Habitual Caffeine Consumption Research Articles

The Caffeine Dose Response in Habitual Consumers Performing a 90‐s Wingate Test

Caffeine is the most commonly used substance to enhance athletic performance; however, the ideal dosage of caffeine to improve long anaerobic exercise is unknown. The purpose of this study was to investigate the caffeine dose response in habitual consumers using the 90‐s Wingate Anaerobic Test (WAnT90). Seven (2 F, 5 M; mean+SD: age = 20.4+1.0 y; body mass = 59.4+7.9 kg) recreationally fit habitual caffeine users (consumption > 2 servings/d) volunteered for a randomized counterbalanced double‐blind study. Subjects ingested 3, 5, or 7 mg.kg‐1 caffeine or placebo (PLB) 1h prior to testing. The testing protocol included a 3 min warm‐up and a WAnT90 with a resistance of 0.05kg.kg‐1. Peak power (PP), total power (TP), and total power decline (PD) as well as TP and PD for each 30‐s interval were calculated (TP30, TP60, TP90, PD30, PD60, and PD90). Rating of perceived exertion (RPE) was recorded following each test. One‐way ANOVA was conducted to compare each dosage of caffeine with each variable across the WAnT90. Caffeine intake log analysis revealed that the subjects were habitual users with 4.0 + 1.7 servings/day. No significant differences were found for PP and TP however, a significant increase in PD was seen for 7 mg.kg‐1 caffeine. No significant differences were found for each 30‐s interval across the test (TP30, TP60, TP90, PD30, PD60, and PD90) and there were no differences in RPE among doses. Although previous research on collegiate athlete habitual caffeine consumers showed improvement in power output for anaerobic exercise, our research on recreationally fit consumers showed 7 mg.kg‐1 to be associated with an increase in fatigue. Thus, more research is needed to confirm the effects of caffeine with long anaerobic activity and the efficacy of specific dosing strategies.

Hemispheric bases for emotion and memory.

Hemispheric bases for emotion and memory.

Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption.

Two genetic loci, one in the cytochrome P450 1A1 (CYP1A1) and 1A2 (CYP1A2) gene region (rs2472297) and one near the aryl-hydrocarbon receptor (AHR) gene (rs6968865), have been associated with habitual caffeine consumption. We sought to establish whether a more refined and comprehensive assessment of caffeine consumption would provide stronger evidence of association, and whether a combined allelic score comprising these two variants would further strengthen the association. We used data from between 4,460 and 7,520 women in the Avon Longitudinal Study of Parents and Children, a longitudinal birth cohort based in the United Kingdom. Self-report data on coffee, tea and cola consumption (including consumption of decaffeinated drinks) were available at multiple time points. Both genotypes were individually associated with total caffeine consumption, and with coffee and tea consumption. There was no association with cola consumption, possibly due to low levels of consumption in this sample. There was also no association with measures of decaffeinated drink consumption, indicating that the observed association is most likely mediated via caffeine. The association was strengthened when a combined allelic score was used, accounting for up to 1.28% of phenotypic variance. This was not associated with potential confounders of observational association. A combined allelic score accounts for sufficient phenotypic variance in caffeine consumption that this may be useful in Mendelian randomization studies. Future studies may therefore be able to use this combined allelic score to explore causal effects of habitual caffeine consumption on health outcomes.

The effect of acute caffeine ingestion on coincidence anticipation timing in younger and older adults

ObjectivesThis study compared the effect of acute caffeine ingestion on coincidence timing accuracy in younger and older adults.MethodsThirteen young (aged 18–25 years, age: 20 ± 2 years, 7 females, 5 males) and 13 older (aged 61–77 years, age: 68 ± 6 years, 9 females, 3 males) adults, all who were habitual moderate caffeine consumers undertook measures of coincident anticipation timing performance pre- and post-acute caffeine (3 mg/kg) or placebo ingestion administered in a double blind, randomized fashion.ResultsResults indicated significant pre-to-post X substance (caffeine vs. placebo) interactions for absolute (P = 0.02, Pη2 = 0.204) and variable error (P = 0.015, Pη2 = 0.221). In both cases, error (absolute or variable) improved pre-to-post ingestion in the caffeine condition but not in the placebo condition. There were no significant differences due to age (younger vs. older adults, P > 0.05) in any of the analyses.DiscussionThe results of this study suggest that acute caffeine ingestion positively influence coincidence anticipation timing performance in both younger and older adults, who are moderate habitual caffeine consumers. Such effects might therefore be useful for older adults in enhancing ability to undertake cognitive-perceptual tasks which involve interceptive actions.

