Ivy

Ivy (Hedera helix L.): A Comprehensive Reference on the Dietary Supplement and Medicinal Herb

1. Identity, Botanical Classification, and Natural Source

Hedera helix, commonly known as English ivy, common ivy, or European ivy, is a species of flowering plant in the family Araliaceae. It is an evergreen dioecious woody liana, one of the 15 species of the genus Hedera. Hedera is a small genus distributed through Europe to East Asia; Hedera helix occurs through Europe into south-west Asia.

The whole leaves are coriaceous, 4–10 cm long and wide, cordate at the base. The lamina is palmately 3–5 lobed. The upper surface is dark green with a paler, radiate venation. Hedera, the Latin name for ivy, is found as early as Virgil and Pliny, and is said to derive from the Greek hédra or haerere, meaning "to sit," referring to the grasp of its roots. The Greek word helix means "winding" or "spiral-shaped."

The medicinal part used is the dried leaf, designated in pharmacopeial nomenclature as Hederae helicis folium (ivy leaf). Hedera helix L. is an important traditional medicinal plant recorded in the European Pharmacopoeia. There are more than 500 ivy species in the world; most are used for ornamental purposes. Hedera helix is the most common ivy source with medical purpose and is used in dietary supplement formulas.

Common Forms and Preparations

Ivy leaf preparations are obtained as dry, liquid, and soft extracts by putting the plant material in a solvent (such as ethanol) to dissolve compounds and form a liquid extract. The solvent is then partially or completely evaporated to obtain a soft or dry extract. Herbal medicines containing ivy leaf are usually available in solid or liquid forms to be taken by mouth.

The EMA's EU herbal monograph specifies the following standardized preparations for well-established use:

• Dry extract (DER 4–8:1), extraction solvent ethanol 24–30% m/m; dry extract (DER 6–7:1), extraction solvent ethanol 40% m/m; dry extract (DER 3–6:1), extraction solvent ethanol 60% m/m; liquid extract (DER 1:1), extraction solvent ethanol 70% V/V; and soft extract (DER 2.2–2.9:1), extraction solvent ethanol 50% V/V: propylene glycol (98:2).

Two common galenical formulations of ivy herbal extract are cough syrup and cough drops. It also comes in several formulations including tablets, liquids, and topical ointments.

The standardized extract contains hederacoside C and α-hederin as its primary bioactive constituents, comprising 3–6% of the standardized extract, depending on the processing method. A widely studied proprietary extract, EA 575®, is a specific extract of Hedera helix, produced by a patented extraction process, and is distinct from other ivy leaf extracts. Since being developed over 65 years ago, it has been researched in clinical trials and scientific studies covering more than 65,000 patients around the world.

These products are primarily available in Europe, particularly Germany, Austria, Switzerland, and Eastern European countries. Availability varies by region, with fewer registered pharmaceutical products in North America, where ivy extract is more commonly marketed as a dietary supplement rather than a medicine.

2. Traditional and Historical Use

Classical Antiquity

Ivy's symbolic use extends at least as far back as celebrations of Dionysian and Bacchanalian rites in Ancient Greece and Rome. In ancient Egypt, ivy was holy to Osiris, the god of fertility and ruler of the underworld. Its medicinal record is equally ancient: the Greek physician Dioscorides (Materia Medica, 1st century AD) mentioned "Hedera" as a remedy for coughs and dropsy, praising decoctions of ivy leaves for loosening phlegm.

According to later scholarly accounts, ivy leaf was mentioned since Dioscorides and Hippocrates. Phytotherapeutical books of the 16th century described very different indications including jaundice, lithiasis, dysentery, and as an emmenagogue.

Medieval European Use

In the medieval period, European monasteries cultivated English ivy alongside other healing herbs; their manuscripts note its topical use in poultices for skin ulcers and chronic wounds. Ivy was associated with Bacchus, the Roman god of revelry. Maude Grieve notes in A Modern Herbal that ivy was also a symbol of fidelity and was presented to newlyweds in ancient Greece, and that during the early Christian church, Councils forbade the decoration of houses and churches with ivy because of the plant's pagan associations.

