Priess, J. A.; Mimler, M.; Klein, A. M.; Schwarze, S.; Tscharntke, T.; Steffan-Dewenter, I.
The ecological and economic consequences of rain forest conversion and fragmentation for biodiversity, ecosystem functioning, and ecosystem services like protection of soils, water retention, pollination, or biocontrol are poorly understood. In human-dominated tropical landscapes, forest remnants may provide ecosystem services and act as a source for beneficial organisms immigrating into adjacent annual and perennial agro-ecosystems. In this study, we use empirical data on the negative effects of increasing forest distance on both pollinator diversity and fruit set of coffee to estimate future changes in pollination services for different land use scenarios in Sulawesi, Indonesia. Spatially explicit land use simulations demonstrate that depending on the magnitude and location of ongoing forest conversion, pollination services are expected to decline continuously and thus directly reduce coffee yields by up to 18%, and net revenues per hectare up to 14% within the next two decades (compared to average yields of the year 2001). Currently, forests in the study area annually provide pollination services worth 46 Euros per hectare. However, our simulations also revealed a potential win-win constellation, in which ecological and economic values can be preserved, if patches of forests (or other natural vegetation) are maintained in the gricultural landscape, which could be a viable near future option for local farmers and regional land use planners.
Source : Ecol Appl 2007 vol.17 (2), pp 407 - 417 (not available on line)
Rustenbeck, I.
The current pharmacological therapy of type 2 diabetes reduces the risk of diabetic complications, but is not able to achieve a long-lasting normalization of the metabolic disorder. Thus diabetic patients in increasing numbers are taking dietary supplements and herbs from which they expect additional health benefits. These unconventional antidiabetic agents consist mainly in trace metals like chromium, vanadium and zinc and a heterogeneous group of traditionally used antidiabetic herbs (e. g. Momordica charantia, Gymnema sylvestre, Trigonella foenum-graecum) often derived from the ayurvedic medicine. In this overview the current evidence for the antidiabetic effect is presented. The trace elements chromium and vanadium have a number of potentially antidiabetic actions in vitro, however, the results obtained with diabetic patients are not convincing so far. Similarly, the available data on the therapeutic use of herbs suggest that in principle a number of them possess a blood glucose-lowering effect, but at present no firm conclusions as to their efficacy and safety can be made. To set up reliable dose-effect relationships requires the identification of the relevant antidiabetic molecules as was apparently achieved by isolating 4hydroxyisoleucine from the seeds of T. foenum-graecum. This requirement is also valid in the case of the antidiabetic action of cinnamon. Coffee and a moderate alcohol consumption were found to be surprisingly effective in lowering the risk of type 2 diabetes manifestation, their effect being roughly equal to that of conventional drugs used in diabetes prevention trials. Diabetic patients should inform their physician about the use of unconventional agents and should be warned against uncontrolled starting or stopping their use.
Source : Med Monatsschr.Pharm 2007 vol.30 (4), pp 131 - 137 (not available on line)
De Nardi, B.; Dreos, R.; Del Terra, L.; Martellossi, C.; Asquini, E.; Tornincasa, P.; Gasperini, D.; Pacchioni, B.; Rathinavelu, R.; Pallavicini, A.; Graziosi, G.
Coffea arabica is susceptible to several pests and diseases, some of which affect the leaves and roots. Systemic acquired resistance (SAR) is the main defence mechanism activated in plants in response to pathogen attack. Here, we report the effects of benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester (BTH), a SAR chemical inducer, on the expression profile of C. arabica. Two cDNA libraries were constructed from the mRNA isolated from leaves and embryonic roots to create 1587 nonredundant expressed sequence tags (ESTs). We developed a cDNA microarray containing 1506 ESTs from the leaves and embryonic roots, and 48 NBS-LRR (nucleotide-binding site leucine-rich repeat) gene fragments derived from 2 specific genomic libraries. Competitive hybridization between untreated and BTH-treated leaves resulted in 55 genes that were significantly overexpressed and 16 genes that were significantly underexpressed. In the roots, 37 and 42 genes were over and underexpressed, respectively. A general shift in metabolism from housekeeping to defence occurred in the leaves and roots after BTH treatment. We observed a systemic increase in pathogenesis-related protein synthesis, in the oxidative burst, and in the cell wall strengthening processes. Moreover, responses in the roots and leaves varied significantly.
Teodoro, A. V.; Reis, P. R.
The flat-mite Brevipalpus phoenicis (Geijskes, 1939) (Acari: Tenuipalpidae) is considered important incitrus (Citrus spp.) and coffee plants (Coffea spp.) in Brazil, and is known as the leprosis and coffee ring spot mite, as being a vector of the Citrus Leprosis Rhabdovirus - CitLV and Coffee Ring Spot Virus -CoRSV. The objective of this work is to find out about the reproductive success of B. phoenicis on citric fruits and coffee leaves by fertility life table parameters and its biology. The experiments were carried out in laboratory conditions at 25 +/- 2 degrees C, 70 +/- 10% of relative humidity and 14 h of photophase. The lengths of embryonic and post-embryonic periods were different due to the host where the mite was reared. B. phoenicis showed better development and higher survival and fecundity in citric fruits than coffee leaves. The intrinsic rate of the population increase (r(m)) was 0.128 and 0.090 -females/female/day on citric fruits and coffee leaves, respectively. The citric fruits were more appropriate for the development of B. phoenicis than coffee leaves.
Bustamante-Porras, J.; Campa, C.; Poncet, V.; Noirot, M.; Leroy, T.; Hamon, S.; de Kochko, A.To understand the importance of ethylene receptor genes in the quality of coffee berries three full-length cDNAs corresponding to a putative ethylene receptor gene (ETR1) were isolated from Coffea canephora cDNA libraries. They differed by their 3'UTR and contained a main ORF and a 5'UTR short ORF putatively encoding a small polypeptide. The CcETR1 gene, present as a single copy in the C. canephora genome, contained five introns in the coding region and one in its 5'UTR. Alternative splicing can occur in C. canephora and C. pseudozanguebariae, leading to a truncated polypeptide. C. pseudozanguebariae ETR1 transcripts showed various forms of splicing alterations. This gene was equally expressed at all stages of fruit development. A segregation study on an inter-specific progeny showed that ETR1 is related to the fructification time, the caffeine content of the green beans, and seed weight. Arabidopsis transformed etiolated seedlings, which over-expressed CcETR1, displayed highly reduced gravitropism, but the triple response was observed in an ethylene enriched environment. These plants behaved like a low-concentration ethylene-insensitive mutant thus confirming the receptor function of the encoded protein. This gene showed no induction during the climacteric crisis but some linkage with traits related to quality.
Filippi, S. B.; Azevedo, R. A.; Sodek, L.; Mazzafera, P.
In plants the ureides allantoin (ALN) and allantoic acid (ALA) are formed in purine metabolism, and in some legumes both compounds play an important role as nitrogen (N) sources. In coffee plants, ALN and ALA are catabolites of caffeine degradation. Caffeine is found throughout the coffee plant and in some parts this alkaloid can accumulate up to 4% dry basis. Therefore, caffeine degradation via ureides may make an important contribution to N metabolism of the plant. Using coffee cell suspension as a model we investigated the contribution of ALN as a source of N in coffee. ALN was incorporated in the liquid medium and after 20 d of cultivation, cell mass, NO(3), NH(4), amino acids, soluble proteins, ALN and caffeine were determined in the cells. The activity of glutamine synthetase was also studied. The results showed that despite being taken up by cells ALN does not contribute significantly as a source of N in coffee cells. Compared with mineral N sources, cells grown with ALN-N accumulated much less mass. The inclusion of ALN in the medium caused significant alterations in the content of some N compounds indicating a stress condition.
Mahe, L.; Le Pierres, D.; Combes, M. C.; Lashermes, P.
The importance of introgressive hybridization in plant evolution has long been recognized. Nevertheless, information on gene flow between allopolyploids and their diploid relatives is very limited, even though gene flow could play a major role in polyploid establishment and evolution. Here, we investigated the processes governing hybrid formation and introgression between the allotetraploid Coffea arabica and one of its ancestral diploid progenitors, C. canephora, in a sympatric zone of New Caledonia. The occurrence of a large assortment of hybridization events between the 2 coffee species is clearly established. First-generation hybrids (F1) and post-F1 hybrids were characterized. The involvement of unreduced gametes of C. canephora is suggested, because tetraploid F1 hybrid plants were detected. Moreover, although bidirectional mating was observed, only unidirectional gene flow from C. canephora to C. arabica was noted in post-F1 hybrids. Most of the collected post-F1 hybrid plants exhibited a high level of introgression, and the frequency of introgression observed among the different analyzed loci was homogeneous, suggesting no significant counterselection against introgressions from C. canephora. Overall, the New Caledonian central mountains appear to be a highly favourable environment for introgressive hybridization and a genetic diversity center for C. Arabica.
Source : Genome 2007 vol.50 (3), pp 316 - 324
Mandal, A.; Batabyal, S. K.; Poddar, M. K.
Inhibitory action of caffeine (a tri-methylxanthine alkaloid) on progression or pathogenesis of lung, breast and ovarian cancer including Ehrlich ascites carcinoma (EAC) cell development has been reported. This information led the authors to study the effect of long-term administration of caffeine (20 mg/kg/day; po for 22-27 consecutive days) on the development of EAC cells in relation to serum gonadal hormones (LH, FSH, 17-OH-beta-estradiol (E2) and progesterone) in adult Swiss albino female mice. Measurement of gonadal hormones in serum using RIA showed that (a) long-term caffeine treatment significantly increased LH (except for 27 consecutive days) and decreased FSH (except for 24 and 27 consecutive days) and both E2 and progesterone (except for 22 and 24 consecutive days) levels, (b) development of EAC cell for 10-15 days, significantly increased LH but decreased FSH, E2 and progesterone levels and (c) long-term caffeine consumption during the development of EAC cell (i) restored the EAC cell- or caffeine-induced induction of LH and reduction of FSH level to their normal levels and (ii) withdrew/reduced the EAC cell-induced reduction in only E2 but not progesterone level. These results therefore, suggest that prolonged affeine exposures may inhibit the development of EAC cell through the reduction or restoration of EAC cell-induced disruption of ovarian hormonal status to their normal status via the modulation of Hypothalamic-Pituitary-Gonadal (HPG) axis.
McCarthy, A. A.; McCarthy, J. G.
Caffeine (1,3,7-trimethylxanthine) is a secondary metabolite produced by certain plant species and an important component of coffee (Coffea arabica and Coffea canephora) and tea (Camellia sinensis). Here we describe the structures of two S-adenosyl-l-methionine-dependent N-methyltransferases that mediate caffeine biosynthesis in C. canephora 'robusta', xanthosine (XR) methyltransferase (XMT), and 1,7- dimethylxanthine methyltransferase (DXMT). Both were cocrystallized with the demethylated cofactor, Sadenosyl-l-cysteine, and substrate, either xanthosine or theobromine. Our structures reveal several elements that appear critical for substrate selectivity. Serine-316 in XMT appears central to the recognition of XR. Likewise, a change from glutamine-161 in XMT to histidine-160 in DXMT is likely to have catalytic consequences. A phenylalanine-266 to isoleucine-266 change in DXMT is also likely to be crucial for the discrimination between mono and dimethyl transferases in coffee. These key residues are probably functionally important and will guide future studies with implications for the biosynthesis of caffeine and its derivatives in plants.
Source : Plant Physiol 2007 vol.144 (2), pp 879 - 889
Finzer, J. R. D.; Sfredo, M. A.; Sousa, G. D. B.; Limaverde, J. R.
