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The prevalence of ED consumption has increased over the past 10-15 years. Studies describing the effects of caffeine and caffeinated beverages show confusing results, so it seems important to regularly summarize the available facts, and in more detail. By a thorough analysis of more than 156 scientific papers, the authors describe the molecular background of absorption, as well as the positive and negative effects of different dosages of caffeine, just like its effects in physical activity and performance. ED and EDwA consumption is a regular habit of not only adults, but nowadays even of children and adolescents. There are no safe dosages described of caffeine or ED consumption for children. There are no positive short- or long-term effects of these compounds/products concerning developing brain functions, psycho-motor functions, or social development. Instead, there are many unpleasant side effects, and symptoms of regular or higher-dose ED consumption, especially at younger ages. This mini review describes many details of these unpleasant side effects, their severity, and motivations for consuming these compounds/products. In a quantitative research in Hungary (10-26 years, mean age: 15.6 ± 3.8 y, 1459 subjects, randomly chosen population), a survey based on a questionnaire asking people about their ED consumption habits was conducted. According to the data, 81.8% of the participants consumed EDs at least once, and 63.3% tried several products of the kind. A positive correlation was found between age and consumption ( p < 0.001). The results show that a high proportion of this group often consumed EDwA, in many cases leading to harmful side-effects of caffeine overdose. In a sample of Hungarian high school and college students (17-26 years), ED consumption matched the international data, and only 19.7% of respondents did not use EDs at all (had never tasted an ED in their life).

