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PubMed1988

Caffeine promotes in vitro fertilization of mouse ova within 15 minutes.

Epididymal sperm were collected from C57Bl6/J X DBA2/J (B6D2) males and allowed to capacitate for 2 hr. When cumulus-free oocytes were exposed to sperm for 15 min in either the presence (6.0 mM) or absence of caffeine, fertilization did not occur. However, when cumulus cells were left intact, 23% of oocytes were fertilized in caffeine-free medium and 62% in caffeine-containing medium. When cumulus-free oocytes were incubated with sperm for 30 min, none was fertilized in the absence of caffeine, but 33% were fertilized when 6.0 mM caffeine was present (P less than .02). These effects of caffeine were on the sperm, as sperm exposed to caffeine and then coincubated with oocytes for 15 min in essentially caffeine-free media fertilized a similar percent of oocytes (93%) as when sperm and oocytes were exposed to caffeine during the fertilization period (86%). When sperm were capacitated in caffeine-containing medium, the percentage of ova fertilized was similar to capacitation without caffeine. We conclude that both cumulus cells and caffeine speed up the fertilization process with mouse gametes and that the effect of caffeine is on the sperm, but not due to more rapid capacitation.

Animals↗
PubMed1986

Caffeine inhibition of calcium accumulation by the sarcoplasmic reticulum in mammalian skinned fibers.

Oxalate-supported Ca accumulation by the sarcoplasmic reticulum (SR) of chemically skinned mammalian skeletal muscle fibers is activated by MgATP and Ca2+ and partially inhibited by caffeine. Inhibition by caffeine is greatest when Ca2+ exceeds 0.3 to 0.4 microM, when free ATP exceeds 0.8 to 1 mM, and when the inhibitor is present from the beginning of the loading period rather than when it is added after Ca oxalate has already begun to precipitate within the SR. Under the most favorable combination of these conditions, this effect of caffeine is maximal at 2.5 to 5 mM and is half-maximal at approximately 0.5 mM. For a given concentration of caffeine, inhibition decreases to one-half of its maximum value when free ATP is reduced to 0.2 to 0.3 mM. Varying free Mg2+ (0.1 to 2 mM) or MgATP (0.03 to 10 mM) has no effect on inhibition. Average residual uptake rates in the presence of 5 mM caffeine at pCa 6.4 range from 32 to 70% of the control rates in fibers from different animals. The extent of inhibition in whole-muscle homogenates is similar to that observed in skinned fibers, but further purification of SR membranes by differential centrifugation reduces their ability to respond to caffeine. In skinned fibers, caffeine does not alter the Ca2+ concentration dependence of Ca uptake (K0.5, 0.5 to 0.8 microM; Hill n, 1.5 to 2.1). Reductions in rate due to caffeine are accompanied by proportional reductions in maximum capacity of the fibers, and this configuration can be mimicked by treating fibers with the ionophore A23187. Caffeine induces a sustained release of Ca from fibers loaded with Ca oxalate. However, caffeine-induced Ca release is transient when fibers are loaded without oxalate. The effects of caffeine on rate and capacity of Ca uptake as well as the sustained and transient effects on uptake and release observed under different conditions can be accounted for by a single mode of action of caffeine: it increases Ca permeability in a limited population of SR membranes, and these membranes coexist with a population of caffeine-insensitive membranes within the same fiber.

Adenosine Triphosphate↗
PubMed1980

[Modification of the caffeine metabolism in mouse liver slices by previous treatment of the experimental animals with ethanol, aminophenazone and phenobarbital].

The influence of ethanol, aminophenazon, and phenobarbital on the caffeine metabolism of mice liver slices was tested using 1-methyl-14C-caffeine as the marker substance. In these experiments the following results were obtained: 1. Caffeine metabolism was increased by the extension of the incubation time. The caffeine metabolism increased almost linearly up to 60 min, and during this time 109.5 nmol caffeine were metabolized per gram liver wet weight. 2. Ethanol decreased the caffeine metabolism of mice liver slices. Ethanol concentrations of 23.36, 46.72 and 93.44 mM showed a clear and dose-dependent inhibition of caffeine metabolism, reaching a maximal value of 67.1%. 3. Aminophenazon also decreased the metabolism of caffeine. This effect was augmented by increasing the concentrations of aminophenazon (10.4, 20.8, 41.6, 104.0 M) and an inhibition of 63.8% was observed after giving the highest concentration. 4. Pretreatment of mice with phenobarbital, producing an enzyme induction of the liver, clearly increased the metabolism of caffeine of mice liver slices. Under these conditions, the caffeine metabolism was increased by more than 300%. 5. In contrast to liver slices no important caffeine metabolism could be detected in kidney or brain slices of mice. 6. Mice liver slices were able to metabolize caffeine more quickly than liver slices of the rat. Within 60 min the metabolized caffeine per gram liver wet weight was more than twice higher for mice as compared to rats.