Information on residence time distribution of particles flowing in equipment is important for determining the dynamics of the process and characteristics of the finished product. This study examined the residence time distribution of coffee berries on a vibrated dryer with recycle, and determined the dispersion coefficients and Peclet number. The free dispersion equation estimated dispersion coefficient, and the coffee variety with the highest value was Catuai, which was composed of smaller particles, with greater sphericity. Flow velocity variation of coffee beans was the same magnitude as dispersion coefficient variation, and the authors conclude that convection was the dominant effect on flow of coffee berries in the vibrated tray dryer.
Source : Finzer, J. R. D.; Sfredo, M. A.; Sousa, G. D. B.; Limaverde, J. R.
Kalikake, K.; Hoaki, K.; Sunada, H.; Prasad-Dhakal, R.; Baba, Y.
Coffee bean wastes (after dripping and degreasing; DCB) were characterized and tested as a sorption material for base metals such as copper(II), zinc(II), lead(II), iron(III) and cadmium(II). Analysis of DCB wastes using FT-IR spectroscopy, SEM and fluorescent X-rays revealed a material with a porous cell wall structure, a specific surface area of 1.2 m2/g and a composition including sulfur and calcium. Batch sorption tests at varying pH showed adsorption of all metals at pH 3-5, whilst, at pH 8, cadmium(II) adsorption isotherms showed a good fit to the Langmuir equation. The adsorption equilibrium constant and adsorption capacity of cadmium(II) at pH 8 were 55.2 mmol/dm3 and 5.98 x 10-2 mmol/g, respectively. Over 90% desorption of cadmium(II) from DCB was achieved by a single step treatment with aqueous solutions of hydrochloric or nitric acid. It is concluded from these results that DCB is acting as a cation exchanger.
Source : Bioresource Technology 2007 vol.98(15), pp 2787 - 2791
Mateus, M. L.; Rouvet, M.; Gumy, J. C.; Liardon, R.
Three complementary techniques were used in this study to investigate the physical changes during wetting of roasted and ground coffee. Scanning electron microscopy (SEM) was found to provide indirect evidence of the presence of liquid water in the coffee particles. The effect of wetting on coffee closed porosity was studied by helium pycnometry, and finally, particle sizing was used to determine the swelling kinetics of coffee after wetting. Due to the solubilization of compounds, the presence of liquid water could be detected in the coffee cells by SEM. The technique was then used to investigate different water contents; for example, for roasted and ground coffee containing 1 g of water per gram of coffee on a dry basis, liquid water was present in cells only at the periphery of approximately 1.0 mm diameter particles. Coffee closed porosity decreased with increasing water content, as evidenced by pycnometry. For roasted and ground coffee containing 1 g of water per gram of coffee, results showed a closed porosity lower that 0.1 cm3/g ( approximately 20% of the closed porosity measured in dry particles). The decrease of closed porosity may be attributed to both (1) water filling cells' lumen and (2) plasticization of cell wall polymers, resulting in the matrix relaxation and increase of helium accessibility to the pores. Water binding to the matrix polymers was further investigated by calorimetric measurements. The integration of the endothermic peak of freezing water showed that approximately 0.15 g of water/g of coffee is nonfreezable water, that is, water bound to the matrix polymers. Finally, the use of particle sizing showed that the average volume of the coffee particles with 1 g of water/g of coffee increased by up to 20-23% at 10-15 min following wetting. Moisture diffusion coefficients in coffee particles [(approximately 2-3) x 10(- 11) m2 s(-1)] were approximated by fitting the swelling curves with a model of diffusion. The observed results may give information about homogeneity and the physical state of water in wetted roasted coffee and thus increase the understanding of the mechanisms of molecular mass transfer during extraction.
Palacios-abrera, H. A.; Menezes, H. C.; Iamanaka, B. T.; Canepa, F.; Teixera, A. A.; Carvalhaes, N.; Santi, D.; Leme, P. T. Z.; Yotsuyanagi, K.; Taniwaki, M. H.
Variations in temperature can result in increased moisture content in coffee beans during transport and this can lead to fungal growth and mycotoxin production. This study investigated the effects of storage conditions during shipping on levels of ochratoxin A in coffee beans. It was found that beans stored in a hold had a 3% increase in moisture content, coffee transported on deck had a 2% increase and beans stored in a container on the first floor had a 0.7% increase. Beans stored at the top of a container on deck, and those in wet bags in the hold were found to contain the highest levels of ochratoxin A.
Pittia, P.; Nicoli, M. C.; Sacchetti, G.
Raw and roasted coffee beans are hygroscopic and they may absorb moisture during storage, which will alter their brittleness and grinding characteristics. This work investigated the effects of moisture and water activity (Aw) on the texture of raw and roasted (light, medium and dark) coffee beans. Moisture adsorption isotherms for raw and roasted coffee beans between 0-0.95 Aw are presented. Roasted beans were not as strong or tough as raw beans. There was an increase in strength and toughness up to a critical Aw of 0.75 for raw beans and 0.86 for roasted beans. Above these Aw values, there was a progressive softening and loss of brittleness caused by the plasticising effect of water. This information might be useful for optimising grinding conditions in relation to coffee Aw.
Saragoni, P.; Aguilera, J. M.; Bouchon, P.
Changes in the projected area (PA) of particles of an instant coffee powder were followed in real time
by videomicroscopy and image analysis. Particles were placed inside a transparent acrylic chamber
(7x7x3cm) where the relative humidity RH (43%, 52%, 67% and 74%) and temperature T (20, 25 and
30°C) were controlled and measured in the head space. A 'caking index', phi, was defined as the change
in PA at any time t with respect to the initial PA. At any temperature, there was an increasing effect in phi
as RH increased and the shape of phi versus time curves closely followed that of caking, measured by
sieving techniques. The exponential kinetic model adequately fitted the data. The PA method could be
used as a first approximation to predict the tendency to caking of amorphous particles.
Arya, M.; Rao, L. J.
Coffee is one of the most popular beverages in the world. It is consumed for its refreshing and stimulating properties. Carbohydrates are the major constituents of coffee beans and serve various functions like binding of aroma, stabilization of foam, formation of sedimentation, and increased viscosity of the extract. The principal low molecular weight carbohydrate is sucrose and no evidence of other simple oligosaccharides has been found. Polysaccharide fraction from green coffee is dominated by arabinogalactan, galactomannan, and cellulose. The polysaccharide content is reduced during roasting due to degradation to low molecular weight carbohydrates (viz., mono and oligosaccharide) and become more extractable. Various methods that can be employed to extract the carbohydrate from roasted coffee are sequential extraction, acid hydroloysis, hot water extraction, enzymatic extraction etc. Carbohydrates from coffee can be quantitatively determined by liquid chromatography, high performance anion exchange chromatography, size exclusion chromatography, and high performance liquid chromatography. Besides improving the organoleptic quality of the coffee beverage, carbohydrates also possess various biological activities such as lowering colon cancer risk. Besides their sheer mass, a variety of evidences testify to the important contribution that the polysaccharide content makes to the character of the final brew. Although a number of chemical and enzymatic methods have been devised to isolate and quantify the carbohydrates of R&G coffee, till date hot water extraction is the only method which can be accepted as a most feasible process and hence, there is wide scope of further research for the efficient and economically viable technology for extraction of carbohydrates from coffee.
Babu, V. R.; Patra, S.; Karanth, N. G.; Kumar, M. A.; Thakur, M. S.
We have utilized a microbe, which can degrade caffeine to develop an Amperometric biosensor for determination of caffeine in solutions. Whole cells of Pseudomonas alcaligenes MTCC 5264 having the capability to degrade caffeine were immobilized on a cellophane membrane with a molecular weight cut off (MWCO) of 3000-6000 by covalent crosslinking method using glutaraledhyde as the bifunctional crosslinking agent and gelatin as the protein based stabilizing agent (PBSA). The biosensor system was able to detect caffeine in solution over a concentration range of 0.1 to 1 mg mL(-1). With read-times as short as 3 min, this caffeine biosensor acts as a rapid analysis system for caffeine in solutions. Interestingly, successful isolation and immobilization of caffeine degrading bacteria for the analysis of caffeine described here was enabled by a novel selection strategy that incorporated isolation of caffeine degrading bacteria capable of utilizing caffeine as the sole source of carbon and nitrogen from soils and induction of caffeine degrading capacity in bacteria for the development of the biosensor. This biosensor is highly specific for caffeine and response to interfering compounds such as theophylline, theobromine, paraxanthine, other methyl xanthines and sugars was found to be negligible. Although a few biosensing methods for caffeine are reported, they have limitations in application for commercial samples. The development and application of new caffeine detection methods remains an active area of investigation, particularly in food and clinical chemistry. The optimum pH and temperature of measurement were 6.8 and 30+/-2 degrees C, respectively. Interference in analysis of caffeine due to different substrates was observed but was not considerable. Caffeine content of commercial samples of instant tea and coffee was analyzed by the biosensor and the results compared well with HPLC analysis.
Gianni, S.; Armando, F.; Gabriella, M.; Massimo, R.; Sauro, V.; Sergio, A.
Acrylamide is a carcinogenic and mutagenic compound found in many industrially processed foods and beverages, including coffee. The aim of this work is to determine the acrylamide level in some Italian coffees by using a mass spectrometry method and an enzymatic test kit. Comparison of average values in four Italian coffees determined using the two methods permitted us to validate the results obtained with the kit, hence the kit itself, showing that acrylamide is present in low amount. The amount of acrylamide was also determined in other foods, by using the kit. This work shows that there is a correspondence between the two methods and that the kit provides a cost-effective method to determine the amount of acrylamide in food.
Source : Food Control 2007 vol.18(10), pp 1267 - 1271 (not available on line)
Keast, R. S.; Riddell, L. J.
Over 60% of soft-drinks sold in the United States contain caffeine, a mildly addictive psycho-active chemical, as a flavor additive. Using sweeteners as controls, we assessed whether caffeine has flavor activity in a cola soft-drink. A forced-choice triangle discrimination methodology was used to determine detection thresholds of caffeine in sweeteners and a cola beverage. The subjects (n=30, 28 female, 23+/- 4 years old) were trained tasters and completed over 1600 discrimination tests during the study. The mean detection thresholds for caffeine in the sweet solutions were: 0.333+/-0.1mM sucrose; 0.467+/- 0.29mM aspartame; 0.462+/-0.3mM sucralose, well below the concentration in common cola beverages (0.55-0.67mM). A fixed concentration of caffeine, corresponding to the concentration of caffeine in a common cola beverage (0.67mM) was added to the sweeteners and a non-caffeinated cola beverage. Subjects could distinguish between caffeinated and non-caffeinated sweeteners (p<0.001), but all subjects failed to distinguish between caffeinated and non-caffeinated cola beverage (p=1.0). Caffeine has no flavor activity in soft-drinks yet will induce a physiologic and psychologic desire to consume the drink.
Lo-Coco, F.; Lanuzza, F.; Micali, G.; Cappellano, G.
Theobromine, theophylline, and caffeine are determined simultaneously by a rapid and selective reversed-phase high-performance liquid chromatography (HPLC) method with UV detection in byproducts of cupuacu and cacao seeds. The determination is carried out in the raw and roasted ground cupuacu seeds and in the corresponding powders obtained after pressure treatment. The by-products of both cupuacu seeds and cacao seeds are obtained under the same technological conditions. The HPLC method uses isocratic elution with a mobile phase of methanol-water-acetic acid (80:19:1) (v/v) at a flow rate of 1 mL/min and UV absorbance detection at 275 nm. Total elution time for these analytes is less than 10 min, and the detection limit for all analytes is 0.1 mg/g. The amounts of theobromine and caffeine found in all the cupuacu samples are one or more orders of magnitude lower than those from cacao. Theophylline is found in all cacao samples except for the roasted ground paste, and it is only found in the roasted ground paste in the cupuacu samples.
