***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Caffeine , an adenosine receptor antagonist , has shown to improve performance in normal ambient temperature , presumably via an effect on dopaminergic neurotransmission through the antagonism of adenosine receptors . However , there is very limited evidence from studies that administered caffeine and examined its effects on exercise in the heat . Therefore , we wanted to study the effects of caffeine on performance and thermoregulation in high ambient temperature . Eight healthy trained male cyclists completed two experimental trials ( in 30 ° C ) in a double-blind-r and omized crossover design . Subjects ingested either placebo ( 6 mg/kg ) or caffeine ( 6 mg/kg ) 1 h prior to exercise . Subjects cycled for 60 min at 55 % Wmax , immediately followed by a time trial to measure performance . The significance level was set at p < 0.05 . Caffeine did not change performance ( p = 0.462 ) . Rectal temperature was significantly elevated after caffeine administration ( p < 0.036 ) . Caffeine  significantly increased B-endorphin plasma concentrations at the end of the time trial ( p = 0.032 ) . The present study showed no ergogenic effect of caffeine when administered 1 h before exercise in 30 ° C . This confirms results from a previous study that examined the effects of caffeine administration on a short ( 15 min ) time trial in 40 ° C . However , caffeine  increased core temperature during exercise . Presumably , the rate of increase in core temperature may have counteracted the ergogenic effects of caffeine . However , other factors such as interindividual differences in response to caffeine and changes in neurotransmitter concentrations might also be responsible for the lack of performance improvement of caffeine in high ambient temperature This study compared the effects of a single and divided dose of caffeine on endurance performance and on  postexercise urinary caffeine and plasma paraxanthine concentrations .  Nine male cyclists and triathletes cycled for 90 min at 68 % of maximal oxygen uptake , followed by a self-paced time trial ( work equivalent to 80 % of maximal oxygen uptake workload over 30 min ) with three r and omized , balanced , and double-blind interventions : 1 ) placebo 60 min before and 45 min into exercise ( PP ) ; 2 ) single caffeine dose ( 6 mg/kg ) 60 min before exercise and placebo 45 min into exercise ( CP ) ; and 3 ) divided caffeine dose ( 3 mg/kg ) 60 min before and 45 min into exercise ( CC ) . Time trial performance was unchanged with caffeine ingestion ( P = 0.08 ) , but it tended to be faster in the caffeine trials ( CP : 24.2 min and CC : 23.4 min ) compared with placebo ( PP : 28.3 min ) . Postexercise urinary caffeine concentration was significantly lower in CC ( 3.8 micro g/ml ) compared with CP ( 6.8 micro g/ml ) . Plasma paraxanthine increased in a dose-dependent fashion and did not peak during exercise . In conclusion , dividing a caffeine dose provides no ergogenic effect over a bolus dose but reduces postexercise urinary concentration The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson 's disease ( PD ) . Little is known , however , about the mechanism underlying the placebo effect . Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography , we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo . Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system Purpose Many studies have examined the effect of caffeine on exercise performance , but findings have not always been consistent . The objective of this study was to determine whether variation in the CYP1A2 gene , which affects caffeine metabolism , modifies the ergogenic effects of caffeine in a 10-km cycling time trial . Methods Competitive male athletes ( n = 101 ; age = 25 ± 4 yr ) completed the time trial under three conditions : 0 , 2 , or 4 mg of caffeine per kilogram body mass , using a split-plot r and omized , double-blinded , placebo-controlled design . DNA was isolated from saliva and genotyped for the −163A > C polymorphism in the CYP1A2 gene ( rs762551 ) . Results Overall , 4 mg·kg−1 caffeine  decreased cycling time by 3 % ( mean ± SEM ) versus placebo ( 17.6 ± 0.1 vs 18.1 ± 0.1 min , P = 0.01 ) . However , a significant ( P < 0.0001 ) caffeine – gene interaction was observed . Among those with the AA genotype , cycling time decreased by 4.8 % at 2 mg·kg−1 ( 17.0 ± 0.3 vs 17.8 ± 0.4 min , P = 0.0005 ) and by 6.8 % at 4 mg·kg−1 ( 16.6 ± 0.3 vs 17.8 ± 0.4 min , P < 0.0001 ) . In those with the CC genotype , 4 mg·kg−1 increased cycling time by 13.7 % versus placebo ( 20.8 ± 0.8 vs 18.3 ± 0.5 min , P = 0.04 ) . No effects were observed among those with the AC genotype . Conclusion Our findings show that both 2 and 4 mg·kg−1 caffeine improve 10-km cycling time , but only in those with the AA genotype . Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg·kg−1 in those with the CC genotype . CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance Aim The purpose of this study was to examine the effect of CYP1A2 -163C > A polymorphism on the ergogenic effects of caffeine supplementation during a resistance exercise ( RE ) session . Methods In a r and omized , double-blind , placebo (PL)-controlled , crossover study , 30 resistance-trained men took part in two RE sessions ( three sets to failure at 85 % of one repetition maximum , 2-min rest between sets ) , including bench press ( BP ) , leg press ( LP ) , seated cable row , and shoulder press ( SP ) following caffeine ( CAF ) ( 6 mg kg−1 ) or PL ( 6 mg kg−1 of maltodextrin ) ingestion 1 h prior to the trial . The number of repetitions was recorded after each set , along with calculation of total number of repetitions for each exercise . Genomic DNA was isolated from the whole blood sample s for analyzing the CYP1A2 -163C > A polymorphism through amplification refractory mutation system – polymerase chain reaction ( ARMS – PCR ) . Subjects were classified as either AA ( n = 14 ) or AC/CC genotypes ( n = 16 ) . Results The two-way ANOVA with repeated measures revealed differences between AAs and AC/CCs under CAF conditions for repetitions performed in sets 1 , 2 , and 3 of BP ( F(1 , 28 ) = 14.84 , P = 0.001 , ƞ2 = 0.34 ) , LP ( F(1 , 28 ) = 8.92 , P = 0.006 , ƞ2 = 0.24 ) , SR ( F(1 , 28 ) = 17.38 , P = 0.0001 , ƞ2 = 0.38 ) , and SP ( F(1 , 28 ) = 3.76 , P = 0.063 , ƞ2 = 0.11 ) . CAF also increased the total number of repetitions performed for all three sets in AAs versus AC/CCs for BP ( F(1 , 28 ) = 8.72 , P = 0.006 , ƞ2 = 0.23 ) , LP ( F(1 , 28 ) = 4.67 , P = 0.03 , ƞ2 = 0.14 ) , SR ( F(1 , 28 ) = 5.54 , P = 0.02 , ƞ2 = 0.16 ) , and SP ( F(1 , 28 ) = 3.89 , P = 0.058 , ƞ2 = 0.12 ) in athletes who were homozygous carriers of the A allele , compared to the C allele carriers . Therefore , AA homozygotes were able to carry out a greater total volume of RE work under CAF but not PL conditions , compared to the C allele carriers . Conclusion In conclusion , acute ingestion of CAF significantly enhanced RE performance in resistance-trained men who were homozygous for the A allele , but not for C allele carriers . Further studies are needed to replicate the potential role of the CYP1A2 -163C > A polymorphism on the ergogenic effects of CAF in other modes of exercise and in other population PURPOSE To determine the effects of ingesting caffeine ( CAFF ) and sodium bicarbonate ( SB ) , taken individually and simultaneously , on 3-km cycling time-trial ( TT ) performance . METHOD Ten well-trained cyclists , age 24.2 ± 5.4 yr , participated in this acute-treatment , double-blind , crossover study that involved four 3-km cycling TTs performed on separate days . Before each TT , participants ingested either 3 mg/kg body mass ( BM ) of CAFF , 0.3 g · kg⁻¹ · BM⁻¹ of SB , a combination of the two ( CAFF+SB ) , or a placebo ( PLAC ) . They completed each 3-km TT on a laboratory-based cycle ergometer , during which physiological , perceptual , and performance measurements were determined . For statistical analysis , the minimal worthwhile difference was considered ~1 % based on previous research . RESULTS Pretrial pH and HCO₃ were higher in SB and CAFF+SB than in the CAFF and PLAC trials . Differences across treatments for perceived exertion and gastric discomfort were mostly unclear . Compared with PLAC , mean power output during the 3-km TT was higher in CAFF , SB , and CAFF+SB trials ( 2.4 % , 2.6 % , 2.7 % respectively ) , result ing in faster performance times ( -0.9 , -1.2 , -1.2 % respectively ) . Effect sizes for all trials were small ( 0.21 - 0.24 ) . CONCLUSIONS When ingested individually , both CAFF and SB  enhance high-intensity cycling TT performance in trained cyclists . However , the ergogenic effect of these 2 popular supplements was not additive , bringing into question the efficacy of coingesting the 2 supplements before short- duration high-intensity exercise . In this study there were no negative effects of combining CAFF and SB , 2 relatively inexpensive and safe supplements Hudson , GM , Green , JM , Bishop , PA , and Richardson , MT . Effects of caffeine and aspirin on light resistance training  performance , RPE , and pain perception . J Strength Cond Res 22(6 ) : 1950 - 1957 , 2008-This study compared independent effects of caffeine and aspirin on muscular endurance ( repetitions ) , heart rate ( HR ) , perceived exertion ( RPE ) , and perceived pain index ( PPI ) during light resistance training bouts performed to volitional failure . It was hypothesized that the hypoalgesic properties of these ergogenic aids would decrease pain perception and potentially result in enhanced performance . College-aged men ( n = 15 ) participated in a within-subjects , double-blind study with three independent , counterbalanced sessions wherein aspirin ( 10 mg·kg−1 ) , caffeine ( 6 mg·kg−1 ) , or matched placebo were ingested 1 hour before exercise , and  RPE , HR , PPI , and repetitions  ( per set and total per exercise ) were recorded at 100 % of individual , predetermined , 12-repetition maximum for leg extensions ( LE ) and seated arm curls ( AC ) . Repeated- measures analyses of variance were used for between-trial comparisons . Caffeine result ed in significantly greater ( p < 0.05 ) HR ( LE and AC ) , total repetitions ( LE ) , and repetitions in set 1 ( LE and AC ) compared with aspirin and placebo . Aspirin result ed in significantly higher PPI in set 1 ( LE ) . In LE , 47 % of participants ' performance exceeded the predetermined effect size ( ≥ 5 repetitions ) for total repetitions , with 53 % exceeding the effect size ( ≥ 2 repetitions ) for repetitions in set 1 with caffeine ( vs. placebo ) . In AC , 53 % ( total repetitions ) and 47 % ( set 1 repetitions ) of participants exceeded effect sizes with caffeine ( vs. placebo ) , with only 13 % experiencing decrements in performance ( total repetitions ) . Aspirin also produced a higher PPI and RPE overall and in set 1 ( vs. placebo ) . This study demonstrates that caffeine significantly enhanced resistance training performance in LE and AC , whereas aspirin 
    Output:
    
Firstly , previous experience/habituation has been suggested as a factor that provides learning and information about the treatment [ 11 ] , thereby driving participants ’ expectations about caffeine ’s ergogenic effects .