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REVIEW ARTICLE

Sports Med 2009; 39 (10): 813-832 0112-1642/09/0010-0813/$49.95/0

2009 Adis Data Information BV. All rights reserved.

Caffeine and Anaerobic Performance


Ergogenic Value and Mechanisms of Action
J.K. Davis1 and J. Matt Green2
1 Department of Health and Human Performance, Texas A&M University-Commerce, Commerce, Texas, USA 2 Department of Health, Physical Education and Recreation, University of North Alabama, Florence, Alabama, USA

Contents
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Ergogenic Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Wingate/Sprint Cycling Power . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Sprinting/Sport-Specific Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Agility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Speed Endurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.5 Muscular Endurance/One-Repetition Maximum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.6 Isokinetic Peak Torque . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.7 Isometric Maximal Force and Endurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.8 Interindividual Variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Mechanisms of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Peripheral Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Catecholamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Lactic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Blood Glucose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Potassium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Calcium/Phosphodiesterase Inhibition/Cyclic Adenosine Monophosphate Cascade. . . . . . . . . 3. Central Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Adenosine Antagonism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Pain Perception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Rating of Perceived Exertion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Conclusion and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813 814 814 816 817 817 818 819 820 820 821 821 821 821 822 822 823 823 823 823 826 827 827

Abstract

The effect caffeine elicits on endurance performance is well founded. However, comparatively less research has been conducted on the ergogenic potential of anaerobic performance. Some studies showing no effect of caffeine on performance used untrained subjects and designs often not conducive to observing an ergogenic effect. Recent studies incorporating trained subjects and paradigms specific to intermittent sports activity support the notion that caffeine is ergogenic to an extent with anaerobic exercise. Caffeine seems highly ergogenic for speed endurance exercise ranging in duration from 60 to 180 seconds. However, other traditional models examining power output (i.e. 30-second Wingate test) have shown minimal effect of caffeine on performance. Conversely, studies employing sport-specific methodologies

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(i.e. hockey, rugby, soccer) with shorter duration (i.e. 46 seconds) show caffeine to be ergogenic during high-intensity intermittent exercise. Recent studies show caffeine affects isometric maximal force and offers introductory evidence for enhanced muscle endurance for lower body musculature. However, isokinetic peak torque, one-repetition maximum and muscular endurance for upper body musculature are less clear. Since relatively few studies exist with resistance training, a definite conclusion cannot be reached on the extent caffeine affects performance. It was previously thought that caffeine mechanisms were associated with adrenaline (epinephrine)-induced enhanced free-fatty acid oxidation and consequent glycogen sparing, which is the leading hypothesis for the ergogenic effect. It would seem unlikely that the proposed theory would result in improved anaerobic performance, since exercise is dominated by oxygen-independent metabolic pathways. Other mechanisms for caffeine have been suggested, such as enhanced calcium mobilization and phosphodiesterase inhibition. However, a normal physiological dose of caffeine in vivo does not indicate this mechanism plays a large role. Additionally, enhanced Na+/K+ pump activity has been proposed to potentially enhance excitation contraction coupling with caffeine. A more favourable hypothesis seems to be that caffeine stimulates the CNS. Caffeine acts antagonistically on adenosine receptors, thereby inhibiting the negative effects adenosine induces on neurotransmission, arousal and pain perception. The hypoalgesic effects of caffeine have resulted in dampened pain perception and blunted perceived exertion during exercise. This could potentially have favourable effects on negating decreased firing rates of motor units and possibly produce a more sustainable and forceful muscle contraction. The exact mechanisms behind caffeines action remain to be elucidated.

Caffeine a 1,3,7 trimethylxanthine is commonly found in over-the-counter medications, coffee, tea, cola, chocolate and in various other products. It is metabolized in the liver to dimethyxanthines (paraxanthine, theobromine, theophylline) and is proposed to affect various tissues throughout the body, including peripheral and central tissues.[1] The popularity of caffeine as an ergogenic aide has increased dramatically over the last decade, and various forms of administration (i.e. sports drinks, sports gels, energy drinks) have become more available in recent years. Athletes commonly consume caffeine in an attempt to enhance performance. However, ethical considerations have been raised regarding the effect of caffeine on performance, leading the National Collegiate Athletic Association (NCAA) to implement urinary caffeine restrictions. Numerous reviews[1-8] have examined the effects on performance that caffeine elicits, but this has primarily been directed toward aerobic performance.
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Few reviews have examined the effect of caffeine solely on anaerobic performance. Rather, they have treated the effects on anaerobic performance merely as a subset of the review.[1-8] In the current review we exclusively examine anaerobic performance. More specifically, exercise bouts of 4180 seconds in duration are examined. The first section explores the influence of caffeine in various anaerobic paradigms with particular attention given to the impact on performance variables. The second section focuses on various mechanisms, both peripheral and central, that may contribute to the ergogenic effect of caffeine. 1. Ergogenic Effect
1.1 Wingate/Sprint Cycling Power

The Wingate test is a widely accepted measure of power output and anaerobic capacity[9] and has been commonly employed when assessing
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ergogenic aids and anaerobic performance. Three 30-second repeated Wingate tests have shown the highest percentage of energy production from anaerobic metabolism consisting of 6084% of oxygen-independent ATP production.[10-13] Studies examining effects of caffeine on Wingate performance have typically shown minimal ergogenic effects.[14-22] Greer et al.[17] actually showed an ergolytic effect of caffeine with a decrease in power-output on the fourth Wingate bout compared with placebo. Only one study supports the notion of that caffeine is ergogenic within this paradigm.[23] Testing untrained subjects presents problems in interpreting the ergogenic potential of caffeine in trained individuals. Most studies failing to show ergogenic potential have incorporated untrained subjects (not specifically accustomed to intermittent-sprint exercise),[14,15,17,18,20-22] with only one study incorporating trained subjects[16] for single[15,18-20,22] and repeated[14,16,17,21] Wingate tests. Using untrained subjects may not be the best model to assess the ergogenic effect of caffeine within this exercise paradigm. The only study to support an ergogenic effect with caffeine on Wingate performance was by Kang et al.,[23] who tested both trained (professional cyclists) and untrained subjects. Kang et al.[23] had subjects perform a single traditional 30-second Wingate test. Subjects consumed 2.5 and 5.0 mg/kg mass caffeine and placebo in counterbalanced order. Caffeine significantly increased total power, mean power and peak power in both groups compared with placebo, with no difference noted between caffeine doses. It is unclear why untrained subjects improved performance for Kang et al.,[23] considering other studies utilizing untrained subjects have found no change in performance.[14,15,17,18] Beck et al.[16] had resistance-trained subjects perform two Wingate tests, consuming 201 mg 1 hour prior to the trial. There were no differences between caffeine and placebo for peak power, mean power and percentage decrease in performance. However, these results should be interpreted with caution considering resistance-trained subjects were employed. While likely accustomed to high-intensity anaerobic exercise, subjects participating in reg 2009 Adis Data Information BV. All rights reserved.

