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Quercetin Does Not Affect Rating ofPerceived Exertion in Athletes Duringthe Western States Endurance RunAlan C. Utter a , David C. Nieman a , Jie Kang b , Charles L. Dumke a

, John C. Quindry a , Steven R. McAnulty a & Lisa S. McAnulty ca Department of Health, Leisure, and Exercise Science , AppalachianState University , Boone, North Carolina, USAb Department of Health and Exercise Science , The College of NewJersey , Ewing, New Jersey, USAc Department of Family and Consumer Sciences , Appalachian StateUniversity , Boone, North Carolina, USAPublished online: 10 Jun 2009.

To cite this article: Alan C. Utter , David C. Nieman , Jie Kang , Charles L. Dumke , John C. Quindry ,Steven R. McAnulty & Lisa S. McAnulty (2009) Quercetin Does Not Affect Rating of Perceived Exertionin Athletes During the Western States Endurance Run, Research in Sports Medicine: An InternationalJournal, 17:2, 71-83

To link to this article: http://dx.doi.org/10.1080/15438620902901474

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Research in Sports Medicine, 17:71–83, 2009Copyright © Taylor & Francis Group, LLC ISSN: 1543-8627 print/1543-8635 onlineDOI: 10.1080/15438620902901474

GSPM1543-86271543-8635Research in Sports Medicine, Vol. 17, No. 2, Apr 2009: pp. 0–0Research in Sports Medicine

ORIGINAL RESEARCH

Quercetin Does Not Affect Rating of Perceived Exertion in Athletes During the Western

States Endurance Run

Quercetin and RPEA.C. Utter et al.

ALAN C. UTTER and DAVID C. NIEMANDepartment of Health, Leisure, and Exercise Science, Appalachian State University,

Boone, North Carolina, USA

JIE KANGDepartment of Health and Exercise Science, The College of New Jersey, Ewing, New Jersey, USA

CHARLES L. DUMKE, JOHN C. QUINDRY, and STEVEN R. McANULTYDepartment of Health, Leisure, and Exercise Science, Appalachian State University,

Boone, North Carolina, USA

LISA S. MCANULTYDepartment of Family and Consumer Sciences, Appalachian State University,

Boone, North Carolina, USA

The purpose of this study was to measure the influence of quercetinsupplementation on ratings of perceived exertion in ultramarathonrunners competing in the 160-km Western States Endurance Run(WSER). Sixty-three runners were randomized to quercetin (Q) andplacebo (P) groups, and under double blinded methods ingested foursupplements per day with or without 250 mg quercetin for 3 weeksbefore the WSER. Thirty-nine of the 63 subjects (quercetin N = 18,placebo N = 21) finished the race. At the completion of exercise ratings

Received 6 August 2008; accepted 6 January 2009.This research was partially supported by a grant from the Defense Advanced Research

Projects Agency (DARPA) and the Army Research Office (ARO), award number W911NF-06-0014.We acknowledge Quercegen Pharma (Newton, MA) for providing QU995 soft chews andplacebo for this research project.

Address correspondence to Alan C. Utter, Ph.D., M.P.H., Department of Health, Leisure,and Exercise Science, Appalachian State University, Boone, North Carolina 28608, USA. E-mail:utterac@appstate.edu

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of perceived exertion (RPE) were assessed at aid stations located at40, 90, 125, 150, and 160 km (finish line). The pattern of changein RPE over time was not significantly different between the Q andP groups. Ratings of perceived exertion (RPE) did not significantlyincrease throughout the race (15.2 ± 2.9 at 40 km –14.2 ± 4.0 at160 km) for both groups combined. Race times were not differentbetween the groups (Q = 26.4 ± 0.7 h and P = 27.5 ± 0.6 h).Significant time main effects (p < 0.001) were found for bothserum glucose and cortisol throughout the race. Quercetin supple-mentation for 3 weeks prior to the WSER had no effect on RPEduring competitive self-paced ultramarathon running. Ratings ofperceived exertion (RPE) did not increase in a linear fashion butinstead fluctuated nonmonotonically throughout the self-pacedendurance running event.

