Nettles

Scientific Name(s): Urtica dioica L., Urtica urens L. Family: Urticaceae (nettles)

Common Name(s): Stinging nettle , nettle . Commercial preparations include Bazoton , Prostaherb , Prostamon , Prostatin , Simic , Urtica Plus , Urtidin .

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

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 LD 50 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

Bibliography

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