ular sprints, particularly cycling, might be better adapted to perform repeat Wingate tests. Additionally, caffeine was not administered relative to body mass, and when the mean mass for subjects is equated with dose administered (200 mg) mean consumption per subject is 2.4 mg/kg (2.13.0 mg/kg), potentially negating an ergogenic effect. However, other studies have found improved performance with similar doses of caffeine.[23-25] Consequently, the dose may have been inadequate to enhance performance and the subjects training background (resistance-trained vs cyclist) could account for equivocal results. Future studies using the Wingate protocol with repeated bouts should use highly anaerobictrained subjects accustomed to intermittent bouts of cycling to ascertain whether caffeine is ergogenic in this paradigm. Although the Wingate test is typically used to examine anaerobic capacity, it does not reflect the performance requirements of sports involving intermittent high-intensity efforts (e.g. ice hockey, soccer, field hockey, American football), and consequently it is uncertain whether the results of caffeine on Wingate performance would be observed during sports-specific activities. Court or field-base team sports often consist of short bouts of intermittent sprints (25 seconds), performed over short distances (1020 m), and with brief rest periods between bouts.[26] In order to mimic athletic competition more closely, Schneiker et al.[27] assessed the effects of caffeine on amateur level team sport athletes from local and state clubs (e.g. football, soccer and hockey), consuming 6 mg/kg of caffeine. To simulate a sportsspecific paradigm, subjects (n = 10) performed 2 36-minute halves, with each half composed of 18 4-second maximal exertion. cycling bouts with 2 minutes recovery at 35% VO2 max between sprints. Compared with placebo, caffeine use resulted in a significant improvement for the first half (8.5%) and second half (7.6%) for total work. Similarly, there was a significant improvement for the first half (7.0%) and second half (6.6%) for peak power. These results show that when the testing protocol more closely mimics athletic competitions with trained subjects accustomed to intermittent-sprint bouts, caffeine does provide
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an ergogenic effect. Anselm et al.[28] found a 7% increase in maximal anaerobic power (Wmax) with untrained subjects during a single 6-second sprint following consumption of 250 mg of caffeine. However, Williams et al.[19] found no benefit from caffeine (7 mg/kg) during maximal exercise (15 seconds) for peak power, total power and fatigue index with untrained subjects. Although Williams et al.[19] failed to find improved performance during a 15-second Wingate test, results indicate that caffeine is beneficial for trained and untrained subjects when bouts are 46 seconds duration, which may more closely mimic the time frame associated with high-intensity sports.[27,28]
1.2 Sprinting/Sport-Specific Testing

Few studies have examined the effects of caffeine on sprinting performance and agility.[29-31] Paton et al.[29] had 16 team sport athletes (e.g. basketball, hockey, rugby) perform 10 20 m sprints with 10 seconds recovery between sprints. Bouts were completed following 6 mg/kg caffeine consumption and placebo. Caffeine resulted in significantly slower mean sprint time (0.1%): compared with the first sprint, a 14.0% increase in time over 10 sprints was noted for placebo versus 14.7% for caffeine. One potential problem discussed in the article, possibly due to lack of space, is that at the end of the 20 m sprint, subjects had to decelerate. Anticipation of deceleration likely impaired sprint times and could have masked any ergogenic effects of caffeine. Stuart et al.[30] simulated a rugby game with Australian rugby players performing seven circuits in each 2 40-minute half, with 10 minutes half-time rest after consuming 6 mg/kg of caffeine. Skill tasks assessed included sprinting, agility, power generation and passing accuracy. Eleven stations were performed per circuit with 30-second intervals between stations, and two stations consisted of straight-line sprinting (2030 m sprints). Caffeine significantly improved sprint time by 0.52.9% for the entire trial (all sprints combined); specifically, performance improved in the first half for 2030 m (0.5, 2.3%) and second half for 2030 m sprints (1.4, 3.4%). Reasons for equivocal results between Stuart et al.[30] and Paton et al.[29] are un 2009 Adis Data Information BV. All rights reserved.

clear. Although distances were relatively the same, recovery duration between sprints was different (10 seconds[29] vs 30 seconds[30]). The rest : work ratio used by Paton et al.[29] was between 2 : 1 and 3 : 1, depending on how long it took the subject to complete the 20 m sprint, where Stuart et al.[30] employed a 4.5 : 1 ratio for rest to work. The rest : work ratio could have a dramatic effect on recovery, and the short rest : work ratio employed by Paton et al.[29] could have prevented the authors from observing any ergogenic effect. Thus, the effect of rest : work might play a crucial role in allowing caffeine to magnify its effect. Future studies should investigate to what extent rest work or total volume plays on allowing caffeine to elicit its effect on performance. Only one study to date has examined the effects of caffeine on anaerobic performance in swimmers.[31] Collomp et al.[31] used a withinsubjects design in order to examine the effects of caffeine 250 mg on a 2 100 m maximal exertion freestyle swim, with 20 minutes passive recovery between bouts, on trained and untrained swimmers. Overall, trained swimmers significantly improved swimming velocity with caffeine (vs placebo) compared with untrained subjects, with greater improvement noted during the second 100 m. Trained swimmers had been competitive for 5 years and had been training 56 days a week for 4 consecutive months at the time of the study. These results[31] seem promising; however, future studies are warranted. Considering the 2007 NCAA 100 m freestyle final for first and second place was separated by 0.73 seconds and first and tenth by 1.58 seconds, if caffeine could elicit similar results shown with trained subjects as Stuart et al.[30] showed on sprint performance (0.52.9%), a competitive advantage is plausible. While worthy of further inquiry, it should also be noted that precise simulation of the competitive environment in a controlled laboratory setting is difficult. It is possible that if caffeine acts via CNS function (discussed in detail later in section 3), the level of arousal typically associated with competition may mask ergogenic properties that might be observed during laboratory testing. However, it could still be an important training tool during practice.
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1.3 Agility

Athletic competitions involving brief periods of high-intensity exercise consist of a combination of sprints and agility-based performances. Studies on the ergogenic effect caffeine has on agility performance have shown equivocal results.[20,30] Conflicting results could stem from the methodology employed between these studies. Stuart et al.[30] examined agility by having participants perform three agility sprints (22, 33 and 31 m) performed in a swerving (or zigzag) pattern. Caffeine improved overall mean agility sprint performance for all three sprints by 2.2% compared with placebo in the first half, with second half performance improved by 1.7%; however, whether this was significant was not reported. Lorino et al.[20] had 16 subjects perform three pro-agility tests: this test is commonly known as the 20-yard shuttle run and is used as an indicator of athletic performance in American football at the high school, collegiate and professional level. They failed to find a significant difference between caffeine and placebo for the pro-agility test. The reasons for conflicting results could be due to exercise paradigm and the subject familiarity. Although both studies incorporated a double-blind, crossover design, Stuart et al.[30] used trained subjects (rugby players) where Lorino et al.[20] used untrained subjects who were unaccustomed to the pro-agility test. Thus, untrained subjects not commonly performing agility work on a regular basis could have negated a potential ergogenic effect. Future investigations examining agility skills should incorporate trained subjects commonly performing agility drills on a weekly basis in order to understand what impact caffeine has on this type of performance.
1.4 Speed Endurance

