Stinging Nettle

Stinging Nettle is quite a nasty plant to touch, but oral ingestion of pills without spikes results in a moderately potent anti-inflammatory that can reduce the sniffles. Does not boost Testosterone despite being claims to, although it can help Benign Prostatic Hyperplasia and urine abnormalities.

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Also Known As

Urtica dioica, Radix Urticae, Common Nettle, Greater Nettle, Ortica, Tsuknida


Things to Note

  • Quite a bit of the trials decided to just throw in multiple herbs, so benefits seen cannot be attributed to Urdica Dioica in isolation for these studies
  • Apparently, rubbing the leaves of Urdica Dioica onto sore joints (despite supplements being from the roots, due to higher levels of active ingredients) might aid in joint pain

120mg of Stinging Nettle (root) taken three times a day (totalling 360mg) is associated with benefit in Benign Prostate Hyperplasia.


The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Stinging Nettle has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CAnti-Oxidant Enzyme Profile

Minor

An increase in glutathione peroxidase has been detected

CLipid Peroxidation

No significant effect on lipid peroxidation has been noted.

CInflammation

Minor

Appears to reduce LPS-stimulated proinflammatory cytokine release, and thus is likely to have anti-inflammatory effects. The potency of this is not overly remarkable

CC-Reactive Protein

Minor

Minor decrease in C-reactive protein concentrations

CWeight

No significant influence on body weight with consumption of stinging nettle

CInsulin Sensitivity

No significant interactions between insulin sensitivity and stinging nettle yet detected

CTNF-Alpha

No apparent effect on circulating TNF-a at baseline (may reduce TNF-a secretion from proinflammatory signals, see inflammation)

CTestosterone

No detectable influence on testosterone levels

CSymptoms of Benign Prostatic Hyperplasia

Minor

Appears to increase urinary flow rate in persons with benign prostatic hyperplasia

CProstate Hypertrophy

No significant influence on prostatic hypertrophy despite reducing symptoms

CSymptoms of Osteoarthritis

Highly difficult to assess the efficacy of stinging nettle on osteoarthritic symptoms due to a wide degree of variance in study methodology

CAllergies

Minor

A small decrease in allergic symptoms with oral stinging nettle consumption

CNasal Congestion

Minor

A slight decrease in nasal congestion seen with stinging nettle


Studies Excluded from Consideration


Disagree? Join the Stinging Nettle Discussion

Table of Contents:


Edit1. Sources and Composition

1.1. Background

Stinging Nettle, also known as Urtica dioica from the family Urticaceae, is a widespread herbal used frequently for 'male health'; usually referring to the prostate and urinary tract. Initially indigenous to Africa and some parts of Asia, it is now located in all temperate zones across continents.[5] It has sometimes been used to promote hair growth and to promote lactation and prevent uterine bleeding after childbirth.

1.2. Composition

As a herbal supplement, Stinging Nettle contains a variety of nutrients. These include:

  • The glycoside Beta-sitosterol, and related compounds daucosterol and campesterol[6]
  • Scopoletin[6]
  • Stigmasterol
  • Lignans such as (+)-neoolivil, isolariciresinol, and pinoresinol.[7]
  • Secoisolariciresinol and its main intestinal metabolites, enterofuran and 3,4-divanillyltetrahydrofuran[7], the latter of which appears to have great affinity for binding to SHBG[8]
  • Ursolic Acid[9]
  • 14-octacosanol[9]
  • Oleanolic Acid[9]
  • A lectin localized to the roots with affinity for N-Acetylglucosamine moeities[10]
  • The fatty acids of oleic, gadoleic, stearic, palmitoleic and erucic acids[11]
  • Quercetin, Kaempferol, and Isorhamnetin as well as some glycosides (mostly rutinoside and Isorhamnetin-3-O-neohesperidoside)[12]
  • Coumaric Acid, of which p-coumaric acid is at 5mcg/g[12][13]
  • Chlorogenic Acid and caffeic acid (a metabolite of chlorogenic acid)[12]
  • Vanillic and and structurally related compounds (homovanillyl alcohol at 8mcg/g, hydroxycinnamic acids, ferulic acid at 20mcg/g)[14][13][15]
  • Some Anthocyanins, particularly Pelargonidin[16]
  • Vitamin C (Ascorbic Acid) at 130mg per kg fresh plant[12]
  • A serotonin, acetylcholine, and histamine content in the hairs;[12] these may contribute to the blushing/burning sensation seen when touching fresh nettle[17]