Aminopyrine↗
PubMed2002

Subchronic caffeine administration sensitizes rats to the motor-activating effects of dopamine D(1) and D(2) receptor agonists.

RATIONALE: Dopamine transmission acting at either the D(1) or D(2) receptor level is known to influence the stimulant properties of caffeine, an antagonist of adenosine A(1) and A(2) receptors. In contrast, how caffeine influences the motor stimulant properties of selective D(1) and D(2) receptor agonists is still undefined. OBJECTIVES: In this study the acute motor response to the dopamine D(1) receptor agonist SKF 77434 and the D(2)/D(3) receptor agonist quinpirole was studied in rats treated subchronically with caffeine (15 mg/kg i.p., on alternate days) or vehicle, either in the test cage (paired group) or in the home cage (home group). METHODS AND RESULTS: Repeated caffeine administration did not induce any significant increase in motor activity or in stereotyped behavior during the course of treatment, indicating that the response to caffeine itself did not develop sensitization. Three days after the last caffeine or vehicle administration, rats were challenged with caffeine, SKF 77434, or quinpirole. Caffeine (5 mg/kg i.p.) elicited the same motor stimulant effects in both caffeine- and vehicle-pretreated rats, confirming the presence of neither tolerance nor sensitization to caffeine itself. SKF 77434 (3 mg/kg s.c.) elicited a higher locomotor activation in caffeine- than in vehicle-pretreated rats, whereas quinpirole (0.15 mg/kg s.c.) induced a similar locomotor activation and a higher stereotyped behavior in caffeine-pretreated rats as compared to rats pretreated with vehicle. The sensitized response to SKF 77434 and quinpirole was not due to environmental conditioning since the responses were similar in either paired or home group. CONCLUSIONS: The results provide support for the presence of long-term functional interactions between drugs acting at the adenosine and dopamine receptor levels. Subchronic caffeine, by sensitizing the motor stimulant effects of dopamine D(1) and D(2) receptor agonists, produces adaptive changes which might result in a potentiation of the dopaminergic component of drugs of abuse.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type.

Psychopharmacological studies using caffeinated beverages or caffeine have rarely considered temporal effects on psychological and physiological function or the specific contribution of caffeine, hot water, or beverage type to the observed effects. The effect of 400 ml hot tea, coffee, and water consumption on systolic and diastolic blood pressure (SBP and DBP), heart rate, skin conductance (a measure of sympathetic nervous system activation), skin temperature, salivary cortisol, and mood were monitored in 16 healthy caffeine-withdrawn (14 h) subjects in a complete crossover design. Beverages were ingested with/without 100 mg caffeine and milk (tea/coffee only). Hot beverage ingestion rapidly increased skin conductance and temperature (+1.7 degrees C) with peak effects observed only 10-30 min post-consumption. Caffeine in the beverage rapidly augmented skin conductance responses but, in contrast to the effect of hot water, reduced the skin temperature response and increased SBP (+2.8 mmHg) and DBP (+2.1 mmHg) 30-60 min post-consumption. Both caffeine and milk addition to beverages independently improved mood and reduced anxiety 30 and 60 min post-consumption. Milk addition had no other effects apart from attenuating the transient increase in physiological responses associated with the drinking phase. There were no effects of beverage consumption on salivary cortisol or of beverage vehicle on salivary caffeine levels, the latter indicating that caffeine pharmacokinetics was similar in both tea and coffee, and not different from caffeinated water. In keeping with this, the responses to tea and coffee ingestion were similar and largely accounted for by the effects of hot water and caffeine. However, tea potentiated the increase in skin temperature compared to coffee and water indicative of a greater vasodilatory response plausibly related to the presence of flavonoids in tea. We conclude that ingestion of hot caffeinated beverages stimulates physiological processes faster than hitherto described, primarily via the effects of hot water and caffeine, but with beverage type and milk playing important modulatory roles.

