Pelargonium Sidoides

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1. What Pelargonium Sidoides Is

Pelargonium sidoides is a plant native to southern Africa from the geranium family (Geraniaceae). The phytomedicinally investigated material is an extract from the root, described as a multi-substance mixture: basic research deals with the plant’s metabolites and tests extracts and individual constituents for antibacterial activity. Review articles trace the historical, scientific and commercial development of this use; species conservation is also discussed in this context.

One point is decisive for the assessment of all studies: a defined special extract from the root is usually investigated, not the plant as such. Almost all controlled human studies work with the preparation EPs 7630, sometimes as a liquid, sometimes as a tablet. A plant extract is a mixture whose composition depends on the starting material and the manufacturing process; results therefore cannot readily be transferred to other extracts, to tea preparations or to other dosage forms. There is also the question of measurement: clinical endpoints are predominantly symptom scores and time to freedom from complaints, not viral load or pathogen elimination. Cell cultures work with concentrations that need not be reached in tissue.

2. What the Studies Show in Detail

The key human studies and the most important reviews — by indication, with population, duration, preparation, measure and result as reported in the original papers. Numbers appear only where the study states them.

Distribution of controlled human studies by indication — the figures are not additive, as one study may be assigned to several areas:

Immune System

The Cochrane review of 2013 [1] examined efficacy and safety of Pelargonium sidoides preparations in acute respiratory infections in children and adults. Double-blind, randomised controlled trials against placebo or another treatment were included; the primary endpoint was defined as complete resolution of all symptoms, with additional resolution of pre-specified key symptoms. Searches were conducted in April 2013 in, among others, MEDLINE, EMBASE, the Cochrane Library, CINAHL, LILACS, Global Health and AMED as well as the registers ClinicalTrials.gov, DRKS, WHO ICTRP, Current Controlled Trials and EU Clinical Trials Register.

The 2008 version [13] documents the methodological approach in detail: three authors extracted and assessed the data independently, analyses were run separately by age group and disease pattern, heterogeneity was tested with the I² statistic. Pooled relative risks were calculated with a fixed-effect model when heterogeneity was absent (I² < 5 %; P > 0.1); when heterogeneity was substantial (I² > 50 %; P < 0.10) no pooled effect was calculated. The question therefore remains open as to which pooled effect size results across the included studies.

Two randomised dose-finding studies clarify the dose-response relationship. In the adult study [57], 406 patients with acute bronchitis outside the strict antibiotic indication were randomised in an adaptive group-sequential design to 10 mg, 20 mg or 30 mg EPs 7630 tablets three times daily (30-mg, 60-mg and 90-mg group) or placebo three times daily, treatment duration 7 days. The total BSS score decreased from baseline to day 7 by 2.7 ± 2.3 (placebo), 4.3 ± 1.9 (30 mg), 6.1 ± 2.1 (60 mg) and 6.3 ± 2.0 points (90 mg); the differences versus placebo were each significant with p < 0.0001, the secondary endpoints showed comparable results, tolerability was good. In the child and adolescent study [52], 400 patients aged 6 to 18 years were randomised to 30 mg, 60 mg or 90 mg EPs 7630 daily or placebo, the primary endpoint was the change in BSS from day 0 to day 7. After 7 days, the change in BSS in the 60-mg and 90-mg groups was significantly better than under placebo, with no relevant differences between these two doses; 'cough', 'sputum' and 'rales on auscultation' improved particularly, onset of action was faster, bed rest shorter, treatment outcome and satisfaction better, tolerability comparable to placebo. For doses below 60 mg daily in children and adolescents, the 30-mg dose has already been tested in a controlled manner.

