by Gayle Engels, Josef Brinckmann
HerbalGram. 2016; American Botanical Council
INTRODUCTION
Urtica dioica, known as stinging nettle,1,2 greater nettle,2 common nettle,3-5 giant nettle,3 European nettle,3 or simply “nettle,”1,5 and U. urens (burning nettle, lesser nettle, or dwarf nettle) are native to Europe and Eurasia and grow wild throughout temperate parts of the world.1,2 The family name Urticaceae, generic name Urtica, and species name urens are derived from the Latin verb urere, meaning “to burn,” a reference to the plant’s stinging hairs.1,2 The species name dioicacomes from the Greek for “two houses,” which refers to the male and female flowers that occur on separate plants (i.e., they are dioecious).1,2
The materials of commerce may originate from either species or hybrids or mixtures of the two.6 Urtica urens is a low-growing, monoecious (each plant has both male and female reproductive organs) annual that typically is only 20-30 cm (7.9-11.8 in) in height, but can grow up to 80 cm (2.6 ft). Urtica dioica is a dioecious perennial that reaches up to 150 cm (4.9 ft) in height.6 There are significant differences in the contents of biologically active compounds between leaves of male and female U. dioica plants.7
While the American Herbal Products Association’s Herbs of Commerce, 2nd ed., narrowly defines stinging nettle as a subspecies (U. dioica subsp. dioica),8 the European Pharmacopoeia does not make such a distinction. Version 1.1 of The Plant List states that U. dioica subsp. dioica is a synonym of U. dioica.9 The taxonomy of U. dioica remains controversial, as demonstrated by the conflicting information in Herbs of Commerce and The Plant List. There is also some disagreement about the classification of U. dioica subsp. gracilis (California nettle). Many authors (likely incorrectly) state that U. dioica (or subspecies) is native to the Americas and eastern Asia. While older literature suggests that U. dioica is native throughout the entire Holarctic region (non-tropical parts of Europe, Asia, northern Africa, and North America), new taxonomic research calls this into question, suggesting that, for example, American species are distinct and should be removed from U. dioicaand placed instead into U. gracilis as the “New World-sister” to U. dioica. In particular, it is proposed that U. dioica subsp.gracilis be changed to U. gracilis subsp. gracilis.10
The weedy, sprawling plants emerge in early spring from spreading rhizomatous roots, and bear opposite, toothed, variable leaves (ovate, elliptical, or lanceolate) and minute green, greenish-white, or pink flowers that form in clusters in the leaf axils.4,5 The stem and leaves are pubescent, and the stinging hairs (trichomes) can be distinguished from the other hairs by their shape and larger size.5 Each of the stinging hairs has at its base a secretory structure, a hollow, elongated tube like a syringe, and a bulbous tip that breaks off easily.4 The gland-like secretory structure supplies a combination of chemicals (see Modern Research section) responsible for the stinging, itching, or mild to severe burning sensation that can continue for minutes, or even hours, after contact with nettle.4,11 However, if the plant is dried and powdered, extracted, or cooked, no reaction takes place.11
Several plant parts are used medicinally, including the dried leaf, the dried herb (aerial parts collected in the flowering period), dried fruit (seed), and the dried root and rhizome. These are obtained primarily from wild-collection in eastern Europe, in particular Bulgaria, Hungary, Poland,12 the Czech Republic,13 and Romania,14 and in southern Europe, especially Albania, Croatia,15 Bosnia and Herzegovina,16 Kosovo,17 Serbia,18 Slovenia,19 and Macedonia.20 Wild-collection also takes place in western Asia, including Georgia21 and Turkey,22 and Central Asia, especially Kazakhstan.23
Commercial cultivation takes place in Canada,24 Mexico, and the United States,23 in African countries, especially Egypt,25and in European countries, particularly the United Kingdom and Germany. Several named cultivars are protected in Germany, including “Urimed” (owned by Pharmaplant GmbH; Artern, Germany), and “Nesselgold” and “Wulfsdorf” (both owned by the University of Hamburg; Hamburg, Germany).6
This article does not address other Urtica species, such as U. fissa, for example, the dried leaves and roots of which are wild-collected in China, exported and traded under the English common name nettle23 or the Chinese name qian ma (荨麻).
