Low Doses Of Caffeine Research Articles

Chronic treatment with caffeine and its withdrawal modify the antidepressant-like activity of selective serotonin reuptake inhibitors in the forced swim and tail suspension tests in mice. Effects on Comt, Slc6a15 and Adora1 gene expression

Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity. A decrease in the level of escitalopram and an increase in the level of caffeine in serum were observed after concomitant administration of these compounds, while the joint administration of caffeine and fluoxetine was not associated with changes in their levels in serum or brain. Caffeine withdrawal caused a decrease in Adora1 mRNA level in the cerebral cortex (Cx). Administration of escitalopram or fluoxetine followed by caffeine withdrawal caused an increase in this gene expression, whereas administration of escitalopram, but not fluoxetine, on day 15th together with caffeine caused a decrease in Adora1 mRNA level in the Cx. Furthermore, antidepressant-like activity observed after joint administration of the tested drugs with caffeine was associated with decreased Slc6a15 mRNA level in the Cx. The results show that withdrawal of caffeine after its chronic intake may change activity of antidepressants with concomitant alterations within monoamine, adenosine and glutamate systems.

Acute Ingestion of Caffeinated Chewing Gum Improves Repeated Sprint Performance of Team Sport Athletes With Low Habitual Caffeine Consumption.

The effects of acute ingestion of caffeine on short-duration high-intensity performance are equivocal, while studies of novel modes of delivery and the efficacy of low doses of caffeine are warranted. The aims of the present study were to investigate the effect of acute ingestion of caffeinated chewing gum on repeated sprint performance (RSP) in team sport athletes, and whether habitual caffeine consumption alters the ergogenic effect, if any, on RSP. A total of 18 male team sport athletes undertook four RSP trials using a 40-m maximum shuttle run test, which incorporates 10 × 40-m sprints with 30s between the start of each sprint. Each participant completed two familiarization sessions, followed by caffeine (CAF; caffeinated chewing gum; 200mg caffeine) and placebo (PLA; noncaffeinated chewing gum) trials in a randomized, double-blind manner. RSP, assessed by sprint performance decrement (%), did not differ (p = .209; effect size = 0.16; N = 18) between CAF (5.00 ± 2.84%) and PLA (5.43 ± 2.68%). Secondary analysis revealed that low habitual caffeine consumers (<40mg/day, n = 10) experienced an attenuation of sprint performance decrement during CAF relative to PLA (5.53 ± 3.12% vs. 6.53 ± 2.91%, respectively; p = .049; effect size =0.33); an effect not observed in moderate/high habitual caffeine consumers (>130mg/day, n = 6; 3.98 ± 2.57% vs. 3.80 ± 1.79%, respectively; p = .684; effect size = 0.08). The data suggest that a low dose of caffeine in the form of caffeinated chewing gum attenuates the sprint performance decrement during RSP by team sport athletes with low, but not moderate-to-high, habitual consumption of caffeine.

Histological and biochemical effects of caffeine on bone of growing rats

The present study has been carried out to evaluate the histological and biochemical effects of caffeine on bone of growing rats.A total of 25 rats (8 weeks old) were divided randomly into three groups: Group 1(n = 5), serve as the control group, group 2 (n = 10), caffeine-low dose; group 3 (n =10), caffeine high dose. The caffeine was fed by gastric tube daily and the high dose of caffeine=10 mg/100 g body weight/day, and the low dose of caffeine=2.5 mg/100g body weight/day. Body weight was measured weekly. After sacrifice, blood samples were collected in tubes, and serum samples were separated for the determination of Ca, ALP, Zn and Mn. Femoral bones of rats were used for histopathological assessment. The results showed that serum Ca, Zn and Mn levels for high dose group is significantly lower than the low dose than the control group. The Alkaline phosphatase in low dose group is not significant smaller than the control group, but the high dose group has significantly elevation value than the control group. Thickness of epiphyseal plate especially proliferating and hypertrophic zones compared to control group was observed in the group which received low dose of caffeine. Section of diaphysis of low-dose treated group showed thinning out of the outer compact bone with multiple osteoporotic cavities in the bone matrix. The epiphyseal plates of caffeine-high dose showed disturbance of bone growth as revealed by presence of numerous clefts among rows of cartilage cells of the epiphyseal plate, between the proliferating and hypertrophic zone and between calcified and ossified zones.Thus, it can be concluded that the oral administration of caffeine lead to a significant reduction in serum Ca, Zn and Mn; and a significant elevation in serum ALP together with a dose dependent histological changes in the bone of treated rats according to the increase of caffeine dose.

