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Uva Ursi

Scientific Name(s): Arctostaphylos uva ursi (L.) Sprenge. folium, Uvae ursi folium
Common Name(s): Achelblätter, Achelkraut, Arberry, Arctostaphylos, Bear's grape, Bearberry, Beredruif, Berry leaves, Brockberry, Busserole, Bärenkraut, Bärentraube, Bärentraubenblätter, Coralillo, Crowberry, Dogberry, Enab edhdhib, Feuille de busserole, Feuille de raisin d'ours, Folia artostaphyli, Folia garjubae, Folia uvae-ursi, Folia vaccinil ursi, Foxberry, Gayuba, Herba garjubae, Hog cranberry, Hojas de gayuba, Kinnikinnick, Leesikas, Lisc maçznicy, Mealyberry, Medvescölölevel, Moosebeerenblätter, Mountain box, Ptarmigan berry, Raisin d'ours, Red bearberry, Sagochomi, Sandblätter, Upland cranberry, Uva ursi, Uvaursina, Uwaurushi, Wolfsbeerenblätter

Clinical Overview

Use

Uva ursi has been traditionally used to treat symptoms of mild urinary tract infections. However, there are no clinical trials demonstrating the safety, efficacy, or toxicity of its use. In vitro research supports its use as a urinary antiseptic.

Dosing

Dosing and formulations of uva ursi products available in the United States vary. Doses of arbutin 400 to 840 mg have been used.

Contraindications

Uva ursi is contraindicated during pregnancy and lactation.

Pregnancy/Lactation

Avoid use. Uva ursi is contraindicated during pregnancy and lactation.

Interactions

Uva ursi should not be administered with foods or drugs that acidify the urine.

Adverse Reactions

Ingestion of the dried leaves of uva ursi may cause a greenish-brown discoloration of the urine. Ingestion of uva ursi leaves may cause nausea and vomiting due to its high tannin content. Bull's eye maculopathy has been reported with long-term ingestion (3 years).Topical application has caused leukoderma, erythema, and allergic contact dermatitis.

Toxicology

While uva ursi leaves are not carcinogenic, hydroquinone, a primary constituent of the plant, may be carcinogenic. A recommended therapeutic human daily dose of bearberry leaf extract (420 mg of hydroquinone derivatives calculated as anhydrous arbutin) liberates free hydroquinone in urine at a maximum exposure level of 11 mcg/kg of body weight per day. However, the daily exposure dose, below which there is negligible risk to humans, is 100 mcg/kg.

Botany

Uva ursi is found in North America, Asia, and northern Europe. It is a procumbent evergreen shrub with trailing stems and leaves and flowers that cluster at the ends of its branches. The dried leaves are slightly aromatic and have an astringent, bitter taste.WHO 2004 Synonyms include Arbutus uva ursi L.; Arctostaphylos media Greene; Arctostaphylos officinalis Wimm.; Arctostaphylos procumbens Patzke; Mairania uva-ursi Desv.; Uva-ursi buxifolia S.F. Gray; and Uva-ursi procumbens Moench.

Arctostaphylos adenotricha and Arctostaphylos coactylis Fern et Macbr. have also been termed "uva ursi" by some authors.

History

Uva ursi has been used extensively in native cultures since the Middle Ages and is listed in the pharmacopoeias of many Western societies for the treatment of urinary conditions, primarily symptoms of urinary tract infection.EMA 2012 From 1820 to 1936, a fluid extract made from the leaves of the herb was listed as a urinary antiseptic in the US Pharmacopeia and US National Formulary.

Chemistry

The primary chemical component of uva ursi is arbutin or hydroquinone-O-beta-D-glucose (5% to 16%). The arbutin content varies seasonally. Other hydroquinone derivatives include methyl arbutin, galloyl derivatives of arbutin, free hydroquinone, and methylhydroquinone. Other components include polyphenols (tannins), phenolic acids (mainly gallic), piceoside, flavonoids, iridoid glucoside, triterpenes, enzymes (beta-glucosidease), allantoin, resin, volatile oil, and wax.EMA 2012, WHO 2004

Uses and Pharmacology

Although clinical trials are lacking, uva ursi has been described for various conditions in pharmacopeias and used in traditional medicine as a mild urinary antiseptic for conditions such as cystitis, urethritis, and dysuria.WHO 2004