Objectives: Both exercise and a ketogenic (low-carbohydrate) diet favor glycogen depletion and increase ammonemia, which can impair physical performance. Caffeine supplementation has been routinely used to improve exercise performance. Herein, the effect of xanthine was evaluated on ammonemia in cyclists who were placed on a ketogenic diet and engaged in prolonged exercise., Methods: Fourteen male cyclists followed a ketogenic diet for 2 d before and during the experimental trial. The cyclists were assigned to either the caffeine- (CEx; n = 7) or placebo-supplemented (LEx; n = 7) group. Blood samples were obtained during cycling and the recovery periods., Results: The CEx group showed a significant decrease (up to 25%) in blood ammonia at 60, 90, and 120 min after beginning exercise compared with the LEx group. A higher concentration of apparent blood urea was observed in the LEx group than in the CEx group at 60 to 90 min of exercise (~10%). In addition, a significant increase in blood glucose levels was evident at 30 min of exercise (~28%), and an increase in blood lactate levels was visible during the first 30 to 60 min of exercise (~80%) in the CEx group., Conclusions: Our results suggest that the consumption of caffeine might attenuate the increase in ammonemia that occurs during exercise., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Previously, we systemically confirmed that prenatal caffeine exposure (PCE) could cause intrauterine growth retardation (IUGR) and adrenal steroid synthesis dysfunction in offspring rats. However, the multi-generation inheritance of adrenal dysfunction and its epigenetic mechanism has not been reported. In this study, the PCE rat model was established, part of the pregnant rats were executed on gestational day 20, while the others were delivered normally and the fetal rats were reared into adulthood. The PCE female rats of filial generation 1 (F1) were mated with wild males to produce F2 offspring, and the same way to produce F3 offspring. All the adult female rats of three generations were sacrificed for the related detection. Results showed that PCE could decrease fetal weight, increase IUGR rate, and elevate serum corticosterone level. Meanwhile, the expression of fetal adrenal GR, DNMT3a/3b, miRNA let-7c increased while those of CTCF, H19, and StAR decreased, and the total methylation rate of the H19 promoter region was enhanced. We used SW-13 cells to clarify the molecular mechanism and found that cortisol-induced in vitro changes of these indexes were consistent with those in vivo. We confirmed that high level of cortisol through activating GR, on the one hand, promoted let-7 expression and inhibited StAR expression; on the other hand, caused high methylation and low expression of H19 by down-regulating CTCF and up-regulating DNMT3a/3b, then enhanced let-7 inhibitory effect on StAR by "molecular sponge" effect. Finally, in vivo experiments showed that the adrenal steroid synthesis function and H19/let-7 axis presented the glucocorticoid-dependent changes in the adult female F1, F2, and F3. In conclusion, PCE can cause female adrenal dysfunction with matrilineal multi-generation inheritance, which is related to the programming alteration of the H19/let-7 axis. This study provides a novel perspective to explain the multi-generation inheritance of fetal-originated disease in IUGR offspring., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ovarian dysfunction has an intrauterine origin, and prenatal caffeine exposure (PCE) could lead to abnormal follicle counts in offspring after birth. However, the effect of PCE on offspring ovarian function and its mechanism of intrauterine programming have not been reported thus far. In this study, pregnant Wistar rats were intragastrically administered caffeine (30 and 120 mg/kg·d) at gestational days 9-20 (GD9-20). Certain tests were performed on the blood, ovaries and hypothalamus of female offspring at different time points. PCE female offspring had ovarian dysfunction in adulthood compared with the control. Further results showed that in utero ovarian morphological development and estradiol synthesis were inhibited but rapidly increased during puberty in the PCE group. The histone 3 lysine 27 acetylation (H3K27ac) level of the insulin-like growth factor 1 (IGF1) promoter region and its expression were decreased in the ovary, which was due to exposure to high levels of fetal blood corticosterone, and the H3K27ac level of IGF1 and its expression shifted to increase after birth with a decrease in serum corticosterone levels. Chronic stress led to increased serum corticosterone levels in adult offspring, whereas ovarian morphological development, the H3K27ac level of IGF1 and its expression, and estradiol synthesis were significantly inhibited. Moreover, the activity of the hypothalamic-pituitary-ovarian (HPO) axis was increased in the early postnatal period of PCE offspring, and chronic stress reversed these changes. In the KGN cell line, it was found that cortisol could promote the translocation of the glucocorticoid receptor (GR) into the nucleus and upregulate histone deacetylase 10 (HDAC10) to inhibit the H3K27ac level of IGF1 and its expression and estradiol synthesis. In summary, PCE is associated with ovarian dysfunction in female adult offspring, and the potential mechanism is related to intrauterine high glucocorticoid exposure by activating the GR and recruiting HDAC10 to affect ovarian glucocorticoid-IGF1 axis programming and to inhibit estradiol synthesis., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this research, we addressed a challenge while measuring the penetration performance of caffeine (CAF) using confocal Raman spectroscopy (CRS). Normally in the process of CRS analysis, skin sample was moved from an incubation setup to a specified CRS-measuring sample holder. Accurate data collection may be questioned due to the variation of the environment the skin placed in. Therefore, two critical parameters including the CRS measuring temperature and proper skin hydration were focused; accordingly, four different conditions were designed. First, the skin was incubated in a real-time device with the skin placing onto PBS-filled chamber where the temperature was adjusted to 32℃. This device can be fixed under the CRS microscope, enabling simultaneous skin incubation and dynamic CRS measurements (condition i, reference). The other conditions referred to skins incubated in Franz diffusion cells for simulating the common experimental procedures. In order to control variables of CRS measuring condition, skins were transferred from cells to real-time device and open device. In real-time device, proper skin hydration was maintained and the skin temperature was adjusted to 32℃ (condition ii) and room temperature (condition iii). In open device, the skin was in a less hydrated state by moving onto a PBS-soaked filter paper and wrapped with aluminum foil at room temperature (condition iv). The skin penetration performances measured in these conditions were compared with reference. Caffeine solution and gel formulation were separately applied to the skin. The results showed in both cases that the decrease of skin temperature and hydration in condition iii and iv would apparently induce the decrease of detected caffeine signal, resulting in the inaccurate data collection. To this point, it indicates the reduction of solubilized caffeine in skin layer. We suggest the forming of caffeine crystallization at varied skin conditions to be the factor. Achieved video image, CRS spectrum collection and surface scan demonstrated the caffeine crystallization process on superficial skin layer. Polarized microscopic images exemplified the crystalline drug on tape stripped skin layers. It can be a potential support of caffeine crystallization inside skin. In short, we suggest the consideration of these parameters during CRS measurements for accurate monitoring of topical drug delivery. Meanwhile, the use of real-time device for dynamic skin incubation and data collection provides advantages in saving time and efforts in this study., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The increasing numbers of elderly Alzheimer's disease (AD) patients because of a steady increase in the average lifespan and aging society attract great scientific concerns, while there were fewer effective treatments on AD progression due to unclear exact causes and pathogenesis of AD. Moderate (200-500 mg/d) and regular caffeine consumption from coffee and tea are considered to alleviate the risk of AD and have therapeutic potential. This paper reviewed epidemiological studies about the relationship of caffeine intake from coffee or/and tea with the risk of AD and summarized the caffeine-related AD therapies based on experimental models. And further well-designed and well-conducted studies are suggested to investigate the optimal dosages, frequencies, and durations of caffeine consumption to slow down AD progression and treat AD., Competing Interests: This study does not have any conflicts of interest., (Copyright © 2021 Xiangyu Zhou and Lin Zhang.)

Purpose: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS)., Methods: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment., Results: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A)., Conclusions: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS., Trial Registration: ISRCTN89898870. Registration date: July 24, 2014., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

A short-cut review of the literature was carried out to examine the benefits of caffeine as an analgesic adjunct in tension-type and migraine-type headache. Six papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that caffeine provides effective analgesia as an adjunctive treatment in the management of secondary headache syndromes., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A systematic literature review of publications from 2000 to 2020 was carried out to identify research trends on adsorbent materials for the removal of caffeine from aqueous solutions. Publications were retrieved from three databases (Scopus, Web of Science, and Google Scholar). Words "adsorption AND caffeine" were examined into titles, abstracts, and keywords. A brief bibliometric analysis was performed with emphasis on the type of publication and of most cited articles. Materials for the removal of caffeine were classified according to the type of material into three main groups: organic, inorganic, and composites, each of them subdivided into different subgroups consistent with their origin or production. Tables resume for each subgroup of adsorbents the key information: specific surface area, dose, pH, maximum adsorption capacity, and isotherm models for the removal of caffeine. The highest adsorption capacities were achieved by organic adsorbents, specifically those with granular activated carbon (1961.3 mg/g) and grape stalk activated carbon (916.7 mg/g). Phenyl-phosphate-based porous organic polymer (301 mg/g), natural sandy loam sediment (221.2 mg/g), composites of MCM-48 encapsulated graphene oxide (153.8 mg/g), and organically modified clay (143.7 mg/g) showed adsorption capacities lower than those of activated carbons. In some activated carbons, a relation between the specific surface area (SSA) and the maximum adsorption capacity ( Q max ) was found., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Javier Andrés Quintero-Jaramillo et al.)