Caffeine improves anaerobic performance in a 90‐s Wingate test in habitual caffeine users

The purpose of this study was to evaluate the effects of caffeine on a maximal anaerobic exercise protocol using the 90‐s Wingate Test (WAnT90). 29 (11 females, 17 males) anaerobically‐conditioned athletes volunteered for a randomized counterbalanced double‐blind study. Subjects were classified as either habitual consumers (n=15) or caffeine naïve (n=13) based on daily caffeine consumption habits. One h after ingesting caffeine (5mg/kg) or placebo participants completed a WAnT90 using a resistance of 0.05g/kg. In addition to peak power (PP), total power (TP), and total power decline (PDT), power and power decline were calculated for each 30‐s interval of the test (TP30, TP60, TP90, PD30, PD60, PD90). Paired t‐tests compared caffeine vs placebo in each group, and significance was set at p<0.05. In the habitual caffeine consumption group TP, TP30, and TP60 were significantly greater in the caffeine trial. In the caffeine naïve group PD30 was greater in the caffeine trial; there were no other significant effects of caffeine on this group. This study suggests an ergogenic effect of caffeine for those who regularly consume caffeine but not for those who do not. These results imply a possible learning effect for caffeine; further research should focus on a mechanism.

Impact of Caffeine on Heart Rate Variability: A Systematic Review

Background: The consumption of caffeinated drinks stimulates the autonomic nervous system (ANS). The heart rate (HR), blood pressure, or likewise parameters of the cardiovascular activity have been extensively investigated. However, studies on the influence of caffeine on heart rate variability (HRV) are rare. This systematic review summarizes current findings on the influence of caffeine on time- and frequency-domain measures of HRV. Methods: A systematic search of electronic databases (PubMed, PsycInfo, and EMBASE) according to the PRISMA statement was employed. Results: The search revealed a total of 68 articles after removing duplicates. Thirteen studies fitting the inclusion criteria were included in the systematic review. Conclusions: Best evidence in this qualitative synthesis is given for an increase in vagally mediated HRV (as indexed by high-frequency components) caused by caffeine ingestion. However, due to large variations in the study designs, participants, methods of measurement, and measures recorded within the included studies, evidence on the impact of caffeine on HRV is not exactly clear. Existing studies are well designed and controlled, but address such specific questions that the results can hardly be integrated within a systematic review. Further studies that extensively control for the influence of experimental conditions, participants caffeine consumption, health status, and baseline ANS activity seem to be necessary. Furthermore, long-term studies on the impact of habitual caffeine consumption and caffeine withdrawal in habitual users on HRV should be investigated.

Effects of ingestion of a commercially available thermogenic dietary supplement on resting energy expenditure, mood state and cardiovascular measures

BackgroundIncreasing metabolism is a primary focus of many commercially available dietary supplements marketed to support weight management. Caffeine (e.g. anhydrous and herbal) and green tea are key ingredients in such products, augmenting resting energy expenditure (REE) and improving reported mood states (alertness, fatigue, focus, etc.). The purpose of this study was to evaluate the effects of a thermogenic dietary supplement (DBX) on REE, respiratory exchange ratio (RER), reported measures of alertness, focus, energy, concentration, fatigue, and hunger, as well as the general safety of the product based on electrocardiogram (ECG) and hemodynamic responses in habitual caffeine consumers.MethodsSix male and six female subjects (mean ± SD; 22.50 ± 3.22 years; 76.94 ± 14.78 kg; 22.7 ± 9.5% body fat), physically active (≥12 months), and moderate habitual caffeine consumers (<200 mg/day) received either two capsules of DBX containing 340 mg of total caffeine plus green tea extract, yerba mate extract, carnitine tartrate and other active ingredients or a placebo (PLC) in a double-blinded, crossover design. Heart rate (HR), blood pressure (BP), REE, RER and perceived mood states were measured at baseline and then hourly for four hours after ingesting either treatment.ResultsResting energy expenditure was significantly increased at all four time points and significant increases were determined for perceived alertness (p = 0.026) and focus (p = 0.05) at hour 1 and for energy at 1 and 2 hours after treatment for the DBX group (p = 0.008 and p = 0.017, respectively). Additionally, perceived fatigue was decreased at the hour 1 assessment (p = 0.010). No significant differences were seen between DBX and placebo for hunger, anxiety, HR, BP, ECG patterns or RER.ConclusionsThe results of this investigation support that the proprietary blend of this thermogenic aid is capable of increasing REE for four hours post-ingestion while supporting increased focus, alertness, and energy as well as decreasing fatigue without promoting anxiety or causing significant changes in HR, BP, or ECG measurements in habitual caffeine consumers.