Broader Folk and Ethnobotanical Traditions

Ivy has traditionally been used to treat rheumatism. The herb can be taken internally or applied externally, directly on the affected joints. A decoction of fresh leaves (200 g/l water) may be used externally for rheumatism, or a poultice can be made by mixing fresh Hedera helix leaves with linseed meal at a 1:3 ratio.

In the region of Kirklareli Province in Turkey, a decoction of the leaves of Hedera helix was used for diabetes and as a "blood depurative," with a reported dosage of one teacup two times daily for 7–8 days. Ivy leaves were also incorporated into topical cosmetic preparations, for example, for the treatment of cellulite and in shampoos.

The ivy leaf has served various purposes in traditional medicine, believed to have expectorant properties. Historically, Hedera helix has found diverse applications, addressing medical matters ranging from digestive issues to general wound care.

German Commission E, ESCOP, and EMA Recognition

The German Commission E monograph lists the indications for ivy leaf as catarrh of the airways and symptomatic treatment of chronic inflammatory bronchial diseases. ESCOP monographs cite indications including cough, especially with excessive secretion of viscous mucus, and supportive treatment of inflammatory bronchial diseases. The HMPC monograph recognizes well-established use as dry, liquid, and thick extracts for use as an expectorant for productive coughs, and clinically proven indications including relief of symptoms in chronic inflammatory bronchial diseases and colds of the respiratory tract.

3. Key Constituents and Active Compounds

Chemical constituents isolated from Hedera helix include triterpene saponins, flavonoids, polyacetylenes, and some phenolic compounds.

Triterpene Saponins (Primary Active Constituents)

Triterpenoid saponins constitute about 2.5% to 6% of ivy leaves. The main saponin is hederasaponin C (hederacoside C), with other hederasaponins (B, D, E, F, G, H, and I). The content ratios of the hederasaponins are 1000:70:45:10:40:15:6:5 accordingly.

The active principles are pentacyclic triterpene saponins. The major one is hederacoside C, a bidesmosidic glycoside that in the body is transformed into the monodesmosidic α-hederin, which is the main compound responsible for pharmacological activity. Saponins (hederacoside C and α-hederin), flavonoid (rutin), and phenolic derivatives (chlorogenic acid) are the main components of the dry extract of Hedera helix.

Flavonoids and Phenolic Compounds

There are many components in ivy leaf; the main categories include triterpene saponins and flavonoids. The phenolic fraction includes rutin, caffeic acid, and chlorogenic acid, which contribute antioxidant properties to the plant.

Polyacetylenes

Common ivy (Hedera helix subsp. helix) contains three compounds that are powerful irritants and moderate sensitizers. Only two of these constituents—falcarinol and didehydrofalcarinol—are present in the plant throughout the whole year. These polyacetylenic compounds, while not pharmacologically active in the same manner as saponins, are responsible for contact sensitization (see Safety section).

4. Mechanisms of Action

Secretolytic and Expectorant Action

Mucolytic and expectorant action is based on indirect beta2 adrenergic effects; this action results from saponins alpha-hederin and hederacoside C, the latter of which is metabolized to alpha-hederin when ingested. Alpha-hederin inhibits intracellular uptake of beta2 receptors and leads to increased beta2 adrenergic response of the cell.

The mechanism of action of ivy leaf extract is believed to be twofold. The secretolytic and expectorant action involves a reflex pathway: when the saponins are ingested, they cause a mild irritation of the gastric mucosa, which stimulates afferent parasympathetic nerve fibers, which in turn triggers a signal in the brainstem.

Spasmolytic (Bronchodilatory) Action

Alpha-hederin has been shown in in-vitro studies to have a mild spasmolytic effect on the smooth muscles of the bronchi. The proposed mechanism is that alpha-hederin inhibits the internalization of beta2-adrenergic receptors on the surface of lung cells. By keeping these receptors on the cell surface for longer, they remain more available to be stimulated by adrenaline. Activation of beta2-receptors leads to the relaxation of bronchial smooth muscle, resulting in bronchodilation. This action helps relieve the chest tightness and coughing spasms accompanying bronchitis.