The effects of low and moderate doses of caffeine supplementation on upper and lower body maximal voluntary concentric and eccentric muscle force.

Despite the growing quantity of literature exploring the effect of caffeine on muscular strength, there is a dearth of data that directly explores differences in erogenicity between upper and lower body musculature and the dose-response effect. The present study sought to investigate the effects of low and moderate doses of caffeine on the maximal voluntary strength of the elbow flexors and knee extensors. Ten nonspecifically strength-trained, recreationally active participants (aged 21 ± 0.3 years) completed the study. Using a randomised, counterbalanced, and double-blind approach, isokinetic concentric and eccentric strength was measured at 60 and 180°/s following administration of a placebo, 3 mg·kg-1 body mass caffeine, and 6 mg·kg-1 body mass caffeine. There was no effect of caffeine on the maximal voluntary concentric and eccentric strength of the elbow flexors, or the eccentric strength of the knee extensors. Both 3 and 6 mg·kg-1 body mass caffeine caused a significant increase in peak concentric force of the knee extensors at 180°/s. No difference was apparent between the 2 concentrations. Only 6 mg·kg-1 body mass caused an increase in peak concentric force during repeated contractions. The results infer that the effective caffeine concentration to evoke improved muscle performance may be related to muscle mass and contraction type. The present work indicates that a relatively low dose of caffeine treatment may be effective for improving lower body muscular strength, but may have little benefit for the strength of major muscular groups of the upper body.

Caffeine has no effect on eyeblink conditioning in mice

Caffeine is one of the most widely used drugs in the world. In the brain, caffeine acts as an antagonist for the adenosine A1 and A2B receptors. Since A1 receptors are highly concentrated in the cortex of the cerebellum, we hypothesized that caffeine could potentially affect learning tasks that require the cerebellar cortex, such as eyeblink conditioning. To test this hypothesis, we examined the effect of low (5mg/kg) and high (50mg/kg) doses of caffeine, injected intraperitoneally before training, on eyeblink conditioning in mice. The results show that, at the dosages we used, caffeine affects neither the rate of acquisition, nor the timing of the onset or peak of the conditioned blink responses. Therefore, we conclude that caffeine neither improves nor worsens performance on eyeblink conditioning.

To Evaluate and Compare Therapeutic Effect of High Dose versus Low Dose Caffeine Citrate for Treatment of Apnea in Preterm Infants

To Evaluate and Compare Therapeutic Effect of High Dose versus Low Dose Caffeine Citrate for Treatment of Apnea in Preterm Infants

Nonfatal and fatal intoxications with pure caffeine – report of three different cases

Caffeine is not usually perceived as a drug by most people because it is found in many foods and drinks, including caffeinated energy drinks, as well as in over the counter analgesics and cold preparations. Recently in Poland it has become increasingly common to take pure caffeine, bought through online stores, as a psychoanaleptic. This creates a much higher risk of severe and even fatal poisoning in comparison with the risk associated with the abuse of food products and non-prescription medicines containing low doses of caffeine. This paper presents three different cases of poisoning that occurred when pure caffeine was taken as psychostimulant; in cases 1 and 2 poisoning was the result of a single overdose, while in the case 3 poisoning resulted from a cumulative overdose. In the case 1 there was a severe intoxication (persistent vomiting, hypotension, tremor), and the concentration of caffeine in the blood was found to be 80.16μg/mL. The patient was treated using hemodialysis, which caused a rapid decrease in blood levels of caffeine and relief of the clinical symptoms of poisoning. Cases 2 and 3 were fatal poisonings, and recorded levels of caffeine in post mortem blood samples were 140.64μg/mL and 613.0μg/mL. In case 2 the patient died 10min after admission to hospital as a result of sudden cardiac arrest, which was preceded by an attack of convulsions, and in case 3 death occurred in home and was also sudden in nature. Taking pure caffeine as a stimulant is associated with a high risk of overdose and the development of serious and even fatal poisoning, and those using pure caffeine are generally completely unaware of these risks. In such cases, death is usually sudden due to functional mechanisms.

The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats.

Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3g/L) or high (0.8g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.

