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Comparative stimulant and diuretic actions of caffeine and theobromine in man

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Abstract

Human subjects ingested measured quantities of caffeine and theobromine, separately and together, at random. The double-blind technique was used. Caffeine altered self-estimates of sleep latency and sleep quality in a dose-dependent fashion and increased overnight urinary sodium excretion. Theobromine in equivalent doses had no detectable effect on sleep parameters or on urine composition, nor did it interact significantly with caffeine when the two were ingested together. Theobromine is much weaker than caffeine or entirely inert in these situations.

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... It is widely accepted that caffeine and other methylxanthines act by antagonizing the effects of adenosine through competitive interactions with adenosine receptors A 1 , A 2 , A 3 , and A 4 (3). It has been reported that the acute administration of caffeine in healthy volunteers results in an increase in diuresis and urinary excretion of electrolytes (10,23). A previous study showed that caffeine has an antagonistic effect on adenosine receptors, and it has been proposed that this may contribute to the prevention of renal damage from ischemia (22). ...
... Therefore, as physical exercise is essential in combating obesity, it is necessary to prescribe exercise in a way that does not cause progression of renal damage. As mentioned above (10,22,23), caffeine may be protective against renal damage, through antagonistic action at the adenosine receptor. Moreover, caffeine may aid in BW reduction through an increase in energy expenditure (2,12). ...
... After the treatment, an increase in UV, Ccr, and electrolyte excretion was observed in the caffeine-intake groups, which may have been the result of caffeine acting as an antagonist of adenosine A 1 -Rs, which most likely functions to directly inhibit tubular absorption of sodium, and might further promote salt and water excretion from the kidney (10,22,23). ...
Article
This study was performed to examine the effects of long-term caffeine-intake, with and without exercise, on the progression of diabetic nephropathy (DN) in an obese diabetic rat model. Thirty-two male Otsuka Long Evans Tokushima Fatty (OLETF) rats were assigned to sedentary (OLETF-Sed), exercise (OLETF-Ex), caffeine-intake (OLETF-Caf), and combined (OLETF-Caf & Ex) groups. Caffeine-intake groups were fed rat chow containing caffeine (90.7 ± 4.7 mg/kg/day). The OLETF-Ex and OLETF-Caf & Ex groups were able to run voluntarily at any time using a rotatory wheel. Body weight (BW) and blood pressure (BP) were measured weekly from 24 to 29 weeks of age. Pre- and post-treatment serum glucose, insulin, and creatinine concentrations were measured, and a 24 h urine sample was collected for measurement of creatinine clearance (Ccr) and albumin excretion (UEAlb). After treatment, the kidneys were removed for morphological analysis. The OLETF-Caf and OLETF-Caf & Ex groups exhibited no BP increase during the study. Both the caffeine-intake groups exhibited a significant increase in urine volume (UV), electrolyte excretion, and Ccr, and decreased UEAlb, following treatment. Furthermore, no structural damage was observed in the kidneys of rats from either caffeine-intake group, whereas the OLETF-Sed and OLETF-Ex groups exhibited DN progression. This study demonstrates that caffeine-intake alone and/or combined with exercise significantly decreases BW and improves glucose intolerance, without the progression of DN. Further research should be performed to examine whether the quantities of caffeine contained in a normal human daily intake also have a protective effect against kidney damage.
... Only a very few early publications have reported individual and combined effects of caffeine and theobromine. Dorfman and Jarvik (1970) gave volunteers 300 mg caffeine and/or 300 mg theobromine before the volunteers retired for the evening. Those in the caffeine and caffeine + theobromine condition showed a longer sleep latency and lower sleep quality than those in the theobromine condition. ...
... Because theobromine has a lower overall adenosine receptor affinity than caffeine and theophylline, though all three methylxanthines are non-selective adenosine antagonists (Fredholm and Lindström 1999), a small, but possibly insignificant, diuretic effect of theobromine would be predicted not to be functionally different from the other methylxanthines. Indeed, despite a previous and unjustified claim that theobromine has a stronger effect on the kidney than caffeine (Czok 1974), Dorfman and Jarvik (1970) and Massey and Whiting (1993) reported that unlike caffeine, oral administration of 300 mg theobromine did not increase urinary calcium or sodium excretion, although Dorfman and Jarvik (1970) found no change in the overnight urine volume following oral administration of 300 mg caffeine or 300 mg theobromine compared with 'no drug'. ...
... Because theobromine has a lower overall adenosine receptor affinity than caffeine and theophylline, though all three methylxanthines are non-selective adenosine antagonists (Fredholm and Lindström 1999), a small, but possibly insignificant, diuretic effect of theobromine would be predicted not to be functionally different from the other methylxanthines. Indeed, despite a previous and unjustified claim that theobromine has a stronger effect on the kidney than caffeine (Czok 1974), Dorfman and Jarvik (1970) and Massey and Whiting (1993) reported that unlike caffeine, oral administration of 300 mg theobromine did not increase urinary calcium or sodium excretion, although Dorfman and Jarvik (1970) found no change in the overnight urine volume following oral administration of 300 mg caffeine or 300 mg theobromine compared with 'no drug'. ...
Article
The effects of theobromine in man are underresearched, possibly owing to the assumption that it is behaviourally inert. Toxicology research in animals may appear to provide alarming results, but these cannot be extrapolated to humans for a number of reasons. Domestic animals and animals used for racing competitions need to be guarded from chocolate and cocoa-containing foods, including foods containing cocoa husks. Research ought to include caffeine as a comparative agent, and underlying mechanisms need to be further explored. Of all constituents proposed to play a role in our liking for chocolate, caffeine is the most convincing, though a role for theobromine cannot be ruled out. Most other substances are unlikely to exude a psychopharmacological effect owing to extremely low concentrations or the inability to reach the blood-brain barrier, whilst chocolate craving and addiction need to be explained by means of a culturally determined ambivalence towards chocolate.
... Only a very few early publications have reported individual and combined effects of caffeine and theobromine. Dorfman and Jarvik (1970) gave volunteers 300 mg caffeine and/or 300 mg theobromine before the volunteers retired for the evening. Those in the caffeine and caffeine + theobromine condition showed a longer sleep latency and lower sleep quality than those in the theobromine condition. ...
... Because theobromine has a lower overall adenosine receptor affinity than caffeine and theophylline, though all three methylxanthines are non-selective adenosine antagonists (Fredholm and Lindström 1999), a small, but possibly insignificant, diuretic effect of theobromine would be predicted not to be functionally different from the other methylxanthines. Indeed, despite a previous and unjustified claim that theobromine has a stronger effect on the kidney than caffeine (Czok 1974), Dorfman and Jarvik (1970) and Massey and Whiting (1993) reported that unlike caffeine, oral administration of 300 mg theobromine did not increase urinary calcium or sodium excretion, although Dorfman and Jarvik (1970) found no change in the overnight urine volume following oral administration of 300 mg caffeine or 300 mg theobromine compared with 'no drug'. ...