Adult↗
PubMed1984

Cardiovascular effects of coffee and caffeine.

This study evaluated the cardiovascular effects and elimination kinetics of coffee and caffeine in 54 volunteers selected according to 3 gradations of daily caffeine consumption, cigarette smoking status and the presence of caffeine intolerance. After 24 hours of caffeine abstinence, subjects received coffee and 2.2 mg/kg of caffeine (equivalent to 2 cups of coffee). Blood pressure, heart rate, systolic time intervals and plasma concentrations of caffeine were measured before and at timed intervals after coffee and caffeine. There were no differences in response to coffee and caffeine. The average systolic/diastolic blood pressure increased 9/10 mm Hg. The maximal decrease in heart rate averaged 10 beats/min, and there were small increases in the systolic time intervals. There were no cardiovascular differences among the various groups. Caffeine in the smokers and heavy caffeine users had a shorter half-life (3.2 and 4.1 hours) than that in nonsmokers and nonusers (5.1 and 5.3 hours). In the caffeine-intolerant group it had a longer half-life, while the cardiovascular effects were similar to those of the other groups. Thus, irrespective of the amount of daily caffeine consumption, smoking status or caffeine intolerance, the cardiovascular responses were similar and tolerance, if present, was gone by 24 hours.

Adult↗
PubMed1995

Sympathomimetic effects of paraxanthine and caffeine in humans.

Caffeine is metabolized extensively (on average 80%) to paraxanthine. With regular caffeine consumption, average serum levels of paraxanthine are two thirds those of caffeine. Both caffeine and paraxanthine competitively and nonselectively inhibit adenosine receptors in vitro. To examine the contribution of paraxanthine to the pharmacologic activity of caffeine, we administered to 12 subjects in a crossover design oral caffeine (2 or 4 mg/kg) versus placebo or oral paraxanthine (same dose as caffeine) versus placebo, each after 3 days of methylxanthine abstinence. Both caffeine and paraxanthine significantly increased diastolic blood pressure, plasma epinephrine levels, and free fatty acids. Caffeine and paraxanthine produced a similar magnitude of response at 4 mg/kg; however, caffeine appeared to produce greater responses than paraxanthine at 2 mg/kg. Caffeine and paraxanthine have similar sympathomimetic actions. The activity of paraxanthine needs to be considered in understanding the clinical pharmacology of caffeine, particularly with chronic, repetitive caffeine consumption.

Adult↗
PubMed1994

The effect of caffeine on food intake in rats: involvement of corticotropin-releasing factor and the sympatho-adrenal system.

The involvement of CRH and the sympatho-adrenal system in the effects of caffeine on food intake and body weight gain has been investigated in rats. Food intake and body weight gain were measured in male rats after the treatment with caffeine in combination with either an injection of the CRH antagonist alpha-helical CRH(9-41), a surgical adrenal demedullation (medullectomy), or a ganglionic blockade. Alpha-helical CRH(9-41) was injected in the lateral ventricle of the brain and hexamethonium was used to chemically block the ganglionic transmission. From 4 to 24 h following a caffeine injection, spontaneous food intake, which was cumulated from the time caffeine was injected, was significantly (p < 0.01) lower in caffeine- than in saline-treated rats. In food-deprived rats, the anorectic effect of caffeine was biphasic, being significant at 0.5 and 1 h after the caffeine administration, then vanishing for 3 h, and becoming significant again 6 h after the caffeine administration. In both the spontaneously fed and food-deprived rats, caffeine reduced the rate of weight gain, which was measured at the end of a 12- or a 24-h period following the caffeine injection. A significant (p < 0.05) interaction effect of caffeine and alpha-helical-CRH(9-41) was found on the cumulative food intake at 1, 6, and 8 h, and on the amount of food eaten between the 4-6-h interval following the injection of caffeine; the effects of caffeine on food intake and body weight gain seem largely prevented by the use of a CRH antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1983

Role of calcium in the inotropic effects of caffeine in cardiac Purkinje fibers.

