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The ergogenic effect of acute caffeine ingestion has been widely investigated; however, scientific information regarding tolerance to the performance benefits of caffeine, when ingested on a day-to-day basis, is scarce. The aim of this investigation was to determine the time course of tolerance to the ergogenic effects of a moderate dose of caffeine. Eleven healthy active participants took part in a cross-over, double-blind, placebo-controlled experiment. In one treatment, they ingested 3 mg/kg/day of caffeine for 20 consecutive days while in another they ingested a placebo for 20 days. Each substance was administered daily in an opaque unidentifiable capsule, and the experimental trials started 45 min after capsule ingestion. Two days before, and three times per week during each 20-day treatment, aerobic peak power was measured with an incremental test to volitional fatigue (25 W/min) and aerobic peak power was measured with an adapted version of the Wingate test (15 s). In comparison to the placebo, the ingestion of caffeine increased peak cycling power in the incremental exercise test by ~4.0 ±1.3% for the first 15 days (P<0.05) but then this ergogenic effect lessened. Caffeine also increased peak cycling power during the Wingate test on days 1, 4, 15, and 18 of ingestion by ~4.9 ±0.9% (P<0.05). In both tests, the magnitude of the ergogenic effect of caffeine vs. placebo was higher on the first day of ingestion and then progressively decreased. These results show a continued ergogenic effect with the daily ingestion of caffeine for 15–18 days; however, the changes in the magnitude of this effect suggest progressive tolerance. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effects of a single instance of caffeine intake on neurocognitive functions and driving performance in healthy subjects using an established cognitive battery and a driving simulator system. Methods: This study was conducted in a double-blind, randomized, placebo-controlled manner from February 19, 2016 to August 6, 2016. Caffeine intake was discontinued 3 days prior to the study. Participants were randomly assigned to receive 200-mg doses of caffeine or a placebo. Thirty minutes after administration, cognitive functions were evaluated via the Symbol Digit Coding Test (SDC), the Stroop Test (ST), the Shifting Attention Test (SAT) and the Four Part Continuous Performance Test (FPCPT). After the cognitive function tests were conducted, driving performance was evaluated using a driving simulator. We measured the brake reaction time (BRT) in the Harsh-braking test and the standard deviation of the lateral position (SDLP) in the Road-tracking test. Results: Of 100 randomized subjects, 50 (50%) of 100 in the caffeine group and 50 (50%) of 100 in the placebo group completed the study. Participants in the caffeine group had more correct responses than participants in the placebo group on the SAT (P = 0.03) and made fewer errors (P = 0.02). Participants in the caffeine group exhibited shorter times in the Harsh-braking test than participants in the placebo group (P = 0.048). Conclusions: A single instance of caffeine intake changed some neurocognitive functions and driving performance in healthy volunteers. Trial registration: . [ABSTRACT FROM AUTHOR]

