Caffeine
Supporting Human Studies
Caffeine (4 mg/kg) influences sustained attention and delayed free recall but not memory predictions (Kelemen and Creeley, 2001)
This experiment was conducted to examine the influence of a moderate dose of caffeine (4 mg/kg) on delayed memory, metamemory, and sustained attention. One hundred and forty-two volunteers ingested either caffeine or placebo during a study session which included three different memory tasks (free recall, cued recall, and recognition), and they made predictions of future memory performance. On day 2, participants again ingested either caffeine or placebo and completed memory tests. Sustained attention performance was measured on both days, and caffeine reliably improved hit rates and response latencies. A reliable drug-state interaction was detected only in the free recall test of memory. Caffeine did not affect the magnitude or accuracy of memory predictions, but there was some evidence that expectancies about caffeine were related to cognitive performance. Overall, caffeine's impact on memory and metamemory was not robust in this study.
Effects of caffeine on mood and performance: a study of realistic consumption (Brice and Smith, 2002)
There is a vast literature on the behavioural effects of caffeine. Many of the studies have involved single administration of a large dose of caffeine that is not representative of the way in which caffeine is usually ingested. Further information is required, therefore, on the behavioural effects of realistic patterns of consumption. The present study aimed to determine whether a realistic drinking regime (multiple small doses – 4×65 mg over a 5-h period) produced the same effects as a single large dose (200 mg). The smaller doses were selected so that the amount of caffeine present in the body after 5 h would be equivalent to that found with the single dose. A double-blind, placebo-controlled, within-subjects experiment was, therefore, carried out. The participants (n=24) attended for four sessions. Each session started with a baseline measurement of mood and performance at 0930 hours. On two of the sessions, coffee was then consumed at 1000, 1100, 1200 and 1300 hours. In one of these sessions 65 mg caffeine was added to the de-caffeinated coffee. In the other two sessions, the participants consumed coffee at 1300 hours and 200 mg caffeine was added in one of the sessions. The volunteers completed the battery of tests again at 1500 hours. The results showed that in both consumption regimes caffeine led to increased alertness and anxiety and improved performance on simple and choice reactive tasks, a cognitive vigilance task, a task requiring sustained response and a dual task involving tracking and target detection. These results suggest that previous findings from studies using a large single dose may be applicable to normal patterns of caffeine consumption.
Caffeine modulates attention network function (Brunye et al, 2010)
The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a flanker task designed to test Posner’s three visual attention network functions: alerting, orienting, and executive control. In a placebo-controlled, double-blind study using a repeated-measures design, we found that the effects of caffeine on visual attention vary as a function of dose and the attention network under examination. Caffeine improved alerting and executive control function in a dose–response manner, asymptoting at 200 mg; this effect is congruent with caffeine’s adenosine-mediated effects on dopamine-rich areas of brain, and the involvement of these areas in alerting and the executive control of visual attention. Higher doses of caffeine also led to a marginally less efficient allocation of visual attention towards cued regions during task performance (i.e., orienting). Taken together, results of this study demonstrate that caffeine has differential effects on visual attention networks as a function of dose, and such effects have implications for hypothesized interactions of caffeine, adenosine and dopamine in brain areas mediating visual attention.
The influences of age and caffeine on psychomotor and cognitive function (Rees et al, 1999)
The response to caffeine is affected by a number of factors, including age. Older subjects may be more sensitive to the objective effects than younger but report fewer subjective effects. This study assessed the influence of age on the effects of caffeine on a variety of psychomotor, cognitive and subjective tests. Forty-eight healthy subjects, male and female, were recruited, 24 in the age range 20–25 and 24 in the range 50–65 years. All subjects were regular moderate caffeine drinkers and were not withdrawn from caffeine before entry to the study. A double-blind parallel group design was used with two groups of 12 subjects in each age range. One group in each age range received placebo and the other 250 mg caffeine B.P. A range of tests was used to assess psychomotor, cognitive and subjective functioning before and 1 h post-treatment. Before treatment, young subjects generally performed better than older on psychomotor and cognitive tests. On the subjective tests, however, older subjects rated themselves as more alert and less tired than the younger ones. After placebo, performance and alertness improved in the younger group but declined in the older. After caffeine there were improvements in psychomotor performance and cognitive functioning in both groups, particularly in offsetting declining performance over time in the older subjects. It also produced subjective improvements in alertness. One factor to emerge was that on most assessments older subjects were better earlier in the day whereas in younger subjects performance did not show the same magnitude of decline throughout the day. Caffeine induced small but significant improvements in vigilance and psychomotor performance.
Does caffeine intake enhance absolute levels of cognitive performance? (Jarvis, 1993)
The relationship between habitual coffee and tea consumption and cognitive performance was examined using data from a cross-sectional survey of a representative sample of 9003 British adults (the Health and Lifestyle Survey). Subjects completed tests of simple reaction time, choice reaction time, incidental verbal memory, and visuo-spatial reasoning, in addition to providing self-reports of usual coffee and tea intake. After controlling extensively for potential confounding variables, a dose-response trend to improved performance with higher levels of coffee consumption was observed for all four tests (P<0.001 in each case). Similar but weaker associations were found for tea consumption, which were significant for simple reaction time (P=0.02) and visuo-spatial reasoning (P=0.013). Estimated overall caffeine consumption showed a dose-response relationship to improved cognitive performance (P<0.001 for each cognitive test, after controlling for confounders). Older people appeared to be more susceptible to the performance-improving effects of caffeine than were younger. The results suggest that tolerance to the performance-enhancing effects of caffeine, if it occurs at all, is incomplete.
Influence of caffeine on selective attention in well-rested and fatigued subjects (Lorist et al, 1994)
Effects of caffeine were studied in a visual focused selective search task in well-rested and fatigued subjects. A dose of 200 + 50 mg caffeine or placebo, dissolved in decaffeinated coffee, was administered in a double-blind and deceptive fashion. The task was to detect a target letter on one diagonal of a visual display designated as relevant and ignore stimuli presented on the irrelevant diagonal. Behavioral measures were supplemented by event-related potential (ERP) measures. Subjects reacted faster in the caffeine condition. Caffeine enhanced the N1 and the N2b components. Selection of relevant information apparently was more adequate in this condition. Search negativity was not affected by caffeine. Caffeine effects on the P3 elicited by target letters were more pronounced in the fatigued than in the well-rested subjects, indicating that the effects of caffeine are dependent on the state of the subject. The results suggest that caffeine has specific rather than general effects on information processing.
The effects of caffeine on two computerized tests of attention and vigilance (Frewer and Lader, 1991)
Single doses of caffeine (250 mg, 500 mg) or placebo were administered double-blind to healthy volunteer subjects (n = 12), using a fully balanced crossover design (Williams square) with 1-week washout. Assessments were made predrug, and at 45 min and 165 min post-drug administration. The test battery comprised physiological measures (blood pressure, heart rate and urinary volume), subjective measures of alertness, a letter cancellation task (one-target, two-target and four-target versions), and two computerized measures of attention and vigilance: a rapid information processing task and a continuous attention task. Physiological variables did not alter following caffeine administration, but subjective and cognitive variables showed significant changes in the predicted direction. Thus, doserelated changes in subjective calmness and interest were observed, together with changes in performance for the letter cancellation task at low and intermediate difficulty levels. A dose-related performance improvement was observed for the rapid information processing task. The continuous attention task was also sensitive to the effects observed for the rapid information processing task. The continuous attention task was also sensitive to the effects of caffeine. The 250 mg dose offset the decline in attention observed under placebo, and indeed facilitated performance at both post-drug administration times. The 500 mg dose impaired performance at 45 min and improved it at the 165 min post-administration time. Sensitivity to vigilance change was also observed within test sessions for this test, indicating that the continuous attention task was more sensitive to caffeine-induced changes in attention than the rapid information processing task.
Slow release caffeine and prolonged (64-h) continuous wakefulness: effects on vigilance and cognitive performance (Beaumont et al, 2001)
Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow-release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double-blind, randomised, placebo controlled, two-way crossover study. A total of 300-mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD-NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop’s test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00–04:00 h, 14:00–16:00 h) and hypervigilance (10:00–12:00 h, 22:00–00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop’s test (P=0.048). We showed that 300-mg SRC given twice daily during a 64-h SD is able to antagonize the impairment produced on vigilance and cognitive functions.
Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training (Lieberman et al, 2002)
When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.
Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers (Smith et al, 2005)
Evidence for behavioural effects of caffeine is well documented in the literature. It is associated with increased subjective alertness, improved reaction time and enhanced encoding of new information. These effects are most prominent in low arousal situations. However, there is an ongoing debate as to whether such changes are in fact improvements or merely a reversal of the negative effects of a period of caffeine withdrawal (e.g. overnight abstinence). To avoid such a confound this study included multiple doses of caffeine which were administered under double-blind conditions to participants who had ingested their normal daily quota of caffeine. In the present study participants were fatigued by carrying out a prolonged testing schedule in the evening. Sixty volunteers, all regular caffeine consumers, took part in the study. They attended for three sessions on separate days. They were instructed to consume normal amounts of caffeinated beverages. Consumption was measured by a diary and saliva samples were taken and caffeine assays conducted. A baseline test session was carried out at 18.00h and following this a double blind placebo controlled caffeine challenge (1.5mg/kg) conducted. The test battery was repeated twice approximately 30 minutes after the caffeine challenge. Following this another drink was administered and the test battery repeated twice more. On one test session volunteers had placebo in both drinks, in another they had caffeine in both drinks and another caffeine in the first and placebo in the second. Order of conditions was balanced across subjects. The results showed that caffeine led to a more positive mood and improved performance on a number of tasks. Different effects of caffeine were seen depending on the person’s level of arousal. Linear effects of caffeine dose were also observed. This is evidence against the argument that behavioural changes due to caffeine are merely the reversal of negative effects of a long period of caffeine abstinence. The findings are discussed in relation to both noradrenergic and cholinergic neurotransmitter systems.
Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine (Haskell et al 2005)
The cognitive and mood effects of caffeine are well documented. However, the majority of studies in this area involve caffeine-deprived, habitual caffeine users. It is therefore unclear whether any beneficial findings are due to the positive effects of caffeine or to the alleviation of caffeine withdrawal. The present placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of caffeine in habitual users and habitual non-users of caffeine. Following overnight caffeine withdrawal, 24 habitual caffeine consumers (mean=217 mg/day) and 24 habitual non-consumers (20 mg/day) received a 150 ml drink containing either 75 or 150 mg of caffeine or a matching placebo, at intervals of ≥48 h. Cognitive and mood assessments were undertaken at baseline and 30 min post-drink. These included the Cognitive Drug Research computerised test battery, two serial subtraction tasks, a sentence verification task and subjective visual analogue mood scales. There were no baseline differences between the groups’ mood or performance. Following caffeine, there were significant improvements in simple reaction time, digit vigilance reaction time, numeric working memory reaction time and sentence verification accuracy, irrespective of group. Self-rated mental fatigue was reduced and ratings of alertness were significantly improved by caffeine independent of group. There were also group effects for rapid visual information processing false alarms and spatial memory accuracy with habitual consumers outperforming non-consumers. There was a single significant interaction of group and treatment effects on jittery ratings. Separate analyses of each groups’ responses to caffeine revealed overlapping but differential responses to caffeine. Caffeine tended to benefit consumers’ mood more while improving performance more in the non-consumers. These results do not support a withdrawal alleviation model. Differences in the patterns of responses to caffeine by habitual consumers and habitual non-consumers may go some way to explaining why some individuals become caffeine consumers.
Effects of caffeine on performance and mood depend on the level of caffeine abstinence (Yeomans et al, 2002)
Most studies of the effects of caffeine on performance have used regular caffeine consumers who are deprived at test. Thus the reported effects of caffeine could be explained through reversal of caffeine withdrawal. To test how preloading deprived caffeine consumers with 0, 1 or 2 mg/kg caffeine altered the subsequent ability of caffeine to modify mood and performance. Thirty moderate caffeine consumers were given a drink containing 0, 1 or 2 mg/kg caffeine at breakfast followed 60 min later by a second drink containing either 0 or 1 mg/kg caffeine. Performance on a measure of sustained attention and mood were measured before and after each drink. Administration of both 1 and 2 mg/kg caffeine at breakfast decreased reaction time and 1 mg/kg caffeine also increased performance accuracy on the sustained attention (RVIP) task relative to placebo. Both breakfast doses of caffeine also improved rated mental alertness. Similarly, 1 mg/kg caffeine administered 60 min after breakfast decreased reaction time and increased rated mental alertness in the group who had not been given caffeine at breakfast. However, this second dose of caffeine had no effect on subsequent performance or mood in the two groups who had received caffeine at breakfast. Caffeine reliably improved performance on a sustained attention task, and increased rated mental alertness, in moderate caffeine consumers who were tested when caffeine-deprived. However, caffeine had no such effects when consumers were no longer caffeine deprived. These data are consistent with the view that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance.
Effects of caffeine on cognitive and autonomic measures in heavy and light caffeine consumers (Lyvers et al, 2007)
Caffeine effects on arousal and cognition were assessed in relation to habitual caffeine intake. After drinking either decaffeinated coffee or decaffeinated coffee plus 300 mg caffeine, 22 heavy caffeine consumers (HCCs) and 26 light caffeine consumers (LCCs) were examined on various cognitive, autonomic, and anxiety measures. In LCCs only, caffeine significantly improved performance of the Wisconsin Card Sorting Test, and significantly increased state anxiety scores. Caffeine significantly increased spontaneous skin conductance responses in HCCs and LCCs alike. The HCCs and LCCs did not differ on measures of trait anxiety or neuroticism. Results are discussed in terms of the cognitive enhancing and nonspecific arousing effects ofcaffeine in relation to caffeine tolerance.
