Caffeine and Cognitive Functions in Sports: A Systematic Review and Meta-Analysis

Nutrients 2021, 13, 868. https://doi.org/10.3390/nu13030868 www.mdpi.com/journal/nutrients Review Caffeine and Cognitive Functions in Sports: A Systematic Review and Meta-Analysis Jorge Lorenzo Calvo 1, Xueyin Fei 2,*, Raúl Domínguez 3,4 and Helios Pareja-Galeano 2 1 Sports Department, Facultad de Ciencias de la Actividad Física y del Deporte, Universidad Politécnica de Madrid, 28040 Madrid, Spain; [email protected] 2 Faculty of Sports Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain; helios.parej[email protected] 3 Studies Research Group in Neuromuscular Responses (GEPREN), University of Lavras, Lavras 37200-000, Brazil; raul_dominguez_herrer[email protected] 4 Departamento de Motricidad Humana y Rendimiento Deporte, Universidad de Sevilla, 41013 Sevilla, Spain * Correspondence: [email protected]; Tel.: +86-153-6930-8755 Abstract: Cognitive functions are essential in any form of exercise. Recently, interest has mounted in addressing the relationship between caffeine intake and cognitive performance during sports practice. This review examines this relationship through a structured search of the databases Medline/PubMed and Web of Science for relevant articles published in English from August 1999 to March 2020. The study followed PRISMA guidelines. Inclusion criteria were defined according to the PICOS model. The identified records reported on randomized cross-over studies in which caffeine intake (as drinks, capsules, energy bars, or gum) was compared to an identical placebo situation. There were no filters on participants’ training level, gender, or age. For the systematic review, 13 studies examining the impacts of caffeine on objective measures of cognitive performance or selfreported cognitive performance were selected. Five of these studies were also subjected to metaanalysis. After pooling data in the meta-analysis, the significant impacts of caffeine only emerged on attention, accuracy, and speed. The results of the 13 studies, nevertheless, suggest that the intake of a low/moderate dose of caffeine before and/or during exercise can improve self-reported energy, mood, and cognitive functions, such as attention; it may also improve simple reaction time, choice reaction time, memory, or fatigue, however, this may depend on the research protocols. Keywords: caffeine; cognitive function; ergogenic drinks; sport 1. Introduction Caffeine (1,3,7-trimethylxanthine) is among the supplements most commonly used by athletes of all sports modalities [1–4]. Since 2004, when caffeine was removed from the list of banned substances for sports, caffeine supplementation has reached a prevalence rate of 76% among international competition athletes [5]. In the 1970s, the first studies addressing the effect of caffeine on sports performance started to emerge. These studies identified an improvement in time to exhaustion in an endurance test, and such ergogenic effects were attributed to increased lipolysis and sparing of muscle glycogen [6]. Currently, the ergogenic capacity of caffeine is explained by its blocking effect on adenosine receptors [7] A1, A2A, and A2B [8], due to the similar chemical structure of caffeine and adenosine. By blocking adenosine receptors at the neuromuscular level [9], caffeine enhances neuromuscular recruitment [10]. In addition, caffeine potentiates the Na+-K+ pump [11] and increases Ca2+ bioavailability at the myoplasm by inducing Ca2+ release from the sarcoplasmic reticulum and inhibition of its reuptake [12], resulting in the translocation of glycogen phosphorylase-b into isoform-a [13]. Furthermore, caffeine maximizes glycolytic activity through increased activity of the enzyme phosphofructokinase [14]. This means that, after ~60 min of caffeine supplementation coinciding with peak blood levels Citation: Lorenzo Calvo, J.; Fei, X.; Domínguez, R.; Pareja-Galeano, H. Caffeine and Cognitive Functions in Sport: A Systematic Review and Meta-Analysis. Nutrients 2021, 13, 868. https://doi.org/10.3390/ nu13030868 