Antiinflammatory and antiinfective effect of caffeine in a mouse model of disseminated salmonellosis.

Caffeine has been reported for its antiinflammatory properties by stimulating phagocytosis. In this study, we investigated the antiinflammatory and antiinfective potential of caffeine in murine macrophage cell cultures and Swiss mice infected with virulent Salmonella enterica serotype typhimurium. Peritoneal macrophages (pMØ) were treated with caffeine on 96-well plates for 24 hr and then infected with Salmonella for 4 hr. In another experiment, the pMØ were first infected with the bacterium for 4 hr and then treated with caffeine for 24 hr. In addition, Swiss mice were inoculated, intraperitoneally, with S. typhimurium and then received caffeine intravenously. Control groups received phosphate-buffered saline (PBS) or dexamethasone. We found that treatments with caffeine increased the macrophage cell viability and reduced the intracellular bacterial load. The administration of caffeine to Swiss mice reduced the infiltration of leukocytes into the peritoneal cavity after the bacterial challenge. Furthermore, the bacterial burdens in the peritoneal fluid, bloodstream, spleen, and liver were decreased by caffeine treatment. The expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and inducible nitric oxide synthase (iNOs) were down-regulated after infection in caffeine-treated mice. We can conclude that caffeine has both antiinflammatory and antiinfective properties that can be useful for management of bacterial infections along with antibiotics.

Caffeine modulates brain purinergic signaling in Nile tilapia (Oreochromis niloticus) under hypoxia conditions: improvement of immune and inflammatory responses.

Purinergic signaling is linked to neurodegenerative and proinflammatory damage during pathological conditions such as hypoxia, but involvement of this pathway in brain damage in fish exposed to environmental hypoxia remains unknown, and we propose dietary supplementation with caffeine in order to improve the immune response. Therefore, the aim of the study was to evaluate whether the enzymatic purinergic signaling pathway is associated with inflammatory brain damage in Nile tilapia (Oreochromis niloticus) exposed to environmental hypoxia and whether dietary supplementation with caffeine (5% and 8%) can prevent these changes in purinergic signaling. Animals were randomly divided into six groups (A-F, n = 6 per group, in triplicate), as follows: groups A-C were submitted to normoxia, while groups D-F were submitted to hypoxia. Groups A and D received the basal diet, while groups B and D and groups C and F received a diet containing 5% and 8% caffeine, respectively, and fed with their respective diets for 21 days. After 21 days, aeration was disconnected (groups D-F) and the dissolved oxygen levels were maintained as follows: group A (6.55 ± 0.23 mg/L), group B (6.51 ± 0.24 mg/L), group C (6.58 ± 0.22 mg/L), group D (1.23 ± 0.11 mg/L), group E (1.20 ± 0.15 mg/L), and group F (1.18 ± 0.13 mg/L). Cerebral triphosphate diphosphohydrolase (NTPDase) using adenosine triphosphate (ATP) as a substrate and 5'-nucleotidase activities decreased in fish exposed to 72 h of hypoxia compared with the normoxia group, while adenosine deaminase (ADA) activity and levels of nitric oxide (NOx) metabolites were higher. Dietary supplementation with 5% and 8% caffeine prevented all alterations elicited by hypoxia, with the exception of ADA activity in the case of 5% caffeine. Based on this evidence, our findings reveal that nucleotide/nucleoside hydrolysis is modified in the brains of fish exposed to 72 h of hypoxia, contributing to inflammatory damage, which apparently is mediated by excessive ATP content in the extracellular medium and by excessive NOx production. Also, the use of a diet containing 5% and 8% caffeine prevented these alterations (except 5% of dietary caffeine on ADA activity) and can be considered an interesting approach to preventing the impairment of immune and inflammatory responses elicited by hypoxia, principally the inclusion of 8% caffeine.

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours.

Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep.

Acute Caffeine Ingestion on Performance in Young Judo Athletes.

PURPOSE: To compare the acute effect of caffeine ingestion on performance in young judo athletes. METHOD: In a randomized double-blind design, eighteen judo athletes (16.1 ± 1.4 yrs.) were evaluated on three nonconsecutive days. On the first day, the special judo fitness test (SJFT) was used as a control session. On the second day, the sample was randomly divided into two equal groups. One group received 4 mg.kg-1 of caffeine (capsule) and the other group received a placebo. After resting for 60 min, the sample performed the SJFT. On the final day of testing, the same procedure was performed but the substance ingested was exchanged between the groups. RESULTS: Heart rate (HR) and rating of perceived exertion (RPE) were recorded throughout the applications of the SJFTs. Caffeine ingestion did not induce changes in HR, but reduced the RPE compared with the placebo session (7.0 ± 1.1 vs 8.2 ± 2.0; p < .05), increased the number of throws applied (29.0 ± 2.6 vs 22.1 ± 3.4; p < .01) and reduced the SJFT index (12.2 ± 0.5 vs. 15.7 ± 0.9; p < .001). CONCLUSION: 4 mg.kg-1 did not alter HR but improved performance on SJFT in young judo athletes and reduced the RPE.