Several studies have evaluated high-intensity exercise lasting between 60 and 180 seconds. A method that has commonly been employed to assess speed endurance has involved protocols using maximal accumulated oxygen deficit (MAOD). The MAOD model is considered a suitable test for a non-invasive indirect measure 2009 Adis Data Information BV. All rights reserved.

ment of anaerobic ATP metabolism,[32,33] although others have argued its value.[34,35] MAOD involves running at a supramaximal intensity (e.g. 125% . VO2 max ), with volitional fatigue typically occurring at 23 minutes,[15,32,36] depending upon a participants level of training. MAOD allows for a unique exercise paradigm, with duration of time similar to short-term track events (800 m). Doherty[32] was the first to examine the MAOD paradigm with caffeine. His group showed caffeine (vs placebo) improved run time to exhaustion by 14% (29 6 seconds). In a similar study, Doherty et al.[36] had subjects perform supramaximal . 125% VO2 max to exhaustion, with subjects supplementing with caffeine or placebo after a 7-day loading phase with oral creatine (20 g/day). Time to fatigue was significantly greater by 23.8 seconds with caffeine plus creatine compared with placebo (creatine only), and 21.3 seconds compared with baseline measurements. The results indicated caffeine is ergogenic within this paradigm, highlighting the potential use of acute caffeine ingestion after oral creatine loading. This brings novel insight to stacking these ergogenic aids in this manner because when caffeine is taken throughout the loading phase of creatine a synergistic effect has not been shown.[37,38] Caffeine inhibits elevations in intramuscular phosphocreatine levels.[37] Bell et al.[15] employed the MAOD model using cycle ergometry instead of a . treadmill.[32,36] Time to fatigue at 125% VO2 max significantly increased by 8.8 seconds with caffeine compared with placebo. Time to fatigue for Bell et al.[15] was not as great compared with Doherty et al.;[32,36] however, a possible explanation is the use of trained[32,36] compared with untrained subjects.[15] Collectively, studies using the MAOD model seem favourable regarding the ergogenic effects of caffeine, with positive results shown regardless of training status,[15,32,36] but seem to impact performance to a greater extent for trained subjects. Several studies have examined speed endurance using various protocols other than the MAOD model. Doherty et al.[39] had subjects cycle for 2 minutes at 100% maximal power output, immediately followed by a 1-minute all-out sprint. Mean power output for the 1-minute all-out sprint was significantly higher with caffeine (794 164 W)
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compared with placebo (750 163 W). Wiles et al.[40] examined performance time, mean speed and peak power with trained cyclists across three 1 km cycling bouts. Using caffeine resulted in significantly improved performance (2.3 seconds), and significantly greater mean power (18.1 W) and peak power (75.5 W), and faster mean speed (1.6 km/h). Crowe et al.[41] showed an ergolytic effect with caffeine 6 mg/kg during two 60-second maximal cycling bouts (separated by 3 minutes passive seated recovery) with recreationally trained subjects (i.e. soccer, rugby, basketball). Use of caffeine resulted in a significantly slower time to reach peak power in exercise bout two compared with placebo, and in a greater decrease in peak power and total work from bout one to two, although this was not statistically significant. While there are inconsistencies, collectively caffeine supplementation for maximal exertion bouts lasting 60180 seconds seems beneficial for trained and untrained individuals.[15,32,36,39,40]
1.5 Muscular Endurance/One-Repetition Maximum

Compared with other popular ergogenic aids, few studies have assessed the effects of caffeine on resistance training performance. However, with studies showing ergogenic effects of caffeine during anaerobic performance, it is plausible that caffeine may affect resistance training, which is also dominated by oxygen-independent metabolic pathways. Common methods for examining muscular fitness are to assess strength by determining a one-repetition maximum (1RM) or to assess muscular endurance using repetitions to failure. Repetitions to failure involve performing an all-out effort of repetitions to volitional fatigue, usually performed at a percentage of 1RM or multiple repetitions max test (i.e. 1012 repetitions). The majority of studies examining repetitions to failure have used subjects with various resistance training histories (8 weeks,[42,43] 1 year,[16] 2 years,[44] 6 years[45]), performing resistance training bouts 24 (times) per week.[16,42-45] Green et al.[42] tested 17 subjects (13 males, 4 females) performing three sets of bench presses and leg presses to failure
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at 80% of 1RM in a double-blind, placebocontrolled design, with a dosage of 6 mg/kg of caffeine. No significant difference was shown for bench presses or sets one and two for the leg presses between caffeine and placebo. However, the third set for leg presses showed a significant improvement for the caffeine trial. Hudson et al.[43] had 15 subjects perform four sets of arm flexion and knee extension exercises to exhaustion, using a 12RM resistance model performed to volitional fatigue. Compared with placebo, caffeine use resulted in significantly greater total repetitions (knee extension) and repetitions in the first set (knee extension and arm flexion), and approached significance for the fourth set (knee extensions; p = 0.051). The effect size for knee extension and arm flexion was 5 repetitions. Performance for 53% of subjects exceeded this number for total repetitions (all combined) for knee extension and arm flexion, while 47% of subjects exceeded this number for the first set alone in both exercises. This study emphasizes the importance of evaluating individual data versus group means only. That is, it is possible that in many data sets half the subjects could be labelled as responders (benefitting from caffeine), while the other half are nonresponders (for unknown reasons, they do not benefit). This situation may result in non-significant differences when evaluating mean data. However, it would be inaccurate to conclude caffeine has no ergogenic properties from such a data set. Further work is needed to elucidate interindividual responses to caffeine. Also, it is advisable for future studies to also examine data in a manner that permits close evaluation of individual responses. Beck et al.[16] used a randomized, double-blind design where participants in both caffeine and placebo arms performed one set at 80% 1RM to failure for bench press and leg extension. The mean increase in bench press for total volume of weight lifted to failure was greater for caffeine (34.0 kg) versus placebo (24.0 kg), with the difference approaching significance (p = 0.074). No significant difference was observed for leg extension between caffeine and placebo. Williams et al.[44] recently examined one set of repetitions to failure for bench press and leg press at 80% 1RM
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with caffeine (300 mg). No significant difference was found with caffeine on muscular endurance for bench press or leg press. A similar study by Astorino et al.[45] had subjects perform one set of repetitions to failure for bench press and leg press at 60% 1RM with 6 mg/kg of caffeine. No significant difference was found for bench press or leg press with caffeine compared with placebo; however, an 11% and 12% improvement was noted for bench press and leg press, respectively. Jacobs et al.[46] studied 13 male subjects who were either currently involved in a resistance training programme or had been involved within the preceding year. The subjects consumed 4 mg/kg of caffeine 90 minutes prior to performing supersets of leg press (80% 1RM) immediately followed by bench press (70% 1RM) to failure. Subjects completed a total of three supersets with 2 minutes recovery between each superset. No significant difference was noted for caffeine compared with placebo during the three supersets or between exercises for bench press or leg press. The effects of caffeine on 1RM have received very little attention until recently, showing conflicting results. Beck et al.[16] examined 1RM for bench press and leg extension. Caffeine use resulted in a significant improvement in 1RM for bench press (2.1 kg) but failed to show an effect for leg extension. Williams et al.[44] and Astorino et al.[45] both failed to find an effect for 1RM with caffeine for bench press and leg press. A reason for these discrepancies between studies is unclear. It appears caffeine has minimal effects of 1RM, and further studies are needed before a definite conclusion can be reached. Studies of caffeine and resistance training are sparse, with results being equivocal and implications of the ergogenic potential of caffeine unclear. Typically within the first set for muscular endurance involving leg musculature no difference has been reported for caffeine compared with placebo.[16,42,44-46] However, in one study[43] improvement was observed in early sets. Multiple sets offer evidence[42,43] that caffeine may elicit its effects for the leg musculature later when fatigue may play a more prominent role compared with earlier sets. Although this was not shown by Jacobs et al.,[46] the subjects training background
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may have potentially affected the results. Caffeine effects on upper body musculature offer opposite results compared with lower body exercises, showing greater improvements in the first sets.[16,43] Overall, the majority of studies do not support an ergogenic effect with caffeine on muscle endurance.[42,44-46] This raises the question whether the ergogenic properties of caffeine are limited by the amount of muscle mass recruited and by the total number of sets performed. Potential limitations of these studies include incorporating only one upper and lower body exercise, typically with a low number of sets being performed. Considering typical resistance training programmes use multiple exercises for upper and lower body, future investigations should seek to use multiple exercises, with a greater number of sets, in order to understand whether caffeine is ergogenic within a more ecologically valid paradigm. Although relatively few studies have been conducted in this area, it appears caffeine has minimal effects with upper body exercise for 1RM and muscle endurance. Multiple sets of resistance training with caffeine offer introductory evidence for enhanced performance on lower body musculature. However, 1RM does not appear to be affected.
1.6 Isokinetic Peak Torque