K. Fujioka, T. Shibamoto
Twelve commercial brewed coffees (seven regular and five decaffeinated) were analyzed for chlorogenic acids (CGA) and caffeine by HPLC. Their pH and UV–Vis absorbances were also measured. The CGAs identified were three caffeolylquinic acids (3-CQA, 4-CQA, and 5-CQA), three feruloylquinic acids (3-FQA, 4-FQA, and 5-FQA), and three dicaffeoylquinic acids (3,4-diCQA, 3,5-diCQA, and 4,5-diCQA). The total CGAs ranged from 5.26 mg/g to 17.1 mg/g in regular coffees and from 2.10 mg/g to 16.1 mg/g in decaffeinated coffees. Among CGA, 5-CQA was present at the highest level, ranging from 2.13 mg/g to 7.06 mg/g coffee, and comprising 36–42% and 37–39% of the total CGA in the regular and decaffeinated coffees, respectively. CGA isomer contents were, in decreasing order, 5-CQA > 4-CQA > 3-CQA > 5-FQA > 4-FQA > 3-FQA > 3,4-diCQA > 4,5-diCQA, 3,5-diCQA. The caffeine content in regular and decaffeinated coffees ranged from 10.9 mg/g to 16.5 mg/g and from 0.34 mg/g to 0.47 mg/g, respectively. The pH of regular and decaffeinated coffees ranged from 4.95 to 5.99 and from 5.14 to 5.80, respectively. The relationship between the pH and the UV–Vis absorbance at 325 nm was moderately correlated (R2 = 0.7829, p < 0.001, n = 12).
Source : Food Chem 2008 Vol. 106, pp 217-221
Mendonca, J.-C. F.; Franca, A. S.; Oliveira, L. S.
The main objective of this study was to compare methods for mass loss evaluation in green coffee to water content determination by Karl Fischer titration (KFT). The following methodologies were tested: (i) ISO 6673 (oven drying at 105°C for 16 h); (ii) the reference method employed by the Brazilian Agriculture Ministry (oven drying at 105°C for 24 h)-BRAMw, employing whole beans and BRAMg, employing ground beans; and (iii) infrared drying (IRD). Reference oven drying methodologies ISO 6673 and BRAMw presented results statistically equivalent (p >0.05) to those from KFT in the moisture content range that is of interest for green coffee commercialization (8-13 g/100 g), whereas IRD results were lower than those for KFT. ISO 6673 and BRAMw also presented the highest values of correlation coefficients to KFT. Differences in moisture content determination became more significant for lower moisture content values (4-7g/100g), probably due to loss of organic volatile substances during drying and occurrence of moisture loss during sample grinding.
Source : LWT Food Sci Technol 2007 vol.40(7), pp 1300 - 1303
Muller, C.; Hofmann, T.
To gain a more comprehensive knowledge of the contribution of recently identified phenol/thiol conjugates to the storage-induced degradation of odorous thiols, the concentrations of the sulfury-roasty smelling key odorant 2-furfurylthiol and the concentrations of the putative thiol-receptive di- and trihydroxybenzenes pyrogallol (1), hydroxyhydroquinone (2), catechol (3), 4-ethylcatechol (4), 4-methylcatechol (5), and 3-methylcatechol (6), as well as of the phenol/thiol conjugates 3-[(2-furylmethyl)sulfanyl]catechol (7), 3-[(2-furylmethyl)sulfanyl]-5-ethylcatechol (8), 4-[(2-furylmethyl)sulfanyl]hydroxyhydroquinone (9), and 3,4-bis[(2-furylmethyl)sulfanyl]hydroxyhydroquinone (10) were quantitatively determined in fresh and stored coffee beverages by means of stable isotope dilution analyses (SIDA). Although 2 was found to be the quantitatively predominant trihydroxybenzene in freshly prepared coffee brew, this compound exhibited a very high reactivity and decreased rapidly during coffee storage to generate the conjugates 9 and 10. After only 10 min, about 60% of the initial amount of 2-furfurylthiol in a coffee beverage reacted with 2 to give 9 and 10. In contrast, conjugate 7 was found to be exclusively formed during coffee roasting because its initial concentration as well as the amount of its putative precursor, phenol 3, was not affected by storage. It is interesting to note that the concentration of 8 was increased with increasing incubation time, but its putative precursor 4 was not affected, thus indicating another formation pathway most likely via the chlorogenic acid degradation product 4-vinylcatechol. This study demonstrates for the first time that the loss of 2-furfurylthiol during coffee storage is mainly due to the oxidative coupling of the odorant to hydroxyhydroquinone (2), giving rise to the conjugates 9 and 10.
Murkovic, M.; Bornik, M. A.
Coffee was roasted at <less than or equal to>240°C for 10 min in the laboratory and analysed for formation of 5-hydroxymethyl-2-furfural (HMF) and its metabolite 5-hydroxymethyl-2-furoic acid (HMFA). Formation of these 2 compounds during heating of model systems and during industrial coffee roasting was also determined. HMF concn. in laboratory roasted coffee reached a max value of 909 mug/g after 3 min at 240°C before decreasing to negligible concn. HMFA reached a max concn. of 150 mug/g after 4 min of laboratory roasting. Comparison with industrial processes (using low, medium or high degrees of roasting) showed that HMF decreased with higher degree of roasting, whereas HMFA was relatively unaffected. Max. concn. of HMF and HMFA found in industrially roasted coffee were 350 and 140 mug/g, respectively. Unlike HMF, practically no HMFA was found during heating of model systems comprising sucrose + alanine (with or without chlorogenic acid), indicating that HMFA is generated from different precursors than HMF, such as glyceraldehyde and pyruvate.
Nunes, F. M.; Coimbra, M. A.
A method involving fractionation in ethanol aqueous solutions, anion exchange chromatography, and immobilized copper chelating chromatography was developed to obtain high molecular weight anionic melanoidin populations from coffee infusions. Six anionic fractions with different physicochemical properties (ethanol solubility and chelating ability) and chemical composition regarding carbohydrate as well as protein nature and content were isolated. Fractions with similar chemical composition were obtained for light-, medium-, and dark-roasted coffee infusions. These melanoidin fractions accounted for 30-33% of the cold-water soluble high molecular weight material, independently of the degree of roast in coffee. The nature and abundance of the different polysaccharides in each fraction were dependent on their ethanol solubility. The 50% ethanol insoluble melanoidin populations contained mostly galactomannan-like carbohydrates, and the fractions obtained with 75% ethanol contained mostly arabinogalactan-like carbohydrates. The melanoidin populations with chelating properties presented significantly lower carbohydrate content and, from these, the 75% ethanol soluble fractions were almost devoid of carbohydrate material. The results obtained suggest that the chelating ability of these coffee melanoidins is modulated by their carbohydrates. Keywords: Coffee infusions; roasting; melanoidins; Maillard reaction; phenolic; polysaccharides; protein, CML; CEL; furosine.
Rodrigues, C. I.; Marta, L.; Maia, R.; Miranda, M.; Ribeirinho, M.; Maguas, C.
A solid-phase extraction (SPE) method was adapted to perform brewed coffee sample clean-up for seven organic acids (acetic, citric, formic, malic, pyruvic, quinic and succinic) and caffeine determination by reversed-phase UV high performance liquid chromatography (RP/UV-HPLC). For all analytes the method showed good precision and linearity and, as an application, 20 brewed coffee samples from the two types of coffee (robusta vs. arabica) were tested. Brewed coffee samples were prepared according to ISO 6668 [1991. Green coffee-preparation of samples for use in sensory analysis] and the results were compared to sensory evaluation obtained from a panel of coffee tasters. Robusta coffee demonstrated the highest content of caffeine. Total acid content varied with coffee type and also with the geographic origin of the green coffee. Roasting conditions also seem to affect final acidity in brewed coffee for both coffee types analysed.
Rufian-Henares, J. A.; Morales, F. J.
Melanoidins formed at the last stage of the Maillard reaction have been pointed out to possess certain functional properties. Potential antihypertensive activity of food melanoidins (coffee, beer, and sweetwine) has been evaluated according to in-vitro ACE-inhibitory activity. Precision of the assay (3.2% of coefficient of variation, n = 10) for melanoidins is similar to those reported of well-known antihypertensive peptides. Assay was applied on food melanoidins obtained from coffee (three roasting degrees), beer, and sweet-wine. All samples showed in-vitro ACE-inhibitory activity. The activity in coffee melanoidins was significantly higher at more severe heating conditions. These experiments demonstrate that food melanoidins could inhibit ACE activity. In-vitro ACE-inhibitory activity of coffee melanoidins is likely located within the melanoidin structure. But ACE-inhibitory activity is also partly due to the low-molecular weight compound nonchemically bound to the melanoidin structure, then melanoidins can act as carrier protecting agents. These compounds could be naturally phenolic compounds present in the green beans or intermediary Maillard reaction products with antihypertensive activity.
Ruiz-Matute, A. I.; Montilla, A.; Castillo, M.-D. del; Martinez-Castro, I.; Sanz, M. L.
A GC method to determine polyalcohols and sugars in aqueous extracts from green coffee beans, ground roasted coffee beans submitted to either conventional or torrefacto processes, coffee blends and soluble instant coffees, is reported. Bornesitol, mannitol, myo-inositol, mannose, fructose, galactose, glucose and sucrose were detected. Results indicate that coffee manufacturing processes, such as roasting or decaffeination, do not affect the polyalcohols content. Coffee substitutes based on cereals, carob or chicory, were also studied and the feasibility of determining their presence in coffee extracts was evaluated.
Source : J Separation Sci 2007 vol.30(4), pp Separation - 562
Tzanavaras, P. D.; Themelis, D. G.
The present study reports the development and validation of a high-throughput high-performance liquid chromatographic (HPLC) assay for the determination of caffeine in food samples. The analyte was separated rapidly from sample matrix using a short monolithic column (50 mm x 4.6 mm i.d.). The flow rate was 3.0 mL min(-1), while the mobile phase consisted of ACN/water (10:90, v/v). Caffeine was detected directly at 274n m. Under the optimal HPLC conditions, the sampling rate was 60 h(-1). The assay was validated for linearity, LOD and LOQ, precision, selectivity and ruggedness. The case of external calibration versus standard addition for the analysis of real samples was also examined. The proposed assay was applied to the analysis of beverages and coffee samples.
Aguas, P. C.; Fitzhenry, M. J.; Giannikopoulos, G.; Varelis, P.
An accurate and precise method for the quantification of acrylamide using stable isotope dilution liquid chromatography-tandem mass spectrometry was developed and used to measure acrylamide in coffee and cocoa samples. The sample preparation involved extraction of the analyte and its internal standard, 13C3-acrylamide, into water and subsequent defatting of the aqueous extract with dichloromethane. An aliquot of the resulting aqueous extract was then azeotropically dried under reduced pressure and subsequently purified using an aminopropyl-bonded silica cartridge. The purified extracts were then chromatographed on a 5-microm 2.1 x 150 mm Hypercarb column, the effluent of which was monitored for the analyte and its internal standard using positive-ion APCI-selected reaction monitoring. The intralaboratory reproducibility of the method, expressed as a relative coefficient of variation (%, n=5), was determined at four levels of concentration (12.3, 42.3, 139.3 and 464.8 microg kg(-1)) and was found to vary between 0.6-2.5%. The accuracy of the method was assessed using a reference sample of coffee. The average result obtained using our method differed from the assigned value of the reference material by less than 1%. An analysis of a cocoa sample revealed that the method is capable of precisely estimating acrylamide in challenging matrices down to a level of at least 12.3 microg kg(-1).