The active ingredient tends to be seen as beta-sitosterol; which is the daucosterol molecule after daucosterol is separated from the glucose moiety. There is some confusion as to whether or not it actually is the active molecule, as overall amounts of beta-sitosterol tend to be less than 0.01% if not otherwise concentrated, and isolated beta-sitosterol seems to best influence prostate health (most common usage of Stinging Nettle) at dosages above 60mg.[18]


Edit2. Interactions with Hormones

2.1. Testosterone

In a study on 558 patients of Benign Prostate Hyperplasia, testosterone levels were measured and no statistically significant differences were found between the experimental and control group at 120mg taken thrice daily.[19]

One rat study noted increases in serum testosterone associated with Stinging Nettle, but all experimental groups also had testosterone supplementation.[6] Stinging Nettle was found to further elevate circulating testosterone levels, however, through a5-reductase inhibition.[6] However, Stinging Nettle root also possesses aromatase inhibitors which may contribute to this effect.[9]

Also, lignans from Stinging Nettle may interfere with Sex-Hormone Binding Globulin (SHBG) and prevent it from associated with androgens and estrogens. A 10% hydroalcoholic extract can decrease binding of DHT to SHBG by up to 67%, and slightly lesser effects are seen with aqueous extracts.[20][21] The inhibition appears to be dose dependent in vitro.[22] Isolated lignans retain this potency, inhibiting and even displacing DHT from SHGB by 60%(Secoisolariciresinol), 73%(enterofuran) and 95%((-)-3,4-divanillyltetrahydrofuran).[5]

Stinging Nettle can plausibly increase testosterone, but the one rat study conducted was not geared to answer this question and the human study came back negative. At this moment in time, there is no good evidence to suggest Stinging Nettle can increase testosterone levels


Edit3. Interactions with Organ Health

3.1. Prostate

A large clinical trial of 558 patients showed that Stinging Nettle is able to reduce urinary complications (reduced flow rate) associated with benign prostate hyperplasia at 120mg taken three times daily.[19] Stinging Nettle was also able to reduce the size of the prostate yet had no effect (beneficial or negative) on circulating testosterone levels. Results similar to these have been found in other interventions, although confounded with other nutrients such as sabal fruit[3][1][2] or Serenoa Repens.[4] In studies that continue usage beyond the trial period, benefits are seen over the long-term without an increase in side-effects.[19][23] At least in rats, this alleviation of decreased urinary rate is also seen with the isolated main ingredient, beta-sitosterol.[6]

These effects may be due to Stinging Nettle extract having the ability to act as a 5a-reductase inhibitor, preventing the conversion of testosterone to Dihydrotestosterone (DHT), with an IC50 ranging from 0.12-0.32mg in vitro depending on the extraction method (with petroleum and ethanolic extracts having more potency); about ten-fold less active than finasteride.[6] By inhibiting prostatic conversion of testosterone to DHT, prostate size can be reduced.[24]

Isolated beta-sitosterol appears to be similarily potent as Stinging Nettle when increased to around 60mg, and may be an active ingredient on the prostate.[6] The dose of beta-sitosterol found in Stinging Nettle, however, is lower than the preceding dose. Related compounds campesterol, sigmasterol and stimast-4-en-3-one may also be active ingredients, through inhibiting the prostatic sodium/potassium pump.[25]


Edit4. Interactions with Inflammation

4.1. Mechanisms

Stinging Nettle appears to have the ability to act as a Cyclooxygenase inhibitor (1 and 2), and inhibiting Hematopoietic Prostaglandin D2 synthase; three anti-inflammatory actions.[26] The IC50 value for COX inhibition is 160+/-47ug/mL for COX-1 and 275+/-9ug/mL for COX-2.[26]

4.2. Topical Application

Several human trials have looked at topical application of Stinging Nettle for its ability to reduce joint pain. One exploratory study (not an intervention) suggested that it was helpful to apply the leaves of Urdica Dioica topically[27] yet two double-blind interventions into the matter had conflicting results; leaves of Urdica Dioica applied to the thumb were found to be significantly better than placebo[28] whereas its effects on knee pain were no better than placebo.[29] Better results relative to the leaves have been found in making a topical cream with Stinging Nettle Root, but only one study has looked at this.[30]