Very little work has examined the ergogenic potential of caffeine administration on isokinetic peak torque, with studies showing equivocal results. Bond et al.[47] gave 12 collegiate track sprinters a 5 mg/kg dose of caffeine (compared with placebo). They tested the sprinters for maximal voluntary contraction (MVC) on knee extension and flexion. MVC is defined as a muscle exerting a maximal amount of force during a static contraction against an immovable resistance.[48] Subjects performed six maximum repetitions at three sequential ordered speeds (30, 150 and 300/second). Peak torque, peak power and fatigue index were compared between caffeine and placebo trials. Results showed no difference in peak torque, peak power and fatigue index at any of the velocities with caffeine supplementation. Jacobson and Edwards[49] examined
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isokinetic peak torque on the knee extensor and flexors (75, 180 and 300/second) of 36 untrained subjects (20 male, 16 female) with performance for the first 125 msec and power recorded during 300/second. Subjects were assigned to one of three groups based on a caffeine dosage of 600 mg or 300 mg, or placebo. Caffeine use resulted in no significant performance difference for any dose among velocities. Jacobson et al.[50] performed a follow-up study with trained (division one football players) male athletes (n = 20), who took a 7 mg/kg dose of caffeine (vs placebo). Peak torque of the knee extensor and flexors (30, 150 and 300/second) was examined. Additionally, performance for the first 125 msec and power (W) were recorded at 300/second. Caffeine consumption resulted in significantly greater peak torque for the knee extensors at 30 and 300/second velocities and flexors at all (30, 150 and 300/second) velocities. Performance improvements for the first 125 msec were only significant for knee flexors, where power (W) was significant for knee extensors only. This follow-up study[50] with trained athletes offers introductory evidence that caffeine affects peak torque; however, with only a small volume of research testing this paradigm, many questions still remain.
1.7 Isometric Maximal Force and Endurance

(n = 5,[52] n = 6[51]), which might have potentially negated results. However, Lopes et al.[52] did find a significant effect for other variables with caffeine (i.e. tension developed at lower frequencies). Recent studies using larger sample sizes (n = 1015) have reported an ergogenic effect on sustained endurance with caffeine during submaximal isometric knee extensions (50% MVC) with caffeine 6 mg/kg.[53-55] An increase of 1725% in endurance capacity has been reported with submaximal contractions of the quadriceps,[53-55] but with equivocal results for MVC. An increased MVC force production of 4.4% has recently been reported,[56] with Kalmar and Cafarelli[55] also reporting an increase in MVC. However, other studies have failed to show a difference with caffeine on MVC.[53,57] The reasons for these discrepancies are unclear. It appears caffeine prolongs muscle endurance within this paradigm, but the impact on maximal force-generating capacity when assessed by MVC should be further explored. Although discussed later (section 3), these results may indicate caffeine fails to alter the maximal force-generating capacity of a muscle but may function to extend time to fatigue by acting via altered pain perception. More detail is provided in section 3.
1.8 Interindividual Variability

Studies evaluating the effect of caffeine on isometric contractions have typically examined ergogenic properties by assessing muscular endurance (time to exhaustion or a predetermined minimum force level) and maximal forcegenerating capacity by MVC. Earlier studies do not support an effect on either MVC or muscular endurance with caffeine on isometric contractions.[51,52] Williams et al.[51] showed no difference in endurance or MVC during voluntary isometric handgrip exercise following ingestion of caffeine 7 mg/kg. Lopes et al.[52] also noted no difference with caffeine 500 mg on MVC or endurance time during sustained contractions of the adductor pollicis muscle, although a 12% increase in endurance was shown following caffeine (vs placebo) supplementation. These studies failing to find an effect have used small sample sizes
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The effect of caffeine on performance has commonly been reported as a group mean among subjects, with relatively few studies examining individual response. Studies reporting individual data do not show improved performance for every individual.[32,36,39,40,43,53,56] Future studies should employ a test-retest study design and examine the factors that may influence the effects of caffeine on performance. Studies should be designed to try to elucidate what factor(s) causes a person to be a responder versus a nonresponder. Thus, individuals showing a positive response (responders) with specific supplementation should possibly consider this for practice and competition, while others showing minimal improvements or potential ergolytic effects (nonresponders) should discontinue supplementation. The reason why individuals may not respond to caffeine is
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unclear. Considering most studies assessing differences between habitual and non-habitual users have found no difference in performance parameters for anaerobic[15,32,36,39,57] and aerobic exercise,[58-61] it seems other unknown mediators are involved other than habituation. 2. Mechanisms of Action
2.1 Peripheral Mechanisms

tool for studying glycolysis in the hopes of detecting differences in flux. Although adrenaline might play a permissive role in enhanced performance, it seems unlikely that it acts as the main mechanism responsible for the ergogenic effects of caffeine.
2.3 Lactic Acid

Early mechanisms for a caffeine ergogenic effect with aerobic performance stem from enhanced free-fatty acid oxidation and glycogen sparing primarily thought to occur by an amplified adrenaline (epinephrine) output;[62] however, this notion has been challenged and it seems likely caffeine may operate via alternative mechanisms.[1] It is unlikely a model based on enhanced oxidation of fatty acids would affect exercise dominated by oxygen-independent metabolic pathways, such as high-intensity exercise. Therefore, the following section examines mechanisms by which caffeine may be ergogenic. Peripheral and central pathways are explored.
2.2 Catecholamines

