Nettle Root

Metadata

Approved Indications

Commission E (Germany)

• Approved: Micturition difficulties in BPH stages I and II
• Specifically: difficulties in initiating urination, pollakisuria, nocturia

ESCOP

• Approved: Symptomatic treatment of micturition disorders (nocturia, pollakisuria, dysuria, urine retention) in BPH
• Stages I-II (Alken classification) or stages II-III (Vahlensieck classification)

EMA/HMPC

• Traditional Use only: Relief of lower urinary tract symptoms related to BPH, after serious conditions have been excluded by a medical doctor
• The HMPC determined that effectiveness has NOT been sufficiently proven for “well-established use” status
• Traditional use supported by safe use documentation over 30+ years

Agreement/Disagreement

• Commission E and ESCOP both give positive assessments for BPH
• EMA/HMPC is more cautious, granting only traditional use status
• US authorities (NCCIH) note “limited evidence” and do not recommend
• Key gap: All bodies agree that further confirmatory studies are needed before nettle root can be formally recommended in clinical guidelines

Conditions Treated

• Benign prostatic hyperplasia (BPH) stages I-II — symptomatic relief of:
  • Nocturia
  • Pollakisuria (frequency)
  • Dysuria (painful urination)
  • Urinary retention / incomplete emptying
  • Weak urinary stream
• Most commonly used as combination therapy with saw palmetto, not as monotherapy

Mechanism of Action

Primary Mechanisms

1. SHBG Binding Inhibition

   • Lignans from nettle root extract inhibit the binding of sex hormone-binding globulin (SHBG) to its receptor on human prostatic membranes
   • SHBG receptors on prostate cells are involved in BPH pathogenesis
   • Key compounds: Secoisolariciresinol and other lignans
   • [Source: Hryb et al., 1995, Planta Medica]

2. Aromatase Inhibition

   • Heptane fraction of nettle root extracts inhibits aromatase, blocking conversion of androstenedione to estrogen
   • May also inhibit aromatase gene expression
   • Relevant because estrogen/androgen imbalance contributes to BPH

3. Anti-inflammatory Activity

   • Inhibition of prostatic growth factors
   • Modulation of epidermal growth factor (EGF) receptor activity
   • Prostate steroid membrane receptor interactions

4. Immunomodulation

   • Polysaccharide and lectin fractions stimulate lymphocyte proliferation and interferon secretion

5. 5-alpha-Reductase Inhibition [UNCERTAIN]

   • Some in vitro evidence, but this is less established than for saw palmetto

Key Bioactive Compounds

• Lignans: (-)-3,4-divanillyltetrahydrofuran, secoisolariciresinol (SHBG binding)
• Lectins: Urtica dioica agglutinin (UDA) — immunomodulatory
• Polysaccharides: Glycans, glucogalacturonan, arabinogalactan acid
• Sterols: Beta-sitosterol, stigmasterol, campesterol
• Scopoletin: Coumarin derivative with anti-inflammatory activity

Clinical Evidence Summary

Monotherapy Trials

Randomized Controlled Trials

• Multiple open studies and a small number of RCTs support efficacy
• A 2022 RCT examined nettle root extract in older men with BPH and found improvements in IPSS at follow-ups of up to 12 months [Source: ScienceDirect]
• Meta-analyses show slight IPSS improvement vs. controls, but certainty of evidence is rated “very low”

Systematic Reviews

• Koch (2001): Comprehensive review found that a proprietary methanolic extract (Bazoton) showed efficacy in improving BPH complaints in RCTs
• The significance and magnitude of effect remain to be established in further confirmatory studies [Source: EMA Assessment Report]

Combination Therapy (Saw Palmetto + Nettle Root)

PRO 160/120 / Prostagutt forte (Willmar Schwabe)

• Composition: 160mg saw palmetto (WS 1473) + 120mg nettle root (WS 1031) per capsule
• Dosage: 1 capsule twice daily

Key Combination Trial

• Design: Randomized, double-blind, placebo-controlled trial with open-label extension
• Sample Size: n=129 (initial phase)
• Duration: 24 weeks placebo-controlled phase + 24-week control + 48-week follow-up (total 96 weeks)
• Results: Substantially higher symptom reduction vs. placebo over 24 weeks; benefit maintained over 96-week follow-up period
• Safety: Adverse effect incidence identical to placebo; tolerability comparable to placebo
• [Source: World Journal of Urology, 2005]

Additional Combination Evidence

• The combination product (Prostagutt forte / ProstActive Plus) has been studied in several clinical trials, predominantly in Germany
• Generally positive results showing IPSS improvement

Evidence Limitations

• Most trials have small sample sizes
• Many open-label studies (lower evidence quality)
• The EMA assessment concluded that evidence was insufficient for “well-established use”
• Heterogeneity in extract preparation across trials

European vs US/Anglophone Consensus

Safety Profile

Contraindications

• Known hypersensitivity to Urtica species
• No absolute contraindications identified beyond this

Drug Interactions

• Anticoagulants: Theoretical interaction due to vitamin K content in nettle plant (though root has less vitamin K than leaf) [UNCERTAIN]
• Antihypertensives: May have additive hypotensive effect
• Lithium: May decrease lithium excretion (similar to other diuretic herbs)
• Antidiabetic agents: May affect blood glucose levels [UNCERTAIN]
• Overall: Very few documented interactions; considered low risk

Side Effects

• Very low incidence: Risk for adverse events is very low, as is toxicity
• Occasional: Mild GI disturbances (nausea, bloating, diarrhea)
• Rare: Allergic reactions, skin rash
• Very rare: Sweating

Pregnancy/Lactation

• Not recommended: Insufficient safety data
• Theoretical concerns due to hormonal mechanism of action
• Traditional avoidance during pregnancy

Clinical Dosage

Standardized Dosage Forms

Key Standardized Products

• Prostagutt forte (Willmar Schwabe, Germany): 160mg saw palmetto + 120mg nettle root — the most-studied combination
• Bazoton (methanolic extract): Used in several clinical trials
• ProstActive Plus / Prostol (Nature’s Way, US): OTC version of the Schwabe combination

Duration of Treatment

• Minimum 4 weeks before initial assessment
• Suitable for long-term use (96+ weeks documented in trials)
• European guidance: Consult physician if symptoms persist or worsen after 4 weeks

Sources

• EMA Assessment Report on Urtica dioica/urens radix
• ESCOP Monograph — Urticae radix
• Koch 2001 — Comprehensive Review on Stinging Nettle (PubMed)
• Hryb et al. 1995 — SHBG Binding (PubMed)
• Nettle Root in Older Men with BPH — RCT (ScienceDirect)
• Prostagutt forte Trial (HerbalGram)
• NCCIH — BPH and Complementary Approaches

Connections

• See Saw Palmetto for the most common combination partner
• See Pumpkin Seed for another BPH herb with complementary mechanism
• See Pygeum for an alternative prostate phytotherapeutic