... Because theobromine has a lower overall adenosine receptor affinity than caffeine and theophylline, though all three methylxanthines are non-selective adenosine antagonists (Fredholm and Lindström 1999), a small, but possibly insignificant, diuretic effect of theobromine would be predicted not to be functionally different from the other methylxanthines. Indeed, despite a previous and unjustified claim that theobromine has a stronger effect on the kidney than caffeine (Czok 1974), Dorfman and Jarvik (1970) and Massey and Whiting (1993) reported that unlike caffeine, oral administration of 300 mg theobromine did not increase urinary calcium or sodium excretion, although Dorfman and Jarvik (1970) found no change in the overnight urine volume following oral administration of 300 mg caffeine or 300 mg theobromine compared with 'no drug'. ...
Chapter
The effects of theobromine in man are underresearched, possibly owing to the assumption that it is behaviourally inert. Toxicology research in animals may appear to provide alarming results, but these cannot be extrapolated to humans for a number of reasons. Domestic animals and animals used for racing competitions need to be guarded from chocolate and cocoa-containing foods, including foods containing cocoa husks. Research ought to include caffeine as a comparative agent, and underlying mechanisms need to be further explored. Of all constituents proposed to play a role in our liking for chocolate, caffeine is the most convincing, though a role for theobromine cannot be ruled out. Most other substances are unlikely to exude a psychopharmacological effect owing to extremely low concentrations or the inability to reach the blood–brain barrier, whilst chocolate craving and addiction need to be explained by means of a culturally determined ambivalence towards chocolate. KeywordsChocolate-Cocoa-Comparative-Craving-Liking-Myths-Pharmacology-Psychology-Theobromine-Toxicology
... Theobromine shows also an antitussive and a bronchodilating effect (Simons et al. 1985;Usmani et al. 2005), a diuretic action (Dorfman and Jarvik 1970), and a possible role in reduction of angiogenesis in tumor growth (Smit 2011), all these effects are related to its adenosine receptor antagonistic properties. ...
... He et al. 2009 In Human studies (Table 2) Early publications reported combined and individual effects of caffeine and theobromine in healthy subjects. In the 1970s, Dorfman et al. (Dorfman and Jarvik 1970) showed that the concomitant intake of caffeine and theobromine during evening extended estimated sleep latency and worsened sleep quality with respect to exclusive consumption of theobromine in a group of young volunteers. Few years later, Brunk et al. (Brunk et al. 1973) found a significantly greater subjectively reported stimulation in volunteers receiving caffeine with respect of those receiving theobromine. ...
Article
Full-text available
Nutritional qualities of cocoa have been acknowledged by several authors; a particular focus has been placed on its high content of flavanols, known for their excellent antioxidant properties and subsequent protective effect on cardio- and cerebrovascular systems as well as for neuromodulatory and neuroprotective actions. Other active components of cocoa are methylxanthines (caffeine and theobromine). Whereas the effects of caffeine are extensively researched, the same is not the case for theobromine; this review summarizes evidence on the effect of theobromine on cognitive functions. Considering animal studies, it can be asserted that acute exposition to theobromine has a reduced and delayed nootropic effect with respect to caffeine, whereas both animal and human studies suggested a potential neuroprotective action of long-term assumption of theobromine through a reduction of Aβ amyloid pathology, which is commonly observed in Alzheimer’s disease patients’ brains. Hence, the conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.
... Very few studies have investigated the behavioral effects of theobromine, and thus no clear conclusions can yet be made about its psychoactive profile. Although two early reports found null mood effects from theobromine [14,15], a more recent study by Mumford et al. [16] showed that 5 out of 7 subjects were able to discriminate a high dose of theobromine (560 mg) from a placebo or caffeine dose. The combination of caffeine (19 mg) and theobromine (250 mg) in capsules increased the self-reported mood construct "energetic arousal", and improved cognitive function as measured with a simple reaction time test [1] compared to placebo capsules. ...
Article
Full-text available
The combination of theobromine and caffeine, methylxanthines found in chocolate, has previously been shown to improve mood and cognition. However, it is unknown whether these molecules act synergistically. This study tested the hypothesis that a combination of caffeine and theobromine has synergistic effects on cognition, mood and blood pressure in 24 healthy female subjects. The effects of theobromine (700 mg), caffeine (120 mg) or the combination of both, or placebo were tested on mood (the Bond-Lader visual analog scale), psychomotor performance (the Digit Symbol Substitution Test (DSST)) and blood pressure before and at 1, 2 and 3 h after administration. Theobromine alone decreased self-reported calmness 3h after ingestion and lowered blood pressure relative to placebo 1 h after ingestion. Caffeine increased self-reported alertness 1, 2 and 3h after ingestion and contentedness 1 and 2 h after ingestion, and increased blood pressure relative to placebo (at 1 h). The combination of caffeine+theobromine had similar effects as caffeine alone on mood, but with no effect on blood pressure. There was no treatment effect on DSST performance. Together these results suggest that theobromine and caffeine could have differential effects on mood and blood pressure. It was tentatively concluded that caffeine may have more CNS-mediated effects on alertness, while theobromine may be acting primarily via peripheral physiological changes.
... This appears to be based on studies showing acute increased urine output after caffeine doses in caffeine na ‡ve individuals. [117][118][119][120][121][122][123] However, research shows that a tolerance to caffeine develops. [124][125][126][127][128][129] As such, those who are not caffeine na ‡ve do not experience increased urine output or altered indicators of hydration status after consuming caffeinated beverages. ...
Article
Historically, hydration research reflected critical issues of the day. War, illness, surviving a shipwreck or time in the dessert, supplying fall-out shelters, and space exploration drove hydration research in the first half of the 20th century. The fitness revolution of the 1970s spurred research on dehydration in physically active people and athletes. The 1990s introduced the “fluid/disease relationship.” What will be the driving force behind hydration research in the 21st century? Where are the gaps in our knowledge? This review provides an overview of issues pertinent to determining future directions in hydration research.
... These studies report observations across a range of caffeine forms and doses on various markers of hydration status in either caffeine-habituated or caffeine-naive populations (individuals who do not habitually consume caffeine, or those who have abstained from caffeine consumption for $4 days). Although the data are somewhat varied, the general trend is that higher doses of caffeine in caffeinenaive individuals will elicit an acute increase in urine volume, yet a low to moderate dose of caffeine does not induce a diuretic effect [13][14][15][16][17]. ...
Article
Full-text available
It is often suggested that coffee causes dehydration and its consumption should be avoided or significantly reduced to maintain fluid balance. The aim of this study was to directly compare the effects of coffee consumption against water ingestion across a range of validated hydration assessment techniques. In a counterbalanced cross-over design, 50 male coffee drinkers (habitually consuming 3-6 cups per day) participated in two trials, each lasting three consecutive days. In addition to controlled physical activity, food and fluid intake, participants consumed either 4×200 mL of coffee containing 4 mg/kg caffeine (C) or water (W). Total body water (TBW) was calculated pre- and post-trial via ingestion of Deuterium Oxide. Urinary and haematological hydration markers were recorded daily in addition to nude body mass measurement (BM). Plasma was analysed for caffeine to confirm compliance. There were no significant changes in TBW from beginning to end of either trial and no differences between trials (51.5±1.4 vs. 51.4±1.3 kg, for C and W, respectively). No differences were observed between trials across any haematological markers or in 24 h urine volume (2409±660 vs. 2428±669 mL, for C and W, respectively), USG, osmolality or creatinine. Mean urinary Na(+) excretion was higher in C than W (p = 0.02). No significant differences in BM were found between conditions, although a small progressive daily fall was observed within both trials (0.4±0.5 kg; p<0.05). Our data show that there were no significant differences across a wide range of haematological and urinary markers of hydration status between trials. These data suggest that coffee, when consumed in moderation by caffeine habituated males provides similar hydrating qualities to water.
