Abstract
Following critical evaluation of the available literature to date, The International Society of Sports Nutrition (ISSN) position regarding caffeine intake is as follows:
Supplementation with caffeine has been shown to acutely enhance various aspects of exercise performance in many but not all studies. Small to moderate benefits of caffeine use include, but are not limited to: muscular endurance, movement velocity and muscular strength, sprinting, jumping, and throwing performance, as well as a wide range of aerobic and anaerobic sport-specific actions.
Aerobic endurance appears to be the form of exercise with the most consistent moderate-to-large benefits from caffeine use, although the magnitude of its effects differs between individuals.
Caffeine has consistently been shown to improve exercise performance when consumed in doses of 3–6 mg/kg body mass. Minimal effective doses of caffeine currently remain unclear but they may be as low as 2 mg/kg body mass. Very high doses of caffeine (e.g. 9 mg/kg) are associated with a high incidence of side-effects and do not seem to be required to elicit an ergogenic effect.
The most commonly used timing of caffeine supplementation is 60 min pre-exercise. Optimal timing of caffeine ingestion likely depends on the source of caffeine. For example, as compared to caffeine capsules, caffeine chewing gums may require a shorter waiting time from consumption to the start of the exercise session.
Caffeine appears to improve physical performance in both trained and untrained individuals.
Inter-individual differences in sport and exercise performance as well as adverse effects on sleep or feelings of anxiety following caffeine ingestion may be attributed to genetic variation associated with caffeine metabolism, and physical and psychological response. Other factors such as habitual caffeine intake also may play a role in between-individual response variation.
Caffeine has been shown to be ergogenic for cognitive function, including attention and vigilance, in most individuals.
Caffeine may improve cognitive and physical performance in some individuals under conditions of sleep deprivation.
The use of caffeine in conjunction with endurance exercise in the heat and at altitude is well supported when dosages range from 3 to 6 mg/kg and 4–6 mg/kg, respectively.
Alternative sources of caffeine such as caffeinated chewing gum, mouth rinses, energy gels and chews have been shown to improve performance, primarily in aerobic exercise.
Energy drinks and pre-workout supplements containing caffeine have been demonstrated to enhance both anaerobic and aerobic performance.
Introduction
Caffeine is the world’s most widely consumed psychoactive substance and naturally occurs in dozens of plant species, including coffee, tea and cocoa. Caffeine is ingested most frequently in the form of a beverage such as coffee, soft drinks and tea, although the consumption of many functional beverages, such as energy drinks, has been on a steady rise in the past two decades [Citation1]. In Western countries, approximately 90% of adults consume caffeine on a regular basis, with dietary caffeine consumption of U.S. adult men and women estimated at approximately 200 mg/day in a 2009–2010 survey [Citation2–Citation4]. In young adults and exercising individuals, there has also been a rise in the consumption of other caffeine-containing products, including energy drinks [Citation1, Citation3], ‘pre-workout supplements’, chewing gum, energy gels and chews, aerosols, and many other novel caffeinated food products [Citation5]. Caffeine-containing products have a range of doses per serving, from 1 mg in milk chocolate up to > 300 mg in some dietary supplements [Citation6].
Caffeine and its effects on health have been a longstanding topic of interest, and caffeine continues to be a dietary compound of concern in public health, as indicated by extensive investigations [Citation7–Citation10]. At the same time, caffeine has become ubiquitous in the sporting world, where there is keen interest in better understanding the impact of caffeine on various types of exercise performance. Accordingly, caffeine has dominated the ergogenic aids and sport supplement research domain over the past several decades [Citation11–Citation13].
Caffeine in sport: a brief history
In the early days (1900s) of modern sport, concoctions of plant-based stimulants, including caffeine and other compounds such as cocaine, strychnine, ether, heroin and nitroglycerin, were developed secretly by trainers, athletes and coaches, in what appears to be evidence for early day ergogenic aids designed to provide a competitive advantage [Citation14]. The use of various pharmaceutical cocktails by endurance athletes continued until heroin and cocaine became restricted to prescriptions in the 1920s, and further when the International Olympic Committee (IOC) introduced anti-doping programs in the late 1960s [Citation15].
Some of the earliest published studies on caffeine came from two psychologists and colleagues William Rivers and Harald Webber, at Cambridge University, who both had an interest in disentangling the psychological and physiological effects of substances like caffeine and alcohol. Rivers and Webber, using themselves as subjects, investigated the effects of caffeine on muscle fatigue. The remarkable well-designed studies carried out from 1906 to 1907 used double-blinded placebo-controlled trials and standardization for diet (i.e. caffeine, alcohol), and were described in a 1907 paper in the Journal of Physiology [Citation16]. Significant research on the effects of caffeine on exercise performance with more subjects, different sports, and exploring variables such as the effects between trained and untrained individuals, began and continued through the 1940s [Citation14, Citation17]. However, it was the series of studies investigating the benefits of caffeine in endurance sports in the Human Performance Laboratory at Ball State University in the late 1970s, led by David Costill [Citation18, Citation19] and others [Citation20], that sparked a generation of research on the effects of caffeine in exercise metabolism and sports performance.
Caffeine sources
Along with naturally occurring sources, such as coffee, tea and cocoa, caffeine is also added to many foods, beverages and novelty products, such as jerky, peanut butter, and candy, in both synthetic (e.g. powder) and natural (e.g. guarana, kola nut) forms. Synthetic caffeine is also an ingredient in several over-the-counter and prescription medications, as it is often used in combination with analgesic and diuretic drugs to amplify their pharmacological potency [Citation21].
Approximately 96% of caffeine consumption from beverages comes from coffee, soft drinks and tea [Citation22]. Additionally, there are varying levels of caffeine in the beans, leaves and fruit of more than 60 plants, resulting in great interest in herbal and other plant-based supplements [Citation23–Citation26]. Caffeine-containing energy drink consumption [Citation27–Citation31] and co-ingestion of caffeine with (e.g. “pre-workouts”), or in addition to, other supplements (e.g. caffeine + creatine) is also popular among exercising individuals [Citation32–Citation39]. To date, the preponderance of caffeine and exercise performance literature has utilized anhydrous caffeine (in a capsule) [Citation40–Citation46] for simpler dose standardization and placebo creation. There is also a growing body of literature studying the effects of using alternate delivery methods of caffeine during exercise [Citation5] such as coffee [Citation18, Citation47–Citation56], energy drinks, herbal formulas [Citation57] and ‘pre-workout’ formulas, among others. A review of alternate caffeine forms may be found in the Alternative caffeine sources section and Tables , , , and .
Caffeine legality in sport
Anti-doping rules apply to most sports, especially in those where athletes are competing at national and international levels. The IOC continues to recognize that caffeine is frequently used by athletes because of its reported performance-enhancing or ergogenic effects [Citation109]. Caffeine was added to the list of banned substances by the IOC in 1984 and the World Anti-Doping Agency (WADA) in 2000. A doping offense was defined as having urinary caffeine concentrations exceeding a cut-off of 15 μg/ml. In 1985, the threshold was reduced to 12 μg/ml [Citation110]. The cut-off value was chosen to exclude typical amounts ingested as part of common dietary or social coffee drinking patterns, and to differentiate it from what was considered to be an aberrant use of caffeine for the purpose of sports performance enhancement [Citation111].
The IOC and WADA removed the classification of caffeine as a “controlled” substance in 2004, leading to a renewed interest in the use of caffeine by athletes. However, caffeine is still monitored by WADA, and athletes are encouraged to maintain a urine caffeine concentration below the limit of 12 μg/ml urine which corresponds to 10 mg/kg body mass orally ingested over several hours, and which is more than triple the intake reported to enhance performance [Citation112, Citation113]. Interestingly, caffeine is also categorized as a banned substance by the National Collegiate Athletic Association (NCAA), if urinary caffeine concentration exceeds 15 μg/ml, which is greater than the “monitored substance” level set for WADA [Citation114], and also well above amounts that are deemed ergogenic.
A comparison of caffeine concentrations obtained during in-competition doping control from athletes in several sports federations pre− 2004 versus post-2004, indicated that average caffeine concentrations decreased in 2004 after removal from the prohibited substance list [Citation110]. Reports on over 20,000 urine samples collected and analyzed after official national and international competitions between 2004 and 2008, and again in 2015 using 7500 urine samples found overall prevalence of caffeine use across various sports to be about 74% in the 2004 to 2008 time period and roughly 76% in 2015. The highest use of caffeine was among endurance athletes in both studies [Citation115, Citation116]. Urinary caffeine concentration significantly increased from 2004 to 2015 in athletics, aquatics, rowing, boxing, judo, football, and weightlifting; however, the sports with the highest urine caffeine concentration in 2015 were cycling, athletics, and rowing [Citation116].
Caffeine pharmacokinetics
Caffeine or 1,3,7-trimethylxanthine, is an odorless white powder that is soluble in both water and lipids and has a bitter taste. It is rapidly absorbed from the gastrointestinal tract, mainly from the small intestine but also in the stomach [Citation117]. In saliva, caffeine concentration reaches 65–85% of plasma levels, and is often used to non-invasively monitor compliance for ingestion or abstinence of caffeine [Citation118]. Caffeine is effectively distributed throughout the body by virtue of being sufficiently hydrophobic to allow easy passage through most, if not all biological membranes, including the blood-brain barrier [Citation119]. When caffeine is consumed it appears in the blood within minutes, with peak caffeine plasma concentrations after oral administration reported to occur at times (Tmax) ranging from 30 to 120 min [Citation43, Citation120–Citation122]. The absolute bioavailability of caffeine is very high and reaches near 100% as seen in studies reporting areas under the plasma concentration-time curves (AUC) [Citation120]. Once caffeine is absorbed, there appears to be no hepatic first-pass effect (i.e., the liver does not appear to remove caffeine as it passes from the gut to the general circulation), as evidenced by similar plasma concentration curves when administered by either oral or intravenous routes [Citation123]. Caffeine absorption from food and beverages does not seem to be dependent on age, gender, genetics or disease, or the consumption of drugs, alcohol or nicotine. However, the rates of caffeine metabolism and breakdown appear to differ between individuals through both environmental and genetic influences [Citation3, Citation124, Citation125].
Over 95% of caffeine is metabolized in the liver by the Cytochrome P450 1A2 (CYP1A2) enzyme, a member of the cytochrome P450 mixed-function oxidase system, which metabolizes and detoxifies xenobiotics in the body [Citation126]. CYP1A2 catalyzes the demethylation of caffeine into the primary metabolites paraxanthine (1,7-dimethylxanthine), theobromine (3,7-dimethylxanthine) and theophylline (1,3-dimethylxanthine), which account for approximately 84, 12, and 4%, of total caffeine elimination, respectively [Citation127, Citation128]. These three caffeine metabolites undergo further demethylations and oxidation to urates in the liver with about 3–5% remaining in caffeine form when excreted in the urine [Citation129, Citation130]. While the average half-life (t1/2) of caffeine is generally reported to be between 4 and 6 h, it varies between individuals and even may range from 1.5 to 10 h in adults [Citation120]. The wide range of variability in caffeine metabolism is due to several factors. The rate of caffeine metabolism may be inhibited or decreased with pregnancy or use of hormonal contraceptives [Citation125], increased or induced by heavy caffeine use [Citation131] cigarette smoking [Citation132] or modified in either direction by certain dietary factors [Citation133] and/or variation in the CYP1A2 gene, which will be discussed later [Citation125, Citation132–Citation134].
Several studies have also shown that the form of caffeine or its vehicle for entry into the body can modify the pharmacokinetics [Citation58, Citation81, Citation119, Citation122]. One small trial (n = 3) evaluated Tmax for a variety of beverages that all included 160 mg of caffeine but in different volumes of solution, and reported that Tmax occurs at 0.5, 0.5, and 2 h for coffee, tea and cola, respectively [Citation135]. In another study involving seven participants, caffeine plasma concentrations peaked rapidly at 30 min for capsule form, whereas caffeine absorption from cola and chocolate was delayed and produced lower plasma concentrations that peaked at roughly 90–120 min after consumption. This study also did not control for volume of administered solution (capsules and chocolate ingested with 360 ml water and 800 ml cola) [Citation122]. Liguori et al. [Citation136] evaluated a 400 mg dose of caffeine in 13 subjects and reported salivary caffeine Tmax values of 42, 39 and 67 min, for coffee, sugar-free cola and caffeine capsules, respectively. However, fluid volume was again not standardized (coffee – 12 oz., sugar-free cola – 24 oz., capsules – volume of administered fluid not reported). The impact of temperature or rate of ingestion of caffeine has also been investigated, amidst concerns that cold energy drinks might pose a danger when chugged quickly, compared to sipping hot coffee. One study [Citation121] compared five conditions that included: slow ingestion (20 min) of hot coffee, and fast (2-min) or slow (20-min) ingestion for both cold coffee and energy drinks. Similar to other caffeine pharmacokinetic studies [Citation122, Citation135], White et al. [Citation121] reported that although the rate of consumption, temperature, and source (coffee vs. energy drink) may be associated with slight differences in pharmacokinetic activity, these differences are small.
Chewing gum formulations appear to alter pharmacokinetics, as much of the caffeine released from the gum through mastication can be absorbed via the buccal cavity, which is considered faster due to its extensive vascularization, especially for low molecular weight hydrophobic agents [Citation137]. Kamimori et al. [Citation58] compared the rate of absorption and relative caffeine bioavailability from chewing gum compared to a capsule form of caffeine. Although caffeine administered in the chewing gum formulation was absorbed at a significantly faster rate, the overall bioavailability was comparable to the capsuled 100 and 200 mg caffeine dose groups. These pharmacokinetic findings are useful for military and sport purposes, where there is a requirement for rapid and maintained stimulation over specific periods of time. Chewing gum may also be advantageous due to reduced digestive requirements, where absorption of caffeine in other forms (capsule, coffee etc.) may be hindered by diminished splanchnic blood flow during moderate to intense exercise. Finally, there is a growing prevalence of caffeinated nasal and mouth aerosols administered directly in the mouth, under the tongue or inspired may affect the brain more quickly through several proposed mechanisms [Citation5], although there are only a few studies to date to support this claim. The administration of caffeine via aerosol into the oral cavity appears to produce a caffeine pharmacokinetic profile comparable to the administration of a caffeinated beverage [Citation81]. Nasal and mouth aerosols will be discussed further in another section.
Mechanism of Action (MOA)
Although the action of caffeine on the central nervous system (CNS) has been widely accepted as the primary mechanism by which caffeine alters performance, several mechanisms have been proposed to explain the ergogenic effects of caffeine, including increased myofibrillar calcium availability [Citation138, Citation139], optimized exercise metabolism and substrate availability [Citation45], as well as stimulation of the CNS [Citation140–Citation142]. One of the earlier proposed mechanisms associated with the ergogenic effects of caffeine stemmed from the observed adrenaline (epinephrine)-induced enhanced free-fatty acid (FFA) oxidation after caffeine ingestion and consequent glycogen sparing, resulting in improved endurance performance [Citation18, Citation45, Citation143]. However, this substrate-availability hypothesis was challenged and eventually dismissed, where after several performance studies it became clear that the increased levels of FFAs appeared to be higher earlier in exercise when increased demand for fuel via fat oxidation would be expected [Citation141, Citation144, Citation145]. Furthermore, this mechanism could not explain the ergogenic effects of caffeine in short duration, high-intensity exercise in which glycogen levels are not a limiting factor. Importantly, several studies employing a variety of exercise modalities and intensities failed to show a decrease in respiratory exchange ratio (RER) and/or changes in serum FFAs, which would be indicative of enhanced fat metabolism during exercise when only water was ingested [Citation144, Citation146–Citation148]. Ingestion of lower doses of caffeine (1–3 mg/kg of body mass), which do not result in significant physiological responses (i.e. RER, changes in blood lactate, glucose), also appear to deliver measurable ergogenic effects, offering strong support for the CNS as the origin of reported improvements [Citation43, Citation149, Citation150]. As such, focus has shifted to the action of caffeine during exercise within the central and peripheral nervous systems, which could alter the rate of perceived exertion (RPE) [Citation151–Citation154], muscle pain [Citation151, Citation155–Citation157], and possibly the ability of skeletal muscle to generate force [Citation151].
Caffeine does appear to have some direct effects on muscle which may contribute to its ergogenicity. The most likely pathway that caffeine may benefit muscle contraction is through calcium ion (Ca2+) mobilization, which facilitates force production by each motor unit [Citation138, Citation139, Citation150, Citation158]. Fatigue caused by the gradual reduction of Ca2+ release may be attenuated after caffeine ingestion [Citation139, Citation159]. Similarly, caffeine may work, in part, in the periphery through increased sodium/potassium (Na+/K+) pump activity to potentially enhance excitation-contraction coupling necessary for muscle contraction [Citation160]. Caffeine appears to employ its effects at various locations in the body, but the most robust evidence suggests that the main target is the CNS, which is now widely accepted as the primary mechanism by which caffeine alters mental and physical performance [Citation141]. Caffeine is believed to exert its effects on the CNS via the antagonism of adenosine receptors, leading to increases in neurotransmitter release, motor unit firing rates, and pain suppression [Citation151, Citation155–Citation157, Citation161]. There are four distinct adenosine receptors, A1, A2A, A2B and A3, that have been cloned and characterized in several species [Citation162]. Of these subtypes, A1 and A2A, which are highly concentrated in the brain, appear to be the main targets of caffeine [Citation163]. Adenosine is involved in numerous processes and pathways, and plays a crucial role as a homeostatic regulator and neuromodulator in the nervous system [Citation164]. The major known effects of adenosine are to decrease the concentration of many CNS neurotransmitters, including serotonin, dopamine, acetylcholine, norepinephrine and glutamate [Citation163–Citation165]. Caffeine, which has a similar molecular structure to adenosine, binds to adenosine receptors after ingestion and therefore increases the concentration of these neurotransmitters [Citation163, Citation165]. This results in positive effects on mood, vigilance, focus, and alertness in most, but not all, individuals [Citation166, Citation167].
Researchers have also characterized aspects of adenosine A2A receptor function related to cognitive processes [Citation168] and motivation [Citation169, Citation170]. In particular, several studies have focused on the functional significance of adenosine A2A receptors and the interactions between adenosine and dopamine receptors, in relation to aspects of behavioral activation and effort-related processes [Citation168–Citation171]. The serotonin receptor 2A (5-HT2A) has also been shown to modulate dopamine release, through mechanisms involving regulation of either dopamine synthesis or dopaminergic neuron firing rate [Citation172, Citation173]. Alterations in 5-HTR2A receptors may therefore affect dopamine release and upregulation of dopamine receptors [Citation174, Citation175]. A possible mechanism for caffeine’s ergogenicity may involve variability in 5-HTR2A receptor activity, which may modulate dopamine release and consequently impact alertness, pain and motivation and effort [Citation141]. 5-HTR2A receptors are encoded by the HTR2A gene, which serves as a primary target for serotonin signaling [Citation176], and variations in the gene have been shown to affect 5-HTR2A receptor activity [Citation177, Citation178]. This may therefore modulate dopamine activity, which may help to elucidate some of the relationships among neurotransmitters, genetic variation and caffeine response, and the subsequent impact on exercise performance.
Muscle pain has been shown to negatively affect motor unit recruitment and skeletal muscle force generation proportional to the subjective scores for pain intensity [Citation179, Citation180]. In one study, progressively increased muscle pain intensity caused a gradual decrease in motor firing rates [Citation179]. However, this decrease was not associated with a change in motor unit membrane properties demonstrating a central inhibitory motor control mechanism with effects correlated to nociceptive activity [Citation179]. Other studies also indicate that muscle force inhibition by muscle pain is centrally mediated [Citation181]. Accordingly, caffeine-mediated CNS mechanisms, such as dopamine release [Citation182], are likely imputable for pain mitigation during high-intensity exercise [Citation155–Citation157, Citation181, Citation183–Citation186]. Although there appears to be strong evidence supporting the analgesic effects of caffeine during intense exercise, others have found no effect [Citation185, Citation187].
The attenuation of pain during exercise as a result of caffeine supplementation may also result in a decrease in the RPE during exercise. Two studies [Citation183, Citation184] have reported that improvements in performance were accompanied by a decrease in pain perception as well as a decrease in RPE under caffeine conditions, but it is unclear which factor may have contributed to the ergogenic effect. Acute caffeine ingestion has been shown to alter RPE, where effort may be greater under caffeine conditions, yet it is not perceived as such [Citation12, Citation152–Citation154]. A meta-analysis [Citation12] identified 21 studies using mostly healthy male subjects (74%) between the ages of 20 and 35 years and showed a 5.6% reduction in RPE during exercise following caffeine ingestion. An average improvement in performance of 11% was reported across all exercise modalities. This meta-analysis established that reductions in RPE explain up to 29% of the variance in the improvement in exercise performance [Citation12]. Others have not found changes in RPE with caffeine use [Citation187]. A more recent study by Green et al. [Citation188] also showed that when subjects were instructed to cycle at specific RPE (effort) levels under caffeine conditions, the higher perceived intensity did not necessarily result in greater work and improved performance in all subjects equally. The authors noted that individual responses to caffeine might explain their unexpected findings.
In the last decade, our understanding of CNS fatigue has improved. Historically, it is well- documented that “psychological factors” can affect exercise performance and that dysfunction at any step in the continuum from the brain to the peripheral contractile machinery will result in muscular fatigue [Citation189, Citation190]. The role of the CNS and its ‘motor drive’ effect was nicely shown by Davis et al. [Citation191] who examined the effect of caffeine injected directly into the brains of rats on their ability to run to exhaustion on a treadmill. In this controlled study, rats were injected with either vehicle (placebo), caffeine, 5′-N-Ethylcarboxamido adenosine (NECA), an adenosine receptor agonist, or caffeine NECA together. Rats ran 80 min in the placebo trial, 120 min in the caffeine trial and only 25 min with NECA. When caffeine and NECA were given together, the effects appeared to cancel each other out, and run time was similar to placebo. When the study was repeated with peripheral intraperitoneal (body cavity) injections instead of brain injections, there was no effect on run performance. The authors concluded that caffeine increased running time by delaying fatigue through CNS effects, in part by blocking adenosine receptors [Citation191]. Caffeine also appears to enhance cognitive performance more in fatigued than well-rested subjects [Citation192–Citation194]. This phenomenon is also apparent in exercise performance [Citation195] both in the field [Citation196] and in the lab [Citation60, Citation63, Citation149].
The placebo effect
The placebo effect is a beneficial outcome that cannot be attributed to a treatment or intervention but is brought about by the belief that one has received a positive intervention. For example, an individual may ingest a capsule with sugar or flour (a small amount of non-active ingredient) but believes that he/she ingested caffeine and experiences improvements in performance because of this belief [Citation197]. The nocebo effect is directly opposite to this in that a negative outcome occurs following the administration of an intervention or lack of an intervention (e.g. knowingly ingesting a placebo) [Citation198]. For example, the nocebo may be a substance without medical effects, but which worsens the health status of the person taking it by the negative beliefs and expectations of the patient. Similarly, the nocebo may be a ‘caffeine placebo’, where an individual’s performance is worse based on the belief that they did not ingest caffeine.
Several studies have provided evidence for placebo effects associated with caffeine ingestion [Citation199–Citation201] or other “beneficial” interventions [Citation202] during exercise. An example of this was reported in a study [Citation200] where well-trained cyclists exhibited a linear dose–response relationship in experimental trials from baseline to a moderate (4.5 mg/kg) and high dose (9 mg/kg) of caffeine respectively. Athletes improved as the perceived caffeine doses increased; however, a placebo was used in all interventions. Similarly, Saunders et al. [Citation201] found that correct identification of caffeine appears to improve cycling performance to a greater extent than the overall effect of caffeine, where participants who correctly identified placebo showed possible harmful effects on performance. Therefore, readers are encouraged to consider whether studies that have explored the effects of caffeine on exercise have examined and reported the efficacy of the blinding of the participants.
Caffeine and endurance exercise
Less than a 1% change in average speed is enough to affect medal rankings in intense Olympic endurance events lasting ~ 45 s to 8 min [Citation203]. In other events, such as the men’s individual road race, the difference between the top three medalists was < 0.01% [Citation204]. At the highest level of sports, competitors will be near their genetic potential, will have trained intensively, followed prudent recovery protocols, and will have exploited all strategies to improve their performance—the use of an ergogenic aid, when legal, safe and effective, is an alluring opportunity.
Caffeine has consistently been shown to improve endurance by 2–4% across dozens of studies using doses of 3–6 mg/kg body mass [Citation13, Citation195, Citation205–Citation207]. Accordingly, caffeine is one of the most prominent ergogenic aids and is used by athletes and active individuals in a wide variety of sports and activities involving aerobic endurance. Caffeine has been shown to benefit several endurance-type sports including cycling [Citation60, Citation206, Citation208], running [Citation91, Citation209, Citation210] cross-country skiing [Citation211] and swimming [Citation212].
Much of the caffeine-exercise body of literature has focused on endurance-type exercise, as this is the area in which caffeine supplementation appears to be more commonly used and likely beneficial in most, but not all, athletes [Citation11–Citation13]. For example, the caffeine concentration in over twenty thousand urine samples obtained for doping control from 2004 to 2008 was measured after official national and international competitions [Citation110, Citation115]. The investigations concluded that roughly 74% of elite athletes used caffeine as an ergogenic aid prior to or during a sporting event, where endurance sports are the disciplines showing the highest urine caffeine excretion (and therefore prevalence) after competition [Citation110, Citation115].
A recent meta-analysis reporting on 56 endurance time trials in athletes (79% cycling), found the percent difference between the caffeine and placebo group ranged from − 3.0 to 15.9% [Citation195]. This wide range in performance outcomes highlights the substantial inter-individual variability in the magnitude of caffeine’s effects as reported. These inter-individual differences might be due to the methodological differences between the studies, habitual caffeine intake of the participants, and/or partly due to variation in genes that are associated with caffeine metabolism and caffeine response [Citation213].
