Nettles
Urtica dioica L., Urtica urens L. Family: Urticaceae (nettles)
Stinging nettle , nettle . Commercial preparations include Bazoton , Prostaherb ,   Prostamon , Prostatin , Simic , Urtica Plus , Urtidin .
 
Clinical Overview
Uses
The primary use of nettles is in the management of symptoms due to benign prostatic hyperplasia (BPH). However, limited clinical trials are available. Nettles are also used in arthritis and allergic rhinitis. A role in diabetes is being investigated in animals.

Dosing
Freeze-dried nettle leaf 600 mg has been used in a clinical trial for allergic rhinitis. Clinical trials for BPH have used aqueous extracts of U. dioica root 360 mg daily over 6 months and methanol root extract 600 to 1,200 mg daily for 6 to 9 weeks.

Contraindications
Due to the effects on androgen and estrogen metabolism, nettle preparations are contraindicated in pregnancy and lactation and should not be used in children younger than 12 years.

Pregnancy/Lactation
Documented adverse effects. Avoid use.

Interactions
None well documented.

Adverse Reactions
Nettles are known primarily for their ability to induce topical irritation following contact with exposed skin. The acute urticaria is caused by the release of histamine, serotonin, and choline from the hairs and spines of the leaves and stem and generally resolves spontaneously. Radix urticae extracts and other nettle preparations are generally well tolerated, with minor and transient gastric effects, including diarrhea, gastric pain, and nausea reported.

Toxicology
The acute oral toxicity of nettle preparations is considered to be very low. Mutagenicity and carcinogenicity studies were negative for the aqueous extract.

 
Botany
Nettles are perennial plants native to Europe and found throughout the United States and parts of Canada. U. dioica and U. urens are botanically very similar and are often distributed together in the wild. Therapeutically, they are considered to be interchangeable.
The nettle plant has an erect stalk that grows up to 1 m in height. It has dark green serrated leaves that grow opposite one another along the stalk and contain bristles that transmit irritating principles upon contact. The plant flowers from June to September. Nettle fruit is a small, oval-shaped seed approximately 1 mm wide and yellow-brown in color. 1 , 2 , 3
 
History
The nettle plant is known for its stinging properties. However, it has been used in traditional medicine as a diuretic, antispasmodic, and expectorant, and in the treatment of asthma. The juice has been purported to stimulate hair growth when applied to the scalp. Extracts of the leaves have been used topically for the treatment of rheumatic disorders. The tender tips of young nettles have been used as a cooked pot herb in salads. Claims of activity against diabetes, cancer, eczema, rheumatism, hair loss, and aging have not been substantiated. Other folk medicine applications include wound healing, treatment of scalp seborrhea and greasy hair, and gastric juice secretion. It is considered to be a nourishing plant and has been used to treat scurvy. A combination product includes nettle to treat hyposecretory gastritis. 2
 
Chemistry
Varying chemical constituents of the plant's leaf, flower, seed, and root are used. 2 Compounds thought to have clinical relevance include nettle root lignans (including divanillyltetrahydrofuran), lectin U. dioica agglutinin, 9-hydroxy-10 trans-12-cis-octadecadienic acid, steroidal compounds (including stigmasterol, stimast-4-en-3-one, campesterol, and others), polysaccharides, and caffeic and malic acids. 2 , 4 , 5 , 6 The plant has been used as a commercial source of chlorophyll, and the young shoots are rich in carotene and vitamin C. The plant also contains B-group vitamins and vitamin K, along with other various acids. The stinging trichomes of nettle contain amines, including histamine, serotonin, and choline. Nettle fruit contains protein, mucilage, and fixed oil. 2 , 6 , 7
High performance liquid chromatography, gas chromatography, capillary electrophoresis, and other methods have determined the lectin specific to U. dioica roots, which may help to standardize preparations. 2 , 4 , 5
 