[34] investigated 217 adult outpatients with acute bronchitis in a randomised, double-blind, placebo-controlled manner; the BSS (scale 0 to 20) decreased by 7.6 ± 2.2 points under verum and 5.3 ± 3.2 points under placebo (p < 0.0001). For all recorded symptoms (cough, sputum, rales, dyspnoea, pain on coughing, hoarseness, headache, fatigue, fever, limb pain) a clear improvement was shown, particularly pronounced were antitussive and 'anti-fatigue' effects with early onset; the patients were able to work earlier and were less often bedridden. The open multicentre follow-up study [14] recorded 205 patients with acute bronchitis or acute exacerbation of chronic bronchitis; five leading symptoms (cough, expectoration, wheezing or whistling on expiration, chest pain on coughing, dyspnoea) were assessed on a 5-point scale (0 = absent to 4 = extremely pronounced), four further symptoms on a 4-point scale (0 to 3). The total score of the leading symptoms was 6.1 ± 2.8 points at baseline and decreased by 3.3 ± 3.8 points to 2.8 ± 2.6 points.

The largest evaluated data collection comes from a multicentre, prospective, open observational study at 440 study centres in Germany [62]. 2099 patients aged 0 to 93 years with productive cough for less than six days and without indication for antibiotic treatment received EPs 7630 solution for 14 days in an age-dependent dosage. The mean BSS (cough, sputum, rales or rhonchi, chest pain on coughing, dyspnoea) decreased from 7.1 ± 2.9 points at baseline to 1.0 ± 1.9 points at the individual last visit; in children from 6.3 ± 2.8 to 0.9 ± 1.8 points and in children under three years from 5.2 ± 2.5 to 1.2 ± 2.1 points. Adverse events were reported in 26 of 2099 patients (1.2 %), none serious. Without a control group, this course cannot be distinguished from the spontaneous resolution of an acute infection.

For children, an overview of seven studies with 1067 children under six years who received EPs 7630 is available [15]: In two randomised double-blind studies in acute bronchitis, efficacy regarding symptom intensity and time to complete recovery was significantly better than placebo, two non-comparative observational studies on acute bronchitis showed similar symptom courses, and one open, non-comparative study each on acute tonsillopharyngitis and acute rhinosinusitis reported complete recovery or marked improvement in almost all children. A meta-analysis of randomised placebo-controlled studies with individual participant data [16] included six studies with 523 children aged 6 to 10 years (EPs 7630: 265, placebo: 258) with non-β-haemolytic streptococcal tonsillopharyngitis (three studies) or acute bronchitis (three studies); cumulative paracetamol consumption and the ability to attend school at the end of treatment were examined. A narrative review of eight randomised controlled studies in children and adolescents with acute bronchitis, acute tonsillopharyngitis and respiratory tract infections in chronic pre-existing conditions reports a statistically significant improvement in symptom severity compared with controls [68]. A meta-analysis of 34 randomised controlled studies on herbal medicinal products for cough (N = 7,083) found moderate evidence for Pelargonium sidoides across 11 studies (RR = 4.60; 95 % CI = 2.89, 7.31; P < 0.001) versus placebo for frequency and severity of cough [60]. Its indication is the next number to be clarified.

Viral Infections

The study on the common cold [2] was designed as a multicentre, prospective, randomised, double-blind, placebo-controlled phase-III study with adaptive group-sequential design at eight outpatient departments. The BSS decreased by day 7 by 7.2 ± 3.1 points under verum (n = 64) and 4.9 ± 2.7 points under placebo (n = 60); the 95 % confidence interval for the difference was (1.21; 3.56), p < 0.0001.

For children with transient hypogammaglobulinaemia of infancy, a randomised, placebo-controlled, prospective, monocentre pilot study is available [18]. Of 28 patients diagnosed with THI, 14 received Pelargonium sidoides and 14 placebo during an upper respiratory tract infection; before and after the one-week treatment, blood count, prothrombin time, activated partial thromboplastin time, serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as total and direct bilirubin were measured, and the mothers completed a questionnaire on the resolution of clinical symptoms. Increased appetite in the verum group as well as a favourable influence on nasal congestion and the resolution of complaints during the day and at night are reported. The sample size of 14 patients per arm limits the informative value, and the clinical data come from a maternal questionnaire, not from a validated clinical endpoint.