Low dose of caffeine enhances the efficacy of antidepressants in major depressive disorder and the underlying neural substrates.

Caffeine is one of the most frequently used psychoactive substances ingested mainly via beverage or food products. Major depressive disorder is a serious and devastating psychiatric disorder. Emerging evidence indicates that caffeine enhances the antidepressant-like activity of common antidepressant drugs in rodents. However, whether joint administration of low dose of caffeine enhances the antidepressant actions in depressed patients remains unclear. A total of 95 male inpatients were assigned to three groups and were asked to take either caffeine (60, 120 mg) or placebo (soymilk powder) daily for 4 wk on the basis of their current antidepressant medications. Results showed that chronic supplementation with low dose of caffeine (60 mg) produced rapid antidepressant action by reduction of depressive scores. Furthermore, low dose of caffeine improved cognitive performance in depressed patients. However, caffeine did not affect sleep as measured by overnight polysomnography. Moreover, chronic caffeine consumption elicited inhibition of hypothalamic-pituitary-adrenal axis activation by normalization of salivary cortisol induced by Trier social stress test. These findings indicated the potential benefits of further implications of supplementary administration of caffeine to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder.

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats

Background: Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. Purpose: The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. Methods: A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. Results: GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Conclusion: Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters.

Stair walking is more energizing than low dose caffeine in sleep deprived young women

IntroductionThe acute energizing effect of exercise and caffeine has never been examined in a single study of adults with chronic sleep deprivation but evidence from a study of this type could help individuals choose between these two common alertness-enhancing options. AimThe apriori primary aim of this experiment was to compare the influence of 10-min of low-to-moderate intensity stair walking to the consumption of capsules containing 50mg caffeine or flour (placebo) on feelings of energy in physically active, college female caffeine users with chronic insufficient sleep. Effects on secondary outcomes related to feelings of energy also were assessed. Material-methodA repeated measures crossover experiment was conducted with 18 college women (18–23years) who reported (i) daily caffeine consumption that was not extreme (40–400mg), (ii) typical leisure time physical activity that was not extreme (at least 2 weekly mild 15-min or longer bouts and no >5 strenuous 15-min or longer bouts), and (iii) sleeping <45h per week. Mood states (POMS-BF), focused on energy feelings (vigor), as well as working memory (N-back), sustained attention (CPT), simple reaction time (SRT), and motivation to complete the cognitive tasks were measured before and after a 10-min exercise condition (20min seated rest followed by 10min of low-to-moderate intensity stair walking) and compared to both a caffeine condition (50mg caffeine capsule followed by 30min of seated rest) and a similar flour (placebo) capsule condition. Condition (exercise, caffeine, placebo)×Time (Baseline, Post-1, Post-2, and for mood Post-3) ANCOVAs (controlling for Condition order) tested the hypothesized effects. ResultsCondition×Time interactions showed that stair walking increased POMS-BF vigor at Post-1 compared to both placebo and caffeine. Other interactions were not significant. ConclusionA brief bout of low-to-moderate intensity stair walking has transient energizing effects that exceed a low dose of caffeine for active young women with chronic insufficient sleep.

Local Recovery of CICR Probed by Ultra-Effective Calcium Uncaging

In cardiac myocytes a small amount of Ca2+ enters the cytoplasm upon depolarization and initiates Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs). Ca2+ release occurs via subcellular local Ca2+ signaling events, Ca2+ sparks. Local recovery of Ca2+ release depends on both, SR refilling and restoration of Ca2+ sensitivity of the RyRs. In this work we used two photon (2P) photolysis of the ultra effective caged Ca2+ compound BIST-2EGTA [1] and laser-scanning confocal Ca2+ imaging to probe refractoriness of local Ca2+ release in control conditions and in presence of a low dose of caffeine (to mimic sensitisation of RyRs) or cyclopiazonic acid (CPA, SERCA inhibitor to slow SR refilling). Whole-cell patch-clamped cardiomyocytes were loaded with BIST-2EGTA and rhod-2. Pairs of short 2P photolytic pulses (5 ms, 810 nm) with different intra pulse intervals were applied to test Ca2+ release amplitude recovery. Data recorded in the presence of CPA showed slower recovery with a time constant of ∼76 ms compared to control condition (∼56 ms). In the presence of a low dose of caffeine the recovery was faster than control (∼31 ms). We obtained comparable results with the well established “ryanodine method” [2], where a low dose of ryanodine is used to trigger repetitive sparks from single cluster of RyRs. This new 2P approach provides composite information of Ca2+ release amplitude recovery reflecting both SR refilling and restoration of Ca2+ sensitivity. It can be used to measure the kinetics of local CICR recovery, alterations of which may be related to premature heart beats and arrhythmias. 1. Agarwal, H. K., Janicek, R., Chi, S.-H., Perry, J. W., Niggli, E., and Ellis-Davies, G. C. R. (2016), Calcium uncaging with visible light. JACS 138, 3687-3693. 2. Sobie, E. A., Song, L.-S. and Lederer, W. J. (2005), Local recovery of Ca2+ release in rat ventricular myocytes. J. Physiol, 565, 441-447.

