Soup Kettle Topics: Xanthines

Title: Coffee Drinking and Prevalence of Bronchial Asthma
Author: Annesi, I.; Kauffmann, F.; Oryszczyn, M. P.; Neukirch, F.; Dore, M. F.; (Date: May, 1990)
Journal: Chest; V. 97; Issue: 5; Pages: 1268-9

Notes: Comment

Title: Caffeine for Asthma
Author: Bara, A. I.; Barley, E. A.; 2000)
Journal: Cochrane Database Syst Rev; Issue: 2; Pages: CD001112

Abstract: BACKGROUND: Caffeine has a variety of pharmacological effects. It is chemically related to the drug theophylline which is used to treat asthma. Accordingly, interest has been expressed in its potential role as an asthma treatment. A number of studies have explored the effects of caffeine in asthma, this is the first review to systematically examine and summarise the evidence. OBJECTIVES: Caffeine is a weak bronchodilator and it also reduces respiratory muscle fatigue. It has been suggested that caffeine may reduce asthma symptoms. The objective of this review was to assess the effects of caffeine on lung function and identify whether there is a need to control for caffeine consumption prior to lung function testing. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and the reference lists of articles. We also contacted study authors. SELECTION CRITERIA: Randomised trials of oral caffeine compared to placebo in adults with asthma. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were done independently by two reviewers. MAIN RESULTS: Six trials involving a total of 55 people were included. The studies were all of cross-over design and of high quality. In comparison with placebo, caffeine appears to improve lung function for up to two hours after consumption. Forced expiratory volume in one minute showed a small improvement up to two hours after caffeine use (standardised mean difference -0.73, 95% confidence interval -1.20 to -0.25). Mid-expiratory flow rates also showed a small improvement with caffeine and this was sustained up to four hours. REVIEWER’S CONCLUSIONS: Caffeine appears to improve airways function modestly in people with asthma for up to four hours. People may need to avoid caffeine for at least four hours prior to lung function testing.
Notes: Journal Article
Review, Academic
Author Address: Department of Public Health Sciences, St George’s Hospital Medical School, Cranmer Terrace, Tooting, London, UK, SW17 ORE.

Title: Theophylline in the Management of Asthma: Time for Reappraisal?
Author: Barnes, P. J.; Pauwels, R. A.; (Date: Mar, 1994)
Journal: Eur Respir J; V. 7; Issue: 3; Pages: 579-91

Abstract: Theophylline has been used for several decades in the treatment of asthma and remains the most widely prescribed anti-asthma drug worldwide, although the development of newer anti-asthma medications, especially inhaled steroids, has resulted in declining use of theophylline in industrialized countries. Theophylline is now considered to be a bronchodilator, but it is increasingly recognized that theophylline has other anti-asthma activities, which may be more important. Theophylline, even at low plasma concentrations, inhibits the late asthmatic reaction following allergen challenge. These clinical pharmacological observations are substantiated by experimental animal and in vitro data showing that theophylline has several anti-inflammatory activities relevant to asthma. These include the inhibition of cytokine synthesis and release, the inhibition of inflammatory cell activation and microvascular leakage, and the prevention of airway hyperresponsiveness induced by airway inflammation. Theophylline appears to have immunomodulatory effects, even at relatively low plasma concentrations. Based on these considerations, theophylline can be regarded as a useful alternative to other anti-inflammatory drugs for the chronic treatment of mild to moderate asthma. Theophylline should be used at lower doses to achieve plasma concentrations of 5-10 mg.l-1, which will avoid the risk of side-effects. Further studies are required to evaluate the role of low-dose theophylline as an adjunct to low-dose inhaled steroids in the management of chronic asthma. It may now be appropriate to re-evaluate the role of theophylline in asthma management.
Notes: Journal Article
Review, Tutorial
Author Address: Dept of Thoracic Medicine, National Heart and Lung Institute, London, UK.