Caffeine is a common stimulant consumed daily worldwide and available in a wide variety of over-the-counter formulations. It is a mild central nervous system stimulant when used in recommended doses. However, it can be fatal if taken as an intentional or accidental overdose. We report a case of a 48-year-old lady with depression and post-traumatic stress disorder who consumed a significant overdose of caffeine, triggered by the stress that she had contracted coronavirus disease 19. This led to significant cardiovascular and central nervous system toxicity. The condition was identified early and managed appropriately with early β-blockers and gastric decontamination, which saved her life. There are few studies with regard to such modalities on treatment for caffeine overdose; our patient responded rapidly and favourably to the treatment. Why should an emergency physician be aware of this? Caffeine overdose is uncommon but one that clinicians should be aware of. Early identification and intervention with β-adrenergic antagonists and activated charcoal is paramount in caffeine toxicity., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Australian College of Critical Care Nurses Ltd. All rights reserved.)

Objective: We examined the effects of caffeine, time of day, and alertness fluctuation on plasticity effects after transcranial alternating current stimulation (tACS) or 25 ms paired associative stimulation (PAS25) in caffeine-naïve and caffeine-adapted subjects., Methods: In two randomised, double-blinded, cross-over or placebo-controlled (caffeine) studies, we measured sixty subjects in eight sessions (n = 30, Male: Female = 1:1 in each study)., Results: We found caffeine increased motor cortex excitability in caffeine naïve subjects. The aftereffects in caffeine naïve subjects were enhanced and prolonged when combined with PAS 25. Caffeine also increased alertness and the motor evoked potentials (MEPs) were reduced under light deprivation in caffeine consumers both with and without caffeine. In caffeine consumers, the time of day had no effect on tACS-induced plasticity., Conclusions: We conclude that caffeine should be avoided or controlled as confounding factor for brain stimulation protocols. It is also important to keep the brightness constant in all sessions and study groups should not be mixed with caffeine-naïve and caffeine consuming participants., Significance: Caffeine is one of the confounding factors in the plasticity induction studies and it induces different excitability effects in caffeine-naïve and caffeine-adapted subjects. This study was registered in the ClinicalTrials.gov with these registration IDs: 1) NCT03720665 https://clinicaltrials.gov/ct2/results?cond=NCT03720665&term=&cntry=&state=&city=&dist= 2) NCT04011670 https://clinicaltrials.gov/ct2/results?cond=&term=NCT04011670&cntry=&state=&city=&dist=., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

In the present paper, a nanocomposite of rGO and TiO2 nanoparticles (TiO2/rGO) was prepared by a facile synthesis method with peroxo titanium complexes as TiO2 precursor. The morphology and structure of TiO2/rGO nanocomposite were investigated by X-ray diffraction (XRD), Raman spectroscopy, nitrogen adsorption/desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray (EDX)-elementary mapping spectroscopy. It was found that TiO2/rGO nanocomposites with high surface area were formed involving strong coupling interaction between TiO2 and rGO. Based on the synergistic effect of rGO and TiO2 nanoparticles, an electrochemical sensor for paracetamol (PAR) and codeine (COD) was fabricated by modifying the glassy carbon electrode (GCE) with TiO2/rGO material. The cyclic voltammetry (CV) and differential pulse anodic stripping voltammetry (DP-ASV) were used to determine the electrochemical signals of these analytes. CVs of this sensor provided distinct and sharp oxidation peaks for PAR and COD. The DP-ASV parameters were optimized. It was found that the proposed electrode exhibits excellent electrochemical activity toward PAR and COD. Under the optimal conditions, the A low limit of detection of 0.28 µM for PAR and 0.25 µM for COD were achieved in the linear range from 0.4 to 2.0 µM for both PAR and COD. The proposed method was free from the interference effects of glucose, ascorbic acid, caffeine, and other inorganic salts. This electrode was also highly stable and sensitive making it applicable in the analysis of various real pharmaceutical samples.Graphical abstract: In the present paper, a nanocomposite of rGO and TiO2 nanoparticles (TiO2/rGO) was prepared by a facile synthesis method with peroxo titanium complexes as TiO2 precursor. The morphology and structure of TiO2/rGO nanocomposite were investigated by X-ray diffraction (XRD), Raman spectroscopy, nitrogen adsorption/desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray (EDX)-elementary mapping spectroscopy. It was found that TiO2/rGO nanocomposites with high surface area were formed involving strong coupling interaction between TiO2 and rGO. Based on the synergistic effect of rGO and TiO2 nanoparticles, an electrochemical sensor for paracetamol (PAR) and codeine (COD) was fabricated by modifying the glassy carbon electrode (GCE) with TiO2/rGO material. The cyclic voltammetry (CV) and differential pulse anodic stripping voltammetry (DP-ASV) were used to determine the electrochemical signals of these analytes. CVs of this sensor provided distinct and sharp oxidation peaks for PAR and COD. The DP-ASV parameters were optimized. It was found that the proposed electrode exhibits excellent electrochemical activity toward PAR and COD. Under the optimal conditions, the A low limit of detection of 0.28 µM for PAR and 0.25 µM for COD were achieved in the linear range from 0.4 to 2.0 µM for both PAR and COD. The proposed method was free from the interference effects of glucose, ascorbic acid, caffeine, and other inorganic salts. This electrode was also highly stable and sensitive making it applicable in the analysis of various real pharmaceutical samples. [ABSTRACT FROM AUTHOR]