Treatment of human airway smooth muscle (HASM) cells with α-hederin (1 μM, 24 h) revealed an increased intracellular cAMP level of 13.5±7.0% under stimulating conditions. Notably, structurally related saponins like hederacoside C and hederagenin did not influence either the binding behaviour of β2-adrenergic receptors or the intracellular cAMP level. This specificity confirms α-hederin as the primary pharmacologically active metabolite for the bronchodilatory effect.

Anti-inflammatory Activity

The dry extract of ivy leaves and its saponins are known to act as anti-inflammatory, antibacterial, mucolytic, and antispasmodic agents. In vitro studies of ivy mono-preparations show evidence of potential antispasmodic and bronchodilating activity, anti-inflammatory effects, and antitussive properties.

5. Regulatory Status

In the United States, ivy leaf extract is legal as a dietary supplement ingredient, though it is not an FDA-approved drug. It is classified as a botanical ingredient commonly found in cough syrups, respiratory support supplements, and herbal formulations. While the FDA allows its sale in supplements, manufacturers must ensure good manufacturing practices (GMP) and refrain from making unapproved therapeutic claims.

The European Medicines Agency (EMA) recognizes ivy leaf extract as a traditional herbal medicine used for cough and bronchial relief. It is listed under the EU Herbal Monograph and considered safe and effective when used according to established dosage guidelines. Ivy-based products are widely available as over-the-counter herbal remedies across EU member states.

In Canada, ivy leaf extract is approved as a medicinal ingredient under the Natural Health Products (NHP) framework.

In 2007, more than 80% of herbal expectorants prescribed in Germany comprised ivy extract and amounted to nearly 2 million prescriptions nationwide.

6. Scientific Evidence by Area of Use

6.1 Acute Bronchitis and Upper Respiratory Tract Infections

This is the primary and most thoroughly studied clinical indication for ivy leaf preparations.

Systematic Reviews: Acute cough due to viral upper respiratory tract infections (URTIs) and bronchitis is a common reason for patients to seek medical care. Non-antibiotic over-the-counter cough medications such as ivy leaf extract are frequently used but their efficacy is uncertain. An updated systematic review searched MEDLINE, EMBASE, the Cochrane Library, and clinical trial registries from December 2009 to January 2020. Randomized controlled trials (RCTs), controlled clinical trials (CCTs), and observational studies (OSs) investigating ivy leaf mono- or combination preparations were included. Two independent reviewers assessed records for eligibility and risk of bias and performed data extraction. Six RCTs, 1 CCT, and 4 OSs were identified.

All studies concluded that ivy leaf extract is effective and safe. Three RCTs reported a more rapid reduction in cough severity and/or frequency under ivy leaf treatment as opposed to standard care or placebo; 5 studies utilized the Bronchitis Severity Scale (BSS). The clinical significance of these effects appears to be minimal. No serious adverse effects were reported. The overall quality of reporting was low and the risk of bias was high.

Ivy leaf preparations are safe for use in cough due to acute URTIs and bronchitis. However, effects are minimal at best and of uncertain clinical importance.

Comparison to Acetylcysteine (A Noninterventional Study): A noninterventional study evaluated the efficacy and safety of a cough syrup containing ivy leaf extract EA 575® by assessing its use in children and adults with symptoms of acute bronchitis. Clinical findings and subjective symptoms assessed by physicians showed a statistically significant improvement compared with baseline, which was essentially comparable between the two groups (ivy vs. acetylcysteine). Both preparations were found to be effective and safe in the treatment of bronchitis, and the EA 575® preparation showed effectiveness in children and adults independent of the indication or concomitant disease.

EMA Assessment on Children: Studies in children showed ivy leaf to be comparable to the medicine acetylcysteine in improving symptoms in children with acute bronchitis.

Large Observational Study: A postmarketing study referenced in EMA documentation (Fazio et al., 2009, published in Phytomedicine) enrolled 9,657 patients to evaluate the tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions.

