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CORK Bibliography: Caffeine

83 citations. October 2007 to present

Prepared: September 2008

Anderson C; Horne JA. Placebo response to caffeine improves reaction time performance in sleepy people. Human Psychopharmacology: Clinical and Experimental 23(4): 333-336, 2008. (25 refs.)

Caffeine is the most widely used stimulant to counteract sleepiness. However, little is known about any placebo effect of caffeine in sleepy people and the effect of suggestibility. Over a 95 min test period, and in a counterbalanced design, 16 young healthy adults underwent 3 x 30 min sessions at the psychomotor vigilance test (PVT), during an early afternoon 'dip' enhanced by a prior night's sleep restriction (5 h). On both occasions they were given a cup of a decaffeinated coffee; once when the participant was verbally primed to suggest the coffee was caffeinated (Placebo) and on the other under neutral priming (Control). There were significantly fewer lapses and shorter reaction times following Placebo, for the initial two 30 min sessions, indicating that suggestion about consuming caffeine was effective in improving performance in moderately sleepy people.

Astorino TA; Rohmann RL; Firth K. Effect of caffeine ingestion on one-repetition maximum muscular strength. European Journal of Applied Physiology 102(2): 127-132, 2008. (25 refs.)

Multiple studies corroborate the ergogenic properties of caffeine (CAF) for endurance performance, yet fewer investigations document the efficacy of acute caffeine intake for intense, short-term exercise. The aim of the study was to determine the ergogenic potential of caffeine during testing of muscular strength and endurance. Twenty-two resistance-trained men ingested CAF (6 mg/kg) or placebo (PL) 1 h pre-exercise in a randomized, double-blind crossover design. They refrained from caffeine intake and strenuous exercise 48 and 24 h, respectively, pre-visit. Initially, resting heart rate and blood pressure were obtained followed by one-repetition maximum (1-RM) testing on the barbell bench press and leg press. Upon determination of 1-RM, participants completed repetitions to failure at 60%1-RM. Heart rate, blood pressure, and rating of perceived exertion (RPE) were measured after the final repetition. Compared to PL, there was no effect (P > 0.05) of caffeine on muscular strength, as 1-RM bench press (116.4 +/- 23.6 kg vs. 114.9 +/- 22.8 kg) and leg press (410.6 +/- 92.4 kg vs. 394.8 +/- 95.4 kg) were similar. Total weight lifted during the 60% 1-RM trial was 11 and 12% higher for the bench press and leg press with caffeine compared to placebo, yet did not reach significance. RPE was similar at the end of resistance exercise with CAF vs. PL. Acute caffeine intake does not significantly alter muscular strength or endurance during intense bench press or leg press exercise, yet the practical importance of the increased muscular endurance remains to be explored.

Barry RJ; Johnstone SJ; Clarke AR; Rushby JA; Brown CR; McKenzie DN. Caffeine effects on ERPs and performance in an auditory Go/NoGo task. Clinical Neurophysiology 118(12): 2692-2699, 2007. (41 refs.)

Objective: Previous research has shown that caffeine produces a general increase in arousal. The present study examined caffeine-induced arousal effects on performance and auditory ERPs. We sought components showing amplitude changes without topography changes, as would be expected of a pure arousal amplification of source activity. Methods: The effects of a single oral dose of caffeine (250 mg) were examined in a randomised double-blind placebo-controlled repeated-measures cross-over study. Subjects abstained from caffeine for 4 h before the testing sessions, which were conducted, in the afternoon, one week apart. A simple auditory Go/NoGo task was used, with a random mix of 75 tones at 1000 Hz and 75 at 1500 Hz. All tones were 60 dB SPL, 50 ms duration (rise/fall time 5 ms), with SOA 1100 ms. Results: There was a reduction in RT, but no effects on omission or commission errors. The major ERP effects of caffeine were focal rather than global increases in P1, P2 and P3b amplitudes to Go stimuli, with no changes in latency. There were no effects on NI or N2 to Go stimuli, and no effects on any components in response to NoGo stimuli. Conclusions: The results suggest that caffeine differentially improves aspects of the processing related to response production and task performance, contrary to the widespread amplification of ERP component amplitudes, and latency reductions, expected of an increase in general arousal. Significance: These results add auditory ERP data to the list of complex effects of caffeine on brain function and behaviour. They appear to rule out a simple arousal interpretation, and suggest directions for future research.

Biggs SN; Smith A; Dorrian J; Reid K; Dawson D; van den Heuvel C et al. Perception of simulated driving performance after sleep restriction and caffeine. Journal of Psychosomatic Research 63(6): 573-577, 2007. (32 refs.)

Objective: As feelings of alertness are reported to be highly correlated with performance perception, the objective of this study was to determine whether caffeine, a common countermeasure to driver sleepiness, affected a sleepy driver's ability to monitor his or her simulated driving performance. Methods: Twelve healthy young adults (six males, six females) participated in three counterbalanced, blinded, daytime conditions: control [9 h time in bed (TIB)], 100 mg caffeine (4 h TIB), and placebo (4 h TIB). Driving performance was measured through lane drift on a series of 30-min simulated driving sessions. Subjective sleepiness and perception of driving performance were measured at 5-min intervals during driving sessions via the Karolinska Sleepiness Scale and a corresponding perception scale. Results: Sleep restriction had a significant detrimental effect on driving performance and subjective measures. Caffeine resulted in significant improvements across all measures. Subjective measures were found to be significantly correlated after sleep restriction and prior to caffeine. Correlations between actual and perceived performance were nonsignificant across all conditions. Conclusions: The strong correlation between subjective measures supports the postulation that sleepiness is used as a cue for performance prediction when sleep restricted. The relationship between perceived and actual performance after fatigue countermeasures remains inconclusive. Further research, addressing limitations, is needed.

Blank MD; Kleykamp BA; Jennings JM; Eissenberg T. Caffeine's influence on nicotine's effects in nonsmokers. American Journal of Health Behavior 31(5): 473-483, 2007. (50 refs.)

Objective: To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20). Methods: The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition. Results: Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions: In nonsmokers, nicotine effects are not influenced by moderate caffeine doses.

Boyce EG. Use and effectiveness of performance-enhancing substances. Journal of Pharmacy Practice 16(1): 22-36, 2003

The use and effects of selected performance-enhancing drugs and nutritional supplements are reviewed. Recent sports medicine studies are mostly double blind and placebo controlled but contain relatively small sample sizes. Their data appear reliable and are reported in reputable journals. Definitions and methods used in sports medicine are provided to enhance the understanding of this literature. The use of performance-enhancing substances is probably underreported. Anabolic-androgenic steroids are reportedly used in 0% to 1% of women, 0.5% to 3% of high school girls, 1% to 5% of men, 1% to 12% of high school boys, and up to 67% of some groups of elite athletes. The use of combinations of performance-enhancing substances is common. Carbohydrate loading, adequate protein intake, creatine, blood doping, and erythropoietin (epoetin alfa) appear to enhance performance. Anabolic-androgenic steroids enhance performance, but health risks limit their use. Growth hormones and B2-selective adrenergic agonists may enhance performance, but additional studies are needed. Androstenedione, caffeine, amphetamines, and nonprescription sympathomimetics do not appear to enhance performance. Performance enhancing drugs have shown some benefit in diseased patients with malnutrition and/or decreases in physical ability. Pharmacists and other health care providers have opportunities to improve the understanding, use, and monitoring of performance-enhancing substances.

Bramstedt KA. Caffeine use by children: The quest for enhancement. Substance Use & Misuse 42(8): 1237-1251, 2007. (57 refs.)

Fair play, both in academics and sports, is a concept that is challenged by the notion of performance enhancement. Both cognitive and physical performance can be viewed as potentially enhanceable, and arguments can be made that enhancement can serve two purposes: gaining an edge or keeping up with others (who may or may not have used performance-enhancing substances). Caffeine, a central nervous system and cardiac stimulant, is frequently used by children for both academic and athletic performance enhancement. In fact, the marketplace contains a plethora of caffeinated products marketed directly to children. This article examines safety and ethical issues associated with the use of caffeine by children and explores the question: Can cognitive performance enhancement be ethically permissible if sports performance enhancement is not?

Browne ML; Bell EM; Druschel CM; Gensburg LJ; Mitchell AA; Lin AE et al. Maternal caffeine consumption and risk of cardiovascular malformations. Birth Defects Research. Part A: Clinical and Molecular Teratology 79(7): 533-543, 2007. (36 refs.)

Background: The physiologic effects and common use of caffeine during pregnancy call for examination of maternal caffeine consumption and risk of birth defects. Epidemiologic studies have yielded mixed results, but such studies have grouped etiologically different defects and have not evaluated effect modification. Methods: The large sample size and precise case classification of the National Birth Defects Prevention Study allowed us to examine caffeine consumption and specific cardiovascular malformation (CVM) case groups. We studied consumption of caffeinated coffee, tea, soda, and chocolate to estimate total caffeine intake and separately examined exposure to each caffeinated beverage. Smoking, alcohol, vasoactive medications, folic acid supplement use, and infant gender were evaluated for effect modification. Maternal interview reports for 4,196 CVM case infants overall and 3,957 control infants were analyzed. Results: We did not identify any significant positive associations between maternal caffeine consumption and CVMs. For tetralogy of Fallot, nonsignificant elevations in risk were observed for moderate (but not high) caffeine intake overall and among nonsmokers (ORs of 1.3 to 1.5). Risk estimates for both smoking and consuming caffeine were less than the sum of the excess risks for each exposure. We observed an inverse trend between coffee intake and risk of atrial septal defect; however, this single significant pattern of association might have been a chance finding. Conclusions: Our study found no evidence for an appreciable teratogenic effect of caffeine with regard to CVMs.

Bryan J. Psychological effects of dietary components of tea: Caffeine and L-theanine. (review). Nutrition reviews 66(2): 82-90, 2008. (51 refs.)

This review summarizes the literature on the association between two dietary components of tea, caffeine and L-theanine, and the psychological outcomes of consumption; it also identifies areas for future research. The studies reviewed suggest that caffeinated tea, when ingested at regular intervals, may maintain alertness, focused attention, and accuracy and may modulate the more acute effects of higher doses of caffeine. These findings concur with the neurochemical effects of L-theanine on the brain. L-theanine may interact with caffeine to enhance performance in terms of attention switching and the ability to ignore distraction; this is likely to be reflective of higher-level cognitive activity and may be sensitive to the detrimental effects of overstimulation. Further research should investigate the interactive effects of caffeine, L-theanine, and task complexity, utilize a range of ecologically valid psychological outcomes, and assess the neuroprotective effects of L-theanine using epidemiological or longer-term intervention studies among individuals at risk of neurodegenerative disease.

Burke LM; Millet GE; Tarnopolsky MA. Nutrition for distance events. Journal of Sports Sciences 25(Supplement 1): S29-S38, 2007. (76 refs.)

The goal of training is to prepare the distance athlete to perform at his or her best during major competitions. Whatever the event, nutrition plays a major role in the achievement of various factors that will see a runner or walker take the starting line in the best possible form. Everyday eating patterns must supply fuel and nutrients needed to optimize their performance during training sessions and to recover quickly after-wards. Carbohydrate and fluid intake before, during, and after a workout may help to reduce fatigue and enhance performance. Recovery eating should also consider issues for adaptation and the immune system that may involve intakes of protein and some micronutrients. Race preparation strategies should include preparation of adequate fuel stores, including carbohydrate loading for prolonged events such as the marathon or 50-km walk. Fluid and carbohydrate intake during races lasting an hour or more should also be considered. Sports foods and supplements of value to distance athletes include sports drinks and liquid meal supplements to allow nutrition goals to be achieved when normal foods are not practical. While caffeine is an ergogenic aid of possible value to distance athletes, most other supplements are of minimal benefit.

Chapman RF; Stager JM. Caffeine stimulates ventilation in athletes with exercise-induced hypoxemia. Medicine and Science in Sports and Exercise 40(6): 1080-1086, 2008. (36 refs.)