Title: The Bronchodilator Effects and Pharmacokinetics of Caffeine in Asthma
Author: Becker, A. B.; Simons, K. J.; Gillespie, C. A.; Simons, F. E.; (Date: Mar 22, 1984)
Journal: N Engl J Med; V. 310; Issue: 12; Pages: 743-6

Abstract: We compared the bronchodilator effects and pharmacokinetics of orally administered caffeine (10 mg per kilogram of body weight) and theophylline (5 mg per kilogram) in a double-blind, single-dose study in asthmatic patients 8 to 18 years of age. After 48 hours of withdrawal of all methylxanthines, 13 patients received caffeine and 10 received theophylline. Significant improvements in forced vital capacity, forced expiratory volume in one second, and forced expiratory flow rates occurred from one to six hours after administration of either caffeine or theophylline. The bronchodilator effect of caffeine did not differ significantly from that of theophylline and was maximal two hours after ingestion of each drug. Peak serum levels of caffeine (13.5 +/- 2.9 mg per liter) occurred at one hour, and peak levels of theophylline (8.4 +/- 1.7 mg per liter) at 2.2 +/- 0.8 hours. The mean serum half-time for caffeine was 3.9 +/- 1.4 hours and that for theophylline was 5.8 +/- 1.7 hours. All patients receiving caffeine metabolized it to paraxanthine, theobromine, and theophylline. Mild, transient side effects were seen after both caffeine and theophylline. Vital signs did not change significantly after either drug. We conclude that caffeine, a commonly available chemical, is an effective bronchodilator in young patients with asthma.
Notes: Journal Article

Title: A Review of Latest Research Findings on the Health Promotion Properties of Tea
Author: Dufresne, C. J.; Farnworth, E. R.; (Date: Jul, 2001)
Journal: J Nutr Biochem; V. 12; Issue: 7; Pages: 404-421

Abstract: Important progress has been made in the past five years concerning the effects of green and black tea on health. Experimentation with new accurate tools provide useful information about the metabolism of tea components in the body, their mode of action as antioxidants at the cellular level and their protective role in the development of cancer, cardiovascular disease and other pathologies. The use of tea components as nutraceuticals and functional foods are also discussed.
Author Address: Food Research and Development Centre, Agriculture and Agri-food Canada, 3600 Casavant Boulevard West, J2S 8E3, Saint Hyacinthe, Quebec, Canada

Title: Caffeine Effects on Cardiovascular and Neuroendocrine Responses to Acute Psychosocial Stress and Their Relationship to Level of Habitual Caffeine Consumption
Author: Lane, J. D.; Adcock, R. A.; Williams, R. B.; Kuhn, C. M.; (Date: May-Jun, 1990)
Journal: Psychosom Med; V. 52; Issue: 3; Pages: 320-36

Abstract: The effects of a moderate dose of caffeine on cardiovascular and neuroendocrine stress reactivity were examined in 25 healthy male subjects selected as habitual or light consumers of caffeine. Measurements were taken under resting conditions before and after administration of caffeine (3.5 mg/kg) or placebo, during a stressful laboratory task, and in a post-stress recovery period. Caffeine elevated blood pressure and plasma norepinephrine levels at rest, effects which added significantly to the effects of stress. Caffeine potentiated stress-related increases in plasma epinephrine and cortisol stress, more than doubling the responses observed in the control condition. These effects were present in both habitual and light consumers and level of habitual caffeine consumption did not affect their magnitude. Results indicate that caffeine can potentiate both cardiovascular and neuroendocrine stress reactivity and that the habitual use of caffeine is not necessarily associated with the development of tolerance to these effects.
Notes: Clinical Trial
Controlled Clinical Trial
Journal Article
Author Address: Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.

