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Coffee, Caffeine, and Sleep: a Systematic Review of Epidemiological Studies and Randomized Controlled Trials
... Although caffeine is mostly considered to be non-addictive, the observed physical and psychological dependence 5,6 consolidate its regular consumption [7][8][9] through the caffeineinduced reinforcing effects 10 , as well as the motive to resist withdrawal symptoms 11 and to increase alertness 12 . Higher alertness after acute caffeine intake 13 mirrors a reduced homeostatic sleep pressure, which is also evident in a reduced depth of sleep 14 . The latter is characterized by attenuated electroencephalographic slow-wave activity (EEG SWA, 0. 75 -4.5 Hz) in non-rapid eye movement (NREM) sleep and shortened slow-wave sleep (SWS) [14][15][16][17] . ...
... Higher alertness after acute caffeine intake 13 mirrors a reduced homeostatic sleep pressure, which is also evident in a reduced depth of sleep 14 . The latter is characterized by attenuated electroencephalographic slow-wave activity (EEG SWA, 0. 75 -4.5 Hz) in non-rapid eye movement (NREM) sleep and shortened slow-wave sleep (SWS) [14][15][16][17] . ...
... Our treatment did not elicit a significant effect on SWA in the first NREM sleep episode. The contradiction to earlier findings 14,16,17 can be reconciled within two assumptions: a timing-dependent influence of caffeine on sleep, and a potential development of tolerance in response to the repeated daily intake. Earlier studies indicate that caffeine exerts strong reduction in NREM SWA when caffeine was administered close to bedtime 16,17 while the effects were considerably weaker after morning administration 59 . ...
Disturbed sleep homeostatic states have been found to alter neuronal homeostasis and reduce grey matter (GM) volume. Caffeine intake that interferes with sleep homeostasis through antagonizing adenosine receptors can impair hippocampal synaptic strength, neurogenesis, as well as memory and learning in rats. In this study, reduced medial temporal GM volume was observed after daily caffeine intake in humans (3 x 150 mg x 10 days compared to 10-day placebo administration). The potential bias from reduced cerebral blood flow was controlled, and the GM reduction was independent of the change in sleep pressure. A decrease in working memory during daily caffeine intake was observed, albeit no association with the magnitude of GM changes. The findings indicate that daily caffeine intake might induce rapid cerebral plasticity and be detrimental for higher order cognitive performance in the long run. They may call into question whether the neuroprotective effects of caffeine found in acute or low dose administration in animals are generalizable onto the daily usage in humans.
... Specifically, the presence of caffeine in the body may delay sleep onset, contribute to increased sleep problems throughout the night, and subsequently lead to more sleepiness during the day. These difficulties may also result in a lower total sleep time and increased wake after sleep onset (WASO; Clark & Landolt, 2017;Drake et al., 2013). Accordingly, this study used a multimethod, multirater approach to assessing sleep, including adolescent-report, parent-report, and actigraphy. ...
... Taken together, it may be that caffeine consumption is not impacting the total hours slept, but rather, is impacting subjective experiences of sleep and/or behavioral sleep functioning. Despite literature suggesting associations between caffeine use and increased WASO (Clark & Landolt, 2017), this study did not find significant associations in either the comparison or ADHD group. In a sample of adolescents, Pollak and Bright (2003) found associations between caffeine use and WASO. ...
Objective:
The objective of this study was to compare caffeine consumption in the morning, afternoon, and evening in adolescents with and without attention-deficit/hyperactivity disorder (ADHD) and examine associations with sleep functioning.
Methods:
Participants were 302 adolescents (ages 12-14) with (N = 140) and without (N = 162) ADHD. Adolescents wore actigraph watches to assess total sleep time and wake after sleep onset and reported on sleep-wake problems and the number of caffeinated beverages consumed per day in the morning, afternoon, and evening. Parents reported on adolescents' difficulties initiating and maintaining sleep. Chi-square tests, odds ratios, and path analyses were conducted.
Results:
Analyses controlled for sex, medication status, and pubertal development. Adolescents with ADHD were 2.47 times more likely to consume caffeine in the afternoon and evening than adolescents without ADHD. Path analyses indicated significant associations between afternoon caffeine use and more self-reported sleep problems for adolescents with and without ADHD, and an association between evening caffeine use and self-reported sleep problems only in adolescents with ADHD. Afternoon caffeine use was associated with parent-reported sleep problems in adolescents with ADHD only. Caffeine use was not associated with actigraphy-assessed sleep.
Conclusion:
This is the first study to show that adolescents with ADHD consume more caffeine than peers during later times of the day. Additionally, caffeine use is more consistently associated with poorer subjective sleep functioning in adolescents with ADHD. Pediatricians and mental health professionals should assess for caffeine use in adolescents with ADHD and co-occurring sleep problems.
... A widely available substance acting as a wakefulness promoter is caffeine [for an in depth review on the topic e.g., (104)]. Caffeine intake was shown to reduce sleepiness and to reduce waking EEG theta activity and 0.75-2 Hz band during recovery sleep after SD even if caffeine saliva concentrations were extremely low (below the detection limit for some subjects, population average concentration 1.8 ± 1.0 µmol/l) (105). ...
Sleep deprivation is an ordinary aspect in the global society and its prevalence is increasing. Chronic and acute sleep deprivation have been linked to diabetes and heart diseases as well as depression and enhanced impulsive behaviors. Surgeons are often exposed to long hour on call and few hours of sleep in the previous days. Nevertheless, few studies have focused their attention on the effects of sleep deprivation on surgeons and more specifically on the effects of sleep deprivation on surgical dexterity, often relying on virtual surgical simulators. A better understanding of the consequences of sleep loss on the key surgical skill of dexterity can shed light on the possible risks associated to a sleepy surgeon. In this paper, the authors aim to provide a comprehensive review of the relationship between sleep deprivation and surgical dexterity.
... A study examining the ability of older adults (age 67 or older) found the use of caffeine interfered with their ability to fall asleep [9][10][11][12]. The sleep of older adults may be more sensitive to caffeine compared to younger adults [13,14]. ...