Uses and Pharmacology
Arthritis/analgesia   In vitro studies using human cell lines suggest extracts may down-regulate the inflammation cascade, exert effects on cyclo-oxygenase enzymes, and reduce primary T-cell responses. 8 , 9 , 10
Animal data   In writhing and licking tests in rodent studies, extracts of U. dioica showed analgesic and antinociceptive properties. Reduced inflammation in induced paw edema was also demonstrated. 11 , 12 , 13
Clinical data   Limited clinical trials have been conducted using nettle leaves to reduce pain associated with osteoarthritis. 13 , 14 , 15
Benign prostatic hyperplasia   Experimental studies suggest a number of possible mechanisms of action for extracts of nettle in managing the symptoms of BPH. Reductions in the plasma level of sex hormone-binding globulin (SHBG), the protein involved in binding of circulating androgens and estrogen, have been demonstrated. An effect on enzyme activity, including the conversion of testosterone to estrogens and weak inhibition of 5 alpha-reductase and aromatase, has been demonstrated in vitro. Reduced prostate growth has also been shown by some, but not all, nettle extracts. 2 , 6
Animal data   Animal studies have been conducted to evaluate the effect of extracts of U. dioica in BPH; however, the availability of more recent clinical trial data makes these studies less important. 2 , 6 In vitro and animal studies have examined a potential role of nettle extract in prostate cancer, suggesting inhibition of adenosine deaminase to be a possible mechanism of action. 16
Clinical data   Most trials have been of open-label design, and few high-quality clinical trials have been conducted using U. dioica alone compared with standard therapy. However, some evidence suggests that certain nettle extracts do exhibit efficacy in reducing the symptoms of BPH as measured by the International Prostate Symptom Score. 2 , 6
Increases in urine volume and urinary flow, decreases in frequency of micturition, post-void residual volume, and serum SHBG have been demonstrated. 2 , 6 , 17 No alteration in prostate-specific antigen or testosterone levels was found in one clinical trial. 17
Clinical trials have also evaluated the adjunctive effect of U. dioica in treating bacterial prostatitis. 18 , 19 The Complete German Commission E Monographs support use in inflammation of the urinary tract and in the prevention and treatment of kidney gravel. 3
Cardiovascular effects   Nettles have traditionally been used for their diuretic and hypotensive effects. In vitro studies show that U. dioica extracts inhibit thrombin-induced platelet aggregation, possibly due to flavonoid content. 20
Animal data   Rats fed a high-fat diet and aqueous U. dioica extracts had reductions in total and low-density lipoprotein (LDL) cholesterol, plasma apoprotein B, and LDL/high-density lipoprotein ratio. 21 In a similar study, higher doses resulted in mild steatosis, with lower dosages improving the lipid profile. 22
Diuretic, natriuretic, and hypotensive action have been demonstrated in rats. 23 , 24 In isolated heart studies, decreased heart rate and inotropic activity have been shown, as well as increased left ventricular pressure and vascular contractility. 24 , 25
Clinical data   Research reveals no clinical data regarding the use of nettle in cardiovascular conditions.
Diabetes   Lectins isolated from the seeds and leaves of nettle have been evaluated for a potential role in the management of diabetes. In vitro studies suggest effects on Langerhans and muscle cells with increased glucose uptake into cells, as well as reduced intestinal absorption of glucose. 26 , 27 , 28 , 29
Animal data   In rats with induced diabetes, serum glucose levels were reduced in some, 29 , 30 , 31 but not all, experiments. 29 , 31 , 32 No effect of nettle extracts was demonstrated on renal indices in diabetic rats. 33
Clinical Data   Research reveals no clinical data regarding the use of nettle in diabetes, although case reports of hypoglycemia due to consumption of nettle preparations for prostatic hypertrophy exist. 34
Other effects
Allergic rhinitis   Freeze-dried nettle has been evaluated for allergic rhinitis. In a double-blind trial, freeze-dried nettle leaf 600 mg was more effective than placebo in controlling symptoms. 35 Effects may be due to immunomodulatory or anti-inflammatory actions. 9 , 36 , 37 , 38
Antimicrobial   In vitro studies have shown antiviral action against HIV, cytomegalovirus, and feline immunodeficiency virus. 39 , 40 Antibacterial action has also been described. 11 , 41
Antioxidant   Antioxidant action of U. dioica has been evaluated. The roots and stem have little action, while the leaves and seeds demonstrate high activity. The antioxidant effect may be responsible for a hepatoprotective effect, as well as an anti-apoptotic action in brain cells. 11 , 42 , 43 , 44 , 45 , 46 , 47
 