A recent systematic review was carried out on randomised placebo-controlled studies investigating the effects of caffeine on endurance performance and a meta-analysis was conducted to determine the ergogenic effect of caffeine on endurance time-trial performance [Citation205]. Forty-six studies met the inclusion criteria and were included in the meta-analysis. This meta-analysis found that caffeine has a small but significant effect on endurance performance when taken in moderate doses (3–6 mg/kg) as well as an overall improvement following caffeine compared to placebo in mean power output of 2.9 ± 2.2% and a small effect size of 0.22 ± 0.15. Time-trial completion time showed improvements of 2.3 ± 2.6% with a small effect size of 0.28 ± 0.12. However, there was some variability in outcomes with responses to caffeine ingestion, with two studies reporting slower time-trial performance, and five studies reporting lower mean power output during the time–trial [Citation205].
In summary, caffeine has been consistently shown to be effective as an ergogenic aid when taken in moderate doses (3–6 mg/kg), during endurance-type exercise and sport. Dozens of endurance studies are highlighted through this review is various sections, showing consistent yet wide-ranging magnitudes of benefit for endurance performance under caffeine conditions.
Caffeine and muscular endurance, strength and power
Strength and power development through resistance exercise is a significant component of conditioning programs for both fitness and competitive sport. The most frequently consumed dose of caffeine in studies using strength tasks with trained or untrained individuals usually ranges from 3 to 6 mg/kg body mass (with 2 mg to 11 mg representing the entire range), ingested in the form of pills or capsules 30 to 90 min before exercise. In resistance exercise, strength is most commonly assessed using 1 repetition maximum (1RM) [Citation214], or different isometric and isokinetic strength tests [Citation215]. Muscular endurance assesses the muscle’s ability to resist fatigue and is an important quality in many athletic endeavors (e.g., swimming, rowing). Muscular endurance may be tested with repetitions of squats, maximal push-ups, bench press exercises (load corresponding to 60–70% of 1RM) to momentary muscular failure, or by isometric exercises such as the plank or static squat [Citation216, Citation217].
Although several studies exploring the effects of caffeine on strength performance have been published since the 2010 ISSN caffeine position stand [Citation40], some uncertainty surrounding the benefits of caffeine in activities involving muscular endurance, strength and power remains.
Caffeine was shown to be ergogenic for muscular endurance in two meta-analyses reporting effect sizes ranging from 0.28 to 0.38 (percent change range: 6 to 7%) [Citation158, Citation218]. However, others have shown that it enhances strength but not muscular endurance [Citation219, Citation220], and when studies have examined multiple strength-muscular endurance tasks, there were benefits across the board [Citation67, Citation221], none at all [Citation98, Citation222], or even impairments in muscular endurance with caffeine use [Citation222, Citation223]. Ingesting caffeine prior to a muscular endurance task is likely to delay muscular fatigue, but these effects are not consistent among all studies.
Three meta-analyses explored the acute effects of caffeine on strength, and all reported ergogenic effects [Citation158, Citation224, Citation225]. However, the effects in these meta-analyses were small, ranging from 0.16 to 0.20 (percent change: 2 to 7%). Such small improvements in muscular strength likely have the greatest practical meaningfulness for athletes competing in strength-based sports, such as powerlifting and weightlifting (athletes which already seem to be among the highest users of caffeine [Citation110]).
Power output is often measured during a single-bout sprinting task using the Wingate test, which generally consists of ‘all-out’ cycling for 30 s performed at specific external loads (e.g., 7.5% of body mass). Power output is also assessed during different protocols of intermittent-sprinting and repeated-sprints often with the Wingate cycling test as well as assessments during running [Citation226] or swimming repeated sprints [Citation212].
The data for repeated sprint and power performance using Wingate data has been mixed. In an older study, 10 male team-sport athletes performed 18, 4-s sprints with 2-min active recovery [Citation227]. Here, caffeine ingestion (6 mg/kg) enhanced mean power output and sprint work by 7 and 8.5%, respectively [Citation227]. A more recent study examining the effects of acute caffeine ingestion on upper and lower body Wingate performance in 22 males did not report significant findings when measuring lower body mean and peak power using the Wingate test [Citation228]. An older study by Greer et al. [Citation229] also failed to report caffeine benefits on power output during a 30-s high-intensity cycling bout using the Wingate test. One meta-analysis reported that caffeine ingestion enhances mean and peak power during the Wingate test [Citation230], although the effect sizes of 0.18 (+ 3%) and 0.27 (+ 4%), respectively are modest. In contrast, another meta-analysis that examined the effects of caffeine on muscle power as assessed with the Wingate test for three of the studies, and repeated sprints for a maximum of 10-s for the fourth, did not report benefits from ingestion of caffeine [Citation231]. An average caffeine dose of 6.5 mg/kg of body mass was used across the four studies with no improvements in muscle power under caffeine conditions (effect size = 0.17, p = 0.36) compared to placebo trials, although the data collected spanned only 5 years [Citation231]. A study by Lee et al. [Citation232] reported that caffeine ingestion enhanced sprint performance involving a 90-s rest interval (i.e., intermittent-sprinting) but did not benefit repeated-sprints with a 20-s rest interval. This might suggest that the rest interval between sprints may modulate the ergogenic effects of caffeine. Indeed, a recent meta-analysis that focused on the effects of caffeine on repeated-sprint performance reported that total work, best sprint, and last sprint performance was not affected by caffeine ingestion [Citation226].
Several studies have also shown substantial variability in outcomes. For example, one study [Citation63] found that only 13 of 20 cyclists improved their performance with ~ 3–4 mg/kg of caffeine, while the remaining participants either worsened or did not alter their performance. Similarly, Woolf et al. [Citation233] found that 5 mg/kg of caffeine improved overall peak power performance on the Wingate Test in 18 elite or professional athletes. However, 4 (28%) of the participants did not improve their performance with caffeine. Average power, minimum power, and power drop were not significantly different between treatments, but 72% of the participants obtained a greater peak power during the caffeine trial than during the placebo trial. There was also no overall improvement in average power or fatigue index, despite 13 (72%), and 9 (50%) of the participants, respectively, improving their performance. In summary, caffeine ingestion may be beneficial to enhance single and intermittent-sprint performance, while caffeine’s effects on repeated-sprint performance are inconsistent and require further research to draw stronger conclusions on the topic.
Ballistic movements (such as throws and jumps) are characterized by high motor unit firing rates, brief contraction times, and high rates of force development [Citation234]. Many studies have explored the effects of caffeine on jumping performance [Citation225, Citation235]. The body of evidence has indicated that caffeine supplementation increases vertical jump height during single and repeated jumps; however, the magnitude of these effects is rather modest, with effect sizes ranging from 0.17 to 0.22 (2 to 4%) [Citation225, Citation235]. Besides jumping, several studies have explored the effects of caffeine on throwing performance. These studies reported that: (a) caffeine ingestion enhanced maximal shot put throwing distance in a group of 9 nine inter-collegiate track and field athletes [Citation65]; and (b) caffeine ingestion at a dose of 6 mg/kg of body mass administered 60 min pre-exercise increased maximal medicine ball throwing distance [Citation236]. Overall, the current body of evidence indicates that caffeine supplementation may be useful for acute improvements in ballistic exercise performance in the form of jumps and throws. However, more research is needed to explore the effects of caffeine on different throwing exercise tests, as this has been investigated only in a few studies.
Generally, the primary sports-related goal of strength and power-oriented resistance training programs is to move the force-velocity curve to the right, indicating an ability of the athlete to lift greater loads at higher velocities [Citation237]. Several studies have explored the effects of caffeine on movement velocity and power in resistance exercise using measurement tools such as linear position transducers [Citation238]. These studies generally report that caffeine ingestion provides ergogenic effects of moderate to large magnitudes, with similar effects noted for both mean and peak velocity, and in upper and lower-body exercises [Citation67, Citation221, Citation239]. Even though this area merits further research to fill gaps in the literature, the initial evidence supports caffeine as an effective ergogenic aid for enhancing velocity and power in resistance exercise.
Caffeine and sport-specific performance
Even though caffeine ingestion may enhance performance in the laboratory, there has been a paucity of evidence to support that these improvements transfer directly to sport-specific performance. To address this issue, several studies have also explored the effects of caffeine on sport-specific exercise tasks using sport simulation matches. Many studies conducted among athletes competing in team and individual sports, report that caffeine may enhance performance in a variety of sport tasks. However, there are also several studies that report no effects as outlined below:
Basketball – increased jump height, but only in those with the AA version of the CYP1A2 gene [Citation240], increased number of free throws attempted and free throws made, increased number of total and offensive rebounds [Citation241], but did not improve sprint time [Citation240], nor dribbling speed [Citation242]
Soccer – increased total distance covered during the game, increased passing accuracy, and jumping height [Citation94, Citation243, Citation244], but the consumption of a caffeinated energy drink did not enhance performance in the “T test” in female soccer players [Citation245], nor during match play in young football players [Citation246]
Volleyball – increased number of successful volleyball actions and decreased the number of imprecise actions [Citation247, Citation248], although caffeine did not improve physical performance in multiple sport-specific tests in professional females [Citation249], nor performance in volleyball competition [Citation250]
Football - did not improve performance for anaerobic exercise tests used at the NFL Combine [Citation251]
Rugby – increased the number of body impacts, running pace, and muscle power during jumping [Citation252, Citation253], but did not impact agility [Citation254]
Field hockey – increased high-intensity running and sprinting [Citation255], and may offset decrements in skilled performance associated with fatigue [Citation256]
Ice-hockey - has limited impact on sport-specific skill performance and RPE, but may enhance physicality during scrimmage [Citation257]
Combat sports – increased number of offensive actions and increased the number of throws [Citation258]
Cross-country skiing – reduced time to complete a set distance [Citation259] and improved time to task failure [Citation211]
In summary, although reviews of the literature show that caffeine ingestion is, on average, ergogenic for a wide range of sport-specific tasks, its use might not be appropriate for every athlete. Specifically, the use of caffeine needs to be balanced with the associated side-effects and therefore experimentation is required in order to determine the individual response before assessing whether the benefits outweigh the costs for the athlete. Athletes should gauge their physical response to caffeine during sport practice and competition in addition to monitoring mood state and potentially disrupted sleep patterns.
Interindividual variation in response to caffeine
There is a lack of research examining potential interindividual differences in strength or anaerobic power-type exercise, but this is not the case for endurance exercise. In the myriad of studies examining caffeine on endurance performance, the benefits of caffeine do not appear to be influenced by sex, age, VO2 max, type of sport, or the (equivalent) dose of caffeine [Citation13, Citation195, Citation260]. Nevertheless, there appears to be substantial interindividual variability in response to caffeine under exercise conditions, which may be attributed to several factors outlined below.
Genetics
Genetic variants affect the way we absorb, metabolize, and utilize and excrete nutrients, and gene-diet interactions that affect metabolic pathways relevant to health and performance are now widely recognized [Citation261]. In the field of nutrigenomics, caffeine is the most widely researched compound with several randomized controlled trials investigating the modifying effects of genetic variation on exercise performance [Citation75, Citation208, Citation262, Citation263].
Numerous studies have investigated the effect of supplemental caffeine on exercise performance, but there is considerable inter-individual variability in the magnitude of these effects [Citation11, Citation13, Citation44] or in the lack of an effect [Citation264, Citation265], when compared to placebo. Due to infrequent reporting of individual data it is difficult to determine the extent to which variation in responses may be occurring. The performance of some individuals is often in stark contrast to the average findings reported, which may conclude beneficial, detrimental, or no effect of caffeine on performance. For example, Roelands et al. [Citation265] reported no ergogenic effect of caffeine in a study involving trained male cyclists. The authors concluded that inter-individual differences in response to caffeine might be responsible for the lack of overall performance improvement, as 50% of subjects improved while 50% worsened, in the caffeine compared to the placebo trial.
These inter-individual differences appear to be partly due to variations in genes such as CYP1A2 and possibly ADORA2A, which are associated with caffeine metabolism, sensitivity and response [Citation213]. Over 95% of caffeine is metabolized by the CYP1A2 enzyme, which is encoded by the CYP1A2 gene and is involved in the demethylation of caffeine into the primary metabolites paraxanthine, theophylline and theobromine [Citation127]. The -163A > C (rs762551) single nucleotide polymorphism (SNP) has been shown to alter CYP1A2 enzyme inducibility and activity [Citation132, Citation134], and has been used to categorize individuals as ‘fast’ or ‘slow’ metabolizers of caffeine. In the general population, individuals with the AC or CC genotype (slow metabolizers) have an elevated risk of myocardial infarction [Citation266], hypertension and elevated blood pressure [Citation267, Citation268], and pre-diabetes [Citation269], with increasing caffeinated coffee consumption, whereas those with the AA genotype show no such risk. Additionally, regular physical activity appears to attenuate the increase in blood pressure induced by caffeine ingestion, but only in individuals with the AA genotype [Citation268].
The largest caffeine, genetics and exercise study to date [Citation208] examined the effects of caffeine and CYP1A2 genotype on 10-km cycling time trial performance in competitive male athletes (both endurance and power sports) after ingestion of placebo, and caffeine doses of 2 mg (low dose) or 4 mg (moderate dose) per kg body mass. There was a 3% improvement in cycling time with the moderate dose in all subjects, which is consistent with previous studies using similar doses [Citation13, Citation206]. However, there was a significant caffeine-gene interaction; improvements in performance were seen at both caffeine doses, but only in those with the AA genotype who are ‘fast metabolizers’ of caffeine. In that group, a 6.8% improvement in cycling time was observed at 4 mg/kg, which is greater than the 2–4% mean improvement seen in several other studies using cycling time trials and similar doses [Citation13, Citation201, Citation206, Citation207, Citation270–Citation272]. Among those with the CC genotype (i.e., “slow metabolizers”), 4 mg/kg caffeine impaired performance by 13.7%, whereas no difference was observed between the placebo and 2 mg/kg caffeine trials. In those with the AC genotype there was no effect of either dose [Citation208]. The findings are consistent with a previous study [Citation263] that observed a caffeine-gene interaction indicating improved time trial cycling performance following caffeine consumption only in those with the AA genotype.
In contrast, previous studies either did not observe any impact of the CYP1A2 gene in caffeine-exercise studies [Citation273, Citation274], or reported benefits only in slow metabolizers [Citation75]. There are several reasons that may explain discrepancies in study outcomes. These include smaller samples sizes with few and/or no subjects in one genotype [Citation75, Citation273, Citation274], as well as shorter distances or different types of performance test (power versus endurance) [Citation75] compared to the aforementioned trials, which reported improved endurance after caffeine ingestion in those with the CYP1A2 AA genotype [Citation208, Citation263]. The effects of genotype on performance might be the most prominent during training or competition of longer duration or an accumulation of fatigue (aerobic or muscular endurance) [Citation149], where caffeine appears to provide its greatest benefits, and where the adverse effects to slow metabolizers are more likely to manifest [Citation195, Citation260]. Indeed, in a study of performance in elite basketball players [Citation240], only in those with the AA genotype caffeine improved repeated jumps which requires maintaining velocity at take-off repeatedly as an athlete fatigues throughout a game (muscular endurance) - even though there was no caffeine-genotype interaction effect for this outcome. However, caffeine similarly improved performance in those with the both AA and C-genotypes during a simulated basketball game [Citation240]. In a cross-over design of 30 resistance-trained men, caffeine ingestion resulted in a higher number of repetitions in repeated sets of three different exercises, and for total repetitions in all resistance exercises combined, which resulted in a greater volume of work compared to placebo conditions, but only in those with the CYP1A2 AA genotype [Citation262]. Although more research is warranted, there is a growing body of evidence to support the role of CYP1A2 in modifying the effects of caffeine ingestion on aerobic or muscular endurance-type exercise, which helps to determine which athletes are most likely to benefit from caffeine.
The ADORA2A gene is another genetic modifier of the effects of caffeine on performance. The adenosine A2A receptor, encoded by the ADORA2A gene, has been shown to regulate myocardial oxygen demand and increase coronary circulation by vasodilation [Citation275, Citation276]. The A2A receptor is also expressed in the brain, where it has significant roles in the regulation of glutamate and dopamine release, with associated effects on insomnia and pain [Citation277, Citation278]. The antagonism of adenosine receptors after caffeine ingestion is modified by the ADORA2A gene, which may allow greater improvements in dopamine transmission and lead to norepinephrine and epinephrine release due to increased neuronal firing [Citation168] in some genotypes versus others. Dopamine has been associated with motivation and effort in exercising individuals, and this may be the mechanism by which differences in response to caffeine are manifested [Citation141, Citation168, Citation169].
Currently, only one small pilot study has examined the effect of the ADORA2A gene (rs5751876) on the ergogenic effects of caffeine under exercise conditions [Citation279]. Twelve female subjects underwent a double-blinded, crossover trial comprising two 10-min cycling time trials following caffeine ingestion or placebo. Caffeine benefitted all six subjects with the TT genotype, but only one of the six C allele carriers. Further studies are needed to confirm these preliminary findings and should include a large enough sample to distinguish any effects between the different C allele carriers (i.e. CT vs. CC genotypes) and potential effects related to sex.
The ADORA2A rs5751876 genotype has also been implicated, by both objective and subjective measures, in various parameters of sleep quality after caffeine ingestion in several studies [Citation280–Citation283]. Adenosine promotes sleep by binding to its receptors in the brain, mainly A1 and A2A receptors, and caffeine exerts an antagonist effect, blocking the receptor and reversing the effects of adenosine and promoting wakefulness [Citation280]. This action, as well as the potency of caffeine to restore performance (cognitive or physical) in ecological situations, such as highway-driving during the night [Citation284], supports the notion that the adenosine neuromodulator/receptor system is significantly involved in sleep–wake regulation. This action of caffeine may also serve athletes well under conditions of jetlag, and irregular or early training or competition schedules. Psychomotor speed relies on the ability to respond, rapidly and reliably, to randomly occurring stimuli which is a critical component of, and characteristic of, most sports [Citation285]. Genetic variation in ADORA2A has been shown to be a relevant determinant of psychomotor vigilance in the rested and sleep-deprived state and modulates individual responses to caffeine after sleep deprivation [Citation282]. Those with the CC genotype of ADORA2A rs5751876 consistently performed on a higher level on the sustained vigilant attention task than T-allele -carriers; however, this was tested in ADORA2A haplotypes that included combinations of 8 SNPs. This work provides the basis for future genetic studies of sleep using individual ADORA2A SNPs.
As mentioned, the ADORA2A genotype has also been implicated in sleep quality and increases in sleep disturbance [Citation283]. Consistent with the “adenosine hypothesis” of sleep where the accumulation of adenosine in the brain increases sleep propensity, caffeine prolongs time to fall asleep, decreases the deep stages of non-rapid-eye movement (nonREM) sleep, reduces sleep efficiency, and alters the waking and sleep electroencephalogram (EEG) frequencies, which reliably reflect the need for sleep [Citation286–Citation288]. Increased beta activity in nonREM sleep may characterize individuals with insomnia when compared with healthy good sleepers [Citation289]. A functional relationship between the ADORA2A genotype and the effect of caffeine on EEG beta activity in nonREM sleep has previously been reported [Citation281], where the highest rise was in individuals with the CC genotype, approximately half in the CT genotype, whereas no change was present in the TT genotype. Consistent with this observation, the same study found individuals with the CC and TC genotypes appeared to confer greater sensitivity towards caffeine-induced sleep disturbance compared to the TT genotype [Citation281]. This suggests that a common variant in ADORA2A contributes to subjective and objective responses to caffeine on sleep.
Caffeine, genetics and anxiety
In elite athletes, 50% face mental health issues sometime during their career [Citation290]. Given that anxiety may be normalized in elite sports even at clinical levels, factors that contribute to anxiety should be mitigated whenever possible. Anxiety may be caused by stress-related disorders (burnout), poor quality sleep patterns (often related to caffeine intakes) and possibly as a response to caffeine ingestion due to genetic variation, even at low levels [Citation109].
As previously mentioned, caffeine blocks adenosine receptors, resulting in the stimulating effects of caffeine [Citation213]. A common variation in the ADORA2A (adenosine A2A receptor) gene contributes to the differences in subjective feelings of anxiety after caffeine ingestion [Citation291, Citation292], especially in those who are habitually low caffeine consumers [Citation293]. This may be particularly relevant to athletes who possess the TT variant of rs5751876 in the ADORA2A gene. These individuals are likely to be more sensitive to the stimulating effects of caffeine and experience greater increases in feelings of anxiety after caffeine intake than do individuals with either the CT or CC variant [Citation291–Citation293].
Sport psychologists commonly work with athletes to help them overcome anxiety about performance during competitions. Anxiety before or during athletic competitions can interfere not only in performance, but also in increased injury risk [Citation294]. Athletes who are more prone to performance anxiety may exacerbate their risk for feelings of anxiety depending on their caffeine use and which variant of the ADORA2A gene they possess. Monitoring the actions of caffeine in those individuals who are susceptible, may alleviate some of the related feelings of anxiety with caffeine use. Given that anxiety may disrupt concentration and sleep and negatively impact social interactions, athletes with higher risks and prevalence for anxiety, may want to limit or avoid caffeine consumption (if caffeine is a known trigger) during times where they are feeling anxious or stressed, such as at sporting competitions or social gatherings or other work and school events.
The importance of both sleep and caffeine (as an ergogenic aid) to athletes highlights the importance of optimizing rest and recovery through a better understanding of which athletes may be at greater risk of adverse effects of caffeine on mood and sleep quality, possibly due to genetic variation. This information will allow athletes and coaching staff to make informed decisions on when and if to use caffeine when proximity to sleep is a factor. These considerations will also be in conjunction with the possibility that an athlete will benefit from caffeine in endurance-based exercise as determined in part, by their CYP1A2 genotype, albeit with a clear need for future research.
Habitual caffeine intake
The quantification of habitual caffeine intake is difficult, which is problematic for studies aiming to compare performance outcomes following caffeine ingestion in habitual versus non-habitual caffeine users. This concern is highlighted by reports showing large variability in the caffeine content of commonly consumed beverages, e.g. ~ 8- to 9-fold differences in caffeine content have been reported in coffee beverages purchased from similar retail shops [Citation295] and in pre-workout supplements [Citation296]. Self-reported intakes may therefore be unreliable. Newly discovered biomarkers of coffee consumption may be more useful for quantifying intakes in the future, but currently, these are not widely available [Citation297]. Different protocols for the length of the caffeine abstinence period preceding data collection is also a relevant factor in determining variability in performance outcomes. For example, in shorter caffeine abstinence periods e.g., 12–48 h, reversal of caffeine withdrawal effects by acute caffeine supplementation may have positive effects on performance, i.e. alleviating the negative symptoms of withdrawal, which in itself may improve performance [Citation298]. These effects may be more pronounced in those genetically predisposed to severe withdrawal effects [Citation299]. However, in one study 3 mg/kg caffeine significantly improved exercise performance in trained cyclists (n = 12), irrespective of whether a 4-day withdrawal period was imposed on habitual caffeine users [Citation300]. Another study also reported increased endurance in habitual caffeine users (n = 6) regardless of a 0, 2- or 4-day abstinence period. The authors concluded that improved performance under caffeine conditions at 6 mg/kg is not related to prior caffeine habituation in recreational athletes [Citation301]. Although genes have been associated with habitual caffeine intake using GWAS research [Citation302, Citation303], it is important to highlight that these associations are not directly applicable to determining differences in performance outcomes in response to acute caffeine doses for regular or habitual caffeine users versus non-habitual users. The “caffeine habits” of individuals are more likely related to their personal experience with adverse effects such as feel jittery, experiencing tachycardia or insomnia. Furthermore, associations between genes and habitual caffeine intake do not elucidate potential mechanisms by which caffeine intake behaviors may influence subsequent performance following caffeine supplementation [Citation304, Citation305]. In animal model studies, regular consumption of caffeine has been associated with an upregulation of the number of adenosine receptors in the vascular and neural tissues of the brain [Citation306]. Although, this did not appear to modify the effects of caffeine in one study [Citation307], in another, chronic caffeine ingestion by mice caused a marked reduction in locomotor exploratory activity [Citation308]. Changes in adenosine receptor number or activity have not been studied in humans.
There does not appear to be a consistent difference in the performance effects of acute caffeine ingestion between habitual and non-habitual caffeine users, and study findings remain equivocal. In one study, habitual stimulation from caffeine resulted in a general dampening of the epinephrine response to both caffeine and exercise; however, there was no evidence that this impacted exercise performance [Citation309]. Another study [Citation310] examined the effect of 4 weeks of caffeine supplementation on endurance performance in 18 low-habitual caffeine consumers who were randomly assigned to ingest caffeine or placebo for 28 days. Four weeks of caffeine ingestion resulted in increased tolerance to acute caffeine supplementation in previously low habitual caffeine consumers, with the ergogenic effect of acute caffeine supplementation no longer apparent [Citation310]. These results are in contrast with a recent study in which 20 days of consecutive supplementation with caffeine maintained an ergogenic effect, even though the effect size attenuated over time [Citation311]. More recently, a double-blind, crossover, counterbalanced study was performed [Citation312], where 40 endurance-trained male cyclists were allocated into tertiles according to their daily caffeine intake: low (58 ± 29 mg), moderate (143 ± 25 mg), and high consumers (351 ± 139 mg). Participants completed three trials in which they performed simulated cycling time-trials under three conditions: caffeine (6 mg/kg), placebo, and no supplement (control). Caffeine ingestion improved performance as compared to placebo and control, with no influence of habitual caffeine intake. Additionally, no correlation was observed between habitual caffeine intake and absolute changes in a ~ 30 min cycling time-trial performance with caffeine [Citation312]. However, a limitation of this study is the short 24-h caffeine withdrawal period in all groups which may have resulted in performance improvements due to the reversal of caffeine withdrawal effects, rather than impact of acute-on-chronic caffeine administration and the effects of habituation to caffeine on exercise performance [Citation298, Citation313]. In addition, habitual caffeine intake was estimated using a food frequency questionnaire, which might be a limitation given the already mentioned variation of caffeine in coffee and different supplements.
There is wide variability in caffeine content of commonly consumed items, and as such, an objective measure (e.g., caffeine or metabolite levels) might be considered to reported caffeine intakes [Citation297, Citation313]. Based on these observations, the assumption that habitual and nonhabitual caffeine consumers will or will not respond differently to caffeine supplementation during exercise, requires further study.