Background: European Food Safety Authority (EFSA 2015) reported that moderate daily caffeine consumption at levels up to 400 mg/day do not raise safety concerns and not associated with adverse effects in healthy adult population, while, high levels of caffeine consumption have been linked to a variety of illnesses such as cancer, heart disease, and diabetes. Despite these findings, there remains a gap in research relating to whether caffeine consumption adversely affects one's wellbeing as measured by overall self-rated health. Aim: The aim of this study was to determine the association of caffeine consumption and self-rated health among young and older adults. Settings: Four faculties in the Alexandria University which are Faculty of Commerce, Education, Dentistry and Pharmacy and Six clubs for older adults in Alexandria namely; El-Saada, El-Wafaa, El-Hayia Wl-Amal, El-Omr El-Zahaby, El-Hanan and El-Wedad club. Subjects: Eight hundred college students in 1 st, 2 nd, 3 rd , 4 th grades, and 150 older adults. Tools: (1) Young and Older Adults' Characteristics Structured Questionnaire Sheet, it includes three parts; sociodemographic and lifestyle, anthropometric measurements and self-rated health. (2) Young and Older Adults' structured Questionnaire Sheet it includes two parts i.e. knowledge, awareness and caffeine consumption. (3) Focus Group Discussion Guide. Results: Both groups of young and older adults consume high level of total caffeine /day, which may contribute to increased percent of caffeine toxicity and withdrawal symptoms. There is a statistically significant difference between them p= 0.042. The main sources of caffeine consumption among both groups were tea, coffee and medications. Higher caffeine consumption among young and older adults is associated with poor self-rated health. Conclusion: There is an association between caffeine consumption in both groups and their self-rated health. Poor level of knowledge regarding caffeine was observed in the higher consumers for both groups. Caffeine consumption is also associated with poor lifestyle as smoking, lower tendency to exercise regularly, irregular sleeping habits, overweight and obesity. Recommendations: Awareness program and education is needed to correct the misconceptions college students and older adults have regarding certain aspects of caffeine, to reduce its use and mitigate potential harms.
... A number of studies have indicated that regular daily dietary caffeine intake is associated with disturbed sleep. 9) We recently found that caffeine and EGCG suppressed the anti-stress effect of theanine while epigallocatechin (EGC) and arginine (Arg), other components in green tea, retained these effects. 10) This suggests that balances among theanine, caffeine, catechins and Arg are crucial for green tea to express its anti-stress effect. ...
Theanine, an amino acid in tea, has significant anti-stress effects on animals and humans. However, the effect of theanine was blocked by caffeine and gallate-type catechins, which are the main components in tea. We examined the anti-stress effect of green tea with lowered caffeine, low-caffeine green tea, on humans. The study design was a single-blind group comparison and participants (n=20) were randomly assigned to low-caffeine or placebo tea groups. These teas (≥500 mL/d), which were eluted with room temperature water, were taken from 1 week prior to pharmacy practice and continued for 10 d in the practice period. The participants ingested theanine (ca. 15 mg/d) in low-caffeine green tea. To assess the anxiety of participants, the state-trait anxiety inventory test was used before pharmacy practice. The subjective stress of students was significantly lower in the low-caffeine-group than in the placebo-group during pharmacy practice. The level of salivary α-amylase activity, a stress marker, increased significantly after daily pharmacy practice in the placebo-group but not in the low-caffeine-group. These results suggested that the ingestion of low-caffeine green tea suppressed the excessive stress response of students. This study was registered at the University Hospital Medical Information Network (ID No. UMIN14942).
... 32 It is important to emphasize that our results are purely associative and we should consider causality with caution. Although there are several studies that demonstrated that coffee and caffeine have a negative impact on sleep (increased sleep latency, reduced total sleep time and efficiency, decrease in slow waves, and increased arousals), 33 it is common knowledge that coffee has a positive effect on working performances and a moderate intake is not considered a health hazard. 34 It is thus possible that sleep-deprived residents drink more coffee to overcome sleepiness and that coffee intake does not disrupt sleep. ...
Background: Medical residencies are highly demanding and stressful and have been associated with mental and emotional problems. Studies that evaluated this relationship in Italian psychiatry residents are scarce. In this study, we examined sleep quality and its association with perceived stress and caffeinated beverages consumption in Italian psychiatry residents.
Methods: Seventy-two PGY1–5 psychiatry residents at two University Hospitals in Italy were asked to complete an anonymous questionnaire. The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale were used to determine the sleep quality and the level of daytime sleepiness (EDS). In addition, we investigated perceived stress and caffeinated drinks consumption (coffee, tea, soda, energy drinks).
Results: Seventy psychiatry residents responded to the survey (97.2% response rate) (M = 34.3%, F = 65.7%; mean age = 30.5 ± 4.2 SD years). 44.3% had poor sleep quality and 15.7% had abnormal EDS. 64.3% reported significant perceived stress. Perceived stress score and coffee consumption were associated with greater likelihood of poor sleep quality.
Conclusions: Psychiatry residents have high prevalence of poor sleep quality. Future longitudinal studies are needed to investigate causality and identify appropriate coping strategies and lifestyle changes aimed to improve mental health in psychiatry trainees.
Este artigo tem por objectivo introduzir os principais aportes teóricos da psicodinâmica do trabalho
para a compreensão da relação entre o homem e o trabalho. Com esse intuito, expõe num primeiro
tempo as diferentes fases do confronto entre a subjectividade e o real do trabalho, e procura
evidenciar a natureza fundamentalmente afectiva da experiência do trabalho. Termina, por fim,
evocando brevemente os requisitos individuais e colectivos da saúde mental no trabalho, propondo
uma interpretação etiológica de certos distúrbios mentais relacionados com o trabalho.
Caffeine is one of the most researched food components, with the vast majority of dietary contributions coming from beverage consumption; however, there is little population-level data on caffeine intakes in the U.S. This study estimated the caffeine intakes of the U.S. population using a comprehensive beverage survey, the Kantar Worldpanel Beverage Consumption Panel. A nationally representative sample of 37,602 consumers (aged ⩾2 years) of caffeinated beverages completed 7-day diaries which facilitated the development of a detailed database of caffeine values to assess intakes. Results showed that 85% of the U.S. population consumes at least one caffeinated beverage per day. The mean (±SE) daily caffeine intake from all beverages was 165±1 mg for all ages combined. Caffeine intake was highest in consumers aged 50-64 years (226±2 mg/day). The 90th percentile intake was 380 mg/day for all ages combined. Coffee was the primary contributor to caffeine intakes in all age groups. Carbonated soft drinks and tea provided a greater percentage of caffeine in the younger (<18 years) age groups. The percentage of energy drink consumers across all age groups was low (⩽10%). These data provide a current perspective on caffeinated beverage consumption patterns and caffeine intakes in the U.S. population.
Adolescence is a critical period for brain maturation during which a massive reorganization of cortical connectivity takes place. In humans, slow wave activity (<4.5 Hz) during NREM sleep was proposed to reflect cortical maturation which relies on use-dependent processes. A stimulant like caffeine, whose consumption has recently increased especially in adolescents, is known to affect sleep wake regulation.
The goal of this study was to establish a rat model allowing to assess the relationship between cortical maturation and sleep and to further investigate how these parameters are affected by caffeine consumption. To do so, we assessed sleep and markers of maturation by electrophysiological recordings, behavioral and structural readouts in the juvenile rat. Our results show that sleep slow wave activity follows a similar inverted U-shape trajectory as already known in humans. Caffeine treatment exerted short-term stimulating effects and altered the trajectory of slow wave activity. Moreover, caffeine affected behavioral and structural markers of maturation. Thus, caffeine consumption during a critical developmental period shows long lasting effects on sleep and brain maturation.
Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors - either directly or indirectly - have now entered the clinic. However, only one adenosine receptor-specific agent - the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma) - has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges.