Introduction/Purpose: Many athletes with exercise-induced hypoxemia (EIH) show an insufficient ventilatory response to exercise and low resting ventilatory responsiveness. The purpose of this project was to determine whether a moderate dosage of caffeine, a common ventilatory stimulant, could augment testing ventilatory responsiveness, exercise ventilation (PE), end-tidal 0, partial pressure (PETO2), and arterial oxyhemoglobin saturation (HbSaO(2)) in athletes with EIH. Methods: Eight highly trained males ((V) over dotO(2max), 69.2 +/- 4.0 mL.[kg.min](-1)) who demonstrated EIH at VO2max (HbSaO(2), 88.0 +/- 1.7%), ingested in a randomized design a placebo or caffeine (CAF, 8 mg.kg(-1) body wt) I h before testing. Ventilatory responsiveness at rest was assessed via the isocapnic hypoxic and hyperoxic hypercapnic ventilatory responses (HVR and HCVR, respectively). Dependent measures of metabolic variables, ventilation, and saturation were determined during progressive treadmill exercise to exhaustion. Results: V-E was higher at 75%, 80%, and 100% of VO2max with CAF (P < 0.05). V-E/VO2, PETO2, and HbSaO(2) were increased at 75%, 80%, and 90% of VO2max With CA-F but were not different at VO2max, despite an increase in VE. No change in VO2max was observed between treatments. HVR and HCVR were not different between the two conditions, indicating that the increased V-E likely came from central stimulation or secondary effects of CAF. Conclusion: The failure of HbSaO(2) to increase at VO2max despite an increase in V-E suggests that mechanisms influencing HbSaO(2) other than an inadequate hyperventilatory response may operate to different degrees across individuals as VO2max is approached.

Childs E; de Wit H. Enhanced mood and psychomotor performance by a caffeine-containing energy capsule in fatigued individuals. Experimental and Clinical Psychopharmacology 16(1): 13-21, 2008. (62 refs.)

Caffeine produces mild psychostimulant effects that may be particularly evident in individuals whose mood or performance is impaired by sleep restriction or caffeine withdrawal. Caffeinated energy drinks have been shown to improve energy and cognition but expectancy effects cannot be ruled out in these studies. Very few studies have examined the effects of caffeine-containing energy capsules upon behavioral and subjective measures. This study compared the effects of a caffeine-containing (200 mg) supplement (CAF) or placebo in capsule form after prolonged wakefulness, in participants who varied in their level of habitual caffeine use. Thirty-five healthy volunteers (16 male, 19 female) participated in two experimental sessions in which they remained awake between 5 p.m. and 5 a.m. At 3:30 a.m. they consumed CAF or placebo in random order under double-blind conditions. Participants completed subjective effects questionnaires and performed computerized attention tasks before and after consuming capsules. Heart rate and blood pressure were monitored at regular intervals. Compared to measures at 5 p.m., participants reported more tiredness and mood disturbance at 3 a.m., and exhibited longer reaction times and more attentional lapses. Heavier caffeine consumers exhibited the greatest decreases in Profile of Mood States (POMS) Vigor. CAF produced stimulant-like effects and significantly improved mood and reaction times upon the tasks. These effects did not vary with level of habitual caffeine consumption. These findings indicate that consumption of a caffeine-containing food supplement improves subjective state and cognitive performance in fatigued individuals that is likely a result of its caffeine content.

Clauson KA; Shields KM; McQueen CE; Persad N. Safety issues associated with commercially available energy drinks. Journal of the American Pharmacists Association 48(3): E55-E66, 2008. (53 refs.)

Objective: To describe benefits and adverse effects associated with the consumption of energy drinks. Data sources: Searches were conducted using Medline, IPA (International Pharmaceutical Abstracts), EMBASE, and MANTIS; databases such as Natural Medicines Comprehensive Database, Natural Standard, ALTMEDEX, and AltHealthWatch; and Google (range 1980 to September 2007). Search terms included energy drink, Red Bull, caffeine, glucose, ginseng, guarana, taurine, and bitter orange. Data synthesis: Most energy drinks contain natural products such as guarana, ginseng, and taurine. As much as 80 to 300 mg of caffeine and 35 grams of processed sugar per 8-ounce serving are commonly present in energy drinks such as Cocaine, Pimp Juice, Red Bull, and Spike Shooter. No reports were identified of negative effects associated with taurine, ginseng, and guarana used in the amounts found in most energy drinks. Commonly reported adverse effects seen with caffeine in the quantities present in most energy drinks are insomnia, nervousness, headache, and tachycardia. Four documented case reports of caffeine-associated deaths were found, as well as four separate cases of seizures associated with the consumption of energy drinks. Conclusion: The amounts of guarana, taurine, and ginseng found in popular energy drinks are far below the amounts expected to deliver either therapeutic benefits or adverse events. However, caffeine and sugar are present in amounts known to cause a variety of adverse health effects.

Cornelis MC; El-Sohemy A. Coffee, caffeine, and coronary heart disease. Current Opinion in Clinical Nutrition and Metabolic Care 10(6): 745-751, 2007. (62 refs.)

Disterpenes present in unfiltered coffee and caffeine each appear to increase risk of coronary heart disease. A lower risk of coronary heart disease among moderate coffee drinkers might be due to antioxidants found coffee.

Cysneiros RM; Farkas D; Harmatz JS; von Moltke LL; Greenblatt DJ. Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine. Clinical Pharmacology & Therapeutics 82(1): 54-62, 2007. (59 refs.)

The kinetic and dynamic interaction of caffeine and zolpidem was evaluated in a double-blind, single-dose, six-way crossover study of 7.5 mg zolpidem (Z) or placebo (P) combined with low-dose caffeine (250 mg), high-dose caffeine (500 mg), or placebo. Caffeine coadministration modestly increased maximum plasma concentration (C-max) and area under the plasma concentration-time curve of zolpidem by 30-40%, whereas zolpidem did not significantly affect the pharmacokinetics of caffeine or its metabolites. Compared to P + P, Z + P significantly increased sedation, impaired digit-symbol substitution test performance, slowed tapping speed and reaction time, increased EEG relative beta amplitude, and impaired delayed recall. Caffeine partially, but not completely, reversed most pharmacodynamic effects of zolpidem. Thus, caffeine only incompletely reverses zolpidem's sedative and performance-impairing effects, and cannot be considered as an antidote to benzodiazepine agonists.

Defazio G; Martino D; Abbruzzese G; Girlanda P; Tinazzi M; Fabbrini G et al. Influence of coffee drinking and cigarette smoking on the risk of primary late onset blepharospasm: evidence from a multicentre case control study. Journal of Neurology, Neurosurgery and Psychiatry 78(8): 877-879, 2007. (20 refs.)

Prior coffee and smoking habits were investigated in a multicentre case control study involving 166 patients presenting with primary late onset blepharospasm (BSP), 228 hospital control patients with primary hemifacial spasm and 187 population control subjects from five Italian centres. Information on age at disease onset, smoking and coffee drinking status at the reference age and average number of cups of coffee drunk/cigarettes smoked per day reached high and similar test-retest reproducibility in case and control patients. Unadjusted logistic regression analysis yielded a significant inverse association of prior coffee drinking and cigarette smoking with case status for the control groups. After adjustment for age, sex, referral centre, disease duration, years of schooling and ever coffee drinking/cigarette smoking, as appropriate, the smoking estimate lacked significance whereas the association of coffee intake and BSP did not (cases vs hospital control patients: OR 0.37 (95% Cl 0.20 to 0.67); cases vs population control subjects: OR 0.44 (95% Cl 0.23 to 0.85)). The strength of the inverse association between BSP and coffee intake tended to increase with the average number of cups drunk per day. There was a significant correlation between age of BSP onset and number of cups per day (adjusted regression coefficient 1.73; p = 0.001) whereas no correlation was found with number of packs of cigarettes per day. Coffee drinking may be inversely associated with the development of primary BSP and this association may partly depend on the amount

Del Coso J; Estevez E; Mora-Rodriguez R. Caffeine effects on short-term performance during prolonged exercise in the heat. Medicine and Science in Sports and Exercise 40(4): 744-751, 2008. (29 refs.)

Purpose: To determine the effect of water, carbohydrate, and caffeine ingestion on fatigue during prolonged exercise in the heat. Methods: Seven endurance-trained cyclists ((V) overdot O-2max=61 +/- 8 mL.kg(-1).min(-1)) pedaled for 120 min at 63% (V) overdot O-2max in a hot-dry environment (36 degrees C; 29% humidity), ingesting either no fluid (NF), water (WAT) to replace 97% fluid losses, the same volume of a 6% carbohydrate-electrolyte solution (CES), or each of these treatments along with ingestion of 6 mg of caffeine per kilogram of body weight (NF + C-AFF, WAT + C-AFF, and CES + C-AFF). At regular intervals during exercise, maximal cycling power (P-MAX) was measured. Before and after exercise, maximal voluntary contraction (MVC), voluntary activation (VA), and electrically evoked contractile proper-ties of the quadriceps were determined. Results: Without fluid replacement (NF and NF + C-AFF), subjects were dehydrated by 3.8 +/- 0.3%, and rectal temperature reached 39.4 +/- 0.3 degrees C, while it was maintained at 38.7 +/- 0.3 degrees C in trials with rehydration (P < 0.05). Trials with caffeine ingestion increased P-MAX by 3% above trials without caffeine (P < 0.05). MVC reductions after exercise were larger with NF (-11 +/- 5%) than for the rest of the trials (P < 0.05). MVC was reduced in WAT compared with CES + C-AFF (-6 +/- 4 vs 2 +/- 4%; P < 0.05). However, NF + CAFF maintained MVC at the level of the CES trial. VA showed the same treatment response pattern as MVC. There were no differences in electrically evoked contractile properties among trials. Conclusion: During prolonged exercise in the heat, caffeine ingestion (6 mg.kg(-1) body weight) maintains MVC and increases P-MAX despite dehydration and hyperthermia. When combined with water and carbohydrate, caffeine ingestion increases maximal leg force by increasing VA (i.e., reducing central fatigue).

Desbrow B; Leveritt M. Well-trained endurance athletes' knowledge, insight, and experience of caffeine use. International Journal of Sport Nutrition and Exercise Metabolism 17(4): 328-339, 2007. (17 refs.)

This descriptive cross-sectional study assessed the perceptions, knowledge, and experiences of caffeine use by athletes competing at the 2005 lronman Triathlon World Championships. Questionnaires were distributed to 140 athletes (105 men and 35 women, 40.3 +/- 10.7 y old) representing 16 countries during prerace registration. A large proportion (73%) of these endurance athletes believe that caffeine is ergogenic to their endurance performance, and 84% believe it improves their concentration. The most commonly reported positive caffeine experiences related to in-competition use of cola drinks (65%) and caffeinated gels (24%). The athletes' ability to accurately quantify the caffeine content of common food items was limited. The most popular sources of caffeine information were self-experimentation (16%), fellow athletes (15%), magazines (13%), and journal articles (12%). Over half the athletes (53%) could not identify an amount of caffeine required to improve their triathlon performance. Mean (+/- standard deviation) suggested doses were 3.8 (+/- 3) mg/kg body weight. Few side effects associated with taking caffeine during exercise were reported.

Diana C. Caffeine, carnival and the emergence of eighteenth-century nervous dis-ease. Studies in Symbolic Interaction 28: 219-237, 2005. (83 refs.)

This article contrasts the spirit and attitudes embodied in carnival (pre-Lenten festivity) with those associated with Lenten observances in the 16th and 17th centuries. This is clearly evident in a painting by Brueghel (1559) "The Fight between Carnival and Lent." The tension is viewed as two sides of the coin, neither able to exist without the other, and the dialectic between desire and reason, appetite and intellect, play and piety, dissipation and moderation that was central to the ethos of the era. This article demonstrates how the advent of stimulants -- coffee and tea -- into England facilitated a shift from the relaxed carnival conviviality to nervous Lenten sobriety. The coffee house too is seen as representing the opposite of the alehouse. The high degree of physiological nervous tension associated with caffeinated beverages is seen as the route of the growing dis-ease. The role of caffeine in furthering industrialism and capitalism as well as transforming the public sphere is also addressed. Divergent views as to the value and dangers of caffeinated beverages are presented.

Diego M; Field T; Hernandez-Reif M; Vera Y; Gil K; Gonzalez-Garcia A. Caffeine use affects pregnancy outcome. Journal of Child & Adolescent Substance Abuse 17(2): 41-49, 2007. (18 refs.)

A sample of 750 women were interviewed during pregnancy on their depression and anxiety symptoms, substance use and demographic variables. A subsample was seen again at the neonatal stage (n = 152), and their infants were observed for sleep-wake behavior. Symptoms of depression and anxiety were related to caffeine use. Mothers who consumed more caffeine also smoked more often, were younger, were less educated, reported less sleep effectiveness and more obstetric complications. Their newborns were lower birthweight, they spent less time in REM sleep and they showed more stress behaviors including hiccups, tremors and jerkiness.