Academic Editor: Juan J. Salinero Received: 15 January 2021 Accepted: 1 March 2021 Published: 6 March 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Nutrients 2021, 13, 868 2 of 18 [15], caffeine has confirmed ergogenic effects in a wide range of sports activities [16,17]. These activities include as much of those involving a predominance of oxidative metabolism, such as endurance sport modalities [18,19], as those involving a predominance of non-oxidative metabolism, such as those requiring a high movement velocity [20] and power [21], i.e., the Wingate test [22], or a mixed metabolism, such as team sports [23], combat sports [24], or racquet sports [25]. So far, studies examining this topic have focused on the benefits of caffeine for physical performance, while its impacts on cognitive performance have received less attention. Cognitive functions include a broad range of basic mental operations, such as attention, memory, and executive functions involving working memory, decision-making, and multitasking, among others. An athlete’s attention, defined as the allocation of cognitive resources to internal or external stimuli, is key to successful sports performance [26]. The beneficial effects attributed to caffeine supplementation are based on the notion that, as adenosine inhibits the release of excitatory neurotransmitters, such as dopamine (excitatory neurotransmitter in the brain) [27], the antagonistic effects of caffeine could lead to the release of excitatory neurotransmitters (i.e., dopamine and noradrenaline) [28], and could thus exert central ergogenic effects [29]. Accordingly, caffeine supplementation is thought to promote a more favorable mood [30,31], increasing alertness and reducing the feeling of fatigue [32,33]. These effects could be considered beneficial for athletes practicing sports with high demands at both the physical and cognitive levels. For example, soccer is highly aerobic, but also includes a mix of anaerobic power and cognitive load, with all three contributing to a player’s performance and success [34–36]. In different studies, positive effects of caffeine have been reported in improving word learning speed and delayed recall [37], along with reaction time in response to tests, such as the Stroop test and the Rapid Visual Information Processing test, before and during exercise [38]. In addition, caffeine has been shown to improve reaction time, accuracy, and willingness to put physical effort into exercise [39]. Based on these potential ergogenic effects of caffeine supplementation on both physical and cognitive functions, this systematic review and meta-analysis sought to critically assess the effect of caffeine administered in the form of gum, capsules, drinks, or energy bars on several measures of cognitive performance in sports. 2. Materials and Methods 2.1. Protocol The systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines [40]. To define the inclusion criteria, the PICOS model was followed [41] (see Table 1). Table 1. PICOS criteria for the inclusion of studies in the systematic review. Parameter Inclusion criteria Population Adult athletes Intervention Caffeine supplementation Comparators Placebo supplementation Outcomes Variables related to cognitive performance in sports, including reaction time, memory, focus, concentration, alertness, fatigue, motivation, and attention Study design Double-blind/singleblind and randomized cross-over design Nutrients 2021, 13, 868 3 of 18 2.2. Search Strategy The databases PubMed and Web of Science (WOS) were searched for articles published in English from 1 August 1999 to 18 March 2020 using the terms and operators (“caffeine” OR “energy drinks” OR “beverage”) AND (“cognitive”) AND (“sport” OR “exercise”). 