Influence of a montmorency cherry juice blend on indices of exercise-induced stress and upper respiratory tract symptoms following marathon running—a pilot investigation

Prolonged and exhaustive exercise is often associated with symptoms and signs of respiratory mucosal inflammation [1, 2]. The upper respiratory tract symptoms (URTS) usually seen following prolonged and exhaustive exercise [3, 4] have conventionally been attributed to a transient depression of the innate and adaptive immunity that eventually progresses into infection [5]. However, recent studies that examined the aetiology of URTS following Marathon running reported that half or more than two-thirds of symptomatic cases were attributable to inflammation [6] and/or allergy [7]. This non-infectious hypothesis can be further supported due to the fact, episodes of URTS in athletes are not characterised by usual seasonal patterns and show an unusual short-term duration [8]. Exercise-induced airway inflammation, common in endurance athletes [1, 9-11] can be mediated by a number of factors including the synergistic effect of hyperventilation trauma [2, 12], oxidative stress [13] and inhaled allergens and pollutants [7, 10, 14].

Exercise has shown to up-regulate the chemotactic cytokine expression in the airways [15] causing inflammation, allergic reactions in bronchi, increasing the likelihood of bronchoconstriction and possibly imitating symptoms that resemble respiratory infections [8]. For example, interleukin-8 (IL-8) has been implicated in pulmonary inflammation and hyper-responsiveness under acute oxidative stress [16, 17]. Previous studies have shown a unanimous increase in IL-8 following prolonged and exhaustive exercise [18, 19]. IL-8 is known to be a potent mediator of chemotaxis, and activates neutrophils resulting in the generation of reactive oxygen species (ROS) [20], which might lead to pulmonary inflammation and trauma [13]. Neutrophils increase markedly post-Marathon [19, 21], and pulmonary inflammation is characterised by the migration and activation of neutrophils into the airways [22]. Increased neutrophils in induced sputum post-Marathon have been reported in healthy athletes [1].

Tart Montmorency cherries are purported to be high in numerous phytochemicals, such as anthocyanins, and other polyphenolic compounds such as quercetin that possess anti-inflammatory and anti-oxidative properties [23, 24]. Growing interest in these functional foods has gained momentum in recent years and there is a mounting body of evidence to suggest Montmorency cherries can facilitate exercise recovery [24-28]; this is likely attributable to the increased bioavailability of these anti-inflammatory and anti-oxidative phytochemicals following ingestion [29, 30]. In a recent addition to the literature, Bell et al. [24] showed that in trained cyclists, consumption of a Montmorency cherry concentrate (in comparison to a calorific matched placebo) resulted in a reduction in lipid hyperoxides and a concomitant reduction in inflammation (IL-6 and C-reactive protein) following repeated days strenuous cycling. Additionally, polyphenols such as quercetin (also found in Montmorency cherries), modulate the expression of transcription nuclear factor-kappa B (NF-kappaB), [31, 32], which may in turn decreased the exercised-induced IL-6 production by an attenuation of cytokine transcription for IL-6. Previous studies have also shown these polyphenols to reduce other inflammatory biomarkers such as tumor necrosis factor alpha [32, 33], and macrophage inflammatory protein [33]. Consequently, it is conceivable that the anti-inflammatory and anti-oxidative potential of Montmorency cherries could attenuate the exercise-induced ‘stress’ response, immunity and URTS. Therefore, the aim of the current pilot study was to explore the possibility that Montmorency CJ supplementation before and following Marathon running could modulate markers of stress, immunity and self-reported upper respiratory tract symptoms.

There were no differences between groups for age, stature, mass, previous Marathon history, weekly mileage, longest single training run, predicted and actual Marathon time (Table 1). Post-race body mass was lower than body mass the day before the race (P < 0.001) with similar declines in the CJ group and PL group (1.2 ± 1.3 kg vs. 1.7 ± 1.5 kg, respectively).

Secretory IgA concentration showed no time or interaction effects (Fig. 1A). Conversely, there was a time effect for output (F(_3,54) = 7.560, P < 0.001, η_p ² = 0.296) and decreased immediately post-race in both groups when compared to pre-race levels, and returned to baseline by 24 h post-race. No treatment or interaction effects (P > 0.05) for sIgA were shown (Fig. 1B). Salivary IgG concentration showed no time, treatment or interaction effects (Fig. 1C).