Evidence Summary for Respiratory Use: Evidence from multiple RCTs and observational studies shows that ivy leaf extract produces statistically measurable reductions in cough severity and duration. However, independent systematic review concludes that the clinical significance of these effects is minimal, study quality is generally low, and the risk of bias is high. Ivy leaf is recognized as safe for this indication by the EMA and German Commission E.

6.2 Bronchial Asthma

Dry ivy leaf extract is extensively employed to alleviate symptoms associated with acute or chronic inflammation of the respiratory system. Studies have demonstrated its anti-inflammatory properties in mice with chronic-induced asthma, corroborating its efficacy in managing respiratory conditions. These findings are, however, primarily from animal models. The effect of dry extracts on respiratory functions of children with chronic bronchial asthma and its antitumour activities has been reported. Human evidence in asthma specifically remains limited.

6.3 Anti-inflammatory and Antiarthritic Effects

The ethanol Hedera helix plant extract was tested for its anti-inflammatory properties. Intraperitoneal injections of 7.5 ml/kg body weight of ethanol extract showed anti-inflammatory activity with 88.89% inhibition compared to the reference drug diclofenac, which showed 94.44% inhibition in formalin-induced paw edema. As formalin-induced paw edema closely resembles human arthritis, the antiarthritic property was also investigated. The visible reduction in arthritic symptoms by the extract suggests the potential of the plant extract against inflammation and arthritis.

Research into the anti-arthritic effects of Hedera helix is restricted but shows initial promising results. Ivy leaves (Hedera helix) represent a traditional plant used for common cold, cough, and bronchial disorders, and may be used for rheumatoid arthritis as an attempt in alternative medicine. These findings are primarily from animal and in-vitro models; human clinical trials for arthritis are lacking.

6.4 Antioxidant Activity

Fruit extracts showed the greatest level of antioxidant properties in the FRAP test (75.5 and 62.35 AscE mg/g extract) and also in DPPH tests (IC50 were 3.49 and 8.79 mg/ml for fruit and leaves respectively), demonstrating potent capacity to neutralize free radicals and high reducing power. The extract of H. helix contains compounds with antioxidant properties that protect cells from oxidative damage caused by free radicals, and antioxidants are generally associated with potential health benefits. These are laboratory findings; human clinical data on antioxidant effects are not established.

6.5 Antimicrobial and Antifungal Activity

Ivy leaf extracts exhibit spasmolytic/antispasmodic, anti-inflammatory, antimicrobial, analgesic, anthelmintic, antitrypanosomial, antileishmanial, antitumor, antimutagenic, molluscicidal, antioxidant, and antithrombin activities. Early research examined H. helix saponins' antibacterial and antifungal properties. These findings are predominantly from in vitro studies.

6.6 Antileishmanial and Antitumor Activity

Investigations with α-hederin and β-hederin isolated from Hedera helix, as well as hederacolchiside A1 isolated from Hedera colchica, showed strong antiproliferative activity believed to be due to their ability to react with the Leishmania membrane surface. H. helix leaves contain α-hederin, β-hederin, and hederagenin, which have leishmanicidal activity against Leishmania infantum and L. tropica. Among these, hederagenin has antiamastigote activity, and both α-hederin and β-hederin have antiproliferative activity in human monocytes. All the saponins appear to stop Leishmania promastigotes from growing by acting on the parasite's membrane and causing a reduction in membrane potential.

Preliminary studies have suggested that certain compounds found in H. helix extract may exhibit antitumor properties. These effects are from in vitro and animal work; no human clinical trials have investigated antitumor effects of ivy leaf preparations.

6.7 Potential Role in Glucose Metabolism

Some studies have suggested that ivy may have a role in improving glucose metabolism and insulin sensitivity. However, more research is necessary to determine its effectiveness in managing diabetes. Evidence is entirely preliminary and non-clinical.