Caffeine Promotes Global Spatial Processing in Habitual and Non-Habitual Caffeine Consumers

Information processing is generally biased toward global cues, often at the expense of local information. Equivocal extant data suggests that arousal states may accentuate either a local or global processing bias, at least partially dependent on the nature of the manipulation, task, and stimuli. To further differentiate the conditions responsible for such equivocal results we varied caffeine doses to alter physiological arousal states and measured their effect on tasks requiring the retrieval of local versus global spatial knowledge. In a double-blind, repeated-measures design, non-habitual (Experiment 1; N = 36, M = 42.5 ± 28.7 mg/day caffeine) and habitual (Experiment 2; N = 34, M = 579.5 ± 311.5 mg/day caffeine) caffeine consumers completed four test sessions corresponding to each of four caffeine doses (0, 100, 200, 400 mg). During each test session, participants consumed a capsule containing one of the three doses of caffeine or placebo, waited 60 min, and then completed two spatial tasks, one involving memorizing maps and one spatial descriptions. A spatial statement verification task tested local versus global spatial knowledge by differentially probing memory for proximal versus distal landmark relationships. On the map learning task, results indicated that caffeine enhanced memory for distal (i.e., global) compared to proximal (i.e., local) comparisons at 100 (marginal), 200, and 400 mg caffeine in non-habitual consumers, and marginally beginning at 200 mg caffeine in habitual consumers. On the spatial descriptions task, caffeine enhanced memory for distal compared to proximal comparisons beginning at 100 mg in non-habitual but not habitual consumers. We thus provide evidence that caffeine-induced physiological arousal amplifies global spatial processing biases, and these effects are at least partially driven by habitual caffeine consumption.

Caffeine as an attention enhancer: reviewing existing assumptions

Despite the large number of studies on the behavioural effects of caffeine, an unequivocal conclusion had not been reached. In this review, we seek to disentangle a number of questions. Whereas there is a general consensus that caffeine can improve performance on simple tasks, it is not clear whether complex tasks are also affected, or if caffeine affects performance of the three attention networks (alerting, orienting and executive control). Other questions being raised in this review are whether effects are more pronounced for higher levels of caffeine, are influenced by habitual caffeine use and whether there effects are due to withdrawal reversal. Literature review of double-blind placebo controlled studies that assessed acute effects of caffeine on attention tasks in healthy adult volunteers. Caffeine improves performance on simple and complex attention tasks, and affects the alerting, and executive control networks. Furthermore, there is inconclusive evidence on dose-related performance effects of caffeine, or the influence of habitual caffeine consumption on the performance effects of caffeine. Finally, caffeine's effects cannot be attributed to withdrawal reversal. Evidence shows that caffeine has clear beneficial effects on attention, and that the effects are even more widespread than previously assumed.

Faster but not smarter: effects of caffeine and caffeine withdrawal on alertness and performance

Despite 100years of psychopharmacological research, the extent to which caffeine consumption benefits human functioning remains unclear. To measure the effects of overnight caffeine abstinence and caffeine administration as a function of level of habitual caffeine consumption. Medium-high (n = 212) and non-low (n = 157) caffeine consumers completed self-report measures and computer-based tasks before (starting at 10:30AM) and after double-blind treatment with either caffeine (100mg, then 150mg) or placebo. The first treatment was given at 11:15AM and the second at 12:45PM, with post-treatment measures repeated twice between 1:45PM and 3:30PM. Caffeine withdrawal was associated with some detrimental effects at 10:30AM, and more severe effects, including greater sleepiness, lower mental alertness, and poorer performance on simple reaction time, choice reaction time and recognition memory tasks, later in the afternoon. Caffeine improved these measures in medium-high consumers but, apart from decreasing sleepiness, had little effect on them in non-low consumers. The failure of caffeine to increase mental alertness and improve mental performance in non-low consumers was related to a substantial caffeine-induced increase in anxiety/jitteriness that offset the benefit of decreased sleepiness. Caffeine enhanced physical performance (faster tapping speed and faster simple and choice reaction times) in both medium-high and non-low consumers. While caffeine benefits motor performance and tolerance develops to its tendency to increase anxiety/jitteriness, tolerance to its effects on sleepiness means that frequent consumption fails to enhance mental alertness and mental performance.

Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumption

Recent genome-wide association studies (GWASs) from populations of European descent identified single nucleotide polymorphisms (SNPs) in aryl-hydrocarbon receptor (AHR) and cytochrome P450 1A1 and 1A2 (CYP1A1-CYP1A2) genes that are associated with habitual caffeine and coffee consumption. We examined whether these SNPs (AHR: rs6968865 and rs4410790; CYP1A1-CYP1A2: rs2472297 and rs2470893) and 6 additional tag SNPs in the AHR gene were associated with habitual caffeine consumption in a Costa Rican population. Subjects were from a case-control study of gene-diet interactions and myocardial infarction. Subjects with hypertension or missing information on smoking, caffeine intake, or genotype were excluded. Subjects were genotyped by using polymerase chain reaction with mass spectrometry-based detection, and caffeine intake was assessed by using a validated food-frequency questionnaire. Compared with subjects who consumed <100 mg caffeine/d, subjects who consumed >400 mg caffeine/d were more likely to be carriers of the T, C, or T allele for rs6968865, rs4410790, and rs2472297, respectively. The corresponding ORs and 95% CIs were 1.41 (1.03, 1.93), 1.41 (1.04, 1.92), and 1.55 (1.01, 2.36). Multivariate-adjusted ORs (95% CIs) for rs6968865 were 1.44 (1.03, 2.00) for all subjects, 1.75 (1.16, 2.65) for nonsmokers, 1.15 (0.58, 2.30) for current smokers, 2.42 (1.45, 4.04) for subjects >57 y old, and 1.00 (0.65, 1.56) for subjects ≤57 y old. A similar effect modification was observed for rs4410790 but not for rs2472297. Our findings show that previous associations between SNPs in AHR and CYP1A1-CYP1A2 and caffeine and coffee consumption from GWASs in European populations are also observed in an ethnically distinct Costa Rican population, but age and smoking are important effect modifiers.

Differential cognitive effects of energy drink ingredients: Caffeine, taurine, and glucose

Energy drinks containing caffeine, taurine, and glucose may improve mood and cognitive performance. However, there are no studies assessing the individual and interactive effects of these ingredients. We evaluated the effects of caffeine, taurine, and glucose alone and in combination on cognitive performance and mood in 24-hour caffeine-abstained habitual caffeine consumers. Using a randomized, double-blind, mixed design, 48 habitual caffeine consumers (18 male, 30 female) who were 24-hour caffeine deprived received one of four treatments (200mg caffeine/0mg taurine, 0mg caffeine/2000mg taurine, 200mg caffeine/2000mg taurine, 0mg caffeine/0mg taurine), on each of four separate days, separated by a 3-day wash-out period. Between-participants treatment was a glucose drink (50g glucose, placebo). Salivary cortisol, mood and heart rate were measured. An attention task was administered 30-minutes post-treatment, followed by a working memory and reaction time task 60-minutes post-treatment. Caffeine enhanced executive control and working memory, and reduced simple and choice reaction time. Taurine increased choice reaction time but reduced reaction time in the working memory tasks. Glucose alone slowed choice reaction time. Glucose in combination with caffeine, enhanced object working memory and in combination with taurine, enhanced orienting attention. Limited glucose effects may reflect low task difficulty relative to subjects' cognitive ability. Caffeine reduced feelings of fatigue and increased tension and vigor. Taurine reversed the effects of caffeine on vigor and caffeine-withdrawal symptoms. No effects were found for salivary cortisol or heart rate. Caffeine, not taurine or glucose, is likely responsible for reported changes in cognitive performance following consumption of energy drinks, especially in caffeine-withdrawn habitual caffeine consumers.