Two preclinical studies investigate the effect on viruses directly. In cell culture experiments [58], EPs 7630 at concentrations up to 100 μg/ml impaired the replication of seasonal influenza A strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus and coxsackievirus, but not the replication of highly pathogenic avian influenza A virus (H5N1), adenovirus or rhinovirus. A second cell culture study [59] shows that the root extract protects peripheral mononuclear blood cells and macrophages from infection with various X4- and R5-tropic HIV-1 strains including clinical isolates by acting directly on viral infectivity and blocking the attachment of virus particles to target cells; the inhibition is attributed to several polyphenolic compounds with low cytotoxicity that can be separated from extract components with higher cytotoxicity. A review article [63] classifies that only moderate direct antibacterial capabilities against a spectrum of bacteria including mycobacterial strains have been described, while in vitro an anti-infective effect via activation of the non-specific immune system and inhibition of the interaction between bacteria and host cells is described. Since the extract from [2] ends before the results, the clinical question regarding the effect in the common cold remains open.

Safety and Tolerability

The systematic review and meta-analysis of 2008 [47] searched five electronic databases (Medline 1950 to July 2007, Amed 1985 to July 2007, Embase 1974 to July 2007, CINAHL 1982 to July 2007 and the Cochrane Library, Issue 3, 2007) without language restriction, checked reference lists and contacted manufacturers for published and unpublished material. All randomised clinical trials of Pelargonium sidoides monopreparations versus placebo or standard treatment in acute bronchitis with clinically relevant endpoints were included; two reviewers independently selected the studies, extracted and validated the data, methodological quality was assessed with the Jadad score, and for continuous data a meta-analysis with fixed-effect model was calculated as weighted mean difference with 95 % confidence interval. Six randomised controlled studies met the inclusion criteria, four were suitable for statistical pooling; one study compared EPs 7630 with conventional non-antibiotic treatment (acetylcysteine), the other five with placebo, and the methodological quality of most studies was good. The 2007 review [69] summarises the pharmacological, toxicological and clinical data that led to the approval of the medicinal product by the Federal Institute for Drugs and Medical Devices in December 2005.

Two large placebo-controlled adult studies on acute bronchitis report efficacy data. [49] randomised 468 adults with acute bronchitis of at most 48 hours' duration and a BSS of at least five points at 36 general practitioners; 30 drops three times daily were administered for seven days. The BSS decreased by 5.9 ± 2.9 points under verum (n = 233) and 3.2 ± 4.1 points under placebo (n = 235), the 95 % confidence interval for the difference was [−3.359; −2.060] (p < 0.0001); inability to work decreased to 16 % in the verum group versus 43 % under placebo (p < 0.0001), and disease duration was significantly shorter.

In children and adolescents, two randomised, double-blind, placebo-controlled multicentre studies examined efficacy and tolerability. [53] randomised 200 patients aged 1 to 18 years with acute bronchitis outside the strict antibiotic indication to age-stratified doses (1 to 6 years: three times 10 drops daily; over 6 to 12 years: three times 20 drops daily; over 12 to 18 years: three times 30 drops daily) or placebo for seven days. The BSS improved from baseline to day 7 under verum by 3.4 ± 1.8 versus 1.2 ± 1.8 points under placebo (p < 0.0001); treatment outcome was significantly better (p < 0.0001), satisfaction with treatment more pronounced (77.6 % versus 25.8 %, p < 0.0001), onset of action faster and bed rest shorter; tolerability was equally good in both groups, and all adverse events were rated as non-serious. [54] randomised 220 patients with acute bronchitis to verum (1 to 6 years, over 6 to 12 years, over 12 to 18 years: three times 10, three times 20, three times 30 drops daily) or matching placebo for seven days; the BSS decreased by 4.4 ± 1.6 versus 2.9 ± 1.4 points (p < 0.0001), most markedly for 'cough' and 'rales on auscultation', and tolerability was similarly good in both groups. Observation in these studies ends with the seven-day treatment; statements on application periods beyond this have not yet been examined therein.

Inflammatory Processes

For the question of whether Pelargonium sidoides can prevent asthma attacks in the context of viral infections of the upper respiratory tract, there is a randomised study in 61 asthmatic children with such an infection [11]. The children received Pelargonium sidoides (n = 30) or no treatment (n = 31) daily for five days at random; they were examined and symptom scores determined before and after treatment, after which the occurrence of an asthma attack was recorded. For fever and muscle pain there were no statistically significant differences (p > 0,05, chi-square test), but for cough frequency and nasal congestion there were significant differences (p < 0,05), as well as for the occurrence of an asthma attack (p < 0,05); the frequency of asthma attacks was lower in the verum group.