KEYWORDS RPE, ultramarathon, self-paced running, exercise

INTRODUCTION

Perceived exertion has been defined as the subjective intensity of effort, strain,discomfort, fatigue, or all of these felt during exercise (Noble & Robertson1996). It has been well documented that this subjective measure of intensityis mediated by many physiological alterations that are both central andperipheral in origin. For example, ratings of perceived exertion (RPE) correlatedirectly with heart rate (HR; Borg 1972; Stamford & Noble 1976), and it isbecause of this association that RPE often have been used to monitor exerciseintensity in lieu of HR. In the last 15 years, there has been increasing interestin various physiological/biological factors that mediate RPE (Utter 2002).For instance, numerous previous works have demonstrated that anincreased availability of carbohydrate energy substrates via glucose sup-plementation can serve to attenuate perceived exertion (Burgess, Robert-son, Davis, et al. 1991; Kang, Robertson, Goss, et al. 1996; Utter, Kang,Nieman, et al. 1997; Utter, Kang, Nieman, et al. 1999; Utter, Kang, Nieman,et al. 2004), and such reduction in effort sense has been related to anincrease in endurance performance of constant-load exercise (Kang, Robertson,Goss, et al. 1996). Another mediator of RPE that has received recent attentionis that of caffeine, which consistently has been shown to alter participant’sperceptual responses (Doherty & Smith 2005).

Similar to the effects of caffeine, naturally occurring flavonoids areknown to exhibit potent stimulatory effects (Alexander 2006; Karton, Jiang,Ji, et al. 1996). Plants contain thousands of phenolic compounds, includingmore than 5,000 flavonoids that exhibit antioxidant activity (Erdman, Balentine,Arab, et al. 2007; Manach, Scalbert, Morand, et al. 2004; Manach, Williamson,

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Morand et al. 2005). Flavonols are the most widespread flavonoids in foods,and the most prominent is quercetin (Erdman, Balentine, Arab, et al. 2007). Therichest food sources of quercetin are onions, apples, blueberries, curly kale,tea, and broccoli (Manach, Scalbert, Morand, et al. 2004). Total flavonol intake(with quercetin representing about 75%) varies from 13 to 64 mg/day, depend-ing on the study sample and the population studied (Manach, Williamson,Morand, et al. 2005). Flavonoids, such as quercetin, also have beendescribed to interact with adenosine receptors at the cell surface (Alexander2006). Recently, Alexander (2006) found that in vitro quercetin supplemen-tation exerted a stimulatory effect through antagonistic A1 adenosine receptorinteractions. It has been postulated that chronic exposure to quercetin, acting asan A1 antagonist, could lead to an increased sensitivity of these receptors invivo, in a manner similar to the effects of caffeine (Green and Stiles 1986).In a recent meta-analysis of 21 studies, it was reported that caffeine wasassociated with a significant (5.6% reduction) in RPE, when compared withplacebo (Doherty and Smith 2005). There is a paucity of research, however,on the potential role that antioxidants may have mediating perceptualresponses during exercise. Quercetin has potential antioxidant capabilities,and in vitro data show that quercetin in aglycone form has an antioxidantpotency that is approximately fivefold greater than vitamin C (Chen, Ho,Chao, et al. 2005). A review of the literature found one study in which vita-min C supplementation (either 500 or 1000 mg/d for 2 wk) had no effect onRPE during a 30-minute run at 75% VO2max in a laboratory setting (Goldfarb,Patrick, Bryer, et al., 2005). MacRae and Mefferd (2006) reported, however,that cyclists receiving an antioxidant supplement containing quercetincycled at significantly higher speeds than did those in the placebo group.In that study, it also was found that at a given RPE, power output washigher during high-intensity cycling when subjects were receiving theantioxidant supplement containing quercetin. It should be noted that thestudy of MacRae and Mefferd (2006) employed a self-paced, laboratory-based,exercise session in which subjects strived to maintain the highest possiblepower output throughout the time trial. Aside from the study of MacRaeand Mefferd (2006), it is largely unknown as to whether consumption ofquercetin would affect RPE during endurance exercise.

