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The effects of oral hydrolytic enzymes and flavonoids on inflammatory markers and coagulation after marathon running: study protocol for a randomized, double-blind, placebo-controlled trial

Viola Grabs1*, David C Nieman2, Bernhard Haller3, Martin Halle14 and Johannes Scherr1

Author Affiliations

1 Department of Prevention, Rehabilitation and Sports Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany

2 Human Performance Laboratory, Appalachian State University, North Carolina Research Campus, Kannapolis, NC, USA

3 Institute for Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany

4 DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany

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BMC Sports Science, Medicine and Rehabilitation 2014, 6:8  doi:10.1186/2052-1847-6-8

Published: 22 February 2014



Regular moderate intensity physical activity positively influences the immune system with a lower incidence of upper respiratory tract infections (URTI) and lower levels of pro-inflammatory markers. However, marathon running due to its strenuous and prolonged nature results in immune perturbations with a major increase in pro-inflammatory markers and subsequent increased incidence of URTI. Furthermore, marathon running results in muscle damage and changes in hemostasis that promote a pro-thrombotic state.

Naturally occurring hydrolytic enzymes and flavonoids have antioxidant, anti-inflammatory and fibrinolytic effects, and may serve as countermeasures to exercise-induced inflammation, immune dysfunction and URTI.

The aim of this study is to determine whether the ingestion of oral hydrolytic enzymes and flavonoids before and after a marathon attenuates post-race muscle damage and inflammation, counters pro-thrombotic changes in hemostasis and decreases URTI incidence.


The Enzy-MagIC-study (Enzymes, Marathon runninG, Inflammation, Coagulation) is a randomized, double-blind, placebo-controlled, monocenter phase I trial. 160 healthy males (age 20-65 years) will be randomized to receive either placebo or treatment (Wobenzym, MUCOS Pharma, Berlin, Germany) which contains the hydrolytic enzymes (bromelain, trypsin) and the flavonoid rutoside. One week before the marathon race, participants will begin daily ingestion of the investigational product (3×4 tablets). Intake will be continued for two weeks after the race (3×2 tablets per day). Clinical and laboratory measures will be collected 5-weeks and 1-week before the race, and immediately-, 24-h, 72-h, and 2 weeks after the race. The primary endpoint is the influence of the treatment on the pre-to-post marathon race plasma concentration change of the inflammatory marker interleukin-6 (IL-6). Secondary endpoints include the effect of treatment on salivary IgA concentration and the frequency of upper respiratory tract infections (URTI) for two weeks post-marathon as determined by the Wisconsin Upper Respiratory Symptom Survey (WURSS-24). Furthermore, changes of muscular and rheological parameters will be measured before and after the marathon race.


We hypothesize that marathon-induced inflammatory perturbations and the incidence of subsequent URTI, muscular damage, and changes of hemostasis can be positively influenced by the anti-edematous, anti-inflammatory, antioxidant, and fibrinolytic effects of oral hydrolytic enzymes and flavonoids (Wobenzym).

Trial registration Identifier: NCT01916408

Exercise; Inflammation; Upper respiratory tract illness; Oral hydrolytic enzymes; Flavonoids