Combination of 'green' coagulation and powdered activated carbon adsorption was tested for removal of benzophenone (BP), benzophenone-3 (BP-3) and caffeine (CF) from treated municipal wastewater at realistic concentration levels (1–2 µg/L). At the same time it was tracked how the process affected effluent organic matter (EfOM) by measuring chemical oxygen demand (COD). Green coagulant was produced from dry common bean seed in laboratory. Combined coagulation-adsorption experiments were performed by applying different dosing sequences of process materials. Removal of hydrophobic BP and BP-3 by separate adsorption (from 79 to 98%) was not significantly hindered by the addition of the coagulant (activated carbon dose of 5 or 20 mg/L). However, in some cases negative effects were observed for hydrophilic caffeine, depending on the carbon dose, dosing sequence and presence of total suspended solids (TSS). Thus, when coagulant was firstly added into water without TSS before low activated carbon dose of 5 mg/L, caffeine removal dropped from 26% to 5%. Conversely, when TSS were present in the water sample, the removal of caffeine was not hindered under the same PAC dose and dosing sequence. The importance of the process optimisation related to removal of organic micropollutans of different hydrophilicity has been shown in this paper. Removal of around 30% of COD regardless of the dosing sequence was achieved. [ABSTRACT FROM AUTHOR]

Various natural products are potentially suitable for wood protection, particularly against fungi attack. Caffeine is a well-known compound of natural origin, commercially and economically available, which could facilitate its future use for wood protection. This work investigated the antifungal resistance of the sapwood of Scots pine (Pinus sylvestris L.) treated with a water solution of caffeine and then thermally modified. The samples after impregnation were thermally modified at different temperatures selected on the basis of thermogravimetric analysis (TGA) of caffeine. The paper presents preliminary results of resistance of treated pinewood towards Aspergillus niger van Tieghem (ATCC 6275). The treated samples were subjected to both a leaching procedure and to the artificial aging procedure imitating natural weather conditions. Thermal modification of wood treated with caffeine improved the fungistatic properties of samples after artificial aging. It occurred through partial elimination of caffeine leaching from the wood structure. [ABSTRACT FROM AUTHOR]

Aim: In this work, the effect of supplementing liquid cellulase production media (CPM) with methylxanthines (aminophylline, caffeine and theophylline), with and without the addition of glucose, on the secretion of cellulases by Penicillium echinulatum strain 2HH (wild-type) and the derived mutant strain 9A02S1 was studied. Methods and Results: When compared with unsupplemented CPM, both strains produced higher β-glucosidase and filter paper activities (FPAs) in CPM supplemented with 1 μmol l−1 of caffeine but lower activities with 5 μmol l−1 of caffeine. With theophylline only, strain 9A02S1 produced higher β-glucosidase and FPAs, while aminophylline produced no effect on the cellulase activity of either strain. Supplementation of CPM with 0·5% (w/v) of glucose plus caffeine resulted in higher β-glucosidase and FPAs being produced by strain 2HH, but not strain 9A02S1, than in CPM supplemented with 0·5% (w/v) of glucose only. Conclusions: These results indicate that different concentrations of caffeine and theophylline can increase the β-glucosidase and FPAs produced by P. echinulatum strains 2HH and 9A02S1. Significance and Impact of the Study: The results suggest that some methylxanthines, in adequate concentration, can be used as media components to increase cellulase production. [ABSTRACT FROM AUTHOR]

This paper presents two validated chromatographic methods, namely thin-layer chromatography (TLC)–densitometry and high-performance liquid chromatography (HPLC), for the simultaneous determination of caffeine (CAF), codeine (COD), paracetamol (PAR) in the presence of p-aminophenol (PAP) in their quaternary mixture. Good separation was achieved by using silica gel as the stationary phase and chloroform‒methanol‒acetone‒ammonia (8:1:2:0.1, V/V) as the mobile phase in the case of TLC–densitometry with retardation factor (RF) values of 0.38 ± 0.02, 0.24 ± 0.02, 0.61 ± 0.02 and 0.46 ± 0.02 for PAR, COD, CAF and PAP, respectively. Zorbax ODS column with mobile phase consisting of 0.1% orthophosphoric acid and acetonitrile (92:8, V/V) was used as stationary and mobile phase for HPLC, respectively, with retention time (tR) values of 1.1, 3.5, 4.6 and 8.5 min for CAF, PAP, COD and PAR, respectively. The two proposed methods were validated as per the International Council for Harmonisation guidelines. Finally, they were successfully applied for determination of the cited drugs in their quaternary mixture and marketed formulation. [ABSTRACT FROM AUTHOR]