The combined effects of L-theanine and caffeine on cognitive performance and mood (Owen et al, 2008)
The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L-theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks.
Effects of Evening Meals and Caffeine on Cognitive Performance, Mood and Cardiovascular Functioning (Smith et al, 1994)This experiment was carried out to examine the effects of an evening meal and caffeine (3 mg/kg) on performance, mood and cardiovascular functioning. Subjects given a meal reported that they felt stronger, more proficient and more interested than subjects in the no-meal condition. They also performed a logical reasoning task more quickly than the no-meal group. However, no effects were found on sustained attention tasks or tasks involving recall or recognition of word lists. The effects of evening meals are, therefore, different from either those observed after lunch or breakfast. Caffeine improved alertness and performance on sustained attention tasks for the group as a whole. Interactions between caffeine conditions and levels of impulsivity of the subjects were also found in memory tasks.
The effects of L-theanine, caffeine and their combination on cognition and mood (Haskell, 2008)
L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were comonitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.
Caffeine, cognitive failures and health in a non-working community sample (Smith, 2008)
Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Secondary analyses of a large epidemiological database (N = 3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17–92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140 mg/day, range 0–1800 mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of caffeine was found to be associated with a reduced risk of depression.
Caffeine eliminates psychomotor vigilance deficits from sleep inertia (van Dongen et al, 2001)
This study sought to establish the effects of caffeine on sleep inertia, which is the ubiquitous phenomenon of cognitive performance impairment, grogginess and tendency to return to sleep immediately after awakening. 28 normal adult volunteers were administered sustained low-dose caffeine or placebo (randomized double-blind) during the last 66 hours of an 88-hour period of extended wakefulness that included seven 2-hour naps during which polysomnographical recordings were made. Every 2 hours of wakefulness, and immediately after abrupt awakening from the naps, psychomotor vigilance performance was tested. In the placebo condition, sleep inertia was manifested as significantly impaired psychomotor vigilance upon awakening from the naps. This impairment was absent in the caffeine condition. Caffeine had only modest effects on nap sleep. Caffeine was efficacious in overcoming sleep inertia. This suggests a reason for the popularity of caffeine-containing beverages after awakening. Caffeine's main mechanism of action on the central nervous system is antagonism of adenosine receptors. Thus, increased adenosine in the brain upon awakening may be the cause of sleep inertia.
Caffeine, Cognitive Functioning, and White Matter Lesions in the Elderly: Establishing Causality from Epidemiological Evidence (Ritchie et al, 2010)
The present study examines the epidemiological evidence for a causal relationship between caffeine consumption and cognitive deterioration in the elderly. Using a population of 641 elderly persons, we examined cognitive functioning, caffeine consumption, magnetic resonance imaging volumetrics, and other factors known to affect cognitive performance. Our findings demonstrate the association between caffeine consumption and lower cognitive change over time to be statistically significant for women only, taking into account multiple confounders, to be dose-dependent and temporarily related (caffeine consumption precedes cognitive change). Mean log transformed white matter lesion/cranial volume ratios were found to be significantly lower in women consuming more than 3 units of caffeine per day after adjustment for age (−1.23 SD=0.06) than in women consuming 2−3 units (−1.04 SD=0.04) or one unit or less (−1.04 SD=0.07, −35% in cm^{3}compared to low drinkers). This observation is coherent with biological assumptions that caffeine through adenosine is linked to amyloid accumulation and subsequently white matter lesion formation. The significant relationship observed between caffeine intake in women and lower cognitive decline is highly likely to be a true causal relationship and not a spurious association.
The effect of caffeine on cognitive task performance and motor fatigue (van Duinen et al, 2005)
In everyday life, people are usually capable of performing two tasks simultaneously. However, in a previous study we showed that during a fatiguing motor task, cognitive performance declined progressively. There is extensive literature on the (positive) effects of caffeine on cognitive and motor performance. These effects are most pronounced under suboptimal conditions, for example during fatigue. However, little is known about the effects of caffeine on cognitive performance during a fatiguing motor task. This study was aimed to investigate whether a moderate dose of caffeine could attenuate the decline in cognitive performance during a fatiguing motor task. The study consisted of a placebo and a caffeine (3 mg/kg) session. A total of 23 subjects completed these sessions in a semi-randomized and double-blind order. In each session, subjects performed maximal voluntary contractions of the index finger, a choice reaction time (CRT) task and a dual task consisting of a fatiguing motor task concomitantly with the same CRT task. After the fatiguing dual task, the CRT task was repeated. Caffeine improved cognitive task performance, in both the single and dual task, as shown by decreased reaction times together with unchanged accuracy. Cognitive performance in the dual task deteriorated with increasing fatigue. However, the decrease in cognitive performance in the beginning of the dual task, as observed in the placebo condition, was partly prevented by caffeine administration (i.e., no increase in reaction times). We found no effects of caffeine on motor parameters (absolute force, endurance time or electromyographic amplitude). Caffeine improved cognitive performance. This effect also extends under demanding situations, as was shown by the performance during the dual task, even during progressive motor fatigue.
Caffeine and Central Noradrenaline: Effects on Mood, Cognitive Performance, Eye Movements and Cardiovascular Function (Smith et al, 2003)
There have been numerous studies on the effects of caffeine on behaviour and cardiovascular function. It is now important to clarify the mechanisms that underlie such effects, and the main objective of the present study was to investigate whether changes in central noradrenaline underlie some of the behavioural and cardiovascular effects of caffeine. This was examined using a clonidine challenge paradigm. Twenty-four healthy volunteers were assigned to one of four conditions: (i) clonidine/caffeine; (ii) clonidine/placebo; (iii) placebo/caffeine; (iv) placebo/placebo. Baseline measurements of mood, cognitive performance, saccadic eye movements and cardiovascular function were recorded. Subsequently, volunteers were given either clonidine (200 μg) or placebo and consumed coffee containing caffeine (1.5 mg/kg) or placebo. The test battery was then repeated 30 min, 150 min and 270 min later. A second cup of coffee (with the same amount of caffeine as the first) was consumed 120 min after the first cup. The results showed that clonidine reduced alertness, impaired many aspects of performance and slowed saccadic eye movements; caffeine removed many of these impairments. Both clonidine and caffeine influenced blood pressure (clonidine reduced it, caffeine raised it) but the effects appeared to be independent, suggesting that separate mechanisms were involved. In addition, there were some behavioural effects of caffeine that were independent of the clonidine effect (e.g. effects on speed of encoding of new information) and these may reflect other neurotransmitter systems (e.g cholinergic effects). Overall, the results suggest that caffeine counteracts reductions in the turnover of central noradrenaline. This mechanism may underlie the beneficial effects of caffeine seen in low alertness states.
Effects of breakfast and caffeine on cognitive performance, mood and cardiovascular functioning (Kendrick et al, 1994) Two experiments with 48 university students each examined the effect of breakfast (BF) and caffeine (4 mg/kg) on cognitive performance, mood, and cardiovascular functioning. In Exp 1, BF had no effect on performance of sustained attention tasks, but it increased pulse rate and influenced mood. The mood effects after BF differed between a cooked BF and a cereal/toast BF. The high dose of caffeine improved performance of the sustained attention tasks, increased blood pressure, and increased mental alertness. In Exp 2, effects of a BF and caffeine on mood and cardiovascular functions confirmed the results of the 1st study. BF improved performance on free recall and recognition memory tasks, had no effect on a semantic memory task, and impaired the accuracy of performing a logical reasoning task. In contrast, caffeine improved performance on the semantic memory, logical reasoning, free recall, and recognition memory tasks.
Effects of caffeine on cognition and mood without caffeine abstinence (Warburton, 1995)
The objective of this study was to evaluate the effects of low doses (75 mg and 150 mg) of caffeine on mood and cognition in healthy people, with minimal abstinence of 1 hr from caffeine. Improvements were obtained in cognition for attention, problem solving and delayed recall, but not immediate recall or working memory, but performance in the placebo condition was close to the maximum, giving little margin for improvement. For mood, there were statistically significant increase in clearheadedness, happiness and calmness and decreases in tenseness. These mood and performance-enhancing effects of caffeine cannot be seen as representing an alleviation of deficits induced by caffeine abstinence, because there was only minimal deprivation from caffeine.
The effects of a low dose of caffeine on cognitive performance (Durlach, 2008)
There is little evidence concerning the effects of caffeine in doses typical of one cup of tea. The present study investigated the effect of 60 mg caffeine, consumed in either tea or hot water, on performance on a subset of the CANTAB test battery. Eight males participated in a practice session and four test sessions. In each test session, the participant consumed a different hot beverage and then, over approximately 90 min, completed nine tests from the CANTAB battery. The four beverages were created by crossing beverage identity (tea or hot water) and caffeine dose (0 or 60 mg). Significant speeding of reaction time by caffeine consumption was found in pattern recognition, delayed match to sample, and match to sample visual search. The effect on reaction time of 60 mg caffeine can be detected, and may be evident within minutes of consumption.
Caffeine Consumption and Cognitive Function at Age 70: The Lothian Birth Cohort 1936 Study (Corley et al, 2010)
To investigate the association between caffeine consumption and cognitive outcomes in later life. Participants were 923 healthy adults from the Lothian Birth Cohort 1936 Study, on whom there were intelligence quotient (IQ) data from age 11 years. Cognitive function at age 70 years was assessed, using tests measuring general cognitive ability, speed of information processing, and memory. Current caffeine consumption (using multiple measures of tea, coffee, and total dietary caffeine) was obtained by self-report questionnaire, and demographic and health information was collected in a standardized interview. In age- and sex-adjusted models, there were significant positive associations between total caffeine intake and general cognitive ability and memory. After adjustment for age 11 IQ and social class, both individually and together, most of these associations became nonsignificant. A robust positive association, however, was found between drinking ground coffee (e.g., filter and espresso) and performance on the National Adult Reading Test (NART, p = .007), and the Wechsler Test of Adult Reading (WTAR, p = .02). No gender effects were observed, contrary to previous studies. Generally, higher cognitive scores were associated with coffee consumption, and lower cognitive scores with tea consumption, but these effects were not significant in the fully adjusted model. The present study is rare in having childhood IQ in a large sample of older people. The results suggest that the significant caffeine intake-cognitive ability associations are bidirectional—because childhood IQ and estimated prior IQ are associated with the type of caffeine intake in old age—and partly confounded by social class.
Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together (Rogers et al, 2008)
Although both contain behaviourally significant concentrations of caffeine, tea is commonly perceived to be a less stimulating drink than coffee. At least part of the explanation for this may be that theanine, which is present in tea but not coffee, has relaxing effects. There is also some evidence that theanine affects cognitive performance, and it has been found to reduce blood pressure in hypertensive rats. To study the subjective, behavioural and blood pressure effects of theanine and caffeine administered alone and together, in doses relevant to the daily tea consumption of regular tea drinkers. In a randomised, double-blind, placebo-controlled study, healthy adult participants (n = 48) received either 250-mg caffeine, 200-mg theanine, both or neither of these. They completed ratings of mood, including anxiety, and alertness, and had their blood pressure measured before and starting 40 min after drug administration. Anxiety was also assessed using a visual probe task. Caffeine increased self-rated alertness and jitteriness and blood pressure. Theanine antagonised the effect of caffeine on blood pressure but did not significantly affect jitteriness, alertness or other aspects of mood. Theanine also slowed overall reaction time on the visual probe task. Theanine is a physiologically and behaviourally active compound and, while it is unclear how its effects might explain perceived differences between tea and coffee, evidence suggests that it may be useful for reducing raised blood pressure.
L-Theanine and Caffeine in Combination Affect Human Cognition as Evidenced by Oscillatory alpha-Band Activity and Attention Task Performance (Kelly et al, 2008)
Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8–14 Hz) activity. We found an increase in hit rate and target discriminability (d′) for the combined treatment relative to placebo, and an increase in d′ but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.
Cognitive Performance during Sustained Wakefulness: A Low Dose of Caffeine Is Equally Effective as Modafinil in Alleviating the Nocturnal Decline (Dagan and Doljansky, 2006)
Cognitive performance at night exhibits a substantial drop, typically before dawn. One of the means of dealing with this phenomenon, as well as with the accompanying sleepiness during sustained wakefulness, is the administration of stimulants. The most widely used and well‐documented stimulants are caffeine, amphetamines, and modafinil. Of these, amphetamines are the least recommended, as they may severely affect behavior. Caffeine and modafinil seem to produce relatively milder side effects and usually only at high doses. Previous comparison studies have revealed equal efficacy of both the stimulants in maintaining alertness and performance during sustained wakefulness. However, these studies used relatively high, and thus not completely safe, doses of these drugs (600 mg caffeine and 400 mg modafinil). Therefore, the aim of the present study was to assess the efficacy of a low and medically safe dose of caffeine (200 mg) and modafinil (200 mg) in maintaining cognitive performance during sustained wakefulness. A flight simulation task was chosen for the assessment of the stimulants in a counter‐balanced, within‐subject design under four different conditions: baseline (no drugs), placebo, caffeine (200 mg), and modafinil (200 mg). The equal effectiveness of both drugs in abolishing the nocturnal drop in cognitive performance, as well as of oral temperature and blood pressure, supported the use of low doses of caffeine and modafinil for the maintenance of alertness in healthy subjects during sustained wakefulness.