Title: Comparative Effects of Theophylline and Caffeine on Respiratory Function of Prematurely Born Infants
Author: Laubscher, B.; Greenough, A.; Dimitriou, G.; (Date: Jan 9, 1998)
Journal: Early Hum Dev; V. 50; Issue: 2; Pages: 185-92

Abstract: The aim of this study was to determine the relative effects of theophylline and caffeine on neonatal respiratory function. Fifty-three preterm infants (45 infants with a median gestational age of 28 weeks, range 24-34 weeks completed the protocol) were randomized to receive either theophylline (loading dose 4 mg/kg followed by 4 mg/kg/day) or caffeine (loading dose 10 mg/kg followed by 5 mg/kg/day). Compliance of the respiratory system (CRS), strength of Hering Breuer reflex and the inspired oxygen concentration requirement were measured immediately prior to, 24 h and 7 days after commencing therapy. There was no statistically significant difference in the patient characteristics of the two groups, but only the theophylline group contained immature infants (i.e. < 26 weeks gestational age (n = 7)). At 24 h, there was a significant improvement in CRS and reduction in supplementary oxygen requirements in the caffeine group (p < 0.01), in the theophylline group no such significant effects were seen. In the study population overall, after 7 days of treatment in both the theophylline and caffeine groups there was an improvement in CRS (p < 0.05 and p < 0.01 respectively) and a reduction in the inspired oxygen concentration (p < 0.05 and p < 0.01 respectively). There was, however, a significant reduction in the strength of the Hering Breuer reflex only in the caffeine group (p < 0.05) and this was a decrease which related to the change in CRS (p < 0.05). The only statistically significant difference in the magnitude of change in CRS, reflex strength or supplementary oxygen requirements between the two groups was that the reduction in inspired oxygen requirement in the caffeine group was greater than that in the theophylline treated infants at 24 h (p < 0.05). We conclude theophylline and caffeine have similar effects on neonatal respiratory function, but our results suggest caffeine administration may be associated with an earlier onset of action.
Notes: Clinical Trial
Journal Article
Randomized Controlled Trial
Author Address: Dept of Child Health, King’s College Hospital, London, UK.

Title: Coffee Consumption and Total Body Water Homeostasis as Measured by Fluid Balance and Bioelectrical Impedance Analysis
Author: Neuhauser, Berthold; Beine, S.; Verwied, S. C.; Luhrmann, P. M.; 1997)
Journal: Ann Nutr Metab; V. 41; Issue: 1; Pages: 29-36

Abstract: To investigate the impact of coffee consumption on fluid balance, 12 healthy volunteers were supplied with a standardized diet for 2 days after having abstained from consumption of methylxanthines for 5 days. During the first day, fluid requirement was met by mineral water. On the following day the same amount of fluid was supplied and the mineral water was in part replaced by 6 cups of coffee containing 642 mg of caffeine. This led to an increase in 24-hour urine excretion of 753 +/- 532 ml (p < 0.001), a corresponding negative fluid balance and a concomitant decrease in body weight of 0.7 +/- 0.4 kg (p < 0.001). Total body water as measured with bioelectrical impedance analysis decreased by 1.1 +/- 1.2 kg or 2.7% (p < 0.01). Urinary excretion of sodium and potassium was elevated by 80 +/- 62 mmol or 66% (p < 0.01) and 14 +/- 12 mmol or 28% (p < 0.01), respectively.
Notes: Clinical Trial
Journal Article
Author Address: Institute of Nutritional Sciences, Justus Liebig University, Giessen, Germany.

Title: Coffee Drinking and Prevalence of Bronchial Asthma
Author: Pagano, R.; Negri, E.; Decarli, A.; La Vecchia, C.; (Date: Aug, 1988)
Journal: Chest; V. 94; Issue: 2; Pages: 386-9