Yerba Mate, coffee and tea consumption varies depending on the country, region and cultural background. The highest quantity of tea is consumed in Turkey, coffee in Finland and Yerba Mate in Argentina. The purpose of this paper is to present the economic and qualitative factors that determine the consumption of Yerba Mate, coffee and tea. The determinants and factors influencing the volume of production and consumption were analysed. A comparison of selected qualitative parameters, such as polyphenols, antioxidising effects and caffeine, was drawn. The discussed parameters determine, to a great extent, the demand for these products. The analysis made it possible to conclude that the analysed products can function as substitutes for each other, both in terms of economics and sensory and health-promoting properties. [ABSTRACT FROM AUTHOR]

A clinical trial is currently underway to examine the efficacy of using caffeine citrate to prevent intermittent hypoxemia in late preterm neonates. Determining caffeine concentration using saliva in this population would be preferable as it is less invasive than plasma sampling, but a suitable method of analysis is required. This paper presents the development and validation of a rapid, efficient and reproducible stability-indicating high-performance liquid chromatography (HPLC) method and extraction protocol for the quantification of caffeine present in saliva. The stability of extemporaneously prepared caffeine citrate solutions (at 20–25 °C) was determined, along with the stability of caffeine spiked saliva samples (at 20–25 and 2–8 °C), to ensure the suitability of the developed method in the analysis of clinical trial samples. Protein precipitation using acetonitrile ensured the complete removal of salivary proteins and resulted in extraction recovery of ≥95% for all samples. The HPLC assay following extraction was linear (R2>0.99) over the range 0.3–50 µg/mL (lower limit of quantification 0.3 µg/mL). The accuracy of the quality control samples was 94–100% and the relative standard deviation (RSD) was <7% for all samples. Caffeine-spiked saliva samples were stable for three freeze-and-thaw cycles pre-extraction and up to 72 hr post-extraction. The extraction and HPLC methods described were thus suitable for the analysis of clinical trial samples from the Latte Dosage Trial. All caffeine solutions were physically and chemically stable, with concentrations at the end of the three-month test period being within 4% of the baseline concentrations, indicating appropriateness for use as clinical trial medications. [ABSTRACT FROM AUTHOR]

In this paper, a simple and clean process for the alkylation and arylation of nitrogen containing heterocycles is reported. The reactions were conducted using the Q-tube® as a nonconventional technology, in water as a green solvent, at overboiling temperature. The developed strategy was used to improve two steps in the total synthesis of caffeine, as reported by Narayan, and then extended to the preparation of N-decorated xanthines. Finally, piperidine, methyl piperazine, and isatine were proven to be suitable substrates for the protocol proposed herein. [ABSTRACT FROM AUTHOR]

Background: There is evidence that caffeine increases the maximal fat oxidation rate (MFO) and aerobic capacity, which are known to be lower in the morning than in the afternoon. This paper examines the effect of caffeine intake on the diurnal variation of MFO during a graded exercise test in active men. Methods: Using a triple-blind, placebo-controlled, crossover experimental design, 15 active caffeine-naïve men (age: 32 ± 7 years) completed a graded exercise test four times at seven-day intervals. The subjects ingested 3 mg/kg of caffeine or a placebo at 8 am in the morning and 5 pm in the afternoon (each subject completed tests under all four conditions in a random order). A graded cycling test was performed. MFO and maximum oxygen uptake (VO2max) were measured by indirect calorimetry, and the intensity of exercise that elicited MFO (Fatmax) calculated. Results: MFO, Fatmax and VO2max were significantly higher in the afternoon than in the morning (all P < 0.05). Compared to the placebo, caffeine increased mean MFO by 10.7% (0.28 ± 0.10 vs. 0.31 ± 0.09 g/min respectively, P < 0.001) in the morning, and by a mean 29.0% (0.31 ± 0.09 vs. 0.40 ± 0.10 g/min, P < 0.001) in the afternoon. Caffeine also increased mean Fatmax by 11.1% (36.9 ± 14.4 [placebo] vs. 41.0 ± 13.1%, P = 0.005) in the morning, and by 13.1% (42.0 ± 11.6 vs. 47.5 ± 10.8%, P = 0.008) in the afternoon. Conclusion: These findings confirm the previously reported diurnal variation in the whole-body fat oxidation rate during graded exercise in active caffeine-naïve men, and indicate that the acute ingestion of 3 mg/kg of caffeine increases MFO, Fatmax and VO2max independent of the time of day. Trial registration: NCT04320446. Registered 25 March 2020 - Retrospectively registered [ABSTRACT FROM AUTHOR]