The effect of caffeine on working memory load-related brain activation in middle-aged males

Caffeine is commonly consumed in an effort to enhance cognitive performance. However, little is known about the usefulness of caffeine with regard to memory enhancement, with previous studies showing inconsistent effects on memory performance. We aimed to determine the effect of caffeine on working memory (WM) load-related activation during encoding, maintenance and retrieval phases of a WM maintenance task using functional magnetic resonance imaging (fMRI). 20 healthy, male, habitual caffeine consumers aged 40–61 years were administered 100 mg of caffeine in a double-blind placebo-controlled crossover design. Participants were scanned in a non-withdrawn state following a workday during which caffeinated products were consumed according to individual normal use (range = 145–595 mg). Acute caffeine administration was associated with increased load-related activation compared to placebo in the left and right dorsolateral prefrontal cortex during WM encoding, but decreased load-related activation in the left thalamus during WM maintenance. These findings are indicative of an effect of caffeine on the fronto-parietal network involved in the top-down cognitive control of WM processes during encoding and an effect on the prefrontal cortico-thalamic loop involved in the interaction between arousal and the top-down control of attention during maintenance. Therefore, the effects of caffeine on WM may be attributed to both a direct effect of caffeine on WM processes, as well as an indirect effect on WM via arousal modulation. Behavioural and fMRI results were more consistent with a detrimental effect of caffeine on WM at higher levels of WM load, than caffeine-related WM enhancement.This article is part of a Special Issue entitled ‘Cognitive Enhancers’.

Genetic polymorphisms in AHR and CYP1A2 are associated with habitual caffeine consumption and are modified by age and smoking

Recent genome‐wide association studies (GWAS) from populations of European decent have identified polymorphisms in AHR and CYP1A2 that are associated with caffeine/coffee intake. We examined whether these polymorphisms in AHR (rs6968865 and rs4410790) and CYP1A2 (rs2472297 and rs2470893) were associated with caffeine consumption in a Costa Rican population. Subjects (n=4,612) were participants from a case‐control study of gene‐diet interactions and myocardial infarction. Those with hypertension (n=1,692), or missing information on genotype (n=389), caffeine intake (n=4) or smoking status (n=4) were excluded. Sequenom MassARRAY was used for genotyping, and caffeine intake was assessed by a validated food frequency questionnaire. Compared to those consuming &lt;100 mg/d of caffeine, subjects consuming &gt;400 mg/d were more likely to be carriers of the T, C or T allele for rs6968865, rs4410790 and rs2472297, respectively. The corresponding odds ratios (OR [95% CI]) were 1.41 (1.03–1.93), 1.41 (1.04–1.92) and 1.55 (1.01–2.36). The multivariate‐adjusted ORs (95% CI) for rs6968865 were 1.44 (1.03–2.00) for all subjects, 1.75 (1.16–2.65) for non‐smokers and 1.15 (0.58–2.30) for smokers, and 2.42 (1.45–4.04) for &gt;57 yrs and 1.00 (0.65–1.56) for ≤57 yrs. Our findings confirm previous results from GWAS linking polymorphisms in AHR and CYP1A2 with caffeine consumption, but only in non‐smokers and older adults.Grant Funding Source: Canadian Institutes of Health Research (CIHR)

Behavior, Sleep, and Problematic Caffeine Consumption in a College-Aged Sample

Purpose: The purpose of this study was to evaluate the relationship between habitual caffeine consumption and problem behavior, problematic caffeine use, licit drug use, and sleep problems. Methods: College students (n=225) completed a questionnaire about weekly caffeine consumption, sleep, and symptoms of problematic caffeine use. Eighteen-year-olds (n=60) were also administered the Youth Self Report (YSR), a standardized measure of problematic behavior. Results: A total of 79% of respondents reported using caffeine at least on a weekly basis. About three quarters of the full sample indicated one or more characteristics of problematic caffeine use. The most commonly endorsed characteristic was having tried unsuccessfully to limit caffeine consumption (49.7%). Of those who indicated having had experienced caffeine withdrawal symptoms (32.8%), half reported that withdrawal symptoms interfered with their normal daily activities. The average number of alcoholic drinks consumed in a typical week was positivel...

Caffeine withdrawal, sleepiness, and driving performance: What does the research really tell us?

As a psychostimulant, caffeine is thought to reduce road accidents by keeping drivers alert and wakeful. Studies have found that caffeine can improve performance on vigilance tasks and in driving simulators under normal sleeping conditions and after sleep restriction or deprivation. However, there is increasing evidence that these beneficial effects of caffeine are due to withdrawal reversal. Studies comparing the effects of caffeine versus placebo on driving performance have tested habitual caffeine consumers deprived of caffeine from the evening before the test day. The conclusion from this review is, therefore, that improvements in driving performance and alertness after caffeine are likely to represent withdrawal reversal rather than a net beneficial effect of caffeine. Further research using designs that control for caffeine withdrawal are necessary and, accordingly, advice given to the public on use of caffeine as an antidote to tiredness and impaired performance should be reviewed.

Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4×10−19), near AHR, and 15q24 (P = 5.2×10−14), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2.

