Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run.

RATIONALE: Intense exercise promotes fatigue and can impair cognitive function, particularly toward the end of competition when decision-making is often critical for success. For this reason, athletes often ingest caffeinated energy drinks prior to or during exercise to help them maintain focus, reaction time, and cognitive function during competition. However, caffeine habituation and genetic sensitivity to caffeine (CA) limit efficacy. Paraxanthine (PX) is a metabolite of caffeine reported to possess nootropic properties. This study examined whether ingestion of PX with and without CA affects pre- or post-exercise cognitive function. METHODS: 12 trained runners were randomly assigned to consume in a double-blind, randomized, and crossover manner 400 mg of a placebo (PL); 200 mg of PL + 200 mg of CA; 200 mg of PL + 200 mg of PX (ENFINITY®, Ingenious Ingredients); or 200 mg PX + 200 mg of CA (PX+CA) with a 7-14-day washout between treatments. Participants donated fasting blood samples and completed pre-supplementation (PRE) side effects questionnaires, the Berg-Wisconsin Card Sorting Test (BCST), and the Psychomotor Vigilance Task Test (PVTT). Participants then ingested the assigned treatment and rested for 60 minutes, repeated tests (PRE-EX), performed a 10-km run on a treadmill at a competition pace, and then repeated tests (POST-EX). Data were analyzed using General Linear Model (GLM) univariate analyses with repeated measures and percent changes from baseline with 95% confidence intervals. RESULTS: BCST correct responses in the PX treatment increased from PRE-EX to POST-EX (6.8% [1.5, 12.1], p = 0.012). The error rate in the PL (23.5 [-2.8, 49.8] %, p = 0.078) and CA treatment (31.5 [5.2, 57.8] %, p = 0.02) increased from PRE-EX values with POST-EX errors tending to be lower with PX treatment compared to CA (-35.7 [-72.9, 1.4] %, p = 0.059). POST-EX perseverative errors with PAR rules were significantly lower with PX treatment than with CA (-26.9 [-50.5, -3.4] %, p = 0.026). Vigilance analysis revealed a significant interaction effect in Trial #2 mean reaction time values (p = 0.049, ηp2 = 0.134, moderate to large effect) with POST-EX reaction times tending to be faster with PX and CA treatment. POST-EX mean reaction time of all trials with PX treatment was significantly faster than PL (-23.2 [-43.4, -2.4] %, p = 0.029) and PX+CA (-29.6 [-50.3, -8.80] %, p = 0.006) treatments. There was no evidence that PX ingestion adversely affected ratings of side effects associated with stimulant intake or clinical blood markers. CONCLUSIONS: Results provide some evidence that pre-exercise PX ingestion improves prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance. Adding CA to PX did not provide additional benefits. Therefore, PX ingestion may serve as a nootropic alternative to CA.

Caffeine Improves Sprint Time in Simulated Freestyle Swimming Competition but Not the Vertical Jump in Female Swimmers.

Caffeine (CAF) has been shown to be an effective ergogenic aid in enhancing sports performance, including vertical jump (VJ), sprint, balance, agility, and freestyle swimming performance (FSP). However, whether acute CAF supplementation improves FSP in moderately trained female swimmers has not been well documented. Therefore, this study aimed to investigate the effects of CAF intake on vertical jump, balance, auditory reaction time (ART), and swimming performance in female swimmers. In a double-blind, cross-over design, eight moderately trained female swimmers (age: 21.3 ± 1.4 years, height: 161.2 ± 7.1 cm, body mass: 56.3 ± 6.7 kg, body mass index (BMI): 21.9 ± 1.3 kg/m2, and habitual CAF intake: 246.4 ± 111.4 mg/day) ingested caffeine (CAF) (6 mg/kg) or a placebo (PLA) 60 min before completing VJ, balance, ART, and 25/50 m FSP. CAF supplementation resulted in a significantly lower time both in 25m (p = 0.032) and 50m (p = 0.033) FSP. However, CAF resulted in no significant difference in VJ, ART, and RPE (p > 0.05). Balance test results showed a non-significant moderate main effect (d = 0.58). In conclusion, CAF seems to reduce time in short-distance swimming performances, which could be the determinant of success considering the total time of the race. Thus, we recommend coaches and practitioners incorporate CAF into swimmers' nutrition plans before competitions, which may meet the high performance demands.

Caffeinated Chewing Gum Improves Basketball Shooting Accuracy and Physical Performance Indicators of Trained Basketball Players: A Double-Blind Crossover Trial.