... Urine output is commonly used as an indicator of water turnover. An early study [ 63 ] observed increased urine output after consuming caffeine; therefore it is often extrapolated that caffeine results in dehydration because greater fl uid is excreted from the body (versus placebo). However, a careful examination of caffeine studies in which urine output is measured shows that both placebo and caffeinated trials result in approximately 84 % retention of fl uid (fl uid in − fl uid out/fl uid in × 100). ...
Chapter
Sugar-sweetened beverages (SSB) contribute to fluid intake/requirements in the same manner as water and other fluids. SSB are equally effective in maintaining euhydration as as water alone during everyday conditions. SSB and similar beverages such as carbohydrate-electrolyte solutions (CES) can be ergogenic during endurance exercise by helping spare liver glycogen, maintain blood glucose levels, and increase water absorption. SSB and water are equally effective in maintaining normal thermoregulatory and cardiovascular function during exercise. During rehydration, SSB and CES are more effective in restoring fluid balance back to normal levels compared to water due to their ability to aid in fluid retention and minimize urinary losses. High carbohydrate content of a single type may delay gastric emptying rate and thus fluid delivery. However, ingestion of multiple carbohydrate types, as with SSB, can increase the rate of fluid absorption and delivery from the gastrointestinal tract The carbonation or composition of SSB does not influence the volume of ad libitum fluid intake. The low-to-moderate caffeine levels in most SSB are not detrimental with acute or chronic ingestion.
... In addition, it exhibits inhibitory activity against gallstones and cirrhosis of the liver and may reduce the risk of stroke (Dórea and da Costa, 2005). Additionally, caffeine which acts as diuretic (Nechay, 1964;Dorfman and Jarvik, 1970) is claimed to stimulate tear secretion (Osei et al., 2014) thus can be helpful in the dry eye syndrome treatment (Moss et al., 2000). Its beneficial influence being a result of antioxidant properties is associated with the ability to reduce the risk of terminal diseases including liver, kidney, basal, colorectal and endometrial cancers (Nkondjock, 2009;Bøhn et al., 2014;Song et al., 2012;Li et al., 2013;Hashibe et al., 2015), and the mutagenic effect of ultraviolet radiation (Heffernan et al., 2009;Kerzendorfer and O'Driscoll, 2009;Lu et al., 2002) or anticancer drugs (Sabisz and Skladanowski, 2008). ...
Article
The polymorphism of anhydrous caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) has been studied by 1H-14N NMR-NQR (Nuclear Magnetic Resonance - Nuclear Quadrupole Resonance) double resonance and pure 14N NQR (Nuclear Quadrupole Resonance) followed by computational modelling (Density Functional Theory, supplemented Quantum Theory of Atoms in Molecules with Reduced Density Gradient) in solid state. For two stable (phase II, form β) and metastable (phase I, form α) polymorphs the complete NQR spectra consisting of 12 lines were recorded. The assignment of signals detected in experiment to particular nitrogen sites was verified with the help of DFT. The shifts of the NQR frequencies, quadrupole coupling constants and asymmetry parameters at each nitrogen site due to polymorphic transition were evaluated. The strongest shifts were observed at N(3) site, while the smallest at N(9) site. The commercial pharmaceutical sample was found to contain approximately 20-25% of phase I and 75-80% of phase II. The orientational disorder in phase II with a local molecular arrangement mimics that in phase I. Substantial differences in the intermolecular interactions phases I and II of caffeine were analysed using computational (DFT/QTAIM/RDS) approach. The analysis of local environment of each nitrogen nucleus permitted drawing some conclusions on the topology of interactions in both polymorphs. For the most stable orientations in phase I and phase II the maps of the principal component qz of EFG tensor and its asymmetry parameter at each point of the molecular system were calculated and visualised. The relevant maps calculated for both phases I and II indicates small variation in electrostatic potential upon phase change. Small differences between packings in phases slightly disturb the neighbourhood of the N(1) and N(7) nitrogens, thus are meaningless from the biological point of view. The composition of two phases in pharmaceutical material should not be any obstacle, which is relevant from the pharmaceutical industry point of view.
... When physicians, physiologists, and dietitians recommend that caffeinated beverages not be consumed before or during exercise (16,28), they rarely cite research findings to support their assumptions. Opposing this viewpoint, other professionals view caffeine as a mild diuretic that poses no harm to health or exercise performance (7,9,26). In fact, three previously published review articles (2,20,21) concluded that caffeinated beverages and water affect body water balance similarly during exercise. ...
Article
Recreational enthusiasts and athletes often are advised to abstain from consuming caffeinated beverages (CB). The dual purposes of this review are to (a) critique controlled investigations regarding the effects of caffeine on dehydration and exercise performance, and (b) ascertain whether abstaining from CB is scientifically and physiologically justifiable. The literature indicates that caffeine consumption stimulates a mild diuresis similar to water, but there is no evidence of a fluid-electrolyte imbalance that is detrimental to exercise performance or health. Investigations comparing caffeine (100-680 mg) to water or placebo seldom found a statistical difference in urine volume. In the 10 studies reviewed, consumption of a CB resulted in 0-84% retention of the initial volume ingested, whereas consumption of water resulted in 0-81% retention. Further, tolerance to caffeine reduces the likelihood that a detrimental fluid-electrolyte imbalance will occur. The scientific literature suggests that athletes a...
... When physicians, physiologists, and dietitians recommend that caffeinated beverages not be consumed before or during exercise (16,28), they rarely cite research findings to support their assumptions. Opposing this viewpoint, other professionals view caffeine as a mild diuretic that poses no harm to health or exercise performance (7,9,26). In fact, three previously published review articles (2,20,21) concluded that caffeinated beverages and water affect body water balance similarly during exercise. ...
Article
Recreational enthusiasts and athletes often are advised to abstain from consuming caffeinated beverages (CB). The dual purposes of this review are to (a) critique controlled investigations regarding the effects of caffeine on dehydration and exercise performance, and (b) ascertain whether abstaining from CB is scientifically and physiologically justifiable. The literature indicates that caffeine consumption stimulates a mild diuresis similar to water, but there is no evidence of a fluid-electrolyte imbalance that is detrimental to exercise performance or health. Investigations comparing caffeine (100-680 mg) to water or placebo seldom found a statistical difference in urine volume. In the 10 studies reviewed, consumption of a CB resulted in 0-84% retention of the initial volume ingested, whereas consumption of water resulted in 0-81% retention. Further, tolerance to caffeine reduces the likelihood that a detrimental fluid-electrolyte imbalance will occur. The scientific literature suggests that athletes and recreational enthusiasts will not incur detrimental fluid-electrolyte imbalances if they consume CB in moderation and eat a typical U.S. diet. Sedentary members of the general public should be a less risk than athletes because their fluid losses via sweating are smaller.
... The contributions of theobromine are less clear and its psychoactive effects appear subtle (reviewed in Smit 2011). Although two early studies failed to detect psychopharmacological activity (Brunk et al. 1973;Dorfman and Jarvik 1970), Mumford (1994) found that 5 of 7 participants were able to discriminate 560 mg theobromine from placebo or caffeine, suggesting that theobromine might be about one tenth as potent as caffeine. While theobromine did not significantly increase any subjective or behavioral measures in the Mumford et al. (1994) study when all subjects were combined, the compound increased alertness, headache, and irritability in some individuals, suggesting the possibility of individual differences in sensitivity. ...