The purpose of this study was to measure the influence of quercetinsupplementation on RPE in ultramarathon runners competing in the160-km WSER. This study objective was achieved by using a randomized,double-blinded, placebo-controlled design in which RPE were collectedpostexercise at aid stations located at 40, 90, 125, 150, and 160 km fromrunners who ingested soft-chew supplements with or without 1000 mgquercetin daily for 3 weeks prior to the race event. We hypothesized thatsubjects with quercetin supplementation would have an improved perfor-mance time while experiencing a lower RPE at a given self-paced runningintensity.

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METHODS

Subjects and Race Description

Sixty-three experienced male and female ultramarathoners from the 2006160-km WSER were recruited and randomized to quercetin (Q) and placebo(P) groups. Thirty-nine of the 63 subjects (N = 18 for quercetin, N = 21 forplacebo) finished the race and provided blood samples pre- and postrace.Informed written consent was obtained from each subject, and the experi-mental procedures were approved by the Institutional Review Board ofAppalachian State University. To enter the study, subjects must have completeda 160-km race, and qualified for the 2006 160-km WSER. To qualify for theWSER, runners must have completed a 160-km race in fewer than 24 h, or a100-km race in 12–13 h, depending on age.

The 160-km WSER is a point-to-point trail run in the Sierra NevadaMountains of northern California and is regarded as one of the most arduousorganized running events in the United States. The race starts at Squaw Valley,California (1,890 m altitude), and finishes at Auburn, California (366 m). Thetrail race course ascends 777 m to Emigrant Pass (2,668 m, the highest point)within the first 7 km and then passes through remote and rugged territory toAuburn. The total altitude gain and loss during the race is 5,500 m and 6,700 m,respectively. The race starts at 5:00 a.m., and runners must reach the finishline within 30 hours to be eligible for an award. Up to half of the trail maybe traveled by some runners at night.

Research Design

Following recruitment and randomization, subjects ingested 1000 mg/dayquercetin or placebo using double-blind procedures for 3 weeks before theWSER. Subjects in the Q group ingested four soft, individually wrappedchews (5.3 g/piece) each day (two prior to breakfast, and two prior to din-ner) that contained 250 mg quercetin, 250 mg vitamin C (ascorbic acid andsodium ascorbate), 10 mg niacin, and 20 kilocalories of sugars in a carnaubawax, soy lecithin, corn starch, glycerine, and palm oil base colored with FD&Cyellow #5 and #6 (Nutravail Technologies Inc., Chantilly, VA). Placebosupplements were prepared exactly the same way minus the quercetin, ascorbicacid and sodium ascorbate, and niacin. The quercetin used in the softchews was a 99.5% pure product (QU995 from Merck/Quercegen PharmaLLC, Newton, MA). On race day, subjects ingested all four chews prior tothe 5:00 a.m. start time. During the 3-week supplementation period, subjectswere instructed to ingest their normal intake of food, beverages, andsupplements except to avoid any other supplements containing quercetin. A3-day food record was obtained during the 3-week prerace supplementationperiod and analyzed using the computerized nutrition software program,Food Processor (ESHA Research, Salem, OR).

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Subjects provided blood samples during registration, held the morningbefore the race, and 15–30 minutes postrace. Plasma aliquots weretransported on dry ice and then stored at –80°C until analysis. During raceregistration, body mass was measured, and subjects filled in a questionnaireon basic demographics and training history. On race day, body mass wasmeasured at the 90-km aid station (Michigan Bluff, 1,220 m) and within5–15 minutes postrace at Auburn, CA. Subjects completed a postrace ques-tionnaire indicating adherence to the research design. Subjects consumedfood and beverages ad libitum during the race and provided a list postracefor computerized analysis using the Food Processor.