Background: Caffeine is routinely given to preterm infants hours after birth to treat apnea of prematurity. In view of it’s success, earlier administration in the delivery room is being considered, but little is known about how caffeine may effect the cardiovascular changes during the fetal to neonatal transition. Our aim was to determine the effect of prenatal caffeine administration on haemodynamic parameters in ventilated preterm lambs immediately after birth. Methods: Catheters (carotid artery and jugular vein) and ultrasonic flow probes (pulmonary artery and carotid artery) were implanted in preterm lambs (~126 ±2 days of gestation; term is 147 days), immediately before delivery by caesarean section. Before the cord was clamped, lambs were intubated and a caffeine (10mg/kg caffeine-base; n = 9) or saline (n = 5) infusion was given intravenously to the ewe and lamb over a 15-minute period. Two minutes after clamping the cord, ventilation commenced with a sustained inflation (35 cm H2O for 30 seconds) followed by ventilation for 30 minutes (target tidal volume of 6-8ml/kg). Results: Blood gas parameters and rectal body temperature were not different between the two groups. Changes in pulmonary blood flow (PBF) and carotid blood flow (CBF) did not differ significantly between groups. PBF increased significantly after ventilation onset in both groups (caffeine p = 0.022, saline p <0.001) and remained elevated thereafter. CBF did not increase but decreased after SI in the caffeine group. Blood pressure, heart rate, and peripheral oxygen saturation did not differ between groups at any stage of the study. Conclusion: Prenatal caffeine infusion had no significant effect on acute haemodynamic parameters in ventilated preterm lambs during the cardiorespiratory transition. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this investigation was to analyze the influence of the genetic variations of the -163C>A polymorphism of the CYP1A2 gene on the ergogenic effects of caffeine in elite basketball players. Methods: Nineteen elite basketball players (10 men and 9 women) ingested 3 mg⋅kg-1 of caffeine or a placebo 60 min before performing 10 repetitions of the following series: the Abalakov jump test followed by the Change-of-Direction and Acceleration Test (CODAT). The players then competed in a 20-min simulated basketball game. Self-perceived performance and side effects were recorded by questionnaires after the trials. The effects of caffeine on basketball performance were established according to players’ CYP1A2 genotype (rs762551): AA homozygotes (n = 10) and C-allele carriers (n = 9). Results: In the 10 repetitions, caffeine increased Abalakov jump height by a mean of 2.9±3.6% in AA homozygotes (p = 0.03) while this effect did not reach statistical significance for C-allele carriers (2.3 ± 6.8%; p = 0.33). Caffeine did not affect sprint time in the CODAT test in either genotype group but it increased the number of impacts performed during the simulated game in both AA homozygotes (4.1 ± 5.3%; p = 0.02) and C-allele carriers (3.3 ± 3.2%; p = 0.01). During the 24 h following the test, AA homozygotes tended to experience increased insomnia with caffeine while C-allele carriers did not present this effect. The remaining variables were unaffected by the genotype. Conclusion: The CYP1A2 -163C>A polymorphism minimally altered the ergogenicity derived from the consumption of a moderate dose of caffeine in elite basketball players. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that supports the benefits of early use of caffeine in preterm neonates with RDS; however, no formal recommendations specifying the exact timing of therapy initiation have been provided. Objectives: We compared neonatal outcomes in infants receiving early (initial dose on the 1st day of life) and late (initial dose on day 2+ of life) caffeine therapy. Methods: Using data from a prospective, cohort study, we identified 986 infants ≤32 weeks’ gestation with RDS and assessed the timing of caffeine therapy initiation, need for ventilatory support, mortality and incidence of typical complications of prematurity. To adjust for baseline severity, the early and late caffeine groups were propensity score (PS) matched to 286 infants (1:1). Clinical outcomes were compared between the PS-matched groups. Results: Early treatment with caffeine citrate was associated with a significantly reduced need for invasive ventilation (71.3% vs 83.2%; P = 0.0165) and total duration of mechanical ventilation (mean 5 ± 11.1 days vs 10.8 ± 14.6 days; P = 0.0000) and significantly lower odds of intraventricular hemorrhage (IVH) (OR 0.4827; 95% CI 0.2999–0.7787) and patent ductus arteriosus (PDA) (OR 0.5686; 95% CI 0.3395–0.9523). The incidence of bronchopulmonary dysplasia (BPD) (36.4% vs 45.8%) and rates of moderate and severe BPD were not significantly different between the two groups. The mortality rates were comparable between the two groups (8.6% vs 8.5%, P = ns) Conclusion: Early caffeine initiation was associated with a decreased need for invasive ventilatory support and lower incidence of IVH and PDA. [ABSTRACT FROM AUTHOR]

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours). In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau), in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored. [ABSTRACT FROM AUTHOR]