Article
Background: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. Objectives: We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results: Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. Conclusions: This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.
... Besides, caffeine exhibits inhibitory activity against diabetes II, gallstones and cirrhosis of the liver [81]. It acts as diuretic [82,83] and stimulate tear secretion [84] which makes it helpful in the dry eye syndrome treatment [85]. Antioxidant properties of caffeine and scavenging abilities of reactive oxygen species (ROS) are associated with its ability to reduce the risk of liver, kidney, basal, colorectal and endometrial cancers [86][87][88][89][90]. ...
... (Galeone et al. 2010;Lee et al. 2007;Tavani and La, 2000) Diuretics Weak evidence shows the diuretic effects of coffee and its component caffeine. (Stookey, 1999,Dorfman andJarvik, 1970) Antimicrobial Numerous in vitro and ex vivo studies suggest the significant potential of coffee and its compounds for inhibiting the pathogenic as well as food spoilage bacteria. Antimicrobial effect is also being reported for fungal organisms and viruses. ...
Article
Coffee is a composite mixture of more than a thousand diverse phytochemicals like alkaloids, phenolic compounds, vitamins, carbohydrates, lipids, minerals and nitrogenous compounds. Coffee has multifunctional properties as a food additive and nutraceutical. As a nutraceutical, coffee has anti-inflammatory, anti-oxidant, antidyslipidemic, anti-obesity, type-2 diabetes mellitus (DM), and cardiovascular diseases (CVD), which can serve for the treatment and prevention of metabolic syndrome and associated disorders. On the other hand, as a food additive, coffee has antimicrobial activity against a wide range of microorganisms, inhibits lipid peroxidation (LPO), and can function as a prebiotic. The outcomes of different studies also revealed that coffee intake may reduce the incidence of numerous chronic diseases, like liver disease, mental health, and it also overcomes the all-cause mortality, and suicidal risks. In some studies, high intake of coffee is linked to increase CVD risk factors, like cholesterol, plasma homocysteine and blood pressure (BP). There is also a little evidence that associated the coffee consumption with increased risk of lung tumors in smokers. Among adults who consume the moderate amount of coffee, there is slight indication of health hazards with strong indicators of health benefits. Moreover, existing literature suggests that it may be cautious for pregnant women to eliminate the chances of miscarriages and impaired fetal growth. The primary purpose of this narrative review is to provide an overview of the findings of the positive impacts and risks of coffee consumption on human health. In conclusion, to date, the best available evidence from research indicates that drinking coffee up to 3-4 cups/day provides health benefits for most people.
... Our fl avanol-rich cocoa drink contained about 30 mg caffeine and about 600 mg theobromine; the FRC drink contained nearly the same levels of both these alkaloids per serving. Scant data are available regarding the biologic effects of theobromine, although generally it is considered a weaker stimulant and a milder diuretic than caffeine (Schroeder 1951;Dorfman and Jarvik 1970). The cerebral hemodynamic effects of theobromine have not been reported in humans. ...
Article
Full-text available
Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. We used transcranial Doppler (TCD) ultrasound to measure mean blood flow velocity (MFV) in the middle cerebral artery (MCA) in thirty-four healthy elderly volunteers (72 +/- 6 years) in response to the regular intake of FRC or flavanol-poor cocoa (FPC). In response to two weeks of FRC intake, MFV increased by 8% +/- 4% at one week (p = 0.01) and 10% +/- 4% (p = 0.04) at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p < 0.05). In summary, we show that dietary intake of FRC is associated with a significant increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data suggest a promising role for regular cocoa flavanol's consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.
... This may be accompanied by impairment of sleep quality, characterized by an increased number of spontaneous awakenings and body movements. Doses lower than 100 mg do not appear to have such an effect on sleep in most people [14,329]. Chronic high consumers of caffeine, however, are less likely to report sleep disturbances than individuals consuming caffeine more occasionally, also suggesting the development of tolerance to the effects of caffeine on this parameter [330]. ...
Article
Full-text available
Caffeine (1,3,7-trimethylxanthine) is the most consumed psychoactive substance in the world, acting by means of antagonism to adenosine receptors, mainly A1 and A2A. Coffee is the main natural source of the alkaloid which is quite soluble and well extracted during the brew’s preparation. After consumption, caffeine is almost completely absorbed and extensively metabolized in the liver by phase I (cytochrome P450) enzymes, mainly CYP1A2, which appears to be polymorphically distributed in human populations. Paraxanthine is the major caffeine metabolite in plasma, while methylated xanthines and methyluric acids are the main metabolites excreted in urine. In addition to stimulating the central nervous system, caffeine exerts positive effects in the body, often in association with other substances, contributing to prevention of several chronic diseases. The potential adverse effects of caffeine have also been extensively studied in animal species and in humans. These aspects will be approached in the present review.
... (Galeone et al. 2010;Lee et al. 2007;Tavani and La, 2000) Diuretics Weak evidence shows the diuretic effects of coffee and its component caffeine. (Stookey, 1999,Dorfman andJarvik, 1970) Antimicrobial Numerous in vitro and ex vivo studies suggest the significant potential of coffee and its compounds for inhibiting the pathogenic as well as food spoilage bacteria. Antimicrobial effect is also being reported for fungal organisms and viruses. ...
Article
Coffee is a composite mixture of more than a thousand diverse phytochemicals like alkaloids, phenolic compounds, vitamins, carbohydrates, lipids, minerals and nitrogenous compounds. Coffee has multifunctional properties as a food additive and nutraceutical. As a nutraceutical, coffee has anti-inflammatory, anti-oxidant, antidyslipidemic, anti-obesity, type-2 diabetes mellitus (DM), and cardiovascular diseases (CVD), which can serve for the treatment and prevention of metabolic syndrome and associated disorders. On the other hand, as a food additive, coffee has antimicrobial activity against a wide range of microorganisms, inhibits lipid peroxidation (LPO), and can function as a prebiotic. The outcomes of different studies also revealed that coffee intake may reduce the incidence of numerous chronic diseases, like liver disease, mental health, and it also overcomes the all-cause mortality, and suicidal risks. In some studies, high intake of coffee is linked to increase CVD risk factors, like cholesterol, plasma homocysteine and blood pressure (BP). There is also a little evidence that associated the coffee consumption with increased risk of lung tumors in smokers. Among adults who consume the moderate amount of coffee, there is slight indication of health hazards with strong indicators of health benefits. Moreover, existing literature suggests that it may be cautious for pregnant women to eliminate the chances of miscarriages and impaired fetal growth. The primary purpose of this narrative review is to provide an overview of the findings of the positive impacts and risks of coffee consumption on human health. In conclusion , to date, the best available evidence from research indicates that drinking coffee up to 3-4 cups/day provides health benefits for most people.
... In contrast to the results of these studies, Dorfman & Jarvik (1970) did not find evidence for a diuretic action of 300 mg of caffeine in 10 healthy young volunteers. Subjects took caffeine or placebo before retiring to bed and collected the overnight urine produced over the following 8 h. ...