2.3. Eligibility Criteria Records were identified according to the inclusion criteria: (1) reports with clear information regarding the administration of caffeine (relative dose of caffeine per kg of body weight and/or an absolute dose of caffeine with information about body weight, timing of caffeine intake before the onset of performance tests, etc.); (2) caffeine administered in the form of a beverage, coffee, energy bar, gum, or capsule; (3) studies including a placebo group; (4) experiment is well-designed and involves the ingestion of a dose of caffeine or a caffeine-containing product before and/or during sport or exercise; (5) design is a double-blind, randomized cross-over experiment; and (6) article language is English. The following studies were excluded: (1) those conducted in ill or injured participants; (2) those in which participants were not adults; (3) those in which caffeine doses below 1 mg/kg or above 9 mg/kg were used; (4) those lacking a true placebo condition; and (5) those lacking pre-experimental standardization, such as the elimination of dietary sources of caffeine 24 h before testing. To increase the power of the analysis, no filters were applied to the athletes’ training status or sex. Once the records were identified, duplicates were first removed. Next, based on the titles and abstracts of articles, all of those that did not meet the eligibility criteria were excluded. Finally, the full texts of the resulting articles were read, and those that did not meet the inclusion criteria were removed. The information extracted from the records identified was: study source (including authors and year of publication), study design, caffeine administration (dose and timing), sample size, characteristics of the participants (training status and sex), and outcomes of the interventions. For the meta-analysis, studies were excluded if they did not report adequate performance data (i.e., no mean ± standard deviation (SD) or appropriate effect sizes). If a study contained multiple intervention arms (e.g., involving different doses of caffeine, dosing regimens, or participant populations), more than one of which was eligible for inclusion, the separate arms were treated as discrete studies, termed trials. As single trials often measured performance multiple times and/or used multiple tests that generated several different outcomes, each trial could provide more than one effect estimate (EE). 2.4. Quality Assessment To determine the methodological quality of the quantitative studies reviewed, the criteria of Law et al. were used [42]. According to these criteria, the following factors were assessed as 16 items: purpose, literature background, design, sample, outcomes, intervention, results, dropouts, conclusions, and implications. Each of these items was awarded a score of 1 (meets the criterion), 0 (does not meet the criterion), or NA (not applicable). The score of all 16 items together was the measure of the methodological quality of the study. Studies awarded a score of 12 to 15 were considered to be of good to excellent methodological quality [42]. 2.5. Performance Outcomes All objective and subjective measurements of cognitive performance were considered in the review (see Table 2), while only objective measurements were included in the metaanalysis. Nutrients 2021, 13, 868 4 of 18 Table 2. Subjective scales and score systems used to measure cognitive functions. Scale Score System Cognitive Function Visual analogue scale for fatigue (VAS-F)  Likert-type scale  Fatigue  Energy  Alertness  Focus Profile of mood states (POMS)  5-point scale  Fatigue  Anger  Vigor  Tension  Esteem  Confusion  Depression Felling scale (FS)  11-point scale  Pleasure/Displeasure Felt arousal scale (FAS)  6-point scale  Perceived arousal Rating of perceived exertion (RPE)  6–20 point scale  How hard you are working The different cognitive performance tests assessed the different functions listed in Table 3. Within each domain, response speed and response accuracy data were handled separately. Table 3. Objective tests, dependent variables, and cognitive functions measured. Test Dependent Variables Function Measured Attention SCWT (Stroop Color and Word Test)  Time to read card (s)  Congruent accuracy (%)  Incongruent accuracy (%)  Visual selective attention  Attention bias  Sensitivity to interference  Ability to suppress an automated