The inotropic effects of caffeine (1-3 mM) were studied in the presence and absence of strophanthidin in canine Purkinje fibers perfused in vitro. Caffeine (1 mM) induced a similar initial increase in contractile force in different calcium solutions (+22, +23 and +24% in 0.54, 2.7 and 8.1 mM calcium, respectively) and when propranolol (3.4 X 10(-6) M) was present. Also, caffeine increased contractile force in high potassium (16.2 mM) at a time when the slow action potentials were unaltered. After the increase, 1 mM caffeine decreased force by about 50%, and the decrease was larger when caffeine (3 mM) or [Ca]0 (8.1 mM) was higher. In the presence of caffeine, strophanthidin (3 X 10(-7)-1 X 10(-6) M) increased force (+302%) if caffeine (0.3 mM) and Ca concentrations (0.54 mM) were low. If either caffeine or calcium was increased, strophanthidin had no effect or decreased force. Strophanthidin alone increased force and then decreased it; caffeine increased force in the first stage and decreased it during the second stage. The positive inotropic effect (+224%) of low sodium (78.4 mM versus 149.4 mM in Tyrode solution) was also abolished by caffeine (-24%). In ventricular muscle fibers, caffeine increased force more (+59%) and reduced force less in the presence of strophanthidin. The results indicate that caffeine increases force initially by releasing calcium from intracellular stores. The caffeine-induced decline in force is modulated by calcium in that it is exaggerated by agents or procedures which increase cellular calcium (strophanthidin, high calcium, low sodium solutions) and is reversed in a low calcium solution.

Animals↗
PubMed1988

Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies.

Five surveys, using a previously developed high-performance liquid chromatography procedure to measure caffeine concentrations, indicated great variations in the concentrations of caffeine in tea and coffee. In the study of beverages prepared at home, data on caffeine concentrations in 58 samples of tea and coffee, volumes of cups, and numbers of cups consumed/day, indicated that the range of caffeine intakes for the women participating was 49-1022 mg/day. There were considerable day-to-day variations in caffeine contents in coffee samples from some commercial coffee shops. When 17 samples of five national brands of instant coffee were made into beverages in the laboratory, variations in caffeine concentrations between lots were small but between brands were significant. A considerable range of caffeine concentrations was also found when 12 samples of coffee prepared at work by different individuals using the same jar of instant coffee were analysed. Analysis of tea samples prepared in the laboratory indicated that steeping time had an important influence on resulting caffeine and theobromine concentrations. People preparing their own beverages were found to drink more liquid than the volume offered commerically. The mean caffeine 'contents' of home-made coffee and of coffee prepared by individuals at work were 79.4 and 81.7 mg/cup respectively, indicating a mean intake of approximately 80 mg caffeine/cup. When this amount (80 mg/cup) was used to estimate daily intakes of caffeine from coffee, on the basis of the number of reported cups/day, and the values obtained were compared with the amounts actually consumed by individuals, the potential for misrepresentation of individual consumption became obvious. For example, for subjects consuming three cups of coffee, only 25% would have been correctly categorized in the expected range for the daily intake of caffeine, 39% would have been overestimated and 36% underestimated for the amount of caffeine consumed. These variations in caffeine concentrations and in the volume of coffee consumed have frequently been ignored in examinations of the possible relationship between coffee consumption and various health problems, and this could perhaps partly explain some conflicting results seen in epidemiological studies.

Adult↗
PubMed2005

Effect of methyl-beta-cyclodextrin treatment of pig spermatozoa on in vitro fertilization and embryo development in the absence or presence of caffeine.

