as well as dietary supplements or medicines based on stinging nettle extracts
Use of stinging nettle
Stinging nettles (Urtica) form a genus of plants comprising 30–70 subspecies. The most common in Germany are the common stinging nettle (Urtica dioica) and the annual nettle (Urtica urens), as well as the marsh nettle (Urtica kioviensis).
Stinging nettles have been used for centuries as food (e.g. in salads and soups), as tea and as animal feed (overview at[10 ). Leaves, stems and roots are used in folk medicine for wound treatment, as diuretics, for the treatment of joint pain, as anthelmintics and for respiratory conditions (overview at [12]). In Germany, nettle preparations are marketed as ‘food’ or ‘food supplements’. They contain the leaves of the plant as tea, leaves or roots in powdered form as capsules, or root extracts in capsule form. Stinging nettle skin oil (stinging nettle juice and olive oil in a 1:2 ratio) is marketed as a massage oil. The suppliers of these products do not make any recommendations for use in rheumatic conditions; instead, general information such as “use in naturopathy” is provided.
In Germany, several preparations containing dried nettle leaf extract are available as herbal, over-the-counter medicines available only from pharmacies for rheumatic conditions (source: Gelbe Liste Pharmindex, www.gelbe-liste.de):
- Rheuma Hek forte 600mg® film-coated tablets and Rheuma Hek 268mg® hard capsules (dried nettle leaf extract (8-10 : 1); extraction solvent: ethanol).
- Hox alpha® hard capsules (dried nettle leaf extract 145 mg per capsule (19-33:1); extraction solvent: 95% isopropanol).
- Natu-lind 600mg® coated tablets (dried nettle leaf extract 600 mg per tablet (5-10:1); extraction solvent: ethanol)
The indication for these preparations is: “For the supportive treatment of rheumatic complaints” (Product information for Rheuma Hek forte dated November 20201 , for Hox alpha dated October 20222 , Natu-lind package leaflet dated March 20143 ).
In addition, there is a preparation called “Naturreiner Heilpflanzensaft Brennessel®” (Naturally Pure Medicinal Plant Juice Nettle®), which is a pressed juice made from U. dioica and U. urens (1:0.55–0.82). The package leaflet states under “Indications: ... Relief of mild joint pain. This is a traditional medicinal product registered for this indication solely on the basis of long-standing use.”4
1www.strathmann.de/pdf/GI/GI-08-Rheuma-Hek-forte-01-2022.pdf
2imedikament.de/hox-alpha/fachinformation
3www.apotheken-umschau.de/medikamente/beipackzettel/natulind-600-mg-ueberzogene-tabletten-2680743.html
4api.gebrauchs.info/2a3f2083016859d77d879148d212ba9fi
Chemical and pharmacological composition
The stinging hairs on the upper surface of the leaves and on the stems are responsible for the stinging effect (Latin: urere: to burn) of the stinging nettle [12]. These introduce substances such as formic acid, acetylcholine, histamine and serotonin into the skin [10]. The plant has a high protein content. Dried, powdered leaves have a crude protein content of 33.8%, along with 9.1% crude fibre, 3.6% fat and 37.4% carbohydrates [1]. Nettle leaves and roots contain numerous phytochemicals such as flavonoids, phenolic acids, carotenoids, organic acids and fatty acids (overview at [10, 12]). Steroid-like phytosterols have also been detected in the roots [8]. The composition of these substances in the plant differs between individual plant parts and varies with location [20]. It is also subject to seasonal fluctuations [12].
Effects in vitro and in animal models
In vitro experiments have investigated the potential anti-inflammatory effects of aqueous or ethanolic extracts of U. dioica (overview at [12]). These studies utilised cell culture-based cytokine assays [6, 13], assays for COX-1 inhibition [11], animal models (oedema induction in rat paws) [9] and an experimental model of multiple sclerosis [18]. An in vitro study on various cell cultures demonstrated the inhibition of the pro-inflammatory transcription factor NF-KB by the dried nettle leaf extract IDS23 [25]. In peripheral blood mononuclear cells (PBMCs), IDS23 inhibited the production of IL-2 and gamma-interferon following phytohaemagglutinin stimulation in vitro [16].