We investigated whether caffeine ingestion before submaximal exercise bouts would affect supramaximal oxygen demand and maximal accumulated oxygen deficit (MAOD), and if caffeine-induced improvement on the anaerobic capacity (AC) could be detected by different methods. Nine men took part in several submaximal and supramaximal exercise bouts one hour after ingesting caffeine (5 mg·kg-1) or placebo. The AC was estimated by MAOD, alternative MAOD, critical power, and gross efficiency methods. Caffeine had no effect on exercise endurance during the supramaximal bout (caffeine: 131.3 ± 21.9 and placebo: 130.8 ± 20.8 s, P = 0.80). Caffeine ingestion before submaximal trials did not affect supramaximal oxygen demand and MAOD compared to placebo (7.88 ± 1.56 L and 65.80 ± 16.06 kJ vs. 7.89 ± 1.30 L and 62.85 ± 13.67 kJ, P = 0.99). Additionally, MAOD was similar between caffeine and placebo when supramaximal oxygen demand was estimated without caffeine effects during submaximal bouts (67.02 ± 16.36 and 62.85 ± 13.67 kJ, P = 0.41) or when estimated by alternative MAOD (56.61 ± 8.49 and 56.87 ± 9.76 kJ, P = 0.91). The AC estimated by gross efficiency was also similar between caffeine and placebo (21.80 ± 3.09 and 20.94 ± 2.67 kJ, P = 0.15), but was lower in caffeine when estimated by critical power method (16.2 ± 2.6 vs. 19.3 ± 3.5 kJ, P = 0.03). In conclusion, caffeine ingestion before submaximal bouts did not affect supramaximal oxygen demand and consequently MAOD. Otherwise, caffeine seems to have no clear positive effect on AC. [ABSTRACT FROM AUTHOR]

Objectives: To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca). Methods: Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. Results: Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. Conclusions: Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the effects of caffeine on physiological responses to submaximal exercise, with a focus on blood lactate concentration ([BLa]). Methods: Using a randomised, single-blind, crossover design; 16 endurance-trained, male cyclists (age: 38 ± 8 years; height: 1.80 ± 0.05 m; body mass: 76.6 ± 7.8 kg; : 4.3 ± 0.6 L∙min-1) completed four trials on an electromagnetically-braked cycle ergometer. Each trial consisted of a six-stage incremental test (3 minute stages) followed by 30 minutes of passive recovery. One hour before trials 2–4, participants ingested a capsule containing 5 mg∙kg-1 of either caffeine or placebo (maltodextrin). Trials 2 and 3 were designed to evaluate the effects of caffeine on various physiological responses during exercise and recovery. In contrast, Trial 4 was designed to evaluate the effects of caffeine on [BLa] during passive recovery from an end-exercise concentration of 4 mmol∙L-1. Results: Relative to placebo, caffeine increased [BLa] during exercise, independent of exercise intensity (mean difference: 0.33 ± 0.41 mmol∙L-1; 95% likely range: 0.11 to 0.55 mmol∙L-1), but did not affect the time-course of [BLa] during recovery (p = 0.604). Caffeine reduced ratings of perceived exertion (mean difference: 0.5 ± 0.7; 95% likely range: 0.1 to 0.9) and heart rate (mean difference: 3.6 ± 4.2 b∙min-1; 95% likely range: 1.3 to 5.8 b∙min-1) during exercise, with the effect on the latter dissipating as exercise intensity increased. Supplement × exercise intensity interactions were observed for respiratory exchange ratio (p = 0.004) and minute ventilation (p = 0.034). Conclusions: The results of the present study illustrate the clear, though often subtle, effects of caffeine on physiological responses to submaximal exercise. Researchers should be aware of these responses, particularly when evaluating the physiological effects of various experimental interventions. [ABSTRACT FROM AUTHOR]

