Iberis amara / STW 5

Metadata

• Common Names: Iberogast, STW 5 (product name); Bitter Candytuft (Iberis amara) is the lead herb
• Botanical Name: Multi-herb combination; lead herb Iberis amara L.
• Plant Family: Brassicaceae (for Iberis amara); combination spans multiple families
• Part Used: Liquid combination of nine herbal extracts (see composition below)
• Evidence Quality Rating: Strong (one of the best-studied herbal GI products in Europe)

Composition of STW 5 (Iberogast)

Extraction solvent: 31% v/v ethanol Standard dose: 20 drops (1 mL) three times daily

Note: STW 5-II (Iberogast N) is a six-herb version without greater celandine, milk thistle fruit, or angelica root — developed partly in response to hepatotoxicity concerns related to celandine.

Approved Indications

Commission E

• Not directly applicable as a multi-herb product, but individual components have Commission E monographs
• STW 5 is approved as a registered phytopharmaceutical in Germany for functional GI disorders

ESCOP

• Not directly applicable as a proprietary multi-herb product

EMA/HMPC

• STW 5 is not covered by an EMA herbal monograph (it is a proprietary product registered under German drug law, not through the EU traditional herbal registration pathway)
• Individual components are covered by separate EMA monographs

German Drug Registration (BfArM)

• Registered in Germany as a traditional herbal medicinal product
• Approved indications: Functional dyspepsia (FD) and irritable bowel syndrome (IBS)
• Available over-the-counter in German pharmacies since 1961

Agreement/Disagreement Between Bodies

• STW 5 exists in a unique regulatory space: it is a proprietary product with its own clinical evidence base, rather than a single herb covered by Commission E/ESCOP/EMA monographs
• It is registered in over 30 countries
• The clinical evidence base is entirely product-specific (STW 5 trials cannot be extrapolated to other formulations)

Conditions Treated

• Functional dyspepsia (FD) — primary indication
• Irritable bowel syndrome (IBS) — primary indication
• Functional abdominal pain
• Bloating / Flatulence
• Nausea
• Epigastric pain
• Acid reflux symptoms (emerging evidence)
• Postprandial distress syndrome
• Functional GI disorders in children

Mechanism of Action

Multi-Target Concept

STW 5 is considered the paradigmatic example of the “multi-target” approach in phytotherapy, where a multi-component preparation addresses complex symptom clusters through different pharmacological mechanisms acting on different GI regions.

Dual Action Principle

• Iberis amara (fresh plant extract): Uniquely has a tonic (prokinetic) effect on GI smooth muscle — increases basal muscle tone and motility
• Dried herb extracts (remaining eight herbs): Predominantly spasmolytic (antispasmodic) — relax smooth muscle
• The balance between tonic and spasmolytic effects depends on the predistension state of the GI wall:
  • In a hypomotile/distended gut: the tonic Iberis amara effect predominates, restoring motility
  • In a spastic/hypercontractile gut: the spasmolytic effects of the other herbs predominate, relieving spasm
• This dual regulation is considered a key advantage over single-mechanism drugs

Specific Pharmacological Effects

• Gastric fundus relaxation: Accommodates food bolus (chamomile, lemon balm, peppermint)
• Antral contraction stimulation: Promotes gastric emptying (Iberis amara)
• Intestinal smooth muscle relaxation: Reduces spasm (peppermint, caraway, chamomile)
• Prosecretory action: Increases chloride secretion via CFTR and calcium-dependent ClCa channels in intestinal epithelium; also activates enteric neurons
• Anti-inflammatory: Multiple components reduce mucosal inflammation
• Acid reduction: Some components (licorice, chamomile) have cytoprotective and acid-buffering effects
• Visceral sensitivity reduction: Reduces pain signaling from the gut

Clinical Evidence Summary

Functional Dyspepsia — Strong Evidence

• Meta-analysis (Melzer et al., 2004): Pooled analysis of 3 double-blind RCTs; STW 5 significantly superior to placebo for dyspepsia symptoms; GIS (Gastrointestinal Symptom Score) reduction was clinically and statistically significant
• Vw Arnim et al. (2007): RCT (n=315); STW 5 comparable in efficacy to cisapride (standard prokinetic) for FD
• STW 5-II meta-analysis (2024): Patient data-based meta-analysis of 4 RCTs; favorable safety profile comparable to placebo; significant symptom improvement in FD patients
• Typical GIS improvement: 76% reduction from baseline (from 16.1 to 3.8 in large observational study)

Irritable Bowel Syndrome

• Madisch et al. (2004): RCT (n=208); STW 5 reduced IBS symptom score by 1.5 points more than placebo (p<0.0004), a clinically relevant and statistically significant difference
• Aguilar et al. (2024): RCT using colonic gas tolerance model; STW 5 reduced subjective abdominal symptoms induced by colonic gas filling and improved recovery from objective abdominal distension in IBS patients

Reflux Symptoms

• Raedsch et al. (2024): Double-blind RCT crossover trial; STW 5 reduced reflux symptoms in patients with concurrent dyspeptic symptoms

Observational Data

• Post-marketing surveillance: Over 50 million patient-exposures since 1961
• Adverse drug reaction rate: 0.04%
• Children: Open study showing efficacy and good tolerability in pediatric FGIDs