AbstractEthiopia is the fifth-largest coffee producer in the world. The country has made continuous efforts to enhance the production, productivity and quality of its coffee. Yet, comprehensive data on these issues are scant. This paper aims to document available information on the economic importance, production, productivity, quality and chemical contents of Ethiopian coffee, and to identify developmental and/or research gaps on its productivity and quality. Coffee now accounts for ca. 25–30% of the country’s total foreign currency earnings and the amount of foreign currency earnings from coffee increases over the years with a varying rate. Production and cultivation areas of Ethiopian coffee also increase over the past 60 years, but the changes in its productivity and quality are minor. Also, the share of the top grade (Grade 1 and 2) coffees in Ethiopia has remained lower over time, and the quality and chemical composition of Ethiopian coffee vary with growing region and locality. Compared to others, coffees from Eastern (Harar) and Southern regions are better in overall quality, and coffee from Northwestern region is higher in chlorogenic acid and sucrose contents, whereas those from Harar and Southwestern regions are lower in caffeine and chlorogenic acid contents, respectively. However, Harar coffee is higher in fatty acid content than other region coffees. Overall, the paper shows (1) the economic importance, production, productivity, quality and chemical contents, (2) information gaps on productivity, and quality and chemical profiles, and (3) the existence of a large room for productivity and quality improvements of Ethiopian coffee.

In the current paper, we investigated the electrochemical degradation of some pharmaceuticals, including an antioxidant (vitamin E), anti-coronavirus and anti-skin diseases and supplements (vitamin B1 or thiamin HCL), anti-inflammatories (caffeine, ibuprofen, acetaminophen), and antidepressants antipsychotic medications (quetiapine fumarate). For this purpose, we employed an advanced electrochemical oxidation process using Ti/nano SnO2-α-Fe2O3 electrode by Na2SO4 or NaCl as a supporting electrolyte. We also evaluated the effects of pH and supporting electrolytes. On the degradation of pharmaceuticals and optimized the process. Results showed that the best conditions for supporting electrolytes were a pH of 7 for Na2SO4 or NaCl with a concentration of 1 g/L. Under optimum conditions, we achieved about 100% efficiency in the removal of pharmaceuticals. The total organic carbon (TOC) removal of 98.57% and 99.37% were also obtained, after 270 min of treatment with Na2SO4 and NaCl, respectively. In addition, in the same condition, the removal efficiency of pharmaceuticals after 150 min, was about 80% and TOC removal was equal to 90.21% and 80.74% with Na2SO4 and NaCl, respectively. It was shown that NaCl was stronger than Na2SO4 stronger Ti/nano SnO2-α-Fe2O3 electrode is applicable for the electrochemical treatment of pharmaceutical pollutants simultaneously. [ABSTRACT FROM AUTHOR]

Dietary intake of caffeine has significantly increased in recent years, and beneficial and harmful effects of caffeine have been extensively studied. This paper reviews antioxidant and anti-inflammatory activities of caffeine as well as its protective effects on cardiovascular diseases, obesity, diabetes mellitus, cancers, and neurodegenerative and liver diseases. In addition, we summarize the side effects of long-term or excessive caffeine consumption on sleep, migraine, intraocular pressure, pregnant women, children, and adolescents. The health benefits of caffeine depend on the amount of caffeine intake and the physical condition of consumers. Moderate intake of caffeine helps to prevent and modulate several diseases. However, the long-term or over-consumption of caffeine can lead to addiction, insomnia, migraine, and other side effects. In addition, children, adolescents, pregnant women, and people who are sensitive to caffeine should be recommended to restrict/reduce their intake to avoid potential adverse effects. [ABSTRACT FROM AUTHOR]

Caffeine is described as an essential naturally occurring, viable, and marketable purine alkaloids which can be degraded by bacteria; the competence of bacteria to use caffeine as its sole source of carbon and nitrogen has been elucidated more than four decades ago. This paper presents a review of the potential of microbial decaffeination process using standard techniques of harvesting recent and appropriate information and data from Online and Library sources focusing on to bacterial caffeine degradation processes: N-demethylation and C-8 oxidation. These two processes were observed to be more efficient, safe, specific, and economically crucial to caffeine degradation. Various organisms have been isolated across the globe that are capable to degrading caffeine such as Klebsiella, Rhodococcus, Alcaligenes, Serratia, Phanerochaete, and Bacillus sp. Furthermore, innumerable biotechnological application of the bacterial caffeine degradation has been identified such as bioremediation of caffeine-polluted environment, bio-decaffeination, chemical production, and diagnostic tools. [ABSTRACT FROM AUTHOR]