HISTORY AND CULTURAL SIGNIFICANCE
The use of nettle as a vegetable and folk remedy dates back to ancient times. It was mentioned by Hippocrates (ca. 460-370 BCE) and Theophrastus (ca. 371-287 BCE), by Dioscorides (40-90 CE) in Materia Medica, and by Pliny the Elder (23-79 CE) in Naturalis Historia.26 The Materia Medica suggested nettle for gangrene, rheumatism, tumors, ulcers, and dog bites.
In the medieval period, nettles were recommended by German philosopher, natural historian, and abbess Hildegard von Bingen (1098-1179) in Physica; by the Swiss physician Paracelsus (1493-1541) in his writings on the doctrine of signatures; by English physician Andrew Borde (ca. 1490-1549) in A Dyetary of Helth (1542); and by German botanist and physician Hieronymus Bock (1498-1554) in Kreütterbuch (1546).26
The English herbalist, physician, and botanist Nicholas Culpeper (1616-1654) said nettle was “an herb so well known, that you may find them by the feeling in the darkest night,” likely referring to its stinging hairs.27 He recommended nettle to break up stones, stop bleeding, and increase urination, and for difficulty breathing, pleurisies, cough, and inflammation of the lungs. Culpeper also said that nettles provoke lust and help people hold their necks upright.27
Along with dandelion (Taraxacum officinale, Asteraceae; profiled in HerbalGram issue 109), European elder (Sambucus nigra, Adoxaceae; profiled in HerbalGram issue 97), and the various docks (Rumex spp., Polygonaceae), nettle featured prominently in British folk medicine.28 It was used as a spring tonic “to cleanse blood” of the impurities that were believed to cause clouded eyes, boils, pimples, and various types of sores, and it was eaten to relieve anemia, as a counterirritant for rheumatic conditions, and for nose bleeds, colds, coughs, consumption (tuberculosis), dandruff, diarrhea, dropsy (edema), ear infections, epilepsy, headaches, and heart trouble. Nettle was also used for high blood pressure, insect stings, insomnia, jaundice, nervous conditions, paralyzed limbs, piles (hemorrhoids), ringworm, shingles (herpes zoster), stomach upset/indigestion, swelling (mumps) and swollen glands (goiter), worms, and, externally, for skin-cleansing.28 Nettle beer was a popular remedy for rheumatism during the Middle Ages.29 Additionally, the plant tops were used as a rennet substitute in making cheese, and the leaves were wrapped around fruits to help them ripen.29
Although likely introduced species from Europe, American Indian tribes found uses for both U. dioica and U. urens.30 They used the plants for food and for fiber to make bow strings, cords, ropes, cloth, fishnet, and baskets. Infusions and decoctions were used internally for ague (alternating periods of chills, fever, and sweating, as in malaria), bladder conditions, colds, dysentery, locomotor ataxia (the inability to control bodily movements), bleeding hemorrhoids, headache, hives and itching, paralyzed limbs, upset stomach and stomach pain, skin conditions, and the promotion of urination. They were also used during pregnancy and to support blood flow after childbirth. The Nitinaht tribe (Vancouver Island, British Columbia, Canada) chewed and swallowed young nettle shoots to prevent illness. Externally, steamed nettle leaves and roots were used in poultices and sweat baths for sore and/or swollen arthritic joints, colds, grippe (influenza), heat rash, and pneumonia. Nettles were rubbed on the body for aches, pains, and soreness, and the plant’s juice was rubbed on the scalp to prevent hair loss and as a tonic for growing long, silky hair. More recently, some Native American tribes and others have used nettles to relieve arthritis and rheumatism through the practice of urtication, wherein the afflicted areas are whipped with nettle branches (flagellation). Curiously, this same method was used by married members of the Nitinaht tribe for “affection and faithfulness of spouses.” Stems were put under splints to hasten healing of broken bones, and the plant fiber was used for headaches, inflammation, and was applied to the skin for various ailments. At least one tribe, the Makah of the Olympic Peninsula in Washington state, used the plant as a stimulant by rubbing it into the skin after bathing. They also rubbed whale hunters’ bodies with the plant for strength.30
Modern herbalists and other alternative health care providers use nettle for its astringent, tonic (i.e., nourishing, strengthening, and toning), hypotensive,31 anti-inflammatory,32 anti-hemorrhagic,33,34 diuretic,31,34,35 and hypoglycemic29 actions. It is used to improve urine flow, decrease residual urine volume, and reduce urinary frequency and nocturia (excessive nighttime urination) in early-stage benign prostatic hyperplasia (BPH), to address inflammation in the lower urinary tract and treat renal stones,36 to lower blood sugar levels, to alleviate myalgia (muscle pain), osteoarthritis,31,35 rheumatoid arthritis,31,34,35 allergic rhinitis (hay fever),32,34 childhood and psychogenic (especially nervous) eczema, 31,33 and to detoxify the body.31 Midwives use nettles to address anemia in pregnant women, and, topically, for pruritic urticarial papules and plaques of pregnancy (PUPPP; a hives-like rash that sometimes occurs during pregnancy) in an Aloe vera (Xanthorrhoeaceae) gel, witch hazel (Hamamelisspp., Hamamelidaceae), or cream base.32