A series of findings over the past decade has begun to identify the brain circuitry and neurotransmitters that regulate our daily cycles of sleep and wakefulness. The latter depends on a network of cell groups that activate the thalamus and the cerebral cortex. A key switch in the hypothalamus shuts off this arousal system during sleep. Other hypothalamic neurons stabilize the switch, and their absence results in inappropriate switching of behavioural states, such as occurs in narcolepsy. These findings explain how various drugs affect sleep and wakefulness, and provide the basis for a wide range of environmental influences to shape wake-sleep cycles into the optimal pattern for survival.
Slow wave oscillations in the electroencephalogram (EEG) during sleep may reflect both sleep need and intensity, which are implied in homeostatic regulation. Adenosine is strongly implicated in sleep homeostasis, and a single nucleotide polymorphism in the adenosine deaminase gene (ADA G22A) has been associated with deeper and more efficient sleep. The present study verified the association between the ADA G22A polymorphism and changes in sleep EEG spectral power (from C3-A2, C4-A1, O1-A2, and O2-A1 derivations) in the Epidemiologic Sleep Study (EPISONO) sample from São Paulo, Brazil. Eight-hundred individuals were subjected to full-night polysomnography and ADA G22A genotyping. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the signals from each EEG electrode. The genotype groups were compared in the whole sample and in a subsample of 120 individuals matched according to ADA genotype for age, gender, body mass index, caffeine intake status, presence of sleep disturbance, and sleep-disturbing medication. When compared with homozygous GG genotype carriers, A allele carriers showed higher delta spectral power in Stage 1 and Stages 3+4 of sleep, and increased theta spectral power in Stages 1, 2 and REM sleep. These changes were seen both in the whole sample and in the matched subset. The higher EEG spectral power indicates that the sleep of individuals carrying the A allele may be more intense. Therefore, this polymorphism may be an important source of variation in sleep homeostasis in humans, through modulation of specific components of the sleep EEG.
To identify common genetic variants that predispose to caffeine-induced insomnia and to test whether genes whose expression changes in the presence of caffeine are enriched for association with caffeine-induced insomnia.
A hypothesis-free, genome-wide association study.
Community-based sample of Australian twins from the Australian Twin Registry.
After removal of individuals who said that they do not drink coffee, a total of 2,402 individuals from 1,470 families in the Australian Twin Registry provided both phenotype and genotype information.
A dichotomized scale based on whether participants reported ever or never experiencing caffeine-induced insomnia. A factor score based on responses to a number of questions regarding normal sleep habits was included as a covariate in the analysis. More than 2 million common single nucleotide polymorphisms (SNPs) were tested for association with caffeine-induced insomnia. No SNPs reached the genome-wide significance threshold. In the analysis that did not include the insomnia factor score as a covariate, the most significant SNP identified was an intronic SNP in the PRIMA1 gene (P = 1.4 × 10⁻⁶, odds ratio = 0.68 [0.53 - 0.89]). An intergenic SNP near the GBP4 gene on chromosome 1 was the most significant upon inclusion of the insomnia factor score into the model (P = 1.9 × 10⁻⁶, odds ratio = 0.70 [0.62 - 0.78]). A previously identified association with a polymorphism in the ADORA2A gene was replicated.
Several genes have been identified in the study as potentially influencing caffeine-induced insomnia. They will require replication in another sample. The results may have implications for understanding the biologic mechanisms underlying insomnia.
Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear.
We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline.
During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline.
In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.).
A night without sleep is followed by enhanced sleepiness, increased low-frequency activity in the waking EEG, and reduced vigilant attention. The magnitude of these changes is highly variable among healthy individuals. Findings in young men of low and high subjective caffeine sensitivity suggest that adenosinergic mechanisms contribute to inter-individual differences in sleep deprivation-induced changes in EEG theta activity, as well as optimal performance on the psychomotor vigilance task (PVT). In comparison to young subjects, healthy adults of older age typically feel less sleepy after sleep deprivation, and show fewer response lapses, and faster reaction times on the PVT, especially in the morning after the night without sleep. We hypothesized that age-related changes in adenosine signal transmission underlie reduced vulnerability to sleep deprivation in older individuals. To test this hypothesis, the combined effects of prolonged wakefulness and the adenosine receptor antagonist, caffeine, on an antero-posterior power gradient in EEG theta activity and PVT performance were analyzed in healthy older and caffeine-insensitive and -sensitive young men. The results show that age-related differences in sleep loss-induced changes in brain rhythmic activity and neurobehavioral functions are mirrored in young individuals of low and high sensitivity to the stimulant effects of caffeine. Moreover, the effects of sleep deprivation and caffeine on regional theta power and vigilant attention are inversely correlated across older and young age groups. Genetic variants of the adenosine A(2A) receptor gene contribute to individual differences in neurobehavioral performance in rested and sleep deprived state, and modulate the actions of caffeine in wakefulness and sleep. Based upon this evidence, we propose that age-related differences in A(2A) receptor-mediated signal transduction could be involved in age-related changes in the vulnerability to acute sleep deprivation.
Coffee and other caffeinated beverages are commonly consumed in pregnancy. In adults, caffeine may interfere with sleep onset and have a dose-response effect similar to those seen during insomnia. In infancy, nighttime waking is a common event. With this study, we aimed to investigate if maternal caffeine consumption during pregnancy and lactation leads to frequent nocturnal awakening among infants at 3 months of age.
All children born in the city of Pelotas, Brazil, during 2004 were enrolled on a cohort study. Mothers were interviewed at delivery and after 3 months to obtain information on caffeine drinking consumption, sociodemographic, reproductive, and behavioral characteristics. Infant sleeping pattern in the previous 15 days was obtained from a subsample. Night waking was defined as an episode of infant arousal that woke the parents during nighttime. Multivariable analysis was performed by using Poisson regression.
The subsample included 885 of the 4231 infants born in 2004. All but 1 mother consumed caffeine in pregnancy. Nearly 20% were heavy consumers (≥300 mg/day) during pregnancy and 14.3% at 3 months postpartum. Prevalence of frequent nighttime awakeners (>3 episodes per night) was 13.8% (95% confidence interval: 11.5%-16.0%). The highest prevalence ratio was observed among breastfed infants from mothers consuming ≥300 mg/day during the whole pregnancy and in the postpartum period (1.65; 95% confidence interval: 0.86-3.17) but at a nonsignificant level.
Caffeine consumption during pregnancy and by nursing mothers seems not to have consequences on sleep of infants at the age of 3 months.