Excessive oral intake caffeine altered cerebral cortex histoarchitecture and cell morphologies in adult mice

Caffeine is commonly consumed in an effort to enhance speed in performance and wakefulness. However, little is known about the deleterious effects it can produce on the brain, this study aimed at determining the extents of effects and damage that can be caused by excessive consumption of caffeine on the cerebral cortex of mice models with a view to examining caffeine effects on cerebral cortex histoarchitecture and cell morphologies. Twenty adult mice were used for this study. They were randomly divided into 4 groups of 5 animals each. Control rats were administered normal saline, experimental groups received caffeine through oral cannula at 10, 50 and 120 mg/kg body weight for 28 days to determine effects of graded doses of caffeine administration. The dosage of the caffeine selection was based on previously published work. The result indicates that at low and medium doses of caffeine administration, features of prominent eosinophilic cytoplasm with or without shrunken nuclei was observed in plates 1B, 1C, and 3B, 3C. And at high dose, features of degenerating neurons such as pyknotic nuclei and sparse neuronal population were observed in plates 2D and 3D when compared to the normal appearance of the neurons and the glial cells. In conclusion, low and medium doses of caffeine induced mild changes in cortical neuron morphology and at higher dose of caffeine administration, neurodegenerative changes were observed in cerebral histoarchitecture. This shows that at high dose, caffeine consumption can produce detrimental effects on brain structure as well asfunction in adult mice models.Key Words: Caffeine, histoarchitecture, neuropil, cortical neurons

A Low Dose Caffeine and Carbohydrate Supplement does not Improve Athletic Performance during Volleyball Competition

A Low Dose Caffeine and Carbohydrate Supplement does not Improve Athletic Performance during Volleyball Competition

Acute Low-Dose Caffeine Supplementation Increases Electromyographic Fatigue Threshold in Healthy Men.

Morse, JJ, Pallaska, G, Pierce, PR, Fields, TM, Galen, SS, and Malek, MH. Acute low-dose caffeine supplementation increases electromyographic fatigue threshold in healthy men. J Strength Cond Res 30(11): 3236-3241, 2016-The purpose of this study is to determine whether consumption of a single low-dose caffeine drink will delay the onset of the electromyographic fatigue threshold (EMGFT) in the superficial quadriceps femoris muscles. We hypothesize that the EMGFT values for the caffeine condition will be significantly higher than the EMGFT values for the placebo condition. On separate occasions, 10 physically active men performed incremental single-leg knee-extensor ergometry 1 hour after caffeine (200 mg) or placebo consumption. The EMGFT was determined for each participant for both conditions. The results indicated a significant increase for maximal power output (16%; p = 0.004) and EMGFT (45%; p = 0.004) in the caffeine condition compared with placebo. These findings suggest that acute low-dose caffeine supplementation delays neuromuscular fatigue in the quadriceps femoris muscles.

Chronic ingestion of a low dose of caffeine induces tolerance to the performance benefits of caffeine