Effects of caffeine and glucose, alone and combined, on cognitive performance (Adan and Serra-Grabulosa, 2010)
To study the effects of consuming caffeine and glucose, alone and combined, on cognitive performance. Seventy-two healthy subjects (36 women; age range 18–25) were tested early in the morning, having fasted overnight. Using a double-blind, randomised design, subjects received one of the following beverages: water (150 ml); water plus 75 mg of caffeine; water plus 75 g of glucose; water plus and 75 mg of caffeine and 75 g of glucose. Attention, manual dexterity, visuo-spatial and frontal functions, memory (immediate, consolidation and working) and subjective state were all assessed. The combination of caffeine and glucose had beneficial effects on attention (sequential reaction time tasks) and on learning and consolidation of verbal memory, effects not being observed when either substance was administered alone. Caffeine only showed improvement in simple reaction time and glucose in simple and one sequential reaction time tasks and in the manual dexterity assembly task. The results indicate that the synergistic effects of caffeine and glucose can benefit sustained attention and verbal memory, even with adequate levels of activation of the subjects. However, further studies are required, controlling for different levels of cognitive effort and also considering measurements of neural activity.
Caffeine attenuates scopolamine-induced memory impairment in humans (Reidel et al, 1995)
Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.
Supporting Animal Studies
Effects of caffeine on learning and memory in rats tested in the Morris water maze (Angelucci et al, 2002)
We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. Groups of 12 adult male Wistar rats receiving caffeine (0.3-30 mg/kg, ip, in 0.1 ml/100 g body weight) administered 30 min before training, immediately after training, or 30 min before the test session were tested in the spatial version of the Morris water maze task. Post-training administration of caffeine improved memory retention at the doses of 0.3-10 mg/kg (the rats swam up to 600 cm less to find the platform in the test session, P£0.05) but not at the dose of 30 mg/kg. Pre-test caffeine administration also caused a small increase in memory retrieval (the escape path of the rats was up to 500 cm shorter, P£0.05). In contrast, pre-training caffeine administration did not alter the performance of the animals either in the training or in the test session. These data provide evidence that caffeine improves memory retention but not memory acquisition, explaining some discrepancies among reports in the literature.
Chronic Caffeine Treatment Prevents Sleep Deprivation-Induced Impairment of Cognitive Function and Synaptic Plasticity (Alheider et al , 2010)
Study Objectives: This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. Experimental Design: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. Measurement and Results: The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, short-term memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. Conclusions: The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.
The effect of caffeine in animal models of learning and memory (Angelucci et al, 1999)
In the present investigation we studied the effect of caffeine on memory task inhibitory avoidance and habituation to a new environment. Caffeine impaired retention scores in mice submitted to inhibitory avoidance and habituation when administered 30 min before training at the doses of 10–30 mg/kg. These effects cannot be explained by state-dependency since the administration of caffeine 30 min before the test session did not reverse the effect of pre-training caffeine administration, but can more probably be explained by an impairment in the acquisition or by interference with attentional processes. On the other hand, caffeine improved the inhibitory avoidance (but not habituation) retention scores when administered immediately after the training or 30 min before the test session at the doses of 1–30 mg/kg or 3–10 mg/kg, respectively. These results suggest that caffeine differentially affects the different stages of memory processing and that this effect depends on particularities of the memory task under study.
Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats: Involvement of adenosine A1 and A2A receptors (Prediger et al, 2005)
Caffeine, a non-selective adenosine receptor antagonist, has been suggested as a potential drug to counteract age-related cognitive decline since critical changes in adenosinergic neurotransmission occur with aging. In the present study, olfactory discrimination and short-term social memory of 3, 6, 12 and 18 month-old rats were assessed with the olfactory discrimination and social recognition tasks, respectively. The actions of caffeine (3.0, 10.0 and 30.0 mg/kg, i.p.), the A1 receptor antagonist DPCPX (1.0 and 3.0 mg/kg, i.p.) and the A2A receptor antagonist ZM241385 (0.5 and 1.0 mg/kg, i.p.) in relation to age-related effects on olfactory functions were also studied. The 12 and 18 month-old rats exhibited significantly impaired performance in both models, demonstrating deficits in their odor discrimination and in their ability to recognize a juvenile rat after a short period of time. Acute treatment with caffeine or ZM241385, but not with DPCPX, reversed these age-related olfactory deficits. The present results suggest the participation of adenosine receptors in the control of olfactory functions and confirm the potential of caffeine for the treatment of aged-related cognitive decline.
Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus (Costa et al, 2008)Caffeine is one of the most psychostimulants consumed all over the world that usually presents positive effects on cognition. In this study, effects of caffeine on mice performance in the object recognition task were tested in different intertrial intervals. In addition, it was analyzed the effects of caffeine on brain derived neurotrophic factor (BDNF) and its receptor, TrkB, immunocontent to try to establish a connection between the behavioral finding and BDNF, one of the neurotrophins strictly involved in memory and learning process. CF1 mice were treated during 4 consecutive days with saline (0.9 g%, i.p.) or caffeine (10 mg/kg, i.p., equivalent dose corresponding to 2–3 cups of coffee). Caffeine treatment was interrupted 24 h before the object recognition task analysis. In the test session performed 15 min after training session, caffeine-treated mice recognized more efficiently both the familiar and the novel object. In the test session performed 90 min and 24 h after training session, caffeine did not change the time spent in the familiar object but increased the object recognition index, when compared to control group. Western blotting analysis of hippocampus from caffeine-treated mice revealed an increase in BDNF and TrkB immunocontent, compared to their saline-matched controls. Phospho-CREB immunocontent did not change with caffeine treatment. Our results suggest that acute treatment with caffeine improves recognition memory, and this effect may be related to an increase of the BDNF and TrkB immunocontent in the hippocampus.
Caffeine-induced synaptic potentiation in hippocampal CA2 neurons (Simons et al, 2011)Caffeine enhances cognition, but even high non-physiological doses have modest effects on synapses. A(1) adenosine receptors (A(1)Rs) are antagonized by caffeine and are most highly enriched in hippocampal CA2, which has not been studied in this context. We found that physiological doses of caffeine in vivo or A(1)R antagonists in vitro induced robust, long-lasting potentiation of synaptic transmission in rat CA2 without affecting other regions of the hippocampus.
Supporting Brain Studies
Caffeine strengthens action monitoring: evidence from the error-related negativity (Tieges et al, 2004)
The medial frontal cortex, especially the anterior cingulate cortex (ACC), is involved in action monitoring. We studied the role of moderate amounts of caffeine in action monitoring as expressed by the error-related negativity (ERN), an event-related brain component that reflects ACC activity. In a double-blind, placebo-controlled, within-subjects experiment, two caffeine doses (3 and 5 mg/kg body weight) and a placebo were administered to habitual coffee drinkers. Compared with placebo, both caffeine doses enlarged the ERN. Amplitudes of the P2 and P3 components were not affected by caffeine. Thus, the enlarged ERN after caffeine reflects a specific effect on action monitoring. We conclude that consumption of a few cups of coffee strengthens central information processing, specifically the monitoring of ongoing cognitive processes for signs of erroneous outcomes. Brain areas related to action monitoring such as the ACC presumably mediate these caffeine effects.
Does caffeine modulate verbal working memory processes? An fMRI study (Koppelstaetter et al, 2008)
To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.
Cellular Studies
none
Contradictory Studies
Effects of repeated caffeine administration on cognition and mood (Loke, 1990)
The effects of repeated caffeine administration on cognitive and mood tasks were investigated in a double-blind study of 32 young healthy adults who were randomly assigned to one of the four treatment conditions: 0, 200, 400, or 600 mg of caffeine. Subjects were tested over six alternate days; on each test day they completed various tasks after drug administration. In general, caffeine produced no significant effects on cognitive performance; the exception is that the highest dose (600 mg) reduced the speed of completion of additions relative to the other doses. Also, post-hoc analysis showed that the highest dose impaired performance of the lower caffeine users more than higher users. Mood assessment showed individuals were sensitive to the effects of caffeine but the effect did not interact with cognitive performance. The present data suggest that tolerance to the cognitive effects of caffeine does not develop with continued caffeine administration, given the limitations that the individuals tested were young healthy adults and the testing took place only over 2 weeks.
High doses of caffeine impair performance of a numerical version of the stroop task in men (Foreman et al, 1989)The effects of caffeine ingestion on mid-morning cognitive performance were investigated in thirty-two male subjects. These were given drinks containing either no caffeine, 125 mg caffeine (mean dose: 1.38 mg/kg), or 250 mg caffeine (mean dose: 3.45 mg/kg) and were tested on three tasks: 1) free recall of supraspan word lists, 2) a response time (pointing) task and 3) a numerical Stroop task. There were no significant group differences on the recall task or in response times, but subjects having the higher caffeine dose were seriously impaired on the Stroop test, making particularly slow responses. Caffeine may have a deleterious effect on the rapid processing of ambiguous or confusing stimuli, and this may account for its clearer effect on the Stroop test than on other cognitive tests used hitherto.
Cognitive and psychomotor performance, mood, and pressor effects of caffeine after 4, 6 and 8 h caffeine abstinence (Heatherly et al, 2005)
Many studies have found that caffeine consumed after overnight caffeine abstinence improves cognitive performance and mood. Much less is known, however, about the effects of caffeine after shorter periods of caffeine abstinence. The aim of this study was to measure the effects on psychomotor and cognitive performance, mood, hand steadiness, blood pressure and heart rate of caffeine administration after periods of 4, 6, and 8 h of caffeine abstinence. Participants (n=49, 27 female) were moderate to moderate-high caffeine consumers (mean daily intake 370 mg/day). Following overnight caffeine abstinence, a ‘pre-dose’ of caffeine (1.2 mg/kg) was administered at 9 a.m., 11 a.m. or 1 p.m. The participants started a baseline battery of measurements at 4 p.m. before receiving caffeine (1.2 mg/kg) or placebo at 5 p.m. They then performed the battery of tests again, starting at 5:30 p.m. This was a double-blind, placebo-controlled, randomised study. Performance and mood measurements confirmed a psychostimulant action of caffeine (versus placebo), but only after 8 h of caffeine abstinence. Caffeine also increased blood pressure after 8-h abstinence, whereas hand steadiness was decreased and perception of task demand was increased by caffeine after 4 h, but not after 6- and 8-h abstinence. A second cup-of-coffee equivalent dose of caffeine only reliably affected cognitive performance and mood after an 8-h interval between doses, but not after shorter intervals (when caffeine had some adverse effects). These results show that, apart from caffeine consumption soon after waking, the daily pattern of caffeine intake of many typical caffeine consumers is not well explained by the short-term psychostimulant effects of caffeine.
Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction (Rogers et al, 2004)
It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. Participants were moderate to moderate–high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal effects. Different patterns of effects (or lack of effects) of caffeine and caffeine withdrawal were found for other variables, but overall these results also suggest that there is little benefit to be gained from caffeine consumption.
The effects of habitual caffeine use on cognitive change: a longitudinal perspective (van Boxtel et al, 2003)
The efficiency of higher cortical functions, such as memory and speed of complex information processing, tends to decrease with advancing age in normal healthy individuals. Recently, a high habitual intake of caffeine was found associated with better verbal memory performance and psychomotor speed in several cross-sectional population studies. We tested the hypothesis that habitual caffeine intake can reduce or postpone age-related cognitive decline in healthy adults. For this purpose, the cognitive performance of all participants in the Maastricht Aging Study (MAAS), aged between 24 and 81 years, was reassessed after 6 years. Information on the intake of caffeine-containing beverages was available from the baseline questionnaire. After 6 years, 1376 (75.6%) individuals were available for reassessment. After correction for demographic characteristics, baseline performance and health status, there were small albeit significant associations between the overall estimated caffeine intake at baseline and the 6-year change in complex motor speed (motor choice reaction time). The earlier found association between caffeine intake and verbal memory performance was not apparent in this longitudinal study. These results imply that the longitudinal effect of habitual caffeine intake is limited and will not promote a substantial reduction in age-related cognitive decline at a population level.
Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups (Hameleers et al, 2000)
The present study evaluated the association between habitual caffeine intake via coffee and tea and cognitive performance. This was done as part of a larger research programme into the determinants of cognitive ageing (the Maastricht Aging Study: MAAS). Possible withdrawal effects that may have explained in part the positive association between performance and intake in an earlier study were controlled for. In addition, all cognitive tests in this study were administered under strict laboratory conditions. A group of 1875 healthy adults, stratified for age (range 24 – 81 years), sex, and general ability, were screened for habitual intake of coffee and tea and took part in extensive cognitive testing. Multiple regression analysis with control for age, sex, socio-demographic variables, and substance use showed that habitual caffeine consumption was significantly related to better long-term memory performance and faster locomotor speed. No relationships were found between habitual caffeine consumption and short-term memory, information processing, planning, and attention as measured with the Stroop Test. Moreover, no difference in sensitivity to caffeine intake between different age groups was found, suggesting that caffeine intake did not counteract age-related cognitive decline. Several recommendations are made to improve the design of future studies in this field.