Djordjevic N; Ghotbi R; Bertilsson L; Jankovic S; Aklillu E. Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. European Journal of Clinical Pharmacology 64(4): 381-385, 2008. (27 refs.)

Objectives: To investigate the influence of coffee consumption on CYP1A2 enzyme activity controlling for the effects of smoking and oral contraceptive (OC) use among Serbs and Swedes and to compare CYP1A2 activity between the two populations. Methods: Data on oral contraceptive use, habitual coffee consumption and smoking habits were obtained from 100 Serbian and 149 Swedish healthy volunteers using a detailed questionnaire. CYP1A2 activity was estimated by plasma paraxanthine/caffeine (17X/137X) ratio analysed by reversed-phase HPLC after oral administration of 100 mg caffeine. Results Daily consumption of at least three cups of coffee significantly increased CYP1A2 enzyme activity in both Serbs (P=0.0002) and Swedes (P<0.0001). Among non-smokers and non-OC users, heavy coffee consumption significantly increased CYP1A2 activity in Serbs (mean difference 0.11; 95% CI of the mean difference 0.04, 0.18; P=0.003) and Swedes (mean difference 0.07; 95% CI of the mean difference 0.01, 0.12; P=0.02). Significantly higher 17X/137X ratio was detected in Serbian smokers compared to non-smokers. There was no significant gender difference in CYP1A2 activity in Serbs. Controlling for the effect of smoking, heavy coffee consumption habit and oral contraceptive use, significantly lower 17X/137X ratio was observed in Serbs than in Swedes (P=0.0003). Conclusions: Habitual heavy coffee consumption increases CYP1A2 activity. Polycyclic aromatic hydrocarbons formed during roasting of coffee beans might partly be responsible for this effect. The reason for the observed lower CYP1A2 activity in Serbs as compared to Swedes remains to be investigated.

Dooley JM; Gordon KE; Wood EP; Brna PM; MacSween J; Fraser A. Caffeine as an adjuvant to ibuprofen in treating childhood headaches. Pediatric Neurology 37(1): 42-46, 2007. (33 refs.)

In adults, caffeine has been shown to enhance the effectiveness of most analgesics, including ibuprofen. This double-blind cross-over pilot study evaluated the effect of ibuprofen and caffeine compared with ibuprofen and placebo in 12 children with headaches. Patients completed diaries for both headaches. Outcome measures included a five-faces severity scale, a measure of clinical disability, and a scale of pain severity. Comparison of the cumulative response scores revealed a trend toward a greater response to ibuprofen-caffeine treatment of headaches (P = 0.14, P = 0.09, and P = 0.07 for the three measures, respectively). Further larger studies are needed to confirm this effect and to identify potential responders.

Field T; Yando R; Bendell D; Hernandez-Reif M; Diego M; Vera Y et al. Prenatal depression effects on pregnancy feelings and substance use. Journal of Child & Adolescent Substance Abuse 17(1): 111-125, 2007. (45 refs.)

Depressed (n = 110) and nondepressed (n = 104) mothers were given a set of self-report measures, including the CES-D (depression), the STAI (anxiety), the STAXI (anger), the Perinatal Anxieties and Attitudes Scale, a questionnaire on substance use and the Feelings About Pregnancy and Delivery Scale that was designed for this study and that includes scales on coping, support, intimacy, common knowledge of depression, and cultural effects on pregnancy. During the neonatal period, the depressed mothers scored higher on the depression, anger, and anxiety scales as well as the Perinatal Anxieties and Attitudes Scale. They also reported using more substances including cigarettes, caffeine, and medications (primarily antibiotics). Their scores on the Feelings About Pregnancy and Delivery Scale were lower including the coping, support, intimacy, and cultural effects scores. In addition, they reported having more stressful situations during pregnancy, being less happy when finding out them were pregnant and their significant other being less happy when finding out about the pregnancy. A regression analysis on maternal depression suggested that 28% of the variance was explained by low support scale scores, not co-sleeping with their infant and high caffeine intake.

Foad AJ; Beedie CJ; Coleman DA. Pharmacological and psychological effects of caffeine ingestion in 40-km cycling performance. Medicine and Science in Sports and Exercise 40(1): 158-165, 2008. (27 refs.)

Aim: To explore the psychological and pharmacological effects of caffeine in laboratory cycling performance. Method: Fourteen male competitive cyclists performed 14 40-km time trials (eight experimental interspersed with six baseline). The experimental phase consisted of two trials for each of four experimental conditions: informed caffeine/received caffeine, informed no treatment/received caffeine, informed caffeine/received placebo, and informed no treatment/received no treatment. Conditions were nonrandomized. ANOVA was used to estimate main effects and interactions for mean values of power, heart rate, blood lactate, and maximal oxygen uptake. Probabilistic inferences for mean power were based on a smallest worthwhile change of 1.5%. Results: Relative to baseline, a very likely beneficial main effect of receiving caffeine (3.5%; 95% confidence interval 1.5 to 5.5%), and a possibly beneficial main effect of being informed of caffeine (0.7%; -0.7 to 2.1%) were observed. A substantial interaction between belief and pharmacology indicated that caffeine exerted effect on performance in conditions when subjects were informed that they had not ingested it, whereas belief exerted a greater influence on performance in the absence of caffeine (2.6%; -0.7 to 5.9%). A possibly harmful negative placebo (nocebo) effect was observed when subjects were correctly informed that they had ingested no caffeine (- 1.9%; -4.1 to 0.3%). No clinically significant changes relative to baseline were observed in mean heart rate. Clear and substantial increases in blood lactate were evident after receipt of caffeine. Data for mean oxygen uptake were unclear. Conclusion: Our data support the ergogenic efficacy of caffeine but suggest that both positive and negative expectations impact performance.

Fujioka K; Shibamoto T. Chlorogenic acid and caffeine contents in various commercial brewed coffees. Food Chemistry 106(1): 217-221, 2008. (15 refs.)

Twelve commercial brewed coffees (seven regular and five decaffeinated) were analyzed for chlorogenic acids (CGA) and caffeine by HPLC. Their pH and UV-Vis absorbances were also measured. The CGAs identified were three caffeolylquinic acids (3-CQA, 4-CQA, and 5-CQA), three feruloylquinic acids (3-FQA, 4-FQA, and 5-FQA), and three dicaffeoylquinic acids (3,4-diCQA, 3,5-diCQA, and 4,5-diCQA). The total CGAs ranged from 5.26 mg/g to 17.1 mg/g in regular coffees and from 2.10 mg/g to 16.1 mg/g in decaffeinated coffees. Among CGA, 5-CQA was present at the highest level, ranging from 2.13 mg/g to 7.06 mg/g coffee, and comprising 36-42% and 37-39% of the total CGA in the regular and decaffeinated coffees, respectively. CGA isomer contents were, in decreasing order, 5-CQA > 4-CQA > 3-CQA > 5-FQA > 4-FQA > 3-FQA > 3,4-diCQA > 4,5-diCQA, 3,5-diCQA. The caffeine content in regular and decaffeinated coffees ranged from 10.9 mg/g to 16.5 mg/g and from 0.34 mg/g to 0.47 mg/g, respectively. The pH of regular and decaffeinated coffees ranged from 4.95 to 5.99 and from 5.14 to 5.80, respectively. The relationship between the pH and the UV-Vis absorbance at 325 nm was moderately correlated (R-2 = 0.7829, p < 0.001, n = 12).

Gartrell BD; Reid C. Death by chocolate: A fatal problem for an inquisitive wild parrot. New Zealand Veterinary Journal 55(3): 149-151, 2007. (18 refs.)

CASE HISTORY: An adult male kea (Nestor notabilis) in good body condition was found dead at Aoraki/Mt Cook Village, in the Southern Alps of New Zealand. The bird had previously been involved in behavioural tests of problem-solving ability. CLINICAL AND PATHOLOGICAL FINDINGS: The bird had substantial subcutaneous and abdominal reserves of fat. The crop contained 20 g of what appeared to be dark chocolate; a conservative estimate of the dose of methylxanthines ingested by the bird was 250 mg/kg theobromine, 20 mg/kg caffeine and 3 mg/kg theophylline. Histopathological examination revealed acute degenerative changes to hepatocytes, renal tubules, and cerebrocortical neurons. DIAGNOSIS: Acute combination methylxanthine toxicity after opportunistic ingestion of chocolate. CLINICAL RELEVANCE: This is the first report of the pathological findings of methylxanthine toxicity in a wild parrot, and illustrates the need to ensure that kea are protected from the toxic by-products of human habitation, and the difficulties in ensuring this against a neophilic, inquisitive and innovative parrot.

Ginsburg HJ; Raffeld P; Alanis KL; Boyce AS. Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design. Substance Abuse Treatment, Prevention, and Policy 1: article 4, 2006. (30 refs.)

Background: Establishing more sensible measures to treat cocaine-addicted mothers and their children is essential for improving U.S. drug policy. Favorable post-natal environments have moderated potential deleterious prenatal effects. However, since cocaine is an illicit substance having long been demonized, we hypothesized that attitudes toward prenatal cocaine exposure would be more negative than for licit substances, alcohol, nicotine and caffeine. Further, media portrayals about long-term outcomes were hypothesized to influence viewers' attitudes, measured immediately post-viewing. Reducing popular crack baby stigmas could influence future policy decisions by legislators. In Study 1, 336 participants were randomly assigned to 1 of 4 conditions describing hypothetical legal sanction scenarios for pregnant women using cocaine, alcohol, nicotine or caffeine. Participants rated legal sanctions against pregnant women who used one of these substances and risk potential for developing children. In Study 2, 139 participants were randomly assigned to positive, neutral and negative media conditions. Immediately post-viewing, participants rated prenatal cocaine-exposed or non-exposed teens for their academic performance and risk for problems at age18. Results: Participants in Study 1 imposed significantly greater legal sanctions for cocaine, perceiving prenatal cocaine exposure as more harmful than alcohol, nicotine or caffeine. A one-way ANOVA for independent samples showed significant differences, beyond .0001. Post-hoc Sheffe test illustrated that cocaine was rated differently from other substances. In Study 2, a one-way ANOVA for independent samples was performed on difference scores for the positive, neutral or negative media conditions about prenatal cocaine exposure. Participants in the neutral and negative media conditions estimated significantly lower grade point averages and more problems for the teen with prenatal cocaine exposure than for the non-exposed teen beyond .0001 alpha level. The positive media program closed estimated grade point average differences and risks of later problems to a non-statistically significant margin, p >.05. Conclusion: Ratings for prenatal cocaine were more negative than comparable ratings for alcohol, nicotine or caffeine exposure. Stereotypes can be reduced, showing viewers that positive postnatal environments ameliorate potential teratogenic effects of cocaine. Reducing negative stereotypes for crack babies may be a requisite for substantive changes in current policy.

Giraudon I; Bello PY. Monitoring ecstasy content in France: Results from the National Surveillance System 1999-2004. Substance Use & Misuse 42(10): 1567-1578, 2007. (23 refs.)

The French National Identification System for Drugs and Other Substances (SINTES) is an original scheme gathering analytical information for synthetic drugs, both through police and customs' seizures in the entire country and collection of samples and questionnaires directly from the users by social field workers. Between July 1999 and June 2004, 9543 samples were included. Tablets (7004) were mainly containing MDMA (82%) and caffeine was the most frequent blended psychoactive substance. Mean MDMA dosage of tablets decreased from 1999 to 2003 and dosage for tablets bearing the same logo appeared to be highly variable. Notwithstanding the difficulties for data collection due to the illicit nature of these drugs, this surveillance and early warning system, which combines the cooperative efforts of law enforcement laboratories and social workers, provided relevant and timely information. It is accurate regarding the follow-up of trends in drugs' composition, and the identification of new or potentially dangerous substances, to the professionals, the public, and the European partners.

Gold EB; Bair Y; Block G; Greendale GA; Harlow SD; Johnson S et al. Diet and lifestyle factors associated with premenstrual symptoms in a racially diverse community sample: Study of women's health across the nation (SWAN). Journal of Women's Health 16(5): 641-656, 2007. (62 refs.)

