Stinging Nettle

01 Taxonomy and the English-name collapse

Urtica dioica L. is a perennial in Urticaceae. NCBI Taxonomy records it as taxon 3501 (National Center for Biotechnology Information, Taxonomy Browser). The English name “stinging nettle” also covers Urtica urens L., the annual small nettle. The European Medicines Agency herbal articles for both root and leaf are written on Urtica dioica L. and Urtica urens L. together (European Medicines Agency HMPC, Urticae radix; Urticae folium). Shared genus is not shared chemistry and not a shared trial. Where a paper used U. urens hairs (Czarnetzki et al., 1990), that species is named in the sentence.

The pharmacognostic split is older than the modern trial file. German Commission E treated radix and herba as separate entries (Blumenthal et al., 2000). The 2025 European Union herbal article on Urticae radix is a traditional-use document, adopted 22 January 2025 as EMA/HMPC/322646/2023, for relief of lower urinary tract symptoms related to benign prostatic hyperplasia after serious conditions have been excluded. It is not a well-established-use article. A separate folio article exists. Those two bureaucratic facts are the first reading rule. A capsule labelled “nettle” has not yet declared which article, which organ, or which extract it thinks it is.

LiverTox, updated 2023, records the same split in a toxicology register: fresh leaves sting because they contain histamine and acetylcholine; processed leaves do not sting; root is the organ purported for prostatic hyperplasia; published drug-induced liver injury is absent, likelihood score E (National Library of Medicine, LiverTox, NBK547852). That chapter is not an efficacy finding. It is the shortest available statement that leaf, root and sting are already different objects before anyone opens a trial.

02 Stinging hairs: a different exposure

The trichome is a mineralized injection device. Mustafa and colleagues (2018), in a comparative microscopy study across stinging taxa, recorded a silica apex and a calcium-carbonate shaft on Urtica dioica hairs. That architecture explains why a fresh leaf raises a wheal and a dried or cooked leaf does not. LiverTox makes the same processed-versus-fresh distinction without claiming a mechanism (NBK547852).

Oliver and colleagues (1991) measured mean histamine 6.1 ng and serotonin 33.25 pg per hair, in six people examined at 5 min and 12 h after nettle contact. The sting lasted longer than 12 h. Mast-cell numbers were up at 12 h; mononuclear and polymorphonuclear counts were not. Nettle-sting extracts did not release histamine from dispersed rat mast cells in vitro. The authors read the immediate wheal as introduced histamine and the long sting as something else — a nerve toxin or a secondary mediator — not as simple histamine dump. Collier and Chesher (1956) had already identified 5-hydroxytryptamine in the sting. Czarnetzki and colleagues (1990) found LTB₄ and LTC₄, and histamine, in Urtica urens hair and whole-plant extracts. That is a different species and a mediator assay, not a U. dioica supplement trial.

Anderson, Miller and Adams (2003) described stinging-nettle dermatitis as a clinical contact-urticaria picture. Uslu and colleagues (2011) reported generalized urticaria in a 17-day-old infant after the mother boiled nettle and applied the water to cracked nipples twice a day for two days; infant and mother had high total and nettle-specific IgE, and the infant’s prick test to the boiled water was positive. That case is a lactation-adjacent exposure, not a radix finding. Tiotiu and colleagues (2016) described pollen allergy to nettle. Allergy to airborne Urtica pollen is not evidence that a nettle capsule treats allergic rhinitis. Section 13 keeps those two files apart.

Randall and colleagues later used the live leaf as an experimental intervention on osteoarthritic joints (Randall et al., 2000, 2008). Those trials are sting trials. They do not license an extract. Section 14 takes them on their own terms.

03 Chemistry by organ

Root and leaf do not share a working constituent list. Martz and colleagues (2025) reviewed the underground organ as a source of phytosterols, lignans, coumarins, sugars and lectins, with particular weight on Urtica dioica agglutinin (UDA). Chrubasik and colleagues (2007), reviewing radix pharmacology and trials, judged sex-hormone-binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid-membrane receptors more plausible contributors to an anti-prostatic hypothesis than 5-alpha-reductase or androgen-receptor blockade. They also recorded that only a few components of any “active principle” had been identified and that the mechanism remained unclear.

The binding papers are organ- and solvent-specific. Hryb and colleagues (1995) tested four radix materials against ¹²⁵I-SHBG binding to human prostatic membranes: an aqueous extract, an alcoholic extract, UDA, and stigmasta-4-en-3-one. Only the aqueous extract inhibited binding, in a dose-related manner from about 0.6 mg/ml, with complete inhibition at 10 mg/ml. The alcoholic extract, the lectin and the ketosteroid were inactive in that assay. Schöttner, Gansser and Spiteller (1997) isolated or prepared root lignans — (+)-neoolivil, (−)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol and 3,4-divanillyltetrahydrofuran — and found SHBG affinity for all but (−)-pinoresinol; 3,4-divanillyltetrahydrofuran was outstanding. Wagner and colleagues (1995) put UDA into an in vitro epidermal-growth-factor-receptor binding test. Lichius and Muth (1997) reported inhibition of experimentally induced prostatic hyperplasia in the mouse by root extracts. Konrad and colleagues (2000) reported an antiproliferative effect of a root extract on human prostate-cancer cells in vitro. Those five papers are hypotheses about radix chemistry. They are not International Prostate Symptom Score results.