Adenosine has been implicated in the physiological regulation of sleep propensity. The adenosine-receptor-antagonist, caffeine (100 mg), administered immediately prior to a nocturnal sleep episode, has previously been shown to lower sleep propensity as indexed by a reduced sleep efficiency, a reduced EEG power density in low delta frequencies and enhanced power density in the frequency range of sleep spindles. To further investigate the role of adenosine in sleep regulation we administered 200 mg of caffeine at 07.10 h and analyzed the sleep stages and EEG power spectra during the subsequent night in nine healthy men. Caffeine levels in saliva decreased from a maximum of 17 μmol/l one hour after intake, to 3 μmol/l immediately prior to the sleep episode starting at 23.00 h. Compared to placebo, sleep efficiency and total sleep time were significantly reduced. EEG power density in nonREM sleep was suppressed in the 0.25–0.5 Hz band and enhanced in the frequency range of sleep spindles (11.25–12.0 Hz and 13.25–14.0 Hz). In REM sleep EEG power density was suppressed in the frequency range of 0.75–4.5 and 5.25–6.0 Hz. The data indicate that a saliva level of caffeine as low as 3 μmol/l directly affects sleep propensity or, alternatively, that the presence of caffeine in the central nervous system during the waking episode reduces the progressive increase of sleep propensity associated with wakefulness.
An experiment was carried out to examine the effects of caffeine and evening meals on sleep and performance, mood and cardiovascular functioning in the early morning of the next day. Forty-eight subjects were assigned to one of the four conditions formed by combining caffeine and meal conditions. Subjects in the caffeine condition were given 3 mg/kg caffeine in de-caffeinated coffee. The caffeine manipulation was double blind. Subjects in the meal condition were given a 3-course meal (∼ 1300 calories). Sleep was assessed by subjective ratings and these showed that both caffeine and consumption of the meal influenced sleep, but that there were no interactions between caffeine and meal conditions. Although caffeine disrupted sleep there was no evidence of performance or mood being impaired the next day. However, blood pressure was still higher the next day in subjects given caffeine the previous evening.
To investigate the associations between sleep duration and obesity incidence and risk factors among pre-adolescents and adolescents.
Cross-sectional study of a community based cohort
The Tucson Children's Assessment of Sleep Apnea follow-up study (TuCASA) cohort.
319 Caucasian and Hispanics between 10-17 years.
Parent-reported sleep duration and BMI z-score.
Surveys of electronic screen time, dietary and caffeine intake, exercise and sleep habits by parents, and anthropometric measures.
Parent-reported total sleep time (TST) was inversely associated with BMI z-score, but not significantly correlated with any of the examined nutritional variables or exercise components. Hispanic ethnicity was associated with significantly lower parent-reported TST and higher BMI z-score. Parent-reported TST was inversely related to electronic screen time and caffeine use, but these findings were differentially related to age. Caffeine consumption was associated with decreasing parent-reported TST primarily in older adolescents. Electronic screen time was associated with lower parent-reported TST in younger adolescents.
Hispanic ethnicity and parental reports of TST were found to be the most closely associated with BMI z-score. Decreased TST and increased caffeine intake and screen time may result in higher obesity risk in the adolescent population.
Homeostatically regulated slow-wave oscillations in non–rapid eye movement (REM) sleep may reflect synaptic changes across
the sleep–wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine
deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations.
We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram
(EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive
functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after
sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75-
to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor
were reduced, whereas waking EEG alpha activity (8.5–12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These
convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and
waking quality in humans.
To evaluate the association between the adenosine deaminase polymorphism, sleep architecture, and caffeine consumption.
Genetic association study.
NA.
958 participants who underwent polysomnography and genotyping.
NA.
Individuals carrying the A allele who consumed caffeine in the day prior to polysomnography demonstrated higher sleep efficiency and REM sleep percentage, after adjustment for potential confounders. No effect was observed in the absence of caffeine.
Our data support the role of the ADA G22A polymorphism in sleep, and demonstrate for the first time that caffeine may act as a modulator of its functional effects.
Name: Epidemiology of sleep disturbances among adult population of the Sao Paulo City. URL: http://www.clinicaltrials.gov/ct2/show/NCT00596713?term=NCT00596713&rank=1. Number: NCT00596713
To review the effects, adverse consequences, and extent of energy drink consumption among children, adolescents, and young adults.
We searched PubMed and Google using "energy drink," "sports drink," "guarana," "caffeine," "taurine," "ADHD," "diabetes," "children," "adolescents," "insulin," "eating disorders," and "poison control center" to identify articles related to energy drinks. Manufacturer Web sites were reviewed for product information.
According to self-report surveys, energy drinks are consumed by 30% to 50% of adolescents and young adults. Frequently containing high and unregulated amounts of caffeine, these drinks have been reported in association with serious adverse effects, especially in children, adolescents, and young adults with seizures, diabetes, cardiac abnormalities, or mood and behavioral disorders or those who take certain medications. Of the 5448 US caffeine overdoses reported in 2007, 46% occurred in those younger than 19 years. Several countries and states have debated or restricted energy drink sales and advertising.
Energy drinks have no therapeutic benefit, and many ingredients are understudied and not regulated. The known and unknown pharmacology of agents included in such drinks, combined with reports of toxicity, raises concern for potentially serious adverse effects in association with energy drink use. In the short-term, pediatricians need to be aware of the possible effects of energy drinks in vulnerable populations and screen for consumption to educate families. Long-term research should aim to understand the effects in at-risk populations. Toxicity surveillance should be improved, and regulations of energy drink sales and consumption should be based on appropriate research.
Sleep deprivation is associated with considerable social, financial, and health-related costs, in large measure because it produces impaired cognitive performance due to increasing sleep propensity and instability of waking neurobehavioral functions. Cognitive functions particularly affected by sleep loss include psychomotor and cognitive speed, vigilant and executive attention, working memory, and higher cognitive abilities. Chronic sleep-restriction experiments--which model the kind of sleep loss experienced by many individuals with sleep fragmentation and premature sleep curtailment due to disorders and lifestyle--demonstrate that cognitive deficits accumulate to severe levels over time without full awareness by the affected individual. Functional neuroimaging has revealed that frequent and progressively longer cognitive lapses, which are a hallmark of sleep deprivation, involve distributed changes in brain regions including frontal and parietal control areas, secondary sensory processing areas, and thalamic areas. There are robust differences among individuals in the degree of their cognitive vulnerability to sleep loss that may involve differences in prefrontal and parietal cortices, and that may have a basis in genes regulating sleep homeostasis and circadian rhythms. Thus, cognitive deficits believed to be a function of the severity of clinical sleep disturbance may be a product of genetic alleles associated with differential cognitive vulnerability to sleep loss.
In view of the hypothesis that adenosine is involved in sleep regulation, the effects of the adenosine antagonist caffeine on sleep and sleep EEG were investigated in eight young males. Compared to the placebo condition, caffeine (100 mg) administered at bedtime prolonged sleep latency and reduced sleep efficiency and stage 4 of non-rapid eye movement sleep (NREMS). Electroencephalographic slow-wave activity (SWA, spectral power density in the 1.75-4.5-Hz band) was reduced, whereas power density in the spindle frequency range was slightly enhanced. The suppression of SWA was limited to the first NREMS episode. Caffeine reduced the power density mainly in the lowest delta band, in contrast to the changes during physiological sleep that encompass both the delta and theta bands. Caffeine levels in saliva, assessed in a separate experiment, decreased from 7.5 mumol/l in the first hour of sleep to 3.5 mumol/l in the seventh hour. In the night following caffeine administration, stage 4 sleep had reverted to the baseline level, but sleep latency was still increased, and stage 2 sleep, as well as SWA in the first NREMS episode, were reduced. The data show that even a low dose of caffeine affects the sleep EEG. However, the effects of caffeine did not completely mimic the spectral changes observed during physiological sleep.