Iwai, Y.; Nagano, H.; Gil, Sun Lee; Uno, M.; Arai, Y.
A circulation-type apparatus in combination with an on-line FTIR spectroscopy technique were used to determine the solubility of caffeine in supercritical CO2 (SCO2); SCO2 + water; SCO2 + ethanol; and SCO2 + ethanol + water. Experiments were conducted at 313.2 K and 15.0 MPa, using the peak absorbance of caffeine at 1190 cm-1. Caffeine solubility was max. in the SCO2 + ethanol system, increasing with increasing concn. of ethanol. Solubility was higher in the presence of a single entrainer (water or ethanol) than in the presence of both. It is suggested that the enhancement of caffeine solubility in the presence of ethanol is due to H bonding between caffeine and ethanol
K. W. Andrews , A.Schweitzer, C. Zhao, J. M. Holden, J. M. Roseland, M. Brandt, J. T. Dwyer, M. F. Picciano, L. G. Saldanha, K. D. Fisher, E. Yetley, J. M. Betz, L. Douglass
As part of a study initiating the development of an analytically validated Dietary Supplement Ingredient Database (DSID) in the United States (US), a selection of dietary supplement products were analyzed for their caffeine content. Products sold as tablets, caplets, or capsules and listing at least one caffeine-containing ingredient (including botanicals such as guarana, yerba mate, kola nut, and green tea extract) on the label were selected for analysis based on market share information. Two or three lots of each product were purchased and analyzed using high-pressure liquid chromatography (HPLC). Each analytical run included one or two National Institute of Standards and Technology (NIST) Standard Reference Materials (SRMs) and two products in duplicate. Caffeine intake per serving and per day was calculated using the maximum recommendations on each product label. Laboratory analysis for 53 products showed product means ranging from 1 to 829 mg caffeine/day. For products with a label amount for comparison (n = 28), 89% (n = 25) of the products had analytically based caffeine levels/day of between −16% and +16% of the claimed levels. Lot-to-lot variability (n = 2 or 3) for caffeine in most products (72%) was less than 10%.
Barranco-Quintana, J. L.; Allam, M. F.; Serrano-Del-Castillo, A.; Fernandez-Crehuet-Navajas, R.
To estimate the pooled risk of coffee consumption for Alzheimer's disease (AD). MATERIAL AND METHODS: We have reviewed all observational studies that evaluated the association between AD risk and coffee consumption. Four studies were identified: two case-control studies and two cohorts. These studies were carried out between 1990 and 2002. RESULTS: There was an obvious protective effect of coffee consumption in the pooled estimate [risk estimate: 0.73 (95% confidence interval: 0.58-0.92)]. However, the homogeneity test was highly significant (p<0.01), indicating heterogeneity across the pooled studies. Pooled analysis applying the random effect model was 0.79 with 95% confidence interval overlapping unity (95% confidence interval: 0.46-1.36). Three studies assessed coffee consumption by interview questionnaire. The risk of AD in coffee consumers versus non-consumers in studies that used interview questionnaire had a pooled risk estimate of 0.70 with 95% confidence interval 0.55-0.90.
CONCLUSION: Although our pooled estimates show that coffee consumption is inversely associated with the risk of AD, the four studies had heterogeneous methodologies and results. Further prospective studies evaluating the association between coffee consumption and AD are strongly needed.
Bartling, B.; Fuchs, C.; Somoza, V.; Niemann, B.; Silber, R. E.; Simm, A.
High mobility group box protein 1 (HMGB1) is a nonhistone DNA-binding factor that primarily modulates transcriptional activity in cell nuclei. This study examined effects of feeding a diet rich in advanced glycation end-products from processed foods (coffee or bread crust) on lung expression levels of HMBG1 in a rat model. Administration of these Maillard reaction-products extracted from coffee beverages or bread crusts to rats for 15 days resulted in upregulation of HMGB1 mRNA and protein (particularly for the bread crust diet), but did not significantly affect expression of advanced glycation endproduct receptor. Positive associations were also noted between increased levels of advanced glycation end-products in lungs and HMGB1 expression in experimental but not control animals. Comparison of lung tissue of aged (100 wk) vs. young adult (24 wk) rats, did not find a link between ageing-related advanced glycation end-products and increased expression of HMGB1 in lung tissue.
Bjellaas, T.; Stolen, L. H.; Haugen, M.; Paulsen, J. E.; Alexander, J.; Lundanes, E.; Becher, G.
It has previously been reported that heat-treated carbohydrate rich foods may contain high levels of acrylamide resulting in consumers being inadvertently exposed to acrylamide. Acrylamide is mainly excreted in the urine as mercapturic acid derivatives of acrylamide and glycidamide. In a clinical study comprising of 53 subjects, the urinary excretion of these metabolites was determined using solid-phase extraction and liquid chromatography with positive electrospray MS/MS detection. The median (range) total excretion of acrylamide in urine during 24h was 16 (7-47)mug acrylamide for non-smokers and 74 (38-106)mug acrylamide for smokers, respectively. It was found that the median intake estimate in the study based on 24h dietary recall was 21 (13-178) and 26 (12-67) for non-smokers and smokers, respectively. The median dietary exposure to acrylamide was estimated to be 0.47 (range 0.17- 1.16)mug/kg body weight per day. In a multiple linear regression analysis, the urinary excretion of acrylamide metabolites correlated statistically significant with intake of aspartic acid, protein, starch and coffee. Consumption of citrus fruits correlated negatively with excretion of acrylamide metabolites.
Bland, J. R.; Holeman, M. D.; Wilson, J. A.; Phillips, B. L.; Evans, W. J.; Turley, K. R.
In this study low, moderate, and high doses of caffeine were found to significantly increase DBP at rest. During rest and exercise, moderate and high doses of caffeine significantly lowered HR. Although there was a trend for CAF-5 to elevate BP during exercise, it was not significant.
Source : Med Sci Sports Exerc 2007 vol.39 (5, Suppl), pp S412
Bolignano, D.; Coppolino, G.; Crasci', E.; Aloisi, C.; Campo, S.; Sturiale, A.; Buemi, M.
Caffeine is one of the most frequently consumed substances worldwide. It is present in some common beverages such as tea and coffee and in a variety of drugs, particularly analgesics. Its main mechanisms of action include inhibition of phosphodiesterase enzyme and adenosine receptors; its effects involve the whole body. In recent years there has been a debate in the scientific literature over the relationship between caffeine and the kidney and its possible toxicity. Several experimental studies have demonstrated that caffeine may exacerbate some pathological conditions such as polycystic disease and proteinuria, while others have underlined its protective effects in specific situations. While awaiting new, in-depth studies that will help to solve the debate, we can conclude that there is currently no evidence contraindicating the consumption of moderate quantities of caffeine by healthy subjects or kidney patients.
Source : G Ital Nefrol 2007 vol.24 (3), pp 188 - 194 (not available on line)
Bonita, J. S.; Mandarano, M.; Shuta, D.; Vinson, J.
Coffee is a commonly consumed beverage with potential health benefits. This review will focus on cardiovascular disease. There are three preparations of coffee that are commonly consumed and thus worthy of examination; boiled unfiltered coffee, filtered coffee, and decaffeinated coffee. Coffee has over a thousand chemicals, many formed during the roasting process. From a physiological point of view, the potential bioactives are caffeine, the diterpenes cafestol and kahweol found in the oil, and the polyphenols, most notably chlorogenic acid. We will examine coffee and its bioactives and their connection with and effect on the risk factors which are associated with heart disease such as lipids, blood pressure, inflammation, endothelial function, metabolic syndrome and potentially protective in vivo antioxidant activity. These will be critically examined by means of in vitro studies, cell experiments, animal supplementation, epidemiology, and the most definitive evidence, human trials.
Cadden, I. S.; Partovi, N.; Yoshida, E. M.
Background Coffee is consumed by 50 percent of Americans every day. After oil, coffee is the second most valuable commodity in the world. In recent years a number of studies have suggested potential health risks associated with coffee consumption; however, the results are controversial. Whilst coffee has been reported to increase cardiovascular risk factors, other investigators have demonstrated its protective effects on diseases ranging from type 2 diabetes to Parkinson's disease. A number of investigators have focused their attention on the relationship between the consumption of coffee and liver disease. Aim To examine the published literature to date in an attempt to establish the presence of an hepatoprotective effect of coffee. Methods Using PubMed, we identified published studies and review articles relating to the effect of coffee consumption on diseases of the liver.
Conclusion : A number of studies have reported the beneficial effects of coffee on abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. At the present time the mechanism of this effect remains unclear as does the ''dose'' required to achieve these benefits.
Campos, H.; Baylin, A.
Coffee seems to have distinct acute and long-term effects on health, which can be modified by genetic background. Coffee consumption is potentially protective against the development of type 2 diabetes, but given the lack of a solid biological basis for this association, and the possible adverse cardiovascular effects of coffee, recommendations for optimal coffee intake are difficult to establish.
Source : Nutr Rev 2007 vol.65 (4), pp 173 - 179
Celenza, K. M.; Shugert, E.; Velez, S. J.
Caffeine's unexpected depression of synaptic transmission in the superficial flexor muscle system (SFM) of Procambarus clarkii was studied by looking at three known sites of action of this drug: via adenosine and ryanodine receptors and inhibition of phosphodiesterase.1. JPs did not change in size when exposed to physiological concentrations of adenosine, suggesting that the SFM system lacks presynaptic adenosine receptors.2. JPs slightly increased in size in the presence of a phosphodiesterase inhibitor, the opposite response to that obtained with caffeine, suggesting that caffeine is not acting via this pathway.3. A calcium ionophore immediately enhanced synaptic transmission in the SFM system but when given in combination with caffeine the enhancement is reduced and declines over time.4. Serotonin enhanced synaptic transmission in the SFM system, but when given in combination with caffeine this enhancement was not observed.5. These caffeine effects are interpreted in terms of alterations to the calcium homeostatic mechanisms of the terminals.
Choi, H. K.; Curhan, G.
Coffee is one of the most widely consumed beverages in the world and may affect serum uric acid levels and risk of gout via various mechanisms. Our objective was to evaluate the relationship between coffee, tea, and caffeine intake and serum uric acid level in a nationally representative sample of men and women. METHODS: Using data from 14,758 participants ages >/=20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between coffee, tea, and caffeine intake and serum uric acid level using linear regression. Additionally, we examined the relationship with hyperuricemia (serum uric acid >7.0 mg/dl among men and >5.7 mg/dl among women) using logistic regression. Intake was assessed by a food frequency questionnaire. RESULTS: Serum uric acid level decreased with increasing coffee intake. After adjusting for age and sex, serum uric acid level associated with coffee intake of 4 to 5 and >/=6 cups daily was lower than that associated with no intake by 0.26 mg/dl (95% confidence interval [95% CI] 0.11, 0.41) and 0.43 mg/dl (95% CI 0.23, 0.65; P for trend < 0.001), respectively. After adjusting for other covariates, the differences remained significant (P for trend < 0.001). Similarly, there was a modest inverse association between decaffeinated coffee intake and serum uric acid levels (multivariate P for trend 0.035). Total caffeine from coffee and other beverages and tea intake were not associated with serum uric acid levels (multivariate P for trend 0.15). The multivariate odds ratio for hyperuricemia in individuals with coffee intake >/=6 cups daily compared with those with no coffee use was 0.57 (95% CI 0.35, 0.94; P for trend 0.001).