Antibacterial activity

Extracts of uva ursi have inhibited the in vitro growth of Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Serratia marcescens, Staphylococcus aureus, Streptococcus mutans, Proteus vulgaris, Staphylococcus faecalis, and Enterobacter aerogenes. In an in vitro study, healthy volunteers were given 0.1 to 1 g of arbutin orally. Urine samples were collected 3 hours later and adjusted to a pH level of 8 and, along with 20 other antibacterial compounds, tested against 74 bacterial strains including E. coli, Proteus mirabilis, P. aeruginosa, and S. aureus. Only gentamicin, nalidixic acid, and arbutin (present in urine samples from subjects given arbutin 1 g) were active against all tested strains.WHO 2004

In a double-blind trial (preliminary report), an uva ursi extract or placebo was administered prophylactically for 1 month to 57 women with recurrent cystitis. In the 12 months following treatment, women who received uva ursi had no episodes of cystitis, whereas 23% of placebo-treated women had at least 1 episode of cystitis (P > 0.05).Larsson 1993

Arbutin is the component of uva ursi thought to be most responsible for its antibacterial activity. Following ingestion of the leaves, arbutin is hydrolyzed to hydroquinone. Hydroquinone is then metabolized to glucoronate and sulfate esters, which are excreted in the urine and are responsible for the antiseptic and astringent actions in the urinary tract. Maximum antibacterial action is reached approximately 3 to 4 hours after ingestion and requires an alkaline urinary pH (pH > 7).WHO 2004, Yarnell 2002

Other uses

Extracts also have demonstrated in vitro antiviral activity against herpes simplex virus type 2, influenza virus A2, and vaccinia virus.WHO 2004

Uva ursi has been used in traditional medicine as a diuretic, to stimulate uterine contractions, and to treat diabetes, poor eyesight, renal or urinary calculi, rheumatism, and venereal disease. Topical applications have been used for skin depigmentation.WHO 2004 A controlled study in rats demonstrated significant diuretic activity at a dose of 50 mg/kg, but not at 100 mg/kg.Kurkin 2015 There are published reports demonstrating anti-inflammatory and antitussive activity in animals. Animal studies evaluating glucose-lowering effects and the effect on calcium excretion did not support these uses. Extracts of uva ursi leaves are widely used in cosmetic preparations for skin depigmentation.WHO 2004

An in vitro study evaluated the effects of arbutin on human bladder cancer cell proliferation. Arbutin decreased cell proliferation via extracellular signal-regulated kinase inactivation and p21 upregulation.Li 2011

Dosing

Dosing and formulations of uva ursi products available in the United States vary. Doses of arbutin 400 to 840 mg have been used.

The WHO Monographs on Selected Medicinal Plants lists doses of 3 g in 150 mL as an infusion or cold macerate 3 to 4 times daily; 400 to 840 mg of hydroquinone derivatives; or other preparations accordingly calculated as arbutin.WHO 2004

Because uva ursi's antimicrobial activity can be blocked in acidic urine, ingestion of animal products or other foods known to acidify the urine should be decreased with its use. Administration of sodium or potassium bicarbonate may help to alkalinize the urine. Urinary pH should be greater than 7 for antimicrobial effectiveness. Treatment duration is generally limited to a few weeks because of carcinogenic concerns with long-term hydroquinone use.Yarnell 2002

Herbal teas

Various tea mixtures of uva ursi 1.5 to 4 g in combination with other herbs for the treatment of mild conditions of the urinary tract.EMA 2012

Powdered herbal substances

Six 500 mg tablets 4 times daily for adults and adolescents older than 12 years for inflammatory disease of the urinary tract (Germany); one 270 mg capsule 3 times daily as a diuretic (Spain); two 350 mg capsules twice daily to promote renal elimination of water, as an adjuvant to diuretics, and for treatment of benign urinary tract conditions (France).EMA 2012

