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Nettles

Scientific Name(s): Urtica dioica L., Urtica urens L.
Common Name(s): Nettle, Soii (Kashmiri), Stinging nettle

Clinical Overview

Use

Nettles are primarily used in the management of benign prostatic hyperplasia (BPH), diabetes, and arthritis. However, clinical trials are limited.

Dosing

Clinical trials for BPH have used aqueous extracts of U. dioica root in dosages of 360 mg daily over 6 months and methanol root extract in dosages of 600 to 1,200 mg daily for 6 to 9 weeks. Dosages of 600 mg of freeze-dried nettle leaf have been used in a clinical trial for allergic rhinitis. Standardization of commercial preparations is lacking.

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

Avoid use. Adverse effects have been documented.

Interactions

None well documented.

Adverse Reactions

Nettles are primarily known for their ability to induce acute urticaria following contact with exposed skin. Radix urticae extracts and other nettle preparations are generally well tolerated; minor and transient gastric effects, including diarrhea, gastric pain, and nausea, have been reported.

Toxicology

The possibility of oral toxicity with nettle preparations is considered low. Mutagenicity and carcinogenicity studies using the aqueous extract have been negative.

Scientific Family

  • Urticaceae (nettle)

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; they are often distributed together in the wild and considered therapeutically 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 bristles that transmit irritating principles upon contact. The plant flowers from June to September and its fruit is a small, oval-shaped seed approximately 1 mm wide and yellow-brown in color.1, 2, 3

History

Although known for its stinging properties, the nettle plant has been used in traditional medicine as a diuretic, antispasmodic, and expectorant, as well as in the treatment of asthma. The juice is 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 potherb 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. Nettles are considered to be nourishing plants and have 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 have been used.2 Phenolic compounds in the root, stalk, and leaves have been described.4, 5, 6 Compounds with possible 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, 7, 8, 9 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 acids. The stinging trichomes of nettle contain amines, including histamine, serotonin, and choline. Nettle fruit contains protein, mucilage, and fixed oil (primarily carvacrol [38%], carvone [9%], and naphthalene [9%]).2, 9, 10, 11

High-performance liquid chromatography, gas chromatography, capillary electrophoresis, and other methods have identified the lectin specific to U. dioica roots, which may help to standardize preparations.2, 7, 8, 12

Uses and Pharmacology

Anti-inflammatory effects

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.13, 14, 15, 16, 17, 18, 19

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. 20, 21, 22, 23

Experiments in rats, including induced pancreatitis, colitis, and biliary obstruction, showed that nettle extracts reduce proinflammatory cytokines and markers, and also protect against tissue damage.24, 25, 26

Clinical data

Limited clinical trials using nettle leaves to reduce pain associated with osteoarthritis have been conducted.27, 28 The methodological quality of these small studies is limited29, 30; however, further clinical trials may be warranted based on self-reported measures.31

Benign prostatic hyperplasia

Experimental studies suggest a number of possible mechanisms of action of nettle extracts in managing symptoms of BPH. Reductions in the plasma level of sex hormone–binding globulin involved in binding of circulating androgens and estrogen have occurred. 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.2, 9, 32 Anti-inflammatory effects have also been noted32; therefore, the Complete German Commission E Monographs support use in urinary tract inflammation and in the prevention and treatment of kidney gravel.3

Animal data

Animal studies have been conducted to evaluate the effect of U. dioica extracts in BPH; however, the availability of more recent clinical trial data makes these studies less important.2, 9, 32, 33 In vitro and animal studies have examined a potential role for nettle extract in prostate cancer, suggesting inhibition of adenosine deaminase as a further mechanism of action.32, 34

Clinical data

Most trials have been of open-label design, and few high-quality clinical trials using U. dioica alone compared with standard therapy have been conducted. However, some evidence suggests that certain nettle extracts do exhibit efficacy in reducing symptoms of BPH, as measured by International Prostate Symptom Score (IPSS).2, 9, 32, 33

Improved IPSS scores have been demonstrated in limited placebo-controlled, randomized clinical studies.35, 36, 37 Three clinical studies examined nettle extracts over 8 weeks,37 1 year,36 and 6 months35 in population sizes of 100, 246, and 558 participants, respectively. Not all studies showed improved maximal urinary flow rate. One study35 showed a modest reduction in prostate size when measured via transrectal ultrasound. No alterations in prostate-specific antigen or testosterone levels were reported in a clinical trial.35

Other industry-sponsored clinical studies have used combination preparations, such as saw palmetto with nettle extract, and demonstrated a positive but small effect on nocturia in BPH (absolute reduction of 0.2 voids per night; P = 0.0015).38

American Urological Association guidelines for the management of BPH conclude that there are not sufficient high-quality, single-extract clinical trials using U. dioica to recommend or discourage its use in the treatment of lower urinary tract symptoms secondary to BPH.39

Cardiovascular effects

Nettles have traditionally been used for their diuretic and hypotensive effects. In vitro studies show that U. dioica extracts may inhibit thrombin-induced platelet aggregation, possibly because of flavonoid content, although results of in vitro studies are equivocal.40, 41

Animal data

Improved lipid profiles have been demonstrated in rodent studies; reported effects on indices vary.42, 43, 44 Diuretic, natriuretic, and hypotensive actions have been demonstrated in rats.45, 46 In isolated heart studies, decreased heart rate and inotropic activity, as well as increased left ventricular pressure and vascular contractility, occurred.46, 47

Clinical data

There are no clinical data regarding the use of nettle in cardiovascular conditions.

