Ursolic acid, a naturally occurring compound in fruits and vegetables was found as early as 1920 in the epicuticular waxes of apples.
It can been found in a variety of fruits, herbs, and spices, including rosemary and thyme, and in the peels of many other plants and fruits.
There are many biological effects associated with ursolic acid, such as increasing muscle growth, anti-inflammatory and antioxidant activity, reducing tissue damage, and possibly even anti-cancer effects.
Table of Contents:
Overview
Ursolic acid, a naturally occurring compound in fruits and vegetables, exhibits a range of health benefits.
It appears to increase muscle mass and decrease fat mass, making it a potential body-recomposition agent.
It's also shown to have anti-inflammatory and antioxidant effects.
It has shown potentially significant anticancer properties, particularly in breast cancer, by inhibiting cell proliferation and inducing apoptosis.
It also demonstrates cardio-protective effects, hepato-protective benefits, and neuro-protective benefits.
However, at this time there is limited human research.
What Is Ursolic Acid?
Ursolic Acid (3β-hydroxyurs-12-en-28-oic acid) is a pentacyclic triterpenoid.
It's also known as Prunol, Urson, Malol, and 3β-hydroxyurs-12-en-28-oic acid.
It can be found in a variety of plants, as well as in many fruits and herbs, such as the following.
Apples
Basil and holy basil
Bilberries and cranberries
Elder flower
Peppermint, rosemary, lavender, oregano, thyme, hawthorn
Prunes
A significant amount of ursolic acid and similar chemicals may be found in the peels of fruit, especially apple peel. (1)
Ursolic acid (abbreviated to UA) is one of several plant-based metabolites that has multiple intracellular and extracellular targets that are involved in apoptosis, metastasis, angiogenesis, and inflammatory processes.
How It Works
A variety of possible biological functions of ursolic acid have been studied, but there has been minimal research on the effects of these biological functions.
Most research has been conducted in animals; therefore, the effects may be different in humans.
Ursolic acid works through various mechanisms depending on the specific health context.
For example, in cancer, it may work by inducing cell cycle arrest, regulating signal transduction pathways, and promoting apoptosis.
In metabolic conditions, it influences protein expressions related to energy expenditure and muscle mass.
1. Anti-Cancer Effects
Ursolic acid exhibits anticancer properties, particularly in breast cancer.
Ursolic acid reduces the activity of the STAT3 pathway, induces G1/G2 cell cycle arrest, and regulates key proteins in signalling pathways, potentially reducing proliferation.
It also triggers apoptosis in cancer cells through intrinsic and extrinsic pathways and has antioxidant properties. (Yin et al., 2018)
It may also suppress IL-2 activation and JNK expression, as seen in Jurkat leukemic T Cells. (4)
2. Muscle-Building & Fat-Burning Effects
Studies in mice have shown that with the addition of ursolic acid to their feed, it may increase the amount of muscle mass and brown fat while decreasing white fat, reducing the risk of obesity. (5)
It seems to have anabolic effects by:
Increasing mTOR activity and anabolic cell processes
Increasing IGF-1 levels
Increase growth hormone levels
Increasing Irisin levels
Mice studies have also shown that ursolic acid may decrease muscle atrophy and promote muscular development.
Skeletal muscle mass, grip strength, and physical endurance were all enhanced by ursolic acid along with a decreased expression of genes implicated in muscular atrophy, and decreased exercise-induced stress were observed. (6)
Further Reading: Does ursolic acid help build muscle?
3. Cardio-Protective Effects
Ursolic acid has been found to induce a statistically significant uncoupling of oxidative phosphorylation in isolated rat heart mitochondria and decrease H₂O₂ production, suggesting potential as a cardio-protective compound. (Liobikas et al., 2011)
4. Liver Protective Effects
In mice, ursolic acid also promotes the regeneration of the liver after a partial hepatectomy. (8)
Ursolic acid has shown hepatoprotective effects against ethanol-mediated liver damage in rats, potentially due to its antioxidant activities. (Saravanan et al., 2006)
5. Neuro-Protective Effects
It exhibits neuroprotective properties and has been investigated for its potential in managing neurodegenerative and psychiatric diseases.
Its effects are largely attributed to preventing oxidative damage and reducing inflammation. (Ramos-Hryb et al., 2017)
When mice were subjected to a sciatic nerve lesion, ursolic acid promotes neuronal regeneration, it has also been shown to prevent further neuronal damage and to aid in the regeneration of the protective sheaths that surround neurons. (10, 11)
This effect appears to be due to the suppression of Th17 immune cells and the activation of precursor cells that mature into myelin-sheath-producing cells.