The effects of caffeine on memory for word lists (Eriksen et al, 1985)
The present study investigated the effects of caffeine on memory for supraspan word lists. Twelve groups of male and female college students classified as high or low impulsive were administered (PO) 0 mg/kg, 2 mg/kg or 4 mg/kg of caffeine. Subjects listened to four word lists presented at a fast rate and four at a slow rate. Caffeine inhibited females' recall during the slow rate, but not the fast rate. Caffeine had no effect on the recall performance of males. The observed effects of caffeine were not influenced by subjects' typical amount of caffeine consumption, verbal ability, or level of impulsivity. The results suggest that caffeine may impair the efficiency with which females rehearse information in working memory.
Caffeine and memory performance on the AVLT (Terry and Phifer, 1986)The Auditory-Verbal Learning Test (AVLT) is a memory test that assesses recall of lists of words on single and multiple trials. College students (N = 33) were given the AVLT, either with or without a prior administration of 100 mg caffeine. Caffeine subjects recalled fewer words than did control subjects, both after single presentations of lists and across repeated trials. Caffeine subjects showed a greater deficit in recalling the middle-to-end portions of the lists. Personality scores on the Maudsley Personality Inventory showed a positive correlation of recall on a pretest with Neuroticism, and no correlation with Introversion.
A combination of caffeine and taurine has no effect on short term memory but induces changes in heart rate and mean arterial blood pressure (Bichler et al, 2006)Red Bull energy drink has become extraordinarily popular amongst college students for use as a study aid. We investigated the combined effects of Red Bull’s two active ingredients, caffeine and taurine, on short term memory. Studies on the effects of these two neuromodulators on memory have yielded mixed results, and their combined actions have not yet been investigated. In this double-blind study, college student subjects consumed either caffeine and taurine pills or a placebo and then completed a memory assessment. Heart rate and blood pressure were monitored throughout the testing period. The combination of caffeine and taurine had no effect on short term memory, but did cause a significant decline in heart rate and an increase in mean arterial blood pressure. The heart rate decline may have been caused by pressure-induced bradycardia that was triggered by caffeine ingestion and perhaps enhanced by the actions of taurine.
Combinational Studies
An evaluation of a caffeinated taurine drink on mood, memory and information processing in healthy volunteers without caffeine abstinence (Warburton et al, 2001)
Caffeine is present in a wide variety of beverages, often together with a number of other ingredients, such as sugars, taurine, glucuronolactone and vitamins. However, the majority of psychopharmacological studies have used pure caffeine tablets or drinks with doses in excess of those normally consumed in daily life. In addition, all the participants are usually deprived of caffeine for 10 h or more before the study. Consequently, it has been argued that any improvement in performance is only due to a reversal of caffeine withdrawal. The present two studies tested participants who had minimal deprivation from caffeine (an hour or less) with an 80-mg caffeinated (80 mg/250 ml), taurine-containing beverage (commercially available) verum, which also contained sugars, glucuronolactone and vitamins. The placebos in the two studies were a sugar-free and a sugar-containing drink, in order to examine the effects of the sugar. In total, 42 participants were tested with a rapid visual information test, a verbal reasoning test, a verbal and non-verbal memory test and a set of mood measures. Prior to testing, they were allowed ad libitum caffeinated beverages until 1 h before testing (study 1) and unrestricted caffeine use before testing (study 2). In both studies, the caffeinated, taurine-containing beverage produced improved attention and verbal reasoning, in comparison with a sugar-free and the sugar-containing drinks. The improvement with the verum drink was manifested in terms of both the mean number correct and the reaction times. Another important finding was the reduction in the variability of attentional performance between participants. No effects on memory were found. There were no differences in performance between the glucose and sugar-free drinks. Moderate doses of caffeine and taurine can improve information processing in individuals who could not have been in caffeine withdrawal.
A taurine and caffeine-containing drink stimulates cognitive performance and well-being (Seidl et al, 2000)
Caffeine- and taurine-containing drinks have been on the European market for about a decade, and research on the individual constituents of these drinks indicates an improvement in cognitive performance resulting from consumption of such drinks. In this double-blind, placebo-controlled study using 10 graduate students, we obtained the P300 components of event-related potential (ERP) waveforms following an auditory oddball paradigm, measured motor reaction time, and applied the d2 test for the assessment of attention. Status of mood was assessed by the “Basler-Befindlichkeitsbogen” questionnaire, a standard test for evaluation of feelings of well-being. Measurements were made at night, prior to and starting one hour after consumption of energy drink ingredients or placebo. At the end of the experiment (midnight), P300 latency and motor reaction time were significantly longer compared with baseline measurements in the placebo group, but were unchanged in the energy drink group. In the test system for evaluating feelings of well-being, total scores, vitality scores and social extrovertedness scores were significantly decreased in the placebo group but not in the energy drink group. The findings clearly indicate that the mixture of three key ingredients of Red BullR Energy Drink used in the study (caffeine, taurine, glucuronolactone) have positive effects upon human mental performance and mood. These effects may be mediated by the action of caffeine on purinergic (adenosinergic) receptors and taurine modulation of receptors. As half of the study cohort were non-caffeine users, the described effects cannot be explained in terms of the restoration of plasma caffeine levels to normal following caffeine withdrawal.
Cognitive and physiological effects of an “energy drink”: an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions (Scholey and Kennedy, 2004)
Both glucose and caffeine can improve aspects of cognitive performance and, in the case of caffeine, mood. There are few studies investigating the effects of the two substances in combination. We assessed the mood, cognitive and physiological effects of a soft drink containing caffeine and glucose as well as flavouring levels of herbal extracts. The effects of different drink fractions were also evaluated. Using a randomised, double-blind, balanced, five-way crossover design, 20 participants who were overnight fasted and caffeine-deprived received 250 ml drinks containing 37.5 g glucose; 75 mg caffeine; ginseng and ginkgo biloba at flavouring levels; a whole drink (containing all these substances) or a placebo (vehicle). Participants were assessed in each drink condition, separated by a 7-day wash-out period. Cognitive, psychomotor and mood assessment took place immediately prior to the drink then 30 min thereafter. The primary outcome measures included five aspects of cognitive performance from the Cognitive Drug Research assessment battery. Mood, heart rate and blood glucose levels were also monitored. Compared with placebo, the whole drink resulted in significantly improved performance on “secondary memory” and “speed of attention” factors. There were no other cognitive or mood effects. This pattern of results would not be predicted from the effects of glucose and caffeine in isolation, either as seen here or from the literature addressing the effects of the substances in isolation. These data suggest that there is some degree of synergy between the cognition-modulating effects of glucose and caffeine which merits further investigation.
A glucose-caffeine 'energy drink' ameliorates subjective and performance deficits during prolonged cognitive demand (Scholey and Kennedy, 2004)
Effects of a combination of caffeine and glucose were assessed in two double-blind, placebo-controlled, cross-over studies during extended performance of cognitively demanding tasks. In the first study, 30 participants received two drinks containing carbohydrate and caffeine (68 g/38 mg; 68 g/46 mg, respectively) and a placebo drink, in counter-balanced order, on separate days. In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink. In both studies, participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the Rapid Visual Information Processing task (RVIP), plus a rating of 'mental fatigue', once before the drink and six times in succession commencing 10 min after its consumption. In comparison to placebo, all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study resulted in lower ratings of mental fatigue. These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand.
Effects of caffeine and glucose, alone and combined, on cognitive performance (Adan and Serra-Grabulosa, 2010)
To study the effects of consuming caffeine and glucose, alone and combined, on cognitive performance. Seventy-two healthy subjects (36 women; age range 18–25) were tested early in the morning, having fasted overnight. Using a double-blind, randomised design, subjects received one of the following beverages: water (150 ml); water plus 75 mg of caffeine; water plus 75 g of glucose; water plus and 75 mg of caffeine and 75 g of glucose. Attention, manual dexterity, visuo-spatial and frontal functions, memory (immediate, consolidation and working) and subjective state were all assessed. The combination of caffeine and glucose had beneficial effects on attention (sequential reaction time tasks) and on learning and consolidation of verbal memory, effects not being observed when either substance was administered alone. Caffeine only showed improvement in simple reaction time and glucose in simple and one sequential reaction time tasks and in the manual dexterity assembly task. The results indicate that the synergistic effects of caffeine and glucose can benefit sustained attention and verbal memory, even with adequate levels of activation of the subjects. However, further studies are required, controlling for different levels of cognitive effort and also considering measurements of neural activity.
Enhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individuals (Childs and De Wit, 2008)
Caffeine produces mild psychostimulant effects that may be particularly evident in individuals whose mood or performance is impaired by sleep restriction or caffeine withdrawal. Caffeinated energy drinks have been shown to improve energy and cognition but expectancy effects cannot be ruled out in these studies. Very few studies have examined the effects of caffeine-containing energy capsules upon behavioral and subjective measures. This study compared the effects of a caffeine-containing (200 mg) supplement (CAF) or placebo in capsule form after prolonged wakefulness, in participants who varied in their level of habitual caffeine use. Thirty-five healthy volunteers (16 male, 19 female) participated in two experimental sessions in which they remained awake between 5 p.m. and 5 a.m. At 3:30 a.m. they consumed CAF or placebo in random order under double-blind conditions. Participants completed subjective effects questionnaires and performed computerized attention tasks before and after consuming capsules. Heart rate and blood pressure were monitored at regular intervals. Compared to measures at 5 p.m., participants reported more tiredness and mood disturbance at 3 a.m., and exhibited longer reaction times and more attentional lapses. Heavier caffeine consumers exhibited the greatest decreases in Profile of Mood States (POMS) Vigor. CAF produced stimulant-like effects and significantly improved mood and reaction times upon the tasks. These effects did not vary with level of habitual caffeine consumption. These findings indicate that consumption of a caffeine-containing food supplement improves subjective state and cognitive performance in fatigued individuals that is likely a result of its caffeine content.
Glucose and caffeine effects on sustained attention: an exploratory fMRI study (Serra-Grabulosa et al, 2010)
Caffeine and glucose can have beneficial effects on cognitive performance. However, neural basis of these effects remain unknown. Our objective was to evaluate the effects of caffeine and glucose on sustained attention, using functional magnetic resonance imaging (fMRI). Forty young right-handed, healthy, low caffeine-consuming subjects participated in the study. In a double-blind, randomised design, subjects received one of the following beverages: vehicle (water, 150 ml); vehicle plus 75 g of glucose; vehicle plus 75 mg of caffeine; vehicle plus 75 g of glucose and 75 mg of caffeine. Participants underwent two scanning fMRI sessions (before and 30 min after of the administration of the beverage). A continuous performance test was used to assess sustained attention. Participants who received combined caffeine and glucose had similar performance to the others but had a decrease in activation in the bilateral parietal and left prefrontal cortex. Since these areas have been related to the sustained attention and working memory processes, results would suggest that combined caffeine and glucose could increase the efficiency of the attentional system. However, more studies using larger samples and different levels of caffeine and glucose are necessary to better understand the combined effects of both substances.
The combined effects of L-theanine and caffeine on cognitive performance and mood (Owen et al, 2008)
The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L-theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks.
The effects of L-theanine, caffeine and their combination on cognition and mood (Haskell, 2008)
L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were comonitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.
Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together (Rogers et al, 2008)
Although both contain behaviourally significant concentrations of caffeine, tea is commonly perceived to be a less stimulating drink than coffee. At least part of the explanation for this may be that theanine, which is present in tea but not coffee, has relaxing effects. There is also some evidence that theanine affects cognitive performance, and it has been found to reduce blood pressure in hypertensive rats. To study the subjective, behavioural and blood pressure effects of theanine and caffeine administered alone and together, in doses relevant to the daily tea consumption of regular tea drinkers. In a randomised, double-blind, placebo-controlled study, healthy adult participants (n = 48) received either 250-mg caffeine, 200-mg theanine, both or neither of these. They completed ratings of mood, including anxiety, and alertness, and had their blood pressure measured before and starting 40 min after drug administration. Anxiety was also assessed using a visual probe task. Caffeine increased self-rated alertness and jitteriness and blood pressure. Theanine antagonised the effect of caffeine on blood pressure but did not significantly affect jitteriness, alertness or other aspects of mood. Theanine also slowed overall reaction time on the visual probe task. Theanine is a physiologically and behaviourally active compound and, while it is unclear how its effects might explain perceived differences between tea and coffee, evidence suggests that it may be useful for reducing raised blood pressure.
L-Theanine and Caffeine in Combination Affect Human Cognition as Evidenced by Oscillatory alpha-Band Activity and Attention Task Performance (Kelly et al, 2008)
Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8–14 Hz) activity. We found an increase in hit rate and target discriminability (d′) for the combined treatment relative to placebo, and an increase in d′ but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.
L-Theanine and caffeine improve task switching but not intersensory attention or subjective alertness (Einother et al, 2010)
Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention.
The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness (Giesbrecht et al, 2010)
The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L-theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task.
Safety Studies
Caffeine (4 mg/kg) influences sustained attention and delayed free recall but not memory predictions (Kelemen and Creeley, 2001)
This experiment was conducted to examine the influence of a moderate dose of caffeine (4 mg/kg) on delayed memory, metamemory, and sustained attention. One hundred and forty-two volunteers ingested either caffeine or placebo during a study session which included three different memory tasks (free recall, cued recall, and recognition), and they made predictions of future memory performance. On day 2, participants again ingested either caffeine or placebo and completed memory tests. Sustained attention performance was measured on both days, and caffeine reliably improved hit rates and response latencies. A reliable drug-state interaction was detected only in the free recall test of memory. Caffeine did not affect the magnitude or accuracy of memory predictions, but there was some evidence that expectancies about caffeine were related to cognitive performance. Overall, caffeine's impact on memory and metamemory was not robust in this study.