Leaf chemistry is a different inventory. Obertreis and colleagues (1996) studied IDS 23 (Rheuma-Hek), a leaf extract, in lipopolysaccharide-stimulated whole blood from healthy volunteers. At the highest assay concentration, 5 mg/ml, tumour-necrosis-factor alpha fell 50.8 per cent and interleukin-1 beta fell 99.7 per cent at 24 h. Isolated phenolics — caffeic malic acid, caffeic acid, chlorogenic acid, quercetin, rutin — did not reproduce the effect at concentrations up to 5 × 10⁻⁵ mol/l. Riehemann, Behnke and Schulze-Osthoff (1999) then showed that IDS 23 inhibits NF-kappaB activation by preventing IkappaB-alpha degradation, not by blocking DNA binding. Teucher and colleagues (1996) reported cytokine secretion in whole blood after oral administration of a Urtica dioica plant extract to healthy subjects. Roschek and colleagues (2009) measured in vitro half-maximal inhibitory concentrations for a nettle extract against the histamine H₁ receptor (251 µg/ml), mast-cell tryptase (172 µg/ml), cyclo-oxygenase-1 (160 µg/ml) and cyclo-oxygenase-2 (275 µg/ml). Those IC₅₀ values are assay numbers. They are not a hay-fever trial.

04 What a label does not specify

A retail label that says “stinging nettle” has specified an English name. It has not specified the species pair, the organ, the solvent, the drug-extract ratio, a named proprietary extract, or whether a second plant is in the capsule. The EMA radix article already lists more than one preparation: comminuted herbal substance as tea; dry extracts prepared with methanol 20 per cent V/V (DER 7–14:1); ethanol 20 per cent V/V (DER 5.4–8.3:1); ethanol 70 per cent V/V (DER 12–16:1); and further listed preparations. Bazoton uno is a 459 mg root dry extract in a twelve-month German trial (Schneider and Rübben, 2004). It is not a generic “nettle root 459 mg” capsule. IDS 23 is a leaf extract from a rheumatology file. It is not Bazoton.

Wilt and colleagues (2000), in a systematic review of phytotherapy for symptomatic benign prostatic hyperplasia, found no convincing evidence supporting Urtica dioica alone. Combination products were the setting in which nettle most often appeared. That 2000 sentence is still the correct warning label for any later paper that pools PRO 160/120 with radix monotherapy. Section 08 maps the extracts. Section 12 keeps monotherapy and combination on separate lines. The job of the rest of this document is to stop the English name from doing the pooling that the chemistry and the regulator have already refused.

05 Root extracts and named identities

The radix file is a list of preparations, not a molecule. The 22 January 2025 European Union herbal article on Urticae radix (EMA/HMPC/322646/2023) classifies the substance as traditional use only. The stated traditional indication is relief of lower urinary tract symptoms related to benign prostatic hyperplasia, after serious conditions have been excluded. Well- established use was not granted. The listed preparations include comminuted herbal substance used as a herbal tea; dry extracts with methanol 20 per cent V/V, DER 7–14:1; ethanol 20 per cent V/V, DER 5.4–8.3:1; ethanol 70 per cent V/V, DER 12–16:1; and further dry and liquid extracts named in the article. Gastrointestinal adverse events in that document are nausea, heartburn, a feeling of fullness, and diarrhoea. Allergic reactions are recorded. Pregnancy and lactation are marked not relevant for radix because the stated users are men. Tests for genotoxicity, reproductive toxicity and carcinogenicity were not performed (European Medicines Agency HMPC, Urticae radix).

Named trial identities sit inside that list, they do not exhaust it. Schneider and Rübben (2004) administered Bazoton uno, a 459 mg dry extract of stinging-nettle roots, once daily for twelve months to 246 men in a randomized, double-blind, placebo-controlled multicentre study. That sentence already contains the constraints that later marketing drops: a named dry extract, a stated milligram amount as a study parameter, a twelve-month German BPH/BPS population, and a placebo comparator. Karami and colleagues (2020) administered 450 mg/day of a root extract, or placebo, as tablets for twelve weeks to 60 men with benign prostatic hyperplasia. Safarinejad (2005) enrolled 620 Iranian men in a six-month randomized, placebo-controlled, partial-crossover root study; the published report does not identify the extract by the Bazoton name or by an EMA DER. Those three designs are all radix. They are not one lot.

Chrubasik and colleagues (2007) read the clinical radix file as many open studies and a small number of randomized trials, with a signal attaching to a proprietary methanolic extract and a magnitude that had not been established for guideline adoption. Martz and colleagues (2025) returned to the underground organ as a biomolecule source, not as a completed clinical article. Wilt and colleagues (2000) had already written the monotherapy sentence that those later reviews still have to answer: no convincing evidence for Urtica dioica alone. Section 12 puts the numbers under that sentence rather than above it.

06 Leaf, tea, freeze-dried aerial parts

Folium is a second herbal substance. The EMA leaf article is a separate document from the radix article (European Medicines Agency HMPC, Urticae folium). Commission E likewise kept herba on its own line (Blumenthal et al., 2000). A tea of dried aerial parts is an infusion. A freeze-dried leaf or herb powder is a different solid. A hydroalcoholic leaf extract filled into a capsule is a third object. None of them is Bazoton uno.