Studies examining catecholamine response to high-intensity exercise have shown an increased adrenaline secretion with caffeine administration compared with placebo.[14,15,17,30,36] This is consistent with endurance exercise.[63-65] Only a few studies do not show an increase associated with caffeine ingestion.[66,67] Increased adrenaline levels could potentially enhance performance via an increased glycolytic flux, although studies that have shown enhanced adrenaline levels and improved performance have not always shown greater glycolytic flux (e.g. assessed via lactic acid).[15,36] Also, elevated adrenaline output has not consistently translated to increased performance for all studies.[14,17] In some studies,[17,41] increased adrenaline levels were not observed yet a subsequent increased glycolytic flux was evident via greater production or declined removal. However, studies assessing glycolytic flux have not measured it directly but measured a mixed venous blood,[14,15,17,36] which is a crude
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Caffeine has been shown through various exercise paradigms to result in greater lactic acid concentration for endurance exercise.[64,65,68-72] Lactic acid along with other variables (i.e. K+, glucose) has been shown to increase in resting conditions with caffeine consumption. This has been attributed to hepatic and resting skeletal tissue.[73] However, the results from highintensity exercise have been equivocal. Some studies show increased lactate[14,15,27,28,39,41] and others show no increase.[17,23,32,36] It is interesting to note that despite training status, the majority of studies showing an increase in lactate have also shown an increase in performance.[14,15,27,28,39] Some authors speculate that increased lactate might have been detrimental to performance,[14,41] although a few studies failed to show an effect on performance with an increase in lactate concentration.[14,41] Conversely, studies showing no difference in lactate with caffeine have reported an increase in performance.[23,32,36] Only one study showed no effect on performance.[17] As previously mentioned, the effect of caffeine on increased lactate levels does not always seem to be primarily mediated through adrenaline. A possible explanation for an increase in glycolytic flux could lie with caffeine stimulating the CNS and consequently dampening pain perception. While the role of the CNS and pain perception in fatigue is not well defined, it is plausible that blunting pain perception would mitigate fatigue by extending the timepoint at which a level of pain is experienced that would result in exercise termination. Extended duration consequent to blunted pain may result in greater lactate accumulation. The two may be related by coincidence rather than revealing a mechanistic function of caffeine at the level of the muscle. This is discussed in the following section in greater detail.
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2.4 Blood Glucose

Hepatic output of glucose has been shown to dramatically increase during high-intensity exercise[74,75] as a result of a parallel rise in adrenaline and noradrenaline (norepinephrine).[76] As mentioned earlier (section 2.2), caffeine has been shown to amplify adrenaline output from the adrenal medulla. Therefore, it would seem plausible that blood-borne glucose would subsequently increase more with caffeine administration. The majority of studies support this notion,[14,28,32,77,78] with only a few studies showing no effect.[15,17,41] Although studies not supporting this relationship have used untrained subjects, this does not explain why an increase in adrenaline for both studies did not mirror that of blood-borne glucose. Other studies utilizing untrained subjects have shown a relationship.[14,28] The results of these studies combined with previously mentioned mechanisms (i.e. adrenaline, lactate) do not support any glycogensparing effect, and in fact support the idea of enhanced glycolytic turnover. Previously mentioned by Graham[1] on the aerobic paradigm, these mechanisms seem to offer sparse insight into the influence of caffeine on anaerobic performance. Enhanced glycolytic output does not seem to be directly affected by caffeine but has an indirect effect, primarily acting through the CNS.
2.5 Potassium

The proposed model stating that caffeine could enhance excitation-contraction coupling stems from caffeine facilitating Na+/K+ ATPase activity.[79] Several authors provide evidence for this indirectly through attenuation of plasma K+ levels during rest[40] and exercise.[36,77,80] During muscular contractions, depolarization of a muscle cell results in K+ efflux into the extracellular fluid, which then can diffuse into blood plasma.[81,82]. Maintaining an electrochemical gradient of Na+ and K+ is important if a forceful output of muscle contractions is to occur.[83] Thus, preventing a rise in plasma K+ by enhanced Na+/K+ ATPase activity could create a more favourable environment for excitation-contraction, potentially delaying fatigue.[84] Caffeine metabolites
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(paraxanthine) have been shown to stimulate resting skeletal muscle K+ transport by increasing Na+/K+ ATPase activity.[85] Caffeine has been shown to attenuate the increase in plasma K+ during aerobic work.[77,80] However, comparatively little work has been conducted within the anaerobic paradigm on attenuation of plasma [K+] with caffeine. It is nevertheless reasonable to assume this could be a contributing factor when caffeine use results in enhanced performance. Considering plasma K+ concentrations during exercise have shown a parallel increase with exercise intensity,[86] it seems plausible that caffeine would elicit its effect to a greater extent during high-intensity exercise. However, this has not been the case. Greer et al.[17] showed no significant effect on attenuating plasma K+ levels. Crowe et al.[41] showed a decrease in plasma K+ prior to exercise but failed to show an effect during exercise. Doherty et al.[36] showed a reduction in plasma K+ with caffeine compared with placebo during exercise. Although Doherty et al.[36] showed attenuation of K+ during high-intensity exercise, it should be considered that caffeine was supplemented after the loading phase of creatine when interpreting their results. It is important to note with Lindinger et al.[80] that 9 mg/kg of caffeine had a greater impact on attenuating plasma K+ compared with lower doses (36 mg/kg). They also noted that the attenuated response .of caffeine on K+ was more consistent at 78% VO2 max compared with 85% . VO2 max . Furthermore, in Lindinger et al.,[80] some subjects but not all showed attenuated levels of plasma K+. Studies failing to show an impact on K+ during exercise do not seem to be hindered by relative dose employed, with subjects consuming 5[17] or 6[41] mg/kg. Studies showing an effect used 39 mg/kg.[36,76,79] Recreationally trained[41] and untrained[17] subjects both failed to show an impact on K+ during exercise. Thus, it appears that an intensity-dependent relationship may exist for caffeine attenuation of plasma K+. It is important for future studies to assess what impact caffeine has on attenuating plasma K+ levels and determine whether an intensity-related response for caffeine on K+ levels exists with trained subjects in an environment specific to the sports paradigm.
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2.6 Calcium/Phosphodiesterase Inhibition/Cyclic Adenosine Monophosphate Cascade