Salivary Cortisol showed a significant time effect and was elevated immediately post-race in both groups, (F_(1,18) = 26.291, P < 0.001, η_p ² = 0.594) when compared to pre-race levels, and returned to baseline by 24 h post-race. No significant treatment or treatment by time interaction effects were observed (see Fig. 1D).

Serum CRP showed a significant time effect (F(_3,54) = 247.138, P < 0.001, η_p ² = 0.932), a treatment by time interaction effect (F(_3,54) = 10.667, P < 0.01, η_p ² = 0.372), and a treatment effect F(_1,18) = 12.920, P < 0.01, η_p ² = 0.418). The increase in CRP at 24 and 48 h post-Marathon was significantly lower (F(_1,18) = 12.14, P < 0.01 and F(_1.18) = 9.88, P < 0.01, respectively) in the CJ group compared to PL group (see Fig. 1E).

The incidence and severity of URTS showed a time effect (F(_3,54) = 6.359, P < 0.01, η_p ² = 0.261). URTS were increased at 24 h and 48 h following the race when compared to pre-race levels in the PL group only. A treatment (F(1,18) = 7.826, P < 0.05, η_p ² = 0.303) and interaction effect (F(_3,54) = 6.359, P < 0.01, η_p ² = 0.261) was observed, whereby URTS were significantly higher in the PL group at 24 h (F(_1,18) = 7.57, P < 0.05) and 48 h post-race (F(_1,18) = 5.44, P < 0.05) compared to CJ group (Fig. 1F). No URTS were reported in the CJ group at 24 h and 48 h post-Marathon as opposed to the PL group whom 50 % (5/10) of the runners developed URTS.

In this pilot study, we investigated the effects of a Montmorency tart cherry juice on markers of stress, immunity, and self-reported incidence and severity of upper respiratory tract symptoms following a Marathon. It was hypothesised that CJ supplementation would attenuate the cortisol and inflammatory response, reduce transient suppression of mucosal immunity and lower the development of URTS by protecting the respiratory tract from symptoms associated with infectious and non-infectious inflammatory agents following a Marathon. Despite no apparent change in cortisol or mucosal immunity between groups, runners that consumed Montmorency CJ had a lower CRP response at 24 and 48 h post–Marathon and had zero incidence of reported URTS up to 48 h after the Marathon, suggesting that CJ attenuated the exercise-induced inflammatory response and the subsequent development of URTS compared to the PL group following the race.

The development of URTS observed at 24 and 48 h post-Marathon in the PL group only, might be of a non-infectious nature reflecting a synergistic effect of pulmonary inflammation mediated by exercise-induced hyperventilation trauma [2, 12], oxidative stress [13], allergies [7] and air pollution [14]. A limitation with the current study is that we did not examine the prevalence of URTS beyond 48 h and this could be explored in future work given that URTS might become evident well beyond 48 h. Enhanced airway exposure to inhaled pollutants and/or allergens has been associated with airway hyper-responsiveness in many athletes of different sports [10]. Hyperventilation can cause bronchial dehydration injuries, excessive mucus production and/or airway oedema [40]; symptoms that could resemble an URTI. Airway inflammation is commonly reported in endurance athletes [1, 9-11], and heavy exercise is associated with pulmonary mucosal inflammation [2] induced by repetitive hyperventilation, bronchial dehydration [40], and increased airway osmolarity. Speculatively, these in turn might stimulate the release of chemotactic factors from bronchial epithelial cells [15], further supporting an exercise-induced URTS development attributable to non-infective inflammatory factors [41] in this study. The URTS usually seen following prolonged and exhaustive exercise [3] have conventionally been attributed to a transient immune depression that eventually progresses into infection [5]. However, recent studies that examined the aetiology of URTS following Marathon running reported that equal or more than two-thirds of symptomatic cases were attributable to inflammation [6] and/or allergy [7]. In the present study, CRP was significantly elevated in both groups but its response at 24 and 48 h following the Marathon was blunted in the CJ group compared to the PL. This is consistent with previous studies that used cherry supplementation [24, 28, 42, 43]. Furthermore, the CJ group did not report any URTS at 24 and 48 h post-Marathon as opposed to the PL group that reported a 50 % development of URTS. Further studies are needed to explore this in larger samples using techniques such as endobronchial biopsies and induced bronchoalveolar lavage fluid (BALF) to elucidate this possibility.