Occurrence, fate, persistence and remediation of caffeine: a review.

Pharmaceutical and personal care products (PPCPs) have gained attention in recent years due to their continuous discharge in natural waters. Their persistence in the environment has impacted flora, fauna and human being worldwide. One of the most common PPCPs is caffeine (1, 3, 7-trimethylxanthine) which acts as a stimulant to the central nervous system in humans and is found in nature in about 60 plant species, especially in coffee, tea and cacao plants. Here we discuss the evidence with respect to caffeine occurrence, its persistence and remediation in light of increasing knowledge and the impact of caffeine on the environment. Daily intake of caffeine around the world is found to increase due to the frequent introduction of new caffeinated beverages as well as increased consumption of coffee, tea and carbonated soft drinks, which has led to increase in its concentration in water bodies including agricultural soil. The caffeine concentration in different water system, studied by various authors is also described. Diverse effects of the use of caffeine on several organisms including humans are also briefly presented. Therefore, urgent attention for the removal of caffeine and its derivatives is the need of the hour. Various methods described in literature for caffeine degradation/removal is also presented. Another widely used technique in environmental remediation is molecular imprinting (MIP); however, only few MIPs have been demonstrated for caffeine which is also discussed. Regular monitoring can be useful to control toxic effects of caffeine. Graphical abstract.

Maternal Caffeine Intake Disrupts Eggshell Integrity and Retards Larval Development by Reducing Yolk Production in a Caenorhabditis elegans Model.

During pregnancy, most women are exposed to caffeine, which is a widely consumed psychoactive substance. However, the consequences of maternal caffeine intake on the child remain largely unknown. Here, we investigated the intergenerational effects of maternal caffeine intake on offspring in a Caenorhabditis elegans model. We treated a young mother (P0) with 10 mM of caffeine equivalent to 2-5 cans of commercial energy drinks and examined its reproduction and growth rate from P0 to F2 generation. The fertility decreased and embryonic lethality increased by defective oocytes and eggshell integrity in caffeine-ingested mothers, and F1 larval development severely retarded. These results were due to decreased production of vitellogenin protein (yolk) in caffeine-ingested mothers. Furthermore, effects of RNA interference of vitellogenin (vit) genes, vit-1 to vit-6, in P0 mothers can mimic those by caffeine-ingested mothers. In addition, RNA interference (RNAi) depletion of unc-62 (human Meis homeobox), a transcriptional activator for vit genes, also showed similar effects induced by caffeine intake. Taken together, maternal caffeine intake reduced yolk production mediated by the UNC-62 transcription factor, thereby disrupting oocyte and eggshell integrity and retarding larval development. Our study suggests the clinical significance of caffeine intake for prospective mothers.

Effects of Phosphoethanolamine Supplementation on Mitochondrial Activity and Lipogenesis in a Caffeine Ingestion Caenorhabditis elegans Model.

Caffeine intake is strongly linked to lipid metabolism. We previously reported the age-dependent physiological effects of caffeine intake in a Caenorhabditis elegans model. Since nutritional status can actively influence metabolism and overall health, in this study, we evaluated the effect of caffeine intake on lipid metabolism in adult-stage C. elegans. We found that, in C. elegans, fat storage and the level of phosphoethanolamine (PE) were significantly reduced with caffeine intake. In addition, mitochondrial activity decreased and mitochondrial morphology was disrupted, and the expression of oxidative stress response genes, hsp-6, gst-4, and daf-16, was induced by caffeine intake. Furthermore, the level of an energy metabolism sensor, phospho-AMP-activated protein kinase, was increased, whereas the expression of the sterol regulatory element binding protein gene and its target stearoyl-CoA desaturase genes, fat-5, -6, and -7, was decreased with caffeine intake. These findings suggest that caffeine intake causes mitochondrial dysfunction and reduces lipogenesis. Interestingly, these changes induced by caffeine intake were partially alleviated by PE supplementation, suggesting that the reduction in mitochondrial activity and lipogenesis is in part because of the low PE level, and proper dietary supplementation can improve organelle integrity.

Use of coffee flower as a novel resource for the production of bioactive compounds, melanoidins, and bio-sugars.

Although coffee beans have been widely studied, application of coffee flower (CF) has not been previously investigated. Here, we evaluated the use of CF for the production of bioactive compounds, melanoidins, and bio-sugars through the green process. Pressurized hot water extraction was found to be the most appropriate method for extracting bioactive compounds from CF, which contain high values of total phenolic content and have antioxidant properties. Caffeine and trigonelline were the main compounds in CF with yields of 1070.8 mg and 1092.8 mg/100 g dry weight (DW), respectively. Melanoidins were also identified and quantified in the CF extracts that is approximately 30.2% were efficiently recovered in the initial extracts of CF. Bio-sugar was also obtained from cellulase and pectinase at a 92.8% conversion rate. The aim of this study is to promote a novel approach using high amounts of CFs in the production of functional healthy foods and beverages.