Calcium and phosphodiesterase inhibition have been proposed to play an intimate role in the mechanisms for a caffeine ergogenic effect. Caffeine has been shown to inhibit phosphodiesterase enzymes in vitro,[87] allowing an increase in intracellular cyclic adenosine monophosphate (cAMP).[88] An increase in cAMP would lead to a greater lipolysis, due to the cAMP relationship with regulation of adipose tissue.[89,90] Thus, caffeine potentially plays a mechanistic role for the rationale of caffeine-enhanced free-fatty oxidation (and with a subsequent glycogen sparing) even though, as noted, this mechanism is unlikely to explain any ergogenic value of caffeine during higher-intensity bouts. Caffeine has been shown to cause a greater increase in calcium mobilization from the sarcoplasmic reticulum.[91-93] Additionally, compared with fast twitch fibres, caffeine may have a greater sensitivity for affecting slow twitch muscle fibres[94-96] and slow twitch sarcoplasmic reticulum[97] in vitro. This could have favourable effects on excitation-contraction coupling, potentially attenuating muscle fatigue. Although a strong argument can be made for the effects of caffeine on inhibiting phosphodiesterase and mobilizing calcium in vitro (specifically methylxanthines), in vivo it appears the physiological dose required to do this would be toxic. Thus, it is unlikely that the effects of caffeine would be elicited through these proposed mechanisms.[88,98-100] 3. Central Mechanism
3.1 Adenosine Antagonism

muscle,[107] smooth muscle, the circulatory system and the brain.[109] Specifically, a physiological stimulus is thought to initiate adenosine release from neurons, where degradation of nucleotides occurs later.[107] Adenosine is a molecule similar in structure to caffeine,[98] and has been shown to enhance pain perception,[110,111] induce sleep,[112] reduce arousal,[113] depress spontaneous locomotor activity[114] and act as a neuromodulator.[100,101,115-118] However, caffeine has been shown to counter these inhibitory effects of adenosine.[100,101,112,114,119] Various receptors for adenosine are located throughout the CNS and brain, depending on receptor subtype.[120] Four different receptor subtypes exist for adenosine (A1, A2a, A2b and A3), with various receptors producing varying response with adenosine.[121] Inhibitory effects of adenosine act through A1 receptor activation, while excitatory response occurs with A2 receptors.[107,112] Caffeine is a nonselective adenosine inhibitor and can easily cross the blood-brain barrier by simple diffusion and carrier-mediated transport due to its lipophilic nature.[122] The effects are primarily elicited through the A1 and A2a receptors due to their higher affinity for adenosine compared with A2b and A3 receptors, which have a lower affinity for adenosine and seem to be stimulated under periods of hypoxia or ischaemia.[100,107,123] As discussed below (section 3.2), the hypotheses for caffeine mechanisms are thought to occur from inhibitory effects on adenosine, thus leading to modified pain perception while sustaining motor unit firing rates and neuro-excitability. This then is the leading hypothesis for the ergogenic effect of caffeine on performance, particularly during anaerobic performance.
3.2 Pain Perception

It is commonly known that caffeine stimulates the CNS specifically, with the effects mediated through adenosine receptor antagonism.[101-106] Adenosine is a compound composed of adenine and ribose, and has been shown to be a powerful vasodilator.[107] Adenosine metabolism is regulated primarily through adenine nucleotide (ATP, adenosine diphosphate, adenosine monophosphate) breakdown,[108] thus exercise can increase adenosine concentration in skeletal
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The pain adaptation model states that pain reduces output of muscles when they act as agonists and increases the output when they become antagonists.[124] This leads to a reduction in MVC and velocity of movement.[124] Ultimately, the ability for forceful muscle contraction is reduced.[124] Experimentally, pain has been shown to influence motor unit recruitment (i.e. decreased firing
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rate).[98,125,126] This has been correlated to the intensity of muscle pain[125] through sensory nerve transmission signalling.[102] Pain may be induced intramuscularly by injecting capsaicin[126] or hypertonic saline[127-130] in the masseter muscles or other muscles to try and replicate clinical muscle pain.[126,130] Adenosine has been shown to induce muscle pain when infused intravenously in both healthy subjects and patients with angina.[110,111,131,132] This shows its ability to reduce the pain threshold.[133] Antinociceptive (pain suppression) effects occur from activation of A1 adenosine receptors, where stimulation of A2 receptors elicits a hyperalgesic (pain enhancement) response.[102,134-136] Clinically selective blockade of A2A receptors could play a major role in the therapeutic development of pain medications[137] and may have implications for Huntingtons disease[138] and anti-Parkinson drugs.[139] The majority of studies designed to study pain have used different methods to induce pain. However, naturally occurring pain through exercise is not well understood.[140,141] Caffeine is commonly used in over-the-counter mediations for its pain-relieving effect[142] due to its blockade of adenosine receptors.[104] Clinically it has been commonly used to help reduce headaches.[143,144] Caffeine combined with other analgesic medications (e.g. paracetamol [acetaminophen]) has been shown to enhance pain-relieving ability better than with certain medications alone.[142] Additionally, the analgesic effects of caffeine have been shown to reduce experimental muscle pain.[145] Thus, one of the main concepts behind the caffeine mechanism seems to be concerned with pain perception. If caffeine can decrease naturally occurring pain of exercise and sustain or increase firing rates of motor units, a greater force output should be maintained. This hypothesis might explain the effects of caffeine in studies showing positive effects on anaerobic performance. However, it is crucial to state, as mentioned by Kalmar,[98] that no study data (to our knowledge) have examined the effect of caffeine on motor unit firing rates with experimentally induced pain. Recently, Greer et al.[18] had subjects not accustomed to the rigour of high-intensity exercise each perform a
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traditional 30-second Wingate test. They found that caffeine had no effect on electromyogram (EMG) activity. Williams et al.[19] also failed to find an effect with caffeine on EMG signalling during maximal and submaximal isometric hand grip contraction. Meyers and Cafarelli[54] also found no difference during submaximal isometric contractions on EMG activity for caffeine. These studies imply that caffeine may not affect motor unit recruitment. Recently, more sophisticated techniques were used to examine motor unit firing rates and recruitment with caffeine. No differences were found for either enhanced motor unit recruitment[53-55] or increased output of motor unit firing rates[54] with caffeine compared with placebo during submaximal (e.g. 50% MVC) isometric contractions. Recent work has shown leg muscle pain to be reduced during 30 minutes of cycling at 60% . VO2 max with caffeine.[146] The authors concluded that the ergogenic effects of caffeine might be partially explained by the hypoalgesic (painrelieving) properties of caffeine,[146] postulating A2a receptor blockade exceeded that of A1 receptor antagonist effect of caffeine; i.e. caffeine blocked A2A receptors more compared with A1 receptors, thus producing a hypoalgesic effect. Additionally, a dose-dependent response on reduced pain perception has been shown with 10 mg/kg compared with 5 mg/kg of .caffeine in males for 30 minutes of cycling at 60% VO2 max .[147] However, Motl et al.[148] did not show a dosedependent response for pain perception with females but noted a lower overall muscle pain perception for females compared with males between these studies during 30 minutes of cycling . at 60% VO2 max . Similar results for decreased leg muscle pain during exercise for females have been reported.[149] However, other studies inducing pain experimentally have shown females having a higher muscle pain rating and lower pain threshold.[150,151] What difference in impact caffeine would have on performance between males and females is unclear, considering relatively few studies have included female participants (table I) and no study (to our knowledge) has examined performance measures on sex differences with caffeine.
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Table I. Summary of literature pertaining to caffeine and anaerobic performance Study (year) Isokinetic peak torque Jacobson et al.[50] (1992) Jacobson et al.[49] (1991) Bond et al.[47] (1986) Dynamic training Beck et al.[16] (2006) Green et al.[42] (2007) Hudson et al.[43] (2007) Jacobs et al.[46] (2003) Astorino et al.[45] (2008) Williams et al.[44] (2008) 13 M 13 M 4F 15 M 13 M 22 M 9M 201 mg 6 mg/kg 6 mg/kg 4 mg/kg 6 mg/kg 300 mg Weight-trained subjects (>1 year) Weight-trained subjects (>8 weeks) Weight-trained subjects (>8 weeks) Weight-trained, currently or involved in past year Weight-trained subjects (>6 years) Weight-trained subjects (>2 years) N/S N/S N/S N/S Untrained N/S N/S Untrained 1RM bench press, 2 1RM leg press, 2 reps to failure 2 reps to failure: bench press, leg press reps to failure: leg extension; 2 arm curls 2 reps to failure: leg press, bench press 2 reps to failure: leg press, bench press; 21RM 2 reps to failure: bench press, latissimus dorsi pulldown; 2 1RM peak force, muscle endurance 2 peak force, muscle endurance 2 peak force, muscle endurance 2 peak force, muscle endurance peak force muscle endurance 2 peak force pain perception/attenuated DOMS, peak force power output 2 peak power, mean power, percentage decline in power 2 power output total power, mean power, peak power: both populations 2 mean power, peak power 2 power output 2 power output 2 power output 2 power output Continued next page 20 M 20 M 16 F 12 M 7 mg/kg 600 mg 300 mg 5 mg/kg Elite male athletes Recreationally active Intercollegiate track sprinters peak torque, power output 2 peak torque 2 peak torque No. and sex Dosage Population Findings