Caffeine timing
The most common timing of caffeine supplementation is 60 min before exercise. This timing is used given that it is believed that 60 min post-ingestion, plasma levels of caffeine are at maximal values [Citation314]. However, caffeine appears to be most beneficial during times or in sports where there is an accumulation of fatigue, i.e., exercise over a longer continuous or intermittent duration [Citation64]. Therefore, ingestion of caffeine during exercise (mid/later stages) may be more beneficial than ingestion beforehand for some individuals depending upon the length of the event. A recent review [Citation195] reported that the effect size of caffeine benefits increase with the increasing duration of the time trial event, meaning that timing caffeine intake closer to a time of greater fatigue, i.e., later in the race, may be most beneficial. This supports the notion that endurance athletes (with longer races) may benefit most from caffeine for performance enhancement since they have the greatest likelihood of being fatigued. This also supports findings in other investigations that show ingesting caffeine at various time points including late in exercise may be most beneficial [Citation196].
For example, an early study [Citation196] aimed to understand whether or not there were benefits to a common practice among endurance athletes, such as those participating in marathons and triathlons, which is to drink flat cola toward the end of an event. When researchers investigated the ingestion of a low dose of caffeine toward the end of a race (e.g., in the form of flat cola) it was found to have comparable effects as ingesting higher doses, such as ~ 5 or 6 mg/kg, ingested ~ 60 min before the race. The study also demonstrated that the effect was due to the caffeine and not the carbohydrate, which may also aid performance as fuel stores become depleted [Citation196].
More recently, caffeine gum ingestion enhanced cycling performance when it was administered immediately prior to exercise, but not when administered 1 or 2 h beforehand. This may have been due to the faster absorption with caffeinated gum consumption, and due to the continued increase in plasma caffeine concentrations during the cycling time trial, when athletes may become fatigued (i.e. 30 + minutes into exercise), as the trials also included a 15 min steady-state cycling bout prior to the time trial [Citation60]. Similarly, in a lab setting, a study of athletes completing 120 min of steady-state cycling followed by a time trial under conditions of placebo and caffeine, found that the ingestion of both low and moderate doses of caffeine later in exercise were beneficial [Citation149]. However, there was significant interindividual variability, highlighting the need for athletes to experiment with their own strategies as far as dosing and timing are concerned.
The optimal timing of caffeine ingestion may depend on the source of caffeine. As stated earlier, some of the alternate sources of caffeine such as caffeine chewing gums may absorb more quickly than caffeine ingested in caffeine-containing capsules [Citation60]. Therefore, individuals interested in supplementing with caffeine should consider that timing of caffeine ingestion will likely be influenced by the source of caffeine.
Training status
Training status may mediate the magnitude of caffeine’s ergogenic effect, but studies have reported mixed results. Although a 2010 meta-analysis [Citation158] did not find differences (p = 0.08) in caffeine’s ability to enhance muscle endurance in untrained subjects versus trained subjects, these results were not derived from direct comparisons between trained and untrained subjects. Currently, only a few investigations [Citation96, Citation210, Citation315–Citation318] have included both trained and untrained subjects in their study design.
In a study of elite and occasional swimmers [Citation318], it was reported that 250 mg of supplemental caffeine was ergogenic only for competitive swimmers and not recreational swimmers. A limitation of this study is that the swimming exercise task differed between the trained and untrained participants. Specifically, the study utilized 1600-m swimming for the trained swimmers and 400-m for the untrained swimmers, which is a likely explanation for these findings. However, some have also postulated that this is because athletes perform more reliably on a given task than nonathletes, and increased test-retest reliability might prevent type II errors [Citation319]. In contrast to the above evidence regarding the importance of training status, other research has shown that training status does not moderate the ergogenic effects of caffeine on exercise performance. One study [Citation210] showed similar performance improvements (1.0 and 1.1%) in 15 well-trained and 15 recreational runners performing an outdoor 5 km time trial after 5 mg/kg caffeine intake compared to the placebo trial. Similarly, Astorino et al. [Citation96] found that overall, acute caffeine intake improved 10 km time-trial performance in both endurance-trained athletes and active men, with no differences seen between groups. Likewise, an investigation concluded that there was no ergogenic effect of caffeine at a dose of 5 mg/kg on time to exhaustion in either endurance trained or untrained men [Citation315].
More recently, a small study by Boyett et al. [Citation317] investigated the interactions of 6 mg/kg caffeine on training status and time of day in 20 male subjects. Subjects completed four experimental trials consisting of a 3-km cycling time trial performed in randomized order for each combination of time of day (morning and evening) and treatment. They reported that both untrained and trained subjects improved performance with caffeine supplementation in the morning; however, only the untrained subjects improved when tested in the evening. Although there were some limitations to this study, these observations indicate that trained athletes are more likely to experience ergogenic effects from caffeine in the morning, while untrained individuals appear to receive larger gains from caffeine in the evening than their trained counterparts. This may further complicate the training status data with a possible temporal effect [Citation317]. The concentration of adenosine receptors (the primary target of caffeine) do appear to be higher in trained compared to untrained individuals, but this has only been reported in animal studies [Citation320]. Boyett et al. [Citation317] speculated that the higher concentration of adenosine receptors may increase tissue sensitivity to any given concentration of adenosine.
Although some studies comparing training status of subjects support the notion [Citation318] that training influences response to caffeine during exercise, most do not [Citation96, Citation210, Citation315] and this was also the finding in a subsequent meta-analysis [Citation158]. It is possible that the only difference between trained and untrained individuals is that trained individuals likely have the mental discipline to exercise long or hard enough to benefit more from the caffeine stimulus, which might provide an explanation for why in some studies, trained individuals respond better to caffeine [Citation314]. Currently, it seems that trained and untrained individuals experience similar improvements in performance following caffeine ingestion; however, more research in this area is warranted.
Caffeine and sleep
The impacts of caffeine on sleep and behavior after sleep deprivation are widely reported [Citation321]. Sleep is recognized as an essential component of physiological and psychological recovery from, and preparation for, high-intensity training in athletes [Citation322, Citation323]. Chronic mild to moderate sleep deprivation in athletes, potentially attributed to caffeine intakes, may result in negative or altered impacts on glucose metabolism, neuroendocrine function, appetite, food intake and protein synthesis, as well as attention, learning and memory [Citation323]. These factors can all influence an athlete’s nutritional, metabolic, and endocrine status negatively and hence potentially affect energy levels, muscle repair, immunity, body composition, memory and learning and result in diminished athletic performance [Citation324, Citation325].
Objective sleep measures using actigraphy or carried out in laboratory conditions with EEG have shown that caffeine negatively impacts several aspects of sleep quality such as: sleep latency (time to fall asleep), WASO (wake time after sleep onset), sleep efficiency and duration [Citation321]. Studies in athletes have also shown adverse effects in sleep quality and markers for exercise recovery after a variety of doses of caffeine ingestion [Citation326–Citation328]. Although caffeine is associated with sleep disturbances, caffeine has also been shown to improve vigilance and reaction time and improved physical performance after sleep deprivation [Citation282, Citation329–Citation332]. This may be beneficial for athletes or those in the military who are traveling or involved in multiday operations, or sporting events and must perform at the highest level under sleep-deprived conditions [Citation192, Citation194, Citation330, Citation332].
Even though caffeine ingestion may hinder sleep quality, the time of day at which caffeine is ingested will likely determine the incidence of these negative effects. For example, in one study that included a sample size of 13 participants, ingestion of caffeine in the morning hours negatively affected sleep only in one participant [Citation333]. However, ingestion of caffeine in the late afternoon (18:00 h) resulted in insomnia effects among 6 participants. These results are likely explained by the half-life of caffeine, which is generally around 4 to 6 h (even though it varies between individuals). Unfortunately, athletes and those in the military are unlikely to be able to make adjustments to the timing of training, competition and military exercises or the ability to be combat ready. However, to help avoid negative effects on sleep, athletes may consider using caffeine earlier in the day whenever possible. Pronounced individual differences have also been reported where functional genetic polymorphisms have been implicated in contributing to individual sensitivity to sleep disruption [Citation280, Citation281] and caffeine impacts after sleep deprivation [Citation282] as discussed in the Interindividual variation in response to caffeine: Genetics section of this paper.
Side-effects associated with caffeine intake
As with any supplement, caffeine ingestion is also associated with certain side-effects. Some of the most commonly reported side-effects in the literature are tachycardia and heart palpitations, anxiety [Citation281, Citation291], headaches, as well as insomnia and hindered sleep quality [Citation239, Citation326]. For example, in one study, caffeine ingestion before an evening Super Rugby game resulted in a delay in time at sleep onset and a reduction in sleep duration on the night of the game [Citation327]. Caffeine ingestion is also associated with increased anxiety; therefore, its ingestion before competitions in athletes may exacerbate feelings of anxiety and negatively impact overall performance (see caffeine and anxiety section). Increased jitters/anxiety/arousal associated with caffeine ingestion also needs to be considered within the specific demands of each sport, and even the position within a given sport. For example, athletes competing in sports that heavily rely on the skill component (e.g., tennis players, biathlon shooting) would likely not benefit from caffeine-induced jitters and arousal. However, athletes in sports that depend more on physical capabilities, such as strength and endurance (e.g., football lineman), might actually benefit from increased jitters and arousal before games. These aspects are less explored in research but certainly warrant consideration in the practical context to optimize the response to caffeine supplementation. The primary determinant in the incidence and severity of side-effects associated with caffeine ingestion is the dose used. Side-effects with caffeine seem to increase linearly with the dose ingested [Citation239]. Therefore, they can be minimized—but likely not fully eliminated—by using smaller doses, as such doses are also found to be ergogenic and produce substantially fewer side-effects [Citation112]. In summary, an individual case-by-case basis approach is warranted when it comes to caffeine supplementation, as its potential to enhance performance (benefit) needs to be balanced with the side-effects (risk).
Caffeine and cognitive performance
In addition to exercise performance, caffeine has also been studied for its contribution to athletes of all types (including Special Forces operators in the military) who are routinely required to undergo periods of sustained cognitive function and vigilance due to their job requirements (Table ). A 2016 review [Citation344] concluded that caffeine in doses from 32 to 300 mg (for a 75 kg individual) enhanced specific aspects of cognitive performance, such as attention, vigilance, and reaction time. Spriet [Citation112] also concluded that lower doses of caffeine (approximately 200 mg) improved cognitive processes associated with exercise including vigilance, alertness, and mood. Hogervorst et al. [Citation82] studied 24 well-trained cyclists that were randomized to 3 groups: (1) consumed a bar containing 45 g of carbohydrate and 100 mg of caffeine; (2) an isocaloric non-caffeine performance bar; or, (3) a placebo beverage (non-caloric flavored water) immediately before performing a 2.5-h ride followed by a time to exhaustion trial. They found that caffeine in a carbohydrate-containing performance bar significantly improved both endurance performance and complex cognitive ability during and after exercise [Citation82]. Antonio et al. [Citation345] assessed the effects of an energy drink on psychomotor vigilance in a small cohort of 20 exercise-trained men and women. The acute consumption of 300 mg of caffeine in a commercially available energy drink produced a significant improvement in psychomotor vigilance mean reaction time in these subjects compared to the placebo trial. This matches a 2001 IOM report [Citation346] that the effects of caffeine supplementation include increased attention and vigilance, complex reaction time, and problem-solving and reasoning.
One confounding factor on cognitive effects of caffeine is the role of sleep. Special Forces military athletes conduct operations where sleep deprivation is common. A series of different experiments [Citation42, Citation329, Citation330, Citation332, Citation334, Citation335, Citation346, Citation347] have examined the effects of caffeine in real-life military conditions. In three of the studies [Citation329, Citation330, Citation334], soldiers performed a series of tasks such as a 4 or 6.3 km run and a marksmanship test, which is a task that requires fine motor coordination and steadiness, observation/reconnaissance, and requires long periods of no movement coupled with alertness and psychomotor vigilance over several days, where opportunities for sleep became more infrequent. Caffeine was provided at doses ranging from 600 to 800 mg in the form of chewing gum, owing to its practicality, i.e., rapid absorption and portability [Citation58]. The investigators found that vigilance was either maintained or enhanced under the caffeine conditions (vs. placebo), in addition to improvements in run times and obstacle course completion [Citation329, Citation330, Citation334]. Similarly, Lieberman et al. [Citation42] examined the effects of caffeine on cognitive performance during sleep deprivation in U. S. Navy Seals. During this investigation, there were multiple doses of caffeine ingested, 100 mg, 200 mg, or 300 mg, in capsule form. Once again, results were also significant for the assessments related to vigilance and reaction time in both the 200 and 300 mg caffeine intervention, suggesting smaller successive doses of caffeine are more beneficial than large boluses, for improving focus and vigilance.
The positive effects of caffeine on cognitive function were further supported by work from Kamimori et al. [Citation332] where 20 special forces operators were randomly assigned to receive four 200-mg doses of caffeine or placebo during a period of low sleep over three successive days. The caffeine intervention maintained psychomotor speed, improved event detection, increased the number of correct responses to stimuli, and increased response speed during logical reasoning tests. Under similar conditions of sleep deprivation, Tikuisis et al. [Citation335] demonstrated that the cognitive component of a shooting task (i.e., target detection) benefited from caffeine. These studies [Citation42, Citation329, Citation330, Citation332, Citation334, Citation335, Citation346, Citation347] demonstrate the effects of caffeine on vigilance and reaction time in a sleep deprived state, in a distinct and highly trained population, usually with repeated ‘lower’ doses, ~ 200 mg of caffeine ingestion. When subjects are not sleep deprived, the effects of caffeine on cognition appear to be less effective. For example, Share et al. [Citation336] did not show any difference in shooting accuracy, reaction time, or target tracking times among the three intervention trials using 2 escalating doses of caffeine at 2 mg/kg and 4 mg/kg.
In addition to the ability of caffeine to counteract the stress from sleep deprivation, it may also play a role in combatting other stressors. Gillingham et al. [Citation339] showed that in 12 reservists who ingested 5 mg/kg body mass of caffeine or placebo 1 h pre- and post-strenuous exercise, that caffeine ingestion mediated stress from sleep deprivation cited above. However, these benefits were not observed during more complex operations [Citation339]. With a different stressor (a simulated firefight), no cognitive effect was seen with a caffeine dose of 400 mg [Citation340]. Crowe et al. [Citation341] examined the effects of caffeine (6 mg/kg dose) on cognitive parameters (visual reaction time and number recall tests) via two maximal 60-s bouts of cycling over three conditions (caffeine, placebo, control). Again, no cognitive benefit was observed.
Other studies [Citation244, Citation338, Citation342, Citation343] support the effects of caffeine on the cognitive aspects of sport performance, even though with some mixed results [Citation348, Citation349]. Foskett et al. [Citation244] determined that a moderate dose (6 mg/kg) of caffeine enhanced the fine motor skills in soccer players as measured by improved ball passing accuracy and control. This was supported by Stuart et al. [Citation342] who examined the effects of the same dose of caffeine (6 mg/kg) and found a 10% improvement in ball-passing accuracy. Equivocal results were reported for distance covered, agility, and accuracy in a review of 19 studies where caffeine ingestion before exercise was between 3 and 6 mg/kg [Citation348]. Data on reactive agility time is split, with one study demonstrating a benefit [Citation343] and another one [Citation349] did not showing any benefit, despite using the same dose of caffeine (6 mg/kg). Finally, caffeine (5 mg/kg) was shown to enhance cognitive performance after an upper-body Wingate test, which may be beneficial in sports or occupational activities where there is a need for anaerobic performance concurrent with decision making (e.g. firefighting, military related tasks, wheelchair basketball) [Citation338].
The exact mechanism of how caffeine enhances cognition in relation to exercise is not fully elucidated and appears to work through both peripheral and central neural effects [Citation350]. In a study by Lieberman et al. [Citation42], 8 h after caffeine administration, caffeine continued to enhance motor learning and short-term memory via performance of repeated acquisition. Repeated acquisition are behavioral tests in which subjects are required to learn new response sequences within each experimental session [Citation351]. The researchers [Citation42] speculated that caffeine exerted its effects from an increased ability to sustain concentration, as opposed to an actual effect on working memory. Other data [Citation352] were in agreement that caffeine reduced reaction times via an effect on perceptual-attentional processes (not motor processes). This is in direct contrast to earlier work that cited primarily a motor effect [Citation353]. Another study with a sugar free energy drink showed similar improvements in reaction time in the caffeinated arm; however, they attributed it to parallel changes in cortical excitability at rest, prior, and after a non-fatiguing muscle contraction [Citation354]. The exact cognitive mechanism(s) of caffeine have yet to be elucidated.
Based on some of the research cited above, it appears that caffeine is an effective ergogenic aid for individuals either involved in special force military units or who may routinely undergo stress including, but not limited to, extended periods of sleep deprivation. Caffeine in these conditions has been shown to enhance cognitive parameters of concentration and alertness. It has been shown that caffeine may also benefit sport performance via enhanced passing accuracy and agility. However, not all of the research is in agreement. It is unlikely that caffeine would be more effective than actually sleeping, i.e. you cannot ‘outcaffeinate’ poor sleep.
Environmental influences on response to caffeine
Physical activity and exercise in extreme environments are of great interest as major sporting events (e.g. Tour de France, Leadville 100, Badwater Ultramarathon) are commonly held in extreme environmental conditions. Events that take place in the heat or at high altitudes bring additional physiological challenges (i.e., cardiovascular strain, thermoregulation, diuresis) for athletes, which may be potentially compounded if caffeine is consumed prior to and/or during training or competition in such environments [Citation355]. Nonetheless, caffeine is widely used by athletes as an ergogenic aid when exercising or performing in extreme environmental situations. The current understanding of caffeine’s impact on exercise performance is based largely on the findings of analyses conducted in controlled, temperate environments, whereas data collected on the ergogenic effect of caffeine consumption by individuals performing in the heat or at altitude are limited and have resulted in inconsistent findings.
Heat
The ability to perform prolonged exercise is impaired in hot and/or humid environments [Citation355, Citation356]. The use of caffeine in conjunction with exercise in the heat has been proposed to increase the risk for various heat-related illnesses with particular concerns regarding caffeine’s effect on body temperature and hydration status [Citation357]. Ely et al. [Citation358] concluded that caffeine dosages as high as 9 mg/kg did not substantially alter body heat balance during endurance exercise performance at 40 °C. Further, a recent study demonstrated that while caffeine ingestion increased blood lactate and heart rate during exercise in the heat (42 °C and 20% relative humidity), endurance capacity and thermoregulation were unaffected in both male and female participants [Citation359]. Although caffeine may induce mild fluid loss, the majority of research has confirmed that caffeine consumption does not significantly impair hydration status, exacerbate dehydration, or jeopardize thermoregulation (i.e., body temperature regulation) when exercising in the heat [Citation360, Citation361].
Several trials have observed no benefit of acute caffeine ingestion on cycling and running performance in the heat (Table ) [Citation265, Citation362, Citation364]. However, Ganio and colleagues [Citation365] found caffeine (2 dosages of 3 mg/kg) to be similarly ergogenic under both cool (12 °C) and warm (33 °C) environmental conditions. Likewise, others [Citation366] have reported a non-significant, yet notable, improvement in cycling time trial performance in the heat (35 °C and 25% relative humidity) after caffeine consumption (3 mg/kg) compared with placebo ingestion. While caffeine’s effect on performance in the heat remains somewhat unclear to date, positive support exists for dosages between 3 and 6 mg/kg. Further, there does not appear to be sufficient evidence to interdict the use of caffeine by individuals who exercise in heat if consumed in dosages of 9 mg/kg or less.
Altitude
It is well established that caffeine improves performance and perceived exertion during exercise at sea level [Citation260, Citation314, Citation368, Citation369]. Despite positive outcomes at sea level, minimal data exist on the ergogenic effects or side effects of caffeine in conditions of hypoxia, likely due to accessibility of this environment or the prohibitive costs of artificial methods. To date, only four investigations (Table ) have examined the effects of caffeine on exercise performance under hypoxic conditions [Citation211, Citation370–Citation372]. In an initial study by Berglund and colleagues [Citation370], caffeine (6 mg/kg) significantly improved 21 km time trial performance 2300 m above sea level in 14 well-trained cross-country skiers. Likewise, [Citation371] positive outcomes were reported after caffeine (4 mg/kg) ingestion on endurance performance in acute hypoxic conditions of 4300 m above sea level. Specifically, significant improvements in time to exhaustion in eight young adults cycling at 80% of their altitude specific VO2max was reported. More recently, 13 skiers were examined at an altitude of 2000 m above sea level and it was reported that caffeine (4.5 mg/kg) significantly improved time to exhaustion while double poling during cross-country skiing at 90% of altitude-specific VO2max [Citation211]. In a more recent double-blind, randomized, counterbalanced cross-over investigation [Citation372], seven adult males significantly improved time to exhaustion by 12% following consumption of 4 mg/kg caffeine. Overall, results to date appear to support the beneficial effects of caffeine supplementation that may partly reduce the negative effects of hypoxia on the perception of effort and endurance performance [Citation211, Citation370–Citation372].
Alternate caffeine sources
Sources other than commonly consumed coffee and caffeine tablets have garnered interest, including caffeinated chewing gum, mouth rinses, aerosols, inspired powders, energy bars, energy gels and chews, among others. While the pharmacokinetics [Citation18, Citation373–Citation376] and effects of caffeine on performance when consumed in a traditional manner, such as coffee [Citation47, Citation49, Citation55, Citation153, Citation368, Citation377, Citation378] or as a caffeine capsule with fluid [Citation55, Citation203, Citation379, Citation380] are well understood, curiosity in alternate forms of delivery (as outlined in pharmacokinetics section) have emerged due to interest in the speed of delivery [Citation81]. A recent review by Wickham and Spriet [Citation5] provides an overview of the literature pertaining to caffeine use in exercise, in alternate forms. Therefore, here we only briefly summarize the current research.
Caffeinated chewing gum
Several investigations have suggested that delivering caffeine in chewing gum form may speed the rate of caffeine delivery to the blood via absorption through the extremely vascular buccal cavity [Citation58, Citation381]. Therefore, caffeine via chewing gum may be absorbed via two passageways: the buccal mucosa in the oral cavity and/or gut absorption due to the swallowing of caffeine-containing saliva [Citation58, Citation381, Citation382]. Kamimori and colleagues [Citation58] compared the rate of absorption and relative caffeine bioavailability from caffeinated chewing gum and caffeine in capsule form. The results suggest that the rate of drug absorption from the gum formulation was significantly faster. In the groups ingesting 100 and 200 mg, both gum and capsule formulations provide near comparable plasma caffeine concentrations to the systemic circulation. These findings suggest that there may be an earlier onset of pharmacological effects from caffeine delivered through the gum formulation. Further, while no data exist to date, it has been suggested that increasing absorption via the buccal cavity may be preferential over oral delivery if consumed closer to or during exercise, as splanchnic blood flow is often reduced [Citation383], potentially slowing the rate of caffeine absorption.
To date, five studies [Citation59–Citation63] have examined the potential ergogenic impact of caffeinated chewing gum on aerobic performance, commonly administered in multiple sticks (Table ). To note, all studies have been conducted using cycling interventions, with the majority conducted in well-trained cyclists. Results from these investigations suggest that caffeinated chewing gum delivered in total dosages ranging 200–300 mg, closer to initiation of exercise or during a prolonged endurance event may be most beneficial, specifically for individuals with a higher training status. However, more research is needed, especially in physically active and recreationally training individuals.
Four studies [Citation64, Citation66, Citation68, Citation384] have examined the effect of caffeinated chewing gum on more anaerobic type activities (Table ). Specifically, Paton et al. [Citation64] administered 3 mg/kg caffeinated gum to male cyclists during repeat sprint cycling, resulting in greater attenuation of fatigue, compared to a placebo. The reduced fatigue in the caffeine trials equated to a 5.4% performance enhancement in power during sprints, in favor of caffeinated gum. A study [Citation384] assessing 100 mg caffeinated chewing gum on shot-put performance during an early morning trial resulted in overall improvements in shot-put distance thrown compared to a placebo. Caffeinated gum consumption also positively influenced performance in two out of three soccer-specific (Yo-Yo Intermittent Recovery Test and CMJ) tests used in the assessment of performance in soccer players [Citation66]. A recent study also explored the effects of 300 mg of caffeine provided in caffeine chewing gum and found that its consumption 10 min pre-exercise resulted in ergogenic effects on jumping performance, isokinetic peak torque, upper body movement velocity and whole-body power output during a rowing test [Citation68]. These results suggest that caffeine chewing gums may provide ergogenic effects across a wide range of exercise tasks. To date, only Bellar et al. [Citation384] has examined chewing gum with caffeine on cognitive function, specifically reporting improved alertness as assessed by a psychomotor vigilance test. Future studies may consider comparing the effects of caffeine in chewing gums to caffeine ingested in capsules.
Caffeine mouth rinsing
Caffeine mouth rinsing (CMR; 5–20 s in duration) may have the potential to enhance exercise performance due to the activation of sensorimotor brain cortices [Citation79]. Specifically, the mouth contains bitter taste sensory receptors that are sensitive to caffeine [Citation385]. It has been proposed that activation of these bitter taste receptors may activate neural pathways associated with information processing and reward within the brain [Citation385–Citation387]. Physiologically, caffeinated mouth rinsing may also reduce gastrointestinal distress potential that may be caused when ingesting caffeine sources [Citation388, Citation389].