Treatment of rats with collagen-induced arthritis using an oral herbal preparation containing stinging nettle led to a slight clinical improvement, but did not alter the histological picture of the arthritis [14].
Assays for COX-1 induction revealed significant variations between plant extracts from different regions [11]. These differences could be partly explained by the variable content of phenolic acids and hydroxyfatty acids in the samples, suggesting which of the numerous constituents might be responsible for potential anti-inflammatory effects [11]. A dominant phenolic component of U. dioica is caffeoyl-malic acid [21], which is regarded by some authors as the key antioxidant [5] and anti-inflammatory [19] substance in nettle preparations.
1www.strathmann.de/pdf/GI/GI-08-Rheuma-Hek-forte-01-2022.pdf
2imedikament.de/hox-alpha/fachinformation
3www.apotheken-umschau.de/medikamente/beipackzettel/natulind-600-mg-ueberzogene-tabletten-2680743.html
4api.gebrauchs.info/2a3f2083016859d77d879148d212ba9fi
Results of a PubMed search:
A PubMed search for scientific articles using the keyword ‘Urtica dioica’ yielded (as of 12 July 2024) 856 references, and 935 references for the keyword ‘stinging nettle’. Of these, 38 are clinical studies. These predominantly concern non-rheumatological indications such as prostatic hyperplasia and lower urinary tract symptoms, diabetes and hypertension, as well as gynaecological applications (menopausal symptoms, milk production, wound healing following episiotomy). The majority of studies use nettle components in combination preparations with other phytotherapeutics such as Rosa canina (dog rose) [15]. Studies on diabetes and benign prostatic hyperplasia were conducted using both combination preparations [7, 17] and pure nettle preparations [2, 3]. Seven systematic reviews on Urtica dioica were identified, six of which were dedicated to the role of these herbal preparations in diabetes and other non-rheumatological conditions.
Use of fresh nettle leaves for joint pain
In naturopathy and folk medicine, fresh plants were applied directly to the skin over painful joints. Randall et al. conducted structured interviews with 18 patients suffering predominantly from degenerative joint diseases. These patients were recruited via newspaper advertisements and radio broadcasts [23]. It is possible that this method primarily attracted individuals who had had positive experiences with the plant. The participants had applied fresh stinging nettle leaves directly to the painful areas for a few seconds to a few minutes. Seventeen of them reported pain relief, which set in within a period of 10 minutes to less than 24 hours and occurred in most users even with repeated application. No serious side effects were reported; 14 out of 18 reported a “not unpleasant sensation of warmth” [23]. In a randomised crossover study by the same researchers, 17 patients with rhizarthrosis pressed fresh stinging nettle leaves or a placebo onto the thumb saddle joint once a day for 30 seconds. Leaves of white dead-nettle (Lamium album) were used as the placebo [24]. After one week, a small but statistically significant reduction in pain was recorded on a visual analogue scale. The same authors conducted a randomised controlled trial on the external application of U. dioica for painful knee osteoarthritis, in which 42 patients participated [22]. Leaves of Urtica galeopsifolia, a subspecies without stinging hairs, served as the control. The intervention consisted of applying fresh leaves for a total of 6 × 10 seconds over 7 days. The study found no significant differences in the outcome parameters (WOMAC pain score, visual analogue scales, global patient assessment) between the two groups [22].
Use of medicinal products based on nettle extracts for rheumatological indications
The active ingredient in nettle preparations available in Germany (IDS23) was investigated in vitro [25] and in vivo: a study in healthy volunteers showed no effect of taking this substance on levels of inflammatory cytokines (all of which were below the limit of detection) [27]. After 7 and 21 days of administration, a reduced release of TNF-alpha and IL-1 beta from LPS-stimulated PBMCs of the subjects was measured, as well as an increased release of IL-6 without LPS stimulation [27]. In vitro, inhibition of the synthesis of leukotriene B4 by the preparation was also observed. The results do not allow for any definitive conclusions regarding an anti-arthritic effect in vivo in patients with inflammatory rheumatic diseases. There are no published studies on the clinical efficacy of the medicinal products in question. An article in the Deutsches Ärzteblatt from 1999 [26] refers to a case series involving 8,955 patients. However, no scientific publication exists on this subject.
The Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA) published an ‘Assessment report on Urtica dioica L., Urtica urens L., folium’ on 14 January 20101 .
The report lists five post-marketing surveillance studies (PMS) on IDS23, including the aforementioned PMS involving 8,955 patients with rheumatoid arthritis or osteoarthritis. The other PMS were significantly smaller in scale and included patients with “inflammatory and degenerative joint diseases” or “various, mostly degenerative rheumatic diseases”. None of these studies are available in published scientific form2 .
The conclusion states under “Assessor’s overall conclusions”3: “The traditional use of nettle leaf in minor articular pain is supported by pharmacological data, as IDS 23 hinders the production of cytokines? IL-1β and TNF-α, so the use of the nettle leaf extract might be useful.... Results of clinical studies in this therapeutic area are not sufficient to attribute an indication based on well-established use. Nevertheless, the results support the plausibility of the traditional use in minor joint pain.”
1https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-urtica-dioica-l-urtica-urens-l-folium_en.pdf, accessed on 12 June 2024
2 Ibid., p. 23 ff
3 Ibid., p. 29
The direct application of fresh nettle leaves for the treatment of joint pain may be found helpful in individual cases. However, due to the limited data available, the complexity of the application and the poor controllability, its use should be discouraged in favour of better-defined pharmacological treatment approaches.
Preparations based on dry extract of nettle leaves are recommended by manufacturers “for the supportive treatment of rheumatic complaints”. This labelling does not allow for a clear classification of the preparations within a rheumatological treatment plan.
The risk of significant side effects from oral nettle preparations is considered low. There are no reports of such complications in the literature. The allergenic potential of nettle pollen is very low [28]. Applying fresh nettle leaves to the skin causes contact dermatitis, which in sensitive individuals can lead to persistent pain, skin irritation and possible shock reactions [4].
The product information for Rheuma-Hek, Hox Alpha and Natu-lind does not recommend use during pregnancy and breastfeeding or in children under 12 years of age; nettle juice is not recommended for persons under 18 years of age.
The product information for Hox Alpha1 and Rheuma-Hek2 contains warnings regarding interactions with antidiabetic agents and vitamin K antagonists. The following side effects are listed there: Occasional hypersensitivity reactions of the skin (e.g. pruritus, exanthema, urticaria) as well as gastrointestinal complaints (nausea, diarrhoea and vomiting) and increased urge to urinate. Very rarely, an increase in blood sugar levels in patients with diabetes mellitus, which subsided after discontinuation of the medicine. Mild hypersensitivity reactions of the skin and gastrointestinal complaints are also reported for Natu-lind3 and Brennnesselpresssaft4 , without specifying the frequency.
In principle, the problem is that treatment with nettle preparations may delay effective and indicated therapy for inflammatory rheumatic diseases.
1imedikament.de/hox-alpha/fachinformation
2www.strathmann.de/pdf/GI/GI-08-Rheuma-Hek-forte-01-2022.pdf
3www.apotheken-umschau.de/medikamente/beipackzettel/natulind-600-mg-ueberzogene-tabletten-2680743.html
4api.gebrauchs.info/2a3f2083016859d77d879148d212ba9fi
The scientific evidence is insufficient to recommend the prescription and use of nettle preparations for patients with symptoms arising from a defined inflammatory rheumatic condition.
The effects of components from nettle extracts on inflammatory mediators in vitro do not allow conclusions to be drawn that the plant’s anti-inflammatory components are effective in vivo. There are no systematic controlled clinical trials in patient cohorts with clearly defined rheumatological conditions.
If, from a rheumatological perspective, there is no indication for a new or intensified anti-rheumatic therapy, but the patient has an urgent desire for treatment, treatment initiated by the patient using commercially available nettle preparations need not be discouraged.
Last updated: September 28, 2024