Thirty healthy volunteers were randomly assigned to either a caffeine or a placebo group to investigate the alerting effects of caffeine at night. Subjects adhered to a simulated night-shift schedule for 5 consecutive nights. On the first 3 nights, 2 mg/kg caffeine was added to decaffeinated coffee at 2220 and 0120 hours for the caffeine group. On nights 4 and 5 both groups received placebo. Each night, subjects completed five 60-minute sessions of a computerized simulated assembly line performance task (SALT), a multiple sleep latency test (MSLT) and questionnaires. Daytime sleep was recorded in the laboratory between 0900 and 1700 hours each day following nighttime testing. Caffeine decreased physiological sleep tendency on the night shift compared with placebo; however, the two groups performed at equivalent levels on the SALT. On nights 4 and 5, when both groups received placebo, there were no differences between the groups on the MSLT, suggesting the absence of a discontinuation effect. There were no differences on daytime polysomnograms between the groups.
During the middle years of life, sleep becomes more fragile and its sensitivity to psychostimulants may increase. This study evaluated the effects of 200 mg and 400 mg of caffeine on sleep in young and middle-aged adults. The sleep of 22 young (23.5 ± 1.9 years) and 24 middle-aged (51.7 ± 11.5 years) adults was recorded using polysomnography in two conditions (placebo and caffeine) in a double-blind cross-over design. Compared to placebo, caffeine increased sleep latency, shortened total sleep duration and reduced sleep efficiency. At the higher dose, these effects were more pronounced in middle-aged than in young adults. Furthermore, the higher dose of caffeine increased absolute stage 1 sleep in young adults, whereas it decreased absolute stage 2 sleep in middle-aged adults. Caffeine also induced dose-dependent increases in relative stage 1 sleep and reductions in absolute and relative slow wave sleep and absolute rapid eye movement sleep in both age groups. There was no dose- or age-related modulation of the effects of caffeine on quantified electroencephalographic measures. These results indicate that, compared to young adults, middle-aged adults are generally more sensitive to the effects of a high dose of caffeine on sleep quantity and quality.
© The Author(s) 2015.
Sales of caffeinated energy drinks and shots saw double-digit growth in the past few years. Whereas the number of athletes who use energy drinks is unknown, the number of college athletes who report using energy drinks is about 45%. Caffeine in small doses (2–3 mg/kg per body weight) is an effective ergogenic aid, acting on the central nervous system to delay fatigue and increase alertness. Energy drinks claim to have other functional ingredients that enhance athletic performance, but research on energy drinks in athletes is scant and results equivocal. If there is a positive effect, it is the caffeine in energy drinks that provides a performance boost. This article reviews use and safety concerns of energy drinks, the role of caffeine on sports performance, and guidelines for use in athletes.
Benzodiazepines (BDZs) are the most widely prescribed class of psychoactive drugs in current therapeutic use, despite the important unwanted side-effects that they produce such as sedation, myorelaxation, ataxia, amnesia, ethanol and barbiturate potentiation and tolerance. Searching for safer BDZ-receptor (BDZ-R) ligands we have recently demonstrated the existence of a new family of ligands which have a flavonoid structure. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have shown to possess a selective and relatively mild affinity for BDZ-Rs and a pharmacological profile compatible with a partial agonistic action. In a logical extension of this discovery various synthetic derivatives of those compounds, such as 6,3′-dinitroflavone were found to have a very potent anxiolytic effect not associated with myorelaxant, amnestic or sedative actions. This dinitro compound, in particular, exhibits a high affinity for the BDZ-Rs (Ki = 12–30 nM). Due to their selective pharmacological profile and low intrinsic efficacy at the BDZ-Rs, flavonoid derivatives, such as those described, could represent an improved therapeutic tool in the treatment of anxiety. In addition, several flavone derivatives may provide important leads for the development of potent and selective BDZ-Rs ligands.
Sleep hygiene recommendations are widely disseminated despite the fact that few systematic studies have investigated the empirical bases of sleep hygiene in the home environment. For example, studies have yet to investigate the relative effects of a given dose of caffeine administered at different times of day on subsequent sleep.
This study compared the potential sleep disruptive effects of a fixed dose of caffeine (400 mg) administered at 0, 3, and 6 hours prior to habitual bedtime relative to a placebo on self-reported sleep in the home. Sleep disturbance was also monitored objectively using a validated portable sleep monitor.
Results demonstrated a moderate dose of caffeine at bedtime, 3 hours prior to bedtime, or 6 hours prior to bedtime each have significant effects on sleep disturbance relative to placebo (p < 0.05 for all).
The magnitude of reduction in total sleep time suggests that caffeine taken 6 hours before bedtime has important disruptive effects on sleep and provides empirical support for sleep hygiene recommendations to refrain from substantial caffeine use for a minimum of 6 hours prior to bedtime.
Drake C; Roehrs T; Shambroom J; Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med 2013;9(11):1195-1200.
In our study, we hypothesized that higher caffeine intake would be associated with lower sleep duration among 13-year-old adolescents. In addition, we aimed to identify food sources of caffeine intake in this sample. Eligible participants were adolescents who were born in 1990 and attended school in Porto, Portugal, in 2003/2004. Self-administered questionnaires were used, and diet was evaluated using a food frequency questionnaire. From the 2160 eligible participants, only 1522 with valid information regarding their diet were included in this study. In our sample, the median intake of caffeine was 23.1 mg/d, with soft drinks being the major source. Ice tea presented the highest median (25th-75th percentiles) contribution (33.1% [14.0-52.1]), followed by cola (21.1% [6.4-37.6]). Regarding cocoa products, chocolate bars presented a median contribution of 5.1% (1.0-14.0), and snacks containing chocolate had a contribution of 3.0% (0.5-7.2). Coffee and tea presented a negligible contribution. Adolescents who reported less sleep duration and those who spent more time watching TV during the weekend had a significantly higher caffeine intake. Overall, boys had higher intakes of caffeine from soft drinks, and private school attendees, those who had parents with more education, who reported less television viewing time and had lower body mass index presented higher intakes of caffeine from chocolate. Considering sleeping more than 9.5 hours as a reference class, for each increase of 10 mg/d in caffeine intake, we found that the odds ratio of sleeping 8.5 hours or less was 1.12 (95% confidence interval, 1.06-1.19). Our results support the hypothesis that caffeine intake was inversely associated with sleep duration in adolescents.
