by inhibiting spermatogenesis.[63] Specifically, it causes breaking of bridges in between cells that are soon to be sperm, and the damaged cells then collect to form symplasts in the Seminiferous Tubules that are associated with male infertility. It does not appear to cause long-term damage to the testes.

At least one other in vitro study noted that ursolic acid was able to reduce sperm motility.[64]


One study noted that ursolic acid was able to induce cell death in endothelial cells when the concentration exceeded 12.5uM, and that the mechanism of death was apoptosis related; DNA strand breaks were noted 6 hours after incubation via p53.[23] The DNA strand breaks were later seen in vivo in ApoE deficient mice when the water was spiked with 10uM or 30uM of ursolic acid.


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