IDS 23 (Rheuma-Hek) is the named leaf extract in the ex-vivo cytokine papers (Obertreis et al., 1996; Riehemann et al., 1999). Teucher and colleagues (1996) gave a Urtica dioica plant extract by mouth to healthy subjects and measured cytokine secretion in whole blood. Mittman (1990) used a freeze-dried preparation of Urtica dioica in a one-week allergic-rhinitis trial; 98 people enrolled and 69 completed. That product is an aerial-part solid, not a root dry extract. Bakhshaee and colleagues (2017), by contrast, used a root extract (Urtidin, 150 mg) in allergic rhinitis. The organ in that allergy trial is radix. Section 13 refuses to let Mittman and Bakhshaee become one “nettle for hay fever” warrant.

Kianbakht, Khalighi-Sigaroodi and Dabaghian (2013) administered a leaf extract, 500 mg every 8 hours for three months, to 46 adults with advanced type 2 diabetes already using insulin and oral antihyperglycaemic drugs, against 46 placebo controls. Namazi and colleagues (2011, 2012) administered a hydroalcoholic extract at 100 mg/kg body weight, in three portions a day, for eight weeks to 50 adults with type 2 diabetes. The recovered Namazi abstracts do not name the plant part. Those two programmes are therefore not pooled here as “the leaf metabolic file.” The later metas collapse the distinction again (Ziaei et al., 2020; Tabrizi et al., 2022). Section 15 keeps the collapse visible.

07 Combination products

The largest human numbers attached to the English word “nettle” in the prostatic literature are combination numbers. They cannot be attributed to Urtica.

PRO 160/120 is a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule. Sökeland and Albrecht (1997) compared that combination with finasteride for 48 weeks in 543 men (double-dummy); maximum flow rose 1.9 ml/s with PRO 160/120 and 2.4 ml/s with finasteride, International Prostate Symptom Scores moved similarly, and tolerability favoured the combination. Sökeland (2000) re-analysed 431 of those men by baseline prostate volume and found the same pattern in glands ≤ 40 ml and > 40 ml. Lopatkin and colleagues (2005) compared PRO 160/120 with placebo in 257 men; at 24 weeks the International Prostate Symptom Score fell 6 points versus 4 points on placebo (p = 0.003, one-tailed). Engelmann and colleagues (2006) compared the combination with tamsulosin, 0.4 mg/day, for 60 weeks in 140 men; both arms reduced the symptom score by a median of 9 points, and the authors claimed non-inferiority. Lopatkin and colleagues (2007) followed 219 of the placebo-controlled cohort in an open 96-week extension in which everyone received PRO 160/120. Every one of those papers is a sabal-plus-urtica paper. Saw palmetto is not a spectator.

Krzeski and colleagues (1993) compared two dose levels of an urtica-plus-pygeum preparation (300 mg Urtica dioica root extract plus 25 mg Pygeum africanum bark extract per standard capsule) for eight weeks in 134 men. There was no placebo arm. Melo and colleagues (2002) compared pygeum 25 mg plus nettle 300 mg with placebo for six months; the International Prostate Symptom Score fell 21.6 per cent versus 19.7 per cent (p = 0.928). That combination was a null.

Pain combinations are the same class of error. Jacquet and colleagues (2009) tested Phytalgic — fish oil, vitamin E and Urtica dioica — for three months in 81 people with knee or hip osteoarthritis. Christensen and Bliddal (2010) judged that trial at high risk of bias: registration after completion, and a fish-oil taste that would unblind. Moré and colleagues (2017) tested MA212 (Rosaxan): rosehip puree or juice concentrate, nettle leaf extract, and devil’s-claw root, 40 ml daily for twelve weeks in 92 people with gonarthritis. A combination superiority on WOMAC is not a nettle-leaf finding. Section 14 leaves those products on the combination line.

08 Extract heterogeneity

Two facts make pooling illegal. First, the regulator already lists multiple DERs and solvents for radix alone, and a second article for folium. Second, the trial file uses named products that do not match those listings one-for-one and do not match each other. Aqueous root extract inhibited SHBG binding; alcoholic extract, UDA and stigmasta-4-en-3-one did not (Hryb et al., 1995). A proprietary methanolic radix extract is the preparation Chrubasik and colleagues (2007) treated as the least-thin clinical signal. Bazoton uno is a 459 mg root dry extract (Schneider and Rübben, 2004). Karami used 450 mg/day of a root extract for twelve weeks (Karami et al., 2020). Safarinejad (2005) used an unspecified Urtica dioica preparation in 620 men. IDS 23 is leaf. Mittman’s freeze-dried powder is aerial. Bakhshaee’s Urtidin is root used for an allergy endpoint. PRO 160/120 is sabal plus urtica root. Phytalgic and MA212 are multi-ingredient pain products, and MA212 uses leaf.

A meta-analysis that searches “Urtica dioica” and returns a fasting-glucose weighted mean difference has already performed the collapse this section forbids, unless it stratifies by organ and extract. Ziaei and colleagues (2020) and Tabrizi and colleagues (2022) are read in Section 15 with that caveat attached to the number. The figure below is a map, not a ranking.

09 Prostate hypotheses

The prostatic story is a stack of in-vitro and mouse findings asked to explain a traditional-use indication. Chrubasik and colleagues (2007) ranked the stack. SHBG, aromatase, epidermal growth factor and prostate steroid-membrane receptors looked more likely than 5-alpha-reductase or androgen-receptor blockade. Extract and a polysaccharide fraction showed anti-inflammatory activity in the papers they reviewed. A proprietary methanolic root extract and particular fractions inhibited cell proliferation. Isolated UDA looked immunomodulatory, with antiviral and fungistatic notes attached. The same review then wrote the sentence that governs this section: it is unclear whether the in-vitro or animal data are a surrogate for clinical effects.