(1) Background: This study investigated the effects of caffeinated chewing gum on the basketball-specific performance of trained basketball players. A double-blind, randomized crossover design was employed. (2) Methods: Fifteen participants (age: 20.9 ± 1.0 years; height: 180.9 ± 5.4 cm; mass: 77.2 ± 7.5 kg; training age: 8.2 ± 0.3 years) were recruited and divided into a caffeine trial (CAF) and placebo trial (PL). The participants in the CAF trial chewed gum containing 3 mg/kg of caffeine for 10 min, while those in the PL trial chewed a placebo gum without caffeine. Following a 15 min rest, all the participants completed basketball-specific performance tests. (3) Results: The free throw accuracy for the CAF trial was significantly higher than that for the PL trial (CAF: 79.0 ± 4.31%; PL: 73.0 ± 9.16%; p = 0.012; Cohen's d = 0.94). Additionally, the CAF trial demonstrated significantly better performance in the 20 m segmented dash (CAF: 2.94 ± 1.12 s; PL: 3.13 ± 0.10 s; p < 0.001; Cohen's d =1.8) and squats (p < 0.05), and exhibited lower fatigue indexes (CAF: 3.6 ± 1.6%; PL: 5.2 ± 1.6%; p = 0.009; Cohen's d =1.0). (4) Conclusions: These findings suggest that chewing gum containing 3 mg/kg of caffeine offers moderate-to-large improvements in key performance aspects relevant to professionally trained basketball players.

Effects of Acute Ingestion of Caffeine Capsules on Muscle Strength and Muscle Endurance: A Systematic Review and Meta-Analysis.

This study aimed to explore the effects of acute ingestion of caffeine capsules on muscle strength and muscle endurance. We searched the PubMed, Web of Science, Cochrane, Scopus, and EBSCO databases. Data were pooled using the weighted mean difference (WMD) and 95% confidence interval. Fourteen studies fulfilled the inclusion criteria. The acute ingestion of caffeine capsules significantly improved muscle strength (WMD, 7.09, p < 0.00001) and muscle endurance (WMD, 1.37; p < 0.00001), especially in males (muscle strength, WMD, 7.59, p < 0.00001; muscle endurance, WMD, 1.40, p < 0.00001). Subgroup analyses showed that ≥ 6 mg/kg body weight of caffeine (WMD, 6.35, p < 0.00001) and ingesting caffeine 45 min pre-exercise (WMD, 8.61, p < 0.00001) were more effective in improving muscle strength, with the acute ingestion of caffeine capsules having a greater effect on lower body muscle strength (WMD, 10.19, p < 0.00001). In addition, the acute ingestion of caffeine capsules had a greater effect in moderate-intensity muscle endurance tests (WMD, 1.76, p < 0.00001). An acute ingestion of caffeine capsules significantly improved muscle strength and muscle endurance in the upper body and lower body of males.

Chronic caffeine decreases anxiety-like behavior in the marble burying task in adolescent rats.

Exposure to chronic caffeine during adolescence has been shown to produce decreased anxiety-like behaviors in rats as well as decreased immobility in the forced swim test (FST) suggesting an antidepressant-like effect. The effects of chronic caffeine on anxiety, however, have been found to be test-dependent and sexually dimorphic. In addition, decreased immobility in the FST has been argued to reflect a shift toward active coping behavior as opposed to an antidepressant-like effect. In order to further characterize the effects of adolescent caffeine exposure, the present experiment assessed the effects of caffeine on marble burying behavior in a two-zone marble burying task. There was no difference in the amount of time rats spent in the two zones failing to support a shift in coping strategy. Caffeine-exposed rats spent less time engaged in marble burying activity and buried slightly fewer marbles, suggesting an anxiolytic effect of caffeine. In addition, caffeine treated rats spent less time engaged in nondirected burying and slightly more time actively engaging with the marbles; however, these effects appeared to be sexually dimorphic as they were driven by larger changes in the females. Overall, these results support an anxiolytic effect of adolescent caffeine, with female behavior appearing to be more affected by caffeine than males.

Association of Caffeine Daily Dose With Respiratory Outcomes in Preterm Neonates: A Retrospective Cohort Study.