Selected C8 two-chain linkers enhance the adenosine A1/A2A receptor affinity and selectivity of caffeine.

Recent research exploring C8 substitution on the caffeine core identified 8-(2-phenylethyl)-1,3,7-trimethylxanthine as a non-selective adenosine receptor antagonist. To elaborate further, we included various C8 two-chain-length linkers to enhance adenosine receptor affinity. The results indicated that the unsubstituted benzyloxy linker (1e A1Ki = 1.52 µM) displayed the highest affinity for the A1 adenosine receptor and the para-chloro-substituted phenoxymethyl (1d A2AKi = 1.33 µM) linker the best A2A adenosine receptor affinity. The position of the oxygen revealed that the phenoxymethyl linker favoured A1 adenosine receptor selectivity over the benzyloxy linker and, by introducing a para-chloro substituent, A2A adenosine receptor selectivity was obtained. Selected compounds (1c, 1e) behaved as A1 adenosine receptor antagonists in GTP shift assays and therefore represent selective and non-selective A1 and A2A adenosine receptor antagonists that may have potential for treating neurological disorders.

Effect of caffeine on cycling time-trial performance in the heat.

OBJECTIVES: The purpose of this investigation was to determine whether a moderate dose of caffeine would improve a laboratory simulated cycling time-trial in the heat. METHODS: Nine well-trained male subjects (VO2max 64.4±6.8mLmin(-1)kg(-1), peak power output 378±40W) completed one familiarisation and two experimental laboratory simulated cycling time-trials in environmental conditions of 35°C and 25% RH 90min after consuming either caffeine (3mgkg(-1) BW) or placebo, in a double blind, cross-over study. RESULTS: Time-trial performance was faster in the caffeine trial compared with the placebo trial (mean±SD, 3806±359s versus 4079±333s, p=0.06, 90%CI 42-500s, 86% likelihood of benefit, d=-0.79). Caffeine ingestion was associated with small to moderate increases in average heart rate (p=0.178, d=0.39), VO2 (p=0.154, d=0.45), respiratory exchange ratio (p=0.292, d=0.35) and core temperature (p=0.616, d=0.22) when compared to placebo, however, these were not statistically significant. Average RPE during the caffeine supplemented time-trial was not significantly different from placebo (p=0.41, d=-0.13). CONCLUSION: Caffeine supplementation at 3mgkg(-1) BW resulted in a worthwhile improvement in cycling time-trial performance in the heat. DESIGN: Double-blind cross-over study.

Does caffeine ingestion before a short-term sprint interval training promote body fat loss?

We investigated the effect of caffeine ingestion combined with a 2-wk sprint interval training (SIT) on training-induced reductions in body adiposity. Twenty physically-active men ingested either 5 mg/kg of cellulose as a placebo (PLA, n=10) or 5 mg/kg of caffeine (CAF, n=10) 60 min before each SIT session (13×30 s sprint/15 s of rest). Body mass and skinfold thickness were measured pre- and post-training. Energy expenditure was measured at rest, during exercise, and 45 min after exercise in the first SIT session. Body fat was similar between PLA and CAF groups at pre-training (P>0.05). However, there was a significant decrease in body fat after training in the CAF group (−5.9±4.2%, P<0.05) but not in PLA (1.5±8.0%, P>0.05). There was no difference in energy expenditure at rest and during exercise between PLA and CAF groups (P>0.05), but the post-exercise energy expenditure was 18.3±21.4% greater in the CAF than in the PLA group (P<0.05). In conclusion, caffeine ingestion before SIT sessions induced a body fat loss that may be associated with higher post-exercise energy expenditure.

Caffeine in Brazil: intake, socioeconomic and demographic determinants, and major dietary sources

Background: The objectives of the study were to describe caffeine intake by 10 years of age or older Brazilian individuals and to investigate possible associations with demographic and socioeconomic determinants as well as the major dietary sources. Methods: The data used are from the personal food consumption module (n= 34,003) of a country-representative household budget survey. Consumed foods and beverages were identified during the application of food diaries. Caffeine contents in food and beverage sources were obtained primarily in national publications. Multivariate regressions were calculated to assess the correlations between population factors and caffeine intake. Results: The daily intake per person was estimated as 115.7 mg, ranging from 84.7 mg, for 10­13 years of age children and adolescents, to 139.8 mg, for individuals with no education. The percentage of individuals whom diet reveals daily caffeine intake higher than 400 mg is up to 3.0 %, according to age groups. Males and individuals living in the Northeast or South regions or in the states of Minas Gerais, Rio de Janeiro, and Espírito Santo are likely to ingest higher contents of the substance. The major dietary sources are coffee (63.1 %) and coffee with milk (24.9 %), cola soft drinks (3.6 %) and yerba mate (1.9 %).Conclusions: Caffeine intake in Brazil is below the recommended limit reference value for adults, and the percentage of individuals whom diet reveals excessive content of caffeine is low. Thus, excessive caffeine intake may not be a health issue in Brazil and depends on the domicile and gender. The major source in the Brazilian diet is coffee.