4.3. Oral application in vivo

One study looking at osteoarthritis investigated oral ingestion of Stinging Nettle and found benefit, but was confounded with coingestion of Fish Oil.[31]

Mixed effects have been seen in regards to biomarkers of inflammation. One study noted a decrease in IL-6 with oral administration in type II diabetics[32] while another noted an increase in IL-6 when baseline levels were low to normal.[33] Additionally, the former study noted no significant effects on TNF-a[32] while the latter noted an impaired secretion of TNF-a in response to LPS administration.[33] It is plausible Stinging Nettle may be immunomodulatory, but currently this claim is unsubstantiated.

Possesses anti-inflammatory potential, but the studies currently done in humans are lacklustre and vary too widely in their methods of application to be compared. More studies need to be done with some dosage consistency.


Edit5. Interactions with Sinuses

5.1. Allergic Rhinitus

Stinging Nettle seems to have some societal usages as a 'natural' alternative for clearing the sinuses from allergies.[34] This usage of stinging nettle has both been said to be free from side-effects[35] as well as associated with them[36] depending on who you ask.

One double-blind study investigating the effects of Stinging Nettle on Allergic Rhinitus found that 600mg was able to reduce the side-effects associated with Allergic Rhinitus, and that 48% of persons found it better than other over-the-counter medications (unlisted).[37]

These effects appear to be mediated through anti-inflammatory pathways. In particular, Stinging Nettle has been shown to be a histamine antagonist and inhibit mast cell tryptase; two mechanisms of action seen as anti-allergenic.[26] The IC50 values were 251+/-13ug/mL (antagonism) and 193+/-71ug/mL (negative agonism) for the histamine receptor and 172+/-28ug/mL for mast cell inhibition.[26] Other anti-inflammatory effects of Stinging Nettle, such as COX1 and COX2 inhibition, may also contribute to anti-sinusitis effects.[26]


Edit6. Safety and Toxicology

6.1. General

The LD50 of stinging nettle of an aqueus extract, when injected, is 1.72g/kg bodyweight; it is heightened to 1.93g/kg when using a root extract.[5]

Oral administration up to 1.31g/kg in rats has been well tolerated.[5]

6.2. Allergies and Irritation

Urdica Dioica leaves are dubbed 'stinging nettle' because, well, they sting when they touch the skin. The leaves seem to mechanically irritate the skin[38] and the body responds by releasing factors that cause itching, dermatitis (rash) and urticaria (hives) moments later.[39] The leaves also contain various chemical irritants, such as 5-hydroxytryptamine, acetylcholine, histamine, formic acid, and leukotrienes.[40][41]

For the most part, transient contact with stinging nettle is harmless, although annoying.

Despite this irritation, it is folk remedy to press leaves of Urdica Dioica into sore joints to alleviate pain. Three trials have looked at this method of administration with mixed results.[27][29][28] Subjects tend to report the application as being irritating, but not to a degree that acts as a deterrent.