CONCLUSION: These findings from a nationally representative sample of US adults suggest that coffee consumption is associated with lower serum uric acid level and hyperuricemia frequency, but tea consumption is not. The inverse association with coffee appears to be via components of coffee other than caffeine.
Choi, H. K.; Willett, W.; Curhan, G.
Coffee is one of the most widely consumed beverages in the world and may affect the risk of gout via various mechanisms. We prospectively evaluated the relationship between coffee intake and the isk of incident gout in a large cohort of men. METHODS: Over a 12-year period, we studied 45,869 men with no history of gout at baseline. Intake of coffee, decaffeinated coffee, tea, and total caffeine was assessed every 4 years through validated questionnaires. We used a supplementary questionnaire to ascertain whether participants met the American College of Rheumatology survey criteria for gout. RESULTS: We documented 757 confirmed incident cases of gout. Increasing coffee intake was inversely associated with the risk of gout. The multivariate relative risks (RRs) for incident gout according to coffee consumption categories (0, <1, 1-3, 4-5, and >/=6 cups per day) were 1.00, 0.97, 0.92, 0.60 (95% confidence interval [95% CI] 0.41-0.87), and 0.41 (95% CI 0.19-0.88), respectively (P for trend = 0.009). For decaffeinated coffee, the multivariate RRs according to consumption categories (0, <1, 1-3, and >/=4 cups per day) were 1.00, 0.83, 0.67 (95% CI 0.54-0.82), and 0.73 (95% CI 0.46-1.17), respectively (P for trend = 0.002). Total caffeine from all sources and tea intake were not associated with the risk of gout.
CONCLUSION: These prospective data suggest that long-term coffee consumption is associated with a lower risk of incident gout.
Cureton, K. J.; Warren, G. L.; Millard-Stafford, M. L.; Wingo, J. E.; Trilk, J.; Buyckx, M.
This double-blind experiment examined the effects of a caffeinated sports drink during prolonged cycling in a warm environment. Sixteen highly trained cyclists completed 3 trials: placebo, carbohydrateelectrolyte sports drink (CES), and caffeinated sports drink (CES+CAF). Subjects cycled for 135 min, alternating between 60% and 75% VO2max every 15 min for the first 120 min, followed by a 15-min performance ride. Maximal voluntary (MVC) and electrically evoked contractile properties of the knee extensors were measured before and after cycling. Work completed during the performance ride was 15- 23% greater for CES+CAF than for the other beverages. Ratings of perceived exertion were lower with CES+CAF than with placebo and CES. After cycling, the MVC strength loss was two-thirds less for CES+CAF than for the other beverages (5% vs. 15%). Data from the interpolated-twitch technique indicated that attenuated strength loss with CES+CAF was explained by reduced intrinsic muscle fatigue.
Source : Int J Sport Nutr Exerc Metab 2007 vol.17 (1), pp 35 - 55 (not available on line)
Gurpegui, M.; Jurado, D.; Luna, J. D.; Fernandez-Molina, C.; Moreno-Abril, O.; Galvez, R.
Some studies find a relationship between certain personality traits, as impulsivity or sensation seeking, and caffeine consumption, but these studies do not consider the potential confounding effect of smoking on caffeine intake, a co-occurrence that has been well demonstrated in epidemiological and clinical studies. The main objective of this cross-sectional study was to analyze the association of personality with caffeine intake controlling for the effects of smoking; a secondary objective was to explore the effect of caffeine intake on the previously known relationship between personality and smoking. METHODS: A sample of 498 adults answered a self-questionnaire including socio-demographic variables, and items regarding consumption of tobacco and caffeine. Personality was measured by the Temperament and Character Inventory (TCI-125). We analyzed the association of personality traits with both caffeine intake and smoking, controlling the possible confounding effects of sex, age and each substance with the other one. RESULTS: Logistic regression analyses showed that the temperamental dimension of novelty seeking was associated with heavy caffeine consumption (>200 mg/day) (adjusted OR=2.0; 95% CI: 1.1-3.9), controlling for the effect of smoking. Moreover, novelty seeking was associated with both smoking (adjusted OR=1.8; 95% CI: 1.1-2.9) and heavy smoking (>20 cigarettes/day) (adjusted OR=1.8; 95% CI: 1.0-3.7), after controlling for the effect of caffeine intake. CONCLUSION: Our study offers an epidemiological evidence of the relationship of novelty seeking, considered to be associated with low basal dopaminergic activity, with both nicotine consumption and heavy caffeine intake, two substances that enhance dopaminergic neurotransmission.
Source : Prog Neuropsychopharmacol Biol Psychiatry 2007 vol.31 (5), pp 997 - 1005
Hancock, D. B.; Martin, E. R.; Stajich, J. M.; Jewett, R.; Stacy, M. A.; Scott, B. L.; Vance, J. M.; Scott, W. K.
To assess associations between Parkinson disease (PD) and putatively protective factorssmoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). DESIGN: Family-based case-control study. SETTING: Academic medical center clinic. PARTICIPANTS: A total of 356 case subjects and 317 family controls who self-reported environmental exposures. MAIN OUTCOME MEASURES: Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti- inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex. RESULTS: Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (P<.05) and trends in odds ratios (P<.005). Increasing intensity of coffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD. CONCLUSIONS: Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.
Hancock, D. B.; Martin, E. R.; Stajich, J. M.; Jewett, R.; Stacy, M. A.; Scott, B. L.; Vance, J. M.; Scott, W. K.
To assess associations between Parkinson disease (PD) and putatively protective factorssmoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). DESIGN: Family-based case-control study. SETTING: Academic medical center clinic. PARTICIPANTS: A total of 356 case subjects and 317 family controls who self-reported environmental exposures. MAIN OUTCOME MEASURES: Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti- inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex. RESULTS: Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (P<.05) and trends in odds ratios (P<.005). Increasing intensity of coffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD.
CONCLUSIONS: Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.
Ilbaeck, N. G.; Siller, M.; Stalhandske, T.
Caffeine (1,3,7 trimethylxanthine) affects the cardiovascular system, with potential toxic effects ranging from a moderate increase in heart rate to more severe cardiac arrhythmias. Telemetrytransmitters were implanted in Wistar rats in the peritoneal cavity with a pressure catheter in the aorta and electrodes for electrocardiogram (ECG) recording subcutaneously. After a single oral administration of saline, each rat was administered single oral doses of 5, 15 and 45mg/kg b.w. of caffeine. Caffeine was found to induce, to various degrees, a dose-dependent early increase in spontaneous physical activity, heart rate, dp/dt and systolic-diastolic blood pressure. No arrhythmias or visual changes were observed in the ECG complex. High doses induced more strong responses and of longer duration. The increase in systolic blood pressure at the median dose remained in the rats until 20h after administration. However, the highest dose of caffeine (45mg/kg b.w.) induced a biphasic response, with an early and pronounced increase in body temperature, spontaneous physical activity, systolic and diastolic blood pressure that later decreased, except for the systolic blood pressure. The results show that the dose level for longlasting signs of intoxication to develop in the rat, in terms of effects on spontaneous physical activity, body temperature and cardiovascular function, was reached after a single oral dose of caffeine at 45mg/kg b.w.
Infante-Rivard, C.
The relationship between caffeine consumption and small-for-gestational-age (SGA) birth remains uncertain. However, factors that can influence caffeine metabolism, such as genetic polymorphisms, have not been considered, while other similar factors such as smoking and ethnicity have not always been fully accounted for in the interpretation of results. A case-control study was carried out comprising 493 cases and 472 controls. Cases were newborns whose birthweight was below the 10th percentile according to gestational age and sex, based on national norms, and controls were at or above the 10th percentile. Caffeine consumption from beverages was estimated for each pregnancy trimester. Maternal and newborn variants in the CYP1A2 and CYP2E1 genes involved in the metabolism of caffeine were determined. Contrasting consumption >/=300 mg/day with a lower level, or using caffeiwne as a continuous measure, while adjusting for smoking and nausea, showed no increased risk for SGA. However, when stratifying for cigarette smoking, caffeine odds ratios (for the continuous and dichotomous measures) in the first trimester were statistically heterogeneous, suggesting a greater risk among nonsmokers. Using birthweight as the outcome and caffeine as a continuous measure, a small 38 g [95% confidence interval -68, -8] decrement for every 100 mg of daily caffeine was observed in the third trimester. The studied polymorphisms did not modify the effect of caffeine. Caffeine consumption is unlikely to be a major risk factor for SGA or low birthweight in pregnant women
Source : Paediatr Perinat Epidemiol 2007 vol.21 (4), pp 300 - 309
Judd, K.; Shugert, E.; Velez, S. J.
The response of crayfish synaptic terminals to drugs began to be studied to characterize the terminal's physiological characteristics. Caffeine, the first drug to be studied, was selected to enhance synaptic transmission because of its ability to increase calcium release from internal stores.1. The largest excitor neuron to the superficial flexor muscle system of Procambarus clarkii was stimulated at 10 Hz while recording junction potentials from several lateral muscle fibers.2. Caffeine unexpectedly decreased synaptic transmission in this system in a dosage-dependent manner. The depressing effect of caffeine was observed at 5 mM caffeine and junction potentials disappeared completely at 50 mM. Washing the preparation in fresh control Ringers did not restore the amplitudes of the junction potentials.3. Changes in extracellular calcium concentrations delayed or depressed the caffeine effect depending on the calcium gradient across the membrane or the caffeine dosage.The data suggest that calcium is involved in caffeine's response in this system in a way yet to be determined.
Lainez, M. J.; Galvan, J.; Heras, J.; Vila, C.
In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min (P < 0.05), phonophobia at 60, 90, and 120 min (P < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min (P < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine (P < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mildto-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction.
Larsson, S. C.; Wolk, A.
Mounting evidence indicates that coffee drinking may protect against liver injury and lower the risk of liver cancer. We quantitatively assessed the relation between coffee consumption and the risk of liver cancer in a meta-analysis of epidemiologic studies. Methods: Relevant studies were identified by searching MEDLINE (from 1966 to February 2007) and the reference lists of retrieved articles. We included cohort and case-control studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) of primary liver cancer or hepatocellular carcinoma by quantitative categories of coffee consumption. Study-specific RRs were pooled using a random-effects model. Results: Four cohort and 5 case-control studies, involving 2260 cases and 239,146 noncases, met the inclusion criteria. All studies observed an inverse relation between coffee consumption and risk of liver cancer, and in 6 studies the association was statistically significant. Overall, an increase in consumption of 2 cups of coffee per day was associated with a 43% reduced risk of liver cancer (RR, 0.57; 95% CI, 0.49-0.67). There was no statistically significant heterogeneity among studies (P = .17). In stratified analysis, the summary RRs of liver cancer for an increase in consumption of 2 cups of coffee per day were 0.69 (95% CI, 0.55-0.87) for persons without a history of liver disease and 0.56 (95% CI, 0.35-0.91) for those with a history of liver disease.
CNCLUSIONS: Findings from this meta-analysis suggest that an increased consumption of coffee may reduce the risk of liver cancer.
Mao, X.; Chai, Y.; Lin, Y. F.