The control group in this study received no treatment, there was no blinding, and the sample size is small with 30 versus 31 children; the work itself describes itself as an investigation into the efficacy of a five-day therapy without varying the treatment duration. Hypothesis: The inhibition of replication of seasonal influenza A strains, respiratory syncytial virus and other respiratory viruses by EPs 7630 described in cell cultures [58] could explain why cough frequency and nasal congestion decreased in [11]; whether this mechanism is responsible for the lower asthma attack rate is not examined by the study. What is missing is a blinded, placebo-controlled study with a larger sample size that uses the asthma attack as a predefined primary endpoint.

Gut and Microbiome

The 24-week COPD study [17] examined whether EPs 7630 prolongs the time to acute exacerbation. Patients with COPD stage II/III were randomised, double-blind and placebo-controlled in addition to standardised basic therapy, with three times 30 drops daily (n = 99) or placebo (n = 101). The median time to the first exacerbation was significantly prolonged under verum (57 versus 43 days, Kaplan-Meier estimate; p = 0,005, one-sided centre-stratified log-rank test). The secondary endpoints also confirmed superiority: fewer exacerbations, fewer patients with antibiotic intake, improved quality of life, higher patient satisfaction and fewer days of incapacity for work. The frequency of mild gastrointestinal adverse events was higher in the verum group.

The overview of systematic reviews on adverse effects of herbal medicinal products [64] evaluated 50 systematic reviews on 50 different medicinal plants; most had only minor methodological weaknesses. Serious adverse effects were reported for only four medicinal plants (Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna), the most severe being liver or kidney damage, intestinal perforation, carcinoma, coma and death. Moderate adverse effects were recorded for 15 medicinal plants, including Pelargonium sidoides; mild adverse effects for 31 others, including Thymus vulgaris, Lavandula angustifolia and Boswellia serrata.

The review on medicinal properties and protection of Pelargonium sidoides [67] notes that the plant was used in traditional medicine for the treatment of gastrointestinal complaints and is only used as a phytopharmaceutical for respiratory tract infections. In vitro, the results indicate that the bioactive constituents do not exert a direct antimicrobial effect but disrupt the binding of microorganisms to host cell receptors, inhibit key enzymes and stimulate the formation of antimicrobial effector molecules such as nitric oxide and interferons in the host cells; the increasing international demand has led to local overexploitation of wild stocks in South Africa, and the work identifies knowledge gaps in these research areas. For adhesion in the stomach there is an ex-vivo experiment on intact human gastric tissue from resections [61]: Helicobacter pylori bacteria labelled with fluorescent dye adhered to untreated samples; after pretreatment of the bacteria with the root extract, the anti-adhesive activity was pronounced and clearly dose-dependent in the range of 0,001 to 10 mg/ml, while no direct cytotoxicity against H. pylori occurred in the agar diffusion test. This finding comes from preclinical ex-vivo experiments; what is missing is a clinical study that examines inhibition of colonisation or a change in the microbiome in humans.

Further Investigations

The overview of commercially important South African medicinal plants [65] examined the development of scientific publications and patents on 38 medicinal plant species via the Scopus reference system; 15 species of particular commercial interest were presented in more detail, including Pelargonium sidoides alongside Agathosma betulina, Aloe ferox, Artemisia afra, Aspalathus linearis, Cyclopia genistoides, Harpagophytum procumbens, Hoodia gordonii, Hypoxis hemerocallidea, Lippia javanica, Mesembryanthemum tortuosum, Siphonochilus aethiopicus, Sutherlandia frutescens, Warburgia salutaris and Xysmalobium undulatum. The work reports a strong increase in research and development of new medicinal products and cultivated plants in the years before; although an estimated 10 % of the world's plant species occur in South Africa, only a few are fully commercialised.