7. Body Systems and Health Areas Associated with Ivy Leaf

• Respiratory system: Hederae helicis folium is used for the treatment of respiratory tract diseases with intense mucous formation, respiratory tract infections, and irritating cough stemming from the common cold. It can be used in common cold associated with cough and for the symptomatic treatment of acute and chronic inflammatory bronchial disorders.
• Musculoskeletal system: Traditional and limited preclinical evidence supports use for rheumatism and arthritis (external and internal application).
• Immune and antimicrobial: As a medicinal plant, H. helix has been approved by the German Commission E due to its antispasmodic, spasmolytic, antimicrobial, anti-inflammatory, anthelmintic, antioxidative, antitumor, and antileishmanial activities.
• Gastrointestinal system: The reflex secretolytic mechanism operates via gastric mucosal stimulation; traditional uses also include gastrointestinal complaints.
• Dermatology (topical): Historical use in poultices for wounds and skin conditions; modern investigational use in cosmetic preparations for cellulite.

8. Dosage Forms and Dosages Reported in Studies

English ivy is commonly available in cough syrups made with ivy leaf dry extract. These products are used to help relieve cough with phlegm and may also support easier breathing. The amount of English ivy per dose is typically 35 mg per 5 mL of cough syrup. These products are taken by mouth, and dosing varies by age. Typical label directions are: children 2 to 5 years, 2.5 mL twice per day (daily dose 5 mL); children 6 to 11 years, 5 mL twice per day (daily dose 10 mL); adults and children age 12 and over, 5 mL three times per day (daily dose 15 mL).

Cough syrups (Prospan; Panoto-s; Athos; Abrilar) or herbal drops (Prospan) containing English ivy leaf extract are possibly safe when taken by mouth three times daily for up to 20 days in children.

With respect to the standardized extract specifications recognized in EMA documentation, clinical studies demonstrate efficacy of the hydroalcoholic extract (EtOH 30%, DER: 5–7.5:1) in the treatment of acute respiratory tract infections accompanied by cough and chronic inflammatory bronchial conditions, as well as its excellent tolerability in children and adults.

9. Safety Considerations and Notable Interactions

General Tolerability of Standardized Extracts

Ivy leaf preparations are safe for use in cough due to acute URTIs and bronchitis. No serious adverse effects were reported across the studies identified in the updated 2021 systematic review.

Gastrointestinal Adverse Effects

Side effects affecting the stomach and gut are the most commonly reported adverse events with oral ivy leaf preparations. Overdose can provoke nausea, vomiting, diarrhoea, and agitation. One case of a 4-year-old child who developed aggressivity and diarrhoea after accidental intake of an ivy extract corresponding to 1.8 g herbal substance has been reported.

Contact Dermatitis (Topical Exposure)

Common ivy can cause contact dermatitis, including contact urticaria. The main allergen it contains is falcarinol. Of 127 Danish patients tested with falcarinol, 10 (8%) tested positive; seven were occupationally sensitized. Most adult cases of dermatitis associated with the plant arise following pruning; such reactions can be severe and usually occur 24 to 48 hours after pruning. The resulting dermatitis ranges from mild to moderately severe reactions, characterized by intense itching and "nettle rash."

Experimental and chemical investigations revealed that common ivy contains three compounds which are powerful irritants and moderate sensitizers; only two of these constituents, falcarinol and didehydrofalcarinol, are present in the plant throughout the whole year. Between 1994 and 2009, 28 new cases of contact dermatitis from ivy were reported in the published literature, 2 of which were occupational.

Fresh Plant Toxicity

Ivy leaf, the medicinal part of the ivy plant used in remedies, is processed into a dry extract. Fresh leaves are toxic and must not be consumed directly. This extract appears in cough syrups for phlegmy coughs or in capsules, available at pharmacies or drugstores. Ivy berry ingestion is toxic due to high saponin content and can cause severe gastrointestinal distress.

Pregnancy and Lactation

The safety of Hedera helix extract during pregnancy was not established yet at the time regulatory guidance was formalized. A retrospective cohort study (Alkattan et al., 2021) addressed this question directly: a retrospective multicenter cohort study was conducted during the fourth quarter of 2020 on 245 pregnant women and their newborns in two hospitals in Riyadh, Saudi Arabia. The women were divided into an exposed group (N=165) who used English ivy leaf extract syrup during pregnancy, and a control group (N=80). The mean weight of the newborns in the exposed group was 3 kg compared to 2.8 kg in the control group. The authors concluded that Hedera helix (English ivy) leaf extract syrup was safe to be used short-term during pregnancy for the fetus. This single retrospective study has significant methodological limitations, and formal regulatory guidance continues to advise caution.