ABSTRACTThis study examined effects of 4 weeks of caffeine supplementation on endurance performance. Eighteen low-habitual caffeine consumers (<75 mg · day−1) were randomly assigned to ingest caffeine (1.5–3.0 mg · kg−1day−1; titrated) or placebo for 28 days. Groups were matched for age, body mass, V̇O2peak and Wmax (P > 0.05). Before supplementation, all participants completed one V̇O2peak test, one practice trial and 2 experimental trials (acute 3 mg · kg−1 caffeine [precaf] and placebo [testpla]). During the supplementation period a second V̇O2peak test was completed on day 21 before a final, acute 3 mg · kg−1 caffeine trial (postcaf) on day 29. Trials consisted of 60 min cycle exercise at 60% V̇O2peak followed by a 30 min performance task. All participants produced more external work during the precaf trial than testpla, with increases in the caffeine (383.3 ± 75 kJ vs. 344.9 ± 80.3 kJ; Cohen’s d effect size [ES] = 0.49; P = 0.001) and placebo (354.5 ± 55.2 kJ vs. 333.1 ± 56.4 kJ; ES = 0.38; P = 0.004) supplementation group, respectively. This performance benefit was no longer apparent after 4 weeks of caffeine supplementation (precaf: 383.3 ± 75.0 kJ vs. postcaf: 358.0 ± 89.8 kJ; ES = 0.31; P = 0.025), but was retained in the placebo group (precaf: 354.5 ± 55.2 kJ vs. postcaf: 351.8 ± 49.4 kJ; ES = 0.05; P > 0.05). Circulating caffeine, hormonal concentrations and substrate oxidation did not differ between groups (all P > 0.05). Chronic ingestion of a low dose of caffeine develops tolerance in low-caffeine consumers. Therefore, individuals with low-habitual intakes should refrain from chronic caffeine supplementation to maximise performance benefits from acute caffeine ingestion.

Protective effect of low dose caffeine on psychological stress and cognitive function

IntroductionCaffeine is an adrenergic antagonist that enhances neuronal activity. Psychological stress depresses cognitive function. AimTo investigate the effects of acute and chronic low dose caffeine on anxiety-like behavior and cognitive functions of acute or chronic psychological stressed rats. Material-methodAcute or chronic caffeine (3mg/kg) was administered to male Sprague Dawley rats (200–250g, n=42) before acute (cat odor) and chronic variable psychological stress (restraint overcrowding stress, elevated plus maze, cat odor, forced swimming) induction. Anxiety and cognitive functions were evaluated by hole-board and object recognition tests. The brain glutathione and malondialdehyde assays, myeloperoxidase, nitric oxide (NO), superoxide dismutase (SOD), luminol and lucigenin activity and histological examination were done. ANOVA and Student's t-test were used for statistical analysis. ResultsThe depressed cognitive function with chronic stress exposure and the increased anxiety-like behavior with both stress inductions were improved via both caffeine applications (p<0.05–0.001). Both caffeine pretreatments in chronic stressed rats, and chronic caffeine in acute stressed ones reduced the elevated myeloperoxidase activities (p<0.05–0.01). The increased malondialdehyde, lucigenin and NO levels with acute stress were inhibited with chronic caffeine (p<0.05–0.01), malondialdehyde and NO levels were declined by acute caffeine (p<0.001). Acute caffeine decreased SOD activity (p<0.01) and improved glutathione (p<0.01) and luminol levels (p<0.05). The induced histological damage with both stress exposures was ameliorated with chronic caffeine. ConclusionThe increased anxiety-like behavior and depleted cognitive functions under stress conditions were improved with both acute and predominantly chronic caffeine pretreatments by decreasing oxidative damage parameters.

P.1.j.032 - Perinatal administration of caffeine in mice affects the cognition and spatial memory later in adult life

Caffeine, one of the most widely consumed psychoactive substance in the world, has been shown to affect mood, memory, alertness, and cognitive performance. This study aimed to assess the effect of sub-chronic oral gavage of caffeine on memory and the phosphorylation levels of hippocampal Akt (protein kinase B), GSK-3β (Glycogen Synthase Kinase-3beta) and ERK (extracellular signal-regulated kinase) in mice. Adult male NMRI mice were administered with caffeine at the doses of 0.25, 0.5, 0.75 and 1.5 mg/kg/oral gavage for 10 days before behavioral assessments. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of Akt, GSK-3β and ERK proteins. The results showed that sub-chronic caffeine ingestion at the dose of 0.5 mg/kg improves memory in mice both in passive avoidance and novel object recognition tasks. Furthermore, this memory enhancing dose of caffeine elevated the ratios of phosphorylated to total contents of hippocampal Akt, GSK-3β and ERK. This study suggests that sub-chronic low dose of caffeine improves memory and increases the phosphorylation of hippocampal Akt, GSK-3β and ERK proteins.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats

ABSTRACTSeveral studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl4)-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl4-induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl4 -induced liver damage in rats.