Perceived Exertion

Ratings of perceived exertion (RPE) were determined using the Borg15-point rating (6–20) of perceived exertion scale (Borg 1972). During preraceblood sampling, the subjects were given a handheld laminated RPE scalewith instructions to rate their RPE at aid stations located at 40, 90, 125, 150,and 160 km. The instructions emphasized that the perceptual ratings shouldreflect sensations of exertion, strain, discomfort, fatigue, or all of these inthe limbs and respiratory system. Each rating was limited to a single num-bered response. This pocket-sized RPE scale also was used during trainingfor the 3-week supplementation period prior to the race. The distribution ofthe pocket-sized RPE scale was done to promote familiarization andenhance recall capabilities of the perceptual responses when assessed duringthe actual ultramarathon. During collection of postrace blood samples, subjectswere asked to assign a number that best described their intensity of effort,stress, discomfort, and fatigue at the listed points on the race course. Theassessment of perceived exertion after the completion of exercise previ-ously has been shown to be a valid method to assess effort sense in bothgeneral and athletic populations (Day, McGuigan, Brice, et al. 2004; Foster,Florhaug, Franklin, et al. 2001).

Plasma Quercetin

Total plasma quercetin (quercetin and its primary conjugates) was measuredfollowing solid-phase extraction via reverse–phase HPLC (High PerformanceLiquid Chromatography) with UV detection as described by Quercegen Pharma(Newton, MA, personal communication). This procedure is similar to thatpreviously published by Ishii, Furuta, and Kasuya (2003). Quercetin conjugateswere hydrolyzed by incubating 250–500 uL plasma aliquots with 10 uL 10%DL-Dithiothreitol (DTT) solution, 50 μL 0.58 M acetic acid, 50 μL of a mixtureof b-glucuronidase and arylsulfatase, and crude extract from Helix pomatia(Roche Diagnostics GmbH, Mannheim, Germany) for 40 min at 37oC. Afterincubation, 500 μL of 0.01 M oxalic acid was added, and then each sample

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was vortexed and centrifuged for 5 min at 10000 rpm. One mL of supernatantsthen was applied to solid-phase extraction cartridges (Oasis HLB 1cc [30 mg]SPE cartridge; Waters Corporation, Milford, MA) that were preconditionedwith 1 mL methanol (MeOH), 0.5 mL 0.01 M oxalic acid, and 1 mL dH2O anddrawn through at a rate of 0.5 mL/min using a vacuum manifold (WatersCorp., Milford MA). Cartridges then were washed with 0.5 mL of MeOH x 2.Eluant was collected into 1.5 mL microcentrifuge tubes. Ten μL of 10% DTTsolution were added to the combined eluant, and the samples then werevortexed for 1 minute and placed into a vacuum concentrator (Savant SpeedVac SC 110, Savant Instruments Inc., Farmindale, NY) until MeOH was com-pletely evaporated. The residue was reconstituted with 150 μL MeOH/dH2O(1/1). Fifty μL injections were used for HPLC analysis.

Hormones, Glucose, Cortisol, and Plasma Volume

Blood samples were drawn from an antecubital vein with subjects in the seatedposition. Routine CBCs were assayed using a Coulter STKS instrument(Coulter Electronics, Inc., Hialeah, FL) and provided hemoglobin andhematocrit. Plasma cortisol was assayed using a competitive solid-phase 125Iradioimmunoassay (RIA) technique (Diagnostic Products Corporation, LosAngeles, CA). Plasma was analyzed spectrophotometrically for glucose. Plasmavolume changes were estimated from blood hematocrit and hemoglobinvalues using the method of Dill and Costill (1974).