The historical, scientific and commercial overview [66] traces the ethnobotany and commercial history of Pelargonium sidoides and summarises preclinical and clinical results that support its use in modern phytopharmaceuticals. According to the available ethnobotanical information, several tuber-forming Pelargonium species, including Pelargonium sidoides, are important traditional remedies with a rich ethnobotanical history; the work presents the history of the commercial development of a preparation introduced in Europe. As a scientific basis, it cites numerous in-vitro studies and 18 clinical studies, predominantly on the treatment of acute bronchitis, and describes the botanical identity of the plant as well as its complex mixture of coumarins and other constituents. The use of Pelargonium stems or tubers for various complaints including complications of dysentery is described as an important, previously underestimated part of traditional medicine in southern Africa. What is missing is an analysis of which of these 18 clinical studies examined which endpoint with which sample size.

Overall Picture

Across the areas, acute bronchitis carries the most robust statements. For adults there are several randomised, double-blind, placebo-controlled studies with a consistent direction of BSS reduction: 7,2 ± 3,1 versus 4,9 ± 2,7 points [46], 7,6 ± 2,2 versus 5,3 ± 3,2 points in two studies [34], [51], 5,9 ± 2,9 versus 3,2 ± 4,1 points [49] as well as dose-dependent reductions of 2,7 over 4,3 and 6,1 to 6,3 points [57]. In children and adolescents the same picture emerges with 3,4 ± 1,8 versus 1,2 ± 1,8 points [53] and 4,4 ± 1,6 versus 2,9 ± 1,4 points [54]; for children under six years the statement comes predominantly from non-comparative observational data [15]. For cough as a symptom there is moderate evidence from a meta-analysis of 11 studies (RR = 4,60; 95 % CI = 2,89, 7,31; P < 0,001) [60].

The investigation in transient hypogammaglobulinaemia comprises 14 patients per arm, and its data are based on a questionnaire from the mothers [18]; the asthma study compares 30 children against 31 children without treatment [11]; the 24-week COPD study shows a prolongation of the time to exacerbation from 43 to 57 days, but more mild gastrointestinal events [17]. The virus and adhesion findings come from cell culture and ex-vivo tissue [58], [59], [61]. Across all areas, the testing of applications outside acute bronchitis is therefore at the beginning; in particular, it remains open which effects can be reproduced in blinded, placebo-controlled studies with predefined endpoints.

3. How Robust the Research Is

The literature comprises basic and cell research; controlled human studies form a distinct, clearly delineated block within it, supplemented by observational human studies, mechanism reviews, animal and environmental studies. Within the controlled studies, one area of application dominates: acute respiratory tract infections, above all acute bronchitis, alongside the common cold, sinusitis and tonsillitis. Safety endpoints are included in a large proportion of the studies; the immune system is a frequent investigation target. Antiviral and inflammatory questions are predominantly preclinical; for the gut, fatigue, the musculoskeletal system and bioavailability, only isolated controlled studies exist.

For acute bronchitis in adults and in children and adolescents, several randomised, double-blind, placebo-controlled studies are available, together with a systematic review with meta-analysis and a dose-finding study. Proven: in this indication is an influence on the symptom course in randomised, placebo-controlled studies; Plausible: are the subsequent explanations regarding immunological effects, which to date derive predominantly from the laboratory. Methodological strengths are randomisation, placebo control and separate investigation of children and adults. The weaknesses concern breadth: a single preparation, short observation periods, symptom scores rather than hard disease endpoints and limited independent replication by other research groups.

4. What Is Frequently Claimed — and What the Data Provide

5. Profile: Molecule and Charge

Pelargonium sidoides is not a single molecule but a mixture — there is no molecular formula and no fixed molecular mass. What can be described are functional groups, charge behaviour and redox properties; that is exactly what the next section addresses.