A factorial design with a duplicate in the central point was used to investigate the effect of treating arabica coffee beans with asparaginase. The investigated factors were enzymatic load (1000 and 5000 ASNU/Kg), water percentage (30 and 90%), and hydrolysis time (1 and 3 h). The acrylamide content was determined by UPLC-MS/MS, and the caffeic acid, chlorogenic acid and caffeine concentrations were determined by HPLC-DAD. The statistical analysis was carried out in the R platform using RStudio graphical interface. The results indicated the importance of coffee bean pretreatment with steam, and that the enzyme load reduced the acrylamide content to 65 mg/kg in coffee beans. The predicted reduction was obtained with hydrolysis time of 2 h, water content of 90%, and asparaginase load of 5000 ASNU/kg. The asparaginase treatment did not influence the major bioactive compounds in coffee., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This work presents the application of EC-SERS spectroscopy for the detection of caffeine consumption from human saliva. Caffeine and paraxanthine as the major metabolite of caffeine were tested. Model samples of saliva spiked with caffeine were investigated, and detection of caffeine in real-life saliva samples was tested in order to ensure the viability of the method for clinical applications. Two doses of caffeine (2 mg/kg and 3.5 mg/kg) were ingested by volunteers, and their saliva samples were taken at different time periods ranging from 1 h to 10 h after the consumption. Density functional theory calculations of caffeine and paraxanthine adsorbed on the silver surface were performed in order to better understand the adsorption of the investigated molecules and to make a correct assignment of the experimental spectral bands of the EC-SERS spectra. It was determined that a low dose caffeine consumption can be detected by the appearance of the SERS spectral marker band of caffeine and paraxanthine at 692 cm -1 . The intensity of this band is mostly reasoned by the paraxanthine concentration since the intensity changes of the band over time correlates to the concentration changes of paraxanthine determined by the pharmacokinetic studies of paraxanthine and caffeine in the human saliva. It was found that the limit of detection paraxanthine in saliva by means of EC-SERS is as low as 15 μM and can be further improved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cold-adapted endo-β-1,4-glucanases hold great potential for industrial processes requiring high activity at mild temperatures such as in food processing and extraction of bioactive compounds from plants. Here, we identified and explored the specificity, mode of action, kinetic behavior, molecular structure and biotechnological application of a novel endo-β-1,4-glucanase (XacCel8) from the phytopathogen Xanthomonas citri subsp. citri. This enzyme belongs to an uncharacterized phylogenetic branch of the glycoside hydrolase family 8 (GH8) and specifically cleaves internal β-1,4-linkages of cellulose and mixed-linkage β-glucans releasing short cello-oligosaccharides ranging from cellobiose to cellohexaose. XacCel8 acts in near-neutral pHs and in a broad temperature range (10-50 °C), which are distinguishing features from conventional thermophilic β-1,4-glucanases. Interestingly, XacCel8 was greatly stimulated by cobalt ions, which conferred higher conformational stability and boosted the enzyme turnover number. The potential application of XacCel8 was demonstrated in the caffeine extraction from guarana seeds, which improved the yield by 2.5 g/kg compared to the traditional hydroethanolic method (HEM), indicating to be an effective additive in this industrial process. Therefore, XacCel8 is a metal-stimulated and cold-adapted endo-β-1,4-glucanase that could be applied in a diverse range of biotechnological processes under mild conditions such as caffeine extraction from guarana seeds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This paper aimed to: (a) critically review studies that explored the isolated and combined effects of caffeine and sodium bicarbonate ingestion on exercise performance; (b) discuss some of the possible reasons for the discrepancy in findings; and, (c) provide suggestions for future studies. Out of the eight studies that examined this topic, only one study found that the combined ingestion of both supplements provided additive effects. In other studies, the following findings were observed: (a) only caffeine was ergogenic; (b) isolated and combined ingestion of both supplements was comparably ergogenic; (c) neither isolated nor combined ingestion of caffeine and sodium bicarbonate provided a performance-enhancing effect; and, (d) caffeine and caffeine plus sodium bicarbonate improved performance compared to sodium bicarbonate (but not as compared to placebo). Even though studies used currently recommended protocols of caffeine supplementation and exercise tasks for which the isolated ergogenic effects of caffeine and sodium bicarbonate are already established, the response to sodium bicarbonate supplementation was very variable, which might largely explain the discrepancies in the findings. The protocols of sodium bicarbonate ingestion generally resulted in high incidence and severity of side-effects, which might have had a negative effect on exercise performance. Future studies that optimize protocols of sodium bicarbonate supplementation are needed to fully explore if combining caffeine and sodium bicarbonate indeed provides any additive effects on exercise performance.