Statistical Analysis

Statistical significance was set at the p < 0.05 level, and values were expressedas mean ± SE. Q and P groups were compared for subject characteristicsand race performance measures using Student’s t tests (Table 1). Ratings ofperceived exertion (RPE) were analyzed using 2 (quercetin and placeboconditions) × 5 (times of measurement) repeated measures ANOVA. Hormonevalues were analyzed using 2 (quercetin and placebo groups) × 2 (times ofmeasurement) repeated measures ANOVA When the interaction effect was

TABLE 1 Subject Characteristics (Mean ± SE)

Variable Quercetin (N = 18) Placebo (N = 21) P value

Age (years) 44.2 ± 2.0 46.0 ± 2.3 0.575Running experience (years) 13.0 ± 2.3 13.3 ± 1.7 0.780Ultramarathons raced 39.6 ± 10.6 37.9 ± 6.0 0.988Training distance (km/wk) 83.4 ± 5.0 75.8 ± 7.1 0.398Race time (h) 26.4 ± 0.7 27.5 ± 0.6 0.237Body mass (prerace; kg) 68.9 ± 2.7 73.9 ± 2.7 0.168Body mass (90 km; kg) 68.9 ± 2.3 73.4 ± 2.3 0.169Body mass (postrace; kg) 68.0 ± 2.3 73.0 ± 2.3 0.140

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significant (p ≤ 0.05), pre- to postrace changes were calculated and com-pared between Q and P groups using Student’s t tests, with significance setat p ≤ 0.05.

RESULTS

Thirty-nine of 63 subjects (N = 18 including four females for quercetin, N = 21including three females for placebo) completed the 160-km race event. Nosignificant differences in subject characteristics were found between the Qand P groups (Table 1). Male (N = 32) and female (N = 7) runners did notdiffer significantly in race time (27.0 ± 0.5 h versus 27.0 ± 1.39 h, respec-tively, p = 0.992) or change in any of the other variables measured in thisstudy, except for those related to body mass and composition. Thus, maleand female runners were combined for this data analysis.

Air temperature was 22ºC at the start of the race at 5:00 a.m. (SquawValley, CA), 38ºC by 2:00 p.m. (Michigan Bluff), 27ºC by 12:00 a.m. (racefinish, Auburn, CA), and 31ºC by 11:00 a.m. The humidity ranged from 25% to58% during the last half of the race. Plasma volume did not change apprecia-bly and did not differ significantly between Q and P groups (−0.3 ± 0.5% and−0.3 ± 0.4%, respectively, p = 0.928). Body mass was maintained within onekilogram of prerace levels for quercetin and placebo groups (body masspostrace, 68.0 ± 2.3 and 73.0 ± 2.7, respectively). Three-day food recordsprior to the race event indicated no significant differences in macronutrientintakes between groups, with a mean energy intake for all subjects com-bined of 11.0 ± 0.8 MJ.day−1 (2620 ± 184 kcal.day−1), and percent of energyintakes of 51.1 ± 2.3% carbohydrate, 31.5 ± 1.8% fat, and 18.0 ± 1.2% protein.

Ratings of perceived exertion (RPE) were not significantly differentbetween Q and P groups [F(4,148) = 0.43, p = 0.79] throughout the ultramar-athon (Figure 1). Ratings of perceived exertion (RPE) also did not increaseover time for all subjects combined [F(4,148) = 1.27, p = 0.28]. Average RPEthroughout the race were not significantly different between the placebo(14.9 ± 0.5) and quercetin (14.9 ± 0.3) conditions (p = 0.98). After 3 weeks ofsupplementation, plasma quercetin levels were 6.6-fold higher in the Qcompared with the P group [F(1,36) = 28.72, p < 0.001], and 3.1-fold higherpostrace (Table 2). Significant time main effects were found for serum glu-cose and cortisol throughout the race (Table 2).

DISCUSSION

Results of the present investigation demonstrated quercetin supplementation for3 weeks prior to the 160-km WSER had no effect on RPE during competitive

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ultramarathon running, despite a significant increase in plasma quercetin. Itwas our initial hypothesis that an increase in plasma quercetin level wouldcounter the effect of muscle fatigue by minimizing oxidative damage tomuscle cells and act as an A1 adenosine receptor antagonist, thereby attenu-ating perceived exertion at a given level of self-paced exercise intensity.Based upon the present findings, however, this was not the case as bothRPE and running performance times were similar between the Q and Pgroups. Therefore, it is our contention that it is premature to preclude anybeneficial effects of quercetin supplementation on perceptual responsesduring a self-paced, competitive, endurance event.