AIM: The aim of this study was to examine whether caffeine abstinence in the evening could improve the sleep quality of those who habitually consume coffee. DESIGN: A double-blind control group design (caffeine and caffeine-free groups). SETTING: A university. SUBJECTS: A convenience sampling of 10 students (mean age 21.4years). METHODS: It was a 14-day experiment. For the first 7days, all participants consumed caffeinated coffee. In the following 7days, subjects consumed caffeinated or decaffeinated coffee according to their assigned group. MEASURES: Sleep-wake parameters, self-reported sleep quality and level of refreshment. RESULTS: There were no significant differences (p>.05) among the data of the two groups identified. No significant changes (p>.05) were found in the sleep quality of either group during the study. CONCLUSION: This study confirms that caffeine abstinence in the evening might not be helpful in sleep promotion. It highlights the need to implement evidence-based practice in health promotion.
170 undergraduates were asked to indicate their daily caffeine consumption, habitual sleep duration, and sleep satisfaction. Essentially, the data replicated H. L. Hollingworth's (1912) study that found an inverse relationship between level of daily consumption of caffeinated drinks and habitual sleep duration and a nonsignificant relationship between caffeine use and sleep satisfaction. (8 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Two problems affecting school-aged children in the United States are inadequate sleep and an increased prevalence of obesity. The purpose of this study was to quantify media-related technology use and caffeine consumption in order to assess their potential effects on sleep duration and body mass index (BMI) in children.
The study was a secondary analysis of children 6 to 10 years of age (N = 625) from the National Sleep Foundation's Sleep in America Poll. Regression analysis was used to assess the relationship between caffeine and technology use, sleep variables, and BMI, adjusting for age, race, gender, and general health.
Almost 30% (29.5%) of the children consumed a daily caffeinated beverage, and 42.4% had a television in the bedroom. Children who drank caffeinated beverages had 15 fewer minutes of sleep per night than did children who did not drink such beverages (b = -0.27, p = .002). Children with three technology items in their bedroom received 45 fewer minutes of sleep than did children without these items in their bedroom (b = -0.75, p = .010). Having adjusted for variables, only drinking caffeinated beverages was associated with a BMI z score.
The complex relationships between caffeine intake and the use of technology with shortened periods of sleep and increased BMI need further study. Future research should explore how these risk factors for shortened periods of sleep can be modified in this young population.
1 The effect of caffeine alkaloid base (300 mg) on whole night sleep was investigated by electrophysiological techniques in six late middle age subjects (mean age 56 years), comparison being made with decaffeinated coffee and with no drink prior to sleep, using each condition five times in a balanced order on non-consecutive nights. 2 After caffeine the mean total sleep time decreased on average by 2 h, the mean sleep latency increased to 66 minutes. The number of awakenings increased and the mean total intervening wakefulness was more than doubled after caffeine. 3 In the first 3 h of sleep a decreased amount of stage 3 + 4 was observed, accompanied by an increased amount of stage 2 and of intervening wakefulness, without a significant change in the amount of rapid eye movement sleep. 4 The change in sleep pattern observed suggests an increased capability for arousal and decreased ability to develop or sustain deeper stages of non-rapid eye movement sleep after caffeine.
Forty normal subjects (mean age 36) had their caffeine intake estimated by keeping a diary (n=40) and also by analysing provided samples of tea and coffee (n=28). A test dose of caffeine (500 mg) was given and a series of salivary samples analysed to estimate pharmacokinetic measures of the rate of caffeine metabolism. They then underwent 48 h of placebo substitution using double-blind procedures. A wide range of physiological, psychological and subjective measures were taken on successive days during withdrawal and resumption of caffeine. On withdrawal, 27 subjects reported tiredness and 18 developed headache. Electroencephalograph, skin conductance and blood pressure changes were apparent. Sleep improved on withdrawal but subjects reported feeling less alert and more tired. The higher the usual caffeine intake, the greater the unpleasant feelings on withdrawal and the more marked the reversal of feelings on resumption. The faster the metabolism of caffeine, the less the drop in anxiety during withdrawal and the less its return on resumption. These correlations were, however, rather weak and sporadic.
Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers.
Shift work is highly prevalent in industrialized societies (>20%) but, when it includes night work, it has pronounced negative effects on sleep, subjective and physiological sleepiness, performance, accident risk, as well as on health outcomes such as cardiovascular disease and certain forms of cancer. The reason is the conflict between the day oriented circadian physiology and the requirement for work and sleep at the "wrong" biological time of day. Other factors that negatively impact work shift sleepiness and accident risk include long duration shifts greater than 12 hours and individual vulnerability for phase intolerance that may lead to a diagnosis of shift work disorder; i.e., those shift workers with the greatest sleepiness and performance impairment during the biological night and insomnia during the biological day. Whereas some countermeasures may be used to ameliorate the negative impact of shift work on nighttime sleepiness and daytime insomnia (combined countermeasures may be the best available), there seems at present to be no way to eliminate most of the negative effects of shift work on human physiology and cognition.
Little is known about adolescents' caffeine use, yet caffeinated soda, and more recently coffee and energy drinks, are part of youth culture. This study examines adolescents' caffeine use and, using cluster analysis, identifies three groups of caffeine users who differed in their reasons for use, expectancies, and sleep behaviors. In this high school student sample (N = 197), 95% of participants reported recent caffeine use-most often soda-where typical first use of the day was in the evening. Results reveal that adolescents in the mixed use and high soda use groups consumed similar amounts of soda, reporting significantly more use than the low caffeine use group. In contrast with high soda users, mixed users drank more coffee, expected more dependence symptoms and energy enhancement from caffeine, and were more likely to report getting up early, daytime sleepiness, and using caffeine to get through the day.
Adolescents may not receive the sleep they need. New media technology and new, popular energy drinks may be implicated in sleep deficits. In this pilot study we quantified nighttime technology use and caffeine consumption to determine effects on sleep duration and daytime behaviors in adolescents. We hypothesized that with increased technology use, adolescents increase caffeine consumption, resulting in insufficient sleep duration.
Subjects were recruited from a pediatric office in a proximal suburb of Philadelphia, Pennsylvania. Inclusion criteria for this study were middle and high school subjects aged 12 to 18 years old. The questionnaire, Adolescent Sleep, Caffeine Intake, and Technology Use, was developed by the investigators to measure adolescents' intake of caffeinated drinks, use of nighttime media-related technology, and sleep behaviors. Descriptive statistics characterized the subjects, their caffeine and technology use, and sleep variables. Regression models assessed the relationships between caffeine, technology use, and sleep variables, having adjusted for age, race, gender, and BMI.
Sleep was significantly related to the multitasking index. Teenagers getting 8 to 10 hours of sleep on school nights tended to have 1.5- to 2-fold lower multitasking indices compared with those getting less sleep. Thirty-three percent of the teenagers reported falling asleep during school. Caffeine consumption tended to be 76% higher by those who fell asleep. The log-transformed multitasking index was significantly related to falling asleep during school and with difficulties falling asleep on weeknights.
Many adolescents used multiple forms of technology late into the night and concurrently consumed caffeinated beverages. Subsequently, their ability to stay alert and fully functional throughout the day was impaired by excessive daytime sleepiness. Future studies should measure more than television hours when evaluating the impact of nighttime activities on sleep patterns in adolescents.