Aims: We sought to determine if the frequency of reported physical or emotional premenstrual symptoms (PMSx) was associated with (1) dietary intake of phytoestrogens, fiber, fat, or calcium, (2) consumption of alcohol or caffeine, (3) active or passive smoke exposure or lack of physical exercise, and (4) race/ethnicity or socioeconomic status. Methods: A cross-sectional analysis was conducted of PMSx and demographic and lifestyle factors reported at baseline in the multiethnic sample of 3302 midlife women in the Study of Womens Health Across the Nation (SWAN). Stepwise multiple logistic regression analyses were performed for the overall sample and for each racial/ethnic group for each of five PMSx groupings. Results: Most dietary factors were not related to PMSx. Fat intake was negatively associated with craving and bloating (adjusted odds ratio [AOR] = 0.56, p = 0.024), and fiber intake was positively associated with breast pain (AOR = 1.39, p = 0.037). Alcohol intake was negatively associated with anxiety and mood changes (AOR = 0.63, p = 0.045) and headaches (AOR = 0.50, p = 0.009). Current smoking (AOR = 1.60, p = 0.028) and passive smoke exposure (AOR = 1.56, p = 0.050) were positively associated with cramps and back pain. Symptom reporting differed significantly by race/ethnicity. PMSx were also associated with comorbidities, early perimenopausal status, depressive symptoms, and symptom sensitivity. Conclusions: We found little evidence to support a role for diet in PMSx reporting. However, alcohol intake was positively associated with premenstrual anxiety and mood changes, and active and passive smoke exposure was associated with a number of PMSx. Ethnic differences in symptom reporting and associations of comorbidities, early perimenopausal status, depressive symptoms, and symptom sensitivity with reported PMSx were also observed.

Graham AW; Schultz TK; Mayo-Smith MF; Ries RK; Wilford BB, eds. Principles of Addiction Medicine. Chevy Chase MD: American Society of Addiction Medicine, 2003. (Chapter refs.)

This volume is a comprehensive text on addictions. It is organized into 14 major sections, each of which has multiple chapters. There are over 200 contributors. The sections deal with the following themes: basic science and core concepts; pharmcology; diagnosis, assessment and early intervention; overview of addiction treatment; management of intoxication and withdrawal; pharmacologic interventions; behavioral interventions; 12-step programs and other recovery-oriented interventions; alcohol and drug problems in the workplace; medical disorders and complications of addiction; co-occurring addictive and psychiatric disorders; pain and addiction; and children and adolescents. There are also six appendices.

Grattan-Miscio KE; Wickenden M; Crotteau P; Ward A. Examining the myth of the caffeine expectation: Influencing intentional control of behavior under alcohol. International Journal on Disability and Human Development 6(2): 207-214, 2007. (26 refs.)

This experiment was designed to examine the effects of caffeine expectancy on intentional control of behavior under alcohol. Method: A process dissociation paradigm was used to measure the separate influence of automatic and intentional controlled processes on performance of a word-stem completion task. Forty social drinkers studied a list of words, received either alcohol or a placebo, and then performed a word-stem completion task designed to measure intentional control of behavior. Before performing the task, two groups (i.e., one alcohol and one placebo group) also received decaffeinated coffee, which has been shown effectively to establish caffeine expectancy. The results indicated that the expectation of receiving caffeine was sufficient to counteract the impairment of intentional control seen under alcohol. Those individuals who received both alcohol and decaffeinated coffee demonstrated better intentional control than those who received alcohol alone. Moreover, the performance of the alcohol-decaffeinated coffee group did not differ from placebo. No treatment significantly affected automatic processes. Conclusion(s): The expectation of receiving caffeine under alcohol is sufficient to counter-act the impairing effects of the drug.

Gurpegui M; Jurado D; Luna JD; Fernandez-Molina C; Moreno-Abril O; Galvez R. Personality traits associated with caffeine intake and smoking. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 31(5): 997-1005, 2007. (64 refs.)

Objectives: Some studies find a relationship between certain personality traits, as impulsivity or sensation seeking, and caffeine consumption, but these studies do not consider the potential confounding effect of smoking on caffeine intake, a co-occurrence that has been well demonstrated in epidemiological and clinical studies. The main objective of this cross-sectional study was to analyze the association of personality with caffeine intake controlling for the effects of smoking; a secondary objective was to explore the effect of caffeine intake on the previously known relationship between personality and smoking. Methods: A sample of 498 adults answered a self-questionnaire including socio-demographic variables, and items regarding consumption of tobacco and caffeine. Personality was measured by the Temperament and Character Inventory (TCI-125). We analyzed the association of personality traits with both caffeine intake and smoking, controlling the possible confounding effects of sex, age and each substance with the other one. Results: Logistic regression analyses showed that the temperamental dimension of novelty seeking was associated with heavy caffeine consumption (> 200 mg/day) (adjusted OR=2.0; 95% CI: 1.1-3.9), controlling for the effect of smoking. Moreover, novelty seeking was associated with both smoking (adjusted OR=1.8; 95% CI: 1.1-2.9) and heavy smoking (> 20 cigarettes/day) (adjusted OR=1.8; 95% CI: 1.0-3.7), after controlling for the effect of caffeine intake. Conclusion: Our study offers an epidemiological evidence of the relationship of novelty seeking, considered to be associated with low basal dopaminergic activity, with both nicotine consumption and heavy caffeine intake, two substances that enhance dopaminergic neurotransmission.

Haller CA; Duan MJ; Jacob P; Benowitz N. Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. British Journal of Clinical Pharmacology 65(6): 833-840, 2008. (29 refs.)

AIMS: Dietary supplements (DS) promoted to enhance athletic performance often contain herbal sympathomimetics such as Citrus aurantium (synephrine) and caffeine. We aimed to characterize the pharmacology of a performance-enhancing DS in the setting of exercise. METHODS: Ten healthy adults (three women) aged 20-31 years participated in a three-arm, double-blind, placebo-controlled, crossover study. Subjects ingested one dose of DS (Ripped Fuel Extreme Cut((R)) with 21 mg synephrine and 304 mg caffeine by analysis) under resting conditions and 1 h prior to moderately intense exercise (30 min on cycle ergometer at 75-80% HRmax), with a placebo (PLC)/exercise control. Plasma synephrine and caffeine concentrations were measured over 12 h, and vital signs, serum electrolytes, oxygen consumption and perceived exercise exertion were monitored. RESULTS: No significant adverse events occurred. Synephrine and caffeine pharmacokinetics were unaffected by exercise. Post-exercise diastolic blood pressure was higher after DS (peak mean 71.7 +/- 8.7 mmHg) than PLC (63.0 +/- 4.9 mmHg) (p = 0.007). There were no substantial treatment-related differences in post-exercise HR, systolic blood pressure, or temperature. Postprandial plasma glucose increased to 121.0 +/- 31.6 mg dl(-1) with DS and exercise vs. 103.7 +/- 25.5 mg dl-1 with PLC and exercise (P = 0.004). No treatment differences in exercise-related oxygen consumption, serum lactate, or insulin were observed. Exercise was rated less difficult with DS than PLC (P = 0.001). CONCLUSIONS: Blood pressure and plasma glucose increased post-exercise with DS use, which could be detrimental in some people. Exercise was perceived as less strenuous after DS, presumably due to the stimulant effects of caffeine.

Hewlett P; Smith A. Effects of repeated doses of caffeine on performance and alertness: New data and secondary analyses. Human Psychopharmacology: Clinical and Experimental 22(6): 339-350, 2007. (23 refs.)

Rationale The effects of caffeine on mood and performance are well established. Some authors suggest that caffeine merely reverses effects of caffeine withdrawal rather than having direct behavioural effects. It has also been suggested that withdrawal may be removed by a first dose of caffeine and further doses have little subsequent effect. These issues are examined here. Objectives The present study aimed to determine whether caffeine withdrawal influenced mood and performance by comparing regular consumers who had been withdrawn from caffeine overnight with non-consumers. Following this repeated caffeine doses were administered to test the claim that repeated dosing has no extra effect on mood or performance. Secondary analyses of data collected after a day of normal caffeine consumption were also carried out to examine some alternative explanations of their results which showed effects of caffeine after a day of normal caffeine consumption. Methods One hundred and twenty volunteers participated in the study. Regular caffeine consumption was assessed by questionnaire and this showed that 36 of the volunteers did not regularly consume caffeinated beverages. Volunteers were instructed to abstain from caffeine overnight and then completed a baseline session measuring mood and a range of cognitive functions at 08.00 the next day. Following this volunteers were given 0, or I mg/kg caffeine in a milkshake, glucose solution or water (at 09:00), followed by a second 0 or I mg/kg caffeine dose (at 09:40) and the test battery repeated at 10:00. Results The baseline data showed no effect of overnight caffeine withdrawal on mood or performance. In contrast, caffeine challenge improved vigilance performance and prevented decreases in alertness induced by completion of the task battery. The magnitude of these effects increased as a function of the number of doses of caffeine given. Secondary analyses of data from Christopher et al. (2003) also confirmed that effects of caffeine did not depend on length of withdrawal. Conclusions The present findings show no effect of overnight caffeine withdrawal on mood and performance. Caffeine challenge did have the predicted effect on alertness and vigilance, with the size of the effects increasing with caffeine dose. These findings suggest that the effects of caffeine are not due to reversal of effects of withdrawal, a view confirmed by secondary analyses of data collected after a day of normal caffeine consumption.

Hu G; Jousilahti P; Nissinen A; Bidel S; Antikainen R; Tuomilehto J. Coffee consumption and the incidence of anti hypertensive drug treatment in Finnish men and women. American Journal of Clinical Nutrition 86(2): 457-464, 2007. (40 refs.)

Background: Only 2 prospective studies have previously investigated the association between coffee consumption and incident hypertension, and the findings are equivocal. Objective: The objective was to determine the relation between coffee consumption and the incidence of antihypertensive drug treatment. Design: We prospectively followed 24 710 Finnish subjects aged 25-64 y without a history of antihypertensive drug treatment, coronary heart disease, or stroke at baseline. Daily coffee consumption was assessed by questionnaires. Results: During a mean follow-up period of 13.2 y, 2505 participants started antihypertensive drug treatment. The multivariate-adjusted (age, sex, study year, education, leisure-time physical activity, smoking, body mass index, high total cholesterol, history of diabetes, and alcohol, tea, fruit, vegetable, sausage, and bread consumption) hazard ratios for antihypertensive drug treatment associated with the amount of coffee consumed daily (0-1, 2-3, 4-5, 6-7, or >= 8 cups) were 1.00, 1.29 (95% CI: 1.09, 1.54), 1.26 (95% CI: 1.06, 1.49), 1.24 (95% CI: 1.04, 1.48), and 1.14 (95% CI: 0.94, 1.37) (P for trend = 0.024), respectively. This trend became marginally significant after additional adjustment for baseline systolic blood pressure (P for trend = 0.077). Conclusions: The results indicate that coffee drinking seems to increase the risk of antihypertensive drug treatment, and this risk was higher in subjects with low-to-moderate coffee intakes; however, there was no significantly increased trend in drinkers of approximate to 1 cup (100 mL)/d or >= 8 cups/d.

Ide R; Fujino Y; Hoshiyama Y; Mizoue T; Kubo T; Pham TM et al. A prospective study of green tea consumption and oral cancer incidence in Japan. Annals of Epidemiology 17(10): 821-826, 2007. (29 refs.)

To examine the relation of green tea consumption with oral carcinogenesis, we prospectively analyzed data from a nationwide large-scale cohort study in Japan. METHODS: A total of 20,550 men and 29,671 women aged 40-79 years, without any history of oral and pharyngeal cancer at baseline survey, were included in the present study. During a mean follow-up period of 10.3 years, 3 7 oral cancer cases were identified. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for oral cancer according to green tea consumption by sex, while adjusting for age, smoking, alcohol drinking, and other dietary factors. RESULTS: For women, the HRs of oral cancer for green tea consumption of 1-2, 3-4, and 5 or more cups per day were 0.51 (95% CI: 0.10-2.68), 0.60 (95% CI: 0.17-2.10), and 0.31 (95% CI: 0.09-1.07), respectively, compared with those who drank less than one cup per day (p for trend, 0.08). For men, no such trends were observed. CONCLUSIONS: Our findings did not suggest a prominent inverse association of green tea consumption with oral cancer, although there was a tendency for a reduced risk in women.

James JE; Keane MA. Caffeine, sleep and wakefulness: Implications of new understanding about withdrawal reversal. (review). Human Psychopharmacology: Clinical and Experimental 22(8): 549-558, 2007. (80 refs.)