response Flanker test  RT (ms)  Congruent accuracy (%)  Incongruent accuracy (%)  Visual selective attention  Ability to manage interference RVIP (rapid visual information p rocessing task)  RT (ms)  True positive (TP) rate (%)  Miss rate (%)  Visual selective attention  Working memory Visual search test  RT for correct responses (ms)  Accuracy (%)  Attention shifting SDT (signal d etection task)  RT (ms)  Efficiency (%)  Efficiency of visual signal detection (A’)  Speed of signal detection  Efficiency of signal detection/attention shifting Nutrients 2021, 13, 868 5 of 18 Reaction Time Simple visual reaction time test  RT (ms)  Simple psychomotor speed MCRT (motor c hoice reaction time test)  Simple RT (ms)  Choice RT (ms)  S- R incompatible choice RT (ms)  Simple psychomotor speed  Complex decision speed  Complex response preparation speed Choice r eaction time (CRT) test  Choice RT (ms)  Decisionmaking time Inhibitory Control Go/no-go task  Choice RT (ms)  Choice RT score (%)  Complex decision speed and accuracy  Inhibitory control Go/no-go and cognitive load task  Cognitive load RT (ms)  Cognitive load RT score (%)  Inhibitory control Simon task  Congruent RT  Incongruent RT  Errors rate (%)  The ability to inhibit pre-potent responses Memory VVLT (Visual Verbal Learning Test)  RT (ms)  Recognition of words (0~15)  Speed of retrieval from long-term memory  Storage in longterm memory Number recall test  Percentage number recall  Short-term memory Internal Time-Keep- ing Mechanisms Duration production task  Produced duration (ms)  Variance (ms)  Effect of changes in the speed of internal timekeeping mechanisms 2.6. Data Synthesis and Meta-Analysis For each performance outcome, independent-group Hedges’ g intervention EEs [43] were calculated by standardizing the mean difference between the control and intervention performance scores against the pooled SD and correcting for bias due to a small sample size. The magnitude of the effect was as defined by Cohen [44]: Hedges’ g ≤ 0.2 = small, 0.2–0.5 = medium, and ≥ 0.8 = large, whereby a positive value indicated a beneficial effect of caffeine, irrespective of the performance outcome measured. If a trial repeated the same performance test two (or more) times within a 6 h period, and no additional caffeine was provided between tests, the resulting Hedges’ g values were averaged into a single EE (with the sample size increased accordingly). Meta-analyses were performed to determine the effect of caffeine on: (1) attention (response speed and accuracy); (2) simple reaction time (response speed); (3) choice reaction time (response speed and accuracy); and (4) inhibitory control (response speed and accuracy). Remaining performance outcomes (i.e., memory and detection) were unsuitable for meta-analysis, either because the data were Nutrients 2021, 13, 868 6 of 18 derived from too small a number of studies or performance tests and outcomes were too heterogeneous for a meaningful meta-analysis. When fixed-effect models were not suitable for the studies, weighted mean treatment effects were calculated using random-effect models, whereby trials were weighted by the inverse variance of the performance change. Significance was considered if the 95% confidence interval (CI) did not include zero. Heterogeneity was assessed using Cochran’s Q and  index. For Cochran’s Q, a p-value < 0.10 was used to indicate significant heterogeneity. Low, moderate, and high heterogeneity was indicated by an  value of 25, 50, and 75%, respectively [45]. All statistical tests were performed using the software packages IBM SPSS version 25.0 and Review Manager version 5.3. All data are provided as mean ± SD. 3. Results 3.1. Selection of Studies In the database search, 190 records were identified. Of these, 29 duplicates were removed and 132 articles were excluded after their titles and abstracts had been screened for eligibility. This left 29 studies for which the full-text articles were screened. After removing a further 16 reports according to our inclusion/exclusion criteria, 13 studies remained