Cognitive deficits caused by domoic acid, a high-fat diet, and D-galactose in mice and rats are reduced via ursolic acid inhibiting particular inflammatory pathways. (12, 13, 14)
It reduces the severity of lipopolysaccharide-induced cognitive impairments in mice via inhibition of the p38/NF-B inflammatory pathways in the brain of the mice. (15)
Other Effects
Ursolic acid may also cause eryptosis; the reduction in defective red blood cells. (9)
There are various other functions and effects of ursolic acid, most of this research has only been conducted in animal studies and requires replication in human studies before conclusions can be made.
Benefits of Ursolic Acid
The possible effects of ursolic acid supplementation are vast.
Based on the minimal human research that exists, it seems to be a potential body recomposition agent, with the ability to increase muscle mass ands strength while simultaneously decreasing body fat.
However, it is possible that it may be detrimental to fertility.
The possible benefits of ursolic acid are as follows.
1. Increased Muscle Mass & Strength
Though there has been no conclusive human studies of the effect of ursolic acid on muscle growth and strength, there are animal studies and theory suggesting a positive effect.
One study has shown ursolic acid enhances IGF-1 and Akt cell signalling, improving muscle growth. (16)
Supplementation with ursolic acid has been shown to increase the size of both fast and slow-twitch muscle fibres.
Ursolic acid increases brown fat tissue, which is found in the same areas of the body as skeletal muscle, increasing the muscles' physical dimensions and size.
Grip strength has also been shown to be enhanced.
2. Decreased White Fat
White fat is also known as the "bad" fat.
It is the non-metabolically active type of fat tissue and is the type of fat seen in obese humans and animals.
White fat is the fat tissue that stores lipids and energy.
Due to ursolic acids effect on increasing energy expenditure, it can help to reduce white fat.
3. Increased Brown Fat
Brown fat is known as the "good" fat, this is because brown fat is metabolically active and has increased levels of mitochondria.
Due to the increased levels of mitochondria seen in brown fat tissue, it increases energy expenditure and has other beneficial effects on insulin resistance and glucose metabolism.
Ursolic acid likely increases brown fat via causing an increase in irisin, a hormone responsible for multiple effects on fat tissue, metabolism and energy.
Irisin levels are increased significantly higher than placebo alone. (17)
4. Reduced Obesity, Glucose Intolerance & Fatty Liver Disease
As a result of an increase in irisin, brown fat, and muscle tissue, basal daily energy expenditure is increased.
Meaning a higher caloric intake is required to increase fat storage.
The growth of new muscle tissue also requires energy.
Brown fat and irisin have beneficial effects on glucose sensitivity and intolerance as well as hepatic glucose and lipid metabolism.
Therefore, ursolic acid can help reduce diet-induced obesity, glucose intolerance and fatty liver disease. (5)
5. May Have Anti-Cancer Activity
Ursolic acid may be a potential anti-cancer agent through a variety of mechanisms. (18)
It may inhibit multiple cellular pathways in cancer cells, resulting in reduced proliferation, metastasis, and growth.
There are some energy-related mechanisms associated with ursolic acid that may also have a regulatory effect on cancer cells. (19)
However, because no human research on ursolic acids effect on cancer cells exists, it cannot be concluded that it reduces cancer growth.
Dosage & How to Take
A 0.05-0.2% concentration of ursolic acid in animal feed, equal to 10-40 mg/kg (depending on the animals weight and food consumption), has been shown to be beneficial in animal experiments.
The estimated human dosage comparable to this is 1.6-6.4 mg/kg of bodyweight.
For a 180lb (81.6kg) adult, this range would be about 130-520mg.
One human study used the upper end of this dosage range; 150mg three times a day with food, totalling 450mg each day.
This study discovered some biological activity in the participants.
Therefore, if you are willing to take ursolic acid, 150mg three times day with food is suggested until more research is conducted.
However, be warned there is no safety information available and there is the potential for adverse effects.
If are going to take this supplement, be sure to get ursolic acid from a trusted vendor, such as this product on Amazon.
It can be found mostly in capsule form and is usually extracted from a plant or herb, such as rosemary leaf.
Possible Adverse Effects
At this time, there is inadequate evidence to determine the short and long-term safety of ursolic acid consumption.
While phase 1 safety tests have shown that ursolic acid has acceptable side-effects, the long-term safety of this compound is still very much unknown.
Three minor safety studies have been conducted to assess the safety of ursolic acid.
As reported by the researchers, ursolic acid was acceptable, and the majority of the adverse effects were mild to moderate in severity. (20, 21, 22)
The fact that these trials solely looked at the safety of ursolic acid is essential to keep in mind.
There is no conclusive evidence to suggest that ursolic acid is effective in the treatment of cancer, or anything else for that matter.
Some of the side-effects from ursolic acid usage are listed below.
Nausea
Swelling in the abdomen
The presence of trace quantities of blood in the urine
Sodium levels that are abnormally high
Rashes on the skin
Diarrhoea and liver damage are the two most frequent side-effects which induced dose-limiting.