ATP-sensitive potassium (K(ATP)) channels couple cellular metabolic status to changes in membrane electrical properties. Caffeine (1,2,7-trimethylxanthine) has been shown to inhibit several ion channels; however, how caffeine regulates K(ATP) channels was not well understood. By performing single-channel recordings in the cell-attached configuration, we found that bath application of caffeine significantly enhanced the currents of Kir6.2/SUR1 channels, a neuronal/pancreatic K(ATP) channel isoform, expressed in transfected human embryonic kidney (HEK)293 cells in a concentration-dependent manner. Application of nonselective and selective phosphodiesterase (PDE) inhibitors led to significant enhancement of Kir6.2/SUR1 channel currents. Moreover, the stimulatory action of caffeine was significantly attenuated by KT5823, a specific PKG inhibitor, and, to a weaker extent, by BAPTA/AM, a membrane-permeable Ca(2+) chelator, but not by H-89, a selective PKA inhibitor. Furthermore, the stimulatory effect was completely abrogated when KT5823 and BAPTA/AM were co-applied with caffeine. In contrast, the activity of Kir6.2/SUR1 channels was decreased rather than increased by caffeine in cellfree inside-out patches, while tetrameric Kir6.2LRKR368/369/370/371AAAA channels were suppressed regardless of patch configurations. Caffeine also enhanced the single-channel currents of recombinant Kir6.2/SUR2B channels, a nonvascular smooth muscle K(ATP) channel isoform, although the increase was smaller. Moreover, bidirectional effects of caffeine were reproduced on the K(ATP) channel present in the Cambridge rat insulinoma G1 (CRI-G1) cell line. Taken together, our data suggest that caffeine exerts dual regulation on the function of K(ATP) channels: an inhibitory regulation that acts directly on Kir6.2 or some closely associated regulatory protein(s), and a sulfonylurea receptor (SUR)-dependent stimulatory regulation that requires cGMP-PKG and intracellular Ca(2+)-dependent signaling.
Source : Am J Physiol Cell Physiol 2007 vol.292 (6), pp C2239 - C2258
Maridakis, V.; O'Connor, P. J.; Dudley, G. A.; McCully, K. K.
This double-blind, placebo-controlled, repeated-measures experiment examined the effects of a 5 mg . kg(-1) body weight dose of caffeine on delayed-onset muscle pain intensity and force loss in response to 64 eccentric actions of the dominant quadriceps induced by electrical stimulation. Low caffeineconsuming college-aged females (n = 9) ingested caffeine or placebo 24 and 48 hours following electrically stimulated eccentric exercise of the quadriceps. One hour after ingestion, maximal voluntary isometric contractions (MVIC) and submaximal voluntary eccentric actions were used to determine force loss during activation of damaged quadriceps and whether caffeine attenuates muscle pain intensity. Pain intensity was measured using a 0 to 100 visual analog scale. Caffeine produced a large (12.7 raw visual analog scale [VAS] units; -48%; Cohen's d effect size = -0.88), statistically significant hypoalgesia during the MVIC (t = -2.52; df = 8; P = .036). The reduction in pain scores during submaximal voluntary eccentric movements was smaller (7.8 raw VAS units; -26%, d = -0.34), as was the increase in MVIC force (4.4%; d = 0.13). PERSPECTIVE: Eccentric exercise occurs when skeletal muscles produce force while being lengthened. For example, the biceps brachii muscles act eccentrically when a cup of coffee is lowered from the mouth to a tabletop. This experiment found that caffeine (equal to approximately 2 cups of brewed coffee) could produce a large reduction in pain resulting from eccentric exercise-induced, delayed-onset muscle injury. This finding may improve the quality of life of individuals who experience skeletal muscle pain after engaging in unaccustomed, eccentrically biased exercise.
Source : J Pain 2007 vol.8 (3), pp 237 - 243
Menegaux, F.; Ripert, M.; Hemon, D.; Clavel, J.
We investigated the role of maternal alcohol and coffee drinking during pregnancy and that of parental smoking in the aetiology of childhood leukaemia. A French, population-based, case-control study was conducted, comparing 472 [407 acute lymphoblastic leukaemia (ALL) and 62 acute myeloblastic leukaemia] cases of childhood acute leukaemia (AL) and 567 population controls, frequency-matched with cases on age, gender and region of residence. Both case and control mothers filled in a comprehensive self-administered standardised questionnaire, eliciting detailed data on maternal alcohol and coffee consumption during pregnancy and parental smoking before, during and after pregnancy. Maternal alcohol consumption of more than 1 drink per day was related to ALL (OR = 2.8 [95% CI 1.8, 5.9]). While maternal coffee consumption was not significantly related to AL (OR = 1.4 [95% CI 0.9, 2.3]), highest intake of coffee (more than 3 cups per day) during pregnancy was associated with AL in children whose mothers were non-smokers (OR = 1.9 [95% CI 1.0, 3.5]). No association with parental smoking, either maternal or paternal, was observed with AL. The present results suggest a possible role of the highest consumption of alcohol by the mother during pregnancy in the aetiology of childhood AL.
Source : Paediatr Perinat Epidemiol 2007 vol.21 (4), pp 293 - 299
Millard-Stafford, M. L.; Cureton, K. J.; Wingo, J. E.; Trilk, J.; Warren, G. L.; Buyckx, M.
Caffeine is regarded as a diuretic despite evidence that hydration is not impaired with habitual ingestion. The purpose of this study was to determine whether a caffeinated sports drink impairs fluid delivery and hydration during exercise in warm, humid conditions (28.5 degrees C, 60% relative humidity). Sixteen cyclists completed 3 trials: placebo (P), carbohydrate-electrolyte (CE), and caffeinated (195 mg/L) sports drink (CAF+CE). Subjects cycled for 120 min at 60-75%VO2max followed by 15 min of maximal-effort cycling. Heart rate and rectal temperature were similar until the final 15 min, when these responses and exercise intensity were higher with CAF+CE than with CE and P. Sweat rate, urine output, plasmavolume losses, serum electrolytes, and blood deuterium-oxide accumulation were not different. Serum osmolality was higher with CAF+CE vs. P but not CE. The authors conclude that CAF+CE appears as rapidly in blood as CE and maintains hydration and sustains cardiovascular and thermoregulatory function as well as CE during exercise in a warm, humid environment.
Source : Int J Sport Nutr Exerc Metab 2007 vol.17 (2), pp 163 - 177
Montandon, G.; Kinkead, R.; Bairam, A.
Caffeine is commonly used to treat respiratory instabilities related to prematurity. However, the role of adenosinergic modulation and the potential long-term effects of neonatal caffeine treatment (NCT) on respiratory control are poorly understood. To address these shortcomings, we tested the following hypotheses: 1) adenosine A(1)- and A(2A)-receptor antagonists modulate respiratory activity at rest and during hypercapnia; 2) NCT has long-term consequences on adenosinergic modulation of respiratory control. Rat pups received by gavage either caffeine (15 mg/kg) or water (control) once a day from postnatal days 3 to 12. At day 20, rats received intraperitoneal injection with vehicle, DPCPX (A(1) antagonist, 4 mg/kg), or ZM-241385 (A(2A) antagonist, 1 mg/kg) before plethysmographic measurements of resting ventilation, hypercapnic ventilatory response (5% CO(2)), and occurrence of apneas in freely behaving rats. In controls, data show that A(2A), but not A(1), antagonist decreased resting ventilation by 31% (P = 0.003). A(1) antagonist increased the hypercapnic response by 60% (P < 0.001), whereas A(2A) antagonist increased the hypercapnic response by 42% (P = 0.033). In NCT rats, A(1) antagonist increased resting ventilation by 27% (P = 0.02), but the increase of the hypercapnic response was blunted compared with controls. A(1) antagonist enhanced the occurrence of spontaneous apneas in NCT rats only (P = 0.005). Finally, A(2A) antagonist injected in NCT rats had no effect on ventilation. These data show that hypercapnia activates adenosinergic pathways, which attenuate responsiveness (and/or sensitivity) to CO(2) via A(1) receptors. NCT elicits developmental plasticity of adenosinergic modulation, since neonatal caffeine persistently decreases ventilatory sensitivity to adenosine blockers.
Source : Am J Physiol Regul Integr Comp Physiol 2007 vol.292 (4), pp R1621 - R1631
Murray, J. E.; Li, C.; Palmatier, M. I.; Bevins, R. A.
The present research sought to test whether caffeine functioned as a Pavlovian cue in two ways-as a positive drug feature or as a conditional stimulus (CS). As a positive feature (Experiment 1), brief light presentations were followed by sucrose only on sessions in which caffeine (10 mg/kg) was administered. On intermixed saline sessions, light presentations were not followed by sucrose. The light came to control robust goal tracking (i.e., conditioned responding) only in caffeine sessions. Thus, caffeine disambiguates when the light was paired with sucrose. Decreasing the dose of caffeine decreased the conditioned responding evoked by the light (ED(50)=4.16 mg/kg). Neither nicotine nor amphetamine substituted for the caffeine feature. As a CS, caffeine (10 or 30 mg/kg, Experiments 2a and 2b, respectively) signaled intermittent access to sucrose-no light presentations. No sucrose or lights were presented on intermixed saline sessions. The caffeine CS, regardless of training dose, acquired the ability to evoke only a weak goal-tracking CR. The nature of this dissociation between caffeine as a drug feature and a CS is discussed within the context of past research finding a similar dissociation with amphetamine and chlordiazepoxide, but not with nicotine.
Source : Pharmacol Biochem Behav 2007 vol.86 (4), pp 838 - 846
Myoung, Eun Han; Kyu, Hyun Park; Sun, Yong Baek; Bong, Seon Kim; Jae, Bong Kim; Hak, Jin Kim; Sae, Ock Oh
Caffeine is one of the most extensively consumed psychostimulants in the world. However, compared to short-term effects of caffeine, the long-term effects of caffeine consumption on learning and memory are poorly characterized. The present study found that long-term consumption of low dose caffeine (0.3 g/L) slowed hippocampus-dependent learning and impaired long-term memory. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls. From these results, we concluded that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis.
Source : Biochem Biophysl Res Com 2007 vol.356(4), pp 976 - 980
Nardi, A. E.; Lopes, F. L.; Valenca, A. M.; Freire, R. C.; Veras, A. B.; Melo-Neto, V. L.; Nascimento, I.; King, A. L.; Mezzasalma, M. A.; Soares-Filho, G. L.; Zin, W. A.
Our aim was to observe if patients with panic disorder (PD) and patients with major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) respond in a similar way to the induction of panic attacks by an oral caffeine challenge test. We randomly selected 29 patients with PD, 27 with MDP, 25 with major depression without panic attacks (MD), and 28 healthy volunteers. The patients had no psychotropic drug for at least a 4-week period. In a randomized doubleblind experiment performed in 2 occasions 7 days apart, 480 mg caffeine and a caffeine-free (placebo) solution were administered in a coffee form and anxiety scales were applied before and after each test. A total of 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2) of control subjects had a panic attack after the 480-mg caffeine challenge test (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers. No panic attack was observed after the caffeine-free solution intake. The patients with MD had a lower heart rate response to the test than all the other groups (2-way analysis of variance, group by time interaction with Greenhouse-Geisser correction: F(3,762) = 2.85, P = .026). Our data suggest that there is an association between panic attacks, no matter if associated withPD or MDP, and hyperreactivity to an oral caffeine challenge test.
Nardi, A. E.; Valenca, A. M.; Lopes, F. L.; Melo-Neto, V. L.; Freire, R. C.; Veras, A. B.; Nascimento, I.; King, A. L.; Soares-Filho, G. L.; Mezzasalma, M. A.; Zin, W. A.