The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61) exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to investigate whether caffeine intake is associated with urinary incontinence (UI) and quality of life (QOL) in Korean postmenopausal women. Materials and Methods: We included 4,028 postmenopausal women who had participated in the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). From the KNHANES questionnaire data, we ascertained the UI status of participants, defined as self-reported or medically diagnosed UI, and calculated their total daily caffeine intake through questions regarding the frequency of food consumption. The EuroQoL-5 Dimension (EQ-5D) descriptive system was used to evaluate QOL among the study population. Results: The mean age of the study population was 63.19±0.25 years. Among the 4,028 women, the prevalence of medically diagnosed UI was 2.6% (n = 151), the prevalence of self-reported UI was 11.9% (n = 483), and the lifetime prevalence of UI was 15.8% (n = 639). In the study population, the presence of UI was not significantly different by age group, but daily caffeine consumption and the percentage of caffeine consumer decreased with age (P<0.001). Higher caffeine intake led to significantly higher prevalence of both medically diagnosed UI (p = 0.012) and self-reported UI (p = 0.040) in the study population. Even after adjusting for factors including age, parity, smoking status, hypertension and diabetes in logistic regression analysis, the positive association between caffeine intake and UI prevalence was observed in both medically diagnosed UI and self-reported UI (P = 0.017) among participants. In a subgroup analysis for EQ-5D (using continuous variables) in which we categorized participants into four groups according to UI presence and caffeine consumption, the EQ-5D scores were lower in the caffeine non-user group with UI than in the caffeine consumer group with or without UI. Conclusion: In a sample of Korean postmenopausal women, the prevalence of UI increased with higher caffeine consumption. Additionally, QOL was lower in caffeine non-users with UI than in the caffeine consumer groups. However, additional prospective studies are required to identify clear causation between caffeine consumption, UI prevalence and QOL. [ABSTRACT FROM AUTHOR]

We have demonstrated that the activation of apoptosis-like programmed cell death (AL-PCD) was a secondary result of caffeine (CF) induced premature chromosome condensation (PCC) in hydroxyurea-synchronized Vicia faba root meristem cells. Initiation of the apoptotic-like cell degradation pathway seemed to be the result of DNA damage generated by treatment with hydroxyurea (HU) [double-stranded breaks (DSBs) mostly] and co-treatment with HU/CF [single-stranded breaks (SSBs) mainly]. A single chromosome comet assay was successfully used to study different types of DNA damage (neutral variant–DSBs versus alkaline–DSBs or SSBs). The immunocytochemical detection of H2AXS139Ph and PARP-2 were used as markers for DSBs and SSBs, respectively. Acridine orange and ethidium bromide (AO/EB) were applied for quantitative immunofluorescence measurements of dead, dying and living cells. Apoptotic-type DNA fragmentation and positive TUNEL reaction finally proved that CF triggers AL-PCD in stressed V. faba root meristem cells. In addition, the results obtained under transmission electron microscopy (TEM) further revealed apoptotic-like features at the ultrastructural level of PCC-type cells: (i) extensive vacuolization; (ii) abnormal chromatin condensation, its marginalization and concomitant degradation; (iii) formation of autophagy-like vesicles (iv) protoplast shrinkage (v) fragmentation of cell nuclei and (vi) extensive degeneration of the cells. The results obtained have been discussed with respect to the vacuolar/autolytic type of plant-specific AL-PCD. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the effect of caffeine ingestion on performance and estimated energy system contribution during simulated taekwondo combat and on post-exercise parasympathetic reactivation. Methods: Ten taekwondo athletes completed two experimental sessions separated by at least 48 hours. Athletes consumed a capsule containing either caffeine (5 mg∙kg-1) or placebo (cellulose) one hour before the combat simulation (3 rounds of 2 min separated by 1 min passive recovery), in a double-blind, randomized, repeated-measures crossover design. All simulated combat was filmed to quantify the time spent fighting in each round. Lactate concentration and rating of perceived exertion were measured before and after each round, while heart rate (HR) and the estimated contribution of the oxidative (WAER), ATP-PCr (WPCR), and glycolytic (W[La-]) systems were calculated during the combat simulation. Furthermore, parasympathetic reactivation after the combat simulation was evaluated through 1) taking absolute difference between the final HR observed at the end of third round and the HR recorded 60-s after (HRR60s), 2) taking the time constant of HR decay obtained by fitting the 6-min post-exercise HRR into a first-order exponential decay curve (HRRτ), or by 3) analyzing the first 30-s via logarithmic regression analysis (T30). Results: Caffeine ingestion increased estimated glycolytic energy contribution in relation to placebo (12.5 ± 1.7 kJ and 8.9 ± 1.2 kJ, P = 0.04). However, caffeine did not improve performance as measured by attack number (CAF: 26. 7 ± 1.9; PLA: 27.3 ± 2.1, P = 0.48) or attack time (CAF: 33.8 ± 1.9 s; PLA: 36.6 ± 4.5 s, P = 0.58). Similarly, RPE (CAF: 11.7 ± 0.4 a.u.; PLA: 11.5 ± 0.3 a.u., P = 0.62), HR (CAF: 170 ± 3.5 bpm; PLA: 174.2 bpm, P = 0.12), oxidative (CAF: 109.3 ± 4.5 kJ; PLA: 107.9 kJ, P = 0.61) and ATP-PCr energy contributions (CAF: 45.3 ± 3.4 kJ; PLA: 46.8 ± 3.6 kJ, P = 0.72) during the combat simulation were unaffected. Furthermore, T30 (CAF: 869.1 ± 323.2 s; PLA: 735.5 ± 232.2 s, P = 0.58), HRR60s (CAF: 34 ± 8 bpm; PLA: 38 ± 9 bpm, P = 0.44), HRRτ (CAF: 182.9 ± 40.5 s, PLA: 160.3 ± 62.2 s, P = 0.23) and HRRamp (CAF: 70.2 ± 17.4 bpm; PLA: 79.2 ± 17.4 bpm, P = 0.16) were not affected by caffeine ingestion. Conclusions: Caffeine ingestion increased the estimated glycolytic contribution during taekwondo combat simulation, but this did not result in any changes in performance, perceived exertion or parasympathetic reactivation. [ABSTRACT FROM AUTHOR]