Therefore, ursolic acid has side-effects which need to be managed, the best advice is to not use this supplement and if you do, limit it to a short period of time.
References
This section contains links to research, studies, and sources of information for this article, as well as authors, contributors, etc. All sources, along with the article and facts, are subjected to a series of quality, reliability, and relevance checks.
Real Muscle primarily uses high-quality sources, such as peer-reviewed publications, to back up the information in our articles. To understand more about how we fact-check and keep our information accurate, dependable, and trustworthy, read more about us.
This evidence-based analysis of ursolic acid features 22 references, listed below.
1. Simone Tasca Cargnin, Simone Baggio Gnoatto. Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties. Food Chemistry. (2017)
2. Ashutosh K. Pathak, Manisha B, Asha S. Nair, Kwang SA, Arup C, Humam K, Sushovan G, Gautam S, Bharat BA. Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells. Mol Cancer Res. (2007)
3. Chen CJ, Shih YL, Yeh MY, Liao NC, Chung HY, Liu KL, Lee MH, Chou PY, Hou HY, Chou JS, Chung JG. Ursolic Acid Induces Apoptotic Cell Death Through AIF and Endo G Release Through a Mitochondria-dependent Pathway in NCI-H292 Human Lung Cancer Cells In Vitro. In Vivo. (2019, Mar-Apr) ✔
4. Narawan Kaewthawee, Sirikalaya Brimson. The Effects of Ursolic Acid on Cytokine Production via the Mapk Pathways in Leukemic T-Cells. (2013, Feb) ✔
5. Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, Bullard SA, Adams CM. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One. (2012) ✔
6. Jeong JW, Shim JJ, Choi ID, Kim SH, Ra J, Ku HK, Lee DE, Kim TY, Jeung W, Lee JH, Lee KW, Huh CS, Sim JH, Ahn YT. Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle. J Med Food. (2015, Dec) ✔
7. Uncoupling and Antioxidant Effects of Ursolic Acid in Isolated Rat Heart Mitochondria. J Nat Prod. (2011)
8. Jin YR, Jin JL, Li CH, Piao XX, Jin NG. Ursolic acid enhances mouse liver regeneration after partial hepatectomy. Pharm Biol. (2012, Apr) ✔
9. Triggering of Erythrocyte Cell Membrane Scrambling by Ursolic Acid. J Nat Prod. (2011)
10. Liu B, Liu Y, Yang G, Xu Z, Chen J. Ursolic acid induces neural regeneration after sciatic nerve injury. Neural Regen Res. (2013, Sep 25) ✔
11. YuanZhang, XingLi, BogoljubCiric, Mark T.Curtis, Wan-JunChen, AbdolmohamadRostami, Guang-XianZhang. A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination. Pro of the Nat Acad of Sciences. (2020, Apr) ✔
12. Dong-mei Wu, Jun Lu, Yan-qiu Z, Yuan-lin Z, Bin Hu, Wei C, Zi-feng Z, Meng-qiu Li. Ursolic acid improves domoic acid-induced cognitive deficits in mice. Toxicology and Applied Pharmacology. (2013)
13. Jun L, Dong MW, Yuan LZ, Bin H, Wei C, Zi-feng Z, Qun S. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice. Brain, Behavior, and Immunity. (2011)
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15. Wang YJ, Lu J, Wu DM, Zheng ZH, Zheng YL, Wang XH, Ruan J, Sun X, Shan Q, Zhang ZF. Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways. Neurobiol Learn Mem. (2011, Sep) ✔
16. Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, Bullard SA, Adams CM. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One. (2012) ✔
17. Bang, Hyun & Seo, Dae & Chung, Yong & Oh, Kyoung-Mo & Park, Jung & Figueroa, Arturo & Jeong, Seung & Kim, Nari & Han, Jin. Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men. The Korean Journal of Physiology & Pharmacology. (2014)
18. Ursolic Acid Simultaneously Targets Multiple Signaling Pathways to Suppress Proliferation and Induce Apoptosis in Colon Cancer Cells. PLOS ONE. ✔
19. Feng XM, Su XL. Anticancer effect of ursolic acid via mitochondria-dependent pathways. Oncol Lett. (2019, Jun) ✔
20. Wang XH, Zhou SY, Qian ZZ, Zhang HL, Qiu LH, Song Z, Zhao J, Wang P, Hao XS, Wang HQ. Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors. Expert Opin Drug Metab Toxicol. (2013, Feb) (Clinical Trial) ✔
21. Qian Z, Wang X, Song Z, Zhang H, Zhou S, Zhao J, Wang H. A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors. Biomed Res Int. (2015) (Clinical Trial) ✔
22. Zhu Z, Qian Z, Yan Z, Zhao C, Wang H, Ying G. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors. Int J Nanomedicine. (2013) (Clinical Trial) ✔
✔ Citations with a tick indicate the information is from a trusted source.
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