24. J.F.Neil, “Caffeinism Complicating Hypersomnic Depressive Syndromes,” Comprehensive Psychiatry 19 (1978): 377–85.
25. D.R.Cherek, “Effects of Caffeine on Human Aggressive Behavior,” Psychiatry Research, 8 (1983): 137–45, and “Regular or Decaffeinated Coffee and Subsequent Human Aggressive Behavior” Psychiatry Research 11 (1984): 251–58.
26. Roache and Griffiths (see note 15).
27. Sleep and wakefulness occur as phases of a cycle called the “circadian rhythm,” with a natural length of about twenty-five hours, a peak in the late afternoon, and a trough between three and four in the morning. Though the pattern of the circadian rhythm is determined primarily from within, external factors, such as the alternation of light and dark and habits of work and leisure, conjoin to “squash” it into twenty-four hours.
28. These characteristic regular patterns in the sleep state, as measured by the EEG, are termed the “sleep structure” and are taken to represent the quality and depth of sleep.
29. Edwards, America’s Favorite Drug, p. 71.
30. As Jan Snel suggests in his paper “Coffee and Caffeine: Sleep and Wakefulness,” the “effects of caffeine on the sleep-wake cycle depend both on the level of arousal, determined by more or less constant ‘trait’ factors, such as age and personality, and by short-term ‘state’ factors, such as time of day, fatigue, or nutritional items” (Garattini, Caffeine, Coffee, and Health, p. 256).
31. Edwards, America‘s Favorite Drug, p. 71.
32. Quentin R. Regestein, “Pathologic Sleepiness Induced by Caffeine,” American Journal of Medicine 87 (1989): 587–88.
33. A. Goldstein, “Wakefulness Caused by Caffeine,” Archiv fur Experimentelle Pathologie und Pharmakologie 248 (1964): 269–78.
34. A recent fad in the United States, using the hormone melatonin to sleep better, as well as to stay young and cure most of humanity’s ills, is interesting for our subject, because caffeine may be a potent suppressor of it. Melatonin is thought to be the natural hormone that some say regulates our internal time clock and sleep patterns. Twenty-five subjects who were given 200 mg of caffeine tablets experienced a significant reduction in melatonin levels in their blood that persisted for eight hours. The peak serum levels of melatonin averaged 25 mg/ml without caffeine but only 14 mg/ml when caffeine had been ingested. According to Jo Robinson, the co-author of a recent authoritative book on melatonin, “If you drink coffee and are under bright lights, you will get an even greater reduction in melatonin levels. Taking supplemental melatonin will offset this effect.” V.K.P.Wright, “Effects of Caffeine, Bright Lights, and Their Combination on Nighttime Melatonin,” Sleep Research 24 (1995): 458.
CHAPTER 17
caffeine dependence intoxication and toxicity
1. N.Bridge, “Coffee-drinking as a Frequent Cause of Disease,” Trans Assoc Am Physicians 8 (1893): 281–88.
2. R.R.Griffiths et al., “Human Coffee Drinking: Manipulation of Concentration and Caffeine Dose” Journal of the Experimental Analysis of Behavior 45 (1986): 133–48.
3. K.Silverman et al., “Withdrawal Syndrome after the Double-Blind Cessation of Caffeine Consumption,” NEJM 327 (1992): 1109–14.
4. See Spiller, Methylxanthine Beverages, and Jack James, Caffeine and Health, p. 33.
5. R.Reeves et al., “Quantitative Changes During Caffeine Withdrawal,” presented at the annual meeting of the College of Problems on Drug Dependence, Palm Beach, Florida, June 1994.
6. Conversation with an anonymous registered nurse. She suggested that clinics performing ambulatory or outpatient surgeries and the American Society of Post Anesthesia Nurses might be able to provide more information about this effect.
7. J.D.McGowan et al., “Neonatal Withdrawal Symptoms after Chronic Ingestion of Caffeine,” Soutbern Medical Journal 81 (1988): 1092–94.
8. Eric Strain et al., “Caffeine Dependence Syndrome: Evidence from Case Histories and Experimental Evaluations,” JAMA 272 (1994): 1043–48.
9. For an expansion of this viewpoint, see Griffiths et al., “Caffeine Dependence,” JAMA, October 1994.
10. Garattini, Caffeine, Coffee, and Health, p. 213.
11. R.R.Griffiths et al., “Relative Abuse Liability of Triazolam: Experimental Assessment in Animals and Humans,” Neuroscience and Biobehavioral Reviews 9 (1985): 133–51.
12. R.R.Griffiths and P.P.Woodson, “Reinforcing Properties of Caffeine: Studies in Humans and Laboratory Animals,” Pharmacology, Biochemistry, and Behavior 29 (1988): 419–27.