Apnea and poor respiratory drive increase the risk of extubation failure (EF) and prolonged invasive mechanical ventilation (IMV) in preterm neonates (pre-nates) with respiratory distress. Caffeine citrate (CC) is often prescribed for pre-nates in doses of 5-10 mg/kg in 24 h. This study aimed to evaluate the most effective dosage regimen (5 mg/kg/day vs >5-10 mg/kg/day) to prevent apnea and EF with minimal caffeine-associated potential side effects (CC-APSEs) in pre-nates. This one-year retrospective cohort study included all the eligible neonates admitted to NICU and received CC-therapy till 28 days of life (DOL) or discharge. Based on CC-daily dose formed LD-caffeine-group (5 mg/kg/day) and HD-caffeine-group (>5-10 mg/kg/day). Antenatal, prenatal, and postnatal characteristics, CC-regimen, comorbidities, and CC-APSEs were compared between the groups. Predictors of apnea and EF were analyzed through logistic regression. There were 181 and 72 neonates in the LD and HD-caffeine-groups respectively. In HD-caffeine-group daily CC-dose was 7 to 7.5 mg/kg/day in 93% of neonates and >7.5 to 10 mg/kg/day in only 7%. Significantly fewer neonates experienced apnea and EF in the HD-caffeine-group till 28DOL or discharge. This difference was even greater in the subgroup of ≤28 weeks GA (15.6% vs 40.0%; P < .01). In HD-caffeine-group the incidence of severe/moderate-BPD was significantly lower and the frequency of CC-APSEs was higher. Multivariate analysis showed that; the smaller the GA higher the risk of apnea (AOR = 0.510, 95% CI 0.483-0.999) and EF (AOR = 0.787, 95% CI 0.411-0.997). The HD-caffeine was inversely associated with developing apnea (AOR = 0.244, 95% CI 0.053-0.291) and EF (AOR = 0.103, 95% CI 0.098-2.976). IMV-duration before extubation (AOR = 2.229, 95% CI 1.672-2.498) and severe/moderate-BPD (AOR = 2.410, 95%CI 1.104-2.952) had a high risk of EF. Initiating early HD-caffeine may prevent apnea and extubation failure in preterm neonates. Optimization of caffeine initiation time and dosages can be a safe and feasible approach to decrease the burden of neonatal respiratory morbidities.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

Change in Caffeine Consumption after Pandemic (CCAP-Study) among University Students: A Cross-Sectional Study from Italy.

(1) Background: The lockdown, imposed to limit the pandemic evolution, impacted the social habits and lifestyle of inhabitants also from many countries other than Italy. Caffeine consumption could be a useful option to improve mood, as the lockdown strongly affected mental health, particularly increasing anxiety and sleep disorders. (2) Methods: It was a cross-sectional study aimed to evaluate the change in caffeine consumption after the pandemic period in a sample of Italian University students. It investigated coffee and products containing caffeine consumption, the anxiety level by State Trait Anxiety Inventory (STAI) and sleep quality with the Insomnia Severity Index (ISS). (3) Results: A total of 404 participants were enrolled in the study. During the lockdown period, 23% of subjects consumed more coffee compared to the pre-pandemic period. Daily coffee consumption also changed after the lockdown period compared to the pre-pandemic period, with 36.1% of subjects that increased their consumption. Comparing other caffeine-based products, energizing supplement consumption showed a greater increase after the lockdown period than energy drinks. Regarding anxiety, subjects who reported increased coffee consumption reported higher STAI scores and ISS. (4) Conclusions: About a quarter of university students increased their consumption of caffeine-based products after the pandemic, reporting higher levels of anxiety and poor sleep quality.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Impact of Viloxazine Extended-Release Capsules (Qelbree®) on Select Cytochrome P450 Enzyme Activity and Evaluation of CYP2D6 Genetic Polymorphisms on Viloxazine Pharmacokinetics.