A sample of 144 inmates from a maximum security penitentiary responded to a request for information regarding their average daily intake of nicotine and caffeine. They also rated the quality of their appetite and sleep, their level of concentration, their mood and specific feelings of anger, anxiety, frustration, and irritability. Factor analysis generated a two-factor solution of these variables, namely general mood state (mood, anxiety, anger, frustration, and irritability) and a somatic state (appetite, concentration, and sleep). Analysis of variance showed an interaction between level of smoking (nonsmokers, low and high cigarette smokers) and caffeine use (moderate vs. high) on the general mood factor. Nonsmokers who consumed high levels of caffeine experienced poorer general mood than any other group. There was a main effect of cigarette smoking status on the somatic factor, such that greater dissatisfaction was associated with greater consumption. Caffeine consumption was generally high, averaging 800 mg of caffeine per day, per inmate, well above the amount considered to be potentially damaging to health.
In vitro autoradiography with 125I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific 125I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific 125I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific 125I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.
A total of 2714 people, aged 20-45 years from the Brighton area who completed a questionnaire were interviewed on their sleep patterns and complaints, medication, behavioural aids, and consumption of caffeine and alcohol. Analysis showed that 24% had delayed sleep onset, 23% awakened frequently, 19% awakened early, 21% were dissatisfied with sleep, and 8% took medication to aid sleep. Of those on night shifts, 29% awakened frequently and 25% awakened early. There were 648 responses describing behavioural sleeping aids. The moderate consumption of caffeine and alcohol had no significant effect on sleep. The main differences between this survey and other published data relate to the comparison of sleep reports from men with those from women, the sleep of nightshift and dayshift workers and the effects of caffeine and alcohol. These differences may arise from sampling characteristics and the form of the questionnaire.
Subjects were given varying doses of a placebo, consisting of decaffeinated coffee, with double-blind or deceptive instructions. Deceptive administration simulated clinical situations in that subjects were led to believe that they were receiving an active drug. In contrast, subjects in double-blind conditions were aware that they might receive a placebo. Double-blind and deceptive administration of the placebo produced different, and in some instances, opposite effects on pulse rate, systolic blood pressure, and subjective mood. Deceptive administration produced an increase in pulse rate, whereas double-blind administration did not. A theoretically predicted curvilinear effect on systolic blood pressure, alertness, tension, and certainty of having consumed caffeine was confirmed with deceptive administration, but not with double-blind administration. Double-blind administration produced curves in the opposite direction on each of these variables. The effects of the placebo on motor performance varied as a function of subject's beliefs about the effects of caffeine. These data challenge the validity of double-blind experimental designs and suggest that this common method of drug assessment may lead to spurious conclusions.
Eleven mother-infant pairs were studied to determine the effect of maternal caffeine ingestion (500 mg/day) on heart rate and sleep time of the infants. In a balanced cross-over design, mothers ingested 5 cups of decaffeinated coffee daily during one 5-day period and 5 cups of decaffeinated coffee with added caffeine (100 mg/cup) during another 5-day period. Concentrations of caffeine in milk on the last day of the caffeine period ranged from 1.6 to 6.2 micrograms/ml and the intake of caffeine by the infants was estimated to be 0.3-1.0 mg/kg/day. Infant serum did not contain detectable amounts of caffeine on the last day of either experimental period. Performance during the caffeine and no-caffeine periods was not significantly different with respect to either 24-hour heart rate or sleep time.
By means of a questionnaire, information was gathered about coffee drinking and its effects in 239 young housewives. The group was divided into roughly equal parts with respect to daily coffee consumption: abstainers, light users (I to 2 cups); moderate users (3 to 4 cups); and heavy users (5 or more cups). The respondents were asked why they drink coffee in the morning, what behavioral changes it produces, and what effects would ensue i f morning coffee were omitted. They were also asked if coffee makes them wakeful at night. The results indicate substantial differences in the responses correlated with the extent o f coffee use. Heavy users reported less wakefulness caused by coffee at night and less nervousness caused by coffee in the morning as compared with light users. On the other hand, heavy users reported more of the desirable stimulant and euphoriant effects than did light users. Heavy users also described a characteristic set of dysphoric symptoms attributed to omission of morning coffee: irritability, inability to work effectively, nervousness, restlessness, lethargy, and headache. The validity of these results was confirmed in an experimental study on some of the same subjects reported in the accompanying paper.
1 Effects of the heterocyclic amphetamine derivatives, pemoline (20 and 40 mg), prolintane hydrochloride (5 and 10 mg), methylphenidate hydrochloride (10 and 20 mg) and fencamfamine hydrochloride (10 and 20 mg), and of caffeine anhydrous (100, 200 and 300 mg) on sleep, were compared with placebo in six young adults (20-31 years) using electroencephalography for sleep measures and analogue scales for subjective assessments of well-being and sleep quality. The study was double-blind.2 No consistent effect was found with pemoline.3 With prolintane there were no changes in sleep latencies, or in slow wave sleep (SWS). Rapid eye movement (REM) sleep was reduced during the first 2 h after sleep onset.4 With methylphenidate and fencamfamine latencies to sleep onset and to stage 3 sleep were unchanged. The higher dose of each drug delayed the first and subsequent REM periods. Both drugs reduced the duration of REM sleep, and the higher dose of each drug reduced the percentage REM sleep. Methylphenidate also reduced total sleep time (TST). There was no evidence of reduced SWS with either drug. Impairment of sleep was reported with each drug.5 With caffeine there were no changes in latencies to sleep onset or to the first REM period, though in one study with 300 mg subsequent REM periods were delayed. Awake activity and drowsy sleep were increased and TST and SWS were decreased. With 300 mg only, REM sleep was decreased though percentage REM sleep was not altered. Impaired sleep was reported with all doses of caffeine.
The most important enzyme immunoassay techniques are described. The enzymes currently used as labels, the methods of coupling them to antigens or haptens and the possible applications of these assays are reviewed. Furthermore, an overview is given of the reliability and practicability of commercially available enzyme immunoassay kits used in clinical chemical laboratories. Special consideration is given to possible interferences, the detection limits and the mechanization of these tests. Various methods for curve-fitting are listed. It is concluded that most of the currently commercially available enzyme immunoassays are suitable for routine application in appropriate centers like clinical chemical laboratories of larger hospitals. The future role of enzyme immunoassays in clinical chemistry is briefly discussed.
The effects of continuous and intermittent caffeine abstinence and their time course were investigated under field conditions. After 3 days with habitual coffee, subjects were switched for 9 days to regular instant coffee (n = 40), decaffeinated coffee (n = 40), or an intermittent regime (2 days decaff, 1 day caff, repeated, n = 40). Subjects were blind to the caffeine treatment. Motor activity was assessed continuously; subjective variables, blood pressure (BP), and heart rate (HR) were assessed by the subjects six times per day (electronic diary). Compliance was confirmed by the different caffeine concentrations in daily saliva samples. Continued caffeine consumption showed no effects. Caffeine abstinence resulted in increased HR, decreased motor activity, subjective wakefulness, and well-being, and in increased headaches and use of analgetics. The subjective effects and headaches were transient, i.e., they disappeared after a few days of abstinence and weakened over successive, separated abstinence periods. BP was not affected by the caffeine treatment. The intermittent onset of caffeine consumption resulted in increased wakefulness, whereas the other variables normalized to baseline level.