for review and meta-analysis (see Figure 1). Figure 1. Selection of studies. Nutrients 2021, 13, 868 7 of 18 3.2. Quality Assessment of Studies Scores awarded to the 13 reviewed studies are provided in Table 4. According to these scores, the methodological quality of one study (8%) was classified as excellent [38], of nine studies (69%) as very good [33,37,39,46–51], and of three studies (23%) as good [52–54]. Table 4. Methodological quality of the studies (n = 13). Item 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Total MQ Study Ali et al. [33] 1 1 1 1 1 1 1 1 1 1 0 1 1 0 1 1 14 VG Hogervorst et al. [37] 1 1 1 1 0 1 1 1 1 1 0 1 1 0 1 1 13 VG Hogervorst et al. [38] 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 15 E Bello et al. [39] 1 1 1 1 0 1 1 1 1 1 0 1 1 1 1 1 14 VG Crowe et al. [46] 1 1 1 1 0 1 1 1 1 1 1 1 1 0 1 1 14 VG Church et al. [47] 1 1 1 1 0 1 1 1 1 1 1 1 1 0 1 1 14 VG Mumford et al. [48] 1 1 1 1 0 1 1 1 1 1 1 1 1 0 1 1 14 VG Pomportes et al. [49] 1 1 1 1 0 1 1 1 1 1 1 1 1 0 1 1 14 VG Cesareo et al. [50] 1 1 1 1 0 1 1 1 1 1 1 1 1 0 1 1 14 VG Duncan et al. [51] 1 1 1 1 0 1 1 1 1 1 0 1 1 0 1 1 13 VG Russell et al. [52] 1 1 1 1 0 1 1 1 1 1 0 1 1 0 1 0 12 G Share et al. [53] 1 1 1 1 0 1 0 0 1 1 1 1 1 0 1 1 12 G Foskett et al. [54] 1 1 1 1 0 1 1 1 1 0 0 1 1 0 1 1 12 G Item score: 1 = criterion fulfilled; 0 = criterion not fulfilled. MQ: methodological quality (MQ); G: good (11–12 points); VG: very good (13–14 points); E: excellent (15 points). 3.3. Caffeine Supplementation Participants were adult athletes of both genders (158 men and 36 women) who took part in professional/elite (n = 42), semi-professional (n = 14), or amateur (n = 109) sports activities. In one study, participants were ten athletes from recreational to professional levels without specifying training status in detail. Of the 13 studies reviewed, six included female athletes. In five of the 13 studies, participants were team sport players (n = 80). In seven of the 13 studies reviewed, caffeine was administered based on the subject’s body weight, while an absolute dose was provided for the participants of six studies. The caffeine dose employed was less than 3 mg/kg in four studies, 3 mg/kg to 6 mg/kg in eight, and different doses (2 and 4 mg/kg) in one. The caffeine administration mode was capsules in five studies, energy drinks in three, a 68.8 mg/l carbohydrate solution in one, chewing gum in one, mouth wash in one, tablets in one, and a 45 g carbohydrate energy bar in the final one. Most investigations administered caffeine 30–60 min prior to testing (n = 8). In the studies conducted by Cesareo et al. [50] and Hogervorst et al. [37], caffeine was ingested 1.5 h before the start of exercise. Furthermore, in four studies, besides administrating caffeine before the start of exercise, the supplement was also taken during exercise [37,38,49,52]. Hogervorst et al. [37] used a protocol that included the ingestion of caffeine 1 h before the test and every 20 min during the protocol. Mumford et al. [48] administered caffeine 120 min after starting a game of golf. Finally, Russell et al. [52] employed caffeine 15 min during exercise through the use of caffeinated gums. In summary, the different studies examined the effect of acute caffeine supplementation taken from 5–60 min prior to testing on cognitive performance during sports activity. Nutrients 2021, 13, 868 8 of 18 3.4. Outcome Measures Tables 5 and 6 provide information about the studies reviewed: author/s, year of publication, and participants and their characteristics; the study design, including the control group; the supplementation mode, dose, and timing; the outcomes analyzed or the main effects on cognitive performance measured using objective tools (n = 10; Table 5) or selfreports (n = 6; Table 6); and finally, the results or main conclusions. Table 5. Details and results of the studies reviewed investigating the effect of acute caffeine supplementation compared to a placebo on objective measures of cognitive performance. Study Population Intervention Outcomes