Recent evidence suggests that quercetin undergoes considerable chemicalmodification during both digestion and absorption and is metabolized tomethylated, glucurono-sulfated derivatives (Manach, Williamson, Morand, et al.2005; Walle, Walle, & Halushka 2001). The quercetin conjugates may havealtered biological properties and potencies when compared with in vitro

FIGURE 1 The effect of quercetin or placebo on perceived exertion over the course of theWestern States Endurance Run (WSER).

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40 90 125 150 160Distance (km)

RP

ERPE P

RPE Q

TABLE 2 Glucose, Cortisol, and Quercetin Values Throughout the Western StatesEndurance Run (WSER; Mean ± SE)

Variable Prerace PostraceTime; InteractionEffects, P value

Glucose (mmol·L−1)Quercetin 5.17 ± 0.17 6.49 ± 0.33 <0.001; 0.355Placebo 5.54 ± 0.20 6.38 ± 0.28

Cortisol (nmol·L−1)Quercetin 434 ± 34 835 ± 80 <0.001; 0.956Placebo 412 ± 29 806 ± 97

Quercetin (ug·L−1)Quercetin 649 ± 110 114 ± 28.9 <0.001; <0.001Placebo 97.8 ± 34.4 31.3 ± 10.5

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quercetin aglycone experiments, but few human data are available (Chen,Ho, Chao, et al. 2005; Rahman, Biswas, & Kirkham 2006). We had hypothe-sized that a strong antioxidant such as quercetin would prove more usefulthan vitamins C or E (Chen, Ho, Chao, et al. 2005) as a nutritional counter-measure to exercise-induced oxidative damage and subsequently lower RPE forendurance athletes, but our findings were not in support of this outcome. Thisis the first study of human athletes using high-dose quercetin supplementsprior to ultramarathon competition, and we found that plasma quercetindropped substantially more than expected. Ingestion of quercetin supple-ments throughout the race may have maintained plasma quercetin at ahigher level with perhaps different outcomes.

The results of the present study, however, are in disagreement with arecent study of MacRae and Mefferd (2006). They found that at a given RPE,power output was higher during a 30-km cycling time trial when subjectswere receiving an antioxidant supplement quercetin that supports a perceptualeffect. The perceptual findings of MacRae and Mefferd (2006) are similar toa recent study in which it was found that runners ingesting carbohydratecompared with placebo were able to run at a higher intensity at a given RPEthroughout a competitive marathon (Utter, Kang, Robertson, et al. 2002). Itshould be mentioned that, in laboratory time trials or competitive field-based events, athletes attempt to cycle/run at the fastest speeds possible.Although we also adopted a race event in which exercise intensity was alsoself-paced, direct comparison between the study of MacRae and Mefferd(2006) and the present study are tenuous. Differences between the twostudies in part may be due to the following: exercise mode (i.e., cycling vs.running), duration of supplement administration duration (i.e., 6 weeks vs.3 weeks), and environmental conditions (i.e., laboratory-based vs. uncon-trolled field event).

An intriguing finding of the present study was that RPE did not increaselinearly during the race, for either condition, despite a significant increase inplasma cortisol concentrations. In fact, there was a trend toward a decreasein RPE especially during the last 10 km. The fluctuation of RPE throughoutthe WSER ultramarathon is in contrast to our previous study in which wefound that RPE increased progressively during an 80-km ultramarathonevent (Utter, Kang, Nieman, et al. 2003). It should be noted that the fieldevent (i.e., WSER) used in the present study was more difficult (i.e., altitudegain and loss during the race is 5,500 m and 6,700 m, respectively) than the80-km ultramarathon event (i.e., a flat 16-km closed loop) used in our previ-ous investigation (Utter, Kang, Nieman et al. 2003). Given the extraordinaryphysically challenging nature of the WSER, it is our contention that RPE canbe readily dissociated with some of the physiological cues previously provenvalid in mediating perceived exertion. Failure for RPE to increase as the raceprogressed may be attributable to the fact that intensity of running decreasedsignificantly, despite an increase in plasma cortisol levels previously found to

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be associated with an increase in RPE (Utter, Kang, Nieman, et al. 2003). WhileHR was not measured in the present study, our earlier study demonstrated asignificant decrease in HR during later stages of the 80-km ultramarathon, likelyindicating a decline in speed (Utter, Kang, Nieman, et al. 2003).