In this paper, Chemometric assisted UV spectrophotometric and RP-HPLC methods were developed and compared for simultaneous determination of Paracetamol, Diphenhydramine Hydrochloride, Caffeine and Phenylephrine Hydrochloride in tablet dosage form. UV-Spectrophotometric analysis was carried out by applying two chemometric models namely, Principal Component Regression method (PCR) and Partial Least Squares Regression method (PLSR). Chromatographic method was developed and optimized by applying Response surface methodology -Central Composite Design (CCD). These methods were considered first for the quantification of the drugs present in the selected formulation. PCR and PLSR models were successfully validated and applied for resolving the complex UV-spectra in the wavelength range of 240-320 nm with a data interval of 1 nm. In RP-HPLC method, the identified critical factors were methanol content (45-55% v/v) and flow rate (0.75-0.85 mL/min) and the selected responses were retention time (Rt 4 ) of fourth eluted component and resolution (RS 1,2 ) between first and second eluted components. Derringer's desirability function was used for the optimization of the chromatographic method conditions which comprised of mobile phase consisting of methanol‑potassium dihydrogen orthophosphate buffer (pH 3; 10 mM) (50: 50, v/v) and at a flow rate of 0.81 mL/min with a detection wavelength of 220 nm. One-way ANOVA in 95% confidence interval revealed that there were no significant differences among the developed methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aging is a multifactorial process accompanied by loss of cell function. Science has been looking for factors responsible for aging for many years. However, despite identifying a number of possible causes, the definite reason for aging has been elusive so far. One of the factors contributing to aging is oxygen free radicals. In this context, beneficial effects of coffee on various organisms, including humans, were investigated, although the results are far from unequivocal. In our research, we used the budding yeast-something of a workhorse in many studies, including the studies of aging. So far, the impact of coffee on the aging of cells in the budding yeast experimental setup has little known about it. Here, we provide strong evidence that coffee compounds, particularly flavonoids, are responsible for scavenging free radicals and longevity in yeast lacking Sod1, Sod2 and Rad52 proteins. In this paper, we compared Arabica and Robusta coffee types. We present an analysis of the concentration of caffeine and flavonoids measured by the High-Performance Liquid Chromatography method. We show that Robusta has a much greater antioxidant capacity than Arabica. We also conclude that coffee infusions significantly extend the chronological lifespan of the Saccharomyces cerevisiae yeast cells by protecting cells against reactive oxygen species, double DNA-strand break and decrease in metabolic activity.

Smoking cigarettes and drinking coffee are common habits in today's society. However, it is not easy to get up-to-date information on smoking prevalence and caffeine consumption as it is usually obtained from population surveys. To overcome this limitation and complement epidemiological information, we employed wastewater-based epidemiology (WBE) to gain a picture of the consumption of cigarettes and caffeine per day per person in Italy. A nationwide study was conducted by measuring two urinary metabolites of nicotine (cotinine and trans-3'-hydroxycotinine) and a caffeine metabolite (1,7-dimethyluric acid) in untreated wastewater from 16 cities. The spatial profiles of use depended mostly on the specific population habits in each city, not on the geographical area or the population size. The patterns of consumption were stable over the week, except in Milan where the use of both substances decreased on Sundays, probably because there were no commuters. In Milan, the use of nicotine decreased from 2013 to 2015. There was a significant relationship between smoking and consumption of products containing caffeine (mainly coffee), thus in cities where more cigarettes were smoked, more caffeine was drunk. These results are generally in accordance with findings from epidemiological studies, but provide some additional local profiles of use and closely follow changes over the years. This information could be useful for healthcare professionals and policy-makers to monitor progress towards the reduction of prevalence in tobacco use, and set up new health campaigns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Klein-Levin Syndrome (KLS) is a rare disorder identified by recurrent hypersomnia, over-eating, or hypersexuality and is associated with cognitive dysfunction or abnormal behaviors. Case presentation: In this paper, we presented a 36-year-old single female with chief complaints of headaches, tiredness, and sleepiness. She reported attacks of hypersomnia and memory deficits from childhood. She experienced addiction to alcohol, caffeine, and sugar, also depression, and suicidal taught. The full medical work-up did not indicate any organic illness. Polysomnography and Multiple Sleep Latency Tests indicated narcolepsy. Finally, she was diagnosed with Klein-Levin syndrome. Conclusion: Kleine-Levin Syndrome is a challenging diagnosis. The medical history of clinical symptoms and exclusion of other diagnoses can lead to better diagnosis in patients with hypersomnolence. [ABSTRACT FROM AUTHOR]

Objective: Lack of mental energy is one of the leading reasons adults turn to dietary supplements, with three out of ten supplement users hoping to improve their energy level; even more consume caffeine-containing products for the same reason. Despite this interest from consumers, there is no consensus scientific definition of mental energy or sole validated instrument for measuring it. We performed this review to summarize main findings from research regarding the influence of natural dietary compounds on three aspects of mental energy: cognition (vigilance), motivation (to do mental work), and mood (feelings of energy and/or absence of feelings of fatigue). Methods: A narrative review of key papers. Results: In addition to caffeine, a number of other compounds, including the polyphenols, which are found in all plant-derived products, and the phytochemicals in culinary herbs and herbal products such as Panax ginseng and Ginkgo biloba, have been shown in animal models to modulate neurotransmitter activity potentially relevant to mental energy. Inadequate intake of B vitamins could also potentially have a negative effect on mental energy due to their role in overall energy production, as precursors of key cofactors in the citric acid cycle, as well as their role in brain function and neurotransmitter synthesis. Consumption of some of these products may have direct or indirect effects on one or more elements of mental energy. Conclusion: Large, prospective clinical trials of these products using appropriate, validated instruments designed to measure mental energy may be worthwhile if sufficient evidence exists to justify such trials. [ABSTRACT FROM AUTHOR]