6. Charge, Electrons, Radicals

Radicals and electron transfer have so far been measured for Pelargonium sidoides in cell culture and basic research studies. The DPPH radical-scavenging activity of an extract was 14.7±0.85 μg/ml (IC50) 27. Across 0.001 to 2 mg/mL, DPPH•- and ABTS•+-radical scavenging, β-carotene-linoleic acid co-oxidation and protection of 2-deoxyribose and phospholipids from bovine brain against hydroxyl-radical-mediated degradation were examined 28. In callus tissue, DPPH radical scavenging, the β-carotene-linoleic acid assay and ORAC were used 30; likewise ORAC, DPPH and minimum inhibitory concentrations against bacterial and fungal strains 25. These studies do not measure charge or cation exchange.

In cell culture, an extract of P. sidoides lowered mitochondrial membrane potential, increased the number of reactive oxygen species (ROS) in the cell and released NADH; this is regarded as a sign of mitochondrial dysfunction 26. Another preparation, PELIRGOSTIM, lowered ROS and nitrite levels, correlated with reduced IL-1β release after LPS treatment 29. Both findings are preclinical and were not obtained in humans. Redox or charge data measured in humans are lacking; what remains to be clarified is whether the radical-scavenging values are reproduced in vivo and whether the ROS reduction 29 and the ROS increase 26 result from different preparations or concentrations.

7. Interactions with Other Substances

With which other substances on the platform this substance has been jointly investigated or discussed in human studies and reviews — combination, comparison or shared mechanism of action. The number indicates studies in which both appear.

A combination preparation of Pelargonium sidoides extract and Coptis extract is described as an expectorant and antitussive 31; in this controlled human study, food influenced the systemic exposure and bioavailability of berberine and epicatechin 31. Plausible: In a review article, the enhanced antimicrobial effect is attributed to the interaction of a metallic silver core with phytochemicals from P. sidoides on the surface of nanoparticles, which contributes to the colloidal stability of the silver nanoparticles at physiological pH values 34. It would need to be examined whether food influences the absorption of the Pelargonium constituents.

A rat animal study examined whether the Pelargonium sidoides extract EPs 7630 alters coagulation parameters or interacts with coumarin anticoagulants 35; the treatment had no influence on coagulation parameters or the pharmacokinetics of warfarin 35. Hypothesis: An interaction risk with anticoagulants such as warfarin and platelet aggregation inhibitors such as aspirin is described 32. In human tissue, 420 antibiotic-plant combinations were tested, including Pelargonium sidoides 33; 14.29 % were synergistic and 7.56 % antagonistic 33. It would need to be clarified whether the animal finding transfers to humans and whether CYP enzymes are involved.

8. Overdosage, Tolerability, Limits

As adverse effects, a controlled human study lists 25 of 124 patients; of these, 15 of 64 were in the verum group and 10 of 60 in the placebo group 3. In a further controlled study, adverse effects occurred in 36 of 468 patients, of which 20 of 233 under verum and 16 of 235 under placebo 5. All recorded events were assessed as not serious 3; serious adverse effects did not occur in several controlled studies 4610. Also in children and adolescents, the events were assessed as not serious 8, and tolerability was comparably good in both groups 9.

Regarding dose: In a controlled human study, three tested doses of the preparation EPs 7630 were superior to placebo 10, and all doses were described as tolerable 10. Weighing efficacy and safety, the authors designate 20 mg tablets three times daily as the optimal dose in the benefit-risk ratio 10. Data on toxicity, upper limits or contraindications are still lacking in the cited works; events and tolerability within the tested dose range are reported. It would need to be clarified which doses above 20 mg three times daily were tested and for which patient groups no investigation is available 10.

9. The Most Robust Works

Ordered by strength of evidence, not by familiarity. The complete evaluation comprises considerably more works; the most robust ones are listed here.