Administration & Dosage
Freeze-dried nettle leaf 600 mg has been used in a clinical trial for allergic rhinitis. 35 Clinical trials for BPH have used aqueous extracts of U. dioica root 360 mg daily over 6 months 17 and methanol root extract 600 to 1,200 mg daily for 6 to 9 weeks. 2
 
Pregnancy/Lactation
Documented adverse effects; reputed abortifacient and effects on androgen and estrogen metabolism. Avoid use. 2 , 48
 
Interactions
Case reports are lacking 2 ; however, the American College of Cardiology Foundation recommends caution due to possible potentiation of the effects of diuretics. 49 In an experiment with rat platelets, crude aqueous extracts as well as the isolated flavonoids inhibited platelet aggregation. 20
 
Adverse Reactions
Nettles are known primarily for their ability to induce topical irritation following contact with exposed skin. The acute urticaria is caused by the release of histamine, serotonin, and choline from the hairs and spines of the leaves and stem and generally resolves spontaneously. Treatment with systemic antihistamines and topical steroids may be of benefit. Case reports of prolonged effects exist. 8 , 50
Radix urticae extracts and other nettle preparations are generally well tolerated, with minor and transient gastric effects, including diarrhea, gastric pain, and nausea reported. 2 Case reports of hypoglycemia due to consumption of nettle preparations for prostatic hypertrophy exist, as well as gynaecomastia and galactorrhea. 34 , 51 Due to the effects on androgen and estrogen metabolism, nettle preparations are contraindicated in pregnancy and lactation and should not be used in children younger than 12. 2 , 48
 
Toxicology
The acute oral LD50 in rats has been estimated to be greater than 30 g/kg for the aqueous leaf extract and 1.3 g/kg for the root. 2 , 6 , 21 Liver function tests in rats fed aqueous nettle extracts for 30 days were normal. 21 Older mutagenicity and carcinogenicity studies have been negative for the aqueous extract. 6
 
References
 

1. Urtica dioica L. USDA, NRCS. 2010. The PLANTS Database ( http://plants.usda.gov , August 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.

 

2. Radix Urticae . In: WHO Monographs on Selected Medicinal Plants . Vol. 2. Geneva, Switzerland: World Health Organization; 2004:329-341.

 

3. Blumethal M, Busse WR, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines . Austin, TX: American Botanical Council; 1998:216.

 

4. Pinelli P, Ieri F, Vignolini P, Bacci L, Baronti S, Romani A. Extraction and HPLC analysis of phenolic compounds in leaves, stalks, and textile fibers of Urtica dioica L. J Agric Food Chem . 2008;56(19):9127-9132.  PubMed

 

5. Ganzera M, Piereder D, Sturm S, Erdelmeier C, Stuppner H. Urtica dioica agglutinin: separation, identification, and quantitation of individual isolectins by capillary electrophoresis and capillary electrophoresis-mass spectrometry. Electrophoresis . 2005;26(9):1724-1731.  PubMed

 

6. Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik S. A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix. Phytomedicine . 2007;14(7-8):568-579.  PubMed

 

7. Bisset NG, trans-ed. Herbal Drugs and Phytopharmaceuticals . Boca Raton, FL: CRC Press; 1994:5027.

 

8. Anderson BE, Miller CJ, Adams DR. Stinging nettle dermatitis. Am J Contact Dermat . 2003;14(1):44-46.  PubMed

 

9. Roschek B Jr, Fink RC, McMichael M, Alberte RS. Nettle extract ( Urtica dioica ) affects key receptors and enzymes associated with allergic rhinitis. Phytother Res . 2009;23(7):920-926.  PubMed

 

10. Broer J, Behnke B. Immunosuppressant effect of IDS 30, a stinging nettle leaf extract, on myeloid dendritic cells in vitro. J Rheumatol . 2002;29(4):659-666.  PubMed

 

11. Gülçin I, Küfrevioglu OI, Oktay M, Büyükokuroglu ME. Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle ( Urtica dioica L.). J Ethnopharmacol . 2004;90(2-3):205-215.  PubMed

 

12. Marrassini C, Acevedo C, Miño J, Ferraro G, Gorzalczany S. Evaluation of antinociceptive, antinflammatory activities and phytochemical analysis of aerial parts of Urtica urens L. Phytother Res . 2010;(12):1807-1812.  PubMed