Effects of caffeine on mood and performance: a study of realistic consumption (Brice and Smith, 2002)
There is a vast literature on the behavioural effects of caffeine. Many of the studies have involved single administration of a large dose of caffeine that is not representative of the way in which caffeine is usually ingested. Further information is required, therefore, on the behavioural effects of realistic patterns of consumption. The present study aimed to determine whether a realistic drinking regime (multiple small doses – 4×65 mg over a 5-h period) produced the same effects as a single large dose (200 mg). The smaller doses were selected so that the amount of caffeine present in the body after 5 h would be equivalent to that found with the single dose. A double-blind, placebo-controlled, within-subjects experiment was, therefore, carried out. The participants (n=24) attended for four sessions. Each session started with a baseline measurement of mood and performance at 0930 hours. On two of the sessions, coffee was then consumed at 1000, 1100, 1200 and 1300 hours. In one of these sessions 65 mg caffeine was added to the de-caffeinated coffee. In the other two sessions, the participants consumed coffee at 1300 hours and 200 mg caffeine was added in one of the sessions. The volunteers completed the battery of tests again at 1500 hours. The results showed that in both consumption regimes caffeine led to increased alertness and anxiety and improved performance on simple and choice reactive tasks, a cognitive vigilance task, a task requiring sustained response and a dual task involving tracking and target detection. These results suggest that previous findings from studies using a large single dose may be applicable to normal patterns of caffeine consumption.
Caffeine modulates attention network function (Brunye et al, 2010)
The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a flanker task designed to test Posner’s three visual attention network functions: alerting, orienting, and executive control. In a placebo-controlled, double-blind study using a repeated-measures design, we found that the effects of caffeine on visual attention vary as a function of dose and the attention network under examination. Caffeine improved alerting and executive control function in a dose–response manner, asymptoting at 200 mg; this effect is congruent with caffeine’s adenosine-mediated effects on dopamine-rich areas of brain, and the involvement of these areas in alerting and the executive control of visual attention. Higher doses of caffeine also led to a marginally less efficient allocation of visual attention towards cued regions during task performance (i.e., orienting). Taken together, results of this study demonstrate that caffeine has differential effects on visual attention networks as a function of dose, and such effects have implications for hypothesized interactions of caffeine, adenosine and dopamine in brain areas mediating visual attention.
The influences of age and caffeine on psychomotor and cognitive function (Rees et al, 1999)
The response to caffeine is affected by a number of factors, including age. Older subjects may be more sensitive to the objective effects than younger but report fewer subjective effects. This study assessed the influence of age on the effects of caffeine on a variety of psychomotor, cognitive and subjective tests. Forty-eight healthy subjects, male and female, were recruited, 24 in the age range 20–25 and 24 in the range 50–65 years. All subjects were regular moderate caffeine drinkers and were not withdrawn from caffeine before entry to the study. A double-blind parallel group design was used with two groups of 12 subjects in each age range. One group in each age range received placebo and the other 250 mg caffeine B.P. A range of tests was used to assess psychomotor, cognitive and subjective functioning before and 1 h post-treatment. Before treatment, young subjects generally performed better than older on psychomotor and cognitive tests. On the subjective tests, however, older subjects rated themselves as more alert and less tired than the younger ones. After placebo, performance and alertness improved in the younger group but declined in the older. After caffeine there were improvements in psychomotor performance and cognitive functioning in both groups, particularly in offsetting declining performance over time in the older subjects. It also produced subjective improvements in alertness. One factor to emerge was that on most assessments older subjects were better earlier in the day whereas in younger subjects performance did not show the same magnitude of decline throughout the day. Caffeine induced small but significant improvements in vigilance and psychomotor performance.
Does caffeine intake enhance absolute levels of cognitive performance? (Jarvis, 1993)
The relationship between habitual coffee and tea consumption and cognitive performance was examined using data from a cross-sectional survey of a representative sample of 9003 British adults (the Health and Lifestyle Survey). Subjects completed tests of simple reaction time, choice reaction time, incidental verbal memory, and visuo-spatial reasoning, in addition to providing self-reports of usual coffee and tea intake. After controlling extensively for potential confounding variables, a dose-response trend to improved performance with higher levels of coffee consumption was observed for all four tests (P<0.001 in each case). Similar but weaker associations were found for tea consumption, which were significant for simple reaction time (P=0.02) and visuo-spatial reasoning (P=0.013). Estimated overall caffeine consumption showed a dose-response relationship to improved cognitive performance (P<0.001 for each cognitive test, after controlling for confounders). Older people appeared to be more susceptible to the performance-improving effects of caffeine than were younger. The results suggest that tolerance to the performance-enhancing effects of caffeine, if it occurs at all, is incomplete.
Influence of caffeine on selective attention in well-rested and fatigued subjects (Lorist et al, 1994)
Effects of caffeine were studied in a visual focused selective search task in well-rested and fatigued subjects. A dose of 200 + 50 mg caffeine or placebo, dissolved in decaffeinated coffee, was administered in a double-blind and deceptive fashion. The task was to detect a target letter on one diagonal of a visual display designated as relevant and ignore stimuli presented on the irrelevant diagonal. Behavioral measures were supplemented by event-related potential (ERP) measures. Subjects reacted faster in the caffeine condition. Caffeine enhanced the N1 and the N2b components. Selection of relevant information apparently was more adequate in this condition. Search negativity was not affected by caffeine. Caffeine effects on the P3 elicited by target letters were more pronounced in the fatigued than in the well-rested subjects, indicating that the effects of caffeine are dependent on the state of the subject. The results suggest that caffeine has specific rather than general effects on information processing.
The effects of caffeine on two computerized tests of attention and vigilance (Frewer and Lader, 1991)
Single doses of caffeine (250 mg, 500 mg) or placebo were administered double-blind to healthy volunteer subjects (n = 12), using a fully balanced crossover design (Williams square) with 1-week washout. Assessments were made predrug, and at 45 min and 165 min post-drug administration. The test battery comprised physiological measures (blood pressure, heart rate and urinary volume), subjective measures of alertness, a letter cancellation task (one-target, two-target and four-target versions), and two computerized measures of attention and vigilance: a rapid information processing task and a continuous attention task. Physiological variables did not alter following caffeine administration, but subjective and cognitive variables showed significant changes in the predicted direction. Thus, doserelated changes in subjective calmness and interest were observed, together with changes in performance for the letter cancellation task at low and intermediate difficulty levels. A dose-related performance improvement was observed for the rapid information processing task. The continuous attention task was also sensitive to the effects observed for the rapid information processing task. The continuous attention task was also sensitive to the effects of caffeine. The 250 mg dose offset the decline in attention observed under placebo, and indeed facilitated performance at both post-drug administration times. The 500 mg dose impaired performance at 45 min and improved it at the 165 min post-administration time. Sensitivity to vigilance change was also observed within test sessions for this test, indicating that the continuous attention task was more sensitive to caffeine-induced changes in attention than the rapid information processing task.
Slow release caffeine and prolonged (64-h) continuous wakefulness: effects on vigilance and cognitive performance (Beaumont et al, 2001)
Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow-release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double-blind, randomised, placebo controlled, two-way crossover study. A total of 300-mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD-NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop’s test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00–04:00 h, 14:00–16:00 h) and hypervigilance (10:00–12:00 h, 22:00–00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop’s test (P=0.048). We showed that 300-mg SRC given twice daily during a 64-h SD is able to antagonize the impairment produced on vigilance and cognitive functions.
Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training (Lieberman et al, 2002)
When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.
Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers (Smith et al, 2005)
Evidence for behavioural effects of caffeine is well documented in the literature. It is associated with increased subjective alertness, improved reaction time and enhanced encoding of new information. These effects are most prominent in low arousal situations. However, there is an ongoing debate as to whether such changes are in fact improvements or merely a reversal of the negative effects of a period of caffeine withdrawal (e.g. overnight abstinence). To avoid such a confound this study included multiple doses of caffeine which were administered under double-blind conditions to participants who had ingested their normal daily quota of caffeine. In the present study participants were fatigued by carrying out a prolonged testing schedule in the evening. Sixty volunteers, all regular caffeine consumers, took part in the study. They attended for three sessions on separate days. They were instructed to consume normal amounts of caffeinated beverages. Consumption was measured by a diary and saliva samples were taken and caffeine assays conducted. A baseline test session was carried out at 18.00h and following this a double blind placebo controlled caffeine challenge (1.5mg/kg) conducted. The test battery was repeated twice approximately 30 minutes after the caffeine challenge. Following this another drink was administered and the test battery repeated twice more. On one test session volunteers had placebo in both drinks, in another they had caffeine in both drinks and another caffeine in the first and placebo in the second. Order of conditions was balanced across subjects. The results showed that caffeine led to a more positive mood and improved performance on a number of tasks. Different effects of caffeine were seen depending on the person’s level of arousal. Linear effects of caffeine dose were also observed. This is evidence against the argument that behavioural changes due to caffeine are merely the reversal of negative effects of a long period of caffeine abstinence. The findings are discussed in relation to both noradrenergic and cholinergic neurotransmitter systems.
Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine (Haskell et al 2005)
The cognitive and mood effects of caffeine are well documented. However, the majority of studies in this area involve caffeine-deprived, habitual caffeine users. It is therefore unclear whether any beneficial findings are due to the positive effects of caffeine or to the alleviation of caffeine withdrawal. The present placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of caffeine in habitual users and habitual non-users of caffeine. Following overnight caffeine withdrawal, 24 habitual caffeine consumers (mean=217 mg/day) and 24 habitual non-consumers (20 mg/day) received a 150 ml drink containing either 75 or 150 mg of caffeine or a matching placebo, at intervals of ≥48 h. Cognitive and mood assessments were undertaken at baseline and 30 min post-drink. These included the Cognitive Drug Research computerised test battery, two serial subtraction tasks, a sentence verification task and subjective visual analogue mood scales. There were no baseline differences between the groups’ mood or performance. Following caffeine, there were significant improvements in simple reaction time, digit vigilance reaction time, numeric working memory reaction time and sentence verification accuracy, irrespective of group. Self-rated mental fatigue was reduced and ratings of alertness were significantly improved by caffeine independent of group. There were also group effects for rapid visual information processing false alarms and spatial memory accuracy with habitual consumers outperforming non-consumers. There was a single significant interaction of group and treatment effects on jittery ratings. Separate analyses of each groups’ responses to caffeine revealed overlapping but differential responses to caffeine. Caffeine tended to benefit consumers’ mood more while improving performance more in the non-consumers. These results do not support a withdrawal alleviation model. Differences in the patterns of responses to caffeine by habitual consumers and habitual non-consumers may go some way to explaining why some individuals become caffeine consumers.
Effects of caffeine on performance and mood depend on the level of caffeine abstinence (Yeomans et al, 2002)
Most studies of the effects of caffeine on performance have used regular caffeine consumers who are deprived at test. Thus the reported effects of caffeine could be explained through reversal of caffeine withdrawal. To test how preloading deprived caffeine consumers with 0, 1 or 2 mg/kg caffeine altered the subsequent ability of caffeine to modify mood and performance. Thirty moderate caffeine consumers were given a drink containing 0, 1 or 2 mg/kg caffeine at breakfast followed 60 min later by a second drink containing either 0 or 1 mg/kg caffeine. Performance on a measure of sustained attention and mood were measured before and after each drink. Administration of both 1 and 2 mg/kg caffeine at breakfast decreased reaction time and 1 mg/kg caffeine also increased performance accuracy on the sustained attention (RVIP) task relative to placebo. Both breakfast doses of caffeine also improved rated mental alertness. Similarly, 1 mg/kg caffeine administered 60 min after breakfast decreased reaction time and increased rated mental alertness in the group who had not been given caffeine at breakfast. However, this second dose of caffeine had no effect on subsequent performance or mood in the two groups who had received caffeine at breakfast. Caffeine reliably improved performance on a sustained attention task, and increased rated mental alertness, in moderate caffeine consumers who were tested when caffeine-deprived. However, caffeine had no such effects when consumers were no longer caffeine deprived. These data are consistent with the view that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance.
Effects of caffeine on cognitive and autonomic measures in heavy and light caffeine consumers (Lyvers et al, 2007)
Caffeine effects on arousal and cognition were assessed in relation to habitual caffeine intake. After drinking either decaffeinated coffee or decaffeinated coffee plus 300 mg caffeine, 22 heavy caffeine consumers (HCCs) and 26 light caffeine consumers (LCCs) were examined on various cognitive, autonomic, and anxiety measures. In LCCs only, caffeine significantly improved performance of the Wisconsin Card Sorting Test, and significantly increased state anxiety scores. Caffeine significantly increased spontaneous skin conductance responses in HCCs and LCCs alike. The HCCs and LCCs did not differ on measures of trait anxiety or neuroticism. Results are discussed in terms of the cognitive enhancing and nonspecific arousing effects ofcaffeine in relation to caffeine tolerance.
The combined effects of L-theanine and caffeine on cognitive performance and mood (Owen et al, 2008)
The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L-theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks.