Summary of Evidence Strength

• 5 controlled, randomized double-blind studies in FD
• 1 controlled RCT in IBS
• Additional controlled studies for specific symptoms
• Large post-marketing safety database
• This makes STW 5 one of the best-studied herbal GI products globally

European vs US/Anglophone Consensus

• Major divergence: STW 5 (Iberogast) is one of the top-selling OTC products in German pharmacies and is well-known across continental Europe and Australia
• In the US, Iberogast is available as a dietary supplement but is not widely known among gastroenterologists
• German and Australian clinical guidelines mention Iberogast as an option for functional dyspepsia
• No US gastroenterology guideline currently recommends Iberogast
• The “multi-target” phytotherapy concept that STW 5 exemplifies is central to German phytotherapy philosophy but has limited acceptance in US evidence-based medicine
• In Europe, Iberogast is often recommended before or alongside conventional therapies (PPIs, prokinetics); in the US, herbal approaches are typically considered only after conventional therapies fail

Safety Profile

Contraindications

• Known allergy to any of the nine component herbs
• Children under 3 years (Iberogast Classic) or under 12 years (some formulations)
• Contains ethanol (31% v/v); caution in patients with alcohol dependency, liver disease, or epilepsy

The Hepatotoxicity Controversy

• Greater celandine (Chelidonium majus): This component has been associated with rare cases of liver injury
  • Over a dozen publications describe clinically apparent acute liver injury attributable to greater celandine, with jaundice and elevated aminotransferases
  • Liver injury typically appears after 1-6 months of celandine-containing product use
• STW 5 context: The celandine dose in STW 5 is approximately 100-200 times lower than doses associated with hepatotoxicity in case reports
• Case reports: Several individual case reports of Iberogast-induced acute liver injury exist, including one case with positive rechallenge
• Overall perspective: The manufacturer and supporting literature argue that the 0.04% ADR rate over 50+ years and billions of daily doses demonstrates safety; however, the hepatotoxicity signal has led to:
  • Development of STW 5-II (Iberogast N) without celandine
  • Updated product labeling including liver toxicity warnings in some countries
  • Lareb (Netherlands pharmacovigilance) signal report (2021)

Drug Interactions

• Contains licorice root: potential interaction with corticosteroids, antihypertensives, and medications affected by potassium levels
• Contains peppermint: potential interaction with antacids/PPIs (see Peppermint)
• Ethanol content may interact with disulfiram, metronidazole, and CNS depressants
• No severe drug interactions documented in clinical trials

Side Effects

• Very low incidence (0.04% in post-marketing surveillance)
• Mild GI complaints: nausea, bloating (uncommon)
• Allergic reactions (rare)
• Hepatotoxicity (very rare; see controversy above)

Pregnancy/Lactation

• Not recommended during pregnancy (insufficient data; contains multiple herbs with individual pregnancy cautions)
• Not recommended during breastfeeding (ethanol content; insufficient data)

Clinical Dosage

STW 5 (Iberogast Classic)

• Adults and adolescents over 12 years: 20 drops (1 mL) three times daily before or during meals, diluted in water or other liquid
• Children 6-12 years: 15 drops three times daily
• Children 3-6 years: 10 drops three times daily
• Duration: Can be used for several weeks; for chronic FD/IBS, may be taken long-term under medical supervision

STW 5-II (Iberogast N)

• Six-herb formulation without celandine, milk thistle, or angelica
• Same dosing regimen
• Developed as alternative for patients with hepatotoxicity concerns

Key Products

• Iberogast (Steigerwald/Bayer): Original STW 5 formulation; available in pharmacies across Europe, Australia, Canada
• Iberogast N (STW 5-II): Newer six-herb formulation
• Both available as oral liquid (tincture)

Sources

• Melzer J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther. 2004;20(11-12):1279-1287
• Madisch A, et al. Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial. Aliment Pharmacol Ther. 2004;19(3):271-279
• Vw Arnim U, et al. STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study. Am J Gastroenterol. 2007;102(6):1268-1275
• Aguilar M, et al. Effect of Iberogast (STW5) on tolerance to colonic gas in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2024;36(4):e14765
• Raedsch R, et al. The effect of STW5 (Iberogast) on reflux symptoms. J Neurogastroenterol Motil. 2024;30(1):62-68
• Abdel-Aziz H, et al. STW 5 (Iberogast) — a safe and effective standard in the treatment of functional gastrointestinal disorders. Wien Med Wochenschr. 2013;163(3-4):159-164
• Lareb Netherlands Pharmacovigilance Report: Liver toxicity of Iberogast. 2021
• Bayer Clinical Trials Explorer: Study 21970 (NCT04656730)

Connections

• Contains multiple herbs from this collection: Chamomile, Peppermint, Milk Thistle, Caraway
• Exemplifies the “multi-target” approach central to German phytotherapy philosophy
• The hepatotoxicity controversy connects to broader safety themes in phytotherapy
• Compare with Peppermint for IBS: both have strong evidence, but peppermint oil has more US/international acceptance
• STW 5 is arguably the most important single product in the European evidence-based phytotherapy tradition for GI disorders