Few investigations on aerobic [Citation69, Citation74–Citation76, Citation390] and anaerobic [Citation72, Citation73, Citation78] changes in performance, as well as cognitive function [Citation70, Citation71] and performance [Citation77], following CMR have been conducted to date (Table ). One study [Citation390] demonstrated ergogenic benefits of CMR on aerobic performance, reporting significant increases in distance covered during a 30-min arm crank time trial performance. Likewise, in a separate study [Citation74], a 5 s CMR (containing 32 mg of caffeine dissolved in 125 ml water) improved 30 min cycling performance, without concurrent increases in ratings of perceived exertion or heart rate. With regard to anaerobic trials, other researchers [Citation72] have also observed improved performance, where recreationally active males significantly improved their mean power output during repeated 6-s sprints after rinsing with a 1.2% caffeine solution. A follow-up study [Citation73] reported that recreationally active males who were deemed ‘glycogen depleted’ increased mean and peak power during the 3rd sprint of repeat cycling, as well as decreased perception of pain during the 4th and 5th sprints following a 10 s rinse of a 2% caffeine rinse. While CMR has demonstrated positive outcomes for cyclists, another study [Citation78] in recreationally resistance-trained males did not report any significant differences in the total weight lifted by following a 1.2% caffeine rinse. CMR appears to be ergogenic in cycling to include both longer, lower-intensity and shorter high-intensity protocols. The findings on the topic are equivocal likely because caffeine provided in this source does not increase caffeine plasma concentration and increases in plasma concentration are likely needed to experience an ergogenic effect of caffeine [Citation69]. Details of these studies, as well as additional studies may be found in Table .
Caffeinated nasal sprays and inspired powders
The use of caffeinated nasal sprays and inspired powders are also of interest. Three mechanisms of action have been hypothesized for caffeinated nasal sprays. Firstly, the nasal mucosa is permeable, making the nasal cavity a potential route for local and systemic substance delivery; particularly for caffeine, a small molecular compound [Citation11, Citation12, Citation30, Citation31]. Secondly, and similar to CMR, bitter taste receptors are located in the nasal cavity. The use of a nasal spray may allow for the upregulation of brain activity associated with reward and information processing [Citation391]. Thirdly, but often questioned due to its unknown time-course of action, caffeine could potentially be transported directly from the nasal cavity to the CNS, specifically the cerebrospinal fluid and brain by intracellular axonal transport through two specific neural pathways, the olfactory and trigeminal [Citation392, Citation393].
In two separate trials [Citation79, Citation80], the effects of caffeinated nasal sprays containing 15 mg of caffeine per mL were examined. No significant improvements were reported in either anaerobic and aerobic performance outcome measures despite the increased activity of cingulate, insular, and sensory-motor cortices [Citation79]. Laizure et al. [Citation81] compared the bioavailability and plasma concentrations of 100 mg caffeine delivered via an inspired powder (AeroShot) and an oral solution. Both were found to have similar bioavailability and comparable plasma concentrations with no differences in heart rate or blood pressure (Table ).
Caffeinated gels
While caffeinated gels are frequently consumed by runners, cyclists and triathletes, plasma caffeine concentration studies have yet to be conducted and only three experimental trials have been reported. Cooper et al. [Citation83] and Scott et al. [Citation84] examined the effects of carbohydrate-caffeinated gels, which both included 100 mg caffeine dosages alongside 25 g and 21.6 carbohydrate, respectively. In the study by Cooper et al. the consumption of caffeinated gels 60 min pre-exercise did not enhance intermittent sprint performance. In contrast, Scott et al. utilized a shorter time period from consumption to the start of the exercise (i.e., 10 min pre-exercise) and found significant improvements in 2000-m rowing performance after consumption of caffeinated gels. Another recent study utilized caffeine gels and found that 300 mg of caffeine, provided 10 min pre-exercise increased vertical jump performance, strength, and power in a sample of 17 resistance-trained men [Citation67]. These results tentatively suggest that timing of consumption is important when it comes to caffeinated gels with ergogenic effects found when consuming caffeine gels 10 min but not 60 min before exercise. However, these ideas are based on results from independent studies and therefore, future studies may consider exploring the optimal timing of caffeine gel ingestion in the same group of participants. More details on these studies may be found in (Table ).
Caffeinated bars
Similar to caffeinated gels, no studies measured plasma caffeine concentration following caffeinated bar consumption; however, absorption and delivery likely mimic that of coffee or caffeine anhydrous capsule consumption. While caffeinated bars are commonly found in the market, research on caffeinated bars is scarce. To date, only one study [Citation82] (Table ) has examined the effects of a caffeine bar on exercise performance. Specifically, participants that consumed a carbohydrate-bar containing 100 mg of caffeine significantly improved their time to exhaustion during cycling compared to a carbohydrate bar and placebo with no differences found in ratings of perceived exertion, average heart rate and relative exercise intensity. Furthermore, cyclists significantly performed better on complex information processing tests following the time trial to exhaustion after caffeine bar consumption when compared to the carbohydrate only trial. As there is not much data to draw from, future work on this source of caffeine is needed.
Caffeine in combination with other ingredients
Caffeine and Creatine
A review by Trexler and Smith-Ryan comprehensively details research on caffeine and creatine co-ingestion [Citation32]. With evidence to support the ergogenic benefits of both creatine and caffeine supplementation on human performance—via independent mechanisms—interest in concurrent ingestion is of great relevance for many athletes and exercising individuals [Citation32]. While creatine and caffeine exist as independent supplements, a myriad of multi-ingredient supplements (e.g., pre-workouts) containing both caffeine and creatine are available. It has been reported that the often-positive ergogenic effect of acute caffeine ingestion prior to exercise is unaffected by creatine when a prior creatine loading protocol had been completed by participants [Citation394, Citation395]. However, there is some ambiguity with regard to the co-ingestion of caffeine during a creatine-loading phase (e.g., co-ingestion of coffee and creatine) [Citation396–Citation399]. Studies available to date suggest that high-dose chronic caffeine (> 9 mg/kg) and creatine co-ingestion should be employed cautiously, as counteracting mechanisms on Ca2+ clearance and release, and muscle relaxation time have been hypothesized [Citation396, Citation398]. While favorable data exist on muscular performance outcomes and adaptations in individuals utilizing multi-ingredient supplements (e.g., pre-workouts), these results may be confounded by other ingredients (e.g., beta-alanine, citrulline malate, amino acids) in the supplement [Citation34, Citation95, Citation400, Citation401]. Until future investigations are available, it may be prudent to consume caffeine and creatine separately, or avoid high caffeine intakes when utilizing creatine for muscular benefits [Citation402].
Caffeine and carbohydrate
To date, investigations examining the co-ingestion of carbohydrate and caffeine compared with carbohydrate alone prior to and/or during exercise have produced inconsistent results [Citation196, Citation264, Citation403–Citation405]. This is likely due to the heterogeneity of experimental protocols that have been implemented and examined. Nonetheless, a 2011 systematic review and meta-analysis of 21 investigations [Citation406] concluded the co-ingestion of carbohydrate and caffeine significantly improved endurance performance when compared to carbohydrate alone. However, it should be noted that the magnitude of the performance benefit that caffeine provides is less when added to carbohydrate (i.e., caffeine + carbohydrate vs. carbohydrate) than when isolated caffeine ingestion is compared to placebo [Citation404]. Since the 2011 publication [Citation406], results remain inconclusive, as investigations related to sport-type performance measures [Citation83, Citation250, Citation407–Citation411], as well as endurance performance [Citation84, Citation367, Citation412] continue to be published. Overall, to date it appears caffeine alone, or in conjunction with carbohydrate is a superior choice for improving performance, when compared to carbohydrate supplementation alone.
While the majority of training or performing individuals would choose to supplement with caffeine prior to exercise or during competition, interest in caffeine’s effect on muscle glycogen repletion during the post-exercise period has garnered interest. Few studies to date have investigated the effect of post-exercise caffeine consumption on glucose metabolism [Citation413, Citation414]. While the delivery of exogenous carbohydrate can increase muscle glycogen alone, Pedersen et al. [Citation413] report faster glycogen repletion rates in athletes who co-ingested caffeine (8 mg/kg body mass) and carbohydrate (4 g/kg body mass), compared to carbohydrate alone (4 g/kg body mass). In addition, it has been demonstrated that co-ingestion of caffeine with carbohydrate after exercise improved subsequent high-intensity interval-running capacity compared with ingestion of carbohydrate alone. This effect may be due to a high rate of post-exercise muscle glycogen resynthesis [Citation415]. The data to date indicate that caffeine may potentiate glycogen resynthesis when high dosages of caffeine (~ 8 mg/kg body mass) are consumed during the recovery phase of exercise; though, when adequate carbohydrate is provided post-exercise, caffeine may not provide any glycogen-resynthesizing benefit [Citation414]. Practically, caffeine ingestion in close proximity to sleep, coupled with the necessity to speed glycogen resynthesis, should be taken into consideration, as caffeine before bed may cause sleep disturbances.
Caffeine within brewed coffee
The genus of coffee is Coffea, with the two most common species Coffea arabica (arabica coffee) and Coffea canephora (robusta coffee) used for global coffee production. While coffee is commonly ingested by exercising individuals as part of their habitual diet, coffee is also commonly consumed pre-exercise to improve energy levels, mood, and exercise performance [Citation11, Citation40]. Indeed, a recent review on coffee and endurance performance, reported that that coffee providing between 3 and 8.1 m/kg of caffeine may benefit endurance performance, such as time trial performance or time to exhaustion [Citation11]. To date, research has only examined coffee’s effects on cycling and running exercise performance. Specifically, Higgins et al. [Citation11] highlight that significant improvements over control conditions were found with doses up to 8.1 mg/kg; however, performance benefits were similar to 3 mg/kg servings. Since the release of the Higgins et al. review, three additional studies have been published, examining the effects of coffee on exercise performance. Specifically, Niemen et al. [Citation416] assessed the impact of high chlorogenic acid coffee on performance. Cyclists were asked to consume coffee or placebo (300 ml/day) for 2 weeks prior to completing a 50-km time-trial. Chlorogenic acid coffee provided 1066 mg chlorogenic acid plus 474 mg caffeine, while the placebo consisted of 187 mg chlorogenic acid and 33 mg caffeine. Fifty-km cycling time performance and power did not differ between trials. Participant’s heart rate and ventilation were higher with chlorogenic acid coffee during the time-trial, potentially provoking the non-significant performance outcomes. Regarding resistance exercise performance, only two studies [Citation55, Citation56] have been conducted to date. One study [Citation56] reported that coffee and caffeine anhydrous did not improve strength outcomes more than placebo supplementation. On the other hand, Richardson et al. [Citation55] suggested that coffee consumption may improve lower-body muscular endurance performance similarly as isolated caffeine ingestion. The results between studies differ likely because it is challenging to standardize the dose of caffeine in coffee as differences in coffee type and brewing method may alter caffeine content [Citation417]. Even though coffee may enhance performance, due to the difficulty of standardizing caffeine content most sport dietitians and nutritionists use anhydrous caffeine with their athletes due to the difficulty of standardizing caffeine content.
Caffeine containing energy drinks and pre-workouts
Consumption of energy drinks has become more common in the last decade, and several studies have examined the effectiveness of energy drinks as ergogenic aids (Table ). Souza and colleagues [Citation418] completed a systematic review and meta-analysis of published studies that examined energy drink intake and physical performance. Studies including endurance exercise, muscular strength and endurance, sprinting and jumping, as well as sport-type activities were reviewed. Dosages of caffeine ranged from 40 to 325 mg among the studies, with the majority of drinks also containing taurine. While it was concluded that energy drink consumption increased performance in the aforementioned performance activities, the ergogenic effect was not solely attributed to the amount of caffeine administered, but improved also as a result of taurine content (dosages ranged 71 to 3105 mg) [Citation418]. This is similar to data from another study, reporting that Red Bull (500 ml serving; 160 mg of caffeine/2.25 mg/kg), also containing taurine, glucose, glucuronolactone, and B vitamins, improved 5-km run performance in recreationally athletes [Citation91]. It has been suggested that the additional taurine to caffeine containing energy drinks or pre-workout supplements, as well as the addition of other ergogenic supplements such as beta-alanine, B-vitamins, and citrulline, may potentiate the effectiveness of caffeine containing beverages on athletic performance endeavors [Citation419]. However, other suggest that the ergogenic benefits of caffeine containing energy drinks is likely attributed to the caffeine content of the beverage [Citation420]. For a thorough review of energy drinks, consider Campbell et al. [Citation419]. Table provides a review of research related to energy drinks and pre-workout supplements.
Summary
Caffeine in its many forms is a ubiquitous substance frequently used in military, athletic and fitness populations which acutely enhance many aspects of exercise performance in most, but not all studies.
Supplementation with caffeine has been shown to acutely enhance many aspects of exercise, including prolonged aerobic-type activities and brief duration, high-intensity exercise. Caffeine is ergogenic when consumed in doses of 3–6 mg/kg body mass. The most commonly used timing of caffeine supplementation is 60 min pre-exercise. The optimal timing of caffeine ingestion likely depends on the source of caffeine. Caffeine’s effects seem to be similar in both trained and untrained individuals. Studies that present individual participant data commonly report substantial variation in caffeine ingestion responses. Inter-individual differences may be associated with habitual caffeine intake, genetic variations, and supplementation protocols in a given study. Caffeine may be ergogenic for cognitive function, including attention and vigilance. Caffeine may improve cognitive and physical performance in some individuals under conditions of sleep deprivation. Caffeine at the recommended doses does not appear significantly influence hydration, and the use of caffeine in conjunction with exercise in the heat and at altitude is also well supported. Alternative sources of caffeine, such as caffeinated chewing gum, mouth rinses, and energy gels, have also been shown to improve performance. Energy drinks and pre-workouts containing caffeine have been demonstrated to enhance both anaerobic and aerobic performance. Individuals should also be aware of the side-effects associated with caffeine ingestion, such as sleep disturbance and anxiety, which are often linearly dose-dependent.
Authors’ contributions
N.S.G conceived and outlined the sections to be included in the manuscript, provided the initial draft and oversaw all critical edits and revisions. T.A.V authored multiple sections and participated in final editing and revisions. M.T.N, J. G and B.J.S provided expertise and contributed to the one or more sections of the manuscript. N.D.M.J, S.M.A, J. A, J.R.S, E.T.T, A.E.S-R, E.R.G, and D.S.K provided valuable comments and suggested minor edits to the manuscript. B.I.C. oversaw the writing process, and all authors reviewed and gave final approval of the version to be published.
Ethics approval and consent to participate
This paper was reviewed by the International Society of Sports Nutrition Research Committee and represents the official position of the Society.
Consent for publication
Not applicable.
Competing interests
N.S.G consults for and is on the scientific advisory board of Nutrigenomix, a genetic testing company. T.A.V is on the scientific advisory board for Dymatize Nutrition, a manufacturer of sports supplements; has received research grants related to dietary supplements. B.J.S is on the scientific advisory board for Dymatize Nutrition, a manufacturer of sports supplements. S.M.A has received grants to evaluate the effects of dietary supplements, including caffeine and caffeine-derivatives, serves or has served on scientific advisory boards for sport nutrition companies, has been a paid consultant for a coffee company, and holds patents for an ingredient used in a performance coffee product. J. A is the CEO of the ISSN. The ISSN has received grants from sports supplement companies that sell caffeine-based products. E.T.T earns income as a writer and practitioner within the fitness industry. A.E.S-R has received research grants related to dietary supplements and is a science advisor to Ladder Sport. D.S.K declares that in part, he works for a contract research company that conducts research and human clinical trials for industries including dietary supplements, medical foods, beverages, foods, pharmaceuticals and medical devices. He also sits on the Scientific Advisory Board for Dymatize Nutrition (BellRing Brands) B.I.C is on the scientific advisory board for Dymatize Nutrition, a manufacturer of sports supplements. M.T.N, J. G, N.D.M.J, J.R.S, E.R.G, report no competing interests or conflicts of interest.
Funding
No funding was received for the research, writing or publication of this manuscript.
Availability of data and materials
Not applicable.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- BaileyRLSaldanhaLGDwyerJTEstimating caffeine intake from energy drinks and dietary supplements in the United StatesNutr Rev201472 Suppl 1 9 13 25293539 4658518 https://doi.org/10.1111/nure.12138
- FulgoniVL3rdKeastDRLiebermanHRTrends in intake and sources of caffeine in the diets of US adults: 2001-2010Am J Clin Nutr2015101 5 1081 1087 1:CAS:528:DC%2BC2MXptlCgsL0%3D 25832334 https://doi.org/10.3945/ajcn.113.080077
- RybakMESternbergMRPaoCIAhluwaliaNPfeifferCMUrine excretion of caffeine and select caffeine metabolites is common in the U.S. population and associated with caffeine intakeJ Nutr2015145 4 766 774 1:CAS:528:DC%2BC2MXmsFGmsL0%3D 25833779 5724768 https://doi.org/10.3945/jn.114.205476
- US Department of Agriculture ARS What we eat in America, data tables, 2009–20102012 Washington (DC) US Department of Agriculture
- WickhamKASprietLLAdministration of caffeine in alternate formsSports Med201848 Suppl 1 79 91 29368182 5790855 https://doi.org/10.1007/s40279-017-0848-2
- DoepkerCLiebermanHRSmithAPPeckJDEl-SohemyAWelshBTCaffeine: friend or foe?Annu Rev Food Sci Technol20167 117 137 1:CAS:528:DC%2BC28XnsFGmug%3D%3D 26735800 https://doi.org/10.1146/annurev-food-041715-033243
- WikoffDWelshBTHendersonRBrorbyGPBrittJMyersE et al Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and childrenFood Chem Toxicol2017109 Pt 1 585 648 1:CAS:528:DC%2BC2sXmsFeksb8%3D 28438661 https://doi.org/10.1016/j.fct.2017.04.002
- JiangWWuYJiangXCoffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studiesGynecol Oncol2013129 3 620 629 1:CAS:528:DC%2BC3sXls1Shurc%3D 23535278 https://doi.org/10.1016/j.ygyno.2013.03.014
- JiangXZhangDJiangWCoffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studiesEur J Nutr201453 1 25 38 1:CAS:528:DC%2BC2cXhvFCqsLw%3D 24150256 https://doi.org/10.1007/s00394-013-0603-x
- CaldeiraDMartinsCAlvesLBPereiraHFerreiraJJCostaJCaffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studiesHeart.201399 19 1383 1389 24009307 https://doi.org/10.1136/heartjnl-2013-303950
- HigginsSStraightCRLewisRDThe effects of preexercise caffeinated coffee ingestion on endurance performance: an evidence-based reviewInt J Sport Nutr Exerc Metab201626 3 221 239 1:CAS:528:DC%2BC1cXnt1KktL0%3D 26568580 https://doi.org/10.1123/ijsnem.2015-0147
- DohertyMSmithPMEffects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysisScand J Med Sci Sports200515 2 69 78 1:STN:280:DC%2BD2M7ktlyhtg%3D%3D 15773860 https://doi.org/10.1111/j.1600-0838.2005.00445.x
- GanioMSKlauJFCasaDJArmstrongLEMareshCMEffect of caffeine on sport-specific endurance performance: a systematic reviewJ Strength Cond Res200923 1 315 324 19077738 https://doi.org/10.1519/JSC.0b013e31818b979a
- AsmussenEBojeOThe effect of alcohol and some drugs on the capacity for workActa Physiol Scand194815 2 109 113 1:CAS:528:DyaH1cXisFyqtg%3D%3D 18863134 https://doi.org/10.1111/j.1748-1716.1948.tb00488.x
- LjungqvistABrief history of anti-dopingMed Sport Sci201762 1 10 28571021 https://doi.org/10.1159/000460680
- RiversWHWebberHNThe action of caffeine on the capacity for muscular workJ Physiol190736 1 33 47 1:STN:280:DC%2BD2s%2FntFOmsg%3D%3D 16992882 1533733 https://doi.org/10.1113/jphysiol.1907.sp001215
- HaldiJWynnWAction of drugs on efficiency of swimmersRestor Q194617 96 101 1:STN:280:DyaH28%2FgsF2lug%3D%3D
- CostillDLDalskyGPFinkWJEffects of caffeine ingestion on metabolism and exercise performanceMed Sci Sports197810 3 155 158 1:CAS:528:DyaE1MXms1ygsQ%3D%3D 723503
- IvyJLCostillDLFinkWJLowerRWInfluence of caffeine and carbohydrate feedings on endurance performanceMed Sci Sports197911 1 6 11 1:CAS:528:DyaE1MXkvVemsrk%3D 481158 https://doi.org/10.2165/00007256-199111010-00002
- PerkinsRWilliamsMHEffect of caffeine upon maximal muscular endurance of femalesMed Sci Sports19757 3 221 224 1:STN:280:DyaE28%2FpvFyqtg%3D%3D 1207435
- DurrantKLKnown and hidden sources of caffeine in drug, food, and natural productsJ Am Pharm Assoc (Wash)200242 4 625 637 https://doi.org/10.1331/108658002763029607
- MitchellDCKnightCAHockenberryJTeplanskyRHartmanTJBeverage caffeine intakes in the U.SFood Chem Toxicol201463 136 142 1:CAS:528:DC%2BC3sXhvFylurnP 24189158 https://doi.org/10.1016/j.fct.2013.10.042
- RamarethinamSRajalakshmiNCaffeine in tea plants [Camellia sinensis (L) O. Kuntze]: in situ lowering by Bacillus licheniformis (Weigmann) ChesterIndian J Exp Biol200442 6 575 580 1:CAS:528:DC%2BD2cXhtVakt7jJ 15260108
- AshiharaHSuzukiTDistribution and biosynthesis of caffeine in plantsFront Biosci20049 1864 1876 1:CAS:528:DC%2BD2cXlsFamsLs%3D 14977593 https://doi.org/10.2741/1367
- MisakoKKouichiMCaffeine synthase and related methyltransferases in plantsFront Biosci20049 1833 1842 14977590 https://doi.org/10.2741/1364
- MazzaferaPCatabolism of caffeine in plants and microorganismsFront Biosci20049 1348 1359 1:CAS:528:DC%2BD2cXltl2msr0%3D 14977550 https://doi.org/10.2741/1339
- Al-ShaarLVercammenKLuCRichardsonSTamezMMatteiJHealth effects and public health concerns of energy drink consumption in the United States: a mini-reviewFront Public Health20175 225 28913331 5583516 https://doi.org/10.3389/fpubh.2017.00225
- UtterJDennySTeevaleTSheridanJEnergy drink consumption among New Zealand adolescents: associations with mental health, health risk behaviours and body sizeJ Paediatr Child Health.201754 3 279 283 28905482 https://doi.org/10.1111/jpc.13708
- MarmorsteinNRInteractions between energy drink consumption and sleep problems: associations with alcohol use among young adolescentsJ Caffeine Res20177 3 111 116 1:CAS:528:DC%2BC2sXhsVKgsr7E 28875062 5582584 https://doi.org/10.1089/jcr.2017.0007
- De SanctisVSolimanNSolimanATElsedfyHDi MaioSEl KholyM et al Caffeinated energy drink consumption among adolescents and potential health consequences associated with their use: a significant public health hazardActa Biomed201788 2 222 231 28845841 6166148
- ArriaAMCaldeiraKMBugbeeBAVincentKBO'GradyKETrajectories of energy drink consumption and subsequent drug use during young adulthoodDrug Alcohol Depend2017179 424 432 28797805 5657439 https://doi.org/10.1016/j.drugalcdep.2017.06.008
- TrexlerETSmith-RyanAECreatine and caffeine: considerations for concurrent supplementationInt J Sport Nutr Exerc Metab201525 6 607 623 26219105 https://doi.org/10.1123/ijsnem.2014-0193
- KendallKLMoonJRFairmanCMSpradleyBDTaiCYFalconePH et al Ingesting a preworkout supplement containing caffeine, creatine, beta-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active menNutr Res201434 5 442 449 1:CAS:528:DC%2BC2cXotFynur4%3D 24916558 https://doi.org/10.1016/j.nutres.2014.04.003
- SmithAEFukudaDHKendallKLStoutJRThe effects of a pre-workout supplement containing caffeine, creatine, and amino acids during three weeks of high-intensity exercise on aerobic and anaerobic performanceJ Int Soc Sports Nutr20107 10 20156347 2854104 https://doi.org/10.1186/1550-2783-7-10 1:CAS:528:DC%2BC3cXksFensbk%3D
- TarnopolskyMACaffeine and creatine use in sportAnn Nutr Metab201057 Suppl 2 1 8 1:CAS:528:DC%2BC3MXisVaiurc%3D 21346331 https://doi.org/10.1159/000322696
- FukudaDHSmithAEKendallKLStoutJRThe possible combinatory effects of acute consumption of caffeine, creatine, and amino acids on the improvement of anaerobic running performance in humansNutr Res201030 9 607 614 1:CAS:528:DC%2BC3cXht1OgsbrN 20934602 https://doi.org/10.1016/j.nutres.2010.09.004
- CameronMCamicCLDobersteinSEricksonJLJagimARThe acute effects of a multi-ingredient pre-workout supplement on resting energy expenditure and exercise performance in recreationally active femalesJ Int Soc Sports Nutr201815 1 29311763 5755346 https://doi.org/10.1186/s12970-017-0206-7
- BergstromHCByrdMTWallaceBJClaseyJLExamination of a multi-ingredient pre-workout supplement on total volume of resistance exercise andsubsequent strength and power performanceJ Strength Cond Res.201832 6 1479 1490 29401192 https://doi.org/10.1519/JSC.0000000000002480
- TinsleyGMHammMAHurtadoAKCrossAGPinedaJGMartinAY et al Effects of two pre-workout supplements on concentric and eccentric force production during lower body resistance exercise in males and females: a counterbalanced, double-blind, placebo-controlled trialJ Int Soc Sports Nutr201714 46 29209154 5704438 https://doi.org/10.1186/s12970-017-0203-x 1:CAS:528:DC%2BC1MXis1Kgtb0%3D
- GoldsteinERZiegenfussTKalmanDKreiderRCampbellBWilbornC et al International society of sports nutrition position stand: caffeine and performanceJ Int Soc Sports Nutr20107 1 5 20205813 2824625 https://doi.org/10.1186/1550-2783-7-5 1:CAS:528:DC%2BC3cXksFensb8%3D
- PasmanWJvan BaakMAJeukendrupAEde HaanAThe effect of different dosages of caffeine on endurance performance timeInt J Sports Med199516 4 225 230 1:CAS:528:DyaK2MXnt12guro%3D 7657415 https://doi.org/10.1055/s-2007-972996
- LiebermanHRTharionWJShukitt-HaleBSpeckmanKLTulleyREffects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-LandPsychopharmacology2002164 3 250 261 1:CAS:528:DC%2BD38XosFWgtrY%3D 12424548 https://doi.org/10.1007/s00213-002-1217-9
- GrahamTESprietLLMetabolic, catecholamine, and exercise performance responses to various doses of caffeineJ Appl Physiol (1985)199578 3 867 874 1:CAS:528:DyaK2MXlt1eit7Y%3D https://doi.org/10.1152/jappl.1995.78.3.867
- GrahamTESprietLLPerformance and metabolic responses to a high caffeine dose during prolonged exerciseJ Appl Physiol (1985)199171 6 2292 2298 1:CAS:528:DyaK38XhsVelu78%3D https://doi.org/10.1152/jappl.1991.71.6.2292
- SprietLLMacLeanDADyckDJHultmanECederbladGGrahamTECaffeine ingestion and muscle metabolism during prolonged exercise in humansAm J Phys1992262 6 Pt 1 E891 E898 1:CAS:528:DyaK38XltVCisLo%3D
- McNaughtonLRLovellRJSieglerJMidgleyAWMooreLBentleyDJThe effects of caffeine ingestion on time trial cycling performanceInt J Sports Physiol Perform20083 2 157 163 1:STN:280:DC%2BD1M7jt1OisQ%3D%3D 19208924 https://doi.org/10.1123/ijspp.3.2.157
- HodgsonABRandellRKJeukendrupAEThe metabolic and performance effects of caffeine compared to coffee during endurance exercisePLoS One20138 4 e59561 1:CAS:528:DC%2BC3sXmtFWrt78%3D 23573201 3616086 https://doi.org/10.1371/journal.pone.0059561
- McLellanTMBellDGThe impact of prior coffee consumption on the subsequent ergogenic effect of anhydrous caffeineInt J Sport Nutr Exerc Metab200414 6 698 708 15657474 https://doi.org/10.1123/ijsnem.14.6.698
- GrahamTEHibbertESathasivamPMetabolic and exercise endurance effects of coffee and caffeine ingestionJ Appl Physiol199885 3 883 889 1:CAS:528:DyaK1cXmtVKgtb8%3D 9729561 https://doi.org/10.1152/jappl.1998.85.3.883
- LaminaSMusaDIErgogenic effect of varied doses of coffee-caffeine on maximal aerobic power of young African subjectsAfr Health Sci20099 4 270 274 21503180 3074398
- TriceIHaymesEMEffects of caffeine ingestion on exercise-induced changes during high-intensity, intermittent exerciseInt J Sport Nutr19955 1 37 44 1:STN:280:DyaK2M3mvVCgtQ%3D%3D 7749424 https://doi.org/10.1123/ijsn.5.1.37
- WilesJDBirdSRHopkinsJRileyMEffect of caffeinated coffee on running speed, respiratory factors, blood lactate and perceived exertion during 1500-m treadmill runningBr J Sports Med199226 2 116 120 1:STN:280:DyaK38zitlehtQ%3D%3D 1623356 1478936 https://doi.org/10.1136/bjsm.26.2.116
- RodriguesLORussoAKSilvaACPicarroICSilvaFRZogaibPS et al Effects of caffeine on the rate of perceived exertionBraz J Med Biol Res199023 10 965 968 1:STN:280:DyaK3Mzhs1Clug%3D%3D 2101061
- ButtsNKCrowellDEffect of caffeine ingestion on cardiorespiratory endurance in men and womenRes Q Exerc Sport198556 5 301 305 https://doi.org/10.1080/02701367.1985.10605333
- RichardsonDLClarkeNDEffect of coffee and caffeine ingestion on resistance exercise performanceJ Strength Cond Res201630 10 2892 2900 26890974 https://doi.org/10.1519/JSC.0000000000001382
- TrexlerETSmith-RyanAERoelofsEJHirschKRMockMGEffects of coffee and caffeine anhydrous on strength and sprint performanceEur J Sport Sci201616 6 702 710 26394649 https://doi.org/10.1080/17461391.2015.1085097
- SellamiMSlimeniOPokrywkaAKuvacicG L DH MilicM et al Herbal medicine for sports: a reviewJ Int Soc Sports Nutr201815 14 29568244 5856322 https://doi.org/10.1186/s12970-018-0218-y 1:CAS:528:DC%2BC1MXjtVyrt70%3D
- KamimoriGHKaryekarCSOtterstetterRCoxDSBalkinTJBelenkyGL et al The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteersInt J Pharm2002234 1–2 159 167 1:CAS:528:DC%2BD38XhtFGqu7k%3D 11839447 https://doi.org/10.1016/S0378-5173(01)00958-9
- RyanEJKimCHMullerMDBellarDMBarkleyJEBlissMV et al Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustionJ Strength Cond Res201226 3 844 850 22293680 https://doi.org/10.1519/JSC.0b013e31822a5cd4
- RyanEJKimCHFickesEJWilliamsonMMullerMDBarkleyJE et al Caffeine gum and cycling performance: a timing studyJ Strength Cond Res201327 1 259 264 22476164 https://doi.org/10.1519/JSC.0b013e3182541d03
- LaneSCHawleyJADesbrowBJonesAMBlackwellJRRossML et al Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performanceAppl Physiol Nutr Metab201439 9 1050 1057 1:CAS:528:DC%2BC2cXjt1SrtLc%3D 25154895 https://doi.org/10.1139/apnm-2013-0336
- Oberlin-BrownKTSiegelRKildingAELaursenPBOral presence of carbohydrate and caffeine in chewing gum: independent and combined effects on endurance cycling performanceInt J Sports Physiol Perform201611 2 164 171 26114997 https://doi.org/10.1123/ijspp.2015-0133
- PatonCCostaVGuglielmoLEffects of caffeine chewing gum on race performance and physiology in male and female cyclistsJ Sports Sci201533 10 1076 1083 25517202 https://doi.org/10.1080/02640414.2014.984752
- PatonCDLoweTIrvineACaffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclistsEur J Appl Physiol2010110 6 1243 1250 1:CAS:528:DC%2BC3MXitlahsw%3D%3D 20737165 https://doi.org/10.1007/s00421-010-1620-6
- BellarDMKamimoriGJudgeLBarkleyJERyanEJMullerM et al Effects of low-dose caffeine supplementation on early morning performance in the standing shot put throwEur J Sport Sci201212 1 57 61 https://doi.org/10.1080/17461391.2010.536585
- Ranchordas MK, Pratt H, Parsons M, et al. Effect of caffeinated gum on a battery of rugby-specific tests in trained university-standard male rugby union players. J Int Soc Sports Nutr. 2019;16(17). https://doi.org/https://doi.org/10.1186/s12970-019-0286-7.