Cerebral metabolism is critically dependent on the regulation of cerebral blood flow (CBF), so it would be expected that vascular mechanisms that play a critical role in CBF regulation would be tightly conserved across individuals. However, the relationships between blood pressure (BP) and cerebral blood velocity fluctuations exhibit inter-individual variations consistent with heterogeneity in the integrity of CBF regulating systems. Here we sought to determine the nature and consistency of dynamic cerebral autoregulation (dCA) during the application of oscillatory lower body negative pressure (OLBNP). In 18 volunteers we recorded BP and middle cerebral artery blood flow velocity (MCAv) and examined the relationships between BP and MCAv fluctuations during 0.03, 0.05 and 0.07Hz OLBNP. dCA was characterised using project pursuit regression (PPR) and locally weighted scatterplot smoother (LOWESS) plots. Additionally, we proposed a piecewise regression method to statistically determine the presence of a dCA curve, which was defined as the presence of a restricted autoregulatory plateau shouldered by pressure-passive regions. Results show that LOWESS has similar explanatory power to that of PPR. However, we observed heterogeneous patterns of dynamic BP-MCAv relations with few individuals demonstrating clear evidence of a dCA central plateau. Thus, although BP explains a significant proportion of variance, dCA does not manifest as any single characteristic BP-MCAv function. [ABSTRACT FROM AUTHOR]

This study tests the hypothesis that high levels of high-frequency heart rate variability (HF-HRV) predisposes individuals to affiliate with new groups. Resting cardiac physiological recordings were taken before and after experimental sessions to measure trait high-frequency heart rate variability as an index of dispositional autonomic influence on heart rate. Following an experimental manipulation of priming of caring-related words, participants engaged in a minimal group paradigm, in which they imagined being a member of one of two arbitrary groups, allocated money to members of the two groups, and rated their affiliation with the groups. High levels of HF-HRV were associated with ingroup favouritism while allocating money, an effect largely attributable to a positive relationship between HF-HRV and allocation of money to the ingroup, and less due to a negative relationship between HF-HRV and money allocation to the outgroup. HF-HRV was also associated with increased self-reported affiliation feelings for the ingroup but was unrelated to feelings towards the outgroup. These effects remained substantial even after controlling for age, gender, BMI, mood, caffeine consumption, time of day of data collection, smoking and alcohol behaviour, and respiration rate. Further, the effects were observed regardless of whether participants were primed with caring-related words or not. This study is the first to bridge a long history of research on ingroup favouritism to the relatively recent body of research on cardiac vagal tone by uncovering a positive association between HF-HRV and affiliation with a novel group. [ABSTRACT FROM AUTHOR]

