***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: The purpose of the present study was to examine the duration of caffeine  's ergogenic effect and whether it differs between users and nonusers of the drug . Twenty-one subjects ( 13 caffeine users and 8 nonusers ) completed six r and omized exercise rides to exhaustion at 80 % of maximal oxygen consumption after ingesting either a placebo or 5 mg/kg of caffeine .  Exercise to exhaustion was completed once per week at either 1 , 3 , or 6 h after placebo or drug ingestion . Exercise time to exhaustion differed between users and nonusers with the ergogenic effect being greater and lasting longer in nonusers . For the nonusers , exercise times 1 , 3 , and 6 h after caffeine ingestion were 32.7 + /- 8.4 , 32.1 + /- 8.6 , and 31.7 + /- 12.0 min , respectively , and these values were each significantly greater than the corresponding placebo values of 24.2 + /- 6.4 , 25.8 + /- 9.0 , and 23.2 + /- 7.1 min . For caffeine users , exercise times 1 , 3 , and 6 h after caffeine ingestion were 27.4 + /- 7.2 , 28.1 + /- 7.8 , and 24.5 + /- 7.6 min , respectively . Only exercise times 1 and 3 h after drug ingestion were significantly greater than the respective placebo trials of 23.3 + /- 6.5 , 23.2 + /- 7.1 , and 23.5 + /- 5.7 min . In conclusion , both the duration and magnitude of the ergogenic effect that followed a 5 mg/kg dose of caffeine were greater in the nonusers compared with the users We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake , glycogen synthase ( GS ) activity , and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic ( 100 microU/ml ) clamp . On two occasions , seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp . Caffeine ( 5 mg/kg ) or placebo was administered in a r and omized , double-blind fashion 1 h before the clamp . During the clamp , whole-body glucose disposal was reduced ( P < 0.05 ) in caffeine ( 37.5 + /- 3.1 micromol x min(-1 ) x kg(-1 ) ) vs. placebo ( 54.1 + /- 2.9 micromol x min(-1 ) x kg(-1 ) ) . In accordance , the total area under the curve over 100 min ( AUC(0 - -100 min ) ) for insulin-stimulated glucose uptake in caffeine was reduced ( P < 0.05 ) by approximately 50 % in rested and exercised muscle . Caffeine also reduced ( P < 0.05 ) GS activity before and during insulin infusion in both legs . Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo . Insulin increased insulin receptor tyrosine kinase ( IRTK ) , insulin receptor substrate 1-associated phosphatidylinositol ( PI ) 3-kinase activities , and Ser(473 ) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs . Furthermore , insulin significantly decreased glycogen synthase kinase-3alpha ( GSK-3alpha ) activity equally in both legs . Caffeine did not alter insulin signaling in either leg . Plasma epinephrine and muscle cAMP concentrations were increased in caffeine . We conclude that 1 ) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle ; 2 ) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK , PI 3-kinase , PKB/Akt , or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations ; and 3 ) exercise reduces the detrimental effects of caffeine on insulin action in muscle Objectives The aim of this study was to evaluate the effects of caffeine on physiological responses to submaximal exercise , with a focus on blood lactate concentration ( [ BLa ] ) . Methods Using a r and omised , single-blind , crossover design ; 16 endurance-trained , male cyclists ( age : 38 ± 8 years ; height : 1.80 ± 0.05 m ; body mass : 76.6 ± 7.8 kg ; V˙O2max : 4.3 ± 0.6 L∙min-1 ) completed four trials on an electromagnetically-braked cycle ergometer . Each trial consisted of a six-stage incremental test ( 3 minute stages ) followed by 30 minutes of passive recovery . One hour before trials 2–4 , participants ingested a capsule containing 5 mg∙kg-1 of either caffeine or placebo ( maltodextrin ) . Trials 2 and 3 were design ed to evaluate the effects of caffeine on various physiological responses during exercise and recovery . In contrast , Trial 4 was design ed to evaluate the effects of caffeine  on [ BLa ] during passive recovery from an end-exercise concentration of 4 mmol∙L-1 . Results Relative to placebo , caffeine  increased [ BLa ] during exercise , independent of exercise intensity ( mean difference : 0.33 ± 0.41 mmol∙L-1 ; 95 % likely range : 0.11 to 0.55 mmol∙L-1 ) , but did not affect the time-course of [ BLa ] during recovery ( p = 0.604 ) . Caffeine  reduced ratings of perceived exertion ( mean difference : 0.5 ± 0.7 ; 95 % likely range : 0.1 to 0.9 ) and heart rate ( mean difference : 3.6 ± 4.2 b∙min-1 ; 95 % likely range : 1.3 to 5.8 b∙min-1 ) during exercise , with the effect on the latter dissipating as exercise intensity increased . Supplement × exercise intensity interactions were observed for respiratory exchange ratio ( p = 0.004 ) and minute ventilation ( p = 0.034 ) . Conclusions The results of the present study illustrate the clear , though often subtle , effects of caffeine on physiological responses to submaximal exercise . Research ers should be aware of these responses , particularly when evaluating the physiological effects of various experimental interventions This study examined the acute effects of caffeine on the cardiovascular system during dynamic leg exercise . Ten trained , caffeine-naive cyclists ( 7 women and 3 men ) were studied at rest and during bicycle ergometry before and after the ingestion of 6 mg/kg caffeine or 6 mg/kg fructose ( placebo ) with 250 ml of water . After consumption of caffeine or placebo , subjects either rested for 100 min ( rest protocol ) or rested for 45 min followed by 55 min of cycle ergometry at 65 % of maximal oxygen consumption ( exercise protocol ) . Measurement of mean arterial pressure ( MAP ) , forearm blood flow ( FBF ) , heart rate , skin temperature , and rectal