Our aim was to compare the demographic and clinical features of panic disorder (PD) patients with agoraphobia-DSM-IV-who had a panic attack after both an oral caffeine and the 35% carbon dioxide (CO(2)) challenge tests (responsive group) and compare them with PD patients who did not have a panic attack after both tests (non-responsive group). We examined 83 PD patients submitted to a 35% CO(2) test and to an oral caffeine (480 mg) intake within 1 week interval. A panic attack was induced in 51 (61.4%) patients during the CO(2) test (chi(2) = 31.67, df = 1, p < 0.001) and in 38 (45.8%) patients during the caffeine test (chi(2) = 18.28, df = 1, p = 0.023). All patients who had a panic attack during the caffeine test also had a panic attack during the CO(2) test (n = 38)-responsive group. The responsive had more (chi(2) = 24.55, df = 1, p = 0.008) respiratory PD subtype, disorder started earlier (Mann-Whitney, p < 0.001) had a higher familial prevalence of PD (chi(2) = 20.34, df = 1, p = 0.019), less previous alcohol abuse (chi(2) = 23.42, df = 1, p < 0.001), and had more previous depressive episodes (chi(2) = 27.35, df = 1, p < 0.001). Our data suggest that there is an association between respiratory PD subtype and hyperreactivity to challenge tests: CO(2) and oral caffeine.
Source : Hum Psychopharmacol 2007 vol.22 Issue 4 pp 231 - 240
Natarajan, G.; Botica, M. L.; Thomas, R.; Aranda, J. V.
Our goal was to determine the value of measuring plasma caffeine levels in preterm neonates treated with caffeine for apnea. We evaluated plasma concentrations of caffeine attained in preterm neonates at standard doses, at varying postconceptual ages, with renal or hepatic dysfunction and when there was clinical lack of efficacy. We hypothesized that measurement of plasma caffeine concentrations during apnea therapy is not clinically helpful. PATIENTS/METHODS: An observational study was conducted at Hutzel Women's Hospital between January 2000 and September 2005. Preterm neonates who were being treated with caffeine and who had a plasma caffeine level measured on at least 1 occasion were included. RESULTS: A total of 231 caffeine blood levels were obtained from 101 preterm neonates with a median gestation of 28 weeks (range: 23-32 weeks) and birth weight of 1030 g (range: 540-2150 g). The caffeine citrate dose used ranged form 2.5 to 10.9 mg/kg (median: 5 mg/kg), and the levels ranged from 3.0 to 23.8 mg/L. Levels were between 5.1 and 20 mg/L in 94.8%, <5 mg/L in 2.1%, and >20 mg/L in 3.1%. Levels in the 5.1 to 20 mg/L range were attained on 91.3% of occasions when there was concomitant renal dysfunction (n = 23) and in all cases of hepatic dysfunction (n = 13). The median (25th, 75th quartiles) levels drawn for lack of efficacy (14.1 [10.2, 8.3] mg/L; n = 94) were comparable to those obtained for routine monitoring (13.7 [11, 9] mg/L; n = 107).
CONCLUSIONS: A majority of preterm neonates attain plasma caffeine levels between 5 and 20 mg/L, independent of gestation. This observation held even for the small number of subjects with elevated blood urea nitrogen, serum creatinine, or liver enzyme levels. Therapeutic drug monitoring is not necessary when caffeine is used for the treatment of apnea of prematurity in neonates.
Pan, H. Z.; Chen, H. H.
The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs. OBJECTIVES: The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory. METHODS: Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared. RESULTS: Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats.
CONCLUSION: These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.
Source : Psychopharmacology (Berl) 2007 vol.191 (1), pp 119 - 125
Park, S.; Jang, J. S.; Hong, S. M.
Our previous study demonstrated that long-term cola consumption reduced body weight and improved insulin sensitivity in healthy male rats. In this study, we investigated the effect and mechanism of caffeine and sucrose, major components of cola, on glucose metabolism in 90% pancreatectomized diabetic rats. After a 12-week administration of 0.01% caffeine solution, the rats exhibited reduced body weight, fats, and insulin resistance, without a change in food intake, regardless of an 11% sucrose solution supplementation. In addition, caffeine enhanced glucose-stimulated first- and second-phase insulin secretion and beta-cell hyperplasia. This insulinotropic action was explained by potentiating an insulin/insulin-like growth factor 1 (IGF-1) signaling cascade via induction of insulin receptor substrate 2 in islets. In contrast, sucrose supplementation deteriorated insulin sensitivity and attenuated insulin/IGF-1 signaling in islets, which reduced the number of beta cells. Caffeine nullified the adverse effect of sucrose on glucose homeostasis. These findings indicate that long-term caffeine consumption can help alleviate diabetic symptoms by enhancing insulin sensitivity and beta-cell function through improved insulin/IGF-1 signaling via induction of insulin receptor substrate 2 in mildly diabetic rats
Paterson, L. M.; Wilson, S. J.; Nutt, D. J.; Hutson, P. H.; Ivarsson, M.
Insomnia is a common and disabling complaint for which there is a need for improved treatments. Successful drug discovery relies on the use of appropriate animal models to assess likely outcome in the clinic. OBJECTIVES: The purpose of this study was to develop a translational, caffeine induced model of insomnia in rats and healthy volunteers. We used sleep onset latency (SOL) as a comparable sleep measure between the two species. The model was validated by two effective sleep promoting agents with different pharmacology, zolpidem and trazodone, which have GABA-ergic and serotonergic mechanisms, respectively. MATERIALS AND METHODS: In rats, radiotelemetry transmitters with electroencephalogram and electromyogram electrodes were implanted for sleep recording. Animals were administered with caffeine alone (10 mg/kg) or in combination with zolpidem (10 mg/kg) ortrazodone (20 mg/kg), or vehicle, in crossover experiments. Home polysomnography was performed in 12 healthy male volunteers in a randomised, placebo-controlled, 4-week crossover study. Subjects received placebo, caffeine (150 mg) or caffeine in combination with zolpidem (10 mg) or trazodone (100 mg). Subjective sleep effects in volunteers were assessed using the Leeds Sleep Evaluation Questionnaire. RESULTS: Caffeine caused a significant prolongation in objective SOL in rats and humans. This effect was sensitive to zolpidem and trazodone, both of which attenuated the caffeine-induced increase in SOL. Furthermore, both hypnotics restored the disruption in subjective measures of sleep onset caused by caffeine in volunteers.
CONCLUSIONS: This model therefore provides a promising paradigm in which we can study novel treatments for sleep disorders and an opportunity for direct comparison of results between rodents and humans.
Source : Psychopharmacology (Berl) 2007 vol.191 (4), pp 943 - 950
Rapuri, P. B.; Gallagher, J. C.; Nawaz, Z.
Of the various risk factors contributing to osteoporosis, dietary/lifestyle factors are important. In a clinical study we reported that women with caffeine intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR) variant, tt were at a greater risk for this deleterious effect of caffeine. However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25-Dihydroxy vitamin D(3) (1,25(OH)(2)D(3)) plays a critical role in regulating bone metabolism. The receptor for 1,25(OH)(2)D(3), VDR has been demonstrated in osteoblast cells and it belongs to the superfamily of nuclear hormone receptors. To understand the molecular mechanism of the role of caffeine in relation to bone, we tested the effect of caffeine on VDR expression and 1,25(OH)(2)D(3) mediated actions in bone. We therefore examined the effect of different doses of caffeine (0.2, 0.5, 1.0 and 10mM) on 1,25(OH)(2)D(3) induced VDR protein expression in human osteoblast cells. We also tested the effect of different doses of caffeine on 1,25(OH)(2)D(3) induced alkaline phosphatase (ALP) activity, a widely used marker of osteoblastic activity. Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.
Source : J Steroid Biochem Mol Biol 2007 vol.103 (3-5), pp 368 - 371
Renner, B.; Clarke, G.; Grattan, T.; Beisel, A.; Mueller, C.; Werner, U.; Kobal, G.; Brune, K.
The aim of this study was to determine the analgesic effect of acetaminophen compared to a combination of both caffeine and acetaminophen or caffeine alone using tonic and phasic pain stimulation. Twenty-four subjects were treated orally with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way crossover, double-blind, placebo-controlled study. Pharmacokinetics and analgesic effects were assessed by means of an experimental pain model based on pain-related cortical potentials after phasic stimulation of the nasal mucosa with CO(2) and based on pain ratings after tonic stimulation with dry air. Analgesic effects of acetaminophen and acetaminophen plus caffeine but not caffeine alone caused a significant reduction of pain-related cortical potentials beginning 30 minutes after medication. The combination demonstrated an enhanced effect throughout the observation time up to 3 hours. Caffeine accelerated acetaminophen absorption, indicated by enhanced early AUCs. Significant analgesic effects of the combination on tonic pain ratings were found throughout the observation time as compared to acetaminophen and placebo. In this study, caffeine enhanced and prolonged the analgesic activity of acetaminophen.
Retey, J. V.; Adam, M.; Khatami, R.; Luhmann, U. F.; Jung, H. H.; Berger, W.; Landolt, H. P.
Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-rated caffeine-sensitive individuals, but not in caffeine-insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A2A receptor gene (ADORA2A) differs between caffeine-sensitive and –insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine-induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.
Riddoch, F. C.; Brown, A. M.; Rowbotham, S. E.; Redfern, C. P.; Cheek, T. R.
We have used single cell fluorescence imaging techniques to examine how functional properties of the caffeine-sensitive Ca(2+) store change during differentiation of a sub-population of caffeine-sensitive SHSY5Y cells. Application of caffeine (30 mM) 1-10.5 min after a 'priming' depolarisation pulse of 55 mM K(+) revealed that the caffeine-sensitive store in undifferentiated cells remained replete, whereas that in 9-cis retinoic acid (9cRA)-differentiated cells spontaneously dissipated with a t(1/2) of 2.8 min, and was essentially completely depleted approximately 10 min after priming. In 9cRA-differentiated cells that were stimulated with methacholine (10 microM) 1 min after priming, the amplitude, rate of rise and propagation velocity of the Ca(2+) wave in the neurites were all constant, whereas these kinetic parameters all progressively decreased as the wave travelled along the neurites in cells that were stimulated 10 min after priming. Use-dependent block with ryanodine inhibited the global Ca(2+) signal in 9cRA-differentiated cells stimulated with methacholine 1 min after priming (71+/-8%) but not 10 min after priming. Depolarisation was more effective at priming the caffeine-sensitive Ca(2+) store in 9cRA-differentiated cells, which lack a functional store-operated Ca(2+) entry pathway. We conclude that differentiation of caffeine-sensitive SH-SY5Y cells is accompanied by an increase in lability of the caffeine-sensitive Ca(2+) store, and that spontaneous dissipation of Ca(2+) from the store limits the time course of its molecular 'memory' during which it can amplify the hormone-induced Ca(2+) signal by Ca(2+)-induced Ca(2+) Release.
Shapiro, R. E.
Caffeine is the most widely consumed psychostimulant drug. It is a potent antagonist of adenosine
receptors at dosages consistent with common dietary intake. With infrequent exposure, caffeine may act
as an analgesic for headache or an adjuvant for the actions of other analgesics. With chronic repetitive
intake, caffeine is associated with an increased risk of development of analgesicoveruse headache,
chronic daily headache and physical dependency. Cessation of caffeine use following chronic exposures
leads to a withdrawal syndrome, with headache as a dominant symptom.
Source : Neurol Sci 2007 vol.28 Suppl 2, pp S179 - S183 (not available on line)
Swanson, D. L.; Barnes, S. A.; Mengden-Koon, S. J.; el Azhary, R. A.
Recent animal and human studies have suggested that the therapeutic benefit of methotrexate in the treatment of rheumatoid arthritis may be substantially reduced in patients who are concomitantly consuming caffeine. Here, we aimed to investigate the effect of caffeine consumption on the methotrexate dosing requirements in patients with psoriasis and psoriatic arthritis. METHODS: One hundred and fifty patients with diagnoses of psoriasis or psoriatic arthritis were surveyed for their current weekly methotrexate dosage and their usual daily consumption of caffeine. RESULTS: Seventy-five of the patients given the survey responded; of these, 11 were eliminated because they did not report their
methotrexate dosage or were no longer taking methotrexate. Of the remaining 64 patients, no correlation was found between the methotrexate dosage needed for disease maintenance and the amount of caffeine consumed.