Isometric force production and endurance Kalmar and Cafarelli[55] (1999) Williams[117] (1987) Lopes et al.[52] (1983) Plaskett and Cafarelli[53] (2001) Maridakis et al.[56] (2007) Meyers and Cafarelli[54] (2005) Tarnopolsky and Cupido[57] (2000) Muscle soreness and damage Maridakis et al.[56] (2007) Sprint power cycling Anselm et al.[28] (1992) Greer et al.[18] (2006) Greer et al.[17] (1998) Kang et al.[23] (1998) 10 M 4F 18 M 9M 14 (N/S) 250 mg 5 mg/kg 6 mg/kg 5 mg/kg 2.5 mg/kg 201 mg 450 mg (coffee) 5 mg/kg 6 mg/kg 5 mg/kg Recreationally active Recreationally active Recreationally active Trained cyclist and recreationally active subjects Weight trained Recreationally active Untrained Recreationally active Untrained 9F 5 mg/kg 11 M 6M 5 (N/S) 15 M 9F 10 M 12 M 6 mg/kg 7 mg/kg 500 mg 6 mg/kg 5 mg/kg 6 mg/kg 6 mg/kg

Beck et al.[16] (2006) Hoffman et al.[21] (2007) Collomp et al.[14] (1991) Lorino et al.[20] (2006) Bell et al.[15] (2001)

13 M 8M 2F 3M 3F 16 M 16 M

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Table I. Contd Study (year) Schneiker et al.[27] (2006) Roberts et al.[22] (2007) Speed endurance cycling/running Wiles et al.[40] (2006) Doherty and Smith[7] (2004) Doherty et al.[36] (2002) Doherty[32] (1998) Bell et al.[15] (2001) Crowe et al.[41] (2006) 8F 11 M 14 M 9M 16 M 12 M 5F 5 mg/kg 5 mg/kg 5 mg/kg 5 mg/kg 5 mg/kg 6 mg/kg Trained cyclist Trained cyclist Trained Trained Untrained Recreationally active mean speed, mean power, peak power, performance mean power run time to exhaustion run time to exhaustion cycling time to exhaustion time to peak power (significant), total power, peak power between bouts 1 and 2 (not significant) performance (trained), 2 performance untrained sprint, power, passing performance performance 2 pro-agility agility No. and sex 10 M 5M 5F Dosage 6 mg/kg 450 mg (coffee) Population Team sport athletes Recreationally active Findings total work, mean power 2 mean power, peak power, time to peak power

Sprints Collomp et al.[31] (1992) Stuart et al.[30] (2005) Paton et al. Agility Lorino et al.[20] (2006) Stuart et al.[30] (2005) 16 M 9M 6 mg/kg 6 mg/kg Recreationally active Australian rugby players
[29]

5 M, 9F 9M 16 M

250 mg 6 mg/kg 6 mg/kg

Trained and untrained swimmers Australian rugby players Team sport athletes

(2001)

1RM = one-repetition maximum; DOMS = delayed-onset muscle soreness; F = female subjects; M = male subjects; N/S = not specified; reps = repetitions; indicates decrease; indicates increase; 2 indicates no difference.

Studies examining pain perception with caffeine during an anaerobic paradigm have been sparse. Pain perception index during repetitions to failure for resistance training has shown no difference between caffeine and placebo. However, repetitions were greater at various sets throughout the trial, suggesting pain perception may have been suppressed with caffeine.[43] Caffeine has recently been shown to attenuate delayed-onset muscle pain and force loss following eccentric exercise induced by electrical stimulation of the quadriceps.[56] A statistically significant hypoalgesic effect was shown during maximal voluntary isometric contractions, with a decrease of 12.7 raw visual analogue scale (VAS) units with caffeine compared with 1.9 VAS for placebo. A smaller nonsignificant decrease was reported for caffeine (7.8 VAS) compared with placebo (1.9 VAS) during submaximal voluntary eccentric contractions 1 hour after ingestion of caffeine 5 mg/kg in untrained female subjects. This study shows novel insight of the hypoalgesic effect of
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caffeine within this paradigm. However, whether these results apply to trained subjects using a more practical model assessing pain on eccentric training (i.e. free weights) remains unknown. The effects of caffeine on altering pain perception and affecting the CNS are well documented. Although the mechanisms of the effects of caffeine may act primarily via stimulating the CNS, the role of peripheral tissue should not be diminished. Some studies show an effect with caffeine in which the CNS played a minimal role.[52,57,152] Future investigations should be conducted in order to elucidate the exact mechanisms of caffeine.
3.3 Rating of Perceived Exertion