Article
Caffeine and related methylxanthine compounds are recognized as having a diuretic action, and consumers are often advised to avoid beverages containing these compounds in situations where fluid balance may be compromised. The aim of this review is to evaluate the available literature concerning the effect of caffeine ingestion on fluid balance and to formulate targeted and evidence-based advice on caffeinated beverages in the context of optimum hydration. A literature search was performed using the Medline database of articles published in the medical and scientific literature for the period of January 1966-March 2002. Subject headings and key words used in this search were: tea, coffee, caffeine, diuresis, fluid balance and water-electrolyte balance. A secondary search was performed using the bibliographies of publications identified in the initial search. The available literature suggests that acute ingestion of caffeine in large doses (at least 250-300 mg, equivalent to the amount found in 2-3 cups of coffee or 5-8 cups of tea) results in a short-term stimulation of urine output in individuals who have been deprived of caffeine for a period of days or weeks. A profound tolerance to the diuretic and other effects of caffeine develops, however, and the actions are much diminished in individuals who regularly consume tea or coffee. Doses of caffeine equivalent to the amount normally found in standard servings of tea, coffee and carbonated soft drinks appear to have no diuretic action. The most ecologically valid of the published studies offers no support for the suggestion that consumption of caffeine-containing beverages as part of a normal lifestyle leads to fluid loss in excess of the volume ingested or is associated with poor hydration status. Therefore, there would appear to be no clear basis for refraining from caffeine containing drinks in situations where fluid balance might be compromised.
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The relief of acute migraine attacks with an analgesic/antihistamine combination containing paracetamol, codeine phosphate, doxylamine succinate and caffeine (Mersyndol) compared with that achieved with a placebo has been studied in a double-blind, crossover trial. Mersyndol emerged as significantly better than placebo in the complete relief of migraine pain, and was clearly superior to placebo in partially relieving the pain of migraine. These results suggest that it could be a useful alternative to ergotamine, and a comparative trial with ergotamine is suggested. Side effects with this combination were fairly common but mild, and consisted mainly of drowsiness caused by the antihistamine component.
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Caffeine is a natural constituent of more than 60 plant species and as such is present in the human diet through drinks based on plant extracts. It has also been used as a flavoring agent in food (baked goods, dairy desserts, puddings and fillings, candy) and beverages (Dr. Pepper, Coca-Cola, Pepsi-Cola, Royal Crown Cola) and also in a variety of over-the-counter pharmaceuticals (1). In such pharmaceuticals, caffeine is present in combination with drugs used as stimulants, pain relievers, diuretics, cold remedies, weight control products, bronchial and cardiac stimulants as well as in drugs for the treatment of acne and other skin disorders. The pharmaceutical properties of caffeine described in this report explain its use in these drugs. These multiple sources of caffeine reflect the human search and interest for psychotropic drugs and stimulants from the plant world.
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Caffeine, incorporated into pulverized Purina Rat Chow at a concentration of 0.5%, was fed to male Sprague-Dawley rats for 7 or 8 wk and the effects were compared with those of 0.8% dietary theobromine, fed to male rats for 7 wk. Both dietary methylated xanthines produced significant decreases in food consumption and body-weight gain when compared to their respective control groups. Food consumption of caffeine-fed rats was 57.2% of controls and for theobromine-fed rats it was 77.9% of the respective controls. Theobromine produced significant decreases in thymus weights, with caffeine producing smaller decreases. The theobromine-fed rats showed severe testicular atrophy with extensive spermatogenic cell degeneration and necrosis, while the testes of rats fed caffeine for 7 or 8 wk showed only scattered vacuolar degeneration of spermatogenic cells. Caffeine appears to be more potent than theobromine as an anorexic agent in rats, but to be equivalent to theobromine in its potential for inducing thymic atrophy and spermatogenic cell destruction with testicular atrophy.
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The critical review of the literature cited on pharmacology, toxicology, metabolism, and safety assessment clearly demonstrates that cocoa per se has not attracted a great deal of scientific interest because of its long-term usage with no reported adverse effects that would be injurious to man. On the other hand, a great deal of research has been directed towards understanding the pharmacological properties of the methylxanthines--caffeine, theobromine, and theophylline. Much of the emphasis on metabolism, toxicology, teratogenic potential, and safety assessment has been on the evaluation of caffeine. In light of the serious health concerns ascribed to the effects of caffeine and the lack of basic information on theobromine and theophylline, it is imperative that a major research program be undertaken to evaluate these methylxanthines and, of course, cocoa, coffee, and tea. It only will be through elucidating their mechanism of action that we will be in a position to assess their safety. Before committing research efforts to evaluating the long-term effects of these methylxanthines and their respective foodstuffs, which serve as our primary source of exposure, it is critical to initiate more basic research on the metabolism of caffeine, theophylline, and theobromine in several animal species and man. While published reports do appear in this area, it is essential to understand fully the similarities and differences between various animals and man. The influence of dietary factors and drug interactions must also be determined. Before establishing dosage levels for a chronic toxicity study, the pharmacokinetics of the dose must be determined in the species that will be used in long-term studies. This is necessary if there is a dose-dependency in the animal above which saturation may occur and the plasma half-life kinetics change, or shifts occur either in the metabolic pathways of degradation and/or in the route of excretion from the body. The area of teratology must also be thoroughly evaluated. Studies undertaken should include identification and quantitation of the metabolites of caffeine, theophylline, and theobromine in the pregnant animal, the respective pharmacokinetics of each compound, dose-dependency (if this is the case), and their potential teratogenicity. In addition, the influence of other drugs or dietary variables must be included. In addition to teratology, a great deal of research is needed to assess and quantitate fetal and neonatal metabolism of these compounds.(ABSTRACT TRUNCATED AT 400 WORDS)
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Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies was asked to deliver a scientific opinion on the safety of caffeine, providing advice on caffeine intakes, from all dietary sources that do not give rise to concerns about adverse health effects for the general healthy population and subgroups thereof. Possible interactions between caffeine and other constituents of so-called “energy drinks”, alcohol, p-synephrine and physical exercise should also be addressed. Single doses of caffeine up to 200 mg (about 3 mg/kg bw for a 70-kg adult) do not give rise to safety concerns. The same amount does not give rise to safety concerns when consumed < 2 hours prior to intense physical exercise under normal environmental conditions. Other constituents of “energy drinks” at typical concentrations in such beverages (about 300–320, 4 000 and 2 400 mg/L of caffeine, taurine and d-glucurono-γ-lactone, respectively), as well as alcohol at doses up to about 0.65 g/kg bw, would not affect the safety of single doses of caffeine up to 200 mg. Habitual caffeine consumption up to 400 mg per day does not give rise to safety concerns for non-pregnant adults. Habitual caffeine consumption up to 200 mg per day by pregnant women does not give rise to safety concerns for the fetus. Single doses of caffeine and habitual caffeine intakes up to 200 mg consumed by lactating women do not give rise to safety concerns for breastfed infants. For children and adolescents, the information available is insufficient to derive a safe caffeine intake. The Panel considers that caffeine intakes of no concern derived for acute caffeine consumption by adults (3 mg/kg bw per day) may serve as a basis to derive single doses of caffeine and daily caffeine intakes of no concern for these population subgroups.