BACKGROUND AND OBJECTIVE: Viloxazine extended-release (ER) [Qelbree®] is a nonstimulant attention-deficit/hyperactivity disorder (ADHD) treatment. In vitro studies suggested potential for viloxazine to inhibit cytochrome 450 (CYP) enzymes 1A2, 2B6, 2D6 and 3A4. This clinical study therefore evaluated viloxazine ER effects on index substrates for CYP1A2, 2D6, and 3A4, and secondarily evaluated the impact of CYP2D6 polymorphisms on viloxazine pharmacokinetics. METHODS: Thirty-seven healthy subjects received a modified Cooperstown cocktail (MCC; caffeine 200 mg, dextromethorphan 30 mg, midazolam 0.025 mg/kg) on Day 1, viloxazine ER 900 mg/day on Days 3-5, and a combination of viloxazine ER 900 mg and MCC on Day 6. Viloxazine ER effects on MCC substrates were evaluated using analysis of variance. The impact of CYP2D6 genetic polymorphisms on steady-state viloxazine plasma concentrations was evaluated using Student's t test assessing pharmacokinetic parameter differences between poor versus extensive metabolizers. RESULTS: The least squares geometric mean ratio [GMR%] (90% CI) of MCC substrate + viloxazine ER/MCC substrate alone for caffeine maximum concentration (Cmax), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUCt), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC∞) was 99.11 (95.84-102.49), 436.15 (398.87-476.92), and 583.35 (262.41-1296.80), respectively; 150.76 (126.03-180.35), 185.76 (155.01-222.61), and 189.71 (160.37-224.42) for dextromethorphan Cmax, AUCt, and AUC∞, respectively; and 112.81 (104.71-121.54), 167.56 (153.05-183.45), and 168.91 (154.38-184.80) for midazolam Cmax, AUCt, and AUC∞, respectively. At steady state, viloxazine least squares GMR (90% CI) for poor/extensive CYP2D6 metabolizers were Cmax 120.70 (102.33-142.37) and area under the plasme concentration-time curve from time 0 to 24 hours (AUC0-24 125.66 (105.36-149.87)). CONCLUSION: Viloxazine ER is a strong CYP1A2 inhibitor and a weak CYP2D6 and CYP3A4 inhibitor. CYP2D6 polymorphisms did not meaningfully alter the viloxazine ER pharmacokinetic profile.

The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats.

OBJECTIVE: The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. MATERIALS AND METHODS: A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. RESULTS: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. CONCLUSION: It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.

Effect of Acute Sodium Bicarbonate and Caffeine Coingestion on Repeated-Sprint Performance in Recreationally Trained Individuals: A Randomized Controlled Trial.

INTRODUCTION: The acute and isolated ingestion of sodium bicarbonate (NaHCO3) and caffeine (CAF) improves performance and delays fatigue in high-intensity tasks. However, it remains to be elucidated if the coingestion of both dietary supplements stimulates a summative ergogenic effect. This study aimed to examine the effect of the acute coingestion of NaHCO3 and CAF on repeated-sprint performance. METHODS: Twenty-five trained participants (age: 23.3 [4.0] y; sex [female/male]: 12/13; body mass: 69.6 [12.5] kg) participated in a randomized, double-blind, placebo (PLA) -controlled, crossover study. Participants were assigned to 4 conditions: (1) NaHCO3 + CAF, (2) NaHCO3, (3) CAF, or (4) PLA. Thus, they ingested 0.3 g/kg of NaHCO3, 3 mg/kg of CAF, or PLA. Then, participants performed 4 Wingate tests (Wt), consisting of a 30-second all-out sprint against an individualized resisted load, interspersed by a 1.5-minute rest period between sprints. RESULTS: Peak (Wpeak) and mean (Wmean) power output revealed a supplement and sprint interaction effect (P = .009 and P = .049, respectively). Compared with PLA, NaHCO3 + CAF and NaHCO3 increased Wpeak performance in Wt 3 (3%, P = .021) and Wt 4 (4.5%, P = .047), while NaHCO3 supplementation increased mean power performance in Wt 3 (4.2%, P = .001). In Wt 1, CAF increased Wpeak (3.2%, P = .054) and reduced time to Wpeak (-8.5%; P = .008). Plasma lactate showed a supplement plus sprint interaction (P < .001) when NaHCO3 was compared with CAF (13%, P = .031) and PLA (23%, P = .021). CONCLUSION: To summarize, although the isolated ingestion of CAF and NaHCO3 improved repeated-sprint performance, the coingestion of both supplements did not stimulate a synergic ergogenic effect.

The role of caffeine in headache disorders.

PURPOSE OF REVIEW: Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management. RECENT FINDINGS: Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy. SUMMARY: There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.

ASSESSMENT OF SIMULATED SURGICAL DEXTERITY AFTER MODIFIABLE EXTERNAL EXPOSURES AMONG NOVICE VERSUS EXPERIENCED VITREORETINAL SURGEONS.