- Venier S, Grgic J, Mikulic P. Caffeinated gel ingestion enhances jump performance, muscle strength, and power in trained men. Nutrients. 2019;11(4).
- Venier S, Grgic J, Mikulic P. Acute enhancement of jump performance, muscle strength, and power in resistance-trained men after consumption of caffeinated chewing gum. Int J Sports Physiol Perform. 2019:1–7. https://doi.org/https://doi.org/10.1123/ijspp.2019-0098.
- DoeringTMFellJWLeverittMDDesbrowBShingCMThe effect of a caffeinated mouth-rinse on endurance cycling time-trial performanceInt J Sport Nutr Exerc Metab201424 1 90 97 23980239 https://doi.org/10.1123/ijsnem.2013-0103
- De PauwKRoelandsBKnaepenKPolflietMStiensJMeeusenREffects of caffeine and maltodextrin mouth rinsing on P300, brain imaging, and cognitive performanceJ Appl Physiol2015118 6 776 782 25614603 https://doi.org/10.1152/japplphysiol.01050.2014 1:CAS:528:DC%2BC2MXmtlShtb8%3D
- Pomportes L, Brisswalter J, Casini L, Hays A, Davranche K. Cognitive performance enhancement induced by caffeine, carbohydrate and guarana mouth rinsing during submaximal exercise. Nutrients. 2017;9(6).
- BeavenCMMaulderPPooleyAKilduffLCookCEffects of caffeine and carbohydrate mouth rinses on repeated sprint performanceAppl Physiol Nutr Metab201338 6 633 637 1:CAS:528:DC%2BC3sXnvFyqtLk%3D 23724880 https://doi.org/10.1139/apnm-2012-0333
- KizziJSumAHoustonFEHayesLDInfluence of a caffeine mouth rinse on sprint cycling following glycogen depletionEur J Sport Sci201616 8 1087 1094 27686403 https://doi.org/10.1080/17461391.2016.1165739
- BottomsLHurstHScrivenALynchFBoltonJVercoeLShoneZBarryGSinclairJThe effect of caffeine mouth rinse on self-paced cyclingperformanceCom Ex Phys.201410 4 239 45
- PatakyMWWomackCJSaundersMJGoffeJLD'LugosACEl-SohemyA et al Caffeine and 3-km cycling performance: effects of mouth rinsing, genotype, and time of dayScand J Med Sci Sports201626 6 613 619 1:STN:280:DC%2BC2MbisF2lsQ%3D%3D 26062916 https://doi.org/10.1111/sms.12501
- LesniakADavisSEMoirGL et al The effects of carbohydrate, caffeine and combined rinses on cycling performanceJ Sport Human Perform20164 1 10
- DolanPWitherbeeKEPetersonKMKerksickCMEffect of carbohydrate, caffeine, and carbohydrate + caffeine mouth rinsing on intermittent running performance in collegiate male lacrosse athletesJ Strength Cond Res201731 9 2473 2479 28825605 https://doi.org/10.1519/JSC.0000000000001819
- ClarkeNDKorniliosERichardsonDLCarbohydrate and caffeine mouth rinses do not affect maximum strength and muscular endurance performanceJ Strength Cond Res201529 10 2926 2931 25785703 https://doi.org/10.1519/JSC.0000000000000945
- De PauwKRoelandsBVan CutsemJMarusicUTorbeynsTMeeusenRElectro-physiological changes in the brain induced by caffeine or glucose nasal sprayPsychopharmacology2017234 1 53 62 27664111 https://doi.org/10.1007/s00213-016-4435-2 1:CAS:528:DC%2BC28XhsFKrtrbK
- De PauwKRoelandsBVan CutsemJDecroixLValenteATaeheeK et al Do glucose and caffeine nasal sprays influence exercise or cognitive performance?Int J Sports Physiol Perform201712 9 1186 1191 28182503 https://doi.org/10.1123/ijspp.2016-0598
- LaizureSCMeibohmBNelsonKChenFHuZYParkerRBComparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjectsBr J Clin Pharmacol201783 12 2687 2694 1:CAS:528:DC%2BC2sXhvV2ns7%2FJ 28758694 5698589 https://doi.org/10.1111/bcp.13389
- HogervorstEBandelowSSchmittJJentjensROliveiraMAllgroveJ et al Caffeine improves physical and cognitive performance during exhaustive exerciseMed Sci Sports Exerc200840 10 1841 1851 1:CAS:528:DC%2BD1cXhtFartLjK 18799996 https://doi.org/10.1249/MSS.0b013e31817bb8b7
- CooperRNaclerioFAllgroveJLarumbe-ZabalaEEffects of a carbohydrate and caffeine gel on intermittent sprint performance in recreationally trained malesEur J Sport Sci201414 4 353 361 23837918 https://doi.org/10.1080/17461391.2013.813972
- ScottATO'LearyTWalkerSOwenRImprovement of 2000-m rowing performance with caffeinated carbohydrate-gel ingestionInt J Sports Physiol Perform201510 4 464 468 25365032 https://doi.org/10.1123/ijspp.2014-0210
- AlfordCCoxHWescottRThe effects of red bull energy drink on human performance and moodAmino Acids.200121 2 139 50 1:CAS:528:DC%2BD3MXotFKjs7c%3D 11665810 https://doi.org/10.1007/s007260170021
- CandowDGKleisingerAKGrenierSDorschKDEffect of sugar-free Red Bull energy drink on high-intensity run time-to-exhaustion in young adultsJ Strength Cond Res.200923 4 1271 5 19528841 https://doi.org/10.1519/JSC.0b013e3181a026c2
- WalshALGonzalezAMRatamessNAKangJHoffmanJRImproved time to exhaustion following ingestion of the energy drink amino impactJ IntSoc Sports Nutr.20107 14 https://doi.org/10.1186/1550-2783-7-14 1:CAS:528:DC%2BC3cXlsVyrtrc%3D
- IvyJLKammerLDingZWangBBernardJRLiaoYHHwangJImproved cycling time-trial performance after ingestion of a caffeine energy drinkInt J Sport Nutr Exerc Metab.200919 1 61 78 1:CAS:528:DC%2BD1MXjvVWnsrY%3D 19403954 https://doi.org/10.1123/ijsnem.19.1.61
- SandersGJPevelerWHolmerBPeacockCAThe effect of three different energy drinks on oxygen consumption and perceived exertion during treadmillexerciseJ Int Soc Sports Nutr.201512 1 1 1 https://doi.org/10.1186/1550-2783-12-S1-P1
- Al-FaresMNAlsunniAAMajeedFBadarAEffect of energy drink intake before exercise on indices of physical performance in untrained femalesSaudi Med J.201536 5 580 25935179 4436755 https://doi.org/10.15537/smj.2015.5.11141
- PrinsPJGossFLNagleEFBealsKRobertsonRJLovalekarMT et al Energy drinks improve five-kilometer running performance in recreational endurance runnersJ Strength Cond Res201630 11 2979 2990 26937774 https://doi.org/10.1519/JSC.0000000000001391
- KinsingerKOglesbyBOjiamboRJohannJMLiguoriGEffects of 5-Hour ENERGY® Shot on Oxygen Consumption, Heart Rate, and SubstrateUtilization During Submaximal and Maximal ExerciseInt J Exerc Sci.20169 5 15
- ForbesSCCandowDGLittleJPMagnusCChilibeckPDEffect of Red Bull energy drink on repeated Wingate cycle performance and bench-press muscle enduranceInt J Sport Nutr Exerc Metab.200717 5 433 44 1:CAS:528:DC%2BD2sXht1yktr%2FE 18046053 https://doi.org/10.1123/ijsnem.17.5.433
- Del CosoJMunoz-FernandezVEMunozGFernandez-EliasVEOrtegaJFHamoutiN et al Effects of a caffeine-containing energy drink on simulated soccer performancePLoS One20127 2 e31380 22348079 3279366 https://doi.org/10.1371/journal.pone.0031380 1:CAS:528:DC%2BC38XivFaqsbY%3D
- GonzalezAMWalshALRatamessNAKangJHoffmanJREffect of a pre-workout energy supplement on acute multi-joint resistance exerciseJ Sports Sci Med201110 2 261 266 24149870 3761845
- AstorinoTACTLozanoATAburto-PrattKDuhonJErgogenic effects of caffeine on simulated time-trial performance are independent of fitness levelJ Caffeine Res20111 179 185 1:CAS:528:DC%2BC3MXhs1ajt77P https://doi.org/10.1089/jcr.2011.0022
- CampbellBIRichmondJLDawesJJThe effects of a commercial, pre-exercise energy drink supplement on power, muscular endurance, and repeated sprint speedInt J Exerc Sci.20169 2 9
- EckersonJMBullAJBaechleTRFischerCAO'BrienDCMooreGA et al Acute ingestion of sugar-free red bull energy drink has no effect on upper body strength and muscular endurance in resistance trained menJ Strength Cond Res201327 8 2248 2254 23880655 https://doi.org/10.1519/JSC.0b013e31827e14f2.
- AstleyCSouzaDBPolitoMDAcute Specific Effects of Caffeine-containing Energy Drink on Different Physical Performances in Resistance-trained MenInt J Exerc Sci.201811 4 260 29795732 5955291
- MagriniMAColquhounRJDawesJJSmithDBEffects of a pre-workout energy drink supplement on upper body muscular endurance performanceInt J Exerc Sci.20169 5 667 27990227 5154715
- CampbellBIKilpatrickMWilbornCLa BountyPParkerBGomezBElkinsAWilliamsSdos SantosMGA commercially available energy drinkdoes not improve peak power production on multiple 20-second Wingate testsJ Int Soc Sports Nutr.20107 1 1 2 https://doi.org/10.1186/1550-2783-10-1
- HoffmanJRKangJRatamessNAHoffmanMWTranchinaCPFaigenbaumADExamination of a pre-exercise, high energy supplement on exercise performanceJ Int Soc Sports Nutr.20096 1 2 19126213 2621122 https://doi.org/10.1186/1550-2783-6-2
- Seidl R, Peyrl A, Nicham R, Hauser E. A taurine and caffeine-containing drink stimulates cognitive performance and well-being. Amino Acids. 2000.
- ScholeyABKennedyDOCognitive and physiological effects of an “energy drink”: an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractionsPsychopharmacology.2004176 3–4 320 30 1:CAS:528:DC%2BD2cXps1Wqur8%3D 15549275 https://doi.org/10.1007/s00213-004-1935-2
- Smit HJ, Cotton JR, Hughes SC, Rogers PJ. Mood and cognitive performance effects of “energy” drink constituents: caffeine, glucose and carbonation. Nutr Neurosci. 2004;7(3):127–39.
- RaoAHuHNobreACThe effects of combined caffeine and glucose drinks on attention in the human brainNutr Neurosci.20058 3 141 53 1:CAS:528:DC%2BD2MXpslyku70%3D 16117181 https://doi.org/10.1080/10284150500096994
- HowardMAMarczinskiCAAcute effects of a glucose energy drink on behavioral controlExp Clin Psychopharmacol.201018 6 553 1:CAS:528:DC%2BC3MXht1antLY%3D 21186930 https://doi.org/10.1037/a0021740
- WesnesKABrookerHWatsonAWBalWOkelloEEffects of the Red Bull energy drink on cognitive function and mood in healthy young volunteersJ Psychopharmacol.201731 2 21 https://doi.org/10.1177/0269881116681459
- MaughanRJBurkeLMDvorakJLarson-MeyerDEPeelingPPhillipsSM et al IOC consensus statement: dietary supplements and the high-performance athleteInt J Sport Nutr Exerc Metab201828 2 104 125 1:CAS:528:DC%2BC1MXht1yhtb%2FM 29589768 https://doi.org/10.1123/ijsnem.2018-0020
- Van ThuyneWDelbekeFTDistribution of caffeine levels in urine in different sports in relation to doping control before and after the removal of caffeine from the WADA doping listInt J Sports Med200627 9 745 750 16586337 https://doi.org/10.1055/s-2005-872921 1:CAS:528:DC%2BD28XhtFKjt77L 16586337
- DelbekeFTDebackereMCaffeine: use and abuse in sportsInt J Sports Med19845 179 182 1:CAS:528:DyaL2cXmt1Citr0%3D 6480201 https://doi.org/10.1055/s-2008-1025901 6480201
- SprietLLExercise and sport performance with low doses of caffeineSports Med201444 Suppl 2 S175 S184 25355191 https://doi.org/10.1007/s40279-014-0257-8 25355191
- SprietLLCaffeine and performanceInt J Sport Nutr19955 Suppl S84 S99 7550260 https://doi.org/10.1123/ijsn.5.s1.s84 7550260
- Association TNCA. 2018-19 NCAA banned drugs list. https://www.ncaa.org/sites/default/files/2018-19NCAA_Banned_Drugs_20180608.pdf.
- Del CosoJMunozGMunoz-GuerraJPrevalence of caffeine use in elite athletes following its removal from the World Anti-Doping Agency list of banned substancesAppl Physiol Nutr Metab201136 4 555 561 21854160 https://doi.org/10.1139/h11-052 21854160
- Aguilar-Navarro M, Munoz G, Salinero JJ, Munoz-Guerra J, Fernandez-Alvarez M, Plata MDM, et al. Urine caffeine concentration in doping control samples from 2004 to 2015. Nutrients. 2019;11(2).