Effects of Evening Meals and Caffeine on Cognitive Performance, Mood and Cardiovascular Functioning (Smith et al, 1994)This experiment was carried out to examine the effects of an evening meal and caffeine (3 mg/kg) on performance, mood and cardiovascular functioning. Subjects given a meal reported that they felt stronger, more proficient and more interested than subjects in the no-meal condition. They also performed a logical reasoning task more quickly than the no-meal group. However, no effects were found on sustained attention tasks or tasks involving recall or recognition of word lists. The effects of evening meals are, therefore, different from either those observed after lunch or breakfast. Caffeine improved alertness and performance on sustained attention tasks for the group as a whole. Interactions between caffeine conditions and levels of impulsivity of the subjects were also found in memory tasks.
The effects of L-theanine, caffeine and their combination on cognition and mood (Haskell, 2008)
L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were comonitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.
Caffeine, cognitive failures and health in a non-working community sample (Smith, 2008)
Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Secondary analyses of a large epidemiological database (N = 3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17–92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140 mg/day, range 0–1800 mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of caffeine was found to be associated with a reduced risk of depression.
Caffeine eliminates psychomotor vigilance deficits from sleep inertia (van Dongen et al, 2001)
This study sought to establish the effects of caffeine on sleep inertia, which is the ubiquitous phenomenon of cognitive performance impairment, grogginess and tendency to return to sleep immediately after awakening. 28 normal adult volunteers were administered sustained low-dose caffeine or placebo (randomized double-blind) during the last 66 hours of an 88-hour period of extended wakefulness that included seven 2-hour naps during which polysomnographical recordings were made. Every 2 hours of wakefulness, and immediately after abrupt awakening from the naps, psychomotor vigilance performance was tested. In the placebo condition, sleep inertia was manifested as significantly impaired psychomotor vigilance upon awakening from the naps. This impairment was absent in the caffeine condition. Caffeine had only modest effects on nap sleep. Caffeine was efficacious in overcoming sleep inertia. This suggests a reason for the popularity of caffeine-containing beverages after awakening. Caffeine's main mechanism of action on the central nervous system is antagonism of adenosine receptors. Thus, increased adenosine in the brain upon awakening may be the cause of sleep inertia.
Caffeine, Cognitive Functioning, and White Matter Lesions in the Elderly: Establishing Causality from Epidemiological Evidence (Ritchie et al, 2010)
The present study examines the epidemiological evidence for a causal relationship between caffeine consumption and cognitive deterioration in the elderly. Using a population of 641 elderly persons, we examined cognitive functioning, caffeine consumption, magnetic resonance imaging volumetrics, and other factors known to affect cognitive performance. Our findings demonstrate the association between caffeine consumption and lower cognitive change over time to be statistically significant for women only, taking into account multiple confounders, to be dose-dependent and temporarily related (caffeine consumption precedes cognitive change). Mean log transformed white matter lesion/cranial volume ratios were found to be significantly lower in women consuming more than 3 units of caffeine per day after adjustment for age (−1.23 SD=0.06) than in women consuming 2−3 units (−1.04 SD=0.04) or one unit or less (−1.04 SD=0.07, −35% in cm^{3}compared to low drinkers). This observation is coherent with biological assumptions that caffeine through adenosine is linked to amyloid accumulation and subsequently white matter lesion formation. The significant relationship observed between caffeine intake in women and lower cognitive decline is highly likely to be a true causal relationship and not a spurious association.
The effect of caffeine on cognitive task performance and motor fatigue (van Duinen et al, 2005)
In everyday life, people are usually capable of performing two tasks simultaneously. However, in a previous study we showed that during a fatiguing motor task, cognitive performance declined progressively. There is extensive literature on the (positive) effects of caffeine on cognitive and motor performance. These effects are most pronounced under suboptimal conditions, for example during fatigue. However, little is known about the effects of caffeine on cognitive performance during a fatiguing motor task. This study was aimed to investigate whether a moderate dose of caffeine could attenuate the decline in cognitive performance during a fatiguing motor task. The study consisted of a placebo and a caffeine (3 mg/kg) session. A total of 23 subjects completed these sessions in a semi-randomized and double-blind order. In each session, subjects performed maximal voluntary contractions of the index finger, a choice reaction time (CRT) task and a dual task consisting of a fatiguing motor task concomitantly with the same CRT task. After the fatiguing dual task, the CRT task was repeated. Caffeine improved cognitive task performance, in both the single and dual task, as shown by decreased reaction times together with unchanged accuracy. Cognitive performance in the dual task deteriorated with increasing fatigue. However, the decrease in cognitive performance in the beginning of the dual task, as observed in the placebo condition, was partly prevented by caffeine administration (i.e., no increase in reaction times). We found no effects of caffeine on motor parameters (absolute force, endurance time or electromyographic amplitude). Caffeine improved cognitive performance. This effect also extends under demanding situations, as was shown by the performance during the dual task, even during progressive motor fatigue.
Caffeine and Central Noradrenaline: Effects on Mood, Cognitive Performance, Eye Movements and Cardiovascular Function (Smith et al, 2003)
There have been numerous studies on the effects of caffeine on behaviour and cardiovascular function. It is now important to clarify the mechanisms that underlie such effects, and the main objective of the present study was to investigate whether changes in central noradrenaline underlie some of the behavioural and cardiovascular effects of caffeine. This was examined using a clonidine challenge paradigm. Twenty-four healthy volunteers were assigned to one of four conditions: (i) clonidine/caffeine; (ii) clonidine/placebo; (iii) placebo/caffeine; (iv) placebo/placebo. Baseline measurements of mood, cognitive performance, saccadic eye movements and cardiovascular function were recorded. Subsequently, volunteers were given either clonidine (200 μg) or placebo and consumed coffee containing caffeine (1.5 mg/kg) or placebo. The test battery was then repeated 30 min, 150 min and 270 min later. A second cup of coffee (with the same amount of caffeine as the first) was consumed 120 min after the first cup. The results showed that clonidine reduced alertness, impaired many aspects of performance and slowed saccadic eye movements; caffeine removed many of these impairments. Both clonidine and caffeine influenced blood pressure (clonidine reduced it, caffeine raised it) but the effects appeared to be independent, suggesting that separate mechanisms were involved. In addition, there were some behavioural effects of caffeine that were independent of the clonidine effect (e.g. effects on speed of encoding of new information) and these may reflect other neurotransmitter systems (e.g cholinergic effects). Overall, the results suggest that caffeine counteracts reductions in the turnover of central noradrenaline. This mechanism may underlie the beneficial effects of caffeine seen in low alertness states.
Effects of breakfast and caffeine on cognitive performance, mood and cardiovascular functioning (Kendrick et al, 1994) Two experiments with 48 university students each examined the effect of breakfast (BF) and caffeine (4 mg/kg) on cognitive performance, mood, and cardiovascular functioning. In Exp 1, BF had no effect on performance of sustained attention tasks, but it increased pulse rate and influenced mood. The mood effects after BF differed between a cooked BF and a cereal/toast BF. The high dose of caffeine improved performance of the sustained attention tasks, increased blood pressure, and increased mental alertness. In Exp 2, effects of a BF and caffeine on mood and cardiovascular functions confirmed the results of the 1st study. BF improved performance on free recall and recognition memory tasks, had no effect on a semantic memory task, and impaired the accuracy of performing a logical reasoning task. In contrast, caffeine improved performance on the semantic memory, logical reasoning, free recall, and recognition memory tasks.
Effects of caffeine on cognition and mood without caffeine abstinence (Warburton, 1995)
The objective of this study was to evaluate the effects of low doses (75 mg and 150 mg) of caffeine on mood and cognition in healthy people, with minimal abstinence of 1 hr from caffeine. Improvements were obtained in cognition for attention, problem solving and delayed recall, but not immediate recall or working memory, but performance in the placebo condition was close to the maximum, giving little margin for improvement. For mood, there were statistically significant increase in clearheadedness, happiness and calmness and decreases in tenseness. These mood and performance-enhancing effects of caffeine cannot be seen as representing an alleviation of deficits induced by caffeine abstinence, because there was only minimal deprivation from caffeine.
The effects of a low dose of caffeine on cognitive performance (Durlach, 2008)
There is little evidence concerning the effects of caffeine in doses typical of one cup of tea. The present study investigated the effect of 60 mg caffeine, consumed in either tea or hot water, on performance on a subset of the CANTAB test battery. Eight males participated in a practice session and four test sessions. In each test session, the participant consumed a different hot beverage and then, over approximately 90 min, completed nine tests from the CANTAB battery. The four beverages were created by crossing beverage identity (tea or hot water) and caffeine dose (0 or 60 mg). Significant speeding of reaction time by caffeine consumption was found in pattern recognition, delayed match to sample, and match to sample visual search. The effect on reaction time of 60 mg caffeine can be detected, and may be evident within minutes of consumption.
Caffeine Consumption and Cognitive Function at Age 70: The Lothian Birth Cohort 1936 Study (Corley et al, 2010)
To investigate the association between caffeine consumption and cognitive outcomes in later life. Participants were 923 healthy adults from the Lothian Birth Cohort 1936 Study, on whom there were intelligence quotient (IQ) data from age 11 years. Cognitive function at age 70 years was assessed, using tests measuring general cognitive ability, speed of information processing, and memory. Current caffeine consumption (using multiple measures of tea, coffee, and total dietary caffeine) was obtained by self-report questionnaire, and demographic and health information was collected in a standardized interview. In age- and sex-adjusted models, there were significant positive associations between total caffeine intake and general cognitive ability and memory. After adjustment for age 11 IQ and social class, both individually and together, most of these associations became nonsignificant. A robust positive association, however, was found between drinking ground coffee (e.g., filter and espresso) and performance on the National Adult Reading Test (NART, p = .007), and the Wechsler Test of Adult Reading (WTAR, p = .02). No gender effects were observed, contrary to previous studies. Generally, higher cognitive scores were associated with coffee consumption, and lower cognitive scores with tea consumption, but these effects were not significant in the fully adjusted model. The present study is rare in having childhood IQ in a large sample of older people. The results suggest that the significant caffeine intake-cognitive ability associations are bidirectional—because childhood IQ and estimated prior IQ are associated with the type of caffeine intake in old age—and partly confounded by social class.
Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together (Rogers et al, 2008)
Although both contain behaviourally significant concentrations of caffeine, tea is commonly perceived to be a less stimulating drink than coffee. At least part of the explanation for this may be that theanine, which is present in tea but not coffee, has relaxing effects. There is also some evidence that theanine affects cognitive performance, and it has been found to reduce blood pressure in hypertensive rats. To study the subjective, behavioural and blood pressure effects of theanine and caffeine administered alone and together, in doses relevant to the daily tea consumption of regular tea drinkers. In a randomised, double-blind, placebo-controlled study, healthy adult participants (n = 48) received either 250-mg caffeine, 200-mg theanine, both or neither of these. They completed ratings of mood, including anxiety, and alertness, and had their blood pressure measured before and starting 40 min after drug administration. Anxiety was also assessed using a visual probe task. Caffeine increased self-rated alertness and jitteriness and blood pressure. Theanine antagonised the effect of caffeine on blood pressure but did not significantly affect jitteriness, alertness or other aspects of mood. Theanine also slowed overall reaction time on the visual probe task. Theanine is a physiologically and behaviourally active compound and, while it is unclear how its effects might explain perceived differences between tea and coffee, evidence suggests that it may be useful for reducing raised blood pressure.
L-Theanine and Caffeine in Combination Affect Human Cognition as Evidenced by Oscillatory alpha-Band Activity and Attention Task Performance (Kelly et al, 2008)
Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8–14 Hz) activity. We found an increase in hit rate and target discriminability (d′) for the combined treatment relative to placebo, and an increase in d′ but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.
Cognitive Performance during Sustained Wakefulness: A Low Dose of Caffeine Is Equally Effective as Modafinil in Alleviating the Nocturnal Decline (Dagan and Doljansky, 2006)
Cognitive performance at night exhibits a substantial drop, typically before dawn. One of the means of dealing with this phenomenon, as well as with the accompanying sleepiness during sustained wakefulness, is the administration of stimulants. The most widely used and well‐documented stimulants are caffeine, amphetamines, and modafinil. Of these, amphetamines are the least recommended, as they may severely affect behavior. Caffeine and modafinil seem to produce relatively milder side effects and usually only at high doses. Previous comparison studies have revealed equal efficacy of both the stimulants in maintaining alertness and performance during sustained wakefulness. However, these studies used relatively high, and thus not completely safe, doses of these drugs (600 mg caffeine and 400 mg modafinil). Therefore, the aim of the present study was to assess the efficacy of a low and medically safe dose of caffeine (200 mg) and modafinil (200 mg) in maintaining cognitive performance during sustained wakefulness. A flight simulation task was chosen for the assessment of the stimulants in a counter‐balanced, within‐subject design under four different conditions: baseline (no drugs), placebo, caffeine (200 mg), and modafinil (200 mg). The equal effectiveness of both drugs in abolishing the nocturnal drop in cognitive performance, as well as of oral temperature and blood pressure, supported the use of low doses of caffeine and modafinil for the maintenance of alertness in healthy subjects during sustained wakefulness.