 

13. Alford L. The use of nettle stings for pain. Altern Ther Health Med . 2007;13(6):58.

 

14. Rayburn K, Fleischbein E, Song J, et al. Stinging nettle cream for osteoarthritis. Altern Ther Health Med . 2009;15(4):60-61.  PubMed

 

15. Randall C, Dickens A, White A, Sanders H, Fox M, Campbell J. Nettle sting for chronic knee pain: a randomised controlled pilot study. Complement Ther Med . 2008;16(2):66-72.  PubMed

 

16. Durak I, Biri H, Devrim E, Sözen S, Avci A. Aqueous extract of Urtica dioica makes significant inhibition on adenosine deaminase activity in prostate tissue from patients with prostate cancer. Cancer Biol Ther . 2004;3(9):855-857.  PubMed

 

17. Safarinejad MR. Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study. J Herb Pharmacother . 2005;5(4):1-11.  PubMed

 

18. Cai T, Mazzoli S, Bechi A, et al. Serenoa repens associated with Urtica dioica ( ProstaMEV ) and curcumin and quercitin ( FlogMEV ) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int J Antimicrob Agents . 2009;33(6):549-553.  PubMed

 

19. Giannarini G, Autorino R. Re: Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int J Antimicrob Agents . 2009;34(3):283-284.  PubMed

 

20. El Haouari M, Bnouham M, Bendahou M, et al. Inhibition of rat platelet aggregation by Urtica dioica leaves extracts. Phytother Res . 2006;20(7):568-572.  PubMed

 

21. Daher CF, Baroody KG, Baroody GM. Effect of Urtica dioica extract intake upon blood lipid profile in the rats. Fitoterapia . 2006;77(3):183-188.  PubMed

 

22. Nassiri-Asl M, Zamansoltani F, Abbasi E, Daneshi MM, Zangivand AA. Effects of Urtica dioica extract on lipid profile in hypercholesterolemic rats. Zhong Xi Yi Jie He Xue Bao . 2009;7(5):428-433.  PubMed

 

23. Tahri A, Yamani S, Legssyer A, et al. Acute diuretic, natriuretic and hypotensive effects of a continuous perfusion of aqueous extract of Urtica dioica in the rat. J Ethnopharmacol . 2000;73(1-2):95-100.  PubMed

 

24. Testai L, Chericoni S, Calderone V, et al. Cardiovascular effects of Urtica dioica L. (Urticaceae) roots extracts: in vitro and in vivo pharmacological studies. J Ethnopharmacol . 2002;81(1):105-109.  PubMed

 

25. Legssyer A, Ziyyat A, Mekhfi H, et al. Cardiovascular effects of Urtica dioica L. in isolated rat heart and aorta. Phytother Res . 2002;16(6):503-507.  PubMed

 

26. Domola MS, Vu V, Robson-Doucette CA, Sweeney G, Wheeler MB. Insulin mimetics in Urtica dioica : structural and computational analyses of Urtica dioica extracts [published correction appears in Phytother Res . 2010;(24)(suppl 2):S233-S234]. Phytother Res . 2010;(24)(suppl 2):S175-S182.  PubMed

 

27. Farzami B, Ahmadvand D, Vardasbi S, Majin FJ, Khaghani Sh. Induction of insulin secretion by a component of Urtica dioica leave extract in perifused Islets of Langerhans and its in vivo effects in normal and streptozotocin diabetic rats. J Ethnopharmacol . 2003;89(1):47-53.  PubMed

 

28. Bnouham M, Merhfour FZ, Ziyyat A, Mekhfi H, Aziz M, Legssyer A. Antihyperglycemic activity of the aqueous extract of Urtica dioica . Fitoterapia . 2003;74(7-8):677-681.  PubMed

 

29. Golalipour MJ, Khori V. The protective activity of Urtica dioica leaves on blood glucose concentration and beta-cells in streptozotocin-diabetic rats. Pak J Biol Sci . 2007;10(8):1200-1204.  PubMed

 

30. Kavalali G, Tuncel H, Göksel S, Hatemi HH. Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats. J Ethnopharmacol . 2003;84(2-3):241-245.  PubMed

 