CNS

Animal data

Anti-inflammatory and antioxidant effects of nettle extracts appeared to be protective in models of neurodegeneration in rodent studies.48 In a study in diabetic mice, nettle leaf extract improved memory and reduced depression-like behavior.49 In another study in diabetic rats, nettle extract improved cognitive function and increased pain threshold.50

Clinical data

There are no clinical data regarding the use of nettle in conditions of the CNS.

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 and reduced intestinal absorption of glucose by inhibition of alpha-amylase.51, 52, 53, 54, 55, 56, 57

Animal data

Serum glucose levels were reduced in some44, 50, 54, 58, 59, 60, 61 experiments in rats with induced diabetes.54, 59, 62 Nettle extracts had no effect on renal indices in diabetic rats63; however, protective effects on the liver, seminiferous, and nervous system tissue were observed in diabetic rats.50, 64, 65

Clinical data

Limited clinical studies have been conducted with nettle extracts alone. One small (N = 50) single-blind study using 100 mg/kg of hydroalcoholic nettle extract over 8 weeks showed decreased fasting glucose levels and decreased glycated hemoglobin, but no effect on insulin.66 There is a case report of hypoglycemia due to consumption of nettle preparations for prostatic hypertrophy.67

Other uses

Antimicrobial

In vitro studies have shown antiviral action against HIV, cytomegalovirus, coronavirus, rotavirus, and feline immunodeficiency virus.68, 69, 70, 71 Antibacterial action against both plant and human pathogens has also been described.20, 72, 73, 74, 75, 76, 77 A clinical trial with some methodological limitations78 evaluated the adjunctive effect of U. dioica as a combination preparation in treating bacterial prostatitis.79

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 for anti-apoptotic action in brain cells and protection in ischemia/reperfusion injury.20, 80, 81, 82, 83, 84, 85, 86, 87, 88

Antiproliferative

Screening studies have evaluated nettle extracts for antiproliferative effect with varying results.11, 89 While activity in human prostate cancer cells has been demonstrated,90 no clinically important apoptosis in human cancer cell lines has been reported,89 and no relationship between flavonoid content and antiproliferative effects has been noted.12 Animal and human studies are lacking.

Immune effects

Freeze-dried nettle has been evaluated for allergic rhinitis; in a double-blind trial, 600 mg of freeze-dried nettle leaf was more effective than placebo in controlling symptoms.91 Effects may be due to immunomodulatory or anti-inflammatory actions.14, 18, 92, 93, 94 Other immune effects have been described following in vitro studies, including a cellular response greater than that evoked by Echinacea tincture.95 Beluga sturgeon fed nettles showed increased neutrophil and red blood cell counts, as well as increased hemoglobin and hematocrit values.96

Dosing

Dosages of 600 mg of freeze-dried nettle leaf have been used in a clinical trial for allergic rhinitis.91 Clinical trials for BPH have used aqueous extracts of U. dioica root in dosages of 360 mg daily over 6 months35 and methanol root extract in dosages of 600 to 1,200 mg daily for 6 to 9 weeks.2

Pregnancy / Lactation

Avoid use. Adverse effects have been documented; nettle is a reputed abortifacient and has demonstrated effects on androgen and estrogen metabolism.2, 97

Interactions

Case reports are lacking2; however, the American College of Cardiology Foundation recommends caution because of possible potentiation of diuretic effects.98 In an experiment with rat platelets, crude aqueous extracts and the isolated flavonoids inhibited platelet aggregation40; however, an in vitro study using human blood samples found no effect on platelet function.41 Studies in rats found some effect of the seed extract on the cytochrome P450 enzyme system and on glutathione S-transferase, suggesting potential for interactions.99

Adverse Reactions

Nettles are primarily known for their ability to induce acute urticaria following contact with exposed skin, which generally resolves spontaneously and is caused by the release of histamine, serotonin, and choline from the hairs and spines of the leaves and stem. Treatment with systemic antihistamines and topical steroids may be of benefit.13, 100 Case reports of prolonged effects exist101; 1 case report describes generalized urticaria and elevated IgE levels in a neonate due to contact with maternal skin to which a nettle extract had been applied.84

Radix urticae extracts and other nettle preparations are generally well tolerated; minor and transient gastric effects, including diarrhea, gastric pain, and nausea, have been reported.2 There is a case report of hypoglycemia due to consumption of nettle preparations for prostatic hypertrophy; cases of gynecomastia and galactorrhea due to consumption of nettle tea have also been identified.67, 55 Clinical studies using nettles in BPH report no adverse effects at the doses used.35, 36, 37

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.2, 97

Toxicology

The oral median lethal dose in rats is estimated to be greater than 30 g/kg for the aqueous leaf extract and 1.3 g/kg for the root.2, 9, 42 Liver function tests in rats fed aqueous nettle extracts for 30 days were normal.42 A dose of 2 g/kg of leaf extract caused diarrhea and diuresis in rats.76 Mutagenicity and carcinogenicity studies using the aqueous extract have been negative.9

References

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