The broad aim of this review is to critically examine the implications of new understanding concerning caffeine withdrawal and withdrawal reversal in the context of research concerned with the effects of caffeine on sleep and wakefulness. A comprehensive search was conducted for relevant experimental studies in the PubMED and PsycINFO databases. Studies were assessed with particular reference to methodological adequacy for controlling against confounding due to caffeine withdrawal and withdrawal reversal. This assessment was used to clarify evidence of effects, highlight areas of ambiguity and derive recommendations for future research. It was found that researchers have generally failed to take account of the fact that habitual use of caffeine, even at moderate levels, leads to physical dependence evidenced by physiological, behavioural and subjective withdrawal effects during periods of abstinence. Consequently, there has been near-complete absence of adequate methodological controls against confounding due to reversal of withdrawal effects when caffeine is experimentally administered. The findings of what has been a substantial research effort to elucidate the effects of caffeine on sleep and wakefulness, undertaken over a period spanning decades, are ambiguous. Current shortcomings can be redressed by incorporating suitable controls in new experimental designs.

Kauffman RM; Ferketich AK; Wee AG; Shultz JM; Kuun P; Wewers ME. Factors associated with smokeless tobacco cessation in an Appalachian population. Addictive Behaviors 33(6): 821-830, 2008. (37 refs.)

Identifying factors associated with successful tobacco quit attempts may help in the development and targeting of effective cessation strategies. This paper aims to describe factors associated with smokeless tobacco (ST) cessation and compares the results to findings in the smoking cessation literature. Prospective data on 116 men aged 19 to 70 and participating in a ST cessation program were used to examine correlates of successful ST cessation at 1-year post-intervention. Controlling for age, level of education (p=0.002) and daily coffee consumption (p=0.005) had significant independent associations with successful cessation. No ST use variables were significant predictors of cessation success. In a multivariable logistic regression model three factors were significantly associated with cessation: education (p=0.010), coffee consumption (p=0.019), and age (P=0.029). Factors associated with successful ST cessation in this sample are consistent with predictors of smoking cessation reported in the literature. Based on its widespread use and the strength of its association with successful quitting, the role of caffeine consumption in ST cessation merits further study.

Killgore WDS; Kahn-Greene ET; Killgore DB; Kamimori GH; Balkin TJ. Effects of acute caffeine withdrawal on short category test performance in sleep-deprived individuals. Perceptual and Motor Skills 105(3, Part 2): 1265-1274, 2007. (33 refs.)

Caffeine is a popular stimulant often used to counter the effects of sleep loss and fatigue. Withdrawal from caffeine may produce mild declines in simple cognitive capacities Such as attention and concentration, but it is unclear whether more complex cognitive functions, such as abstract reasoning or concept formation, may be similarly affected. To assess the effect of acute caffeine withdrawal on executive functioning during sleep deprivation, 26 healthy volunteers were administered in double-blind form either repeated doses of caffeine or placebo over two nights of continuous wakefulness. The 108-item Short Category Test was administered after 56 hr. of total sleep deprivation (9 hr. post-caffeine administration). The caffeine group scored significantly more poorly, making approximately 57% more errors on the test than the placebo group. These findings suggest that acute caffeine withdrawal during prolonged sleep deprivation has an adverse effect on abstract reasoning and concept formation.

Killgore WDS; Lipizzi EL; Kamimori GH; Balkin TJ. Caffeine effects on risky decision making after 75 hours of sleep deprivation. Aviation, Space, and Environmental Medicine 78(10): 957-962, 2007. (41 refs.)

Introduction: Recent research indicates that sleep deprivation impairs decision making. However, it is unknown to what extent such deficits are exacerbated in a dose-response manner by increasing levels of sleepiness, and the extent to which such sleep-loss-induced deficits can be reversed by caffeine. Methods: At three time points, 26 healthy subjects completed alternate forms of the Iowa Gambling Task (IGT): rested baseline, 51 h awake, and 75 h awake. Every 2 h each night, 12 volunteers also received 4 200-mg doses of caffeine, with the last dose occurring 3 h prior to the IGT. Results: At baseline, volunteers readily learned to avoid disadvantageous high-risk card decks while progressively choosing more frequently from advantageous low-risk card decks. When sleep deprived, however, these same subjects showed impaired performance, choosing more frequently from the disadvantageous high-risk card decks, particularly during the latter half of the game. Contrary to expectations, the severity of performance impairment did not increase significantly from 51 to 75 h of wakefulness, and caffeine had no significant effects on IGT performance during sleep deprivation. Discussion and Conclusions: As a provisional extension of our previous study, these preliminary findings further suggest that the ability to integrate emotion with cognition to guide decision making, a capacity believed to be mediated by the ventromedial prefrontal cortex, may be particularly vulnerable to sleep loss. Moreover, these capacities may not be significantly improved by moderate doses of caffeine, suggesting that they may function separately from simple arousal and alertness systems.

Killgore WDS; Rupp TL; Grugle NL; Reichardt RM; Lipizzi EL; Balkin TJ. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. Journal of Sleep Research 17(3): 309-321, 2008. (51 refs.)

Prolonged sleep loss impairs alertness, vigilance and some higher-order cognitive and affective capacities. Some deficits can be temporarily reversed by stimulant medications including caffeine, dextroamphetamine, and modafinil. To date, only one study has directly compared the effectiveness of these three compounds and specified the doses at which all were equally effective in restoring alertness and vigilance following 64 h of wakefulness. The present study compared the effectiveness of these same three stimulants/doses following a less extreme period of sleep loss (i.e., 44 h). Fifty-three healthy adults received a single dose of modafinil 400 mg (n = 11), dextroamphetamine 20 mg (n = 16), caffeine 600 mg (n = 12), or placebo (n = 14) after 44 h of continuous wakefulness. After 61 h of being awake, participants obtained 12 h of recovery sleep. Psychomotor vigilance was assessed bi-hourly during waking and following recovery sleep. Relative to placebo, all three stimulants were equally effective in restoring psychomotor vigilance test speed and reducing lapses, although the duration of action was shortest for caffeine and longest for dextroamphetamine. At these doses, caffeine was associated with the highest percentage of subjectively reported side-effects while modafinil did not differ significantly from placebo. Subsequent recovery sleep was adversely affected in the dextroamphetamine group, but none of the stimulants had deleterious effects on postrecovery performance. Decisions regarding stimulant selection should be made with consideration of how factors such as duration of action, potential side-effects, and subsequent disruption of recovery sleep may interact with the demands of a particular operational environment.

Klatsky AL; Koplik S; Kipp H; Friedman GD. The confounded relation of coffee drinking to coronary artery disease. American Journal of Cardiology 101(6): 825-827, 2008. (19 refs.)

After decades of conflicting studies, the relation of coffee drinking to coronary artery disease (CAD) risk remains unresolved. Using Cox proportional-hazards models with 5 covariates, 127,212 subjects who supplied baseline data at voluntary health examinations from 1978 to 1985 were studied. Subsequently, 8,357 subjects were hospitalized for CAD. Coffee drinking was unrelated to CAD risk in 58,888 never smokers, but in ex-smokers and current baseline smokers, daily coffee intake was associated with higher CAD risk. This disparity was generally consistent in stratified subgroups. In conclusion, this relation of coffee consumption to increased CAD risk only in smokers could be explained by incomplete control for smoking, by other traits of smokers, or by an adverse biologic interaction of a coffee ingredient with smoking effect on CAD.

Kobeissi L; Inhorn MC. Male infertility in Lebanon: A case-controlled study. Ethnicity & Disease 17(2, Supplement 3): S33-S38, 2007. (27 refs.)

Objective. The impact of risk factors, such as consanguinity and familial clustering, reproductive infections, traumas, and diseases, lifestyle factors and occupational and war exposures on male infertility, was investigated in a case-controlled study conducted in Lebanon. Study Design. One-hundred-twenty males and 100 controls of Lebanese, Syrian or Lebanese-Palestinian descents were selected from two in-vitro fertilization (IVF) clinics located in Beirut, Lebanon. All cases suffered from impaired sperm count and function, according to World Health Organization guidelines for semen analysis. Controls were the fertile husbands of infertile women. Data were collected using a semi-structured interview, laboratory blood testing and the results of the most recent semen analysis. Univariate, bivariate and multivariate logistic regression analyses were used for data analysis, along with checks for effect modification and control of confounders. Study Results. Consanguinity and the familial clustering of male infertility cases, as well as reproductive illnesses and war exposures were independently significant risk factors for male infertility. The odds of having infertility problems in the immediate family were 2.6 times higher in cases than controls. The odds of reproductive illness were 2 times higher in cases than controls. The odds of war exposures were 1.57 times higher in cases than controls. Occupational exposures, such as smoking and caffeine intake, were not shown to be important risk factors. Conclusion. This case-controlled study highlights the importance of investigating the etiology of male infertility in Middle Eastern communities. It suggests the need to expand research on male reproductive health in the Middle East in order to improve the prevention and management of male infertility and other male reproductive health problems.

Koppelstaetter F; Poeppel TD; Siedentopf CM; Ischebeck A; Verius M; Haala I. Does caffeine modulate verbal working memory processes? An fMRI study. Neuroimage 39(1): 492-499, 2008. (51 refs.)

To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.

Kuczkowski KM. The effects of drug abuse on pregnancy. (review). Current Opinion in Obstetrics & Gynecology 19(6): 578-585, 2007. (114 refs.)

Purpose of review: The present article is an update on the effects of drug abuse on pregnancy outcome. Recent findings Substance abuse in pregnancy is on the increase worldwide. Simultaneously, there is great variability in prevalence rates in different countries, regions of countries and in different ethnic groups. In the United States nearly 90% of drug-abusing women are of reproductive age. Substanceances most commonly abused in pregnancy include cocaine, amphetamines, opioids, marijuana, ethanol, tobacco, caffeine, and toluene-based solvents. Polysubstance abuse is very common. Summary: Substance abuse in pregnancy is associated with significant maternal and fetal morbidity. Risk factors suggesting substance abuse in pregnancy include lack of prenatal care, history of premature labor, and cigarette smoking. In the United States the American College of Obstetricians and Gynecologists has made multiple recommendations regarding management of parturients with drug abuse during pregnancy. Women who acknowledge use of illicit substance during pregnancy should be counseled and offered necessary treatment. The American College of Obstetricians and Gynecologists also acknowledged that some states consider intrauterine fetal drug exposure to be a form of child neglect or abuse under the law.

Lev EI; Arikan ME; Vaduganathan M; Alviar CL; Tellez A; Mathuria N et al. Effect of caffeine on platelet inhibition by clopidogrel in healthy subjects and patients with coronary artery disease. American Heart Journal 154(4): article 694.el, 2007. (20 refs.)

Background: Clopidogrel inhibits the platelet P2Y12 receptor, leading to increased intracellular cyclic AMP (CAMP) levels. Caffeine also causes a rise in platelet CAMP. We aimed to test the effect of acute caffeine administration on platelet inhibition by clopidogrel, in healthy volunteers and patients with coronary artery disease. Methods Cohort 1: 12 healthy subjects were enrolled in a 2-week crossover study. Blood samples were drawn at baseline, 2, 4, and 24 hours after 300 mg clopidogrel intake. At the first week, 6 subjects received caffeine (300 mg pill, equivalent to a medium sized coffee drink) 30 minutes after clopidogrel. At week 2, the other 6 subjects received caffeine. One month later the effect of caffeine alone was tested. Platelet function was evaluated by aggregation in response to 5, 10, and 20 mu mol/L adenosine diphosphate, 1 mu g/mL Collagen, and flow cytometric determination of P-selectin expression, PAC-1 binding, and vasodilator-stimulated phosphoprotein phosphorylation. Cohort 2: 40 patients with coronary artery disease receiving aspirin and clopiclogrel (75 mg daily) for >= 1 week were tested at baseline and 2.5 hours after caffeine (300 mg). Results In cohort 1 (crossover study), caffeine was associated with lower adenosine diphosphate-induced aggregation at 4 hours, lower activation markers at 2 hours, and lower vasodilator-stimulated phosphoprotein phosphorylation at A hours after clopiclogrel. Caffeine alone had no effect on the assessed platelet surface biomarkers. In cohort 2, caffeine administration was associated with lower platelet activation markers (P-selectin, PAC-1 binding), without significant effect on aggregation. Conclusions Acute caffeine administration after clopidogrel loading appears to be associated with enhanced platelet inhibition 2 to 4 hours after clopidogrel intake. The mechanism probably involves synergistic increase in CAMP levels.

Lohi JJ; Huttunen KH; Lahtinen TVM; Kilpelainen AA; Muhli AA; Leino TK. Effect of caffeine on simulator flight performance in sleep-deprived military pilot student. Military Medicine 172(9): 982-987, 2007. (24 refs.)