Subjective insomnia is more prevalent in elderly than in young populations. In order to examine the relationship between caffeine and sleep quality we studied 181 community-dwelling subjects over a wide age range and 53 elderly patients receiving continuing hospital care. Subjects completed a sleep questionnaire and data concerning smoking, alcohol, use of hypnotics and caffeine-containing substances were recorded. Late afternoon plasma caffeine concentrations were measured in a sub-group of 87 of the community-dwelling subjects and in the hospitalized patients.
For the group as a whole, there was a significant negative correlation between age and coffee but not tea consumption (p <0.001). A global score of sleep quality was significantly inversely related to age (p <0.001). For the community-dwelling population, the median plasma caffeine concentration was 1.71 μg/ml (range 0.10–6.74) and showed a significant correlation with sleep quality (p <0.05). In contrast, for the hospital dwelling population, median caffeine concentration was higher in patients reporting sleep problems than in those without (p <0.05). Self-reported consumption of coffee and tea did not correlate with plasma caffeine concentrations.
It is possible that people with poor sleep quality, residing in the community, are aware of the stimulatory effects of caffeine and lower their intake accordingly, whereas hospitalized elderly patients, who have less control over their environment, do not.
Locomotive engineers (train drivers) on irregular work schedules reported a general coffee consumption rate higher than that reported by a comparison sample of permanent shift factory workers. The present study examines the impact of this consumption on workday and non-workday sleep behaviour and mood ratings. Twenty-seven engineers and their spouses each completed daily logs for 30 consecutive days. Daily logs were then sorted into workday and non-workday categories. Workday sleep length was significantly shorter than non-workday sleep length for both engineers and spouses. For the engineers only, coffee consumption on workdays was higher than on non-workdays. This increased coffee consumption was correlated with longer sleep latency, increased negative mood, and decreased positive mood on both work and non-workdays. This was not true for spouses. These results may be related to a days-off carry-over effect of caffeine or a general consumption behaviour characteristic.
Flavone derivatives and other phytochemicals were found to bind to three subtypes of adenosine receptors in the micromolar range. Affinity was determined in radioligand binding assays at rat brain A1 and A2A receptors using [3H]-N6-PIA ([3H]-(R)-N6-phenylisopropyladenosine) and [3H]CGS21680 ([3H]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'- (N-ethylcarbamoyl)adenosine), respectively. Affinity was determined at cloned human and rat brain A3 receptors using [125I]-AB-MECA [N6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamide)]. A structure-activity analysis indicated that the hydroxyl groups of naturally occurring flavones are not essential for affinity at adenosine receptors. Galangin, 14, displayed Ki values of 1 microM at both rat A1 and A2A receptors and 3 microM at human A3 receptors. Methylation but not acetylation of the hydroxyl groups of galangin enhanced A3 affinity. Pentamethylmorin, 20, appeared to bind with 14-17-fold selectivity for human A3 receptors vs rat A1 and A2A receptors, with a Ki value of 2.65 microM. Two flavone derivatives (14 and 15) showed 14-fold greater affinity at human vs rat A3 receptors. Reduction of the 2,3-olefinic bond, as in (+/-)-dihydroquercetin, or glycosidation, as in robinin, greatly diminished affinity. An isoflavone, genistein, also bound only very weakly at A3 receptors. alpha-Naphthoflavone had greater receptor affinity (0.79 microM at A1 receptors) than the beta-isomer. Other natural products of plant origin, including oxogalanthine lactam, hematoxylin, and arborinine were found to bind to A1 adenosine receptors with Ki values of 3-13 microM. These findings indicate that the flavones, flavonols, flavanones, and other phytochemicals may provide leads for the development of novel adenosine antagonists. The unexpected finding of considerable affinity of flavones at both rat and human A3 receptors may explain some of the previously observed biological effects of these compounds.
Scientific literature cites a wide range of values for caffeine content in food products. The authors suggest the following standard values for the United States: coffee (5 oz) 85 mg for ground roasted coffee, 60 mg for instant and 3 mg for decaffeinated; tea (5 oz): 30 mg for leaf/bag and 20 mg for instant; colas: 18 mg/6 oz serving; cocoa/hot chocolate: 4 mg/5 oz; chocolate milk: 4 mg/6 oz; chocolate candy: 1.5-6.0 mg/oz. Some products from the United Kingdom and Denmark have higher caffeine content. Caffeine consumption survey data are limited. Based on product usage and available consumption data, the authors suggest a mean daily caffeine intake for US consumers of 4 mg/kg. Among children younger than 18 years of age who are consumers of caffeine-containing foods, the mean daily caffeine intake is about 1 mg/kg. Both adults and children in Denmark and UK have higher levels of caffeine intake.
Pharmacokinetic and pharmacodynamic responses to caffeine (2.5 mg/kg) were compared between ten healthy self-rated poor sleepers and ten normal sleepers. Sleep pattern assessed by the Pittsburgh Sleep Quality Index (PSQI). There was no significant difference in mean estimated daily caffeine consumption between the groups. The poor sleepers had significantly higher scores for neuroticism on the Eysenck Personality Questionnaire (EPQ) and anxiety on the Hospital Anxiety Depression (HAD) scale, compared with normal sleepers. Caffeine pharmacokinetics were assessed by measurement of saliva caffeine concentrations. Poor sleepers showed significantly greater variability in caffeine Cmax, clearance had half-life, compared to normal sleepers. Pharmacodynamic measures included heart rate, blood pressure, visual analogue scales for concentration, vigilance and relaxation, psychomotor performance [Digit Symbol Substitution Test (DSST) and tapping rate (TR)] and EEG activity [Contingent negative variation (CNV), auditory evoked potential and power spectral analysis]. Prior to caffeine administration, poor sleepers compared to normal sleepers had faster heart rates, lower ratings for concentration and relaxation, poorer performance on the DSST, greater CNV magnitude, faster peak alpha frequency and lower delta, theta and beta power. These differences persisted after caffeine ingestion and overall differences between the groups on these measures were significant (P < 0.01-.001). Post-dose, but not pre-dose, scores for vigilance and TR were significantly lower overall in poor compared with normal sleepers. Despite the baseline differences between poor and normal sleepers, the changes following caffeine administration were similar in direction and magnitude in both groups.
Apnea of prematurity is one of the most common problems in the neonatal intensive care unit. Management of premature infants with apnea involves pharmacologic and nonpharmacologic therapies. Drugs such as theophylline and caffeine are used when nonpharmacologic measures are ineffective. The article discusses the different types of apnea seen in premature infants, how these drugs affect premature infants, how to recognize early signs of toxicity, and implications for nursing assessment and management.