Effects of caffeine and glucose, alone and combined, on cognitive performance (Adan and Serra-Grabulosa, 2010)
To study the effects of consuming caffeine and glucose, alone and combined, on cognitive performance. Seventy-two healthy subjects (36 women; age range 18–25) were tested early in the morning, having fasted overnight. Using a double-blind, randomised design, subjects received one of the following beverages: water (150 ml); water plus 75 mg of caffeine; water plus 75 g of glucose; water plus and 75 mg of caffeine and 75 g of glucose. Attention, manual dexterity, visuo-spatial and frontal functions, memory (immediate, consolidation and working) and subjective state were all assessed. The combination of caffeine and glucose had beneficial effects on attention (sequential reaction time tasks) and on learning and consolidation of verbal memory, effects not being observed when either substance was administered alone. Caffeine only showed improvement in simple reaction time and glucose in simple and one sequential reaction time tasks and in the manual dexterity assembly task. The results indicate that the synergistic effects of caffeine and glucose can benefit sustained attention and verbal memory, even with adequate levels of activation of the subjects. However, further studies are required, controlling for different levels of cognitive effort and also considering measurements of neural activity.
Caffeine attenuates scopolamine-induced memory impairment in humans (Reidel et al, 1995)
Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.
Supporting Animal Studies
Effects of caffeine on learning and memory in rats tested in the Morris water maze (Angelucci et al, 2002)
We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. Groups of 12 adult male Wistar rats receiving caffeine (0.3-30 mg/kg, ip, in 0.1 ml/100 g body weight) administered 30 min before training, immediately after training, or 30 min before the test session were tested in the spatial version of the Morris water maze task. Post-training administration of caffeine improved memory retention at the doses of 0.3-10 mg/kg (the rats swam up to 600 cm less to find the platform in the test session, P£0.05) but not at the dose of 30 mg/kg. Pre-test caffeine administration also caused a small increase in memory retrieval (the escape path of the rats was up to 500 cm shorter, P£0.05). In contrast, pre-training caffeine administration did not alter the performance of the animals either in the training or in the test session. These data provide evidence that caffeine improves memory retention but not memory acquisition, explaining some discrepancies among reports in the literature.
Chronic Caffeine Treatment Prevents Sleep Deprivation-Induced Impairment of Cognitive Function and Synaptic Plasticity (Alheider et al , 2010)
Study Objectives: This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. Experimental Design: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. Measurement and Results: The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, short-term memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. Conclusions: The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.
The effect of caffeine in animal models of learning and memory (Angelucci et al, 1999)
In the present investigation we studied the effect of caffeine on memory task inhibitory avoidance and habituation to a new environment. Caffeine impaired retention scores in mice submitted to inhibitory avoidance and habituation when administered 30 min before training at the doses of 10–30 mg/kg. These effects cannot be explained by state-dependency since the administration of caffeine 30 min before the test session did not reverse the effect of pre-training caffeine administration, but can more probably be explained by an impairment in the acquisition or by interference with attentional processes. On the other hand, caffeine improved the inhibitory avoidance (but not habituation) retention scores when administered immediately after the training or 30 min before the test session at the doses of 1–30 mg/kg or 3–10 mg/kg, respectively. These results suggest that caffeine differentially affects the different stages of memory processing and that this effect depends on particularities of the memory task under study.
Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats: Involvement of adenosine A1 and A2A receptors (Prediger et al, 2005)
Caffeine, a non-selective adenosine receptor antagonist, has been suggested as a potential drug to counteract age-related cognitive decline since critical changes in adenosinergic neurotransmission occur with aging. In the present study, olfactory discrimination and short-term social memory of 3, 6, 12 and 18 month-old rats were assessed with the olfactory discrimination and social recognition tasks, respectively. The actions of caffeine (3.0, 10.0 and 30.0 mg/kg, i.p.), the A1 receptor antagonist DPCPX (1.0 and 3.0 mg/kg, i.p.) and the A2A receptor antagonist ZM241385 (0.5 and 1.0 mg/kg, i.p.) in relation to age-related effects on olfactory functions were also studied. The 12 and 18 month-old rats exhibited significantly impaired performance in both models, demonstrating deficits in their odor discrimination and in their ability to recognize a juvenile rat after a short period of time. Acute treatment with caffeine or ZM241385, but not with DPCPX, reversed these age-related olfactory deficits. The present results suggest the participation of adenosine receptors in the control of olfactory functions and confirm the potential of caffeine for the treatment of aged-related cognitive decline.
Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus (Costa et al, 2008)Caffeine is one of the most psychostimulants consumed all over the world that usually presents positive effects on cognition. In this study, effects of caffeine on mice performance in the object recognition task were tested in different intertrial intervals. In addition, it was analyzed the effects of caffeine on brain derived neurotrophic factor (BDNF) and its receptor, TrkB, immunocontent to try to establish a connection between the behavioral finding and BDNF, one of the neurotrophins strictly involved in memory and learning process. CF1 mice were treated during 4 consecutive days with saline (0.9 g%, i.p.) or caffeine (10 mg/kg, i.p., equivalent dose corresponding to 2–3 cups of coffee). Caffeine treatment was interrupted 24 h before the object recognition task analysis. In the test session performed 15 min after training session, caffeine-treated mice recognized more efficiently both the familiar and the novel object. In the test session performed 90 min and 24 h after training session, caffeine did not change the time spent in the familiar object but increased the object recognition index, when compared to control group. Western blotting analysis of hippocampus from caffeine-treated mice revealed an increase in BDNF and TrkB immunocontent, compared to their saline-matched controls. Phospho-CREB immunocontent did not change with caffeine treatment. Our results suggest that acute treatment with caffeine improves recognition memory, and this effect may be related to an increase of the BDNF and TrkB immunocontent in the hippocampus.
Caffeine-induced synaptic potentiation in hippocampal CA2 neurons (Simons et al, 2011)Caffeine enhances cognition, but even high non-physiological doses have modest effects on synapses. A(1) adenosine receptors (A(1)Rs) are antagonized by caffeine and are most highly enriched in hippocampal CA2, which has not been studied in this context. We found that physiological doses of caffeine in vivo or A(1)R antagonists in vitro induced robust, long-lasting potentiation of synaptic transmission in rat CA2 without affecting other regions of the hippocampus.
Supporting Brain Studies
Caffeine strengthens action monitoring: evidence from the error-related negativity (Tieges et al, 2004)
The medial frontal cortex, especially the anterior cingulate cortex (ACC), is involved in action monitoring. We studied the role of moderate amounts of caffeine in action monitoring as expressed by the error-related negativity (ERN), an event-related brain component that reflects ACC activity. In a double-blind, placebo-controlled, within-subjects experiment, two caffeine doses (3 and 5 mg/kg body weight) and a placebo were administered to habitual coffee drinkers. Compared with placebo, both caffeine doses enlarged the ERN. Amplitudes of the P2 and P3 components were not affected by caffeine. Thus, the enlarged ERN after caffeine reflects a specific effect on action monitoring. We conclude that consumption of a few cups of coffee strengthens central information processing, specifically the monitoring of ongoing cognitive processes for signs of erroneous outcomes. Brain areas related to action monitoring such as the ACC presumably mediate these caffeine effects.
Does caffeine modulate verbal working memory processes? An fMRI study (Koppelstaetter et al, 2008)
To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.
Cellular Studies
none
Contradictory Studies
Effects of repeated caffeine administration on cognition and mood (Loke, 1990)
The effects of repeated caffeine administration on cognitive and mood tasks were investigated in a double-blind study of 32 young healthy adults who were randomly assigned to one of the four treatment conditions: 0, 200, 400, or 600 mg of caffeine. Subjects were tested over six alternate days; on each test day they completed various tasks after drug administration. In general, caffeine produced no significant effects on cognitive performance; the exception is that the highest dose (600 mg) reduced the speed of completion of additions relative to the other doses. Also, post-hoc analysis showed that the highest dose impaired performance of the lower caffeine users more than higher users. Mood assessment showed individuals were sensitive to the effects of caffeine but the effect did not interact with cognitive performance. The present data suggest that tolerance to the cognitive effects of caffeine does not develop with continued caffeine administration, given the limitations that the individuals tested were young healthy adults and the testing took place only over 2 weeks.
High doses of caffeine impair performance of a numerical version of the stroop task in men (Foreman et al, 1989)The effects of caffeine ingestion on mid-morning cognitive performance were investigated in thirty-two male subjects. These were given drinks containing either no caffeine, 125 mg caffeine (mean dose: 1.38 mg/kg), or 250 mg caffeine (mean dose: 3.45 mg/kg) and were tested on three tasks: 1) free recall of supraspan word lists, 2) a response time (pointing) task and 3) a numerical Stroop task. There were no significant group differences on the recall task or in response times, but subjects having the higher caffeine dose were seriously impaired on the Stroop test, making particularly slow responses. Caffeine may have a deleterious effect on the rapid processing of ambiguous or confusing stimuli, and this may account for its clearer effect on the Stroop test than on other cognitive tests used hitherto.
Cognitive and psychomotor performance, mood, and pressor effects of caffeine after 4, 6 and 8 h caffeine abstinence (Heatherly et al, 2005)
Many studies have found that caffeine consumed after overnight caffeine abstinence improves cognitive performance and mood. Much less is known, however, about the effects of caffeine after shorter periods of caffeine abstinence. The aim of this study was to measure the effects on psychomotor and cognitive performance, mood, hand steadiness, blood pressure and heart rate of caffeine administration after periods of 4, 6, and 8 h of caffeine abstinence. Participants (n=49, 27 female) were moderate to moderate-high caffeine consumers (mean daily intake 370 mg/day). Following overnight caffeine abstinence, a ‘pre-dose’ of caffeine (1.2 mg/kg) was administered at 9 a.m., 11 a.m. or 1 p.m. The participants started a baseline battery of measurements at 4 p.m. before receiving caffeine (1.2 mg/kg) or placebo at 5 p.m. They then performed the battery of tests again, starting at 5:30 p.m. This was a double-blind, placebo-controlled, randomised study. Performance and mood measurements confirmed a psychostimulant action of caffeine (versus placebo), but only after 8 h of caffeine abstinence. Caffeine also increased blood pressure after 8-h abstinence, whereas hand steadiness was decreased and perception of task demand was increased by caffeine after 4 h, but not after 6- and 8-h abstinence. A second cup-of-coffee equivalent dose of caffeine only reliably affected cognitive performance and mood after an 8-h interval between doses, but not after shorter intervals (when caffeine had some adverse effects). These results show that, apart from caffeine consumption soon after waking, the daily pattern of caffeine intake of many typical caffeine consumers is not well explained by the short-term psychostimulant effects of caffeine.
Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction (Rogers et al, 2004)
It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. Participants were moderate to moderate–high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal effects. Different patterns of effects (or lack of effects) of caffeine and caffeine withdrawal were found for other variables, but overall these results also suggest that there is little benefit to be gained from caffeine consumption.
The effects of habitual caffeine use on cognitive change: a longitudinal perspective (van Boxtel et al, 2003)
The efficiency of higher cortical functions, such as memory and speed of complex information processing, tends to decrease with advancing age in normal healthy individuals. Recently, a high habitual intake of caffeine was found associated with better verbal memory performance and psychomotor speed in several cross-sectional population studies. We tested the hypothesis that habitual caffeine intake can reduce or postpone age-related cognitive decline in healthy adults. For this purpose, the cognitive performance of all participants in the Maastricht Aging Study (MAAS), aged between 24 and 81 years, was reassessed after 6 years. Information on the intake of caffeine-containing beverages was available from the baseline questionnaire. After 6 years, 1376 (75.6%) individuals were available for reassessment. After correction for demographic characteristics, baseline performance and health status, there were small albeit significant associations between the overall estimated caffeine intake at baseline and the 6-year change in complex motor speed (motor choice reaction time). The earlier found association between caffeine intake and verbal memory performance was not apparent in this longitudinal study. These results imply that the longitudinal effect of habitual caffeine intake is limited and will not promote a substantial reduction in age-related cognitive decline at a population level.
Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups (Hameleers et al, 2000)
The present study evaluated the association between habitual caffeine intake via coffee and tea and cognitive performance. This was done as part of a larger research programme into the determinants of cognitive ageing (the Maastricht Aging Study: MAAS). Possible withdrawal effects that may have explained in part the positive association between performance and intake in an earlier study were controlled for. In addition, all cognitive tests in this study were administered under strict laboratory conditions. A group of 1875 healthy adults, stratified for age (range 24 – 81 years), sex, and general ability, were screened for habitual intake of coffee and tea and took part in extensive cognitive testing. Multiple regression analysis with control for age, sex, socio-demographic variables, and substance use showed that habitual caffeine consumption was significantly related to better long-term memory performance and faster locomotor speed. No relationships were found between habitual caffeine consumption and short-term memory, information processing, planning, and attention as measured with the Stroop Test. Moreover, no difference in sensitivity to caffeine intake between different age groups was found, suggesting that caffeine intake did not counteract age-related cognitive decline. Several recommendations are made to improve the design of future studies in this field.
The effects of caffeine on memory for word lists (Eriksen et al, 1985)
The present study investigated the effects of caffeine on memory for supraspan word lists. Twelve groups of male and female college students classified as high or low impulsive were administered (PO) 0 mg/kg, 2 mg/kg or 4 mg/kg of caffeine. Subjects listened to four word lists presented at a fast rate and four at a slow rate. Caffeine inhibited females' recall during the slow rate, but not the fast rate. Caffeine had no effect on the recall performance of males. The observed effects of caffeine were not influenced by subjects' typical amount of caffeine consumption, verbal ability, or level of impulsivity. The results suggest that caffeine may impair the efficiency with which females rehearse information in working memory.