A series of experiments were carried out to develop a new method to reduce pig polyspermic fertilization and produce more normal embryos, in vitro. Experiment 1 determined the effect of methyl-beta-cyclodextrin (MCD) treatment during cryopreservation on sperm acrosome reaction and sperm fertilization. Compared to the non-MCD-treated control, MCD treatment increased the percentage of acrosome-reacted spermatozoa at thawing and 2h after incubation in fertilization medium (P<0.01). Treatment with MCD also increased (P<0.05) sperm-penetration rate, number of spermatozoa in oocytes, and fertilization efficiency in the caffeine-free fertilization medium. Experiment 2 was designed to examine the effect of withdrawal of caffeine (caffeine-free) from fertilization medium on fertilization parameters and early embryo development. Using MCD-treated spermatozoa, there was no difference in sperm-penetration rate, oocyte cleavage rate, and blastocyst formation rate between the caffeine-free and caffeine-supplemented groups. However, polyspermic fertilization rate was lower, and fertilization efficiency and blastocyst cell number were higher in the caffeine-free group compared to the caffeine-supplemented group (P<0.05). Experiment 3 studied the effect of caffeine and different concentrations of spermatozoa on fertilization parameters. Sperm-penetration rate did not differ between the caffeine-free and the caffeine-supplemented groups at different sperm concentrations. Caffeine and sperm concentration had an effect on the number of spermatozoa in oocytes and on the polyspermic fertilization rate (P<0.002). Caffeine also affected fertilization efficiency (P<0.05). In conclusion, treating spermatozoa with MCD and withdrawing caffeine from fertilization medium may provide a new method to produce a large number of normal embryos, in vitro.

Acrosome Reaction↗
PubMed1997

Prophylactic intravenous administration of caffeine and recovery after ambulatory surgical procedures.

OBJECTIVE: To determine whether prophylactic intravenous administration of caffeine, to daily caffeine users, decreases the frequency of postoperative headache and shortens recovery time. DESIGN: The study was a prospective, randomized, double-blind investigation with predetermined sample size and statistical power. MATERIAL AND METHODS: After Mayo Institutional Review Board approval and informed consent were obtained, 300 adult ambulatory surgical patients were enrolled in this study, which included randomization to receive either placebo or caffeine (200 mg intravenously) in the postanesthesia care unit. While recuperating, patients were allowed their choice of postoperative beverages. Before dismissal, patients completed a questionnaire providing details about intake of caffeine and tobacco, history of headache, and demographic data. Patients were considered "at risk" for symptoms of caffeine withdrawal if they did not drink a caffeinated beverage after the surgical procedure. RESULTS: Completed questionnaires were obtained from 234 patients. Patients at risk for symptoms of caffeine withdrawal were less likely to have a postoperative headache if they received caffeine intravenously rather than placebo-10% versus 23% (P < 0.05). Time until recovery was not significantly different between caffeine and placebo study groups. CONCLUSION: We conclude that prophylactic intravenous administration of caffeine was beneficial for those patients at risk for symptoms of caffeine withdrawal. For patients who consume caffeinated beverages on a daily basis, we recommend prophylactic administration of caffeine on the day of an ambulatory surgical procedure and anesthesia.

Adolescent↗
PubMed2000

Influence of age on the thermic response to caffeine in women.

The purpose of this study was to examine age-related differences in the magnitude of caffeine-induced thermogenesis and the relationship of aerobic fitness, body composition, and hormone and substrate concentrations to the thermic effect of caffeine in younger and older women. Using a placebo-controlled, double-blind study design, 10 older (50 to 67 years) and 10 younger (21 to 31 years) healthy women who were moderate consumers of caffeine (self-reported intake: younger, 139 +/- 152 mg/d; older, 204 +/- 101 mg/d, NS, mean +/- SD) were characterized for fasting plasma glucose, insulin, free fatty acid (FFA), and caffeine levels, energy expenditure, body composition, anthropometry, aerobic fitness, physical activity, and energy intake. Before and after placebo and caffeine ingestion (5 mg/kg fat-free mass [FFM]), the following variables were measured: fasting plasma glucose, insulin, FFA, and energy expenditure, plasma glucose, insulin, and FFA, and energy expenditure in response to placebo and caffeine ingestion. Caffeine ingestion resulted in similar increases in younger and older women for plasma caffeine (younger, 80 +/- 34 to 5,604 +/- 528 ng/mL, P < .01; older, 154 +/- 134 to 5,971 +/- 867 ng/mL, P < .01) and fatty acids (younger, 294 +/- 118 to 798 +/- 248 micromol/L, P < .01; older, 360 +/- 180 to 727 +/- 310 micromol/L, P < .01), whereas plasma insulin and glucose levels remained unchanged from baseline. Energy expenditure increased following caffeine ingestion in both groups (younger, 15.4%, 1.09 +/- 0.14 to 1.24 +/- 0.13 kcal/min, P < .05; older, 7.8%, 0.98 +/- 0.14 to 1.06 +/- 0.12 kcal/min, P < .05), although there was a blunted thermic response in the older versus younger women (older, 6.9 +/- 5 kcal/90 min; younger, 15.5 +/- 7 kcal/90 min, P < .05). In younger women, the thermic response to caffeine was positively correlated with the waist circumference (r = .70, P < .05) and body weight (r = .91; P < .01), whereas aerobic fitness (r = .77; P < .05) was the only significant correlate in older women. In conclusion, older and younger women increase energy expenditure significantly following caffeine ingestion, but older women have a blunted thermic response compared with younger women. Second, the thermic response to caffeine is positively associated with the body weight and waist circumference in younger women, whereas a positive association with aerobic fitness was observed in older women. Thus, the physiologic determinants of the thermic response to caffeine differ among women of different age groups.