Hryb and colleagues (1995) make the solvent split unavoidable. Only the aqueous radix extract inhibited ¹²⁵I-SHBG binding to human prostatic membranes. The alcoholic extract, UDA and stigmasta-4-en-3-one were inactive. A later writer who says “nettle lignans and lectins lower free androgen by occupying SHBG” has already ignored that paper’s negative arms. Schöttner, Gansser and Spiteller (1997) showed that several root lignans bind SHBG in vitro and that 3,4-divanillyltetrahydrofuran is the outstanding ligand in that set. Binding affinity is not occupancy in a man drinking tea, and it is not an International Prostate Symptom Score. Wagner and colleagues (1995) placed UDA in an epidermal-growth-factor-receptor binding assay. Lichius and Muth (1997) inhibited experimentally induced prostatic hyperplasia in the mouse with root extracts. Konrad and colleagues (2000) reported antiproliferation in human prostate-cancer cells in vitro. Martz and colleagues (2025) restated the underground chemistry without converting it into a guideline indication.

Safarinejad (2005) found serum prostate-specific antigen and testosterone unchanged after six months of Urtica dioica in 558 completers, while prostate volume on transrectal ultrasound moved from 40.1 cc to 36.3 cc in the active arm and did not change on placebo. Unchanged circulating androgen and a modest volume shift are compatible with a non-androgen-receptor story. They are also compatible with a small, assay-level change that does not explain the symptom gap between that trial and Schneider and Rübben (2004), in which maximum flow and residual urine did not separate from placebo. A mechanism that is “more likely than 5-alpha-reductase” is still a mechanism that has not been shown to operate, at relevant concentrations, in the men who swallowed the extract. Section 12 leaves the human disagreement in place. This section refuses to settle it with a binding constant.

10 Leaf anti-inflammatory and mast-cell hypotheses

The leaf papers are cleaner as pharmacology than as clinical translation, and they still fail to travel to the sting or to the root.

Obertreis and colleagues (1996) added IDS 23 to lipopolysaccharide-stimulated human whole blood. Tumour-necrosis- factor alpha at 24 h was 50.8 per cent lower, and interleukin-1 beta 99.7 per cent lower, at 5 mg/ml of extract. Isolated caffeic-acid derivatives and flavonoids did not copy the result. The extract, not a named phenolic, did the work in that assay. Riehemann, Behnke and Schulze-Osthoff (1999) then put IDS 23 on several cell types and several NF-kappaB stimuli. Inhibition was common to those stimuli. DNA binding itself was not blocked. IkappaB-alpha was not degraded. That is a pathway finding in cultured cells and in the whole-blood system, at extract concentrations the oral leaf trials do not demonstrate in plasma.

Teucher and colleagues (1996) moved the question to oral administration in healthy subjects and measured cytokine secretion in whole blood. The paper is cited here as an oral-leaf cytokine study. No numbers from it are restated, because this review did not recover a usable abstract. Roschek and colleagues (2009) assigned in-vitro IC₅₀ values to a nettle extract: H₁ antagonist activity 251 µg/ml, H₁ negative-agonist activity 193 µg/ml, mast-cell tryptase 172 µg/ml, cyclo-oxygenase-1 160 µg/ml, cyclo-oxygenase-2 275 µg/ml, haematopoietic prostaglandin-D synthase 295 µg/ml. Those figures are the mechanistic vocabulary of the allergy aisle. They are micrograms per millilitre in an assay. They are not Mittman’s one-week global assessment, and they are not Bakhshaee’s root-extract Sino-Nasal Outcome Test, which moved on placebo as well (Section 13).

The sting literature is sometimes offered as if it confirmed the same mast-cell story. It does not. Oliver and colleagues (1991) found histamine already in the hair (6.1 ng) and did not find histamine release from rat mast cells exposed to sting extract. Mast-cell counts in human skin were up at 12 h, after the hair had already delivered its own mediators. Czarnetzki and colleagues (1990) found leukotrienes in U. urens hairs. That is injection of plant mediators, not oral H₁ blockade. A freeze-dried capsule does not recreate a silica tip.

11 Diuretic and metabolic hypotheses

Diuretic language in the secondary literature traces, when it traces at all, to a rat infusion. Tahri and colleagues (2000) gave anaesthetized male Wistar rats a continuous intravenous perfusion of an aqueous extract of aerial parts for 1.25 h, at 4 mg/kg/h or 24 mg/kg/h, with a furosemide arm at 2 mg/kg/h. Arterial pressure fell 15 per cent at the low extract rate and 38 per cent at the high rate. Diuresis rose 11 per cent and 84 per cent; natriuresis rose 28 per cent and 143 per cent. The high-dose hypotension persisted into recovery, which the authors read as a possible toxic effect. Furosemide lowered pressure 28 per cent, with diuresis +85 per cent and natriuresis +155 per cent, and recovered in about an hour. This is an intravenous aerial extract in the rat. It is not a human randomized diuretic trial. It is not a “detox” endpoint. Detox is not a scientific endpoint in this document.