Abstract: The relationship between coffee consumption and the prevalence of bronchial asthma has been evaluated using data from the 1983 Italian National Health Survey, based on 72,284 individuals aged over 15 years randomly selected within strata of geographic area, size of the place of residence and of the household in order to be representative of the whole Italian population. The prevalence of bronchial asthma was inversely related with the level of coffee intake. Compared with subjects who did not drink coffee, the age- and sex-adjusted relative risks were 0.95 for one cup, 0.77 for two and 0.72 for three or more cups per day. This inverse relation was of comparable magnitude at younger and older ages, not explainable through selection, since the sample was representative of the general Italian population and the participation rate was 93.4 percent, or through confounding by several identified potential distorting factors. Thus, the results of this survey provide epidemiologic confirmation of previous clinical observations that caffeine intake has a bronchodilator effect in asthma, and indirectly suggest that long-term moderate coffee consumption may not only reduce symptoms, but also prevent the clinical manifestation of bronchial asthma. An alternative explanation of these findings is that subjects receiving treatment for asthma might tend to reduce their coffee consumption, in consequence of the side effects shared by sympathomimetics, theophylline and caffeine. Thus, further studies taking simultaneously into account methylxanthine intake from beverages and drug treatments are required before considering causal the apparent protection which emerged.
Notes: Journal Article
Author Address: Istituto Centrale di Statistica, Rome, Italy.

Title: Recent Advances in Our Understanding of the Use of Theophylline in the Treatment of Asthma
Author: Page, C. P.; (Date: Mar, 1999)
Journal: J Clin Pharmacol; V. 39; Issue: 3; Pages: 237-40

Abstract: The use of theophylline for the treatment of asthma for 45 of the past 50 years has been for its ability to dilate bronchi. The problem has been that at the most effective bronchodilating dose, toxicity was too close for comfort. In the past 5 years, there has been resurgence in theophylline use at lower doses because of some well-documented anti-inflammatory and steroid sparing effects.
Notes: Journal Article
Review, Tutorial
Author Address: Sackler Institute of Pulmonary Pharmacology, King’s College London, England.

Title: Behavioral and Cognitive Effects of Methylxanthines. A Meta-Analysis of Theophylline and Caffeine
Author: Stein, M. A.; Krasowski, M.; Leventhal, B. L.; Phillips, W.; Bender, B. G.; (Date: Mar, 1996)
Journal: Arch Pediatr Adolesc Med; V. 150; Issue: 3; Pages: 284-8

Abstract: BACKGROUND: Theophylline has been extensively studied as a treatment of asthma. However, some studies have suggested that theophylline may precipitate adverse behavioral and cognitive effects on children. Other reports have evaluated the effects of caffeine, another commonly used methylxanthine, as a treatment of attention-deficit hyperactivity disorder. OBJECTIVE: To present a meta-analysis of research on the behavioral and cognitive effects of methylxanthines in children. METHODS: The meta-analyses were conducted on 12 studies of theophylline and nine studies of caffeine that met inclusion criteria. RESULTS: In contrast to popular beliefs and earlier scientific reports, meta-analyses of controlled studies did not indicate that either theophylline or caffeine resulted in significant deleterious effects on cognition or behavior. In fact, there was a small, positive effect on parental report of externalizing behavior for both methylxanthines. CONCLUSIONS: There is little evidence to suggest that methylxanthines have adverse cognitive or behavioral effects on children. Questions remain with regard to the identification and determinants of either responsive or sensitive subgroups, dose-response relationships, and the effects of parent-teacher expectancies on behavioral ratings.
Notes: Journal Article
Author Address: Section of Child and Adolescent Psychiatry, Department of Psychiatry, University of Chicago (Ill), USA.

Title: Effects of Tea Consumption on Nutrition and Health
Author: Yang, C. S.; Landau, J. M.; (Date: Oct, 2000)
Journal: J Nutr; V. 130; Issue: 10; Pages: 2409-12

Abstract: Beneficial health effects of tea have been demonstrated in animal experiments and some human studies. The two most extensively investigated diseases are cancer and heart disease. Although mechanisms of protective activity of tea against these diseases have been proposed, there are inconsistencies in the relationship between tea consumption and the risk of these diseases in humans. The bioavailability of active components is beginning to be understood, but further research is required to determine whether the results from animal studies are applicable to humans. Also discussed are the possible effects of tea in increasing thermogenesis and bone density as well as decreasing risk of cataracts and arthritis. The potential health benefits of tea consumption warrant further investigation.
Notes: Journal Article
Review, Tutorial
Author Address: Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.

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