From the 19th century until the end of World War II, U. dioica was cultivated in parts of Europe as a fiber crop alternative to cotton (Gossypium spp., Malvaceae). Due to cotton shortages during the World Wars, Germany switched to nettle fiber to make military uniforms. In the early 1940s, approximately 500 hectares (1,236 acres) of nettle were under cultivation in Austria and Germany, but this came to a halt when the nettle processing facilities were destroyed during World War II. In recent years, U. dioica cultivation has started up again in Germany.37 (Interestingly, there is a German idiom — sich in die Nesseln setzen — which literally means “to sit down in nettles.” In context, it means that someone got himself into trouble.)
In 1986, the German Commission E approved the use of Urticae Radix (subterranean plant parts), prepared as an herbal tea infusion or in other galenical forms, as a nonprescription medicine taken orally to treat urination difficulties in BPH stages I and II.38 Subsequently, in 1987, the Commission E approved the use of both Urticae Folium (leaf) and Urticae Herba (aerial plant parts), as an herbal tea or in other galenical forms, taken orally as irrigation therapy for inflammatory diseases of the lower urinary tract and for the prevention and treatment of kidney stones. For topical application, spirit of nettle (an alcoholic solution of distilled nettle; 50% alcohol by volume)1 was approved as a supportive therapy for rheumatic ailments.38 In the meantime, official national labeling standards monographs of European Union (EU) member states, such as those of the German Commission E, have been superseded by monographs of the European Medicines Agency (EMA).
There are English-language quality standards monographs established by the European Directorate for the Quality of Medicines (EDQM) for two articles, Urticae Folium PhEur and Urticae Radix PhEur,39,40 with corresponding labeling standards monographs established by the EMA.41-43 The United States Pharmacopeia (USP) provides quality standards monographs for the dried roots and rhizomes of U. dioica L. subsp. dioica with U. urens, as well as for the dry extract of the roots and rhizomes.44 Comprehensive monographs (quality and therapeutics) for Urticae Radix are available in theWHO Monographs on Selected Medicinal Plants,45 the English and Russian editions of the WHO Monographs on Medicinal Plants Commonly Used in the Newly Independent States (NIS),46 and the American Herbal Pharmacopoeia and Therapeutic Compendium (AHP).47 There is also an AHP monograph for Stinging Nettle Herb.48
CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the US, plant parts or preparations of U. dioica and/or U. urens are not generally recognized as safe (GRAS) for use in food products, but are permitted as components of dietary supplement products. The US Food and Drug Administration (FDA) requires notification within 30 days of marketing (if a structure-function claim is made) and product manufacturing according to current Good Manufacturing Practices (cGMPs) for dietary supplements.49 In October 2015, nettle (U. dioicasubsp. dioica) leaf was nominated for use in pharmacy compounding and placed on the FDA’s 503A List 1 – Bulk Drug Substances Under Evaluation,50 which means it is viewed as a bulk drug substance that may be eligible for inclusion on the 503A bulks* list, because sufficient supporting information was provided to the FDA for evaluation.51
In Canada, nettle is regulated as an active ingredient of licensed natural health products (NHPs), requiring pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD).52 The authorized uses for labeling of nettle NHPs vary somewhat depending on the plant part(s). Preparations of the aerial parts (as fluid extracts, tinctures, fresh juices, herbal tea decoctions or infusions) may be labeled with claims including “Traditionally used in Herbal Medicine as a diuretic,” and “Used in Herbal Medicine as supportive therapy to help relieve rheumatic complaints, as a nutritive tonic, and to help relieve seasonal [allergies].” Preparations of the root (dry or liquid extracts, herbal tea decoctions or infusions) may be marketed with the claim “Used in Herbal Medicine to help reduce difficulty in urination associated with the early stages of benign prostatic hyperplasia (BPH).”