PURPOSE: To evaluate novice and senior vitreoretinal surgeons after various exposures. Multiple comparisons ranked the importance of these exposures for surgical dexterity based on experience. METHODS: This prospective cohort study included 15 novice and 11 senior vitreoretinal surgeons (<2 and >10 years' practice, respectively). Eyesi-simulator tasks were performed after each exposure. Day 1, placebo, 2.5 mg/kg caffeine, and 5.0 mg/kg caffeine; day 2, placebo, 0.2 mg/kg propranolol, and 0.6 mg/kg propranolol; day 3, baseline simulation, breathalyzer readings of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentrations; day 4, baseline simulation, push-up sets with 50% and 85% repetitions maximum; and day 5, 3-hour sleep deprivation. Eyesi-generated score (0-700, worst-best), out-of-tolerance tremor (0-100, best-worst), task completion time (minutes), and intraocular pathway (in millimeters) were measured. RESULTS: Novice surgeons performed worse after caffeine (-29.53, 95% confidence interval [CI]: -57.80 to -1.27, P = 0.041) and alcohol (-51.33, 95% CI: -80.49 to -22.16, P = 0.001) consumption. Alcohol caused longer intraocular instrument movement pathways (212.84 mm, 95% CI: 34.03-391.65 mm, P = 0.02) and greater tremor (7.72, 95% CI: 0.74-14.70, P = 0.003) among novices. Sleep deprivation negatively affected novice performance time (2.57 minutes, 95% CI: 1.09-4.05 minutes, P = 0.001) and tremor (8.62, 95% CI: 0.80-16.45, P = 0.03); however, their speed increased after propranolol (-1.43 minutes, 95% CI: -2.71 to -0.15 minutes, P = 0.029). Senior surgeons' scores deteriorated only following alcohol consumption (-47.36, 95% CI: -80.37 to -14.36, P = 0.005). CONCLUSION: Alcohol compromised all participants despite their expertise level. Experience negated the effects of caffeine, propranolol, exercise, and sleep deprivation on surgical skills.

Effect of Acute Caffeine Exposure on Blood Glucose and Hepatic Glycogen Content in Normal and Thyroidectomized Male Wistar Rats.

Acute caffeine exposure had been shown to induce hyperglycemia however; the influence of thyroid hormones on the caffeine-induced hyperglycemia is yet to be established. The present study was therefore designed to investigate the effect of caffeine exposure on blood glucose and hepatic glycogen content in thyroidectomized rats. Sixty adult male Wistar rats were randomly divided into 10 groups as I-X (n=6).  Rats in groups I, III, V, VII and IX were given normal saline, caffeine, prazosin + caffeine, propranolol +caffeine, combined prazosin+ propranolol+caffeine injections respectively while rats in groups  II, IV, VI, VIII and X were thyroidectomized  and treated in similar manner as the normal rats respectively. Surgical removal of the thyroid gland was done in the thyroidectomised groups while sham-operation was done in Normal group to serve as control. After healing and following an overnight fast, the rats were anaesthetized and the femoral vein and carotid artery were cannulated for drug administration and blood glucose measurement respectively. After stabilization, following basal measurements, rats from each group were injected normal saline or caffeine (6mg/kg) while another sets were pre-treated prazosin (0.2 mg/kg), propanolol (0.5 mg/kg) or their combination before caffeine administration. Blood glucose was then monitored for 60 minutes post-injection of caffeine at 5 minutes interval. Liver samples were collected at the end of the observation period for glycogen content determination. Caffeine caused significant increased blood glucose levels in both normal and thyroidectomized rats which were up to 210% and 180% respectively at the peak of their responses. Liver glycogen content of the thyroidectomized rats (3.11 ± 0.20 mg/100g tissue weight) was significantly higher than the normal rats (1.91 ± 0.43 mg/100g tissue weight). These glycogen contents were significantly reduced by caffeine in both normal (0.25 ± 0.04 mg/100g tissue weight) and thyroidectomized rats (1.65 ± 0.16 mg/100g tissue weight) when compared with their controls. The caffeine effects on blood glucose and hepatic glycogen content were abolished by pretreatment with propanolol or a combination of prazosin and propanolol in both normal and thyroidectomized rats but pretreatment with prazosin caused only significant reduction in hyperglycemic response to caffeine. The findings of this study suggest that caffeine-induced hyperglycemia in both normal and thyroidectomized rats are mediated through both alpha and beta adrenoceptors.

Effects of Coffee on the Gastro-Intestinal Tract: A Narrative Review and Literature Update.

The objective of the present research was to review the state of the art on the consequences of drinking coffee at the different levels of the gastrointestinal tract. At some steps of the digestive process, the effects of coffee consumption seem rather clear. This is the case for the stimulation of gastric acid secretion, the stimulation of biliary and pancreatic secretion, the reduction of gallstone risk, the stimulation of colic motility, and changes in the composition of gut microbiota. Other aspects are still controversial, such as the possibility for coffee to affect gastro-esophageal reflux, peptic ulcers, and intestinal inflammatory diseases. This review also includes a brief summary on the lack of association between coffee consumption and cancer of the different digestive organs, and points to the powerful protective effect of coffee against the risk of hepatocellular carcinoma. This review reports the available evidence on different topics and identifies the areas that would most benefit from additional studies.