CONCLUSIONS: Our findings suggest that caffeine does not affect methotrexate dosage requirements in patients with psoriasis and psoriatic arthritis. These results do not rule out an effect of caffeine in other inflammatory diseases treated with methotrexate.
Takahama, U.; Tanaka, M.; Oniki, T.; Hirota, S.; Yamauchi, R.
The objective of the present study was to elucidate how chlorogenic acid in coffee was transformed under acidic conditions simulating the mixture of saliva and gastric juice. When coffee was incubated in acidified saliva that contained nitrite and SCN-, in addition to nitric oxide (NO), four major components were detected. Two of the four components (components 3 and 4) were generated when chlorogenic acid was incubated in acidified saliva and when incubated in an acidic buffer solution in the presence of both nitrite and SCN-. By the incubation of chlorogenic acid in acidic nitrite in the absence of SCN-, components 3 and 4 were not formed but the quinone of chlorogenic acid and nitrated chlorogenic acid were formed. The result indicates that SCN- was indispensable for nitrous acid induced formation of components 3 and 4. Component 4 was isolated and its structure was determined to be (E)-5'-(3-(7-hydroxy-2-oxobenzo[d] [1,3]oxathiol-4-yl)acryloyloxy)quinic acid. Component 3, which was suggested to be 2-thiocyanatochlorogenic acid, seemed to be formed by the reaction between SCN- and the quinone of chlorogenic acid. As it has been reported that the quinone of chlorogenic acid can react with thiols and can decompose producing H2O2, the formation of component 4 can reduce the toxic effects of the quinone of chlorogenic acid.
Source : J Agric Food Chem 2007 vol.55 Issue 10 pp 4169 - 4176
Tchekalarova, J.; Kubova, H.; Mares, P.
Postnatal caffeine treatment of rats can influence brain excitability during development. To study the mechanism involved in the alterations of seizure susceptibility, we used an animal model that corresponds to the infants treated with caffeine for apnea of prematurity. Seizure susceptibility to four convulsant drugs (pentetrazol, picrotoxin, bicuculline and aminophylline) was assessed in 12- and 25-day-old rats exposed to caffeine at a daily dose of 10 and/or 20 mg/kg s.c. at postnatal days 7-11. Our results demonstrated that the changes in generalized tonic-clonic seizures (GTCS) are more expressed than changes in minimal clonic seizures. There are marked differences among individual convulsants with the highest sensitivity of aminophylline-induced seizures and nearly complete resistance of bicuculline-induced seizures. The changes in individual models are age specific: aminophylline- and picrotoxin-induced seizures are more affected in 12- than in 25-day-old rats whereas PTZ-induced seizures are more changed by early postnatal caffeine exposure in 25- than in 12-day-old animal. Taken together, repeated caffeine treatment from postnatal day 7 to 11 reduces the seizure susceptibility during development and this reduction is also model specific
Source : Brain Res 2007 vol.1150, pp 32 - 39
Tieges, Z.; Snel, J.; Kok, A.; Plat, N.; Ridderinkhof, R.
Effects of caffeine on task switching were studied using ERPs in a cued task-switch paradigm. The need for advance preparation was manipulated by varying the number of task-set aspects that required switching. In a double-blind, within-subjects experiment, caffeine reduced shift costs compared to placebo. ERPs revealed a negative deflection developing within the preparatory interval, which was larger for shift than for repeat trials. Caffeine increased this shift-induced difference. Furthermore, shift costs increased as a function of the number of task-set features to be switched, but this pattern was not modulated by caffeine. The results suggest that caffeine improves task-switching performance by increasing general effects on task switching, related to task-nonspecific (rather than task-specific) anticipatory processes. Caffeine's actions may be mediated by dopaminergic changes in the striatum or anterior cingulate cortex.
Uiterwaal, C. S. P. M.; Verschuren, W. M. M.; Bueno-de-Mesquita, H. B.; Ocke, M.; Geleijinse, J. M.; Boshuizen, H. C.; Peeters, P. H. M.; Feskens, E. J. M.; Grobbee, D. E.
A Dutch cohort study, involving over 6,000 subjects over a number of years, was used to investigate the relationship between coffee intake and hypertension. The results indicated that subjects who did not drink coffee had a lower risk of hypertension than those who had low coffee consumption. In women, there was an inverse U-shaped relationship between intake of coffee and the risk of hypertension.
Vlachopoulos, C. V.; Vyssoulis, G. G.; Alexopoulos, N. A.; Zervoudaki, A. I.; Pietri, P. G.; Aznaouridis, K. A.; Stefanadis, C. I.
Aortic stiffness and wave reflections are important markers and prognosticators of cardiovascular risk. Caffeine increases acutely aortic stiffness and wave reflections. Furthermore, chronic coffee consumption is associated with increased aortic stiffness and wave reflections in normotensive subjects. In the present study, we aimed to assess the association between chronic coffee consumption, and aortic stiffness and wave reflections in hypertensive patients. DESIGN: Epidemiological survey. SETTING: Hypertension Unit, University Hospital. SUBJECTS-METHODS: We examined 259 never treated hypertensives (age 50+/-12 years, 165 males) without diabetes mellitus, who were asked to describe in detail the type and amount of coffee they consumed. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) were measured non-invasively as indices of aortic stiffness and wave reflections, respectively. RESULTS: When controlled for gender, age, height, smoking status, heart rate, mean pressure, HDL cholesterol and hsCRP, AIx was found to be higher with increasing daily coffee consumption. Post hoc analysis revealed that all groups of coffee consumption had higher AIx compared to no-consumption. PWV did not differ among groups of daily coffee consumption. Each participant had 35% higher relative risk of having high AIx for each cup (150 ml) of coffee per day, and 40% higher relative risk for each 10 cup-years.
CONCLUSIONS: Coffee consumption is associated with increased wave reflections, but not aortic stiffness in never-treated hypertensive patients. This finding may have important clinical implications for cardiovascular health in hypertensive subjects.
Tsubouchi, H.; Shimoya, K.; Hayashi, S.; Toda, M.; Morimoto, K.; Murata, Y.
To investigate the effects of maternal ingestion of an ordinary dose of coffee on maternalstress and placental and fetal blood circulation during the third trimester of pregnancy. METHODS: We performed a Doppler blood flow analysis for 10 women in the third trimester of pregnancy before and after they drank a cup of coffee. Salivary samples were collected from the 10 pregnant women and 14 nonpregnant controls just before coffee intake and 30 min later. Salivary cortisol levels and chromogranin A titers were determined. RESULTS: Coffee intake had no effect on maternal or fetal blood flow. Among the pregnant women, Salivary cortisol levels were significantly reduced after coffee intake but salivary chromogranin A concentration was not significantly different before and after coffee intake.
CONCLUSION: The reduced salivary cortisol levels suggest that coffee intake decreases maternal stress during pregnancy
Vergara, J. L.; Difranco, M.
The effects of caffeine on the process of excitation-contraction coupling in amphibian skeletal muscle fibers were investigated using the confocal spot detection technique. This method permits to carefully discriminate between caffeine effects on the primary sources of Ca2+ release at the Z-lines where the triads are located and secondary actions on other potential Ca Release sources. Our results demonstrate that 0.5 mM caffeine potentiates and prolongs localized action-potential evoked Ca2+ transients recorded at the level of the Z-lines, but that 1mM only prolongs them. The effects at both doses are reversible. At the level of the M-line, localized Ca2+ transients displayed more variability in the presence of 1 mM caffeine than in control conditions. At this dose of caffeine, extra-junctional sources of Ca2+ release also were observed occasionally.
Kotsopoulos, J.; Ghadirian, P.; El Sohemy, A.; Lynch, H. T.; Snyder, C.; Daly, M.; Domchek, S.; Randall, S.; Karlan, B.; Zhang, P.; Zhang, S.; Sun, P.; Narod, S. A.
We have recently reported that, among BRCA1 mutation carriers, the consumption of caffeinated coffee was associated with a significant reduction in breast cancer risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined whether or not the CYP1A2 genotype modifies the association between a history of coffee consumption and the risk of breast cancer. A common A to C polymorphism in the CYP1A2 gene is associated with decreased enzyme inducibility and impaired caffeine metabolism. Information regarding coffee consumption habits and the CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241 controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer associated with the CYP1A2 genotype and a history of coffee consumption before age 35, adjusting for potential confounders. The CYP1A2 genotype did not affect breast cancer risk. Among women with at least one variant C allele (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73). A significant protective effect of coffee consumption was not observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77). Similar results were obtained when the analysis was restricted to caffeinated coffee. This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations.
Source : Cancer Epidemiol Biomarkers Prev 2007 vol.16 (5), pp 912 - 916
Sofi, F.; Conti, A. A.; Gori, A. M.; Luisi, M.-L. E.; Casini, A.; Abbate, R.; Gensini, G. F.
A meta-analysis was conducted of case-control and cohort studies to examine the link between coffee consumption and risk for coronary heart disease (CHD). The analysis of 13 case-control studies (9487 cases of CHD and 27 747 controls in total) revealed significant associations between coffee consumption and CHD for intakes of >4 cups/day (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.49-2.24; P < 0.0001) and 3-4 cups/day (OR 1.33, 95% CI 1.04-1.71; P < 0.0001) but not for intake <less than or equal to>2 cups/day (OR 1.03, 95% CI 0.87-1.21; P = 0.45). No significant associations were observed on analysis of 10 cohort studies (403 631 participants followed for 3-44 yr), with intakes of >4, 3-4 and <less than or equal to>2 cups/day having relative risks of 1.16 (95% CI 0.95-1.41; P = 0.14), 1.05 (95% CI 0.90-1.22; P = 0.57) and 1.04 (95% CI 0.90-1.19; P = 0.60), respectively. Controlling for geographical origin, fatal and non-fatal events, publication year and length of follow-up did not affect the results substantially. It is concluded that even though high coffee consumption and CHD are significantly related in case-control studies, no significant link is observed on analysis of prospective cohort studies with long-term follow-up.
Wang, S. J.
The present study used nerve terminals (synaptosomes) isolated from rat cerebral cortex to investigate the relationship between caffeine and 4-aminopyridine (4AP)-evoked endogenous excitatory neurotransmitter glutamate release. Micromolar concentrations of caffeine facilitated 4AP, but not KCl or ionomycin-evoked glutamate release from synaptosomes. This release facilitation resulted from an enhancement of vesicular and nonvesicular release and associated with an increase both in 4AP-evoked depolarization of the synaptosomal plasma membrane potential and in 4AP-evoked increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](C)). In addition, the release facilitation by caffeine was significantly reduced in synaptosomes pretreated with a wide spectrum blocker of N- and P/Q-type Ca(2+) channels, omega-conotoxin MVIIC. Furthermore, protein kinase C (PKC) activator and inhibitor, respectively, superseding or suppressing the caffeine-mediated facilitation of glutamate release. These results concluded that caffeine exerts their presynaptic facilitatory effect, likely through the activation of PKC pathway, which subsequently enhances terminal excitability and Ca(2+) entry to cause an increase in evoked glutamate release from rat cerebrocortical nerve terminals. Additionally, this release facilitation may involve an interaction of caffeine with presynaptic adenosine A1 receptors as adenosine A1 receptor inhibition abolished the caffeine-mediated facilitation of evoked glutamate release.