In the EU, while it is possible to market nettle leaf-containing products as food products without health claims, various defined therapeutic preparations of nettle leaf, nettle herb, and nettle root are regulated as traditional herbal medicinal products (THMPs), requiring registration and pre-marketing authorization. The EU approves the following therapeutic indications for nettle herb (prepared as an expressed juice, fluid extract, herbal tea, tincture, or dry extract): (1) “THMP to increase the amount of urine to achieve flushing of the urinary tract as an adjuvant in minor urinary complaints”; (2) “THMP for relief of minor articular pain”; and (3) “THMP used in seborrheic (inflammatory) skin conditions.”41 Indications (1) and (2) are also permitted for preparations of nettle leaf.42 Preparations of nettle root (herbal teas or dry or liquid extracts) may be labeled with the claim “THMP for the relief of lower urinary tract symptoms related to benign prostatic hyperplasia after serious conditions have been excluded by a medical doctor.”43For marketing authorization, the applicant must specify the quality of the nettle active ingredients according to pharmacopeial standards and assure consistent quality through implementation of the EMA’s Good Agriculture and Collection Practices (GACP) for starting materials of herbal origin.53
For use in cosmetic products, the European Commission Health and Consumers Directorate lists Urtica Dioica Juice, Urtica Dioica Leaf Extract, Urtica Dioica Root Extract, and Urtica Urens Leaf Extract for skin-conditioning functions.54 An extract of all aerial parts is authorized for antidandruff, astringent, hair-conditioning, skin-conditioning, soothing, and tonic functions.
MODERN RESEARCH
Chemicals produced in the stinging hairs of nettle include histamine, acetylcholine, serotonin, and formic acid.4,34,55 Other constituents found in nettle include leukotrienes, oxalic acid, tartaric acid,11 flavonoids (glucosides and rutinosides of isorhamnetin, kaempferol, and quercetin), caffeoyl-esters (caffeoylmalic acid [U. dioica only], chlorogenic acid, and neochlorogenic acid), caffeic acid, scopoletin (cumarin), sitosterol (-3-0-glucoside), polysaccharides, fatty acids, vitamin C and other vitamins, minerals, protein, and dietary fiber.31,34,55,56
Pharmacological studies of nettle extracts have shown the following effects in vitro and in vivo: analgesic,56,57 anesthetic, antianemic,56 antibacterial,58 anti-inflammatory, antilipidemic, antimicrobial,56 antioxidant,56-58 antiulcer,57 cardiovascular, central depressive, chemopreventive, diuretic, endocrine, gastrointestinal, hepatoprotective, platelet-aggregating, immunomodulatory, and vasoconstrictive.56
Clinical studies and case reports of varying quality have investigated the use of nettle alone, or in combination with other herbs, to address symptoms of type 2 diabetes, urinary conditions related to prostate health, osteoarthritis, allergic rhinitis, excessive bleeding after dental surgery, and episiotomy repair.
Much of the recent research on the use of nettle in treating symptoms of type 2 diabetes has been conducted in Iran and Pakistan. There were 285 million cases of diabetes in the world in 2010, a number expected to increase to 439 million by 2030, and there is considerable interest in these countries as to how traditional medicinal plants can be used for treatment instead of, or in addition to, pharmaceutical drugs.
One randomized, double-blind, placebo-controlled (RDBPC) clinical study published in 2014 investigated the effect of nettle’s aerial parts on glycemic control and insulin resistance in patients with type 2 diabetes.59 Sixty patients were randomly assigned to take either 100 mg/kg per day of nettle extract (no additional information provided) or placebo after each of three main meals for eight weeks. Patients were asked to not make any changes to their current drug treatments, diet, or exercise routines during the study. After eight weeks, the nettle group experienced significantly increased insulin concentration, -cell function, and insulin sensitivity, significantly decreased insulin resistance, and no differences in fasting blood sugar, compared to the placebo group.