The metabolic hypothesis is more often a traditional leaf use plus later type 2 diabetes trials than a demonstrated molecular mechanism. Kianbakht, Khalighi-Sigaroodi and Dabaghian (2013) listed insulin secretagogue, PPAR-gamma agonistic and alpha-glucosidase inhibitory effects as prior pharmacology for the leaf, then ran a three-month leaf-extract trial on advanced type 2 diabetes. Namazi and colleagues (2011) measured interleukin-6 and high-sensitivity C-reactive protein after eight weeks of a hydroalcoholic extract and found those inflammatory markers down; that abstract is not a glucose-primary win. Namazi and colleagues (2012), in the same dose-and-duration programme, found total antioxidant capacity and superoxide dismutase up, with malondialdehyde and glutathione peroxidase unchanged. Those are biomarker movements in defined programmes. They are not a demonstration that an oral extract recreates the Tahri infusion, and they are not a licence to write “nettle is a diuretic that also lowers glucose.”

The human metabolic numbers, including the two metas that collapse plant part, wait for Section 15. The rat hypotensive and diuretic numbers do not become human safety clearance; they become a theoretical interaction on the safety ledger (Section 17). Traditional leaf use as a “spring tonic” or flushing tea is recorded as tradition. It is not promoted to a result.

12 BPH / LUTS: root monotherapy versus combinations

The prostatic human file is three kinds of paper: root monotherapy against placebo; combinations that contain nettle root; and reviews that refuse to treat the first as settled. They disagree. The disagreement is the result.

Safarinejad (2005) randomized 620 Iranian men with lower-urinary-tract symptoms secondary to benign prostatic hyperplasia to Urtica dioica or placebo for six months, with partial crossover after unblinding and follow-up to 18 months. Five hundred and fifty-eight completed (287 of 305 on nettle, 271 of 315 on placebo). By intention-to-treat, 232 of 287 (81 per cent) in the nettle arm reported improved symptoms versus 43 of 271 (16 per cent) on placebo. The International Prostate Symptom Score moved from 19.8 to 11.8 on nettle and from 19.2 to 17.7 on placebo. Peak flow rose 8.2 ml/s versus 3.4 ml/s. Post-void residual urine in the nettle arm fell from 73 to 36 ml. Prostate volume on transrectal ultrasound fell from 40.1 to 36.3 cc. Serum prostate-specific antigen and testosterone did not change. The report states that no side effects were identified in either group. That last sentence is recorded as the authors’ statement and treated sceptically: a 620-man, six-month urological trial that detects zero adverse events has not produced a usable safety ledger. The same paper ends by asking for further trials before concluding that Urtica dioica is effective.

Schneider and Rübben (2004) is the named-extract counterweight. Bazoton uno, 459 mg root dry extract, or placebo, for twelve months, n = 246. The International Prostate Symptom Score fell from 18.7 to 13.0 on extract and from 18.5 to 13.8 on placebo (p = 0.0233). Maximum flow rose 3.0 ml/s versus 2.9 ml/s and did not differ. Residual urine did not differ (35.5 to 20.0 ml versus 40.0 to 21.0 ml). Adverse-event counts were 29 versus 38, with fewer urinary infections on extract (3 versus 10). The authors wrote the limitation into the conclusion: a strong increase in maximum flow, or a reduction of residual urine, is not to be expected. That is a twelve-month German multicentre trial of a named dry extract. It is not Safarinejad’s eight-millilitre flow change.

Karami and colleagues (2020) randomized 60 men to 450 mg/day root extract or placebo for twelve weeks. The authors reported an intermediate effect on the International Prostate Symptom Score, a small effect on high-sensitivity C-reactive protein, an intermediate-to-large effect on malondialdehyde, and an intermediate effect on superoxide dismutase, with other parameters negligible. They also wrote “no side effects.” The same scepticism applies. Ghorbanibirgani, Khalili and Zamani (2013) is a 100-patient randomized trial recovered as a title only. No abstract was obtained. No numbers from that paper are restated here.

Wilt and colleagues (2000) reviewed randomized phytotherapy trials of at least 30 days in symptomatic benign prostatic hyperplasia. For Urtica dioica they found no convincing evidence supporting use alone; combinations with Serenoa or Pygeum were the setting in which nettle appeared. Chrubasik and colleagues (2007) later allowed a methanolic-extract signal in a small randomized set and still withheld guideline status. The EMA radix article of 22 January 2025 is traditional use, not well-established use, after serious disease has been excluded (European Medicines Agency HMPC, Urticae radix). Those three readings survive Safarinejad. They do not delete Safarinejad. They prevent a single large Iranian trial from becoming a product class.

The combination papers are larger and still not nettle. Sökeland and Albrecht (1997): PRO 160/120 versus finasteride, n = 543, 48 weeks; maximum flow +1.9 versus +2.4 ml/s; International Prostate Symptom Score from 11.3 to 6.5 versus 11.8 to 6.2 at week 48; fewer sexual adverse events on the combination. Sökeland (2000): n = 431 with valid volumes; the flow increments were similar in glands ≤ 40 ml and > 40 ml. Lopatkin and colleagues (2005): PRO 160/120 versus placebo, n = 257, 24 weeks; symptom score −6 versus −4 (p = 0.003, one-tailed). Engelmann and colleagues (2006): PRO 160/120 versus tamsulosin 0.4 mg/day, n = 140, 60 weeks; median symptom-score reduction 9 points in both arms; non-inferiority claimed. Lopatkin and colleagues (2007): open extension to 96 weeks, 219 men, all on the combination; symptom score down 53 per cent from baseline in an uncontrolled interval. Krzeski and colleagues (1993): urtica-plus-pygeum at two capsule strengths, n = 134, eight weeks, no placebo. Melo and colleagues (2002): pygeum 25 mg plus nettle 300 mg versus placebo, six months, 27 and 22 men; symptom-score drop 21.6 per cent versus 19.7 per cent (p = 0.928). The last of those is a combination null. The first five cannot be assigned to Urtica.