Foetal response to maternal coffee intake: role of habitual versus non-habitual caffeine consumption

Little is known about the effect on the human foetus of long-term and acute exposure to caffeine. We studied the organisation of foetal sleep-wake states in 13 healthy near-term foetuses over a wide range of maternal plasma caffeine concentrations (0-13 μg/mL) reflecting normal lifestyle conditions (day 0) and again following intake of two cups of regular coffee (~300 mg of caffeine) intermitted by 50 h of abstinence (day 2; acute effects). On either day, 2 h simultaneous recordings were made of foetal heart rate, general-, eye-, and breathing-movements. The recordings were analysed for the presence of each of four foetal behavioural states: quiet- and active-sleep, quiet- and active-wakefulness. There was a linear relationship between maternal caffeine content and the incidence of foetal general movements during active sleep on day 0 (R = 0.74; P < 0.02). After coffee loading on day 2, foetuses of non- or low-caffeine consumers showed increases in active wakefulness (P < 0.001), general movements (P < 0.05) and heart rate variation (P < 0.01) but lower basal heart rate (P < 0.01) compared with their day 0 values. The changes in foetal heart rate (variation) and behaviour occurred between 90 and 180 min post-consumption. In contrast, foetuses of habitual caffeine consumers remained unaffected suggestive of foetal tolerance to caffeine. The results indicate differential performance between foetuses regularly exposed to caffeine and those caffeine-naive, both under normal maternal lifestyle conditions and in response to maternal coffee ingestion.

Effect of Caffeine on Quadriceps Muscle Pain during Acute Cycling Exercise in Low versus High Caffeine Consumers

This experiment examined the effect of a moderate dose of caffeine on quadriceps muscle pain during a bout of high-intensity cycling in low- versus high-caffeine-consuming males. College-age men who were low (< or =100 mg/day; n = 12) or high (> or =400 mg/day; n = 13) habitual caffeine consumers ingested caffeine (5 mg/kg body weight) or a placebo in a counterbalanced order and 1 hr later completed 30 min of cycle ergometry at 75-77% of peak oxygen consumption. Perceptions of quadriceps muscle pain, as well as oxygen consumption, heart rate, and work rate, were recorded during both bouts of exercise. Caffeine ingestion resulted in a statistically significant and moderate reduction in quadriceps muscle-pain-intensity ratings during the 30-min bout of high-intensity cycle ergometry compared with placebo ingestion in both low (d = -0.42) and high (d = -0.55) caffeine consumers. The results suggest that caffeine ingestion is associated with a moderate hypoalgesic effect during high-intensity cycling in college-age men who are low or high habitual caffeine consumers, but future work should consider better defining and differentiating pain and effort when examining the effects of caffeine during acute exercise.

Chapter 16 Modeling Fatigue over Sleep Deprivation, Circadian Rhythm, and Caffeine with a Minimal Performance Inhibitor Model

Sleep loss, as well as concomitant fatigue and risk, is ubiquitous in today's fast-paced society. A biomathematical model that succeeds in describing performance during extended wakefulness would have practical utility in operational environments and could help elucidate the physiological basis of sleep loss effects. Eighteen subjects (14 males, 4 females; age 25.8 +/- 4.3 years) with low levels of habitual caffeine consumption (<300 mg/day) participated. On night 1, subjects slept for 8 h (2300-0700 h), followed by 77 h of continuous wakefulness. They were assigned randomly to receive placebo or caffeine (200 mg, i.e., two sticks of Stay Alert gum) at 0100, 0300, 0500, and 0700 during nights 2, 3, and 4. The psychomotor vigilance test (PVT) was administered periodically over the 77-h period of continuous wakefulness. Statistical analysis reveals lognormality in each PVT, allowing for closed-form median calculation. An iterative parameter estimation algorithm, which takes advantage of MatLab's (R2007a) least-squares nonlinear regression, is used to estimate model parameters from subjects' PVT medians over time awake. In the model, daily periodicity is accounted for with a four-component Fourier series, and a simplified binding function describes asymptotic fatigue. The model highlights patterns in data that suggest (1) the presence of a performance inhibitor that increases and saturates over the period of continuous wakefulness, (2) competitive inhibition of this inhibitor by caffeine, (3) the persistence of an internally driven circadian rhythm of alertness, and (4) a multiplicative relationship between circadian rhythm and performance inhibition. The present inhibitor-based minimal model describes performance data in a manner consistent with known biochemical processes.