Adolescent↗
PubMed2000

Reversal of caffeine withdrawal by ingestion of a soft beverage.

Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects.

Adult↗
PubMed1997

Caffeine mediates cation influx and intracellular Ca2+ release in leech P neurones.

We investigated the effect of caffeine on the intracellular free Ca2+ concentration ([Ca2+]i) of leech P neurones by using the fluorescent indicator Fura-2. Caffeine induced a [Ca2+]i increase that was strongly reduced, but not abolished, in Ca(2+)-free solution. The effect of caffeine on [Ca2+]i was dose-dependent: while 5 mM caffeine evoked a persistent [Ca2+]i increase that could be elicited repetitively, 10 mM caffeine or more induced a transient [Ca2+]i increase that was strongly reduced upon subsequent applications at the same concentration. Surprisingly, the cells remained fully responsive to a moderately increased caffeine concentration. The caffeine-induced [Ca2+]i increase was not blocked by millimolar concentrations of La3+, Mg2+, Cd2+, Zn2+, Co2+, Ni2+, or Mn2+. While La3+ and Mg2+ had no effect on the caffeine response, the other cations caused irreversible changes in the Fura-2 fluorescence. The inhibitors of intracellular Ca2+ pumps-thapsigargin, cyclopiazonic acid (CPA), and 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ)--had no effect on the caffeine-induced [Ca2+]i increase at normal extracellular Ca2+ concentration, but they reduced it in Ca(2+)-free solution. Ryanodine had no effect on the caffeine-induced [Ca2+]i increase at normal extracellular Ca2+ concentration, and also in Ca(2+)-free solution it seemed to be largely ineffective. Caffeine evoked complete fluctuations of the membrane potential. The effect in Ca2+ free and in Na(+)-free solution suggests that the depolarizing response components were mainly due to Na+ influx, while Ca2+ reduced the Na+ influx and/or activated mechanisms which re- or hyperpolarize the cells. It is concluded that leech P neurones possess caffeine-sensitive intracellular Ca2+ stores, as well as caffeine-sensitive ion channels, in the plasma membrane that are activated by a voltage-independent mechanism. The plasma membrane channels are permeable to various divalent cations including Ca2+, and possibly also to Na+.

Animals↗
PubMedDate not supplied

Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy.

Fecundability has been defined as the ability to achieve a recognized pregnancy. Several studies on caffeine and fecundability have been conducted but have been inconclusive. This may be explained partly by lack of stratification by smoking. Furthermore, few researchers have tried to separate the effect of caffeine from different sources (coffee, tea, cola, and chocolate). Clearly, the relationship between caffeine and fecundability needs further research, given the high prevalence of caffeine intake among women of childbearing age. We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception. From 1992 to 1995, a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old, lived with a partner, and had no previous reproductive experience. At enrollment and in six cycles of follow-up, both partners filled out a questionnaire on different factors including smoking habits and their intake of coffee, tea, chocolate, cola beverages, and chocolate bars. In all, 1596 cycles and 423 couples were included in the analyses. The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle (pregnant or not pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR). Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [95% confidence interval (CI) 0.60-1.31], whereas women with a higher caffeine intake had a FR = 0.63 (95% CI 0.25-1.60) after adjusting for female body mass index and alcohol intake, diseases of the female reproductive organs, semen quality, and duration of menstrual cycle. No dose-response relationship was found among smokers. Among males, the same decline in point estimates of the FR was present. Smoking women whose only source of caffeine was coffee (>300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between caffeine and smoking is biologically plausible, and the lack of effect among smokers may be due to faster metabolism of caffeine. Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake.