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Interactions of alcohol and caffeine were studied in two double-blind and crossover trials in which several psychophysiologic functions and subjective effects were measured in healthy men. The effects of alcohol (1 gm/kg) with and without caffeine (200 or 500 mg) were measured in 10 subjects. Two doses (0.7 or 1.5 gm/kg) of alcohol alone and in combination with caffeine (250 + 250 mg) were similarly studied in another 10 subjects. Alcohol impaired psychomotor functions to an extent dependent on dose whereas caffeinated and decaffeinated coffee did not. Both kinds of coffee also failed to modify alcohol effects. Subjectively, caffeine was indistinguishable from placebo and no particular interaction of alcohol and caffeine was detected. Alcohol did elevate serum caffeine concentrations. We conclude that coffee does not counteract alcohol inebriation.
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A series of four trials was carried out to investigate the effects of caffeine and coffee on the metabolic rate and substrate utilization in normal weight and obese individuals. In the first trial 8 mg/kg caffeine was compared with a placebo in normal weight subjects. Metabolic rate increased significantly during the 3 hr after caffeine ingestion. While plasma glucose, insulin, and carbohydrate oxidation did not change significantly, plasma free fatty acid levels rose from 432 +/- 31 to 848 +/- 135 muEq/liter and were accompanied by significant increases in fat oxidation during the last hour of the test. In the second and third trials the effects of coffee providing 4 mg/kg caffeine were studied in control and obese subjects. Metabolic rate increased significantly in both groups; however, significant increases in fat oxidation were only observed in the control group. Plasma free fatty acids did not change in the obese. In the fourth trial, coffee was taken with a 3080 kJ meal. The thermic effect of the meal was significantly greater after coffee than after decaffeinated coffee and again fat oxidation was significantly greater after coffee. In conclusion caffeine/coffee stimulates the metabolic rate in both control and obese individuals; however, this is accompanied by greater oxidation of fat in normal weight subjects.
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Theobromine versus placebo discrimination and caffeine versus placebo discrimination were studied in two consecutive experiments in seven volunteers who abstained from methylxanthines. Daily sessions involved PO double-blind ingestion of two sets of capsules sequentially, one of which contained drug and the other placebo. Subjects attempted to identify, and were later informed, which set of capsules contained the drug. In each experiment subjects were exposed to progressively lower doses. Five subjects acquired the theobromine discrimination; the lowest dose discriminated ranged from 100 to 560 mg. All seven subjects acquired the caffeine discrimination; the lowest dose discriminated ranged from 1.8 to 178 mg. A final experiment evaluated subjective effect ratings following 560 mg theobromine, 178 mg caffeine and placebo, which were administered double-blind in capsules once daily, five times each in mixed sequence. Caffeine produced changes in both group and individual ratings (e.g. increased well-being, energy, social disposition and alert). Theobromine did not produce changes in group ratings but changed ratings in some subjects. Across subjects, sensitivity to caffeine discriminative effects in the discrimination experiment correlated significantly with the number and magnitude of caffeine subjective effects in the final experiment. This study documents modest discriminative effects of theobromine in humans, but the basis of the discrimination is unclear. This study suggests that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine.
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The persistence of cigarette smoking despite widespread awareness of adverse health effects results from an underlying addiction to nicotine. Unaided attempts to quit smoking are generally unsuccessful. This article discusses nicotine addition and therapeutic techniques that have been or are being developed to relieve smoking withdrawal symptoms and promote abstinence from smoking. These techniques include nicotine chewing gum, skin patches, nasal sprays, and inhalers, as well as pharmacotherapies such as mecamylamine and clonidine, serotonergic treatments such as buspirone, and antidepressants such as buproprion. A nondrug approach using cigarette substitutes that mimic the airway sensations produced by cigarette smoke is also discussed.
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To examine the effect of various combinations of beverages on hydration status in healthy free-living adult males. In a counterbalanced, crossover manner, 18 healthy adult males ages 24 to 39, on four separate occasions, consumed water or water plus varying combinations of beverages. Clinical guidelines were used to determine the fluid allowance for each subject. The beverages were carbonated, caffeinated caloric and non-caloric colas and coffee. Ten of the 18 subjects consumed water and carbonated, non-caffeinated, citrus soft drink during a fifth trial. Body weight, urine and blood assays were measured before and after each treatment. Slight body weight loss was observed on all treatments, with an average of 0.30% for all treatments. No differences (p>0.05) among treatments were found for body weight changes or any of the biochemical assays. Biochemical assays conducted on first voids and 24-hour urines included electrolytes, creatine, osmolality and specific gravity. Blood samples were analyzed for hemoglobin, hematocrit. electrolytes, osmolality, urea nitrogen, creatinine and protein. This preliminary study found no significant differences in the effect of various combinations of beverages on hydration status of healthy adult males. Advising people to disregard caffeinated beverages as part of the daily fluid intake is not substantiated by the results of this study. The across-treatment weight loss observed, when combined with data on fluid-disease relationships, suggests that optimal fluid intake may be higher than common recommendations. Further research is needed to confirm these results and to explore optimal fluid intake for healthy individuals.
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With reports of high rates of sleep disruption in Human Immunodeficiency Virus (HIV) + persons, this study tested whether there were differences in sleep quality and well-being between a group of HIV+ persons who reduced their caffeine intake from baseline by 90% or greater for 30 days (n=44) versus a group of HIV+ persons who continued their usual caffeine consumption (n=44). Subjects were administered pre- and post-Pittsburgh Sleep Quality Index (PSQI), Perceived Well-being Scale-Revised (PWB-R) and MOS-HIV Health Survey instruments, with MOS-HIV summary scores used as a covariate. On ANCOVA analysis for sleep quality (F=14.032, P<.001), a 35% improvement in sleep among experimental subjects was identified. There was no significant difference between the two groups on ANCOVA analysis for well-being (F=0.111. P=.739). High levels of caffeine consumption may have an exacerbating effect on already prevalent HIV-related sleep pattern disturbances, and significant reductions of caffeine may improve sleep quality.
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Historically, hydration research reflected critical issues of the day. War, illness, surviving a shipwreck or time in the dessert, supplying fall-out shelters, and space exploration drove hydration research in the first half of the 20th century. The fitness revolution of the 1970s spurred research on dehydration in physically active people and athletes. The 1990s introduced the "fluid/disease relationship." What will be the driving force behind hydration research in the 21st century? Where are the gaps in our knowledge? This review provides an overview of issues pertinent to determining future directions in hydration research.
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The purpose of this study was to assess the influence of rehydration with a caffeinated beverage during nonexercise periods on hydration status throughout consecutive practices in the heat. Ten (7 women, 3 men) partially heat- acclimated athletes (age 24 +/-1y, body fat 19.2 +/- 2 %, weight 68.4 +/- 4.0 kg, height 170 +/- 3 cm) completed 3 successive days of 2-a-day practices (2 h/practice, 4 h/d) in mild heat (WBGT = 23 C). The 2 trials (double-blind, random, cross-over design) included; 1) caffeine (CAF) rehydrated with Coca-Cola and 2) caffeine-free (CF) rehydrated with Caffeine-Free Coca-Cola. Urine and psychological measures were determined before and after each 2-h practice. A significant difference was found for urine color for the post-AM time point, F = 5.526, P = 0.031. No differences were found among other variables (P > 0.05). In summary, there is little evidence to suggest that the use of beverages containing caffeine during nonexercise might hinder hydration status.