13 Allergic rhinitis

Two randomized trials and one in-vitro paper are asked to carry the hay-fever claim. None of them is enough, and they are not the same product.

Mittman (1990) enrolled 98 people in a double-blind comparison of freeze-dried Urtica dioica with placebo for one week; 69 completed. Global assessment at the follow-up visit favoured nettle. Daily symptom diaries were only slightly higher than placebo. One week, a freeze-dried aerial preparation, a global question that moved, and a diary that barely did: that is the oldest clinical allergy paper in this review. It does not establish a season, a dose-response, or a root extract.

Bakhshaee and colleagues (2017) randomized 74 adults with allergic rhinitis and a positive skin-prick test to Urtidin, a 150 mg Urtica dioica root extract, or placebo, for one month. Forty completed. Sino-Nasal Outcome Test-22 scores improved in both arms (p < 0.001). Mean nasal-smear eosinophil count fell after nettle (p < 0.01). Serum IgE, interleukin-4 and interleukin-5 did not change. Interferon-gamma post-treatment change differed between groups (p = 0.017). The authors wrote that placebo also worked and that larger, longer studies were needed. A root capsule used for an allergy endpoint is already a category error relative to Mittman’s freeze-dried herb. A score that falls on placebo as well is not a product demonstration.

Roschek and colleagues (2009) remain an in-vitro extract paper (Section 10). Their IC₅₀ values are not clinical results. Tiotiu and colleagues (2016) described allergy to nettle pollen. That paper belongs on the safety and differential-diagnosis line, not on the efficacy line. The allergy claim, challenged, resolves as: one short freeze-dried trial with a weak diary signal; one root-extract trial in which the symptom score moved on placebo; and an assay paper. Section 19 restates that resolution without softening it.

14 Osteoarthritis and pain

The pain file is a sting file plus two combination products plus a Cochrane judgement. It is not an extract file.

Randall and colleagues (1999) spoke to 18 people already using live Urtica dioica sting on joints. All but one were sure it had helped; the recorded harm was a transient urticarial rash. That is testimony, not a trial. Randall and colleagues (2000) then ran a double-blind crossover in 27 people with osteoarthritic pain at the base of the thumb or index finger. Live nettle leaf was applied daily for one week to the painful area; white dead-nettle (Lamium album) was the placebo leaf, with a five-week washout. Reductions on the visual-analogue pain scale and on the Health Assessment Questionnaire were greater after nettle sting than after placebo (p = 0.026 and p = 0.0027). This is sting, one week, thumb-base osteoarthritis, n = 27. It is not a capsule.

Randall and colleagues (2008) piloted sting on chronic knee pain in 42 people aged 55–80, Urtica dioica versus Urtica galeopsifolia, daily for one week. Mean WOMAC pain reduction was 1.7 (95 per cent CI 0.6 to 2.9) versus 1.6 (0.5 to 2.7). The arms did not separate. The paper is a feasibility result: general practitioners and patients would accept the research; the sting was a minor irritation. It is not a knee-pain efficacy win. Cameron and colleagues (2013), updating the Cochrane review of topical herbal therapy for osteoarthritis, judged it uncertain whether stinging-nettle leaf improves osteoarthritis, on very-low-quality evidence from single trials.

Jacquet and colleagues (2009) found large WOMAC and analgesic-sparing effects for Phytalgic (fish oil, vitamin E, Urtica dioica) over three months in 81 people with knee or hip osteoarthritis already using NSAIDs or analgesics. Christensen and Bliddal (2010) answered that paper directly: registration after the study was finished, and a fish-oil taste that would break the blind; high risk of bias; promising only if those defects are ignored. Moré and colleagues (2017) found MA212 superior to placebo on WOMAC pain (mean pre-post change 29.87 versus 10.23) in 92 people with gonarthritis taking 40 ml daily for twelve weeks. MA212 is rosehip plus nettle leaf plus devil’s claw. Combination superiority is not leaf monotherapy. The pain claim, challenged, resolves as: one small positive sting crossover at the thumb; one negative sting pilot at the knee; Cochrane uncertainty; and two multi-ingredient products that cannot speak for nettle.

15 Glucose and metabolic claims

Namazi and colleagues (2011) randomized 50 adults with type 2 diabetes, adjusted for age, sex and diabetes duration, to a hydroalcoholic extract at 100 mg/kg body weight in three daily portions, or placebo, for eight weeks. Interleukin-6 and high-sensitivity C-reactive protein fell in the extract arm relative to control. That abstract is an inflammatory-marker result. It is not presented here as a fasting-glucose primary win. Namazi and colleagues (2012), same population and exposure, found total antioxidant capacity and superoxide dismutase higher in the extract arm, with malondialdehyde and glutathione peroxidase unchanged. The recovered abstracts do not name the plant part.