In a RDBPC study published in 2012, nettle leaf extract was evaluated for its efficacy in treating type 2 diabetes in patients resistant to conventional oral anti-hyperglycemic drugs who required insulin shots.60 Patients refusing insulin with glycosylated hemoglobin (HbA1c) levels above 200 mg/dL of blood (N = 22) took either placebo or 500 mg of encapsulated nettle leaf extract (70% ethanol, 30% water; solvent removed in a rotary evaporator; extract encapsulated with 12% toast powder excipient) three times per day for three months. Drug treatment, diet, and physical activity did not change during the study. Fasting blood glucose, two-hour postprandial (post-meal) glucose, and HbA1c levels were taken at the beginning and end of the study. After three months, patients in the nettle group experienced a significant lowering of HbA1c levels, and no significant effects on other blood parameter levels, compared with the placebo group. Also, the test group’s fasting glucose and HbA1c levels decreased significantly between baseline and endpoint with no other significant blood parameter changes. The placebo group’s blood parameters did not change significantly between baseline and endpoint. The authors conclude that nettle could be safe and effective in improving glycemic control in patients with type 2 diabetes.
In another RDBPC study published in 2012, 50 diabetic patients were randomized to take either 100 mg/kg of hydroalcoholic nettle extract (45% ethanol, 55% water; 2.7 g dry aerial parts; prepared by the Traditional Medicine Association of Iran-Eastern Azerbaijan and Giah Esanse Company; Gorgan, Iran) or placebo in three portions dissolved in water after each of three main meals every day for eight weeks.61 At the end of the study, the nettle group experienced a significant increase in total antioxidant capacity and superoxide dismutase (an antioxidant enzyme) compared to the placebo group. The authors note that hydroalcoholic nettle extract can improve antioxidant status and may help prevent cardiovascular disease.
A similar randomized, double-blind study published in 2011 examined a hydroalcoholic extract of nettle leaf on insulin sensitivity and inflammatory markers in patients with type 2 diabetes.62 Fifty patients were randomly assigned either 100 mg/kg of nettle extract (45% ethanol, 55% water; 2.7 g dry aerial parts; prepared by the Traditional Medicine Association of Iran-Eastern Azerbaijan and Giah Esanse Company; Gorgan, Iran) or placebo in three portions per day for eight weeks. At the end of the study, there was a significant decrease in interleukin 6 and high-sensitivity C-reactive protein in the nettle group, compared to the placebo group, suggesting that hydroalcoholic nettle extract may protect patients with type 2 diabetes from cardiovascular disease by decreasing certain inflammatory markers.
One large RDBPC crossover study published in 2005 investigated the effect of nettle therapy for relief of lower urinary tract symptoms (LUTS).63 Patients with LUTS (N = 620) were randomized to take either a nettle root fluid extract made by fractional percolation and standardized to 100 mg of root extract per 1 mL (no further information provided) or placebo three times per day with meals. At the end of six months, patients were evaluated using the International Prostate Symptom Score (IPSS). In addition, maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), serum prostate-specific antigen (PSA) levels, testosterone levels, and prostate size were measured. Further, at the end of the trial, both groups took the nettle preparation for up to 18 months. Of the 558 patients who completed the study, 232 of the 287 patients (81%) in the nettle group reported improved LUTS compared to 43 of the 271 subjects (16%) in the placebo group. The IPSS and Qmax improved more with the nettle preparation than with placebo, and PVR decreased in the nettle group only. Neither group experienced changes in serum PSA levels or testosterone levels. Also, patients who took nettle extract for up to 18 additional months experienced even more improvement.
A 2004 RDBPC multicenter study examined Bazoton-uno† (459 mg of stinging nettle root dry extract [drug extract ratio 7.1-14.3:1, solvent 20% methanol] per film tablet; Abbott GmbH & Co.; Wiesbaden, Germany) for its efficacy in the long-term treatment of BPH.64 Patients with BPH (N = 246) were enrolled in the study (which had a four-week placebo run-in phase followed by a 52-week therapy phase) and were randomized to take either Bazoton-uno or placebo once per day after breakfast. Clinical evaluations were performed at weeks four, 12, 24, 36, and 52. During the course of the study, the mean IPSS improved continuously in the test group compared to placebo. Qmax and median volume of residual urine showed a pronounced improvement in the test group compared to the placebo group, but the change was not statistically significant.
