Reviewed: Timmer A, Günther J, Motschall E, Rücker G, Antes G, Kern WV. Pelargonium sidoides extract for treating acute respiratory tract infections. Cochrane Database Syst Rev. 2013;10:CD006323.

Acute respiratory infections can be divided into upper respiratory infections that include sinusitis, common cold, otitis media, and pharyngitis, and lower respiratory infections such as acute bronchitis. Symptoms usually last from one to three weeks and often are treated with medications to alleviate symptoms, or, in more severe cases, they are treated with antibiotics. The ethanolic extract of Pelargonium sidoides (Geraniaceae) root known as EPs® 7630 (Dr. Willmar Schwabe Pharmaceuticals; Karlsruhe, Germany) is available in solution, tablet, and syrup forms that currently are approved in Germany and many other countries for treating acute bronchitis. In vitro, P. sidoides extract has been shown to have an antiviral as well as a weak antibacterial effect, and to increase cilia function, making it a potential expectorant. The purpose of this study was to review studies of the effect of P. sidoides extract on acute respiratory infections.

The following databases were searched up to April 23, 2013, for potential studies to include in the Cochrane systematic review: “MEDLINE, Journals@Ovid, The Cochrane Library, Biosis Previews, Web of Science, CINAHL, CCMed, XToxline, Global Health, AMED, Derwent Drug File and Backfile, IPA, ISTPB + ISTP/ISSHP, EMBASE, Cambase, LILACS, PubMed component ‘Supplied by Publisher,’ TRIPdatabase, the publisher databases: Deutsches Ärzteblatt, Thieme, Springer, ScienceDirect from Elsevier,” along with “ClinicalTrials.gov, Deutsches Register Klinischer Studien DRKS (German Clinical Trials Register), International Clinical Trials Registry Platform (ICTRP) - WHO ICTRP, Current Controlled Trials and EU Clinical Trials Register.”

Only studies that were randomized, controlled, and double-blinded were included in the analyses. Cochrane risk-of-bias analyses were conducted, and studies deemed to be of high bias were excluded. Studies also were excluded if the patients had underlying chronic illnesses, such as chronic obstructive pulmonary disease or asthma. The primary outcome sought by the authors of this systematic review was time until complete resolution of symptoms. Since no studies included this outcome, the severity of symptoms at day seven was analyzed. With sinusitis, a longer timeframe (21 days) was found to be relevant. Adverse side effects from each study were noted. Treatment effects were calculated with risk ratios (RRs), with an RR of less than one corresponding to a decreased risk of having symptoms at day seven. Heterogeneity among studies was compared with the I2 index, which expresses if chance or heterogeneity is the cause of variation among the studies. Studies were separated into those with children and adults, and the type of extract (liquid or tablet) was compared.

Of the 10 eligible studies found, eight met all of the criteria and were included in the analysis. All of these studies were initiated by the manufacturer of the leading P. sidoides extract preparation (EPs® 7630, aka Umckaloabo and Umcka® [the trade name in the United States]) and were conducted in Russia and Ukraine. In two of three studies of acute bronchitis in adults (n=746), a liquid preparation (n=341) of P. sidoides had a positive effect on resolving sputum (RR=0.70), but heterogeneity among the studies was too high to pool the data on cough or resolution of all symptoms.

Of the three studies measuring acute bronchitis in children (n=819), the liquid preparation (n=420) used in two studies was found to have a positive effect on resolving all symptoms and cough (RR=0.82 for both). One study of acute sinusitis in adults (n=104) showed a positive effect of P. sidoides extract on resolution of all symptoms (RR=0.43), as well as nasal discharge (RR=0.21) and headaches (RR=0.23). Lastly, in one study of common colds in adults (n=103), an effect of treatment was found after 10 days (RR=0.41), but not after five days (RR=0.96).

Adverse effects of treatment in all studies were mild and consisted of gastrointestinal discomfort and allergic skin reactions. Pelargonium sidoides root extract has been classified as having moderate adverse effects.

From these analyses, there is evidence that the proprietary ethanolic extract of P. sidoides root made by the German manufacturer reduces the severity of acute bronchitis and sinusitis in adults and acute bronchitis in children.

The authors were concerned about small sample sizes, the initiation of the studies by the manufacturer, the small geographic region in which the studies were conducted, the potential subjectivity of symptom scores, and potential publication bias.

According to the authors, other common treatments of acute respiratory infection have mixed effects on reducing the severity of infection. For instance, they write, mucolytic and antitussive agents do not appear to reduce the severity of infection, while antibiotics may reduce the duration of symptoms by one day; echinacea (Echinacea purpurea and/or other species of Echinacea [Asteraceae]) preparations seem to reduce the duration and severity of common cold symptoms. Some questions have been raised about P. sidoides’ possible association with hepatotoxicity, but no evidence of such was found in these eight clinical trials. More well-designed, independent, and geographically diverse clinical research studies are warranted to confirm the potential positive effects of P. sidoides on acute respiratory infections, according to the authors.

Considering that the Cochrane Reviews tend to be somewhat conservative, the authors’ conclusions that “P. sidoides may be effective in relieving symptoms in acute bronchitis in adults and children, and sinusitis in adults” probably should be considered a positive assessment of the existing clinical trials.

—Cheryl McCutchan, PhD