Objectives: Caffeine is consumed by more than 85% of adults and little is known about its role on erectile dysfunction (ED) in population-based studies. We investigated the association of caffeine intake and caffeinated beverages with ED, and whether these associations vary among comorbidities for ED. Material and Method: Data were analyzed for 3724 men (≥20 years old) who participated in the National Health and Nutrition Examination Survey (NHANES). ED was assessed by a single question during a self-paced, computer-assisted self-interview. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable logistic regression analyses using appropriate sampling weights were conducted. Results: We found that men in the 3rd (85-170 mg/day) and 4th (171-303 mg/day) quintiles of caffeine intake were less likely to report ED compared to men in the lowest 1st quintile (0-7 mg/day) [OR: 0.58; 95% CI, 0.37–0.89; and OR: 0.61; 95% CI, 0.38–0.97, respectively], but no evidence for a trend. Similarly, among overweight/obese and hypertensive men, there was an inverse association between higher quintiles of caffeine intake and ED compared to men in the lowest 1st quintile, P≤0.05 for each quintile. However, only among men without diabetes we found a similar inverse association (Ptrend = 0.01). Conclusion: Caffeine intake reduced the odds of prevalent ED, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive, but not among diabetic men. Yet, these associations are warranted to be investigated in prospective studies. [ABSTRACT FROM AUTHOR]

Hepatic stellate cell (HSC) activation is an essential event during alcoholic liver fibrosis. Evidence suggests that adenosine aggravates liver fibrosis via the adenosine A2A receptor (A2AR). Caffeine, which is being widely consumed during daily life, inhibits the action of adenosine. In this study, we attempted to validate the hypothesis that caffeine influences acetaldehyde-induced HSC activation by acting on A2AR. Acetaldehyde at 50, 100, 200, and 400 μM significantly increased HSC-T6 cells proliferation, and cell proliferation reached a maximum at 48 h after exposure to 200 μM acetaldehyde. Caffeine and the A2AR antagonist ZM241385 decreased the cell viability and inhibited the expression of procollagen type I and type III in acetaldehyde-induced HSC-T6 cells. In addition, the inhibitory effect of caffeine on the expression of procollagen type I was regulated by A2AR-mediated signal pathway involving cAMP, PKA, SRC, and ERK1/2. Interestingly, caffeine’s inhibitory effect on the expression of procollagen type III may depend upon the A2AR-mediated P38 MAPK-dependent pathway. Conclusions: Caffeine significantly inhibited acetaldehyde-induced HSC-T6 cells activation by distinct A2AR mediated signal pathway via inhibition of cAMP-PKA-SRC-ERK1/2 for procollagen type I and via P38 MAPK for procollagen type III. [ABSTRACT FROM AUTHOR]

Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2–4 cups of coffee in humans. After dams gave birth, offspring were examined at 8–10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation. [ABSTRACT FROM AUTHOR]

There is consistent evidence supporting the ergogenic effects of caffeine for endurance based exercise. However, whether caffeine ingested through coffee has the same effects is still subject to debate. The primary aim of the study was to investigate the performance enhancing effects of caffeine and coffee using a time trial performance test, while also investigating the metabolic effects of caffeine and coffee. In a single-blind, crossover, randomised counter-balanced study design, eight trained male cyclists/triathletes (Mean±SD: Age 41±7y, Height 1.80±0.04 m, Weight 78.9±4.1 kg, VO2 max 58±3 ml•kg−1•min−1) completed 30 min of steady-state (SS) cycling at approximately 55% VO2max followed by a 45 min energy based target time trial (TT). One hour prior to exercise each athlete consumed drinks consisting of caffeine (5 mg CAF/kg BW), instant coffee (5 mg CAF/kg BW), instant decaffeinated coffee or placebo. The set workloads produced similar relative exercise intensities during the SS for all drinks, with no observed difference in carbohydrate or fat oxidation. Performance times during the TT were significantly faster (∼5.0%) for both caffeine and coffee when compared to placebo and decaf (38.35±1.53, 38.27±1.80, 40.23±1.98, 40.31±1.22 min respectively, p<0.05). The significantly faster performance times were similar for both caffeine and coffee. Average power for caffeine and coffee during the TT was significantly greater when compared to placebo and decaf (294±21 W, 291±22 W, 277±14 W, 276±23 W respectively, p<0.05). No significant differences were observed between placebo and decaf during the TT. The present study illustrates that both caffeine (5 mg/kg/BW) and coffee (5 mg/kg/BW) consumed 1 h prior to exercise can improve endurance exercise performance. [ABSTRACT FROM AUTHOR]