In 1985, in a nine-week, double-blind study on Bazoton (300 mg of stinging nettle root extract [drug extract ratio 5:1, solvent 20% methanol] per capsule; Kanoldt Arzneimittel GmbH; Hochstadt/Donau, Germany), 50 patients with BPH took one capsule of Bazoton or placebo in the morning and evening.65 Patients were evaluated at three, six, and nine weeks. Regarding subjective symptoms, patients reported no changes in frequency of urination, alguria (painful urination), or night-time dribbling, but dysuria (difficult urination), with delayed onset and respectively diminished flow, improved markedly in the Bazoton group compared to placebo.
At least six studies have been conducted on Prostagutt forte (“PRO”; Dr. Willmar Schwabe Pharmaceuticals; Karlsruhe, Germany), a combination product containing 160 mg of saw palmetto (Serenoa repens, Arecaceae) extract (WS 1473, an ethanolic [90% by weight] extract containing a minimum of 70% fatty acids and esters) and 120 mg of nettle root dry extract. The study evaluated the product’s ability to relieve symptoms of, and to delay surgery for, BPH. One study showed that PRO was equivalent in efficacy to, but had fewer adverse events than, finasteride.66 A study published in 2012 showed that PRO decreased white blood cell counts in prostatic secretion, decreased prostate volume, and relieved inflammation more rapidly than nonsteroidal anti-inflammatory drugs (NSAIDs).67 In a study published in 2007, PRO reduced the IPSS, increased urinary flow, and decreased residual urine volume.68 Another study reported that PRO was not inferior to tamsulosin in relieving LUTS.69 One study reported that a year of PRO therapy was well-tolerated and effective compared to placebo.70 Another study found that treatment with PRO was an effective method for avoiding or delaying surgery for BPH.71
There have been a number of studies on another combination product for prostate health, called ProstaMEV Plus (FarmaceuticaMEV; Siena, Italy), which contains 320 mg of saw palmetto, 0.4% nettle (plant part not specified), and 1600 gelatin digesting units (GDUs) of bromelain (an extract of enzymes found in pineapple; Ananas comosus, Bromeliaceae).72 In one study published in 2015, two groups treated with ProstaMEV Plus for two months experienced greater improvements in IPSS, urinary flow, and sex life than did the groups treated with only 320 mg of saw palmetto, irrespective of antibiotic use.73In another study, ProstaMEV (containing saw palmetto and nettle [plant part not specified], but not bromelain) improved the efficacy of the antibiotic prulifloxacin in bacterial prostatitis patients.74
A RDBPC, parallel-arms clinical study published in 2009 examined the commercially prepared combination food supplement Phytalgic (Phythea Laboratories; Savigny-le-Temple, France) — containing 150 mg of U. dioica dry extract (plant part not specified), 1,350 mg of fish oil, 45.8 mg of microencapsulated zinc sulfate, and 10 mg of vitamin E — for its efficacy in treating osteoarthritis (OA).75 Patients (N = 81) with OA of the knee or hip regularly using NSAIDs and/or analgesics were randomized to take either three capsules per day for three months of Phytalgic or placebo. The primary outcome measure was the use of NSAIDs or analgesics (500 mg of acetaminophen-equivalent tablets/week). After three months, the mean use of NSAIDs and analgesics was significantly different in the test group compared to placebo. The test group also scored significantly better with regard to pain, stiffness, and function.
One randomized, double-blind study published in 1990 investigated the effects of a freeze-dried preparation of nettle, containing 300 mg of nettle leaf (Eclectic Institute; Sandy, Oregon), on symptoms of allergic rhinitis.76 The 98 subjects who volunteered for the study were given either nettle capsules or placebo, and were instructed to take two capsules at the onset of allergy symptoms. Subjects recorded their responses to the medication, along with the total number of doses taken over the course of the one-week study. (The author does not specify how or when the subjects were instructed to take additional doses.) Of the 69 subjects who completed the study, 16 in the test group (n = 31) rated nettle as less effective than conventional pharmaceutical hay fever medicines they had taken previously, and 15 rated it as equally or more effective than previous medicines. Thirty subjects in the placebo group (n = 38) rated it less effective than previous medicines, and eight rated it as equally or more effective. Sixteen subjects in the test group indicated that they would buy and use the medication in future, whereas only seven in the placebo group said they would.