- ChvastaTECookeAREmptying and absorption of caffeine from the human stomachGastroenterology.197161 6 838 843 1:STN:280:DyaE38%2Fls1aqtg%3D%3D 5125686 https://doi.org/10.1016/S0016-5085(19)33396-7 5125686
- CallahanMMRobertsonRSArnaudMJBranfmanARMcComishMFYesairDWHuman metabolism of [1-methyl-14C]- and [2-14C] caffeine after oral administrationDrug Metab Dispos198210 4 417 423 1:CAS:528:DyaL3sXhtFE%3D 6126344 6126344
- CarrilloJABenitezJClinically significant pharmacokinetic interactions between dietary caffeine and medicationsClin Pharmacokinet200039 2 127 153 1:CAS:528:DC%2BD3cXmvVemtrg%3D 10976659 https://doi.org/10.2165/00003088-200039020-00004 10976659
- BlanchardJSawersSJThe absolute bioavailability of caffeine in manEur J Clin Pharmacol198324 1 93 98 1:CAS:528:DyaL3sXhsFCrur8%3D 6832208 https://doi.org/10.1007/BF00613933
- WhiteJRJrPadowskiJMZhongYChenGLuoSLazarusP et al Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adultsClin Toxicol (Phila)201654 4 308 312 https://doi.org/10.3109/15563650.2016.1146740
- MumfordGKBenowitzNLEvansSMKaminskiBJPrestonKLSannerudCA et al Absorption rate of methylxanthines following capsules, cola and chocolateEur J Clin Pharmacol199651 3–4 319 325 1:CAS:528:DyaK2sXosVKrsw%3D%3D 9010706 https://doi.org/10.1007/s002280050205
- ArnaudMJ Metabolism of caffeine and other components of coffee. Caffeine, Coffee, and Health. ed1993 New York Raven Press
- Tang-LiuDDWilliamsRLRiegelmanSDisposition of caffeine and its metabolites in manJ Pharmacol Exp Ther1983224 1 180 185 1:CAS:528:DyaL3sXhtF2jtbo%3D 6848742
- RasmussenBBBrixTHKyvikKOBrosenKThe interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factorsPharmacogenetics200212 6 473 478 1:CAS:528:DC%2BD38XmslejtLk%3D 12172216 https://doi.org/10.1097/00008571-200208000-00008
- NelsonDRZeldinDCHoffmanSMMaltaisLJWainHMNebertDWComparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variantsPharmacogenetics.200414 1 1 18 1:CAS:528:DC%2BD2cXjs1ags7c%3D 15128046 https://doi.org/10.1097/00008571-200401000-00001 15128046
- BegasEKouvarasETsakalofAPapakostaSAsprodiniEKIn vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratiosBiomed Chromatogr200721 2 190 200 1:CAS:528:DC%2BD2sXitVKkurY%3D 17221922 https://doi.org/10.1002/bmc.736
- LeloAMinersJORobsonRABirkettDJQuantitative assessment of caffeine partial clearances in manBr J Clin Pharmacol198622 2 183 186 1:CAS:528:DyaL28Xls1Cnsbs%3D 3756066 1401107 https://doi.org/10.1111/j.1365-2125.1986.tb05247.x
- ThornCFAklilluEMcDonaghEMKleinTEAltmanRBPharmGKB summary: caffeine pathwayPharmacogenet Genomics201222 5 389 395 1:CAS:528:DC%2BC38XlsVars7c%3D 22293536 3381939
- MandelHGUpdate on caffeine consumption, disposition and actionFood Chem Toxicol200240 9 1231 1234 1:CAS:528:DC%2BD38XmsVers7w%3D 12204386 https://doi.org/10.1016/S0278-6915(02)00093-5 12204386
- DjordjevicNGhotbiRJankovicSAklilluEInduction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 -163C>A polymorphismEur J Clin Pharmacol201066 7 697 703 1:CAS:528:DC%2BC3cXntlKqtbo%3D 20390257 https://doi.org/10.1007/s00228-010-0823-4 20390257
- GhotbiRChristensenMRohHKIngelman-SundbergMAklilluEBertilssonLComparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and KoreansEur J Clin Pharmacol200763 6 537 546 1:CAS:528:DC%2BD2sXkslWns70%3D 17370067 https://doi.org/10.1007/s00228-007-0288-2 17370067
- PereraVGrossASMcLachlanAJInfluence of environmental and genetic factors on CYP1A2 activity in individuals of South Asian and European ancestryClin Pharmacol Ther201292 4 511 519 1:CAS:528:DC%2BC38Xhtl2iurfL 22948892 22948892
- DjordjevicNGhotbiRBertilssonLJankovicSAklilluEInduction of CYP1A2 by heavy coffee consumption in Serbs and SwedesEur J Clin Pharmacol200864 4 381 385 1:CAS:528:DC%2BD1cXisFCmsbo%3D 18157525 https://doi.org/10.1007/s00228-007-0438-6 18157525
- MarksVKellyJFAbsorption of caffeine from tea, coffee, and coca colaLancet.19731 7807 827 1:STN:280:DyaE3s7ltlCltg%3D%3D 4121243 https://doi.org/10.1016/S0140-6736(73)90625-9 4121243
- LiguoriAHughesJRGrassJAAbsorption and subjective effects of caffeine from coffee, cola and capsulesPharmacol Biochem Behav199758 3 721 726 1:CAS:528:DyaK2sXmsVWntbw%3D 9329065 https://doi.org/10.1016/S0091-3057(97)00003-8 9329065
- ShargelLYA Applied biopharmaceutics and pharmacokinetics1999 4 Stamford Appleton and Lange
- RousseauELadineJLiuQYMeissnerGActivation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by caffeine and related compoundsArch Biochem Biophys1988267 1 75 86 1:CAS:528:DyaL1MXjsFCltg%3D%3D 2848455 https://doi.org/10.1016/0003-9861(88)90010-0 2848455
- TarnopolskyMCupidoCCaffeine potentiates low frequency skeletal muscle force in habitual and nonhabitual caffeine consumersJ Appl Physiol (1985)200089 5 1719 1724 1:CAS:528:DC%2BD3cXot1ansr0%3D https://doi.org/10.1152/jappl.2000.89.5.1719
- KalmarJMCafarelliECaffeine: a valuable tool to study central fatigue in humans?Exerc Sport Sci Rev200432 4 143 147 15604932 https://doi.org/10.1097/00003677-200410000-00004 15604932
- MeeusenRRoelandsBSprietLLCaffeine, exercise and the brainNestle Nutr Inst Workshop Ser201376 1 12 23899750 https://doi.org/10.1159/000350223 23899750
- NehligADavalJLDebryGCaffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effectsBrain Res Brain Res Rev199217 2 139 170 1:CAS:528:DyaK38Xmt1GlsL0%3D 1356551 https://doi.org/10.1016/0165-0173(92)90012-B 1356551
- ChesleyAHowlettRAHeigenhauserGJHultmanESprietLLRegulation of muscle glycogenolytic flux during intense aerobic exercise after caffeine ingestionAm J Phys1998275 2 Pt 2 R596 R603 1:CAS:528:DyaK1cXlsVyjtLc%3D
- GrahamTEHelgeJWMacLeanDAKiensBRichterEACaffeine ingestion does not alter carbohydrate or fat metabolism in human skeletal muscle during exerciseJ Physiol2000529 Pt 3 837 847 1:CAS:528:DC%2BD3MXjsl2iuw%3D%3D 11118510 2270224 https://doi.org/10.1111/j.1469-7793.2000.00837.x
- GrahamTEBattramDSDelaFEl-SohemyAThongFSDoes caffeine alter muscle carbohydrate and fat metabolism during exercise?Appl Physiol Nutr Metab200833 6 1311 1318 1:CAS:528:DC%2BD1cXhsFSmur7N 19088793 https://doi.org/10.1139/H08-129 19088793
- TarnopolskyMAAtkinsonSAMacDougallJDSaleDGSuttonJRPhysiological responses to caffeine during endurance running in habitual caffeine usersMed Sci Sports Exerc198921 4 418 424 1:CAS:528:DyaL1MXlt1Krurc%3D 2674593 https://doi.org/10.1249/00005768-198908000-00013 2674593
- CasalDCLeonASFailure of caffeine to affect substrate utilization during prolonged runningMed Sci Sports Exerc198517 1 174 179 1:CAS:528:DyaL2MXktVGitr0%3D 3982273 https://doi.org/10.1249/00005768-198502000-00029 3982273
- GlaisterMGissaneCCaffeine and physiological responses to submaximal exercise: a meta-analysisInt J Sports Physiol Perform.201813 4 402 11 28872376 https://doi.org/10.1123/ijspp.2017-0312 28872376
- TalanianJLSprietLLLow and moderate doses of caffeine late in exercise improve performance in trained cyclistsAppl Physiol Nutr Metab201641 8 850 855 1:CAS:528:DC%2BC28XhtFOrsrfK 27426699 https://doi.org/10.1139/apnm-2016-0053 27426699
- CuretonKJWarrenGLMillard-StaffordMLWingoJETrilkJBuyckxMCaffeinated sports drink: ergogenic effects and possible mechanismsInt J Sport Nutr Exerc Metab200717 1 35 55 1:CAS:528:DC%2BD2sXjsFeks7k%3D 17460332 https://doi.org/10.1123/ijsnem.17.1.35 17460332
- BlackCDWaddellDEGonglachARCaffeine's ergogenic effects on cycling: neuromuscular and perceptual factorsMed Sci Sports Exerc201547 6 1145 1158 1:CAS:528:DC%2BC2MXovVKksLw%3D 25211364 https://doi.org/10.1249/MSS.0000000000000513 25211364
- KillenLGGreenJMO'NealEKMcIntoshJRHornsbyJCoatesTEEffects of caffeine on session ratings of perceived exertionEur J Appl Physiol2013113 3 721 727 1:CAS:528:DC%2BC3sXis1Kqurc%3D 22926324 https://doi.org/10.1007/s00421-012-2480-z 22926324
- DemuraSYamadaTTerasawaNEffect of coffee ingestion on physiological responses and ratings of perceived exertion during submaximal endurance exercisePercept Mot Skills2007105 3 Pt 2 1109 1116 18380106 https://doi.org/10.2466/pms.105.4.1109-1116 18380106
- HadjicharalambousMGeorgiadesEKilduffLPTurnerAPTsofliouFPitsiladisYPInfluence of caffeine on perception of effort, metabolism and exercise performance following a high-fat mealJ Sports Sci200624 8 875 887 1:STN:280:DC%2BD28vmt1yhtg%3D%3D 16815783 https://doi.org/10.1080/02640410500249399 16815783
- MotlRWO'ConnorPJTubandtLPuetzTElyMREffect of caffeine on leg muscle pain during cycling exercise among femalesMed Sci Sports Exerc200638 3 598 604 1:CAS:528:DC%2BD28Xitl2mtbY%3D 16540851 https://doi.org/10.1249/01.mss.0000193558.70995.03 16540851
- MotlRWO'ConnorPJDishmanRKEffect of caffeine on perceptions of leg muscle pain during moderate intensity cycling exerciseJ Pain20034 6 316 321 1:CAS:528:DC%2BD3sXms1yjsrg%3D 14622688 https://doi.org/10.1016/S1526-5900(03)00635-7 14622688
- GliottoniRCMeyersJRArngrimssonSABroglioSPMotlRWEffect of caffeine on quadriceps muscle pain during acute cycling exercise in low versus high caffeine consumersInt J Sport Nutr Exerc Metab200919 2 150 161 1:CAS:528:DC%2BD1MXosFGjsLk%3D 19478340 https://doi.org/10.1123/ijsnem.19.2.150 19478340
- WarrenGLParkNDMarescaRDMcKibansKIMillard-StaffordMLEffect of caffeine ingestion on muscular strength and endurance: a meta-analysisMed Sci Sports Exerc201042 7 1375 1387 1:CAS:528:DC%2BC3cXns1ylu7w%3D 20019636 https://doi.org/10.1249/MSS.0b013e3181cabbd8 20019636
- AllenDGLambGDWesterbladHImpaired calcium release during fatigueJ Appl Physiol (1985)2008104 1 296 305 1:CAS:528:DC%2BD1cXhslOisL0%3D https://doi.org/10.1152/japplphysiol.00908.2007
- LindingerMIGrahamTESprietLLCaffeine attenuates the exercise-induced increase in plasma [K+] in humansJ Appl Physiol (1985)199374 3 1149 1155 1:CAS:528:DyaK3sXksVSrur8%3D https://doi.org/10.1152/jappl.1993.74.3.1149
- GonglachARAdeCJBembenMGLarsonRDBlackCDMuscle pain as a regulator of cycling intensity: effect of caffeine ingestionMed Sci Sports Exerc201648 2 287 296 1:CAS:528:DC%2BC28Xhtlymur0%3D 26322555 https://doi.org/10.1249/MSS.0000000000000767 26322555
- FredholmBBAbbracchioMPBurnstockGDalyJWHardenTKJacobsonKA et al Nomenclature and classification of purinoceptorsPharmacol Rev199446 2 143 156 1:CAS:528:DyaK2cXlslSlsbw%3D 7938164 4976594
- FredholmBBBattigKHolmenJNehligAZvartauEEActions of caffeine in the brain with special reference to factors that contribute to its widespread usePharmacol Rev199951 1 83 133 1:CAS:528:DyaK1MXitFWgurk%3D 10049999 10049999
- FredholmBBChenJFCunhaRASvenningssonPVaugeoisJMAdenosine and brain functionInt Rev Neurobiol200563 191 270 1:CAS:528:DC%2BD2MXksF2jtbs%3D 15797469 https://doi.org/10.1016/S0074-7742(05)63007-3 15797469
- FredholmBBAstra award lecture. Adenosine, adenosine receptors and the actions of caffeinePharmacol Toxicol199576 2 93 101 1:CAS:528:DyaK2MXjsl2ns7w%3D 7746802 https://doi.org/10.1111/j.1600-0773.1995.tb00111.x 7746802
- MeeusenRWatsonPHasegawaHRoelandsBPiacentiniMFCentral fatigue: the serotonin hypothesis and beyondSports Med200636 10 881 909 17004850 https://doi.org/10.2165/00007256-200636100-00006 17004850
- NehligAInterindividual differences in caffeine metabolism and factors driving caffeine consumptionPharmacol Rev201870 2 384 411 1:CAS:528:DC%2BC1MXkvVKnsL0%3D 29514871 https://doi.org/10.1124/pr.117.014407 29514871
- SalamoneJDFarrarAMFontLPatelVSchlarDENunesEJ et al Differential actions of adenosine A1 and A2A antagonists on the effort-related effects of dopamine D2 antagonismBehav Brain Res2009201 1 216 222 1:CAS:528:DC%2BD1MXltVCrtbk%3D 19428636 2806666 https://doi.org/10.1016/j.bbr.2009.02.021
- SalamoneJDCorreaMFerrignoSYangJHRotoloRAPresbyREThe psychopharmacology of effort-related decision making: dopamine, adenosine, and insights into the neurochemistry of motivationPharmacol Rev201870 4 747 762 1:CAS:528:DC%2BC1MXhsVyrtrnE 30209181 6169368 https://doi.org/10.1124/pr.117.015107
- MingoteSFontLFarrarAMVontellRWordenLTStopperCM et al Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathwayJ Neurosci200828 36 9037 9046 1:CAS:528:DC%2BD1cXhtFSmsr7K 18768698 2806668 https://doi.org/10.1523/JNEUROSCI.1525-08.2008
- WordenLTShahriariMFarrarAMSinkKSHockemeyerJMullerCE et al The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonistsPsychopharmacology2009203 3 489 499 1:CAS:528:DC%2BD1cXhsVeqsrnJ 19048234 https://doi.org/10.1007/s00213-008-1396-0 19048234
- PorrasGDi MatteoVFracassoCLucasGDe DeurwaerderePCacciaS et al 5-HT2A and 5-HT2C/2B receptor subtypes modulate dopamine release induced in vivo by amphetamine and morphine in both the rat nucleus accumbens and striatumNeuropsychopharmacology.200226 3 311 324 1:CAS:528:DC%2BD38Xht1ajtLs%3D 11850146 https://doi.org/10.1016/S0893-133X(01)00333-5 11850146
- LucasGDe DeurwaerderePCacciaSUmbertoSThe effect of serotonergic agents on haloperidol-induced striatal dopamine release in vivo: opposite role of 5-HT(2A) and 5-HT(2C) receptor subtypes and significance of the haloperidol dose usedNeuropharmacology.200039 6 1053 1063 1:CAS:528:DC%2BD3cXhvVOls7c%3D 10727716 https://doi.org/10.1016/S0028-3908(99)00193-8 10727716
- Di GiovanniGDi MatteoVPierucciMEspositoESerotonin-dopamine interaction: electrophysiological evidenceProg Brain Res2008172 45 71 18772027 https://doi.org/10.1016/S0079-6123(08)00903-5 1:CAS:528:DC%2BD1cXhsV2isbrK 18772027
- VolkowNDWangGJLoganJAlexoffDFowlerJSThanosPK et al Caffeine increases striatal dopamine D2/D3 receptor availability in the human brainTransl Psychiatry20155 e549 1:CAS:528:DC%2BC2MXlvFWqsLc%3D 25871974 4462609 https://doi.org/10.1038/tp.2015.46
- ZhangGStackmanRWJrThe role of serotonin 5-HT2A receptors in memory and cognitionFront Pharmacol20156 225 26500553 4594018
- AbdolmalekyHMFaraoneSVGlattSJTsuangMTMeta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophreniaSchizophr Res200467 1 53 62 14741324 https://doi.org/10.1016/S0920-9964(03)00183-X
- YamadaSAkitaHKanazawaKIshidaTHirataKItoK et al T102C polymorphism of the serotonin (5-HT) 2A receptor gene in patients with non-fatal acute myocardial infarctionAtherosclerosis.2000150 1 143 148 1:CAS:528:DC%2BD3cXisFGrsLo%3D 10781645 https://doi.org/10.1016/S0021-9150(99)00356-1
- FarinaDArendt-NielsenLMerlettiRGraven-NielsenTEffect of experimental muscle pain on motor unit firing rate and conduction velocityJ Neurophysiol200491 3 1250 1259 14614105 https://doi.org/10.1152/jn.00620.2003
- FarinaDArendt-NielsenLGraven-NielsenTExperimental muscle pain reduces initial motor unit discharge rates during sustained submaximal contractionsJ Appl Physiol (1985)200598 3 999 1005 https://doi.org/10.1152/japplphysiol.01059.2004
- Graven-NielsenTLundHArendt-NielsenLDanneskiold-SamsoeBBliddalHInhibition of maximal voluntary contraction force by experimental muscle pain: a centrally mediated mechanismMuscle Nerve200226 5 708 712 12402294 https://doi.org/10.1002/mus.10225
- MartikainenIKNuechterleinEBPecinaMLoveTMCummifordCMGreenCR et al Chronic back pain is associated with alterations in dopamine neurotransmission in the ventral striatumJ Neurosci201535 27 9957 9965 1:CAS:528:DC%2BC2MXht1ejtL7K 26156996 4495244 https://doi.org/10.1523/JNEUROSCI.4605-14.2015
- DuncanMJOxfordSWAcute caffeine ingestion enhances performance and dampens muscle pain following resistance exercise to failureJ Sports Med Phys Fitness201252 3 280 285 1:CAS:528:DC%2BC38Xht1GmsL%2FM 22648466
- DuncanMJStanleyMParkhouseNCookKSmithMAcute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exerciseEur J Sport Sci201313 4 392 399 23834545 https://doi.org/10.1080/17461391.2011.635811
- AstorinoTACottrellTTalhami LozanoAAburto-PrattKDuhonJEffect of caffeine on RPE and perceptions of pain, arousal, and pleasure/displeasure during a cycling time trial in endurance trained and active menPhysiol Behav2012106 2 211 217 1:CAS:528:DC%2BC38XksFegsr8%3D 22349482 https://doi.org/10.1016/j.physbeh.2012.02.006
- MaridakisVO'ConnorPJDudleyGAMcCullyKKCaffeine attenuates delayed-onset muscle pain and force loss following eccentric exerciseJ Pain20078 3 237 243 1:CAS:528:DC%2BD2sXislWntrc%3D 17161977 https://doi.org/10.1016/j.jpain.2006.08.006
- AstorinoTARoupoliLRValdiviesoBRCaffeine does not alter RPE or pain perception during intense exercise in active womenAppetite.201259 2 585 590 1:CAS:528:DC%2BC38Xht1GltbvE 22813436 https://doi.org/10.1016/j.appet.2012.07.008
- GreenJMOlenickAEastepCWinchesterLCaffeine influences cadence at lower but not higher intensity RPE-regulated cyclingPhysiol Behav2017169 46 51 1:CAS:528:DC%2BC28XhvFGru77E 27851893 https://doi.org/10.1016/j.physbeh.2016.11.007
- AsmussenEMuscle fatigueMed Sci Sports197911 4 313 321 1:CAS:528:DyaL3cXhsVeqs74%3D 530021
- MaclarenDPGibsonHParry-BillingsMEdwardsRHA review of metabolic and physiological factors in fatigueExerc Sport Sci Rev198917 29 66 1:STN:280:DyaK3c%2FgsFGktQ%3D%3D 2676550
- DavisJMZhaoZStockHSMehlKABuggyJHandGACentral nervous system effects of caffeine and adenosine on fatigueAm J Phys Regul Integr Comp Phys2003284 2 R399 R404 1:CAS:528:DC%2BD3sXhtlOqsbY%3D
- ChildsEde WitHEnhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individualsExp Clin Psychopharmacol200816 1 13 21 1:CAS:528:DC%2BD1cXivFGksbY%3D 18266548 https://doi.org/10.1037/1064-1297.16.1.13
- LoristMMSnelJKokAMulderGInfluence of caffeine on selective attention in well-rested and fatigued subjectsPsychophysiology.199431 6 525 534 1:STN:280:DyaK2M7kvVOqtg%3D%3D 7846213 https://doi.org/10.1111/j.1469-8986.1994.tb02345.x
- Vital-LopezFGRamakrishnanSDotyTJBalkinTJReifmanJCaffeine dosing strategies to optimize alertness during sleep lossJ Sleep Res201827 5 e12711 29808510 https://doi.org/10.1111/jsr.12711
- Shen JG, Brooks MB, Cincotta J, Manjourides JD. Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: a systematic review and meta-analysis. J Sci Med Sport. 2018.
- CoxGRDesbrowBMontgomeryPGAndersonMEBruceCRMacridesTA et al Effect of different protocols of caffeine intake on metabolism and endurance performanceJ Appl Physiol (1985)200293 3 990 999 https://doi.org/10.1152/japplphysiol.00249.2002
- ClarkVRHopkinsWGHawleyJABurkeLMPlacebo effect of carbohydrate feedings during a 40-km cycling time trialMed Sci Sports Exerc200032 9 1642 1647 1:STN:280:DC%2BD3cvksVGntg%3D%3D 10994918 https://doi.org/10.1097/00005768-200009000-00019
- PolloACarlinoEVaseLBenedettiFPreventing motor training through nocebo suggestionsEur J Appl Physiol2012112 11 3893 3903 22411454 https://doi.org/10.1007/s00421-012-2333-9
- FoadAJBeedieCJColemanDAPharmacological and psychological effects of caffeine ingestion in 40-km cycling performanceMed Sci Sports Exerc200840 1 158 165 1:CAS:528:DC%2BD1cXktVyhug%3D%3D 18091009 https://doi.org/10.1249/mss.0b013e3181593e02
- BeedieCJStuartEMColemanDAFoadAJPlacebo effects of caffeine on cycling performanceMed Sci Sports Exerc200638 12 2159 2164 1:CAS:528:DC%2BD28Xht1Ohu73E 17146324 https://doi.org/10.1249/01.mss.0000233805.56315.a9
- SaundersBde OliveiraLFda SilvaRPde SallesPVGoncalvesLSYamaguchiG et al Placebo in sports nutrition: a proof-of-principle study involvingcaffeine supplementationScand J Med Sci Sports.201727 11 1240 1247 1:STN:280:DC%2BC2snpvFGhuw%3D%3D 27882605 https://doi.org/10.1111/sms.12793
- BeedieCJPlacebo effects in competitive sport: qualitative dataJ Sports Sci Med20076 1 21 28 24149220 3778695
- ChristensenPMShiraiYRitzCNordsborgNBCaffeine and bicarbonate for speed. A meta-analysis of legal supplements potential for improving intense endurance exercise performanceFront Physiol20178 240 28536531 5422435 https://doi.org/10.3389/fphys.2017.00240
- Olympic.org. Rio 2016 Cycling Road 2016.
- SouthwardKRutherfurd-MarkwickKJAliAThe effect of acute caffeine ingestion on endurance performance: a systematic review and meta-analysisSports Med201848 8 1913 1928 29876876 https://doi.org/10.1007/s40279-018-0939-8
- DesbrowBBiddulphCDevlinBGrantGDAnoopkumar-DukieSLeverittMDThe effects of different doses of caffeine on endurance cycling time trial performanceJ Sports Sci201230 2 115 120 22142020 https://doi.org/10.1080/02640414.2011.632431
- Graham-Paulson T, Perret C, Goosey-Tolfrey V. Improvements in cycling but not handcycling 10 km time trial performance in habitual caffeine users. Nutrients. 2016;8(7).
- GuestNCoreyPVescoviJEl-SohemyACaffeine, CYP1A2 genotype, and endurance performance in athletesMed Sci Sports Exerc201850 8 1570 1578 1:CAS:528:DC%2BC1cXhtlWrtrjN 29509641 https://doi.org/10.1249/MSS.0000000000001596
- EvansMTierneyPGrayNHaweGMackenMEganBAcute ingestion of caffeinated chewing gum improves repeated sprint performance of team sport athletes with low habitual caffeine consumptionInt J Sport Nutr Exerc Metab201828 3 221 227 1:CAS:528:DC%2BC1MXhs1Okt7rL 29091470 https://doi.org/10.1123/ijsnem.2017-0217
- O'RourkeMPO'BrienBJKnezWLPatonCDCaffeine has a small effect on 5-km running performance of well-trained and recreational runnersJ Sci Med Sport200811 2 231 233 17544329 https://doi.org/10.1016/j.jsams.2006.12.118
- StadheimHKNossumEMOlsenRSpencerMJensenJCaffeine improves performance in double poling during acute exposure to 2,000-m altitudeJ Appl Physiol (1985)2015119 12 1501 1509 1:CAS:528:DC%2BC28XhtFalu7zE https://doi.org/10.1152/japplphysiol.00509.2015
- LaraBRuiz-VicenteDArecesFAbian-VicenJSalineroJJGonzalez-MillanC et al Acute consumption of a caffeinated energy drink enhances aspects of performance in sprint swimmersBr J Nutr2015114 6 908 914 1:CAS:528:DC%2BC2MXhsVegs77P 26279580 https://doi.org/10.1017/S0007114515002573
- YangAPalmerAAde WitHGenetics of caffeine consumption and responses to caffeinePsychopharmacology2010211 3 245 257 1:CAS:528:DC%2BC3cXntFGltr0%3D 20532872 4242593 https://doi.org/10.1007/s00213-010-1900-1
- NSCA NSCA’s guide to test and assessment’s2018 Champaign Human Kinetics
- CroninJLawtonTHarrisNKildingAMcMasterDTA brief review of handgrip strength and sport performanceJ Strength Cond Res201731 11 3187 3217 28820854 https://doi.org/10.1519/JSC.0000000000002149
- BiancoALupoCAlesiMSpinaSRaccugliaMThomasE et al The sit up test to exhaustion as a test for muscular endurance evaluationSpringerplus.20154 309 26155448 4488239 https://doi.org/10.1186/s40064-015-1023-6
- VanheesLLefevreJPhilippaertsRMartensMHuygensWTroostersT et al How to assess physical activity? How to assess physical fitness?Eur J Cardiovasc Prev Rehabil200512 2 102 114 15785295 https://doi.org/10.1097/00149831-200504000-00004
- PolitoMDSouzaDBCasonattoJFarinattiPAcute effect of caffeine consumption on isotonic muscular strength and endurance: a systematic review and meta-analysisSci Sports201631 3 119 128 https://doi.org/10.1016/j.scispo.2016.01.006
- GrgicJMikulicPCaffeine ingestion acutely enhances muscular strength and power but not muscular endurance in resistance-trained menEur J Sport Sci201717 8 1029 1036 28537195 https://doi.org/10.1080/17461391.2017.1330362
- BeckTWHoushTJSchmidtRJJohnsonGOHoushDJCoburnJW et al The acute effects of a caffeine-containing supplement on strength, muscular endurance, and anaerobic capabilitiesJ Strength Cond Res200620 3 506 510 16937961
- Diaz-LaraFJDel CosoJGarciaJMPortilloLJArecesFAbian-VicenJCaffeine improves muscular performance in elite Brazilian Jiu-jitsu athletesEur J Sport Sci201616 8 1079 1086 26863885 https://doi.org/10.1080/17461391.2016.1143036
- Wilk M, Krzysztofik M, Filip A, Zajac A, Del Coso J. The effects of high doses of caffeine on maximal strength and muscular endurance in athletes habituated to caffeine. Nutrients. 2019;11(8).
- Wilk M, Krzysztofik M, Filip A, Zajac A, Del Coso J. Correction: Wilk et al. “The Effects of High Doses of Caffeine on Maximal Strength and Muscular Endurance in Athletes Habituated to Caffeine”. Nutrients. 2019;11(8):1912.
- GrgicJPickeringCThe effects of caffeine ingestion on isokinetic muscular strength: a meta-analysisJ Sci Med Sport201922 3 353 360 30217692 https://doi.org/10.1016/j.jsams.2018.08.016
- GrgicJTrexlerETLazinicaBPedisicZEffects of caffeine intake on muscle strength and power: a systematic review and meta-analysisJ Int Soc Sports Nutr201815 11 29527137 5839013 https://doi.org/10.1186/s12970-018-0216-0
- Lopes-SilvaJPChooHCFranchiniEAbbissCRIsolated ingestion of caffeine and sodium bicarbonate on repeated sprint performance: a systematic review and meta-analysisJ Sci Med Sport201922 8 962 972 31036532 https://doi.org/10.1016/j.jsams.2019.03.007
- SchneikerKTBishopDDawsonBHackettLPEffects of caffeine on prolonged intermittent-sprint ability in team-sport athletesMed Sci Sports Exerc200638 3 578 585 1:CAS:528:DC%2BD28Xitl2mtbk%3D 16540848 https://doi.org/10.1249/01.mss.0000188449.18968.62
- DuncanMJEyreEGrgicJTallisJThe effect of acute caffeine ingestion on upper and lower body anaerobic exercise performanceEur J Sport Sci.201910 10 1359 1366 https://doi.org/10.1080/17461391.2019.1601261
- GreerFMoralesJColesMWingate performance and surface EMG frequency variables are not affected by caffeine ingestionAppl Physiol Nutr Metab200631 5 597 603 17111014 https://doi.org/10.1139/h06-030
- GrgicJCaffeine ingestion enhances Wingate performance: a meta-analysisEur J Sport Sci201818 2 219 225 29087785 https://doi.org/10.1080/17461391.2017.1394371 29087785
- GonçalvesBMorsalesASampaio-JorgeFTinocoFAcute effects of caffeine intake on athletic performance: a systematic review and meta-analysisRev Chil Nutr201744 3 283 291 https://doi.org/10.4067/S0717-75182017000300283
- LeeCLChengCFLinJCHuangHWCaffeine's effect on intermittent sprint cycling performance with different rest intervalsEur J Appl Physiol2012112 6 2107 2116 1:CAS:528:DC%2BC38Xnt1Cjtb0%3D 21960086 https://doi.org/10.1007/s00421-011-2181-z 21960086
- WoolfKBidwellWKCarlsonAGThe effect of caffeine as an ergogenic aid in anaerobic exerciseInt J Sport Nutr Exerc Metab200818 4 412 429 1:CAS:528:DC%2BD1cXhtVOnu7bI 18708685 https://doi.org/10.1123/ijsnem.18.4.412 18708685
- ZehrEPSaleDGBallistic movement: muscle activation and neuromuscular adaptationCan J Appl Physiol199419 4 363 378 1:STN:280:DyaK2M7lt1Cnuw%3D%3D 7849654 https://doi.org/10.1139/h94-030
- SalineroJJLaraBDel CosoJEffects of acute ingestion of caffeine on team sports performance: a systematic review and meta-analysisRes Sports Med.201927 2 238 256 30518253 https://doi.org/10.1080/15438627.2018.1552146
- Sabol F, Grgic J, Mikulic P. The Effects of 3 Different Doses of Caffeine on Jumping and Throwing Performance: A Randomized, Double-Blind, Crossover Study. Int J Sports Physiol Perform. 2019;1170-1177. https://pubmed.ncbi.nlm.nih.gov/30702372/.