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Non-modulation has been proposed as an intermediate phenotype in human essential hypertension. The trait is characterized by blunted aldosterone and renal plasma flow responses to short-term angiotensin II (Ang II) infusion. Elevated tissue Ang II levels or decreased tissue adenosine levels could account for this decreased sensitivity to Ang II. In support of the latter possibility, endogenous adenosine has been shown to contribute to the renal vasoconstrictive response to Ang II in animals. We therefore tested the hypothesis that endogenous adenosine contributes to modulation of renal plasma flow in sodium-replete humans. We examined the effect of long-term administration of the adenosine receptor antagonist caffeine on baseline renal plasma flow and on the renal plasma flow response to short-term Ang II infusion in six salt-replete normotensive subjects in a single-blind, placebo-controlled study. para-Aminohippurate clearance was used to assess renal plasma flow. Ang II was infused in graded doses (0.3 to 3 ng/kg per minute) in the presence and absence of caffeine (250 mg PO TID for 7 days). Blood pressure, plasma renin activity, Ang II, electrolytes, and para-aminohippurate clearance were measured before and after each dose of Ang II. Caffeine did not alter either baseline blood pressure or the blood pressure response to Ang II but did increase baseline plasma renin activity from 0.72 +/- 0.09 to 1.42 +/- 0.26 ng angiotensin I/mL per hour (P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Cocoa products generally contain considerable amounts of methylxanthines, 80-90% being theobromine and 10-20% being caffeine. These substances may stimulate the central nervous system, the performance of the striated muscles and the renal function. When giving the methylxanthines in form of cocoa products, the mentioned effects are less pronounced than after application of equally dosed pure alcaloids. This difference may be explained by an impaired absorption of the substances due to the presence of polyhydroxyphenols and/or lipids in the cocoa products. When giving 20 mg/kg caffeine and 80 mg/kg theobromine to the mouse, i. e. in the naturally occurring relation, the stimulating effects of caffeine are enhanced after a transitory decrease when compared with those after caffeine alone. It is assumed that at first the stimulation after caffeine is inhibited by theobromine, but subsequently is enhanced by the later formed theobromine metabolites. Side effects of cocoa products have been observed in man in form to headache, trembling and sweating only after consumption of extremely high doses, e. g. 50-100 g cocoa poudre per day; they are essentially referred to the action of theobromine.
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Sleep laboratory investigations constitute a unique noninvasive tool to analyze brain functioning, Polysomnographic recordings, even in the very early phase of development in humans, are mandatory in a developmental plan of a new sleep-acting compound. Sleep is also an interesting tool for the development of other drugs acting on the central nervous system (CNS), Indeed, changes in sleep electroencephalographic (EEG) characteristics are a very sensitive indication of the objective central effects of psychoactive drugs, and these changes are specific to the way the drug acts on the brain neurotransmitter systems. Moreover, new compounds can be compared with reference drugs in terms of the sleep EEG profile they induce. For instance, cognitive enhancers involving cholinergic mechanism have been consistently demonstrated to increase rapid eye movement (REM) sleep pressure, and studying drug-induced slow wave sleep (SWS) alteration is a particularly useful tool for the development of CNS compounds acting at the 5-HT(2A/C) receptor, such as most atypical antipsychotics and some antidepressant drugs. The sleep EEG profile of antidepressants, and particularly their effects on REM sleep, are specific to their ability to enhance noradrenergic or serotonergic transmission, it is suggested that the effects of noradrenergic versus serotonergic reuptake inhibition could be disentangled using specific monoamine depletion tests and by studying drug effects on sleep microsiructure.
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Forty-six novel 3,7-dihydro-purine-2,6-dione derivatives (substituted xanthines) with great structural diversity were synthesized for biological activity screening. Three series of substituted xanthine analogs have been prepared in moderate to excellent yields.
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Background: Large simple trials are potentially efficient and cost-effective approaches to assess interventions to preserve cognitive function in older adults. High-dose cocoa flavanols supplementation is a promising intervention that warrants additional testing. We describe the design, recruitment success, and baseline characteristics of the Cocoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind) trial. Methods: COSMOS-Mind is an ancillary study to the large-scale and predominantly mail-based COSMOS randomized controlled clinical trial. COSMOS is assessing whether cocoa extract (including 600 mg/d cocoa flavanols) and a multivitamin reduce risks for major cardiovascular events and total invasive cancer. COSMOS-Mind uses telephone-based interviews to assess cognitive function and impairment to determine whether cocoa flavanols benefit cognitive function in adults aged 65 years or older, targeting the enrollment of 2000 participants to provide >90% statistical power across 3 years of annual follow-up. Results: Of the 3224 COSMOS screenees who expressed interest in COSMOS-Mind, 2350 (76%) successfully completed baseline cognitive assessments and 2262 (96%) geographically diverse, eligible individuals were ultimately enrolled over one year. At baseline, the primary outcome, a composite of cognitive test scores, was inversely associated with age in a manner consistent with assumptions used in projections of statistical power. Conclusions: Older adults are willing to enroll in large simple trials that include telephone-based cognitive assessments. Embedding these trials in large studies of other health outcomes is efficient and expands the scientific knowledge gained from the research. ClinicalTrials.gov Identifiers: NCT03035201 (COSMOS-Mind); NCT102422745 (parent COSMOS).
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Purpose: This study examined the relationship between caffeine intake and metabolic syndrome in Korean adults using the 2013 ~ 2016 Korea National Health and Nutrition Examination Survey data (KNHANES). Methods: The caffeine database (DB) developed by Food and Drug Safety Assessment Agency in 2014 was used to estimate the caffeine consumption. The food and beverage consumption of the 24 hr recall data of 2013 ~ 2016 KNHANES were matched to items in the caffeine DB and the daily caffeine intakes of the individuals were calculated. The sample was limited to non-pregnant healthy adults aged 19 years and older, who were not taking any medication for disease treatment. Results: The average daily caffeine intake was 41.97 mg, and the daily intake of caffeine of 97% of the participants was from coffee, teas, soft drinks, and other beverages. Multivariate analysis showed that the caffeine intake did not affect metabolic syndrome, hypertension, low HDL-cholesterol, and abdominal obesity. Diabetes and hypertriglyceridemia, however, were 0.76 (95% CI: 0.63 ~ 0.93), and 0.87 (95% CI: 0.77 ~ 0.98) in third quintile (Q3), and 0.66 (95% CI: 0.53 ~ 0.82) and 0.83 (95% CI: 0.73 ~ 0.94) in fourth quintile (Q4) compared to Q1, respectively. Therefore, caffeine intake of 3.66 ~ 45.81 mg per day is related to a lower risk of diabetes and hypertriglyceridemia. Conclusion: The study showed that adequate caffeine intake (approximately 45 mg) was associated with a lower prevalence of diabetes and hypertriglyceridemia. Therefore, it can be used as a guideline for the adequate level of caffeine intake for maintaining health.
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Caffeine, probably the most widely used drug, affects the psychological state of those who consume it. Abuse results in symptoms of caffeinism which include agitation, disorientation and a syndrome which may be mistaken for anxiety/neurosis. It is a habit forming drug in which tolerance develops. It affects sleep in a dose related manner which is dependent on the daily caffeine intake, i.e, high users have less effect. Its central nervous system stimulation can cause pleasant effects with improved attention and concentration at lower doses. At high doses, the reverse may occur. Used judiciously, it may be a useful therapy in the treatment of hyperkinetic children. These and other effects of caffeine are discussed in this review article.