FUTURE OUTLOOK
The International Union for Conservation of Nature (IUCN) European Red List of Medicinal Plants assigns both U. dioicaand U. urens to the conservation category of Least Concern (LC), meaning that these species are not threatened.77 Wild populations of nettle appear to be abundant in Europe and continue to serve as an important source of household income in rural areas throughout eastern and southern Europe.12 Wild-collection enterprises are able to collect nettle herb (aerial parts) and nettle leaf in the summer months, and the subterranean parts (root and rhizome) in the fall. Families that collect nettle for income often collect other economically important wild medicinal plants that grow in the same areas, such as dandelion leaf and root, dog rose (Rosa canina, Rosaceae) hip, European elder flower and fruit, linden (Tilia cordata and T. platyphyllos, Tiliaceae) flower, and raspberry (Rubus idaeus, Rosaceae) leaf, among many others.12
Although trade data are not available through national databases, due to the absence of a species-specific tariff code for nettle, some countries keep records of quantities through export license declarations. For example, wild-collected nettle leaf (Folium Urticae) ranks as Bulgaria’s fourth largest medicinal plant export by volume, with an average of 930,595 kg (more than 2 million lbs) exported annually. Nettle root (Radix Urticae) ranks eleventh, with an average annual export quantity of 432,780 kg (954,117 lbs). Bulgaria also exports a relatively small amount of nettle herb (Herba Urticae, aerial parts), at an average of 53,111 kg (117,090 lbs) annually.78 Romania reportedly exports about 50,000 kg (110,231 lbs) of nettle herb annually.14 In addition, the single most important wild-collected medicinal plant from Poland, in terms of annual quantity harvested, is nettle leaf.79 Another indicator of the widespread use of nettle is the relatively high number of nettle-containing herbal medicinal products with marketing authorizations in European and North American countries. For example, according to the drug information database of the German Federal Institute for Drugs and Medical Devices (BfArM), there are 1,540 medicinal products containing nettle leaf in Germany alone.80 And, in Canada, at the time of this writing (March 2016), the Licensed Natural Health Products Database (LNHPD) listed 650 licensed NHPs that contain U. dioica herb or root as an active ingredient, and 54 NHPs that contain U. urens herb or root as an active ingredient.81
There is evidence that nettle production is occurring increasingly through sustainable wild-collection methods and sustainable agriculture practices. Cultivated certified-organic nettle is presently coming to market from farms in Germany,82 the UK,83 Egypt,26 Canada, Mexico, and the US,23 and many wild-collection operations have implemented the “organic wild-crop harvesting practice standard” for certified-organic wild-collected nettle, particularly in Albania, Bosnia and Herzegovina, Bulgaria, Hungary, Kazakhstan, Macedonia, and Poland. Several organic-wild nettle operations have also implemented the FairWild Standard, which includes criteria not only for ecological sustainability, but also for economic and social sustainability for the harvesters and their communities.12 There is also cultivated nettle with fair trade certification coming from Egypt.25 With the increasing uptake of credible sustainability standards that help protect the ecosystems where nettle and other medicinal plants are harvested, the tradition of wild-collection has a chance to continue, as local and rural people begin to rely on better income through organic and fair trade pricing structures.
—Gayle Engels and Josef Brinckmann
* Per the US FDA Guidance Document: “Section 503A of the FD&C Act includes certain restrictions on the bulk drug substances that can be used in compounding and directs the FDA to develop a list of bulk drug substances that can be used in compounding under that section. FDA is developing this list of bulk drug substances (the 503A bulks list), and this guidance describes FDA’s interim regulatory policy for licensed pharmacists in State-licensed pharmacies and Federal facilities, and for licensed physicians that compound human drug products using bulk drug substances while the list is being developed.”50
† Bazoton products were initially marketed by Kanoldt Arzneimittel GmbH. Kanoldt was acquired in 2000 by Abbott GmbH & Co. In 2014, Abbott was acquired by Mylan Inc. The Bazoton products are now manufactured by Riemser Specialty Production GmbH (Laupheim, Germany), and marketed by Mylan Healthcare GmbH (Hannover, Germany).
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