- HaffGGNimphiusSTraining principles for powerStrength Cond J201234 6 2 12 https://doi.org/10.1519/SSC.0b013e31826db467
- GrgicJMikulicPSchoenfeldBJBishopDJPedisicZThe influence of caffeine supplementation on resistance exercise: a reviewSports Med201949 1 17 30 30298476 https://doi.org/10.1007/s40279-018-0997-y 30298476
- PallaresJGFernandez-EliasVEOrtegaJFMunozGMunoz-GuerraJMora-RodriguezRNeuromuscular responses to incremental caffeine doses: performance and side effectsMed Sci Sports Exerc201345 11 2184 2192 1:CAS:528:DC%2BC3sXhs1Ckt77F 23669879 https://doi.org/10.1249/MSS.0b013e31829a6672 23669879
- PuenteCAbian-VicenJDel CosoJLaraBSalineroJJThe CYP1A2 -163C>A polymorphism does not alter the effects of caffeine on basketball performancePLoS One201813 4 e0195943 29668752 5905997 https://doi.org/10.1371/journal.pone.0195943 1:CAS:528:DC%2BC1cXhsl2gurvL
- Puente C, Abian-Vicen J, Salinero JJ, Lara B, Areces F, Del Coso J. Caffeine improves basketball performance in experienced basketball players. Nutrients. 2017;9(9).
- ScanlanATDalboVJConteDStojanovicEStojiljkovicNStankovicR et al Caffeine supplementation has no effect on dribbling speed in elite basketball playersInt J Sports Physiol Perform201914 7 997 1000 30569790 https://doi.org/10.1123/ijspp.2018-0871
- GantNAliAFoskettAThe influence of caffeine and carbohydrate coingestion on simulated soccer performanceInt J Sport Nutr Exerc Metab201020 3 191 197 1:CAS:528:DC%2BC3cXpt1Wrsr0%3D 20601736 https://doi.org/10.1123/ijsnem.20.3.191
- FoskettAAliAGantNCaffeine enhances cognitive function and skill performance during simulated soccer activityInt J Sport Nutr Exerc Metab200919 4 410 423 1:CAS:528:DC%2BD1MXhtV2isrbE 19827465 https://doi.org/10.1123/ijsnem.19.4.410
- AstorinoTAMateraAJBasingerJEvansMSchurmanTMarquezREffects of red bull energy drink on repeated sprint performance in women athletesAmino Acids201242 5 1803 1808 1:CAS:528:DC%2BC38XlsFert70%3D 21461905 https://doi.org/10.1007/s00726-011-0900-8
- PettersenSAKrustrupPBendiksenMRandersMBBritoJBangsboJ et al Caffeine supplementation does not affect match activities and fatigue resistance during match play in young football playersJ Sports Sci201432 20 1958 1965 25357189 https://doi.org/10.1080/02640414.2014.965189
- Del CosoJPerez-LopezAAbian-VicenJSalineroJJLaraBValadesDEnhancing physical performance in male volleyball players with a caffeine-containing energy drinkInt J Sports Physiol Perform20149 6 1013 1018 24664858 https://doi.org/10.1123/ijspp.2013-0448 24664858
- Perez-LopezASalineroJJAbian-VicenJValadesDLaraBHernandezC et al Caffeinated energy drinks improve volleyball performance in elite female playersMed Sci Sports Exerc201547 4 850 856 25051390 https://doi.org/10.1249/MSS.0000000000000455
- Fernandez-CamposCDengoALMoncada-JimenezJAcute consumption of an energy drink does not improve physical performance of female volleyball playersInt J Sport Nutr Exerc Metab201525 3 271 277 25387127 https://doi.org/10.1123/ijsnem.2014-0101
- PfeiferDRArvinKMHerschbergerCNHaynesNJRenfrowMSA low dose caffeine and carbohydrate supplement does not improve athletic performance during volleyball competitionInt J Exerc Sci201710 3 340 353 28515832 5421974
- WoolfKBidwellWKCarlsonAGEffect of caffeine as an ergogenic aid during anaerobic exercise performance in caffeine naive collegiate football playersJ Strength Cond Res200923 5 1363 1369 19620930 https://doi.org/10.1519/JSC.0b013e3181b3393b 19620930
- PortilloJDel CosoJAbian-VicenJEffects of caffeine ingestion on skill performance during an international female rugby sevens competitionJ Strength Cond Res201731 12 3351 3357 28002181 https://doi.org/10.1519/JSC.0000000000001763 28002181
- Del CosoJPortilloJMunozGAbian-VicenJGonzalez-MillanCMunoz-GuerraJCaffeine-containing energy drink improves sprint performance during an international rugby sevens competitionAmino Acids201344 6 1511 1519 23462927 https://doi.org/10.1007/s00726-013-1473-5 1:CAS:528:DC%2BC3sXnsFGitr8%3D 23462927
- RanchordasMKPrattHParsonsMParryABoydCLynnAEffect of caffeinated gum on a battery of rugby-specific tests in trained university-standard male rugby union playersJ Int Soc Sports Nutr201916 1 17 1:STN:280:DC%2BB3M%2FktVKksQ%3D%3D 30971276 6458642 https://doi.org/10.1186/s12970-019-0286-7
- Del CosoJPortilloJSalineroJJLaraBAbian-VicenJArecesFCaffeinated energy drinks improve high-speed running in elite field hockey playersInt J Sport Nutr Exerc Metab201626 1 26 32 26251550 https://doi.org/10.1123/ijsnem.2015-0128 26251550
- DuncanMJTaylorSLyonsMThe effect of caffeine ingestion on field hockey skill performance following physical fatigueRes Sports Med201220 1 25 36 22242735 https://doi.org/10.1080/15438627.2012.634686 22242735
- Madden RF, Erdman KA, Shearer J, Spriet LL, Ferber R, Kolstad AT, et al. Effects of caffeine on exertion, skill performance, and physicality in ice hockey. Int J Sports Physiol Perform. 2019;1-8. https://pubmed.ncbi.nlm.nih.gov/30958066/.
- FelippeLCLopes-SilvaJPBertuzziRMcGinleyCLima-SilvaAESeparate and combined effects of caffeine and sodium-bicarbonate intake on judo performanceInt J Sports Physiol Perform201611 2 221 226 26182440 https://doi.org/10.1123/ijspp.2015-0020 26182440
- StadheimHKKvammeBOlsenRDrevonCAIvyJLJensenJCaffeine increases performance in cross-country double-poling time trial exerciseMed Sci Sports Exerc201345 11 2175 2183 1:CAS:528:DC%2BC3sXhs1Ckt77J 23591294 https://doi.org/10.1249/MSS.0b013e3182967948 23591294
- DohertyMSmithPMEffects of caffeine ingestion on exercise testing: a meta-analysisInt J Sport Nutr Exerc Metab200414 6 626 646 1:CAS:528:DC%2BD2MXhtVSjtL4%3D 15657469 https://doi.org/10.1123/ijsnem.14.6.626 15657469
- NielsenDEEl-SohemyADisclosure of genetic information and change in dietary intake: a randomized controlled trialPLoS One20149 11 e112665 25398084 4232422 https://doi.org/10.1371/journal.pone.0112665 1:CAS:528:DC%2BC2cXhvFKqsLfO
- RahimiRThe effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo controlled, crossover studyIr J Med Sci.2019188 1 337 345 1:CAS:528:DC%2BC1cXksVegtb8%3D 29532291 https://doi.org/10.1007/s11845-018-1780-7 29532291
- WomackCJSaundersMJBechtelMKBoltonDJMartinMLudenND et al The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeineJ Int Soc Sports Nutr20129 1 7 1:CAS:528:DC%2BC38Xntlegsbw%3D 22420682 3334681 https://doi.org/10.1186/1550-2783-9-7
- HunterAMSt Clair GibsonACollinsMLambertMNoakesTDCaffeine ingestion does not alter performance during a 100-km cycling time-trial performanceInt J Sport Nutr Exerc Metab200212 4 438 452 1:CAS:528:DC%2BD3sXjt1SjsQ%3D%3D 12500987 https://doi.org/10.1123/ijsnem.12.4.438 12500987
- RoelandsBBuyseLPauwelsFDelbekeFDeventerKMeeusenRNo effect of caffeine on exercise performance in high ambient temperatureEur J Appl Physiol2011111 12 3089 3095 1:CAS:528:DC%2BC3MXhsFSjtbfO 21461761 https://doi.org/10.1007/s00421-011-1945-9 21461761
- CornelisMCEl-SohemyAKabagambeEKCamposHCoffee, CYP1A2 genotype, and risk of myocardial infarctionJAMA.2006295 10 1135 1141 1:CAS:528:DC%2BD28XitV2htr0%3D 16522833 https://doi.org/10.1001/jama.295.10.1135 16522833
- PalatiniPCeolottoGRagazzoFDorigattiFSaladiniFPapparellaI et al CYP1A2 genotype modifies the association between coffee intake and the risk of hypertensionJ Hypertens200927 8 1594 1601 1:CAS:528:DC%2BD1MXoslOgtr8%3D 19451835 https://doi.org/10.1097/HJH.0b013e32832ba850 19451835
- SoaresRNSchneiderAValleSCSchenkelPCThe influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption levelVasc Pharmacol2018106 67 73 1:CAS:528:DC%2BC1cXks1yquro%3D https://doi.org/10.1016/j.vph.2018.03.002
- PalatiniPBenettiEMosLGaravelliGMazzerACozzioS et al Association of coffee consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive patientsEur J Epidemiol201530 3 209 217 1:CAS:528:DC%2BC2MXlsVKgtr8%3D 25595320 https://doi.org/10.1007/s10654-015-9990-z 25595320
- SkinnerTLJenkinsDGTaaffeDRLeverittMDCoombesJSCoinciding exercise with peak serum caffeine does not improve cycling performanceJ Sci Med Sport201316 1 54 59 22658588 https://doi.org/10.1016/j.jsams.2012.04.004 22658588
- JenkinsNTTrilkJLSinghalAO'ConnorPJCuretonKJErgogenic effects of low doses of caffeine on cycling performanceInt J Sport Nutr Exerc Metab200818 3 328 342 1:CAS:528:DC%2BD1cXosFGksbc%3D 18562777 https://doi.org/10.1123/ijsnem.18.3.328 18562777
- BortolottiHAltimariLRVitor-CostaMCyrinoESPerformance during a 20-km cycling time-trial after caffeine ingestionJ Int Soc Sports Nutr201411 45 25302056 4190929 https://doi.org/10.1186/s12970-014-0045-8 1:CAS:528:DC%2BC2cXhvFKgsrzI
- Algrain HayaATRMCarrillo AndresERyan EmilyJChul-HoKLettan RobertBIIRyan EdwardJThe effects of a polymorphism in the cytochrome P450 CYP1A2 gene on performance enhancement with caffeine in recreational cyclistsJ Caffeine Res20166 1 34 39 https://doi.org/10.1089/jcr.2015.0029 1:CAS:528:DC%2BC28Xjs1OrtL0%3D
- Salinero JJ, Lara B, Ruiz-Vicente D, Areces F, Puente-Torres C, Gallo-Salazar C, et al. CYP1A2 genotype variations do not modify the benefits and drawbacks of caffeine during exercise: a pilot study. Nutrients. 2017;9(3).
- HigginsJPBabuKMCaffeine reduces myocardial blood flow during exerciseAm J Med2013126 8 730 e1 730 e8 https://doi.org/10.1016/j.amjmed.2012.12.023 1:CAS:528:DC%2BC3sXpt1Cmsrc%3D
- NamdarMSchepisTKoepfliPGaemperliOSiegristPTGrathwohlR et al Caffeine impairs myocardial blood flow response to physical exercise in patients with coronary artery disease as well as in age-matched controlsPLoS One20094 5 e5665 19479069 2682574 https://doi.org/10.1371/journal.pone.0005665 1:CAS:528:DC%2BD1MXms1Clsbo%3D
- Fried NT, Elliott MB, Oshinsky ML. The role of adenosine signaling in headache: a review. Brain Sci. 2017;7(3):30.
- UrryELandoltHPAdenosine, caffeine, and performance: from cognitive neuroscience of sleep to sleep pharmacogeneticsCurr Top Behav Neurosci201525 331 366 24549722 https://doi.org/10.1007/7854_2014_274 24549722
- LoyBOCPLindheimerJ et al Caffeine is ergogenic for adenosine A2A receptor gene (ADORA2A) T allele homozygotes: a pilot studyJ Caffeine Res.20155 2 73 81 1:CAS:528:DC%2BC2MXpt1Wrurc%3D https://doi.org/10.1089/jcr.2014.0035
- NunesRAMazzottiDRHirotsuCAndersenMLTufikSBittencourtLThe association between caffeine consumption and objective sleep variables is dependent on ADORA2A c.1083T>C genotypesSleep Med201730 210 215 28215251 https://doi.org/10.1016/j.sleep.2016.06.038 28215251
- ReteyJVAdamMKhatamiRLuhmannUFJungHHBergerW et al A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleepClin Pharmacol Ther200781 5 692 698 1:CAS:528:DC%2BD2sXlsFCqsLc%3D 17329997 https://doi.org/10.1038/sj.clpt.6100102 17329997
- BodenmannSHohoffCFreitagCDeckertJReteyJVBachmannV et al Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivationBr J Pharmacol2012165 6 1904 1913 1:CAS:528:DC%2BC38XjsVKqu7c%3D 21950736 3372839 https://doi.org/10.1111/j.1476-5381.2011.01689.x
- ByrneEMJohnsonJMcRaeAFNyholtDRMedlandSEGehrmanPR et al A genome-wide association study of caffeine-related sleep disturbance: confirmation of a role for a common variant in the adenosine receptorSleep.201235 7 967 975 22754043 3369232 https://doi.org/10.5665/sleep.1962
- PhilipPTaillardJMooreNDelordSValtatCSagaspeP et al The effects of coffee and napping on nighttime highway driving: a randomized trialAnn Intern Med2006144 11 785 791 16754920 https://doi.org/10.7326/0003-4819-144-11-200606060-00004 16754920
- DrummondSPBischoff-GretheADingesDFAyalonLMednickSCMeloyMJThe neural basis of the psychomotor vigilance taskSleep.200528 9 1059 1068 16268374 16268374
- LandoltHPReteyJVTonzKGottseligJMKhatamiRBuckelmullerI et al Caffeine attenuates waking and sleep electroencephalographic markers of sleep homeostasis in humansNeuropsychopharmacology.200429 10 1933 1939 1:CAS:528:DC%2BD2cXnslSmu7w%3D 15257305 https://doi.org/10.1038/sj.npp.1300526 15257305
- LandoltHPWerthEBorbelyAADijkDJCaffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at nightBrain Res1995675 1–2 67 74 1:CAS:528:DyaK2MXksVylur0%3D 7796154 https://doi.org/10.1016/0006-8993(95)00040-W 7796154
- LandoltHPDijkDJGausSEBorbelyAACaffeine reduces low-frequency delta activity in the human sleep EEGNeuropsychopharmacology.199512 3 229 238 1:CAS:528:DyaK2MXlvFCltrs%3D 7612156 https://doi.org/10.1016/0893-133X(94)00079-F 7612156
- PerlisMLSmithMTAndrewsPJOrffHGilesDEBeta/gamma EEG activity in patients with primary and secondary insomnia and good sleeper controlsSleep.200124 1 110 117 1:STN:280:DC%2BD3M7pt1CgtQ%3D%3D 11204046 https://doi.org/10.1093/sleep/24.1.110 11204046
- AkesdotterCKenttaGElorantaSFranckJThe prevalence of mental health problems in elite athletesJ Sci Med Sport.202023 4 329 335 31806359 https://doi.org/10.1016/j.jsams.2019.10.022 31806359
- ChildsEHohoffCDeckertJXuKBadnerJde WitHAssociation between ADORA2A and DRD2 polymorphisms and caffeine-induced anxietyNeuropsychopharmacology.200833 12 2791 2800 1:CAS:528:DC%2BD1cXht1CmsL7M 18305461 2745641 https://doi.org/10.1038/npp.2008.17
- AlseneKDeckertJSandPde WitHAssociation between A2a receptor gene polymorphisms and caffeine-induced anxietyNeuropsychopharmacology.200328 9 1694 1702 1:CAS:528:DC%2BD3sXmsFeisLo%3D 12825092 https://doi.org/10.1038/sj.npp.1300232 12825092
- RogersPJHohoffCHeatherleySVMullingsELMaxfieldPJEvershedRP et al Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumptionNeuropsychopharmacology.201035 9 1973 1983 1:CAS:528:DC%2BC3cXovFKmsbw%3D 20520601 3055635 https://doi.org/10.1038/npp.2010.71
- ChangCPutukianMAerniGDiamondAHongGIngramY et al Mental health issues and psychological factors in athletes: detection, management, effect on performance and prevention: American medical society for sports medicine position statement-executive summaryBr J Sports Med.202054 4 216 220 31810972 https://doi.org/10.1136/bjsports-2019-101583 31810972
- DesbrowBHMScheelingsPAn examination of consumer exposure to caffeine from commercial coffee and coffee-flavoured milkJ Food Compos Anal201228 2 114 118 1:CAS:528:DC%2BC38XhvVSnurbO https://doi.org/10.1016/j.jfca.2012.09.001
- Desbrow B, Hall S, O’Connor H, Slater G, Barnes K, Grant G. Caffeine content of pre-workout supplements commonly used by Australian consumers. Drug Test Anal. 2019;11(3):523–9.
- RothwellJAFillatreYMartinJFLyanBPujos-GuillotEFezeuL et al New biomarkers of coffee consumption identified by the non-targeted metabolomic profiling of cohort study subjectsPLoS One20149 4 e93474 24713823 3979684 https://doi.org/10.1371/journal.pone.0093474 1:CAS:528:DC%2BC2cXhsFentrbM
- JamesJECaffeine and cognitive performance: persistent methodological challenges in caffeine researchPharmacol Biochem Behav2014124 117 122 1:CAS:528:DC%2BC2cXht1ymsL%2FN 24892519 https://doi.org/10.1016/j.pbb.2014.05.019
- KendlerKSPrescottCACaffeine intake, tolerance, and withdrawal in women: a population-based twin studyAm J Psychiatry1999156 2 223 228 1:STN:280:DyaK1M7kt1Kltg%3D%3D 9989558
- IrwinCDesbrowBEllisAO'KeeffeBGrantGLeverittMCaffeine withdrawal and high-intensity endurance cycling performanceJ Sports Sci201129 5 509 515 21279864 https://doi.org/10.1080/02640414.2010.541480
- Van SoerenMHSathasivamPSprietLLGrahamTECaffeine metabolism and epinephrine responses during exercise in users and nonusersJ Appl Physiol (1985)199375 2 805 812 https://doi.org/10.1152/jappl.1993.75.2.805
- CornelisMCMondaKLYuKPaynterNAzzatoEMBennettSN et al Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumptionPLoS Genet20117 4 e1002033 1:CAS:528:DC%2BC3MXltVWltb0%3D 21490707 3071630 https://doi.org/10.1371/journal.pgen.1002033
- Coffee, Caffeine Genetics C CornelisMCByrneEMEskoTNallsMA et al Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumptionMol Psychiatry201520 5 647 656 https://doi.org/10.1038/mp.2014.107 1:CAS:528:DC%2BC2cXhslartLzN
- JosseARDa CostaLACamposHEl-SohemyAAssociations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumptionAm J Clin Nutr201296 3 665 671 22854411 https://doi.org/10.3945/ajcn.112.038794
- CornelisMCEl-SohemyACamposHGenetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumptionAm J Clin Nutr200786 1 240 244 1:CAS:528:DC%2BD2sXotVynurs%3D 17616786 https://doi.org/10.1093/ajcn/86.1.240
- FredholmBBAdenosine actions and adenosine receptors after 1 week treatment with caffeineActa Physiol Scand1982115 2 283 286 1:CAS:528:DyaL38XitFSqs70%3D 6291335 https://doi.org/10.1111/j.1748-1716.1982.tb07078.x
- JohanssonBGeorgievVLindstromKFredholmBBA1 and A2A adenosine receptors and A1 mRNA in mouse brain: effect of long-term caffeine treatmentBrain Res1997762 1–2 153 164 1:CAS:528:DyaK2sXkt1Sjurs%3D 9262169 https://doi.org/10.1016/S0006-8993(97)00378-8
- NikodijevicOJacobsonKADalyJWLocomotor activity in mice during chronic treatment with caffeine and withdrawalPharmacol Biochem Behav199344 1 199 216 1:CAS:528:DyaK3sXpsVahtQ%3D%3D 7679219 3557839 https://doi.org/10.1016/0091-3057(93)90299-9
- BangsboJJacobsenKNordbergNChristensenNJGrahamTAcute and habitual caffeine ingestion and metabolic responses to steady-state exerciseJ Appl Physiol (1985)199272 4 1297 1303 1:CAS:528:DyaK38XktVagt7c%3D https://doi.org/10.1152/jappl.1992.72.4.1297
- BeaumontRCorderyPFunnellMMearsSJamesLWatsonPChronic ingestion of a low dose of caffeine induces tolerance to the performance benefits of caffeineJ Sports Sci201735 19 1920 1927 27762662 https://doi.org/10.1080/02640414.2016.1241421
- LaraBRuiz-MorenoCSalineroJJDel CosoJTime course of tolerance to the performance benefits of caffeinePLoS One201914 1 e0210275 1:CAS:528:DC%2BC1MXmtFCjsbg%3D 30673725 6343867 https://doi.org/10.1371/journal.pone.0210275
- GoncalvesLSPainelliVSYamaguchiGOliveiraLFSaundersBda SilvaRP et al Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementationJ Appl Physiol (1985)2017123 1 213 220 1:CAS:528:DC%2BC1cXitVeku7nF https://doi.org/10.1152/japplphysiol.00260.2017
- AretaJLIrwinCDesbrowBInaccuracies in caffeine intake quantification and other important limitations in recent publication by Goncalves et alJ Appl Physiol (1985)2017123 5 1414 1:STN:280:DC%2BC1M3ktFGisw%3D%3D https://doi.org/10.1152/japplphysiol.00489.2017
- GrahamTECaffeine and exercise: metabolism, endurance and performanceSports Med200131 11 785 807 1:STN:280:DC%2BD3MrjsFahtw%3D%3D 11583104 https://doi.org/10.2165/00007256-200131110-00002
- PorterfieldSLJLaubachLDapranoCComparison of the effect of caffeine ingestion on time to exhaustion between endurance trained and untrained menJ Exerc Physiol Online201316 90 98
- Brooks JHWK, Chrismas BCR. Acute effects of caffeine on strength performance in trained and untrained individuals. J Athl Enhanc. 2015;4.
- Boyett JC, Giersch GE, Womack CJ, Saunders MJ, Hughey CA, Daley HM, et al. Time of day and training status both impact the efficacy of caffeine for short duration cycling performance. Nutrients. 2016;8(10).
- CollompKAhmaidiSChatardJCAudranMPrefautCBenefits of caffeine ingestion on sprint performance in trained and untrained swimmersEur J Appl Physiol Occup Physiol199264 4 377 380 1:STN:280:DyaK383nsV2kuw%3D%3D 1592065 https://doi.org/10.1007/BF00636227
- BurkeLMCaffeine and sports performanceAppl Physiol Nutr Metab200833 6 1319 1334 1:CAS:528:DC%2BD1cXhsFSmtbfI 19088794 https://doi.org/10.1139/H08-130
- MizunoMKimuraYTokizawaKIshiiKOdaKSasakiT et al Greater adenosine A(2A) receptor densities in cardiac and skeletal muscle in endurance-trained men: a [11C] TMSX PET studyNucl Med Biol200532 8 831 836 1:CAS:528:DC%2BD2MXhtFKhsb%2FI 16253807 https://doi.org/10.1016/j.nucmedbio.2005.07.003
- ClarkILandoltHPCoffee, caffeine, and sleep: a systematic review of epidemiological studies and randomized controlled trialsSleep Med Rev201731 70 78 26899133 https://doi.org/10.1016/j.smrv.2016.01.006
- Robson-AnsleyPJGleesonMAnsleyLFatigue management in the preparation of Olympic athletesJ Sports Sci200927 13 1409 1420 19221925 https://doi.org/10.1080/02640410802702186
- HalsonSLJuliffLESleep, sport, and the brainProg Brain Res2017234 13 31 29031461 https://doi.org/10.1016/bs.pbr.2017.06.006
- LeederJGlaisterMPizzoferroKDawsonJPedlarCSleep duration and quality in elite athletes measured using wristwatch actigraphyJ Sports Sci201230 6 541 545 22329779 https://doi.org/10.1080/02640414.2012.660188
- HalsonSLSleep in elite athletes and nutritional interventions to enhance sleepSports Med201444 Suppl 1 S13 S23 24791913 https://doi.org/10.1007/s40279-014-0147-0
- Ramos-Campo DJ, Perez A, Avila-Gandia V, Perez-Pinero S, Rubio-Arias JA. Impact of caffeine intake on 800-m running performance and sleep quality in trained runners. Nutrients. 2019;11(9).