Contraindications

Avoid in peptic ulcer patients and those with known bile duct obstruction, as saponins can increase bile secretion. Exercise caution in individuals with asthma: paradoxical bronchospasm, though rare, has been documented.

Drug Interactions

No major interactions are well-documented, but theoretically, ivy's expectorant actions might amplify the effects of other mucolytics. The absence of well-documented interactions reflects a limited pharmacokinetic evidence base: no pharmacokinetic data are available according to the EMA EU herbal monograph.

Evidence Quality and Limitations (Overall)

Given the minimal treatment effects reported in the current literature and the natural course of URTIs and bronchitis, it seems unlikely that high-quality, large-scale studies will establish clinically important effects. Human studies on ivy's immunomodulatory effects are sparse, and current animal models offer limited translatability. Debate endures around its diuretic claims, as clinical trials have not conclusively supported significant urinary output changes. Quality variation between commercial products poses challenges for meta-analyses and standardized recommendations.

References

• European Medicines Agency (EMA) – Hederae helicis folium herbal medicinal product summary
• EMA – European Union Herbal Monograph on Hedera helix L., folium (Revision 2, EMA/HMPC/325716/2017)
• EMA – Final Assessment Report on Hedera helix L., folium (Revision 2)
• EMA/HMPC – Community Herbal Monograph on Hedera helix L., folium (2011, EMA/HMPC/289430/2009)
• Schink M et al. – Ivy leaf (Hedera helix) for acute upper respiratory tract infections: an updated systematic review. European Journal of Clinical Pharmacology, 2021 (PMC8275562)
• Kruttschnitt E et al. – Assessment of the Efficacy and Safety of Ivy Leaf Cough Syrup Compared with Acetylcysteine in Adults and Children with Acute Bronchitis. Evidence-Based Complementary and Alternative Medicine, 2020
• Baharara H et al. – The Effects of Ivy (Hedera helix) on Respiratory Problems and Cough in Humans: A Review. Advances in Experimental Medicine and Biology, 2021 (PubMed 34981489)
• Pajankar S et al. – The Antiinflammatory and Antiarthritic Properties of Ethanol Extract of Hedera helix. Journal of Pharmacy and Bioallied Sciences, 2013 (PMC3719157)
• Song KJ et al. – Expectorant and Antitussive Effect of Hedera helix and Rhizoma coptidis Extracts Mixture. Yonsei Medical Journal, 2015 (PMC4397455)
• Alkattan A et al. – Safety of English ivy (Hedera helix) leaf extract during pregnancy: retrospective cohort study. DARU Journal of Pharmaceutical Sciences, 2021
• Shokry AA et al. – Anti-arthritic activity of the flavonoids fraction of ivy leaves (Hedera helix L.) standardized extract in adjuvant induced arthritis model in rats in relation to its metabolite profile using LC/MS. Biomedicine & Pharmacotherapy, 2022 (PubMed 34839259)
• ScienceDirect Topics – Hedera helix overview
• ScienceDirect Topics – Alpha-Hederin overview
• Hausen BM et al. – Allergic and irritant contact dermatitis from falcarinol and didehydrofalcarinol in common ivy (Hedera helix L.). Contact Dermatitis, 1987
• Oxford University Plants 400 – Hedera helix
• Herbal Academy – History and Uses of Common Ivy
• PMC – Molecular insights into the anti-inflammatory efficacy and HPLC analysis of Hedera helix leaf extract (PMC12361965)
• Biomedical and Pharmacology Journal – Anti-inflammatory, Antioxidant, and Wound-healing Properties of Hedera helix Fruits and Leaves
• Altmeyers Encyclopedia – Hederae folium (Phytotherapy)
• Röttger-Lüer P, Staiger C – Review on the Clinical Evidence of the Ivy Leaves Dry Extract EA 575®. Planta Medica, 2015