Kianbakht, Khalighi-Sigaroodi and Dabaghian (2013) randomized 46 plus 46 adults with advanced type 2 diabetes requiring insulin, already on oral antihyperglycaemic drugs, to a leaf extract, 500 mg every 8 hours for three months, or placebo. Fasting blood glucose, two-hour post-prandial glucose and HbA1c fell relative to placebo (p < 0.001, 0.009 and 0.006). Blood pressure, creatinine and the liver enzymes SGOT and SGPT did not differ. That is a leaf-extract trial in insulin-using type 2 diabetes, three months, n = 92. It is the cleanest named-organ metabolic paper in this harvest. It is not a root finding and not a tea finding.

Ziaei and colleagues (2020) pooled eight randomized trials, 401 adults with type 2 diabetes. Fasting blood sugar weighted mean difference −18.01 mg/dl (95 per cent CI −30.04 to −5.97; I² = 94.6 per cent). Insulin, HOMA-IR and HbA1c did not reach significance. Tabrizi and colleagues (2022) pooled thirteen trials. Fasting blood glucose weighted mean difference −17.17 mg/dl (95 per cent CI −26.60 to −7.73; I² = 93.2 per cent); HbA1c −0.93 (−1.66 to −0.17; I² = 75.0 per cent); C-reactive protein −1.09 mg/dl; triglycerides −26.94 mg/dl; systolic blood pressure −5.03 mmHg. Insulin, total cholesterol, LDL, HDL, body-mass index and diastolic blood pressure did not move significantly. Both metas search the binomial. Leaf trials and unspecified-organ trials are collapsed. The I² values say the collapse is not a formality. The numbers are reported as pooled remainders with that defect attached, not as a drug-class effect.

16 Diuretic claims

No adequate human randomized diuretic trial of a defined Urtica preparation was recovered for this build. Tahri and colleagues (2000) remain the quantitative paper people mean when they say nettle is a diuretic: intravenous aerial aqueous extract in the anaesthetized rat, 4 or 24 mg/kg/h for 1.25 h, blood pressure −15 per cent and −38 per cent, diuresis +11 per cent and +84 per cent, with possible toxicity at the persistent high dose (Section 11). Traditional leaf use as a flushing tea is tradition. EMA radix traditional use is a urinary- symptom indication in men after exclusion of serious disease, not a diuretic indication (European Medicines Agency HMPC, Urticae radix). Detoxification is not an endpoint. The diuretic claim, challenged, resolves as a rat infusion plus folklore. It does not resolve as a human result.

17 Safety at the same volume as efficacy

The sting is the most reproducible human harm. Oliver and colleagues (1991) timed it past twelve hours and counted mast cells up at twelve hours after a 6.1 ng histamine, 33.25 pg serotonin hair. Anderson, Miller and Adams (2003) described the resulting dermatitis. Processed leaf does not sting (LiverTox, NBK547852). Contact urticaria is therefore an exposure finding, not a capsule finding, except where a mother applies boiled-leaf water to skin that a neonate then nurses (Uslu et al., 2011).

The EMA radix article lists nausea, heartburn, fullness and diarrhoea, and allergic reactions. Pregnancy and lactation are marked not relevant because the stated users are men. Genotoxicity, reproductive-toxicity and carcinogenicity tests were not performed (European Medicines Agency HMPC, Urticae radix). LiverTox assigns likelihood E: unlikely cause of clinically apparent liver injury; no published drug-induced liver-injury case was recorded as of the 2023 update (NBK547852). That is the hepatic sentence. It is not a general safety clearance.

Safarinejad (2005) and Karami and colleagues (2020) reported no side effects. Those statements are not used as evidence of absence. Schneider and Rübben (2004) at least counted events (29 versus 38) over twelve months of Bazoton uno.

Theoretical interactions sit where the animal and leaf files point, and no further. Tahri and colleagues (2000) lowered rat arterial pressure and raised diuresis with intravenous aerial extract; the high dose did not recover. Traditional leaf use as a flushing tea adds a second, weaker reason to record hypotension and diuresis as interaction hypotheses, not as measured human effects. The leaf type 2-diabetes file (Kianbakht et al., 2013; Namazi et al., 2011) is the reason to record glucose-lowering and blood-pressure interaction as hypotheses in people already using insulin or antihypertensives. This document does not convert those hypotheses into a dose.

Pregnancy is a gap, not a clearance. Radix is labelled not relevant for women in the EMA root article. Leaf has a traditional use history that is not a reproductive-toxicology file. Uslu and colleagues (2011) is a neonate urticaria case after maternal topical boiled nettle. Easton et al. (2021) reported new galactorrhoea in a 30-year-old woman after one month of a 500 mg stinging-nettle supplement taken for environmental allergies, with normal prolactin, TSH and metabolic panel and negative pregnancy test; the discharge stopped one week after the supplement was discontinued. That is a single case. Tiotiu and colleagues (2016) is pollen allergy to nettle, not a treatment harm. The ledger is therefore: sting, gut, rash, a theoretical diuretic and glucose interaction, an empty hepatic file, an empty genotoxicity file, and a pregnancy record that is folklore plus two cases.

18 Five research matrices

Numbers below are reported study or article parameters, not instructions.

Plant part and formulation

Table 1. Plant part and formulation. Root evidence does not travel to leaf. A combination is not monotherapy.

BPH / LUTS

Table 2. BPH. The large Iranian monotherapy signal and the German named-extract trial do not agree on flow. Combinations are a different object.

Allergy

Table 3. Allergy. The clinical file is a weak week and a root trial whose symptom score also moved on placebo.