Controlled Human Studies

• 1 Pelargonium sidoides extract for treating acute respiratory tract infections (2013)
• 2 Efficacy of a pelargonium sidoides preparation in patients with the common cold: a randomized, double blind, placebo-controlled clinical trial (2007)
• 3 Treatment of acute bronchitis in adults with a pelargonium sidoides preparation (EPs 7630): a randomized, double-blind, placebo-controlled trial (2005)
• 4 Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis (2008)
• 5 Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled … (2003)
• 6 Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised, double-blind … (2007)
• 7 Efficacy and tolerability of EPs 7630 in patients (aged 6-18 years old) with acute bronchitis (2010)
• 8 Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis - a randomized, double-blind, placebo-controlled multicenter … (2010)
• 9 Treatment of acute bronchitis with EPs 7630: randomized, controlled trial in children and adolescents (2012)
• 10 Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: a randomised, double-blind, placebo-controlled dose-finding study … (2010)
• 11 Can the Pelargonium sidoides root extract EPs® 7630 prevent asthma attacks during viral infections of the upper respiratory tract in children? (2013)
• 12 EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomised, double-blind, placebo-controlled, multicentre … (2008)
• 13 Pelargonium sidoides extract for acute respiratory tract infections (2008)
• 14 EPs 7630-solution--an effective therapeutic option in acute and exacerbating bronchitis (2007)
• 15 EPs 7630 is effective and safe in children under 6 years with acute respiratory tract infections: clinical studies revisited (2018)
• 16 Faster recovery and reduced paracetamol use - a meta-analysis of EPs 7630 in children with acute respiratory tract infections (2019)
• 17 Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD (2013)
• 18 The efficacy of Pelargonium sidoides in the treatment of upper respiratory tract infections in children with transient hypogammaglobulinemia of … (2012)
• 19 Herbal Drug EPs 7630 versus Amoxicillin in Patients with Uncomplicated Acute Bacterial Rhinosinusitis: A Randomized, Open-Label Study (2020)
• 20 Treatment of signs and symptoms of the common cold using EPs 7630 - results of a meta-analysis (2019)
• 21 Effectiveness of Pelargonium sidoides in pediatric patients diagnosed with uncomplicated upper respiratory tract infection: a single-blind … (2021)
• 22 [A Systematic Review of Phytotherapy for Acute Rhinosinusitis] (2016)
• 23 Effects of Pelargonium sidoides extract EPs 7630 on acute cough and quality of life - a meta-analysis of randomized, placebo-controlled trials (2022)
• 24 Unlocking the therapeutic potential of Pelargonium sidoides natural extract: A scoping review (2024)

10. Summary

Proven For acute bronchitis in adults and in children and adolescents, several randomised, double-blind, placebo-controlled studies show an influence on the course of symptoms. A systematic review with meta-analysis and a dose-finding study support this indication. In the dose-finding study in adults, the total BSS score decreased from baseline to day 7 by 2.7 ± 2.3 (placebo), 4.3 ± 1.9 (30 mg), 6.1 ± 2.1 (60 mg) and 6.3 ± 2.0 points (90 mg); the differences versus placebo were significant with p < 0.0001 in each case. In the study in children and adolescents, the BSS change in the 60-mg and 90-mg groups was significantly better than under placebo.

Plausible are the subsequent explanations regarding immunological effects, which to date have predominantly come from the laboratory. Cell culture experiments show an impairment of the replication of seasonal influenza A strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus and coxsackievirus, but not of the highly pathogenic avian influenza A virus (H5N1), adenovirus or rhinovirus. A second cell culture study shows that the root extract protects peripheral mononuclear blood cells and macrophages from infection with various X4- and R5-tropic HIV-1 strains. Hypothesis: If the immunological mechanisms are confirmed, this could lead to a broader application in respiratory tract infections; however, the transfer to humans remains open.

Similarly, the effect sizes from the meta-analysis with individual participant data in children are missing. The clinical question regarding the effect on the common cold remains open, as the excerpt from the phase III study ends before the results. For the intestine, exhaustion, musculoskeletal system and bioavailability, there are only individual controlled studies; here, the controlled examination is still pending.

11. What Remains Open

• Dose ranges: A dose-finding study for acute bronchitis is available; which preparation and which dose range is to be preferred for which indication is still to be clarified in comparative controlled studies.
• Transferability: Which laboratory findings on antibacterial and antiviral activity can be reproduced in humans is an open, testable question.
• Safety with repeated use: The safety data predominantly come from the short-term treatment of acute diseases; adverse effects with longer or repeated intake are still an open question.

12. Further Paths

Topics, modes of action and chains in which this substance occurs — for all those who wish to look beyond the substance.

• Interaction network