References

  1. Lopatkin N, et al. Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial. World J Urol. (2005)
  2. Bondarenko B, et al. Long-term efficacy and safety of PRO 160/120 (a combination of sabal and urtica extract) in patients with lower urinary tract symptoms (LUTS). Phytomedicine. (2003)
  3. Lopatkin NA, et al. Combined extract of Sabal palm and nettle in the treatment of patients with lower urinary tract symptoms in double blind, placebo-controlled trial. Urologiia. (2006)
  4. Bercovich E, Saccomanni M. Analysis of the results obtained with a new phytotherapeutic association for LUTS versus control. (corrected). Urologia. (2010)
  5. WHO Monograph of Selected Herbals volume 2
  6. Nahata A, Dixit VK. Ameliorative effects of stinging nettle (Urtica dioica) on testosterone-induced prostatic hyperplasia in rats. Andrologia. (2012)
  7. Schöttner M, Gansser D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG). Planta Med. (1997)
  8. Schöttner M, Spiteller G, Gansser D. Lignans interfering with 5 alpha-dihydrotestosterone binding to human sex hormone-binding globulin. J Nat Prod. (1998)
  9. Gansser D, Spiteller G. Aromatase inhibitors from Urtica dioica roots. Planta Med. (1995)
  10. An unusual lectin from stinging nettle (Urtica dioica) rhizomes
  11. Fatty acids and carotenoids from Stinging Nettle (Urticadioica L.)
  12. Otles S, Yalcin B. Phenolic compounds analysis of root, stalk, and leaves of nettle. ScientificWorldJournal. (2012)
  13. Determination of some phenolic compounds in flax seed and nettle roots by HPLC with coulometric electrode array detection
  14. Fiamegos YC, et al. Analytical procedure for the in-vial derivatization--extraction of phenolic acids and flavonoids in methanolic and aqueous plant extracts followed by gas chromatography with mass-selective detection. J Chromatogr A. (2004)
  15. Analysis of flavonoids and phenolic acids in Greek aromatic plants: Investigation of their antioxidant capacity and antimicrobial activity
  16. Anthocyan Glycosides from Urtica dioica
  17. Biological Flora of the British Isles: Urtica dioica L
  18. [No authors listed. Urtica dioica; Urtica urens (nettle). Monograph. Altern Med Rev. (2007)
  19. Safarinejad MR. Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study. J Herb Pharmacother. (2005)
  20. Gansser D, Spiteller G. Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts. Z Naturforsch C. (1995)
  21. Schmidt K. Effect of radix urticae extract and its several secondary extracts on blood SHBG in benign prostate hyperplasia. Fortschr Med. (1983)
  22. Hryb DJ, et al. The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes. Planta Med. (1995)
  23. Lopatkin N, et al. Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms--long-term follow-up of a placebo-controlled, double-blind, multicenter trial. Int Urol Nephrol. (2007)
  24. 5α-Reductase: History and Clinical Importance
  25. Hirano T, Homma M, Oka K. Effects of stinging nettle root extracts and their steroidal components on the Na+,K(+)-ATPase of the benign prostatic hyperplasia. Planta Med. (1994)
  26. Roschek B Jr, et al. Nettle extract (Urtica dioica) affects key receptors and enzymes associated with allergic rhinitis. Phytother Res. (2009)
  27. Randall C, et al. Nettle sting of Urtica dioica for joint pain--an exploratory study of this complementary therapy. Complement Ther Med. (1999)
  28. Randall C, et al. Randomized controlled trial of nettle sting for treatment of base-of-thumb pain. J R Soc Med. (2000)
  29. Randall C, et al. Nettle sting for chronic knee pain: a randomised controlled pilot study. Complement Ther Med. (2008)
  30. Rayburn K, et al. Stinging nettle cream for osteoarthritis. Altern Ther Health Med. (2009)
  31. Jacquet A, et al. Phytalgic, a food supplement, vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial. Arthritis Res Ther. (2009)
  32. Namazi N, et al. The effect of hydro alcoholic Nettle (Urtica dioica) extracts on insulin sensitivity and some inflammatory indicators in patients with type 2 diabetes: a randomized double-blind control trial. Pak J Biol Sci. (2011)
  33. Teucher T, et al. Cytokine secretion in whole blood of healthy subjects following oral administration of Urtica dioica L. plant extract. Arzneimittelforschung. (1996)
  34. Helms S, Miller A. Natural treatment of chronic rhinosinusitis. Altern Med Rev. (2006)
  35. Thornhill SM, Kelly AM. Natural treatment of perennial allergic rhinitis. Altern Med Rev. (2000)
  36. Bielory L. Complementary and alternative interventions in asthma, allergy, and immunology. Ann Allergy Asthma Immunol. (2004)
  37. Mittman P. Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis. Planta Med. (1990)
  38. Cummings AJ, Olsen M. Mechanism of action of stinging nettles. Wilderness Environ Med. (2011)
  39. Anderson BE, Miller CJ, Adams DR. Stinging nettle dermatitis. Am J Contact Dermat. (2003)
  40. Search for the antiprostatic principle of stinging nettle {Urtica dioica} roots
  41. Distribution of Acetylcholine and Histamine in Nettle Plants
  42. Namazi N, Tarighat A, Bahrami A. The effect of hydro alcoholic nettle (Urtica dioica) extract on oxidative stress in patients with type 2 diabetes: a randomized double-blind clinical trial. Pak J Biol Sci. (2012)
  43. Huber R, et al. Arnica and stinging nettle for treating burns - a self-experiment. Complement Ther Med. (2011)

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