To our knowledge, the present study represents the first to evaluate theeffects of quercetin on perceived exertion throughout a challenging 160-kmultramarathon (i.e., WSER). In addition, contrary to previous laboratorystudies (Utter, Kang, Nieman, et al. 1997; Utter, Kang, Nieman, et al. 1999;Utter, Kang, Nieman, et al. 2004) and two previous field-based studies(Utter, Kang, Nieman, et al. 2003; Utter, Kang, Robertson, et al. 2002), thepresent study is the first to demonstrate that RPE does not always increaselinearly throughout prolonged exercise but instead changes monotonicallythroughout the event. This finding in part supports a recent hypothesis thatperception of effort and fatigue are not tightly correlated to any singleperipheral variable, but rather may be generated by subconscious brain centralprocesses that regulate pacing strategy during an athletic event (St ClairGibson, Lambert, Rauch, et al. 2006). This hypothesis argues that brain centrecontrolling pace incorporates knowledge of the race endpoint into an algo-rithm, together with memory of prior events, and knowledge of external(environmental) and internal (metabolic) conditions to set a particular optimalpacing strategy. This calculation will allow the athlete to reach the end ofthe exercise bout at the fastest speed possible without catastrophic failure inany physiological system (St Clair Gibson, Lambert, Rauch, et al. 2006).

Future research should consider the potential beneficial effect of quercetinsupplementation upon perceived exertion under less severe environmentalconditions, a laboratory trial, or both in which exercise intensity is keptconstant. We are cognizant that the race event employed in the presentinvestigation represents an extreme example of endurance performance. Anendurance event such as the WSER can be associated with many unex-pected physiological changes capable of altering the perception of exertion.In addition, it is our contention that the underlying mechanisms mediatingthe perceptual responses in free-living athletic competition are more com-plicated than those of a constant-load exercise. For example, the perceptionof exertion may be dependent upon the integration of both the feedforwardand feedback processes. Effort perception during a running event at a self-selected pace can be constantly modulated by afferent feedback such asmetabolic disturbance, hormonal alterations, muscular strain, or all of theseonce performance is underway. During exercise of a constant load (i.e.,standard laboratory trial), however, such an active communication, betweenboth feedforward and feedback processes, may not occur to the same extentbecause subjects are required to just maintain a given power output for as longas possible. Therefore, a controlled, laboratory trial would minimize many ofthe confounding factors (i.e., heat, wind, altitude, sleep deprivation, etc.)present in prolonged field-based competitions. The strength, however, of a

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field-based event is that it presents the most practical/applicable setting todetermine the potential benefits of a nutritional supplement in an actualcompetitive event. This was the case in the previously mentioned investigationof carbohydrate ingestion on RPE during an actual marathon (Utter, Kang,Robertson, et al. 2002). In addition, as mentioned earlier, other issues suchas duration of use and dosage of quercetin as well as its bioavailabilityshould be carefully scrutinized in future investigations.

In conclusion, quercetin supplementation 1 gram daily for 3 weeksprior to the 160-km WSER had no effect on RPE and endurance perfor-mance during competitive self-paced ultramarathon running. In addition, inneither the quercetin nor placebo condition did RPE increase in a linearfashion throughout the race, despite significant changes in plasma glucoseand cortisol concentrations. Future research examining the role that quercetinmay have in attenuating perceived exertion should employ laboratory-based, steady-state, exercise protocols during which various physiologicaland perceptual responses can be determined systemically.

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