Findings from a previously published study that used the same cohort [28] showed a blunted IL-6 response immediately post-Marathon, and lower uric acid immediately and 24 h post-Marathon in the CJ group compared to the PL group. The bioactive food components (BAFC) contained in cherries have shown, in vitro, to inhibit cyclooxygenase (COX)-1 and COX-2 enzyme activity, by an average of 28 % and 47 % respectively, which is responsible for the inflammatory response [44]. A subsequent study further supported this by showing a COX-2 inhibitory effect of anthocyanins [45]. These aforementioned studies and the results from the cohort of this study suggest that the anti-inflammatory activities in tart cherries could attenuate the exercise-induced inflammatory response, its exacerbation and therefore the development of URTS. This observation adds to the growing body of evidence that shows the potential of tart Montmorency cherries in aiding exercise recovery and improving health indices [23, 24, 30, 32, 46, 47].

The prevalence of allergy and atopy (sensitization to common inhalant allergens) in long-distance runners has been reported to be 40 % and 49 %, respectively [7, 10]. In allergic diseases associated with the respiratory tract (i.e., asthma and rhinitis) the migration of eosinophils to the mucosal surfaces is enhanced [48]. The respiratory tract is rich in cytokines and chemokines (e.g., IL-8), which in turn could activate the eosinophils and possibly participate in the modulation of the local immune response via degranulation [49]. Eosinophil activation has been reported to be a crucial element in upper and lower respiratory inflammation [50]. Exercise-induced recruitment and degranulation of eosinophils and basophils to the respiratory tract due to airway inflammation may possibly explain the exercise-induced URTS development seen in the PL group in this study and the increased incidence of URTI reported previously [3]. Furthermore, a more recent in vitro study showed that the polyphenol quercetin suppresses eosinophil activation [51], suggesting that various BAFC of cherries might modulate eosinophil-mediated diseases, such as allergic rhinitis and asthma, which are very common pathologies in athletes. This idea is further supported by a study that showed that 58 % of runners with reported URTS following the 2010 London Marathon had allergy, as defined by a positive Allergy Questionnaire for Athletes (AQUA) and specific immunoglobulin E (IgE) response to various inhalant allergens [7]. The prevalence of the reported URTS following the 2008 London Marathon in this study were considerably lower (25 %) than previously reported (47 %) by Robson-Ansley et al. [7]. This difference could be partly explained by the daily average tree pollen counts on the day of the 2008 London Marathon that were approximately 9-fold less (Robson-Ansley et al. [7]) than those reported in the 2010 Marathon. Although this suggests a dose-dependent response between pollen counts and URTS, the antioxidant and anti-inflammatory properties of CJ offers a plausible explanation for the complete absence of reported URTS in the CJ group.

Pulmonary inflammation can be exacerbated by concurrent exposure to tropospheric ozone and other pollutants present in Metropolitan cities [14]. Exposure to air pollutants is greater in endurance athletes as they train mostly outdoors, and compete in Marathons that commonly take place in big cities. Furthermore, the shifting from nasal to oronasal or oral breathing leads to a greater inhalation of airborne allergens, pollutants, antigens and untreated air [7]. Pollutants increase the susceptibility to bacterial respiratory infections [14]. However, CJ ingestion could reduce exercise-induced URTI susceptibility since there are several cell culture studies that show the polyphenol quercetin to exert antipathogenic activities against a wide variety of viruses and bacteria, and to reduce infectivity of target cells and virus replication [52]. The results of the present study showed an absence of reported URTS development in the CJ group and might signify a down-regulation of the inflammatory pathways involved in pollutant inhalation. Furthermore, we cannot rule out that the absence of reported URTS in the CJ group might indicate an enhanced anti-pathogenic activity compared to PL. Future studies could investigate the interaction effect between air pollution and prolonged exhaustive exercise on the incidence of respiratory symptoms and bronchoconstriction, and identify possible prophylactic measures against them.

The results of this pilot study showed that a Montmorency cherry juice blend appears to protect the URT from inflammatory symptoms caused by infectious and non-infectious agents, by possibly reducing the exercise-induced pulmonary inflammation. Modulation of the exercise-induced pulmonary inflammation by natural plant products might represent an attractive strategy to protect or alleviate the URT from inflammatory symptoms. This pilot investigation is the first to demonstrate preliminary evidence of the potential role of Montmorency cherry juice in reducing the development of URTS following long duration endurance exercise. Considering the limited sample size and healthy state of this study’s cohort, further studies with a larger sample size and participants with asthma, atopy, allergic rhinitis, exercise induced bronchoconstriction, airway hyper-responsiveness, and other pulmonary pathologies could be performed to explore the potential of cherries and other functional foods that might exert a similar effect.