Dry extracts

Two 500 mg tablets twice daily in adults and adolescents as a urinary antiseptic (Belgium); 2 tablets (239 to 298 mg [corresponding to 70 mg of hydroquinone derivatives]) 3 times daily (Germany); 4 to 5 tablets (114 to 143 mg [31.5 mg of hydroquinone derivatives]) 4 times daily (Germany); 2 to 3 tablets (228 to 315 mg [63 mg of hydroquinone derivatives]) 4 times daily (Germany); 2 tablets (425 to 520 mg [105 mg of hydroquinone derivatives]) 2 to 4 times daily (Germany). In all cases, these products are used for inflammatory disease of the urinary tract. Additional dry extract dosing regimens are four 215 mg tablets (40 mg of arbutin) 3 times daily for uncomplicated infection of the lower urinary tract when antibiotics are not considered essential (Poland); one 200 mg capsule twice daily to promote renal elimination of water and as an adjunct to diuretics (France).EMA 2012

Liquid extracts

101 to 207 mg of anhydrous arbutin 4 times daily to support treatment of inflammatory disease of the urinary tract (Germany).EMA 2012

Pregnancy / Lactation

Avoid use. Uva ursi is contraindicated during pregnancy and lactation.WHO 2004

Interactions

Uva ursi should not be administered with foods or drugs that acidify the urine.WHO 2004

Adverse Reactions

Ingestion of the dried leaves of uva ursi may cause a greenish-brown discoloration of the urine, which darkens upon exposure to air as a result of hydroquinone oxidation.WHO 2004

Ingestion of uva ursi leaves may cause nausea and vomiting due to its high tannin content.WHO 2004

Bull's eye maculopathy has been reported with long-term ingestion (3 years).Wang 2004

The WHO Monographs on Selected Medicinal Plants states that because of the risk of ochronosis, the hydroquinone concentration of topical preparations is limited to 2% in Nigeria, the United Kingdom, and the United States. Topical application has also caused leukoderma, erythema, and allergic contact dermatitis.WHO 2004

Toxicology

When taken orally, the median lethal dose (LD50) of hydroquinone is 300 to 1,300 mg/kg in rodents and dogs, and 42 to 86 mg/kg in cats. Nervous system toxicity (hyperexcitability, tremor, convulsions, coma) and death have been demonstrated with short-term administration of 1,300 mg/kg in rats.WHO 2004

While uva ursi leaves are not carcinogenic, hydroquinone may be carcinogenic.WHO 2004 A recommended therapeutic human daily dose of bearberry leaf extract (420 mg of hydroquinone derivatives calculated as anhydrous arbutin) liberates free hydroquinone in urine at a maximum exposure level of 11 mcg/kg of body weight per day. However, the daily exposure dose, below which there is negligible risk to humans, is 100 mcg/kg.de Arriba 2013

Fetal toxicity was noted in the offspring of rats fed arbutin 400 mg/kg. However, there were no effects on male or female reproduction or on fetal toxicity in rats fed up to 100 mg/kg of arbutin.WHO 2004

References

de Arriba SG, Naser B, Nolte KU. Risk assessment of free hydroquinone derived from Arctostaphylos Uva-ursi folium herbal preparations. Int J Toxicol. 2013;32(6):442-453.24296864
European Medicines Agency. Assessment report on Arctostaphylos uva-ursi (L.) Spreng., folium. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/07/WC500108750.pdf. Published January 24, 2012. Accessed February 19, 2016.
Folium Uvae Ursi. In: WHO Monographs on Selected Medicinal Plants. Vol 2. Geneva, Switzerland: World Health Organization; 2004:342-351. http://apps.who.int/medicinedocs/en/d/Js4927e/32.html.
Kurkin VA, Zaitseva EN, Kurkina AV, Dubishchev AV, Pravdivtseva OE. Comparative study of diuretic activity of hydroalcoholic extracts from medicinal plants containing flavonoids. Bull Exp Biol Med. 2015;159(3):368-371.26212812
Larsson B, Jonasson A, Fianu S. Prophylactic effect of UVA-E in women with recurrent cystitis: a preliminary report. Curr Ther Res. 1993;53(4):441-443.
Li H, Jeong YM, Kim SY, Kim MK, Kim DS. Arbutin inhibits TCCSUP human bladder cancer cell proliferation via up-regulation of p21. Pharmazie. 2011;66(4):306-309.21612160
Wang L, Del Priore LV. Bull's-eye maculopathy secondary to herbal toxicity from uva ursi. Am J Ophthalmol. 2004;137(6):1135-1137.15183807
Yarnell E. Botanical medicines for the urinary tract. World J Urol. 2002;20(5):285-293.12522584

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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