Association Between Homeschooling and Adolescent Sleep Duration and Health During COVID-19 Pandemic High School Closures.

Importance: Although negative associations of COVID-19 pandemic high school closures with adolescents' health have been demonstrated repeatedly, some research has reported a beneficial association of these closures with adolescents' sleep. The present study was, to our knowledge, the first to combine both perspectives. Objective: To investigate associations between adolescents' sleep and health-related characteristics during COVID-19 pandemic school closures in Switzerland. Design, Setting, and Participants: This survey study used cross-sectional online surveys circulated among the students of 21 public high schools in Zurich, Switzerland. The control sample completed the survey under regular, prepandemic conditions (May to July 2017) and the lockdown sample during school closures (May to June 2020). Survey respondents were included in the study if they provided their sex, age, and school. Exposures: High school closures during the first COVID-19 pandemic wave in Switzerland (March 13 to June 6, 2020). Main Outcomes and Measures: Sleep-wake patterns, health-related quality of life (HRQoL, assessed by the KIDSCREEN-10 questionnaire), substance use (caffeine, alcohol, and nicotine), and depressive symptoms (lockdown sample only; assessed using the withdrawn/depressed scale from the Youth Self Report). Multilevel regression models were used to assess sample differences and associations of health-related characteristics with sleep duration and depressive symptoms. Results: The total sample consisted of 8972 students, including 5308 (59.2%) in the control sample (3454 [65.1%] female) and 3664 (40.8%) in the lockdown sample (2429 [66.3%] female); the median age in both samples was 16 years (IQR, 15-17 years). During school closures, the sleep period on scheduled days was 75 minutes longer (semipartial R2 statistic [R2ß*], 0.238; 95% CI, 0.222-0.254; P < .001) and the students had better HRQoL (R2ß*, 0.007; 95% CI, 0.004-0.012; P < .001) and less consumption of caffeine (R2ß*, 0.010; 95% CI, 0.006-0.015; P < .001) and alcohol (R2ß*, 0.014; 95% CI, 0.008-0.022; P < .001). Longer sleep duration was associated with better HRQoL (R2ß*, 0.027; 95% CI, 0.020-0.034; P < .001) and less caffeine consumption (R2ß*, 0.013; 95% CI, 0.009-0.019; P < .001). In the lockdown sample, an inverse association was found between depressive symptoms and HRQoL (R2ß*, 0.285; 95% CI, 0.260-.0311; P < .001) and a positive association was found with caffeine consumption (R2ß*, 0.003; 95% CI, 0.000-0.008; P = .01). Conclusions and Relevance: In this survey study, 2 opposing associations between school closures and adolescents' health were identified: a negative association with psychological distress and a beneficial association with increased sleep duration. These findings should be considered when evaluating and implementing school closures. Furthermore, the findings provide support for delaying school start times for adolescents.

Pharmacokinetic, pharmacological, and genotoxic evaluation of deuterated caffeine.

Altering caffeine's negative physiological effects and extending its duration of activity is an active area of research; however, deuteration as a means of achieving these goals is unexplored. Deuteration substitutes one or more of the hydrogen atoms of a substance with deuterium, a stable isotope of hydrogen that contains an extra neutron. Deuteration can potentially alter the metabolic profile of a substance, while maintaining its pharmacodynamic properties. d9-Caffeine is a deuterated isotopologue of caffeine with the nine hydrogens contained in the 1, 3, and 7 methyl groups of caffeine substituted with deuterium. d9-Caffeine may prove to be an alternative to caffeine that may be consumed with less frequency, at lower doses, and with less exposure to downstream active metabolites of caffeine. Characterization of d9-caffeine's genotoxic potential, pharmacodynamic, and pharmacokinetic behavior is critical in establishing how it may differ from caffeine. d9-Caffeine was non-genotoxic with and without metabolic activation in both a bacterial reverse mutation assay and a human mammalian cell micronucleus assay at concentrations up to the ICH concentration limits. d9-Caffeine exhibited a prolonged systemic and brain exposure time in rats as compared to caffeine following oral administration. The adenosine receptor antagonist potency of d9-caffeine was similar to caffeine.