Systematic Review of Clinical Trials Assessing the Effectiveness of Ivy Leaf (Hedera Helix) for Acute Upper Respiratory Tract Infections

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2011, Article ID 382789, 9 pages doi:10.1155/2011/382789 Review Article Systematic Review of Clinical Trials Assessing the Effectiveness of Ivy Leaf (Hedera Helix) for Acute Upper Respiratory Tract Infections Felix Holzinger and Jean-François Chenot Department of General Practice/Family Medicine, University Medicine Goettingen, Humboldtallee 38, 37073 Goettingen, Germany Correspondence should be addressed to Jean-François Chenot, Received 16 May 2010; Accepted 17 August 2010 Copyright © 2011 F. Holzinger and J.-F. Chenot. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Among nonantibiotic cough remedies, herbal preparations containing extracts from leaves of ivy (Hedera helix) enjoy great popularity. Objective. A systematic review to assess the effectiveness and tolerability of ivy for acute upper respiratory tract infections (URTIs). Methods. We searched for randomized controlled trials (RCTs), nonrandomized controlled clinical trials and observational studies evaluating the efficacy of ivy preparations for acute URTIs. Study quality was assessed by the Jadad score or the EPHPP tool. Results. 10 eligible studies were identified reporting on 17463 subjects. Studies were heterogeneous in design and conduct; 2 were RCTs. Three studies evaluated a combination of ivy and thyme, 7 studies investigated monopreparations of ivy. Only one RCT (n = 360) investigating an ivy/thyme combination used a placebo control and showed statistically significant superiority in reducing the frequency and duration of cough. All other studies lack a placebo control and show serious methodological flaws. They all conclude that ivy extracts are effective for reducing symptoms of URTI. Conclusion. Although all studies report that ivy extracts are effective to reduce symptoms of URTI, there is no convincing evidence due to serious methodological flaws and lack of placebo controls. The combination of ivy and thyme might be more effective but needs confirmation. 1. Introduction Cough is a highly prevalent condition and a common reason for consultations in general practice [1–4]. Most frequently, cough symptoms are caused by acute viral upper respiratory tract infections (URTIs) and the course is mostly benign and self-limiting, although bacterial superinfection may occur in acute bronchitis [5, 6]. For chronic cough, important causes are chronic obstructive pulmonary disease (COPD) and asthma which are characterized by airway obstruction and hypersecretion of mucus, additionally causing symptoms like wheezing or dyspnoea. Inappropriate use of antibiotics for viral respiratory tract infections is a significant problem causing both pathogen resistance and substantial health care expenditure without affecting the resolution of cough [7]. Therefore nonantibiotic alternative treatment options are needed. Commonly used over-the-counter drugs for acute cough in both children and adults are mucolytic agents and antitussives, which are also widely prescribed in primary care settings [8]. In the UK, cough liquids accounted for sales worth 102 million pounds in 2008 [9]. Among these nonantibiotic cough remedies, herbal preparations containing extracts from the leaves of ivy (Hedera helix L.) enjoy great popularity in many European countries [10–12]. In 2007, more than 80% of herbal expectorants prescribed in Germany comprised ivy extract and amounted to nearly 2 million prescriptions nationwide and a volume of sales exceeding 13 million Euros [10]. Ivy leaf contains saponins which are considered to have mucolytic, spasmolytic, bronchodilatory and antibacterial effects [13, 14]. Despite widespread use of ivy leaf extracts, the effectiveness for the treatment of acute cough is not well established. Methodically strong clinical studies seem scarce despite the epidemiological and economic importance. To our knowledge, there is no comprehensive systematic review 2 of the available clinical evidence. A Cochrane Review assessing over-the-counter cough medications does not cover herbal drugs [8]. Other reviews focus on effectiveness of ivy leaf extracts in asthma or COPD [12, 15–17]. Therefore, we performed a systematic review of the effectiveness and tolerability of ivy preparations for the treatment of acute URTIs in children and adults. 2. Methods 2.1. Data Sources. Our search included 3 electronic bibliographic databases: MEDLINE, EMBASE and the Cochrane Library. We included studies published from the respective inception of the databases until 20. December 2009. There was no language restriction. Search terms were: ivy, hedera, respiratory tract diseases, respirat∗ , cough, bronchitis, bronchial. The complete search algorithm with the keywords and MeSH-terms used is available from the authors upon request. Additionally, we hand searched the bibliographies of the publications retrieved. Several manufacturer websites were also scanned manually for references. 2.2. Study Selection 2.2.1. Eligibility Criteria. We did not exclude specific populations or age groups. Our search included published randomized controlled trials (RCTs), controlled clinical trials (CCTs) and noncontrolled observational studies (OSs) evaluating the effectiveness and/or tolerability of medications containing ivy leaf extract for the treatment of acute URTIs including bronchitis. Studies investigating patients with a variety of other acute (e.g., pertussis, pneumonia) and chronic diseases (COPD, asthma) were excluded. However, we did not disregard studies where URTI patients represented the majority of investigated subjects or treatment results were reported separately. Ivy leaf extract could be the only ingredient in the respective drug preparation or could be combined with other herbal components. We restricted the search on studies evaluating oral or rectal administration forms. Outcome measures could be hard clinical endpoints (e.g., morbidity, mortality, health-related quality of life), surrogate values like spirometric parameters, physician’s findings upon clinical examination, assessment of symptoms (e.g., cough) by either physician or patient, and undesirable side effects of treatment. 2.2.2. Screening Process. The titles and abstracts of the citations identified were screened by two independent reviewers (FH and JFC) separately using a predesigned form. Titles and abstracts that clearly did not meet the inclusion criteria regarding indication (respiratory symptoms) or intervention (drug containing ivy leaf extract) were excluded. Duplicate titles were also eliminated. For publications fulfilling the inclusion criteria or for which inclusion or exclusion could not be ascertained, we reviewed the full text. Disagreements were resolved by consensus. A list of references of (...truncated)