As previously mentioned, the effects of caffeine on pain perception are well documented in clinical settings. However, only recently have the analgesic effects of caffeine been applied to naturally occurring pain of exercise. It would seem logical that caffeine could potentially decrease perceived
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exertion, thus possibly allowing athletes to work at a greater intensity or prolong the duration of exercise. In a recent meta-analysis, Doherty and Smith[8] reviewed the effects of caffeine on rating of perceived exertion (RPE), showing that caffeine dampened perceived exertion by 5.6% compared with placebo. Regression analysis revealed that 29% of the variance explained the ergogenic effect of caffeine on performance by decreased RPE. The effects of caffeine on RPE have been extensively examined in the aerobic paradigm,[62,153,154] but research examining the effects of caffeine on anaerobic performance has been scarce. Only a few studies have examined RPE while performing high-intensity exercise, with the majority of studies showing no difference for RPE between caffeine and placebo,[27,42,43] and others showing a decreased RPE,[36,39] or even an increased RPE compared with placebo.[41] Doherty et al.[36] found that caffeine showed a clear trend for decreased RPE at every 30-second timepoint (RPE taken for 2 minutes); however, a significant difference was only noticed at 90 seconds for run time to fatigue at . 125% VO2 max . Doherty et al.[39] also found a decreased RPE of approximately 1 point (Borg Scale) during high-intensity cycling for 3 minutes. However, Crowe et al.[41] found an increased RPE approaching significance (p = 0.055) for caffeine compared with placebo between bouts 1 and 2 during 60 seconds of high-intensity cycling. The effects caffeine exerts on RPE during resistance training have only recently been examined. Green et al.[42] and Hudson et al.[43] both failed to show a difference in RPE with caffeine compared with placebo during resistance training. However, both studies did find an increase in repetitions with caffeine at various sets throughout their protocol, suggesting RPE was blunted to an extent with caffeine. As mentioned previously (section 1.2), caffeine has been shown to enhance short duration high-intensity exercise when the methodology has been matched to mimic athletic competitions (i.e. 46 seconds).[27,30] Schneiker et al.[27] found that caffeine did not decrease RPE compared with placebo; however, total sprint work and peak power were greater. Therefore, participants for Green et al.,[42] Hudson et al.[43] and Schneiker et al.[27] were able
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to accomplish more work despite the same perceived exertion as placebo, offering introductory evidence that caffeine blunts perceived exertion during high-intensity exercise. The lack of differences between studies perhaps suggests the RPE scale is too gross to be used to detect changes in perception at such high exercise intensities. Although these studies offer promising insight on the mechanism of caffeine for improved performance, more research is clearly needed in this area before the extent of the effect of caffeine can be fully understood.
3.4 Fatigue

The effects of fatigue have been associated with both peripheral and central mechanisms. However, it is beyond the scope of this review to evaluate whether fatigue is more a product of peripheral or central fatigue but merely to examine what effects caffeine has on attenuating fatigue during exercise. Caffeine has recently been proposed as a tool to examine fatigue,[155] considering it affects both peripheral and central pathways in vivo and in vitro. When fatigue is evaluated via aerobic performance, caffeine has commonly shown increased time to fatigue for humans[64,65,71,78,152,156] and animals[157] compared with placebo. Recent work from our laboratory (unpublished observation) supports the notion that caffeine attenuates fatigue during sprint-type activity. Studies have attributed enhanced anaerobic performance,[27,30] submaximal isometric contractions,[53-55] and speed endurance protocols[15,32,36,39] to attenuated fatigue. Thus, it appears caffeine not only delays fatigue in aerobic exercise but also in protocols that rely heavily on oxygen-independent metabolic pathways. 4. Conclusion and Future Directions Caffeine seems to be ergogenic during highintensity exercise, depending on the paradigm. Exercises examining isokinetic peak torque, isometric maximal force, muscular endurance for upper body musculature, and 1RM show equivocal results, with caffeine having minimal ergogenic effect within these areas. Studies of
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repetitions to failure for lower body musculature offer introductory evidence that caffeine has an effect on resistance training. Recent work supports the notion that caffeine affects isometric muscle endurance. Considering a relatively large body of research has not been conducted within these areas, more studies are clearly needed before a definite conclusion can be reached on muscular endurance and muscular force. Traditional measures of power output observed during the 30-second Wingate protocol do not seem favourably enhanced by caffeine administration. Yet this has been examined most often in untrained athletes. Speed endurance (i.e. 60180 seconds in duration) seems to be highly affected by caffeine. High-intensity exercise seems to be favourably affected (i.e. sprinting, sprint cycling power) with methodologies employing protocols that mimic sport activities (i.e. 46 seconds), while agility performance remains unclear. Therefore, sports such as soccer, rugby, lacrosse and football would seem to be favourably affected by caffeine. Earlier research examining the effects of caffeine on performance typically employed untrained subjects with methodologies not specific to high-intensity intermittent sport activities. These designs and subject characteristics potentially contributed to the conclusion that caffeine may not be beneficial in this paradigm. However, recent studies have started employing trained subjects accustomed to the rigour of the protocols tested. Therefore, caffeine seems to be the most beneficial for trained subjects, with the majority of studies showing little to no effect on untrained subjects. The reason for such differences in training status between subjects is currently unclear. Additionally, a subjects habituation status with caffeine does not seem to have an effect on either aerobic or anaerobic exercise. Although an argument can be made regarding the impact caffeine has on the peripheral mechanisms, specifically regarding Na+/K+ pumps, it seems likely that caffeine mechanisms act primarily by stimulating the CNS through adenosine antagonism, dampening pain perception, blunting perceived exertion, and delaying fatigue.
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Caffeine has received tremendous attention within exercise models dominating aerobic ATP pathways. It has received relatively less attention with respect to work bouts relying principally on anaerobic ATP pathways, thus leaving many questions unanswered. Future research should examine the impact and the extent caffeine has on high-intensity performance, with individual and group data being assessed, and also whether sex differences exist. Studies are also needed to understand whether individuals respond similarly during repeated bouts of exercise (true responders) with caffeine consumption and elucidate the underlying mechanisms between responders and nonresponders. Furthermore, the acute and chronic effects of caffeine on muscular endurance performance incorporating multiple exercises and sets should be examined further. Finally, work is necessary to isolate the precise mechanisms by which caffeine acts as an ergogenic aid. Acknowledgements
No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content if this review.

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1. Graham TE. Caffeine and exercise: metabolism, endurance and performance. Sports Med 2001; 31: 785-807 2. Spriet LL. Caffeine and performance. Int J Sport Nutr 1995; 5 Suppl.: S84-99 3. Magkos F, Kavouras SA. Caffeine and ephedrine: physiological, metabolic and performance enhancing effects. Sports Med 2004; 34: 871-89 4. Sinclair CJ, Geiger JD. Caffeine use in sports: a pharmacological review. J Sports Med Phys Fitness 2000; 40: 71-9 5. Keisler BD, Armsey TD. Caffeine as an ergogenic aid. Curr Sports Med Rep 2006; 5: 215-9 6. Paluska SA. Caffeine and exercise. Curr Sports Med Rep 2003; 2: 213-9 7. Doherty M, Smith PM. Effects of caffeine ingestion on exercise testing: a meta-analysis. Int J Sport Nutr Exerc Metab 2004; 14: 626-46 8. Doherty M, Smith PM. Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis. Scand J Med Sci Sports 2005; 15: 69-78 9. Inbar O, Bar-or O, Skinner JS. The Wingate anaerobic test. Champaign (IL): Human Kinetics, 1996 10. Smith JC, Hill DW. Contribution of energy systems during a Wingate power test. Br J Sports Med 1991; 25: 196-9

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Correspondence: Dr J.K. Davis, Department of Health and Human Performance, PO BOX 3011, Texas A&M University-Commerce, Commerce, TX 75429, USA. E-mail: JonKyle_Davis@tamu-commerce.edu

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