Pain

Table 4. Pain. The only nettle-specific positive randomized signal is a live-leaf sting on the thumb. The knee did not separate.

Safety

Table 5. Safety at the same volume as efficacy. The sting is certain. The hepatic file is empty. Pregnancy is a gap. Zero-AE trial sentences are not a ledger.

19 Critical questions

These are the questions a careful reader is already asking. They are answered from the tables, not from the English name.

Do prostate claims survive Safarinejad versus Schneider, the EMA traditional-only status, and Wilt’s monotherapy sentence?

They survive only as a contested, preparation-bound file. Safarinejad (2005) is a large Iranian monotherapy trial with an unusually large flow increment and an author who asked for more trials. Schneider and Rübben (2004) is a twelve-month named-extract trial that moved the symptom score a little and did not move maximum flow or residual urine; the authors said not to expect those changes. Wilt and colleagues (2000) found no convincing evidence for Urtica alone. Chrubasik and colleagues (2007) allowed a methanolic-extract signal and withheld guideline magnitude. The 2025 EMA radix article is traditional use after exclusion of serious disease, not well-established use. A market sentence that says “nettle treats BPH” has collapsed those five objects. This document does not.

Do allergy claims survive Mittman, Bakhshaee, and Roschek?

No, not as a product class. Mittman (1990) is one week of freeze-dried aerial Urtica dioica in 69 completers, with a global question that favoured nettle and a diary that barely did. Bakhshaee and colleagues (2017) used a root extract for allergic rhinitis; the Sino-Nasal Outcome Test improved in both arms, and the authors said so. Roschek and colleagues (2009) are in-vitro IC₅₀ values. Pollen allergy to nettle (Tiotiu et al., 2016) is the opposite claim. The aisle treats those four papers as one warrant. They are four different objects, and the two clinical ones are weak.

Does detox or diuretic language survive Tahri?

No. Tahri and colleagues (2000) infused an aqueous aerial extract into rats. Blood pressure fell and urine rose, in proportion to 4 versus 24 mg/kg/h, and the high dose looked possibly toxic because it did not recover. There is no adequate human diuretic randomized trial in the reviewed literature. Detoxification is not an endpoint. Traditional tea use explains why the language exists. It does not make the rat a man.

Can extracts be pooled?

No. The EMA radix list already contains a tea and several methanol- and ethanol-based dry extracts with different DERs. Bazoton uno is not a generic capsule. IDS 23 is leaf. Hryb and colleagues (1995) found SHBG-binding inhibition in the aqueous root extract and not in the alcoholic extract, UDA, or stigmasta-4-en-3-one. Mittman is freeze-dried aerial. Bakhshaee is root used for allergy. Safarinejad does not name the extract that Schneider named. A meta that searches the binomial and reports a fasting- glucose remainder has performed the same illegal pooling unless it stratifies (Ziaei et al., 2020; Tabrizi et al., 2022).

May combination products speak for nettle?

No. PRO 160/120 is sabal fruit extract plus urtica root extract. Its finasteride comparison, its placebo comparison (one-tailed), its tamsulosin non-inferiority claim and its open 96-week extension are combination results (Sökeland and Albrecht, 1997; Sökeland, 2000; Lopatkin et al., 2005, 2007; Engelmann et al., 2006). Krzeski and colleagues (1993) compared two strengths of urtica plus pygeum without placebo. Melo and colleagues (2002) ran the same pairing against placebo and got a null. Phytalgic is fish oil, vitamin E and Urtica, registered after completion (Jacquet et al., 2009; Christensen and Bliddal, 2010). MA212 is rosehip, nettle leaf and devil’s claw (Moré et al., 2017). Those products may have their own files. They do not become nettle monotherapy by sharing an English name.

20 Standing constraint

Sources and provenance

This is a South Beach Longevity science article, not a Radix peptide title. Every PubMed identifier in the reference list was title-checked against its NCBI record before drafting; recalled identifiers that resolved to unrelated papers were discarded, and author lists, titles, journals, years, volumes and pages are read from those records.

Non-PubMed sources are limited to the EMA herbal articles on Urticae radix and Urticae folium, the LiverTox chapter on stinging nettle, the NCBI Taxonomy record for Urtica dioica (taxon 3501), and the Commission E entries for the separate root and herb preparations; these are appended after the PubMed list and are not entered as invented identifiers. The EMA radix article used here is the 22 January 2025 final on Urtica dioica L., Urtica urens L., radix (EMA/HMPC/322646/2023); the leaf article is a separate document. General reference databases were consulted only to locate literature, never as evidence in their own right.

Evidence handling

Study type is named in the reporting sentence. A prostatic- membrane binding assay, a mouse hyperplasia model, an ex-vivo whole-blood cytokine assay, a rat intravenous infusion and a human randomized trial are not pooled as one exposure. Root results are not written as leaf results. Combination products are cited as combinations. Conflicting trials are left in conflict. Safarinejad does not automatically supersede Schneider; Schneider does not automatically cancel Safarinejad. A traditional-use article is cited as a article. “No side effects” in a trial report is cited as the authors’ sentence and is not treated as a safety study. Title-only recoveries (Ghorbanibirgani et al., 2013) contribute no numbers. Quantitative claims in the running text are traceable to the title-checked record. Figures are original schematics and carry no third-party artwork.

Doses, routes and durations appear only as parameters of published studies, always with the population attached. Nothing in the body is a recommendation for any person.

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