temperature and calculation of forearm vascular conductance ( FVC ) were made at baseline and at 20-min intervals . Plasma ANG II was measured at baseline and at 60 min postingestion in the two exercise protocol s. Before exercise , caffeine increased both systolic blood pressure ( 17 % ) and MAP ( 11 % ) without affecting FBF or FVC . During dynamic exercise , caffeine attenuated the increase in FBF ( 53 % ) and FVC ( 50 % ) and accentuated exercise-induced increases in ANG II ( 44 % ) . Systolic blood pressure and MAP were also higher during exercise plus caffeine ; however , these increases were secondary to the effects of caffeine on resting blood pressure . No significant differences were observed in heart rate , skin temperature , or rectal temperature . These findings indicate that caffeine can alter the cardiovascular response to dynamic exercise in a manner that may modify regional blood flow and conductance This study analyzed the effects of caffeine intake on whole-body substrate metabolism and exercise tolerance during cycling by using a more individualized intensity for merging the subjects into homogeneous metabolic responses ( the workload associated with the maximal lactate steady state — MLSS ) . MLSS was firstly determined in eight active males ( 25 ± 4 years , 176 ± 7 cm , 77 ± 11 kg ) using from two to four constant-load tests of 30 min . On two following occasions , participants performed a test until exhaustion at the MLSS workload 1 h after taking either 6 mg/kg of body mass of caffeine or placebo ( dextrose ) , in a r and omized , double-blinded manner . Respiratory exchange ratio was calculated from gas exchange measurements . There was an improvement of 22.7 % in time to exhaustion at MLSS workload following caffeine ingestion ( 95 % confidence limits of ±10.3 % , p = 0.002 ) , which was accompanied by decrease in respiratory exchange ratio ( p = 0.001 ) . These results reinforce findings indicating that sparing of the endogenous carbohydrate stores could be one of the several physiological effects of caffeine during submaximal performance around 1 PURPOSE Performance improvements after caffeine ( CAF ) ingestion are well documented when using a 1-d protocol . In numerous competitions such as the Tour de France , Tour de Ski , world championships , and National College Athletic Association championships , athletes compete for several days in a row . To date , no studies have investigated the effects of CAF when competing for consecutive days in a row . This study aim ed to investigate the effects of placebo ( PLA ) and two different CAF doses ( 3 and 4.5 mg·kg body mass ) on performance in a 10-min all-out , cross-country , double poling ergometer test ( C-PT ) 2 d in a row . METHOD Eight highly trained male cross-country skiers ( V˙O2max-run , 78.5 ± 1.6 mL·kg·min ) participated in the study , which was a r and omized , double-blind , PLA-controlled , crossover design . Performance was assessed as distance covered during a 10-min all-out C-PT . Oral ingestion of CAF or PLA was consumed 75 min before the all-out C-PT . RESULTS Poling distance was improved after CAF ingestions compared with that after PLA on both days . The improvements on day 1 were 4.0 % ( 90 % confidence limits , ±3.3 ) and 4.0 % ± 2.9 % for both CAF doses , respectively ( P < 0.05 ) , whereas improvements on day 2 were 5.0 % ± 3.6 % and 5.1 % ± 2.8 % for CAF3 and CAF4.5 , respectively , compared with those for PLA . Improved performance was associated with increased HR , adrenaline concentration , blood lactate concentration , and V˙O2 consumption after CAF ingestion . Furthermore , performance was elevated despite higher creatine kinase concentration and muscular pain at arrival on day 2 for both CAF doses . CONCLUSIONS Both CAF doses improved performance in the 10-min all-out C-PT compared with PLA over two consecutive days . Therefore , CAF seems useful for athletes competing over consecutive days despite higher muscle damage occurring after enhanced performance on the first day Abstract The aim of this study was to investigate the effects of caffeine supplementation on peak anaerobic power output ( Wmax ) . Using a counterbalanced , r and omised , double-blind , placebo-controlled design , 14 well-trained men completed three trials of a protocol consisting of a series of 6-s cycle ergometer sprints , separated by 5-min passive recovery periods . Sprints were performed at progressively increasing torque factors to determine the peak power/torque relationship and Wmax . Apart from Trial 1 ( familiarisation ) , participants ingested a capsule containing 5 mg·kg−1 of caffeine or placebo , one hour before each trial . The effects of caffeine on blood lactate were investigated using capillary sample s taken after each sprint . The torque factor which produced Wmax was not significantly different ( p ≥ 0.05 ) between the caffeine ( 1.15 ± 0.08 N·m·kg−1 ) and placebo ( 1.13 ± 0.10 N·m·kg−1 ) trials . There was , however , a significant effect ( p < 0.05 ) of supplementation on Wmax , with caffeine producing a higher value ( 1885 ± 303 W ) than placebo ( 1835 ± 290 W ) . Analysis of the blood lactate data revealed a significant ( p < 0.05 ) torque factor × supplement interaction with values being significantly higher from the sixth sprint ( torque factor 1.0 N·m·kg−1 ) onwards following caffeine supplementation . The results of this study confirm previous reports that caffeine supplementation significantly increases blood lactate and Wmax . These findings may explain why the majority of previous studies , which have used fixed-torque factors of around 0.75 N·m·kg−1 and thereby failing to elicit Wmax , 
    Output:
    
This meta- analysis has revealed clear effects of caffeine on various physiological responses during submaximal exercise , which may help explain its ergogenic action