Caffeine has been suggested to act as a countermeasure against fatigue in military operations. In this randomized, double-blind, placebo-controlled study, the effect of caffeine on simulator flight performance was examined in 13 military pilots during 37 hours of sleep deprivation. Each subject performed a flight mission in simulator four times. The subjects received either a placebo (six subjects) or 200 mg of caffeine (seven subjects) 1 hour before the simulated flights. A moderate 200 mg intake of caffeine was associated with higher axillary temperatures, but it did not affect subjectively assessed sleepiness. Flight performance was similar in both groups during the four rounds flown under sleep deprivation. However, subjective evaluation of overall flight performance in the caffeine group tended to be too optimistic, indicating a potential flight safety problem. Based on our results, we do not recommend using caffeine pills in military flight operations.

Luciano M; Zhu G; Kirk KM; Gordon SD; Heath AC; Montgomery GW; Martin NG. "No thanks, it keeps me awake": The genetics of coffee-attributed sleep disturbance. Sleep 30(10): 1378-1386, 2007. (35 refs.)

Study Objectives: Previous genetic investigations of sleep disturbance have shown various measures of sleep quality and sleep pattern to be heritable. But none of these studies have investigated the genetic predisposition to sleep disturbance attributed to caffeine. In this study, the heritability of coffee-attributed sleep disturbance and its relationship with other sleep measures were estimated, and chromosomal regions influencing this trait were identified. Design: A classical twin design was used to estimate the heritability of coffee-attributed sleep disturbance and its genetic covariance with other measures of sleep disturbance (e.g., due to anxiety, depression) and sleep quality (e.g., variability in sleep quality). To locate quantitative trait loci influencing coffee-attributed sleep disturbance, a genome-wide linkage screen of 1395 microsatellite markers was performed. Participants: The study included 3808 Australian adult twin pairs (n = 1799 monozygous pairs; n = 2009 dizygous pairs). A subsample of 1989 individuals from 1175 families was used for the linkage analysis. Measurements and Results: The heritability of coffee-attributed sleep disturbance (measured by self report) was approximately 0.40, with three fourths of this genetic variance explained by genes unrelated to the general sleep disturbance factor. One region of significant linkage to coffee-attributed sleep disturbance was identified on chromosome 2q (LOD score of 2.9). Conclusions: Although no candidate genes known to be related to caffeine metabolism or sleep disorder were identified in the significant linkage region, 2 candidates were found under a smaller peak on chromosome 17q.

Martin CA; Cook C; Woodring JH; Burkhardt G; Guenthner G; Omar HA et al. Caffeine use: Association with nicotine use, aggression, and other psychopathology in psychiatric and pediatric outpatient adolescents. TheScientificWorldJOURAL 8: 513-516, 2008. (8 refs.)

The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents ( average age 14.01 +/- 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained from parents and assent from the youth. High caffeine consumption was associated with daily cigarette use; aggressive behavior; conduct, attention deficit/hyperactivity, and social problems; and increased somatic complaints in adolescents.

Molema MM; Dekker MC; Voermans NC; van Engelen BG; Aarnoutse RE. Caffeine and muscle cramps: A stimulating connection. (letter). American Journal of Medicine 120(8): E1-E2, 2007. (7 refs.)

Mongraw-Chaffin ML; Cohn BA; Cohen RD; Christianson RE. Maternal smoking alcohol consumption and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: A prospective study in the child health and development studies cohort 1959-1967. American Journal of Epidemiology 167(3): 257-261, 2008. (34 refs.)

The Child Health and Development Studies is a >= 40-year follow-up of 20,754 pregnancies occurring between 1959 and 1967 in California. There were 84 cases of undescended testes at birth persisting to at least age 2 years among 7,574 liveborn sons whose mothers were interviewed in early pregnancy. Cases were matched to three controls on birth year and race. Compared with mothers of controls, mothers of cryptorchid boys consumed more caffeine during pregnancy (odds ratio = 1.4, 95% confidence interval: 1.1, 1.9 for an interquartile range equivalent to three cups of coffee per day) but were not more likely to smoke or drink alcohol when all behaviors were considered together. Other maternal and perinatal risk factors were not significantly associated with persistent cryptorchidism and did not confound the association with caffeine.

Moore MT; Greenway SL; Farris JL; Guerra B. Assessing caffeine as an emerging environmental concern using conventional approaches. Archives of Environmental Contamination and Toxicology 54(1): 31-35, 2008. (22 refs.)

Organic wastewater contaminants, including pharmaceuticals, caffeine, and nicotine, have received increased scrutiny because of their detection in water bodies receiving wastewater discharge. Despite recent measurement in United States streams, caffeine's effect on freshwater organisms is not well documented. The present study measured caffeine's lethal and sublethal effects on the freshwater species, Ceriodaphnia dubia, Pimephales promelas, and Chironomus dilutus. These organisms, which are used in standard testing or effluent monitoring, were exposed to aqueous caffeine solutions under static exposure for 48 hours and daily renewed static exposure for 7 days. Averaged responses of 48-hour acute end points indicated that C. dubia was more sensitive to caffeine exposures (LC50 = 60 mg/L) than either P. promelas (LC50 = 100 mg/L) or C. dilutus (LC50 = 1,230 mg/L). Exposure-response slopes confirmed these findings (3% mortality/mg/L for C. dubia; 0.5% mortality/mg/L for P. promelas; and 0.07% mortality/mg/L for C. dilutus). Comparative 7-day responses between C. dubia and P. promelas (LC50 = 46 and 55 mg/L, respectively) were more similar than the broad range of acute values. Sublethal effects measured for caffeine exposure included impaired C. dubia reproduction (IC50 = 44 mg/L) and inhibited P. promelas growth (IC50 = 71 mg/L). According to the results of this study, combined with earlier studies reporting environmental concentrations and product half-lives, caffeine should pose negligible risk for most aquatic vertebrate and invertebrate organisms.

Morales-Suarez-Varela MM; Bech BH; Christensen K; Olsen J. Coffee and smoking as risk factors of twin pregnancies: The Danish National Birth Cohort. Twin Research and Human Genetics 10(4): 597-603, 2007. (39 refs.)

Twinning rates have changed substantially over time for reasons that are only partly known. In this study we studied smoking, coffee and alcohol intake and their possible interaction with obesity as potential determinants of twinning rates using data from the Danish National Birth Cohort between 1996 and 2002. We identified 82,985 pregnancies; 81,954 singleton and 1031 twins. For the twins we had data to classify 121 as monozygotic, 189 dizygotic (same sex), and 313 dizygotic (opposite sex), but, 408 were of the same sex but unknown zygosity. All mothers were interviewed about their pre-pregnancy weight, height, coffee and alcohol intake, smoking habits and potential confounding factors at early sages of pregnancy. We identified smoking (> 10 cigarettes/day) as a possible determinant of twinning, particularly for dizygotic twinning rates (same sex) and further more corroborated that obesity and the mother's age are strong correlates of twinning. Others have found coffee intake to increase twinning rates but that is not seen in these data.

Mort JR; Kruse HR. Timing of blood pressure measurement related to caffeine consumption. Annals of Pharmacotherapy 42(1): 105-110, 2008. (21 refs.)

OBJECTIVE: To determine whether patients should wait 30 minutes after caffeine consumption to have their blood pressure measured. DATA SOURCES: Literature was obtained by searching MEDLINE (1980-September 2007), International Pharmaceutical Abstracts (1980-September 2007), and the Cochrane Database of Systematic Reviews (1994-September 2007). Search terms included caffeine and blood pressure. Literature was a so obtained from citations in relevant articles. STUDY SELECTION AND DATA EXTRACTION: Articles that examined caffeine's acute effect on blood pressure were reviewed, with additional focus on caffeine tolerance and hypertensive status. DATA SYNTHESIS: Caffeine appears to affect blood pressure through adenosine receptor inhibition and an increased release of select neurotransmitters. Caffeine levels peak 30-120 minutes after oral intake and caffeine's half-life is 3-6 hours. The effect of caffeine on blood pressure has been examined for decades, with variable results depending on factors such as population examined (eg, hypertensive status, physical stressors, age) and study design (eg, acute effects, chronic ingestion, retrospective epidemiologic review). Caffeine tolerance diminishes the acute effect of caffeine on blood pressure, and hypertensive individuals are more susceptible to blood pressure changes. Reviews of caffeine's acute effect on blood pressure indicate changes of 3-15 mm Hg systolic and 4-13 mm Hg diastolic. Typically, blood pressure changes occur within 30 minutes, peak in 1-2 hours, and may persist for more than 4 hours. CONCLUSIONS: Having a patient abstain from caffeine for 30 minutes prior to blood pressure monitoring is not adequate to avoid caffeine's potential effects. An alternative approach to blood pressure monitoring would be to ask the patient about recent caffeine consumption and interpret the blood pressure reading based on this information. In addition, healthcare practitioners should provide education regarding caffeine's effects.

Muncie HL. The safety of caffeine consumption. (editorial). American Family Physician 76(9): 1282-+, 2007. (17 refs.)

Nakada N; Komori K; Suzuki Y; Konishi C; Houwa I; Tanaka H. Occurrence of 70 pharmaceutical and personal care products in Tone River basin in Japan. Water Science and Technology 56(12): 133-140, 2007. (6 refs.)

The occurrence of 70 pharmaceutical and personal care products (PPCPs) was investigated in the Tone River. The river has the largest basin in Japan, and the water is utilized not only for farming, but also as a source of water supply. One day in both January and October 2006, surface waters in the river and its tributaries and effluents from sewage treatment plants (STPs) directly discharging into the Tone River were collected, the location of which ranged over 150 km along the river. The 70 PPCPs in the samples were concentrated by solid phase cartridge and were measured by LC-MS/MS using three analytical methods. Fifty-seven PPCPs were detected in one or more samples. Bezafibrate, caffeine, carbamazepine, clarithromycin, crotamiton and sulpiride were frequently detected. Mass flow profiles of some PPCPs (e.g., crotamiton) were comparable to cumulative inhabitants in the basin, suggesting that these PPCPs could be markers of population. Total load of each PPCP into the basin from upstream, the tributaries, and the STPs were calculated. The contribution of selected PPCPs from the tributaries with lower sewerage system coverage was dominant compared to those from upstream and the STPs, suggesting the installation of sewerage systems is necessary to reduce the load of PPCPs in the Tone River basin.

Nelson D. Prevention and treatment of sleep deprivation among emergency physicians. (review). Pediatric Emergency Care 23(7): 498-503, 2007. (54 refs.)

Emergency physicians commonly experience sleep deprivation because of the need to work shifts during evening and late night hours. The negative effects of this problem are compounded by job stress and traditional methods of scheduling work shifts. Sleep deprivation may be reduced by schedules designed to lessen interference with normal sleep patterns and circadian rhythms. Pharmacological treatments for sleep deprivation exist in the form of alertness-enhancing agents, caffeine and modafinil. Sleep-promoting agents may also help treat the problem by helping physicians to sleep during daytime hours. Minimizing sleep deprivation may help prevent job burnout and prolong the length of an emergency physician's career.

O'Rourke MP; O'Brien BJ; Knez W; Paton CD. Caffeine has a small effect on 5-km running performance of well-trained and recreational runners. Journal of Science and Medicine in Sport 11(2): 231-233, 2008. (10 refs.)

The purpose of this study was to investigate if caffeine ingestion improves 5-km time-trial performance in well-trained and recreational runners. Using a double-blind placebo-controlled design, 15 well-trained and 15 recreational runners completed two randomized 5-km time-trials, after ingestion of either 5 mg kg(-1) of caffeine or a placebo. Caffeine ingestion significantly improved 5-km running performance in both the well-trained and recreational runners. In comparison to the placebo trial, the caffeine trial resulted in 1.1% (90% CI 0.4-1.6) and 1.0% (0.2-2%) faster times for the well-trained and recreational runners. Reliability testing of the recreational runners indicated a test-retest error of measurement of 1.4%. We conclude that caffeine ingestion is likely to produce small but significant gains in 5-km running performance for both well-trained and recreational runners.

Otberg N; Patzelt A; Rasulev U; Hagemeister T; Linscheid M; Sinkgraven R et al. The role of hair follicles in the percutaneous absorption of caffeine. British Journal of Clinical Pharmacology 65(4): 488-492, 2008. (30 refs.)

AIMS: The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans. METHODS: Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance. RESULTS: Caffeine (3.75 ng ml(-1)) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml(-1)). Highest values (11.75 ng caffeine ml(-1)) were found 1 h after application when the follicles were open. CONCLUSIONS: Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.

Oteri A; Salvo F; Caputi AP; Calapai G. Intake of energy drinks in association with alcoholic beverages in a cohort of students of the School of Medicine of the University of Messina. Alcoholism: Clinical and Experimental Research 31(10): 1677-1680, 2007. (23 refs.)