- DunicanICHigginsCCJonesMJClarkeMWMurrayKDawsonB et al Caffeine use in a super rugby game and its relationship to post-game sleepEur J Sport Sci201818 4 513 523 29431593 https://doi.org/10.1080/17461391.2018.1433238
- NedelecMHalsonSAbaidiaAEAhmaidiSDupontGStress, sleep and recovery in elite soccer: a critical review of the literatureSports Med201545 10 1387 1400 26206724 https://doi.org/10.1007/s40279-015-0358-z
- McLellanTMKamimoriGHVossDMBellDGColeKGJohnsonDCaffeine maintains vigilance and improves run times during night operations for special forcesAviat Space Environ Med200576 7 647 654 1:CAS:528:DC%2BD2MXmvVaru7k%3D 16018347
- McLellanTMKamimoriGHBellDGSmithIFJohnsonDBelenkyGCaffeine maintains vigilance and marksmanship in simulated urban operations with sleep deprivationAviat Space Environ Med200576 1 39 45 1:CAS:528:DC%2BD2MXhtlSjt7k%3D 15672985
- BchirFDoguiMBen FradjRArnaudMJSaguemSDifferences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjectsC R Biol2006329 7 512 519 1:CAS:528:DC%2BD28XmtVOjuro%3D 16797457 https://doi.org/10.1016/j.crvi.2006.01.006
- KamimoriGHMcLellanTMTateCMVossDMNiroPLiebermanHRCaffeine improves reaction time, vigilance and logical reasoning during extended periods with restricted opportunities for sleepPsychopharmacology2015232 12 2031 2042 1:CAS:528:DC%2BC2cXitFKmtLzP 25527035 https://doi.org/10.1007/s00213-014-3834-5
- Mora-RodriguezRPallaresJGLopez-GullonJMLopez-SamanesAFernandez-EliasVEOrtegaJFImprovements on neuromuscular performance with caffeine ingestion depend on the time-of-dayJ Sci Med Sport201518 3 338 342 24816164 https://doi.org/10.1016/j.jsams.2014.04.010
- McLellanTMKamimoriGHVossDMTateCSmithSJCaffeine effects on physical and cognitive performance during sustained operationsAviat Space Environ Med200778 9 871 877 1:CAS:528:DC%2BD2sXhtVyrs7jJ 17891897
- TikuisisPKeefeAAMcLellanTMKamimoriGCaffeine restores engagement speed but not shooting precision following 22 h of active wakefulnessAviat Space Environ Med200475 9 771 776 15460628
- ShareBSandersNKempJCaffeine and performance in clay target shootingJ Sports Sci200927 6 661 666 19308789 https://doi.org/10.1080/02640410902741068
- PomportesLBrisswalterJHaysADavrancheKEffects of Carbohydrate, Caffeine, and Guarana on Cognitive Performance, Perceived Exertion, and Shooting Performance in High-Level AthletesInt J Sports Physiol Perform.201914 5 576 82 30300016 https://doi.org/10.1123/ijspp.2017-0865
- DuncanMJDobellAPCaygillCLEyreETallisJThe effect of acute caffeine ingestion on upper body anaerobic exercise and cognitive performanceEur J Sport Sci201919 1 103 111 30102874 https://doi.org/10.1080/17461391.2018.1508505
- GillinghamRLKeefeAATikuisisPAcute caffeine intake before and after fatiguing exercise improves target shooting engagement timeAviat Space Environ Med200475 10 865 871 15497366
- ZhangYBalilionisGCasaruCGearyCSchumackerRENeggersYH et al Effects of caffeine and menthol on cognition and mood during simulated firefighting in the heatAppl Ergon201445 3 510 514 23891504 https://doi.org/10.1016/j.apergo.2013.07.005
- CroweMJLeichtASSpinksWLPhysiological and cognitive responses to caffeine during repeated, high-intensity exerciseInt J Sport Nutr Exerc Metab200616 5 528 544 1:CAS:528:DC%2BD28Xht1ehtLrE 17240784 https://doi.org/10.1123/ijsnem.16.5.528
- StuartGRHopkinsWGCookCCairnsSPMultiple effects of caffeine on simulated high-intensity team-sport performanceMed Sci Sports Exerc200537 11 1998 2005 1:CAS:528:DC%2BD2MXht1WksbzI 16286872 https://doi.org/10.1249/01.mss.0000177216.21847.8a
- Duvnjak-ZaknichDMDawsonBTWallmanKEHenryGEffect of caffeine on reactive agility time when fresh and fatiguedMed Sci Sports Exerc201143 8 1523 1530 1:CAS:528:DC%2BC3MXovF2jsLY%3D 21266929 https://doi.org/10.1249/MSS.0b013e31821048ab
- McLellanTMCaldwellJALiebermanHRA review of caffeine’s effects on cognitive, physical and occupational performanceNeurosci Biobehav Rev201671 294 312 1:CAS:528:DC%2BC28XhsFCmt77L 27612937 https://doi.org/10.1016/j.neubiorev.2016.09.001
- Antonio JKM, Horn C, Jiannine L, Carson C, Ellerbroek A, Roberts J, Peacock C, Tartar J. The effects of an energy drink on psychomotor vigilance in trained individuals. J Funct Morphol Kinesiol. 2019;4(47).
- CrawfordCTeoLLaffertyLDrakeABinghamJJGallonMD et al Caffeine to optimize cognitive function for military mission-readiness: a systematic review and recommendations for the fieldNutr Rev201775 suppl_2 17 35 28969341 https://doi.org/10.1093/nutrit/nux007
- McLellanTMBellDGKamimoriGHCaffeine improves physical performance during 24 h of active wakefulnessAviat Space Environ Med200475 8 666 672 1:CAS:528:DC%2BD2cXnt1Kmtro%3D 15328782
- ChiaJSBarrettLAChowJYBurnsSFEffects of caffeine supplementation on performance in ball gamesSports Med201747 12 2453 2471 28741186 https://doi.org/10.1007/s40279-017-0763-6
- PontifexKJWallmanKEDawsonBTGoodmanCEffects of caffeine on repeated sprint ability, reactive agility time, sleep and next day performanceJ Sports Med Phys Fitness201050 4 455 464 1:CAS:528:DC%2BC3MXktVKls70%3D 21178933
- BowtellJLMohrMFulfordJJackmanSRErmidisGKrustrupP et al Improved exercise tolerance with caffeine is associated with modulation of both peripheral and central neural processes in human participantsFront Nutr20185 6 29484298 5816050 https://doi.org/10.3389/fnut.2018.00006 1:CAS:528:DC%2BC1MXitFKhurbM
- CohnJPauleMGRepeated acquisition of response sequences: the analysis of behavior in transitionNeurosci Biobehav Rev199519 3 397 406 1:STN:280:DyaK28%2FjtFyqtw%3D%3D 7566741 https://doi.org/10.1016/0149-7634(94)00067-B 7566741
- SavilleCWNde MorreeHMDundonNMMarcoraSMKleinCEffects of caffeine on reaction time are mediated by attentional rather than motorprocessesPsychopharmacology.2018235 3 749 759 1:CAS:528:DC%2BC2sXitVejt7vP 29273820 https://doi.org/10.1007/s00213-017-4790-7 29273820
- ConnellCJThompsonBKuhnGGantNExercise-induced fatigue and caffeine supplementation affect psychomotor performance but not covert visuo-spatial attentionPLoS One201611 10 e0165318 27768747 5074788 https://doi.org/10.1371/journal.pone.0165318 1:CAS:528:DC%2BC2sXht1Ogsr%2FN
- ConcertoCInfortunaCChusidECoiraDBabayevJMetwalyR et al Caffeinated energy drink intake modulates motor circuits at rest, before and after a movementPhysiol Behav2017179 361 368 1:CAS:528:DC%2BC2sXhtFyns7jJ 28694153 https://doi.org/10.1016/j.physbeh.2017.07.013 28694153
- Gonzalez-AlonsoJCrandallCGJohnsonJMThe cardiovascular challenge of exercising in the heatJ Physiol2008586 1 45 53 1:CAS:528:DC%2BD1cXhtFaqtbk%3D 17855754 https://doi.org/10.1113/jphysiol.2007.142158 17855754
- CheungSSSleivertGGMultiple triggers for hyperthermic fatigue and exhaustionExerc Sport Sci Rev200432 3 100 106 15243205 https://doi.org/10.1097/00003677-200407000-00005 15243205
- NicholsAWHeat-related illness in sports and exerciseCurr Rev Musculoskelet Med20147 4 355 365 25240413 4596225 https://doi.org/10.1007/s12178-014-9240-0
- ElyBRElyMRCheuvrontSNMarginal effects of a large caffeine dose on heat balance during exercise-heat stressInt J Sport Nutr Exerc Metab201121 1 65 70 1:CAS:528:DC%2BC3MXivVSksLo%3D 21411837 https://doi.org/10.1123/ijsnem.21.1.65 21411837
- SuviSTimpmannSTammMAedmaMKreegipuuKOopikVEffects of caffeine on endurance capacity and psychological state in young females and males exercising in the heatAppl Physiol Nutr Metab201742 1 68 76 1:CAS:528:DC%2BC28XitFent7rO 28002684 https://doi.org/10.1139/apnm-2016-0206 28002684
- MaughanRJGriffinJCaffeine ingestion and fluid balance: a reviewJ Hum Nutr Diet200316 6 411 420 1:STN:280:DC%2BD1MnktlKruw%3D%3D 19774754 https://doi.org/10.1046/j.1365-277X.2003.00477.x 19774754
- ZhangYCocaACasaDJAntonioJGreenJMBishopPACaffeine and diuresis during rest and exercise: a meta-analysisJ Sci Med Sport201518 5 569 574 25154702 https://doi.org/10.1016/j.jsams.2014.07.017 25154702
- CohenBSNelsonAGPrevostMCThompsonGDMarxBDMorrisGSEffects of caffeine ingestion on endurance racing in heat and humidityEur J Appl Physiol Occup Physiol199673 3–4 358 363 1:STN:280:DyaK28znsFGmug%3D%3D 8781869 https://doi.org/10.1007/BF02425499
- Del CosoJEstevezEMora-RodriguezRCaffeine effects on short-term performance during prolonged exercise in the heatMed Sci Sports Exerc.200840 4 744 18317369 https://doi.org/10.1249/MSS.0b013e3181621336 1:CAS:528:DC%2BD1cXjtl2nt7c%3D
- CheuvrontSNElyBRKenefickRWMichniak-KohnBBRoodJCSawkaMNNo effect of nutritional adenosine receptor antagonists on exercise performance in the heatAm J Phys Regul Integr Comp Phys2009296 2 R394 R401 1:CAS:528:DC%2BD1MXitVejtL8%3D
- GanioMSJohnsonECLopezRMStearnsRLEmmanuelHAndersonJM et al Caffeine lowers muscle pain during exercise in hot but not cool environmentsPhysiol Behav2011102 3–4 429 435 1:CAS:528:DC%2BC3MXnsFWhsw%3D%3D 21163281 https://doi.org/10.1016/j.physbeh.2010.12.005
- PitchfordNWFellJWLeverittMDDesbrowBShingCMEffect of caffeine on cycling time-trial performance in the heatJ Sci Med Sport201417 4 445 449 23932933 https://doi.org/10.1016/j.jsams.2013.07.004
- BeaumontREJamesLJEffect of a moderate caffeine dose on endurance cycle performance and thermoregulation during prolonged exercise in the heatJ Sci Med Sport201720 11 1024 1028 28420550 https://doi.org/10.1016/j.jsams.2017.03.017
- GrahamTECaffeine, coffee and ephedrine: impact on exercise performance and metabolismCan J Appl Physiol200126 Suppl S103 S119 1:CAS:528:DC%2BD38XhsVOjsro%3D 11897887 11897887
- DohertyMSmithPHughesMDavisonRCaffeine lowers perceptual response and increases power output during high-intensity cyclingJ Sports Sci200422 7 637 643 15370494 https://doi.org/10.1080/02640410310001655741
- BerglundBHemmingssonPEffects of caffeine ingestion on exercise performance at low and high altitudes in cross-country skiersInt J Sports Med19823 4 234 236 1:STN:280:DyaL3s7gslyksA%3D%3D 7152771 https://doi.org/10.1055/s-2008-1026094 7152771
- FulcoCSRockPBTradLARoseMSForteVAJrYoungPM et al Effect of caffeine on submaximal exercise performance at altitudeAviat Space Environ Med199465 6 539 545 1:CAS:528:DyaK2cXmsVKjs78%3D 8074628 8074628
- SmirmaulBPde MoraesACAngiusLMarcoraSMEffects of caffeine on neuromuscular fatigue and performance during high-intensity cycling exercise in moderate hypoxiaEur J Appl Physiol2017117 1 27 38 1:CAS:528:DC%2BC28XhvFCgsbbL 27864638 https://doi.org/10.1007/s00421-016-3496-6 27864638
- DavisJKGreenJMCaffeine and anaerobic performance: ergogenic value and mechanisms of actionSports Med200939 10 813 832 1:STN:280:DC%2BD1MnivVOlsA%3D%3D 19757860 https://doi.org/10.2165/11317770-000000000-00000 19757860
- TeekachunhateanSTosriNRojanasthienNSrichairatanakoolSSangdeeCPharmacokinetics of caffeine following a single administration of coffee enema versus oral coffee consumption in healthy male subjectsISRN Pharmacol20132013 147238 23533801 3603218 https://doi.org/10.1155/2013/147238
- MagkosFKavourasSACaffeine use in sports, pharmacokinetics in man, and cellular mechanisms of actionCrit Rev Food Sci Nutr200545 7–8 535 562 1:CAS:528:DC%2BD2MXhtlakt7%2FP 16371327 https://doi.org/10.1080/1040-830491379245 16371327
- BirkettDJMinersJOCaffeine renal clearance and urine caffeine concentrations during steady state dosing. Implications for monitoring caffeine intake during sports eventsBr J Clin Pharmacol199131 4 405 408 1:CAS:528:DyaK3MXitl2qsr4%3D 2049248 1368325 https://doi.org/10.1111/j.1365-2125.1991.tb05553.x
- CollompKAnselmeFAudranMGayJPChanalJLPrefautCEffects of moderate exercise on the pharmacokinetics of caffeineEur J Clin Pharmacol199140 3 279 282 1:CAS:528:DyaK3MXitl2ru78%3D 2060565 https://doi.org/10.1007/BF00315209 2060565
- HoffmanJRKangJRatamessNAJenningsPFMangineGTFaigenbaumADEffect of nutritionally enriched coffee consumption on aerobic and anaerobic exercise performanceJ Strength Cond Res200721 2 456 459 17530975 17530975
- GlaisterMWilliamsBHMuniz-PumaresDBalsalobre-FernandezCFoleyPThe effects of caffeine supplementation on physiological responses to submaximal exercise in endurance-trained menPLoS One201611 8 e0161375 27532605 4988702 https://doi.org/10.1371/journal.pone.0161375 1:CAS:528:DC%2BC2sXktVSqsr8%3D
- ChengCFHsuWCKuoYHShihMTLeeCLCaffeine ingestion improves power output decrement during 3-min all-out exerciseEur J Appl Physiol2016116 9 1693 1702 1:CAS:528:DC%2BC28XhtFKmsb3F 27372742 https://doi.org/10.1007/s00421-016-3423-x 27372742
- SyedSAKamimoriGHKellyWEddingtonNDMultiple dose pharmacokinetics of caffeine administered in chewing gum to normal healthy volunteersBiopharm Drug Dispos200526 9 403 409 1:CAS:528:DC%2BD28Xot1GqsQ%3D%3D 16158445 https://doi.org/10.1002/bdd.469 16158445
- SadekPPanXShepherdPMalandainECarneyJColemanHA randomized, two-way crossover study to evaluate the pharmacokinetics of caffeine delivered using caffeinated chewing gum versus a marketed caffeinated beverage in healthy adult volunteersJ Caffeine Res20177 4 125 132 1:CAS:528:DC%2BC2sXhvFKitbbP 29230348 5724581 https://doi.org/10.1089/jcr.2017.0025
- PerkoMJNielsenHBSkakCClemmesenJOSchroederTVSecherNHMesenteric, coeliac and splanchnic blood flow in humans during exerciseJ Physiol1998513 Pt 3 907 913 1:CAS:528:DyaK1MXmt1Crug%3D%3D 9824727 2231328 https://doi.org/10.1111/j.1469-7793.1998.907ba.x
- BellarDKamimoriGHGlickmanELThe effects of low-dose caffeine on perceived pain during a grip to exhaustion taskJ Strength Cond Res201125 5 1225 1228 21522070 https://doi.org/10.1519/JSC.0b013e3181d9901f 21522070
- PooleRLTordoffMGThe taste of caffeineJ Caffeine Res20177 2 39 52 28660093 5488350 https://doi.org/10.1089/jcr.2016.0030
- SugitaMYamamotoKHironoCShibaYInformation processing in brainstem bitter taste-relaying neurons defined by genetic tracingNeuroscience.2013250 166 180 1:CAS:528:DC%2BC3sXhsVWjtL3E 23850686 https://doi.org/10.1016/j.neuroscience.2013.06.032 23850686
- MatsumotoIGustatory neural pathways revealed by genetic tracing from taste receptor cellsBiosci Biotechnol Biochem201377 7 1359 1362 1:CAS:528:DC%2BC3sXht1CiurjF 23832339 3804333 https://doi.org/10.1271/bbb.130117
- WilsonPBDietary and non-dietary correlates of gastrointestinal distress during the cycle and run of a triathlonEur J Sport Sci201616 4 448 454 26222930 https://doi.org/10.1080/17461391.2015.1046191 26222930
- BoekemaPJSamsomMvan Berge HenegouwenGPSmoutAJCoffee and gastrointestinal function: facts and fiction. A reviewScand J Gastroenterol Suppl1999230 35 39 1:STN:280:DyaK1MvislyjtA%3D%3D 10499460 10499460
- SinclairJBottomsLThe effects of carbohydrate and caffeine mouth rinsing on arm crank time-trial performanceJ Sports Res.201414 3 259 64
- FingerTEBottgerBHansenAAndersonKTAlimohammadiHSilverWLSolitary chemoreceptor cells in the nasal cavity serve as sentinels of respirationProc Natl Acad Sci U S A2003100 15 8981 8986 1:CAS:528:DC%2BD3sXlvVyiurg%3D 12857948 166424 https://doi.org/10.1073/pnas.1531172100
- PhukanKNandyMSharmaRBSharmaHKNanosized drug delivery systems for direct nose to brain targeting: a reviewRecent Pat Drug Deliv Formul201610 2 156 164 1:CAS:528:DC%2BC28XhtFGlt7fJ 26996366 https://doi.org/10.2174/1872211310666160321123936 26996366
- PardeshiCVBelgamwarVSDirect nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targetingExpert Opin Drug Deliv201310 7 957 972 1:CAS:528:DC%2BC3sXpslChtro%3D 23586809 https://doi.org/10.1517/17425247.2013.790887 23586809
- DohertyMSmithPMDavisonRCHughesMGCaffeine is ergogenic after supplementation of oral creatine monohydrateMed Sci Sports Exerc200234 11 1785 1792 1:CAS:528:DC%2BD38XovVehsrs%3D 12439084 https://doi.org/10.1097/00005768-200211000-00015 12439084
- LeeCLLinJCChengCFEffect of caffeine ingestion after creatine supplementation on intermittent high-intensity sprint performanceEur J Appl Physiol2011111 8 1669 1677 1:CAS:528:DC%2BC3MXhtFKqs7zM 21207054 https://doi.org/10.1007/s00421-010-1792-0 21207054
- VandenbergheKGillisNVan LeemputteMVan HeckePVanstapelFHespelPCaffeine counteracts the ergogenic action of muscle creatine loadingJ Appl Physiol199680 2 452 457 1:STN:280:DyaK2s%2FotlSjuw%3D%3D 8929583 https://doi.org/10.1152/jappl.1996.80.2.452 8929583
- ClarksonPMNutrition for improved sports performance. Current issues on ergogenic aidsSports Med199621 6 393 401 1:STN:280:DyaK28znvFCguw%3D%3D 8784959 https://doi.org/10.2165/00007256-199621060-00001 8784959
- HespelPOp't EijndeBVan LeemputteMOpposite actions of caffeine and creatine on muscle relaxation time in humansJ Appl Physiol200292 2 513 518 1:CAS:528:DC%2BD38XhtlSqtbo%3D 11796658 https://doi.org/10.1152/japplphysiol.00255.2001 11796658
- GreenhaffPLBodinKSoderlundKHultmanEEffect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesisAm J Phys1994266 5 Pt 1 E725 E730 1:CAS:528:DyaK2cXktleqt7s%3D
- SpradleyBDCrowleyKRTaiCYKendallKLFukudaDHEspositoEN et al Ingesting a pre-workout supplement containing caffeine, B-vitamins, amino acids, creatine, and beta-alanine before exercise delays fatigue while improving reaction time and muscular enduranceNutr Metab20129 28 1:CAS:528:DC%2BC38XotlCqt7w%3D https://doi.org/10.1186/1743-7075-9-28
- JoyJMLoweryRPFalconePHVogelRMMosmanMMTaiCY et al A multi-ingredient, pre-workout supplement is apparently safe in healthy males and femalesFood Nutr Res201559 27470 26085481 https://doi.org/10.3402/fnr.v59.27470
- KreiderRBKalmanDSAntonioJZiegenfussTNWildmanRCollinsR et al International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicineJ Int Soc Sports Nutr201714 18 28615996 5469049 https://doi.org/10.1186/s12970-017-0173-z 1:CAS:528:DC%2BC1cXitVKmtb%2FE
- KovacsEMStegenJBrounsFEffect of caffeinated drinks on substrate metabolism, caffeine excretion, and performanceJ Appl Physiol199885 2 709 715 1:CAS:528:DyaK1cXlsFGnsLo%3D 9688750 https://doi.org/10.1152/jappl.1998.85.2.709
- van NieuwenhovenMABrounsFKovacsEMThe effect of two sports drinks and water on GI complaints and performance during an 18-km runInt J Sports Med200526 4 281 285 15795812 https://doi.org/10.1055/s-2004-820931
- SasakiHMaedaJUsuiSIshikoTEffect of sucrose and caffeine ingestion on performance of prolonged strenuous runningInt J Sports Med19878 4 261 265 1:STN:280:DyaL1c%2FjtFymtg%3D%3D 3667022 https://doi.org/10.1055/s-2008-1025666
- CongerSAWarrenGLHardyMAMillard-StaffordMLDoes caffeine added to carbohydrate provide additional ergogenic benefit for endurance?Int J Sport Nutr Exerc Metab201121 1 71 84 1:CAS:528:DC%2BC3MXivVSksLs%3D 21411838 https://doi.org/10.1123/ijsnem.21.1.71
- ClarkeJSHightonJCloseGLTwistCCarbohydrate and caffeine improves high intensity running of elite rugby league interchange players duringsimulated match playJ Strength Cond Res.201933 5 1320 1327 27930447 https://doi.org/10.1519/JSC.0000000000001742
- StevensonEJHayesPRAllisonSJThe effect of a carbohydrate-caffeine sports drink on simulated golf performanceAppl Physiol Nutr Metab200934 4 681 688 1:CAS:528:DC%2BD1MXhtVSjsrvP 19767804 https://doi.org/10.1139/H09-057
- RobertsSPStokesKATrewarthaGDoyleJHogbenPThompsonDEffects of carbohydrate and caffeine ingestion on performance during a rugby union simulation protocolJ Sports Sci201028 8 833 842 20521199 https://doi.org/10.1080/02640414.2010.484069
- LeeCLChengCFAstorinoTALeeCJHuangHWChangWDEffects of carbohydrate combined with caffeine on repeated sprint cycling and agility performance in female athletesJ Int Soc Sports Nutr201411 17 24855458 4012529 https://doi.org/10.1186/1550-2783-11-17 1:CAS:528:DC%2BC2MXivVahsrw%3D
- ClarkeNDDuncanMJEffect of carbohydrate and caffeine ingestion on badminton performanceInt J Sports Physiol Perform201611 1 108 115 26024551 https://doi.org/10.1123/ijspp.2014-0426
- Acker-HewittTLShaferBMSaundersMJGohQLudenNDIndependent and combined effects of carbohydrate and caffeine ingestion on aerobic cycling performance in the fed stateAppl Physiol Nutr Metab201237 2 276 283 1:CAS:528:DC%2BC38Xoslegs7Y%3D 22436075 https://doi.org/10.1139/h11-160
- PedersenDJLessardSJCoffeyVGChurchleyEGWoottonAMNgT et al High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeineJ Appl Physiol2008105 1 7 13 1:CAS:528:DC%2BD1cXps12htrw%3D 18467543 https://doi.org/10.1152/japplphysiol.01121.2007
- BeelenMKranenburgJSendenJMKuipersHLoonLJImpact of caffeine and protein on postexercise muscle glycogen synthesisMed Sci Sports Exerc201244 4 692 700 1:CAS:528:DC%2BC38Xkt1Ols7c%3D 21986807 https://doi.org/10.1249/MSS.0b013e31823a40ef
- TaylorCHighamDCloseGLMortonJPThe effect of adding caffeine to postexercise carbohydrate feeding on subsequent high-intensity interval-running capacity compared with carbohydrate aloneInt J Sport Nutr Exerc Metab201121 5 410 416 1:CAS:528:DC%2BC3MXhsVCns7rP 21832305 https://doi.org/10.1123/ijsnem.21.5.410
- NiemanDCGoodmanCLCappsCRShueZLArnotRInfluence of 2-weeks ingestion of high chlorogenic acid coffee on mood state, performance, and postexercise inflammation and oxidative stress: a randomized, placebo-controlled trialInt J Sport Nutr Exerc Metab201828 1 55 65 1:CAS:528:DC%2BC1MXntFOqs74%3D 29035597 https://doi.org/10.1123/ijsnem.2017-0198
- DesbrowBHughesRLeverittMScheelingsPAn examination of consumer exposure to caffeine from retail coffee outletsFood Chem Toxicol200745 9 1588 1592 1:CAS:528:DC%2BD2sXot12lurs%3D 17412475 https://doi.org/10.1016/j.fct.2007.02.020
- SouzaDBDel CosoJCasonattoJPolitoMDAcute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysisEur J Nutr201756 1 13 27 1:CAS:528:DC%2BC28XhslSlt7zM 27757591 https://doi.org/10.1007/s00394-016-1331-9
- CampbellBWilbornCLa BountyPTaylorLNelsonMTGreenwoodM et al International Society of Sports Nutrition position stand: energy drinksJ Int Soc Sports Nutr201310 1 1 23281794 3538552 https://doi.org/10.1186/1550-2783-10-1
- QuinlivanAIrwinCGrantGDAnoopkumar-DukieSSkinnerTLeverittM et al The effects of red Bull energy drink compared with caffeine on cycling time-trial performanceInt J Sports Physiol Perform201510 7 897 901 25710190 https://doi.org/10.1123/ijspp.2014-0481