Caffeine and memory performance on the AVLT (Terry and Phifer, 1986)The Auditory-Verbal Learning Test (AVLT) is a memory test that assesses recall of lists of words on single and multiple trials. College students (N = 33) were given the AVLT, either with or without a prior administration of 100 mg caffeine. Caffeine subjects recalled fewer words than did control subjects, both after single presentations of lists and across repeated trials. Caffeine subjects showed a greater deficit in recalling the middle-to-end portions of the lists. Personality scores on the Maudsley Personality Inventory showed a positive correlation of recall on a pretest with Neuroticism, and no correlation with Introversion.
A combination of caffeine and taurine has no effect on short term memory but induces changes in heart rate and mean arterial blood pressure (Bichler et al, 2006)Red Bull energy drink has become extraordinarily popular amongst college students for use as a study aid. We investigated the combined effects of Red Bull’s two active ingredients, caffeine and taurine, on short term memory. Studies on the effects of these two neuromodulators on memory have yielded mixed results, and their combined actions have not yet been investigated. In this double-blind study, college student subjects consumed either caffeine and taurine pills or a placebo and then completed a memory assessment. Heart rate and blood pressure were monitored throughout the testing period. The combination of caffeine and taurine had no effect on short term memory, but did cause a significant decline in heart rate and an increase in mean arterial blood pressure. The heart rate decline may have been caused by pressure-induced bradycardia that was triggered by caffeine ingestion and perhaps enhanced by the actions of taurine.
Combinational Studies
An evaluation of a caffeinated taurine drink on mood, memory and information processing in healthy volunteers without caffeine abstinence (Warburton et al, 2001)
Caffeine is present in a wide variety of beverages, often together with a number of other ingredients, such as sugars, taurine, glucuronolactone and vitamins. However, the majority of psychopharmacological studies have used pure caffeine tablets or drinks with doses in excess of those normally consumed in daily life. In addition, all the participants are usually deprived of caffeine for 10 h or more before the study. Consequently, it has been argued that any improvement in performance is only due to a reversal of caffeine withdrawal. The present two studies tested participants who had minimal deprivation from caffeine (an hour or less) with an 80-mg caffeinated (80 mg/250 ml), taurine-containing beverage (commercially available) verum, which also contained sugars, glucuronolactone and vitamins. The placebos in the two studies were a sugar-free and a sugar-containing drink, in order to examine the effects of the sugar. In total, 42 participants were tested with a rapid visual information test, a verbal reasoning test, a verbal and non-verbal memory test and a set of mood measures. Prior to testing, they were allowed ad libitum caffeinated beverages until 1 h before testing (study 1) and unrestricted caffeine use before testing (study 2). In both studies, the caffeinated, taurine-containing beverage produced improved attention and verbal reasoning, in comparison with a sugar-free and the sugar-containing drinks. The improvement with the verum drink was manifested in terms of both the mean number correct and the reaction times. Another important finding was the reduction in the variability of attentional performance between participants. No effects on memory were found. There were no differences in performance between the glucose and sugar-free drinks. Moderate doses of caffeine and taurine can improve information processing in individuals who could not have been in caffeine withdrawal.
A taurine and caffeine-containing drink stimulates cognitive performance and well-being (Seidl et al, 2000)
Caffeine- and taurine-containing drinks have been on the European market for about a decade, and research on the individual constituents of these drinks indicates an improvement in cognitive performance resulting from consumption of such drinks. In this double-blind, placebo-controlled study using 10 graduate students, we obtained the P300 components of event-related potential (ERP) waveforms following an auditory oddball paradigm, measured motor reaction time, and applied the d2 test for the assessment of attention. Status of mood was assessed by the “Basler-Befindlichkeitsbogen” questionnaire, a standard test for evaluation of feelings of well-being. Measurements were made at night, prior to and starting one hour after consumption of energy drink ingredients or placebo. At the end of the experiment (midnight), P300 latency and motor reaction time were significantly longer compared with baseline measurements in the placebo group, but were unchanged in the energy drink group. In the test system for evaluating feelings of well-being, total scores, vitality scores and social extrovertedness scores were significantly decreased in the placebo group but not in the energy drink group. The findings clearly indicate that the mixture of three key ingredients of Red BullR Energy Drink used in the study (caffeine, taurine, glucuronolactone) have positive effects upon human mental performance and mood. These effects may be mediated by the action of caffeine on purinergic (adenosinergic) receptors and taurine modulation of receptors. As half of the study cohort were non-caffeine users, the described effects cannot be explained in terms of the restoration of plasma caffeine levels to normal following caffeine withdrawal.
Cognitive and physiological effects of an “energy drink”: an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions (Scholey and Kennedy, 2004)
Both glucose and caffeine can improve aspects of cognitive performance and, in the case of caffeine, mood. There are few studies investigating the effects of the two substances in combination. We assessed the mood, cognitive and physiological effects of a soft drink containing caffeine and glucose as well as flavouring levels of herbal extracts. The effects of different drink fractions were also evaluated. Using a randomised, double-blind, balanced, five-way crossover design, 20 participants who were overnight fasted and caffeine-deprived received 250 ml drinks containing 37.5 g glucose; 75 mg caffeine; ginseng and ginkgo biloba at flavouring levels; a whole drink (containing all these substances) or a placebo (vehicle). Participants were assessed in each drink condition, separated by a 7-day wash-out period. Cognitive, psychomotor and mood assessment took place immediately prior to the drink then 30 min thereafter. The primary outcome measures included five aspects of cognitive performance from the Cognitive Drug Research assessment battery. Mood, heart rate and blood glucose levels were also monitored. Compared with placebo, the whole drink resulted in significantly improved performance on “secondary memory” and “speed of attention” factors. There were no other cognitive or mood effects. This pattern of results would not be predicted from the effects of glucose and caffeine in isolation, either as seen here or from the literature addressing the effects of the substances in isolation. These data suggest that there is some degree of synergy between the cognition-modulating effects of glucose and caffeine which merits further investigation.
A glucose-caffeine 'energy drink' ameliorates subjective and performance deficits during prolonged cognitive demand (Scholey and Kennedy, 2004)
Effects of a combination of caffeine and glucose were assessed in two double-blind, placebo-controlled, cross-over studies during extended performance of cognitively demanding tasks. In the first study, 30 participants received two drinks containing carbohydrate and caffeine (68 g/38 mg; 68 g/46 mg, respectively) and a placebo drink, in counter-balanced order, on separate days. In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink. In both studies, participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the Rapid Visual Information Processing task (RVIP), plus a rating of 'mental fatigue', once before the drink and six times in succession commencing 10 min after its consumption. In comparison to placebo, all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study resulted in lower ratings of mental fatigue. These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand.
Effects of caffeine and glucose, alone and combined, on cognitive performance (Adan and Serra-Grabulosa, 2010)
To study the effects of consuming caffeine and glucose, alone and combined, on cognitive performance. Seventy-two healthy subjects (36 women; age range 18–25) were tested early in the morning, having fasted overnight. Using a double-blind, randomised design, subjects received one of the following beverages: water (150 ml); water plus 75 mg of caffeine; water plus 75 g of glucose; water plus and 75 mg of caffeine and 75 g of glucose. Attention, manual dexterity, visuo-spatial and frontal functions, memory (immediate, consolidation and working) and subjective state were all assessed. The combination of caffeine and glucose had beneficial effects on attention (sequential reaction time tasks) and on learning and consolidation of verbal memory, effects not being observed when either substance was administered alone. Caffeine only showed improvement in simple reaction time and glucose in simple and one sequential reaction time tasks and in the manual dexterity assembly task. The results indicate that the synergistic effects of caffeine and glucose can benefit sustained attention and verbal memory, even with adequate levels of activation of the subjects. However, further studies are required, controlling for different levels of cognitive effort and also considering measurements of neural activity.
Enhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individuals (Childs and De Wit, 2008)
Caffeine produces mild psychostimulant effects that may be particularly evident in individuals whose mood or performance is impaired by sleep restriction or caffeine withdrawal. Caffeinated energy drinks have been shown to improve energy and cognition but expectancy effects cannot be ruled out in these studies. Very few studies have examined the effects of caffeine-containing energy capsules upon behavioral and subjective measures. This study compared the effects of a caffeine-containing (200 mg) supplement (CAF) or placebo in capsule form after prolonged wakefulness, in participants who varied in their level of habitual caffeine use. Thirty-five healthy volunteers (16 male, 19 female) participated in two experimental sessions in which they remained awake between 5 p.m. and 5 a.m. At 3:30 a.m. they consumed CAF or placebo in random order under double-blind conditions. Participants completed subjective effects questionnaires and performed computerized attention tasks before and after consuming capsules. Heart rate and blood pressure were monitored at regular intervals. Compared to measures at 5 p.m., participants reported more tiredness and mood disturbance at 3 a.m., and exhibited longer reaction times and more attentional lapses. Heavier caffeine consumers exhibited the greatest decreases in Profile of Mood States (POMS) Vigor. CAF produced stimulant-like effects and significantly improved mood and reaction times upon the tasks. These effects did not vary with level of habitual caffeine consumption. These findings indicate that consumption of a caffeine-containing food supplement improves subjective state and cognitive performance in fatigued individuals that is likely a result of its caffeine content.
Glucose and caffeine effects on sustained attention: an exploratory fMRI study (Serra-Grabulosa et al, 2010)
Caffeine and glucose can have beneficial effects on cognitive performance. However, neural basis of these effects remain unknown. Our objective was to evaluate the effects of caffeine and glucose on sustained attention, using functional magnetic resonance imaging (fMRI). Forty young right-handed, healthy, low caffeine-consuming subjects participated in the study. In a double-blind, randomised design, subjects received one of the following beverages: vehicle (water, 150 ml); vehicle plus 75 g of glucose; vehicle plus 75 mg of caffeine; vehicle plus 75 g of glucose and 75 mg of caffeine. Participants underwent two scanning fMRI sessions (before and 30 min after of the administration of the beverage). A continuous performance test was used to assess sustained attention. Participants who received combined caffeine and glucose had similar performance to the others but had a decrease in activation in the bilateral parietal and left prefrontal cortex. Since these areas have been related to the sustained attention and working memory processes, results would suggest that combined caffeine and glucose could increase the efficiency of the attentional system. However, more studies using larger samples and different levels of caffeine and glucose are necessary to better understand the combined effects of both substances.
The combined effects of L-theanine and caffeine on cognitive performance and mood (Owen et al, 2008)
The aim of this study was to compare 50 mg caffeine, with and without 100 mg L-theanine, on cognition and mood in healthy volunteers. The effects of these treatments on word recognition, rapid visual information processing, critical flicker fusion threshold, attention switching and mood were compared to placebo in 27 participants. Performance was measured at baseline and again 60 min and 90 min after each treatment (separated by a 7-day washout). Caffeine improved subjective alertness at 60 min and accuracy on the attention-switching task at 90 min. The L-theanine and caffeine combination improved both speed and accuracy of performance of the attention-switching task at 60 min, and reduced susceptibility to distracting information in the memory task at both 60 min and 90 min. These results replicate previous evidence which suggests that L-theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks.
The effects of L-theanine, caffeine and their combination on cognition and mood (Haskell, 2008)
L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were comonitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.
Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together (Rogers et al, 2008)
Although both contain behaviourally significant concentrations of caffeine, tea is commonly perceived to be a less stimulating drink than coffee. At least part of the explanation for this may be that theanine, which is present in tea but not coffee, has relaxing effects. There is also some evidence that theanine affects cognitive performance, and it has been found to reduce blood pressure in hypertensive rats. To study the subjective, behavioural and blood pressure effects of theanine and caffeine administered alone and together, in doses relevant to the daily tea consumption of regular tea drinkers. In a randomised, double-blind, placebo-controlled study, healthy adult participants (n = 48) received either 250-mg caffeine, 200-mg theanine, both or neither of these. They completed ratings of mood, including anxiety, and alertness, and had their blood pressure measured before and starting 40 min after drug administration. Anxiety was also assessed using a visual probe task. Caffeine increased self-rated alertness and jitteriness and blood pressure. Theanine antagonised the effect of caffeine on blood pressure but did not significantly affect jitteriness, alertness or other aspects of mood. Theanine also slowed overall reaction time on the visual probe task. Theanine is a physiologically and behaviourally active compound and, while it is unclear how its effects might explain perceived differences between tea and coffee, evidence suggests that it may be useful for reducing raised blood pressure.
L-Theanine and Caffeine in Combination Affect Human Cognition as Evidenced by Oscillatory alpha-Band Activity and Attention Task Performance (Kelly et al, 2008)
Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8–14 Hz) activity. We found an increase in hit rate and target discriminability (d′) for the combined treatment relative to placebo, and an increase in d′ but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.
L-Theanine and caffeine improve task switching but not intersensory attention or subjective alertness (Einother et al, 2010)
Tea ingredients L-theanine and caffeine have repeatedly been shown to deliver unique cognitive benefits when consumed in combination. The current randomized, placebo-controlled, double-blind, cross-over study compared a combination of L-theanine (97 mg) and caffeine (40 mg) to a placebo on two attention tasks and a self-report questionnaire before, and 10 and 60 min after consumption. The combination of L-theanine and caffeine significantly improved attention on a switch task as compared to the placebo, while subjective alertness and intersensory attention were not improved significantly. The results support previous evidence that L-theanine and caffeine in combination can improve attention.
The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness (Giesbrecht et al, 2010)
The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L-theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task.
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