Energy drinks (ED) are a widely used group of beverages known for their stimulant effects on central nervous system (CNS). The main components of ED are caffeine, taurine, carbohydrates, glucuronolactone, inositol, niacin, pantenol, and beta-complex vitamins. The studies evaluating the effects of ED describe improvements in attention and/or reaction times and indices of alertness. It has been also shown that combination of caffeine and glucose, fundamental constituents of ED, can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand. Moreover, the associated ingestion of alcohol and ED has recently been observed to be becoming more and more widespread. With the aim to know the habits and uses of students, we administered a questionnaire containing questions regarding ED drinking alone or in association with alcoholic beverages. Five hundred students of the School of Medicine of the University of Messina were interviewed, and 450 filled the questionnaire. A total of 56.9% of students declared using ED. A great part of users (48.4%) associate frequently ED and alcohol. In particular, 35.8% of ED + alcohol users have used ED + alcohol more than 3 times in the last month. Distinguishing the users into 2 groups (users of ED + alcohol and users of both ED and ED + alcohol), we observed in the second group a major use of cocktail containing a mix of ED and alcoholic beverages. This difference between the 2 groups is less represented about the ingestion of ED + alcohol in the night. Our data indicate that association of ED + alcohol is very popular among students. This behavior can be dangerous. In fact, the combination of ED + alcoholic drinks can reduce adversive symptoms of alcohol intoxication including the depressant effects. As consequence, users of ED + alcoholic beverages might not feel the signs of alcohol intoxication, thus increasing the probability of accidents and/or favoring the possibility of development of alcohol dependence.

Palatini P; Dorigatti F; Santonastaso M; Cozzio S; Biasion T; Garavelli G et al. Association between coffee consumption and risk of hypertension. Annals of Medicine 39(7): 545-553, 2007. (44 refs.)

Background. The longitudinal relationship between coffee use and hypertension is not well known. Aim. We did a prospective study to investigate if there is a temporal relationship between coffee consumption and development of sustained hypertension. thod. We assessed 1107 white subjects with elevated blood pressure who were followed up for 6.4 years. Coffee intake and other life-style factors were ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Results: During the follow-up, 561 subjects developed sustained hypertension, whereas 546 subjects did not meet the criteria for treatment. Coffee drinkers developed sustained hypertension more frequently than abstainers (53.1% versus 43.9%, P=0.007). The incidence of hypertension did not differ between moderate and heavy coffee drinkers. Kaplan-Meier analysis confirmed that sustained hypertension was developed more frequently by coffee drinkers compared with nondrinkers (P< 0.00 1). The adjusted relative risk of hypertension was greater in both categories of coffee drinking than in abstainers (hazard ratio, 95% confidence limit (CL)=1.24, 1.06-1.44). The risk of hypertension associated with coffee drinking increased gradually with increasing level of alcohol use (adjusted P for interaction= 0.005). Conclusions. In subjects screened for stage I hypertension a nonlinear association was found between coffee consumption and development of sustained hypertension.

Polychronopoulos E; Zeimbekis A; Kastorini CM; Papairakleous N; Vlachou I; Bountziouka V et al. Effects of black and green tea consumption on blood glucose levels in non-obese elderly men and women from Mediterranean Islands (MEDIS epidemiological study). European Journal of Nutrition 47(1): 10-16, 2008. (28 refs.)

Background: Obesity and diabetes are metabolic disorders that affect a large amount of the elderly population and are related to increased cardiovascular risk. Tea intake has been associated with lower risk of mortality and morbidity in some, but not all studies. We evaluated the association between tea intake, blood glucose levels, in a sample of elderly adults. Methods During 2005-2006, 300 men and women from Cyprus, 142 from Mitilini and 100 from Samothraki islands (aged 65-100 years) were enrolled. Dietary habits (including tea consumption) were assessed through a food frequency questionnaire. Among various factors, fasting blood glucose and body mass index (BMI) were measured. Results Fifty-four percent of the participants reported that they consume tea at least once a week (mean intake 1.6 +/- 1.1 cup/day). A significant interaction was observed between tea intake, obesity status on glucose levels (P < 0.001). After adjusting for various confounders, tea intake was associated with lower blood glucose levels in non-obese (P for trend < 0.001), but not in obese people (P = 0.24). Multiple logistic regression analysis revealed that moderate tea consumption (1-2 cups/day) was associated with 88% (95% CI 76-98%) lower odds of having diabetes among non-obese participants, irrespective of age, sex, smoking, physical activity status, dietary habits and other clinical characteristics. Conclusion: Tea consumption is associated with reduced levels of fasting blood glucose only among non-obese elderly people.

Powers KM; Kay DM; Factor SA; Zabetian CP; Higgins DS; Samii A. Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Movement Disorders 23(1): 88-95, 2008. (27 refs.)

Inverse associations of Parkinson's disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti-inflammatory drug (NSAID) use have been reported individually, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case-control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smoking. coffee, and NSAID consumption. Odds ratios were calculated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumulative exposures, suggesting dose-response relations. With respect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR 0.13, 95% CI = 0.06-0.29). Whether this finding reflects true biologic protection needs to be investigated.

Pucci L; Geppetti A; Maggini V; Lucchesi D; Rossi AM; Longo V. CYP1A2 F21L and F186L Polymorphisms in an Italian population sample. Drug Metabolism and Pharmacokinetics 22(3): 220-222, 2007. (9 refs.)

P450 cytochromes (CYPs) enzymes play a major role in variability of drug response and cancer susceptibility. In particular, up to 60- fold interindividual variation has been detected in the activity of CYP1A2, which is involved in the metabolism of caffeine, several drugs and various toxic and carcinogenic compounds. Aim of this study is to assess the frequency of CYP1A2 F21L and F186L polymorphisms (formerly CYP1A2* 2 and * 11 alleles), up to now found in Asiatic populations only. These variants were absent in 500 Italian healthy subjects. Therefore it can be suggested that the variation of CYP1A2-dependent metabolism in the Caucasian population is not related to these two CYP1A2 polymorphisms. Thus, this study supports the view that ethnicity is a relevant factor to be carefully considered in pharmacogenetic studies.

Ritchie K; Carriere I; de Mendonca A; Portet F; Dartigues JF; Rouaud O. The neuroprotective effects of caffeine : A prospective population study (the Three City Study). Neurology 69(6): 536-545, 2007. (29 refs.)

Objective: To examine the association between caffeine intake, cognitive decline, and incident dementia in a community- based sample of subjects aged 65 years and over. Methods: Participants were 4,197 women and 2,820 men from a population- based cohort recruited from three French cities. Cognitive performance, clinical diagnosis of dementia, and caffeine consumption were evaluated at baseline and at 2 and 4 year follow- up. Results: Caffeine consumption is associated with a wide range of sociodemographic, lifestyle, and clinical variables which may also affect cognitive decline. Multivariate mixed models and multivariate adjusted logistic regression indicated that women with high rates of caffeine consumption (over three cups per day) showed less decline in verbal retrieval (OR = 0.67, CI = 0.53, 0.85), and to a lesser extent in visuospatial memory (OR = 0.82, CI = 0.65, 1.03) over 4 years than women consuming one cup or less. The protective effect of caffeine was observed to increase with age (OR = 0.73, CI = 0.53, 1.02 in the age range 65 to 74; OR = 0.3, CI = 0.14, 0.63 in the range 80 +). No relation was found between caffeine intake and cognitive decline in men. Caffeine consumption did not reduce dementia risk over 4 years. Conclusions: The psychostimulant properties of caffeine appear to reduce cognitive decline in women without dementia, especially at higher ages. Although no impact is observed on dementia incidence, further studies are required to ascertain whether caffeine may nonetheless be of potential use in prolonging the period of mild cognitive impairment in women prior to a diagnosis of dementia.

Rogers PJ; Smith JE; Heatherley SV; Pleydell-Pearce CW. Time for tea: Mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology 195(4): 569-577, 2008. (62 refs.)

Rationale: Although both contain behaviourally significant concentrations of caffeine, tea is commonly perceived to be a less stimulating drink than coffee. At least part of the explanation for this may be that theanine, which is present in tea but not coffee, has relaxing effects. There is also some evidence that theanine affects cognitive performance, and it has been found to reduce blood pressure in hypertensive rats. Objectives To study the subjective, behavioural and blood pressure effects of theanine and caffeine administered alone and together, in doses relevant to the daily tea consumption of regular tea drinkers. Materials and methods In a randomised, double-blind, placebo-controlled study, healthy adult participants (n=48) received either 250-mg caffeine, 200-mg theanine, both or neither of these. They completed ratings of mood, including anxiety, and alertness, and had their blood pressure measured before and starting 40 min after drug administration. Anxiety was also assessed using a visual probe task. Results: Caffeine increased self-rated alertness and jitteriness and blood pressure. Theanine antagonised the effect of caffeine on blood pressure but did not significantly affect jitteriness, alertness or other aspects of mood. Theanine also slowed overall reaction time on the visual probe task. Conclusions: Theanine is a physiologically and behaviourally active compound and, while it is unclear how its effects might explain perceived differences between tea and coffee, evidence suggests that it may be useful for reducing raised blood pressure.

Rudelle S; Ferruzzi MG; Cristiani I; Moulin J; Mace K; Acheson KJ et al. Effect of a thermogenic beverage on 24-hour energy metabolism in humans. Obesity 15(2): 349-355, 2007. (36 refs.)

Objective: To test whether consumption of a beverage containing active ingredients will increase 24-hour energy metabolism in healthy, young, lean individuals. Research Method and Procedures: Thirty-one male and female subjects consumed 3 X 250-mL servings of a beverage containing green tea catechins, caffeine, and calcium for 3 days in a single-center, double-blind, placebo-controlled, cross-over design study. On the 3rd day, 23-hour energy metabolism, extrapolated to 24-hour, was measured in a calorimeter chamber. Blood pressure and heart rate were measured, and total day and night urines were analyzed for urea and catecholamine excretion. Results: Twenty-four-hour energy expenditure (EE) and 24-hour fat oxidation were lower in women than in men (p < 0.0001 and p < 0.015, respectively). Although there were no treatment or treatment/gender effects on substrate oxidation, treatment increased 24-hour EE by 106 +/- 31 kcal/24 hours (p = 0.002), equivalent to 4.7 +/- 1.6 kcal/h (day; p = 0.005) and 3.3 +/- 1.5 kcal/h (night; p = 0.04). No significant differences were observed in hemodynamic parameters. Discussion: The present study provides evidence that consumption of a beverage containing green tea catechins, caffeine, and calcium increases 24-hour EE by 4.6%, but the contribution of the individual ingredients cannot be distinguished. Although this increase is modest, the results are discussed in relation to proposed public health goals, indicating that such modifications are sufficient to prevent weight gain. When consumed regularly as part of a healthy diet and exercise regime, such a beverage may provide benefits for weight control.

Sagaspe P; Taillard J; Chaumet G; Moore N; Bioulac B; Philip P. Aging and nocturnal driving: Better with coffee or a nap? A randomized study. Sleep 30(12): 1808-1813, 2007. (40 refs.)

Study Objective: To test the effects of coffee and napping on nocturnal driving in young and middle-aged participants. Design: A cup of coffee (200 mg of caffeine), a placebo (decaffeinated coffee, 15 mg of caffeine), or a 30-minute nap were tested. Participants drove 125 highway miles between 18:00 and 1930 and between 02:00 and 03:30 after coffee, placebo, or a nap. Setting: Sleep laboratory and open French highway. Participants: Twelve young (range, 20-25 years) and 12 middle-aged participants (range, 40-50 years). Measurements: Inappropriate line crossings, self-perceived fatigue and sleepiness, and polysomnographic recordings were analyzed. Results: Compared to daytime, after placebo the number of inappropriate line crossings was significantly increased (2 versus 73 for young participants, P < 0.01 and 0 versus 76 for the middle-aged participants, P < 0.05). Both coffee and napping reduced the risk of inappropriate line crossings, compared with placebo, in young participants (respectively, by three-quarters, incidence rate ratios [IRR] = 0.26 95% confidence interval [CI], 0.09-0.74, P < 0.05 and by two thirds, IRR = 0.34 95% Cl, 0.20-0.58, P < 0.001) and in middle-aged participants (respectively by nine tenths, IRR = 0.1195% Cl, 0.05-0.21, P < 0.001 and by one fifth, IRR = 0.77 95% Cl, 0.63-0.95, P < 0.05). A significant interaction between age and condition (IRR = 2.27 95% Cl, 1.28-4.16 P < 0.01) showed that napping led to fewer inappropriate line crossings in younger participants than in middle-aged participants. During napping, young participants slept more (P < 0.01) and had more delta sleep (P < 0.05) than middle-aged participants. Self-perceived sleepiness and fatigue did not differ in both age groups, but coffee improved sleepiness (P < 0.05), whereas napping did not. Conclusions: Coffee significantly improves performance in young and middle-aged participants. Napping is more efficient in younger than in older participants. Countermeasures to sleepiness should be adapted according to the age of drivers.