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Thirty women, ages 35–65, on three separate mornings, drank 180 ml decaffeinated coffee to which 0, 3 or 6 mg/kg body weight caffeine had been added. Caffeine increased three hour total urinary calcium excretion from a baseline value of 10.8 to 15.9 and 17.8 mg, respectively. Sodium and magnesium excretion were also increased after caffeine ingestion. Phosphorus, chloride, potassium, creatinine and urine volume were not different after caffeine consumption. Increased urinary outputs of calcium and sodium were due to the increased urinary concentrations of calcium and sodium after caffeine consumption. Twenty of these women also took 650 mg aspirin 10 hours and 1 hour before consuming a second set of beverages containing 0 and 3 mg/kg body weight caffeine. Aspirin preloading did not affect the three hour total excretion or mineral/creatinine ratio of any of the minerals measured. There were no aspirin-caffeine interactions, indicating that the caffeine effect on mineral excretion may not be mediated by prostaglandin production. Estrogen use or menopausal status had no effect on calcium excretion after caffeine or aspirin.
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Like caffeine, theobromine crosses the blood-brain barrier and binds to adenosine receptors, suggesting it might share caffeine's beneficial effects on mood and vigilance. Therefore, the purpose of this study was to assess the effect of theobromine doses commonly found in foods on mood and vigilance parameters sensitive to caffeine. Caffeine was tested as a positive control. Twenty-four men (age, 23 [3] years) completed 6 double-blind trials during which they consumed experimental beverages, assessed their mood using standardized self-report questionnaires, and completed a 2-hour visual vigilance task. Three experimental doses (100, 200, and 400 mg theobromine) were delivered in a cocoa-based beverage; 3 matched control treatments (0 mg theobromine, 400 mg theobromine, and 100 mg caffeine) were delivered in a non-cocoa beverage. Mean salivary concentrations of theobromine exhibited significant dose-dependent differences (400 mg trials > 200 mg trial > 100 mg trial > 0 mg trials; P < 0.005). At every dose tested, theobromine failed to consistently affect mood state or vigilance (P > 0.05), but 100-mg caffeine significantly decreased lethargy/fatigue and increased vigor (P = 0.006 and 0.011, respectively). These findings indicate theobromine does not influence mood and vigilance when administered in nutritionally relevant doses, despite sharing many of caffeine's structural characteristics.
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The contrast of attitudes to the psychiatric effects of caffeine between North America and Britain is highlighted. A summary of the dietary sources, pharmacology and effects of caffeine on normal subjects is given. The emphasis in normal subjects is on the acute, chronic, toxic and withdrawal effects. With this background information, a more specific evaluation of the psychiatric issues are discussed. In conclusion, the case is made for the inclusion of a specific category, in non-dependent abuse of drugs, for caffeine.
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Homoplastic mutations are mutations independently occurring in different clades of an organism. The homoplastic changes may be a result of convergence evolution due to selective pressures. Reports on the analysis of homoplastic mutations in Mycobacterium tuberculosis have been limited. Here we characterized the distribution of homoplastic single nucleotide polymorphisms (SNPs) among genomes of 1,170 clinical M. tuberculosis isolates. They were present in all functional categories of genes, with pe/ppe gene family having the highest ratio of homoplastic SNPs compared to the total SNPs identified in the same functional category. Among the pe/ppe genes, the homoplastic SNPs were common in a relatively small number of homologous genes, including ppe18, the protein of which is a component of a promising candidate vaccine, M72/AS01E. The homoplastic SNPs in ppe18 were particularly common among M. tuberculosis Lineage 1 isolates, suggesting the need for caution in extrapolating the results of the vaccine trial to the population where L1 is endemic in Asia. As expected, homoplastic SNPs strongly associated with drug resistance. Most of these mutations are already well known. However, a number of novel mutations associated with streptomycin resistance were identified, which warrants further investigation. A SNP in the intergenic region upstream of Rv0079 (DATIN) was experimentally shown to increase transcriptional activity of the downstream gene, suggesting that intergenic homoplastic SNPs should have effects on the physiology of the bacterial cells. Our study highlights the potential of homoplastic mutations to produce phenotypic changes. Under selective pressure and during interaction with the host, homoplastic mutations may confer advantages to M. tuberculosis and deserve further characterization.
Article
Twelve female college students drank decaffeinated coffee or tea to which 0, 150 or 300 mg caffeine had been added. Each subject had fasted at least ten hours before drinking each of the three test beverages. Urine samples were collected at one, two and three hours after caffeine consumption. Total urinary three hour excretion of calcium, magnesium and sodium, but not potassium, increased significantly after caffeine intake. The increased output of calcium and sodium was mainly due to significantly increased urinary calcium and sodium concentrations, while the increased output of magnesium appeared to be due to the combination of both a slightly increased urinary magnesium concentration and volume. Total urine volume correlated significantly with dose of caffeine per body weight when 300 mg of caffeine was consumed. The effects of caffeine on mineral excretion were primarily due to changes in mineral concentration and increased urinary volume at one and two hours.
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Caffeine is the most widely consumed centralnervous-system stimulant. Three main mechanisms of action of caffeine on the central nervous system have been described. Mobilization of intracellular calcium and inhibition of specific phosphodiesterases only occur at high non-physiological concentrations of caffeine. The only likely mechanism of action of the methylxanthine is the antagonism at the level of adenosine receptors. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline neurons and seems to affect the local release of dopamine. Many of the alerting effects of caffeine may be related to the action of the methylxanthine on serotonine neurons. The methylxanthine induces dose-response increases in locomotor activity in animals. Its psychostimulant action on man is, however, often subtle and not very easy to detect. The effects of caffeine on learning, memory, performance and coordination are rather related to the methylxanthine action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on anxiety and sleep which vary according to individual sensitivity to the methylxanthine. However, children in general do not appear more sensitive to methylxanthine effects than adults. The central nervous system does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported.
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Numerous studies dissecting the basic mechanisms that control sleep regulation have led to considerable improvement in our knowledge of sleep disorders. It is now well accepted that transitions between sleep and wakefulness are regulated by complex neurobiologic mechanisms, which, ultimately, can be delineated as oscillations between two opponent processes, one promoting sleep and the other promoting wakefulness. The role of several neurotransmitter or neuromodulator systems, including noradrenergic, serotonergic, cholinergic, adenosinergic, and histaminergic systems and, more recently, the hypocretin/orexin and dopamine systems, has been clearly established. Amphetamine-like stimulants are known to increase wakefulness by blocking dopamine reuptake, by stimulating dopamine release, or by both mechanisms. Modafinil may increase wakefulness through activation of noradrenergic and dopaminergic systems, possibly through interaction with the hypocretin/orexin system. Caffeine inhibits adenosinergic receptors, which in turn can produce activation via interaction with GABAergic and dopaminergic neurotransmission. Nicotine enhances acetylcholine neurotransmission in the basal forebrain and dopamine release. Understanding the exact role of the hypocretin/orexin and dopamine systems in the physiology and pharmacology of sleep-wake regulation may reveal new insights into current and future wakefulness-promoting drugs.
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