Adult↗
PubMed1998

Relationship of blood pressure, heart rate and behavioral mood state to norepinephrine kinetics in younger and older men following caffeine ingestion.

OBJECTIVE: To examine age-related differences in blood pressure, heart rate, behavioral mood state and norepinephrine kinetics after caffeine ingestion in younger and older men. DESIGN: Placebo-controlled, double-blind study. SETTING: General Clinical Research Center, University of Vermont. SUBJECTS: 10 older (O) (65-80 y) and 10 younger (Y) (19-26 y) healthy men who were moderate consumers of caffeine (Y= 126+/-30 mg/d; O = 160 44 mg/d:NS; mean +/- s.e.m.). INTERVENTION: All volunteers were characterized for fasting plasma glucose, insulin and caffeine levels, body composition, anthropometry, physical activity, and energy intake. Before and after placebo and caffeine ingestion (5 mg/kg fat-free mass) test days, the following variables were measured in all subjects: heart rate, blood pressure, mood state, and norepinephrine concentrations (NEconc), appearance (NEapp) and clearance (NEcl). MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure, heart rate, mood state, and norepinephrine kinetic responses to placebo and caffeine ingestion. RESULTS: Following caffeine ingestion, plasma caffeine levels were similar in Y and O men. Systolic (SBP) and diastolic (DBP) blood pressure increased significantly (P < 0.01) from baseline by 9% (130+/-6 vs 142+/-6 mmHg) and 3% (75+/-3 vs 77+/-3 mmHg), respectively, in O men following caffeine ingestion, but remained unchanged in Y men. Self-reported feelings of tension (P < 0.05) and anger (P = 0.06) decreased in O men, while anger tended to increase in Y men (P < 0.06) following caffeine ingestion. Heart rates in both groups were unaltered following caffeine ingestion. No differences were noted at baseline between O and Y men for NEconc, NEapp and NEcl. After caffeine ingestion, NEconc were significantly greater in O than Y men, whereas NEapp and NEcl rates did not differ from baseline in either group. Blood pressure and subjective mood state effects of caffeine were not related to changes in norepinephrine kinetics. CONCLUSION: Age may play a role in augmenting blood pressure response and reducing subjective feelings of anger and tension following caffeine ingestion, suggesting that the elderly are more reactive to the pressor and less sensitive to the subjective effects of the drug. These effects do not appear to be mediated by changes in sympathetic nervous system activity.

Adult↗
PubMed1992

Withdrawal syndrome after the double-blind cessation of caffeine consumption.

BACKGROUND: People who stop consuming caffeine may have symptoms, but the incidence and severity of caffeine withdrawal are not known. This study was performed to determine the effects in the general population of ending one's dietary intake of caffeine. METHODS: We studied 62 normal adults whose intake of caffeine was low to moderate (mean amount, 235 mg--the equivalent of 2.5 cups of coffee--per day). They completed questionnaires about symptoms and tests of their mood and performance when consuming their normal diets (base-line period) and at the end of each of two two-day periods during which they consumed caffeine-free diets and under double-blind conditions received capsules containing placebo (placebo period) or caffeine (caffeine period) in amounts equal to their daily caffeine consumption. RESULTS: More subjects had abnormally high Beck Depression Inventory scores (11 percent), high scores on the trait scale of the State-Trait Anxiety Inventory (8 percent), low vigor scores (11 percent) and high fatigue scores (8 percent) on the Profile of Mood States, and moderate or severe headache (52 percent) during the placebo period than during either the base-line period (2, 0, 0, 0, and 2 percent, respectively; P less than 0.05) or the caffeine period (3, 2, 2, 0, and 6 percent; P less than 0.05). More subjects reported unauthorized use of medications during the placebo period (13 percent) than during the caffeine period (2 percent, P = 0.017). Performance of a tapping task was slower during the placebo period than during the base-line and caffeine periods (P less than 0.01). CONCLUSIONS: Persons who consume low or moderate amounts of caffeine may have a withdrawal syndrome after their daily consumption of caffeine ceases.

Adult↗