Savitz DA; Chan RL; Herring AH; Howards PP; Hartmann KE. Caffeine and miscarriage risk. Epidemiology 19(1): 55-62, 2008. (24 refs.)

Background: Coffee and caffeine have been inconsistently found to be associated with increased risk of clinical miscarriage-a potentially important association given the high prevalence of exposure. Methods: Women were recruited before or early in pregnancy and interviewed regarding sources of caffeine, including assessment of changes over the perinatal period. We identified 2407 clinically-recognized pregnancies resulting in 258 pregnancy losses. We examined the relationship of coffee and caffeine intake with clinically-recognized pregnancy loss prior to 20 weeks' completed gestation, using a discrete-time continuation ratio logistic survival model. Results: Coffee and caffeine consumption at all 3 time points were unrelated to total miscarriage risk and the risk of loss after the interview. Reported exposure at the time of the interview was associated with increased risk among those with losses before the interview. Conclusions: There is little indication of possible harmful effects of caffeine on miscarriage risk within the range of coffee and caffeine consumption reported, with a suggested reporting bias among women with losses before the interview. The results may reflect exposure misclassification and unmeasured heterogeneity of pregnancy losses.

Selvanathan S; Selvanathan EA, eds. The Demand for Alcohol, Tobacco and Marijuana: International Evidence. London: Ashgate Publishing, 2005

Using a diverse database with statistics from some 30 developed and developing countries, the authors present a detailed statistical portrait of the consumption of food, soft drinks, tobacco, alcohol, and marijuana around the world. This data is then used to a model developed by the authors for determining the effect of consumer income and the prices of goods on consumption behavior. The model and data are also used to assess the alcohol and tobacco control policies of a number of countries. Data is summarized in over 100 tables and figures.

Silvera SAN; Jain M; Howe GR; Miller AB; Rohan TE. Intake of coffee and tea and risk of ovarian cancer: A prospective cohort study. Nutrition and Cancer 58(1): 22-27, 2007. (47 refs.)

There is some evidence from case-control studies that coffee consumption might be positively associated with ovarian cancer risk, whereas the epidemiologic evidence regarding tea consumption and ovarian cancer is inconsistent. To date, there have been few prospective studies of these associations. Therefore, we examined ovarian cancer risk in association with both coffee and tea intake in a prospective cohort study of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS) who completed a self-administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. Data from the food frequency questionnaire were used to estimate daily intake of coffee and tea. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between categories of coffee and tea intake and ovarian cancer risk. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases. Tea intake was not associated with ovarian cancer risk in our study population. In contrast, a borderline positive association was observed among women who drank >4 cups coffee/day compared to women who did not drink coffee (HR = 1.62, 95% CI = 0.95-2.75, P-trend = 0.06). Given the pervasive use of these beverages, the associations between coffee and tea consumption and ovarian cancer risk warrant investigation in further prospective studies.

Simon DK; Swearingen CJ; Hauser RA; Trugman JM; Aminoff MJ; Singer C et al. Caffeine and progression of Parkinson disease. (review). Clinical Neuropharmacology 31(4): 189-196, 2008. (19 refs.)

Objective: Caffeine use is negatively associated with the risk of developing Parkinson disease (PD) and is protective in animal models of PD, but the relationship between caffeine intake and rate of progression of PD is unknown. We assessed this relationship using data from 2 recent clinical trials of PD. Methods: Data were ascertained from 2 recent 1-year clinical trials that together included 413 early PD subjects who did not require symptomatic therapy at the time of study entry. Exploratory analyses compared caffeine intake with rate of progression of PD, as measured by either the likelihood of progression to the point of requiring symptomatic therapy or by change in the total Unified Parkinson Disease Rating Scale score. Results: Rate of progression of PD did not differ significantly between those in the highest and lowest quartiles for caffeine use for either of the primary measures or for secondary analyses of changes in scores on the motor or activities of daily living subsections of the Unified Parkinson Disease Rating Scale. Other secondary analyses yielded variable results. Conclusions: These data do not reveal a consistent relationship between caffeine intake and rate of progression of PD by these measures, although a larger study is required for sufficient power to more fully assess this relationship.

Soraisham AS; Elliott D; Amin H. Effect of single loading dose of intravenous caffeine infusion on superior mesenteric artery blood flow velocities in preterm infants. Journal of Paediatrics and Child Health 44(3): 119-121, 2008. (20 refs.)

Aim: To evaluate the effects of a single loading dose of caffeine base (10 mg/kg) on superior mesenteric artery (SMA) blood flow velocities (BFV). Methods: Eighteen preterm infants of gestational age <= 32 weeks gestation were investigated prospectively. SMA BFV before infusion, 1 h, 2 h and 6 h after a single loading dose of caffeine were measured using Doppler ultrasonography. Results: The peak systolic velocity in SMA decreased by 18% from baseline at 1 h after caffeine infusion and improved towards the baseline by 6 h after the infusion. The reduction in velocity after caffeine infusion was not statistically significant. No significant changes were observed in heart rate, blood pressure and incidence of necrotising enterocolitis. Conclusion: A single 10 mg/kg intravenous loading dose of caffeine does not cause a significant reduction in SMA BFV and therefore does not place the preterm intestine at increased risk of ischemic injury.

Sun YF; Zhang YL; He N; Liu XF; Miao DM. Caffeine and placebo expectation: Effects on vigilance, cognitive performance, heart rate, and blood pressure during 28 hours of sleep deprivation. Journal of Psychophysiology 21(2): 91-99, 2007. (41 refs.)

Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control), caffeine 200 mg at 00:00 (C200), placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive function were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-P200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects vigilance and cognitive performance.

Thomas JB; Sharpless KE; Mitvalsky S; Roman M; Yen J; Satterfield MB. Determination of caffeine and caffeine-related metabolites in ephedra-containing standard reference materials using liquid chromatography with absorbance detection and tandem mass spectrometry. Journal of AOAC International 90(4): 934-940, 2007. (21 refs.)

The concentrations of caffeine and caffeine-related compounds in 2 ephedra-containing reference materials have been determined by 3 independent methods with measurements performed by the National Institute of Standards and Technology (NIST) and a collaborating laboratory. Results from the 3 methods were used for value assignment of caffeine, theobromine, and theophylline in these Standard Reference Materials (SRMs). The methods used at NIST to determine the concentration levels of caffeine, theobromine, and theophylline in SRM 3243 Ephedra-Containing Solid Oral Dosage Form and SRM 3244 Ephedra-Containing Protein Powder used reversed-phase liquid chromatography with absorbance detection and tandem mass spectrometry. These reference materials are part of the first suite in a series of NIST SRMs that provide concentration values for multiple components in dietary supplements. These SRMs are primarily intended for method validation and for use as control materials to support the analysis of dietary supplements and similar materials.

Topik S; Marichal C; Frank Z, eds. From Silver to Cocaine: Latin American Commodity Chains and the Building of the World Economy, 1500-2000. Durham, NC: Duke University Press, 2006. (Chapter refs.)

This edited collection includes 12 essays with 16 contributors. It examines the "commodity chain approach" to history, with each essay focusing on one commodity taken from Latin America over a 500 year period, and the relationship to the expansion of the world economy. The first of these was silver, which became the "money" of the emerging Atlantic economy. Other raw materials to be appropriated from the continent and which became central to the emerging global economy included indigo, cochineal ( a red dye valued by European nobility), tobacco, coffee, sugar, cacao, bananas, fertilizers (guano and nitrates), rubber, henequen, and, most recently cocaine. Each of these raw materials is examined as a "product" which became central to the international economy. Rather than the nation-state being the focus of analysis, the interest is commodities/products, and which bind different nations and areas in diverse ways. In this view, globalization is not a new phenomenon but a long-standing one. Aside from a vehicle for exploring different approaches to history, this volume considers products of interest to those involved in substance abuse: tobacco, coffee, and cocaine.

Turley KR; DeSisso T; Gerst JW. Effects of caffeine on physiological responses to exercise: Boys versus men. Pediatric Exercise Science 19(4): 481-492, 2007. (47 refs.)

We compared the influence of caffeine on physiological responses to exercise between boys and men. Fifty-two participants (26 boys and 26 men) participated in a double blind, randomized, double crossover study. Each participant received the caffeinated (5 mg/kg) drink (CAF) and placebo (PL) twice each on 4 separate days. One hour after drink consumption preexercise heart rate (HR) and blood pressure (BP) were measured. Then while the participants rode stationary cycle ergometers at two different exercise intensities, HR, BP, and oxygen consumption (VO2) were measured. Blood pressure was not significantly affected by CAF, although on average it was always higher in boys for diastolic BP (3 mmHg) and systolic BP (3-4 mmHg) and men for diastolic BP (2-3 mmHg) and systolic BP (1-6 mmHg) both at rest and during exercise. HR was significantly (p < .05) lower at rest, 25W and 50W in CAF versus PL in boys, with no change in adults. During exercise, VO2 and respiratory exchange ratio (RER) were not different in CAF versus PL in either group. In conclusion, metabolism is not affected by a moderate caffeine dose in children or adults. The same dose has a similar effect on BP in both groups. The effect on HR was different, however, with a significant (p < .05) lowering in children in CAF versus PL, with no adult effects.

Walker GJ; Finlay O; Griffiths H; Sylvester J; Williams M; Bishop NC. Immunoendocrine response to cycling following ingestion of caffeine and carbohydrate. Medicine and Science in Sports and Exercise 39(9): 1554-1560, 2007. (30 refs.)

Purpose: This study investigated the effect of caffeine consumed with and without carbohydrate (CHO) on immunoendocrine responses after exercise. Methods: On four occasions, 12 recreational male cyclists cycled for 2 h at 65% VO2max. Sixty minutes before exercise, participants ingested 6 mg.kg(-1) body mass of caffeine (CAF) or placebo (PLA), then during exercise they consumed a 6% CHO or placebo (PLA) drink, providing CAF/CHO, PLA/CHO, CAF/PLA, and PLA/PLA conditions. Results: f-MLP-stimulated neutrophil oxidative burst responses were significantly higher after exercise on CAF/CHO and PLA/CHO (both P < 0.05) than PLA/PLA when expressed as a percentage of baseline value. The response on CAF/PLA tended to be higher than PLA/PLA at this point (P = 0.056). No significant differences between CAF/CHO, PLA/CHO, and CAF/PLA were observed after exercise; however, only PLA/CHO showed no significant postexercise decline. Coingestion of CAF/CHO significantly attenuated epinephrine (P < 0.05) and IL-6 (P < 0.05) responses that occurred after ingestion of CAF alone (CAF/PLA) and significantly attenuated the transient alterations in circulating leukocyte (P < 0.05) and neutrophil (P < 0.01) counts. Plasma cortisol concentration was significantly lower on PLA/CHO than CAF/PLA and PLA/PLA after exercise (P < 0.05). Perceived exertion during exercise was significantly lower on CAF/CHO than the other three trials (P < 0.05). Conclusion: Taken together, this suggests that coingestion of caffeine and CHO has greater influence on immunoendocrine responses than neutrophil functional responses to prolonged exercise.

West O; Roderique-Davies G. Development and initial validation of a Caffeine Craving Questionnaire. Journal of Psychopharmacology 22(1): 80-91, 2008. (74 refs.)

Craving for caffeine has received little empirical attention, despite considerable research into the potential for caffeine dependence. The main aim of this study was to develop, and initially validate, a multi-item, multidimensional instrument to measure cravings for caffeine. Participants were 189 caffeine consumers who completed the Questionnaire of Caffeine Cravings, which was based on the Questionnaire of Smoking Urges (QSU), in one of five naturally occurring periods of abstinence; 1-15 min; 16-120 mins; 3-7 h; 12-48 h and +48 h. Exploratory factor analysis suggested a three-factor solution best described the data; Factor 1 reflected strong desires, intentions and positive reinforcement; Factor 2 reflected mild/general positive and negative reinforcement and Factor 3 reflected functional/mood-based negat