Analyzed Main Results vs. Placebo Russell et al. [52] 14 male professional academy rugby players (18 ± 1 years) 4.1 ± 0.5 mg/kg of caffeine (gum) 15 min before and during exercise SRT test Stroop test SRT Congruent response accuracy Incongruent response accuracy Duncan et al. [51] 12 male subjects accustomed to regular highintensity exercise (21.4 ± 4.4 years) 5 mg/kg of caffeine (capsules) 60 min before start Modified flanker task ↓ Congruent RT ↓ Incongruent RT Congruent response accuracy Incongruent response accuracy Bello et al. [39] 12 male (21.8 ± 2.53) and 15 female (19.65 ± 3.62) professional soccer players 275 mg (≈3.69 mg/kg) caffeine capsule 30 min before start SRT test Go/no-go Go/no-go and COGRT wrong ↑ SRT CRT CRT score COGRT COGRT score COGRT wrong answer Pomportes et al. [49] 16 male and six female recreational cyclists (26 ± 8) years 67 mg/25 mL (≈0.93 mg/kg) of caffeine + 7% carbohydrate mouthwash Immediately before start and every 13 min during exercise Duration-production task Simon task ↓ Produced duration ↓ Variance ↑ Congruent mean RT ↓ Incongruent mean RT Error rate (%) Ali et al. [33] 10 female team game players from recreational to international (24 ± 4 years) 6 mg/kg caffeine capsule 60 min before start CRT test Stroop test CRT RT CRT accuracy ‡ Stroop test RT † Stroop test accuracy Church et al. [47] 10 male recreationally active subjects (25.5 ± 1.8 years) 3 mg/kg caffeine drink 60 min before start Reaction time test Multiple object tracking Upper body RT Lower body RT Multiple object tracking Share et al. [53] Seven male elite clay target shooters (28.4 ± 9.4 years) 2 or 4 mg/kg caffeine tablets 60 min before start Reaction time test Tracking time of target RT TT1 TT2 Hogervorst et al. [38] 24 well-trained male subjects (23 ± 5 years) 100 mg (≈1.36 mg/kg) of caffeine + 45 g carbohydrate energy bar Stroop Color and Word test RVIP test Visual search test Word learning Test ↓ Stroop RT Stroop accuracy ↓ RVIP RT ↑ RVIP PT rate ↓ RVIP miss rate Nutrients 2021, 13, 868 9 of 18 Immediately before and every 55 min during exercise ↓ Visual Search RT ↑ Visual Search accuracy Delayed recall words Crowe et al. [46] 12 male and five female team sports players (21.1 ± 3.0 years) 6 mg/kg caffeine drink 90 min before start Simple visual reaction time test Number recall test RT Number recall Hogervorst et al. [37] 15 male professional cyclists or triathletes (23.3 ± 3.6 years) 8 mL/kg of 150, 225, or 320 mg/l of caffeine + 68.8 mg/l carbohydrate solution (≈1.2, 1.8, or 2.56 mg/kg of caffeine) 60 min before start 3 mL/kg of 150, 225, or 320 mg/l of caffeine + 68.8 mg/l carbohydrate solution (≈0.45, 0.675, or 0.96 mg/kg of caffeine) every 20 min during exercise Stroop Color and Word Test SDT test Motor choice r eaction time test VVLT ↑ Stroop speed ↑ SDT efficiency ↑ SDT speed ↑ Simple psychomotor speed ↑ Complex psychomotor speed ↑ S-R incompatible choice speed VVLT delayed number recall ↑ VVLT speed ↑ Statistically significant increase; ↓ statistically significant decrease; † increasing tendency; ‡ decreasing tendency. Without any marks indicates that there were no differences between caffeine and the placebo for the measures. RT: reaction time; SRT: simple reaction time; CRT: choice reaction time; COGRT: cognitive load reaction time; RVIP: rapid visual information processing; SDT: signal detection test; VVLT: visual verbal learning test. Table 6. Details and results of the studies reviewed investigating the effect of acute caffeine supplementation compared to a placebo on self-reported measures of cognitive performance. Study Population Intervention Outcomes Analyzed Main Conclusion Duncan et al. [51] 12 male subjects accustomed to regular highintensity exercise (21.4 ± 4.4 years) 5 mg/kg of caffeine (capsules) 60 min before start RPE VAS ↓ RPE RTIPE RTIME Cesareo et al. [50] 12 male resistancetrained subjects (23.2 ± 3.1) 300 mg (≈3.6 mg/kg) caffeine capsule 90 min before start VAS-F ↑ Energy ↑ Focus ↑ Motivation to exercise Fatigue Ali et al. 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