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32. Román Ramos R, Alarcón-Aguilar F, Lara-Lemus A, Flores-Saenz JL. Hypoglycemic effect of plants used in Mexico as antidiabetics. Arch Med Res . 1992;23(1):59-64.  PubMed

 

33. Golalipour MJ, Gharravi AM, Ghafari S, Afshar M. Effect of Urtica dioica on morphometric indices of kidney in streptozotocin diabetic rats—a stereological study. Pak J Biol Sci . 2007;10(21):3875-3879.  PubMed

 

34. Edgcumbe DP, McAuley D. Hypoglycaemia related to ingestion of a herbal remedy. Eur J Emerg Med . 2008;15(4):236-237.  PubMed

 

35. Mittman P. Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis. Planta Med . 1990;56(1):44-47.  PubMed

 

36. Harput US, Saracoglu I, Ogihara Y. Stimulation of lymphocyte proliferation and inhibition of nitric oxide production by aqueous Urtica dioica extract. Phytother Res . 2005;19(4):346-348.  PubMed

 

37. Akbay P, Basaran AA, Undeger U, Basaran N. In vitro immunomodulatory activity of flavonoid glycosides from Urtica dioica L. Phytother Res . 2003;17(1):34-37.  PubMed

 

38. Konrad A, Mähler M, Arni S, Flogerzi B, Klingelhöfer S, Seibold F. Ameliorative effect of IDS 30, a stinging nettle leaf extract, on chronic colitis. Int J Colorectal Dis . 2005;20(1):9-17.

 

39. Balzarini J, Neyts J, Schols D, et al. The mannose-specific plant lectins from Cymbidium hybrid and Epipactis helleborine and the (N-acetylglucosamine)n-specific plant lectin from Urtica dioica are potent and selective inhibitors of human immunodeficiency virus and cytomegalovirus replication in vitro. Antiviral Res . 1992;18(2):191-207.  PubMed

 

40. Uncini Manganelli RE, Zaccaro L, Tomei PE. Antiviral activity in vitro of Urtica dioica L., Parietaria diffusa M. et K. and Sambucus nigra L. J Ethnopharmacol . 2005;98(3):323-327.  PubMed

 

41. Gul N, Ahmed SA, Smith LA. Inhibition of the protease activity of the light chain of type A botulinum neurotoxin by aqueous extract from stinging nettle ( Urtica dioica ) leaf. Basic Clin Pharmacol Toxicol . 2004;95(5):215-219.  PubMed

 

42. Hudec J, Burdová M, Kobida L, et al. Antioxidant capacity changes and phenolic profile of Echinacea purpurea , nettle ( Urtica dioica L.), and dandelion ( Taraxacum officinale ) after application of polyamine and phenolic biosynthesis regulators. J Agric Food Chem . 2007;55(14):5689-5696.  PubMed

 

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44. Celik I, Tuluce Y. Elevation protective role of Camellia sinensis and Urtica dioica infusion against trichloroacetic acid-exposed in rats. Phytother Res . 2007;21(11):1039-1044.  PubMed

 

45. Ozen T, Korkmaz H. Modulatory effect of Urtica dioica L. (Urticaceae) leaf extract on biotransformation enzyme systems, antioxidant enzymes, lactate dehydrogenase and lipid peroxidation in mice. Phytomedicine . 2003;10(5):405-415.  PubMed

 

46. Toldy A, Atalay M, Stadler K, et al. The beneficial effects of nettle supplementation and exercise on brain lesion and memory in rat. J Nutr Biochem . 2009;20(12):974-981.  PubMed

 

47. Toldy A, Stadler K, Sasvári M, et al. The effect of exercise and nettle supplementation on oxidative stress markers in the rat brain. Brain Res Bull . 2005;65(6):487-493.  PubMed

 

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50. Caliskaner Z, Karaayvaz M, Ozturk S. Misuse of a herb: stinging nettle ( Urtica urens ) induced severe tongue oedema. Complement Ther Med . 2004;12(1):57-58.  PubMed

 

51. Sahin M, Yilmaz H, Gursoy A, Demirel AN, Tutuncu NB, Guvener ND. Gynaecomastia in a man and hyperoestrogenism in a woman due to ingestion of nettle ( Urtica dioica ). N Z Med J . 2007;120(1265):U2803.  PubMed