Regular moderate intensity physical activity has been shown to positively influence the immune system [1, 2]. Clinically this is represented by decreased incidence of upper respiratory tract infections (URTI) and pro-inflammatory markers in individuals who participate in regular moderate-intensity physical activity [2, 3]. In contrast, most studies indicate that URTI rates increase during the 1-3 week period following marathon-type race events due to transient alterations in immunosurveillance [4–6]. Strenuous and prolonged exercise such as marathon running results in a major increase in inflammatory markers (e.g. C-reactive protein, interleukin 6) [6–8]. IL-6 is a cytokine with a wide range of biological effects, including pro-inflammatory influences during sepsis . IL-6 is a central mediator of the acute-phase response and primary determinant of hepatic production of C-reactive protein (CRP) . Elevated levels of IL-6 and CRP have been found in low-grade systemic inflammation such as atherosclerosis and diabetes mellitus [11, 12]. In healthy men an elevated IL-6 plasma concentration has been associated with increased vascular risk and myocardial infarction . IL-6 may stimulate blood coagulation and has been suggested to be an independent predictor for sudden death [14, 15].
However, it is discussed equivocally whether IL-6 is primarily a pro- or anti-inflammatory cytokine. IL-6 activity appears to be essential for both the effective management of acute inflammation and to balance pro- and anti-inflammatory activity . Post-exercise increases in plasma IL-6 are related to exercise workloads, with the highest levels found after strenuous and prolonged exercise [6–8]. Plasma IL-6 concentration decreases rapidly after strenuous exercise and is followed by increased levels of anti-inflammatory cytokines such as IL-1ra and IL-10 inducing an anti-inflammatory environment [2, 17, 18]. Chronic exercise, especially when accompanied with weight loss, is associated with decreased CRP and IL-6. This is linked to a reduced atherosclerosis and cardiovascular disease incidence [11, 12].
Besides immune alterations, marathon running results in muscular damage which causes elevated levels of muscle enzymes (e.g. creatine kinase) and muscle soreness . Additionally, changes of hemostasis leading to a pro-thrombotic state can be seen after a marathon race .
Consumption of plant derived foods such as vegetables and fruits has been linked to a reduced incidence of chronic diseases such as cancer and atherosclerosis [21, 22]. The protective effects of these foods are attributed to hydrolytic enzymes and flavonoids that have antioxidant, anti-inflammatory, and anti-microbial effects [23–25]. The most important and therefore most extensive investigated flavonoids are rutosid (synonym rutin) and its glycosyl quercetin. Both flavonoids are mostly found in plants (such as apples) . There are several studies investigating the antioxidant properties of these two flavonoids [26–30]. Whereas bromelain is a protein-digesting enzyme found in pineapple . Nutritional supplements are being investigated as countermeasures to exercise-induced inflammation, immune dysfunction, and URTI . Polyphenol-rich supplements under certain exercise conditions have been shown to exert anti-inflammatory and antioxidant effects [6, 27, 28].
Supplementation with oral hydrolytic enzymes has been reported to have analgetic, anti-edematous and anti-inflammatory influences [33, 34]. Bromelain has the potential to decrease neutrophil migration and secretion of pro-inflammatory cytokines [25, 35]. Furthermore, Bromelain reduces platelet aggregation and exhibits fibrinolytic activities in dissolving fibrin clots . Trypsin has antioxidant effects, influences the activation of protease-activated receptor 2, and decreases the inflammatory response in animal models and in studies with allergic respiratory disease [36–38].
Wobenzym (brand name: Wobenzym® plus, Phlogenzym® or Wobenzym PS® depending on the country) is an orally applied formulation composed of hydrolytic enzymes (bromelain, trypsin) and the flavonoid rutoside. Clinical trials in both humans and animals suggest a beneficial effect of this combination on inflammatory diseases. These include immunologically mediated atherosclerosis in rat aortic allografts and rheumatologic disease [39, 40]. Following injury, Wobenzym has been shown to restore microcirculation, decrease pain, reduce inflammation and swelling, and alleviate musculoskeletal symptoms to the same extent as nonsteroidal anti-inflammatory drugs [34, 36].
Taken together, supplementation with polyphenols and hydrolytic enzymes appears to be a promising approach to mitigate marathon-induced changes in inflammation, muscular damage and soreness, and rheological status.
Therefore, the aim of the study is to investigate the influence of hydrolytic enzyme and flavonoid supplementation on changes in inflammatory, muscular, and rheological status in healthy males participating in a marathon race.