Background: The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P-TEFb) from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing. Methodology/Principal Findings: We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3-kinase-related protein kinases, because inhibition of phosphatidylinositol 3-kinase family members (ATM, ATR and DNA-PK) neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage. Conclusion/Significance: Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated. [ABSTRACT FROM AUTHOR]

Background: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). Methodology/Principal Findings: MBF was measured with 15O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P<0.005), remote (2.40±0.70 vs. 1.78±0.46, P<0.001) and in stenotic segments (1.90±0.41 vs. 1.38±0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). Conclusions: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls. [ABSTRACT FROM AUTHOR]

Mice over-expressing the α1-subunit (pore) of the L-type Ca2+ channel (α1CTG) by 4months (mo) of age exhibit an enlarged heart, hypertrophied myocytes, increased Ca2+ current and Ca2+ transient amplitude, but a normal SR Ca2+ load. With advancing age (8-11 mo), some mice demonstrate advanced hypertrophy but are not in congestive heart failure (NFTG), while others evolve to frank dilated congestive heart failure (FTG). We demonstrate that older NFTG myocytes exhibit a hypercontractile state over a wide range of stimulation frequencies, but maintain a normal SR Ca2+ load compared to age matched non-transgenic (NTG) myocytes. However, at high stimulation rates (2-4 Hz) signs of diastolic contractile failure appear in NFTG cells. The evolution of frank congestive failure in FTG is accompanied by a further increase in heart mass and myocyte size, and phospholamban and ryanodine receptor protein levels and phosphorylation become reduced. In FTG, the SR Ca2+ load increases and Ca2+ release following excitation, increases further. An enhanced NCX function in FTG, as reflected by an accelerated relaxation of the caffeine-induced Ca2+ transient, is insufficient to maintain a normal diastolic Ca2+ during high rates of stimulation. Although a high SR Ca2+ release following excitation is maintained, the hypercontractile state is not maintained at high rates of stimulation, and signs of both systolic and diastolic contractile failure appear. Thus, the dilated cardiomyopathy that evolves in this mouse model exhibits signs of both systolic and diastolic failure, but not a deficient SR Ca2+ loading or release, as occurs in some other cardiomyopathic models. [ABSTRACT FROM AUTHOR]

The alerting effects of both caffeine and short wavelength (blue) light have been consistently reported. The ability of blue light to enhance alertness and cognitive function via non-image forming neuropathways have been suggested as a non-pharmacological countermeasure for drowsiness across a range of occupational settings. Here we compare and contrast the alerting and psychomotor effects of 240 mg of caffeine and a 1-h dose of ~40 lx blue light in a non-athletic population. Twenty-one healthy subjects performed a computer-based psychomotor vigilance test before and after each of four randomly assigned trial conditions performed on different days: white light/placebo; white light/240 mg caffeine; blue light/placebo; blue light/240 mg caffeine. The Karolinska Sleepiness Scale was used to assess subjective measures of alertness. Both the caffeine only and blue light only conditions enhanced accuracy in a visual reaction test requiring a decision and an additive effect was observed with respect to the fastest reaction times. However, in a test of executive function, where a distraction was included, caffeine exerted a negative effect on accuracy. Furthermore, the blue light only condition consistently outperformed caffeine when both congruent and incongruent distractions were presented. The visual reactions in the absence of a decision or distraction were also enhanced in the blue light only condition and this effect was most prominent in the blue-eyed participants. Overall, blue light and caffeine demonstrated distinct effects on aspects of psychomotor function and have the potential to positively influence a range of settings where cognitive function and alertness are important. Specifically, despite the widespread use of caffeine in competitive sporting environments, the possible impact of blue light has received no research attention. [ABSTRACT FROM AUTHOR]