13. J.R.Hughes et al., “Indications of Caffeine Dependence in a Population-Based Sample.” In Problems of Drug Dependence, ed. L.S.Harris. Washington, D.C.: U.S. Government Printing Office, NIDA Research Monograph #132 (NIH Publication No. 93–3505), pp. 19–28, 1993.
14. Stephen J.Heishman et al., “Stimulus Functions of Caffeine in Humans: Relation to Dependence Potential,” Neuroscience and Biobehavioral Reviews 16 (1992): 281.
15. Spiller, Methylxanthine Beverages, p. 287.
16. R.R.Griffiths et al., “Human Coffee Drinking: Reinforcing and Physical Dependence Producing Effects of Caffeine,” Journal of Pharmacology and Experimental Therapeutics 239 (1986): 416–25.
17. J.T.Rugh, “Profound Toxic Effects from the Drinking of Large Amounts of Strong Coffee,” Medical and Surgical Reporter 75 (1896): 549–50.
18. “A Letter to the Editor of JAMA,” 62 (1914): 1828–29, by Otis Orendorff, M.D., Canon City, Colorado.
19. Water intoxication is a result of lowering the sodium balance in the blood, creating sensations similar to drunkenness, and can be achieved only by gulping at least twenty-four quarts of water a day. It’s a transient pleasure at best, vanishing when, as quickly occurs with urination, the body adjusts this level to normal. According to one neuropharmacologist’s report, a man actually died from drinking too much water while high on the drug ecstasy at a rave party.
By the way, someone must have been eating tea as well, at least in the nineteenth century, to judge by Alcott’s comments in 1839 “that the eaters of tea grounds are especially noted for this leathery complexion…as a considerable part of the tanning properties remains in the tea leaves after it has been infused in the usual manner.” William Alcott, Tea and Coffee, Boston 1839, p. 22.
20. Jack James, Caffeine and Health, p. 69.
21. Ibid., p. 68.
22. S.Jokela and A.Vartiainen, “Caffeine Poisoning,” Acta Pharmacologica et Toxicologica 15: (1959): 331–34.
23. J.E.Turner and R.H.Cravey, “A Fatal Ingestion of Caffeine,” Clinical Toxicology 10, no. 3 (1977): 341–44.
24. R.V.Nagesh and K.A.Murphy, “Caffeine Poisoning Treated by Hemoperfusion,” American Journal of Kidney Diseases 12 (1988): 316–18. See also Jack James, Caffeine and Health, p. 68.
25. R.L.Alsott et al., “Report of a Human Fatality Due to Caffeine,” Journal of Forensic Sciences 14 (1972): 135–37. See also J.Bryant, “Suicide by Ingestion of Caffeine—Letter” Archives of Pathology and Laboratory Medicine 105 (1981): 685–86.
26. P.B.Kulkarni and R.D.Dorand, “Caffeine Toxicity in the Neonate,” Pediatrics 64 (1979): 254–55.
27. V.J.M.Dimaio and J.C.Garriott, “Lethal Caffeine Poisoning in a Child,” Forensic Science 3 (1974): 275–78.
EPILOGUE
a toast to the future
1. We don’t know if any autopsy data is available, but probably there is caffeine in most corpses.
2. Pomet, Lemery, and Tournefort, A Compleat History of DRUGGS, “Of FRUITS,” Of Chocolate, p. 132.
3. Spiller, Methylxanthine Beverages, p. 188.
APPENDIX C
additional studies of caffeine physical effects
1. Hypertension Detection and Follow-up Program Cooperative Group, “Five-Year Findings of the Hypertension Detection and Follow-up Program,” JAMA 242 (1979): 2562–71.
2. B.H.Sung, “Caffeine Elevates Blood Pressure Response to Exercise in Mild Hypertensive Men,” American Joumal of Hypertension, December 1995.
3. K.M.Piters, “Coffee Boosts Pain-Free Walking Time for Patients with Chronic Stable Angina” (presented to the Western Section of the American Association for Clinical Research, Carmel, California), Medical World News, March 12, 1984, p. 137.
4. Garattini, Caffeine, Coffee, and Health, p. 178.
5. S.Cohen and J.H.J.Booth, “Gastric Acid Secretion and Lower-Esophagaeal-Sphincter Pressure in Response to Coffee and Caffeine,” NEJM 293 (1975): 897–99.
6. Contradictory data abound. Later studies have suggested that caffeine is capable of stimulating gastric acid secretion and that its effects in this respect are additive to the same effects produced by other ingredients of coffee. Other studies have found that caffeine may be the only agent that stimulates gastric acid secretion without increasing lower esophageal-sphincter pressure.
7. Bruce Goldfarb, “Caffeine Increases Severity of PMS,” USA Today, September 24, 1990, p. 1D, citing Heinke Bonnlander, American Journal of Public Health, September 1990.
8. From a pamphlet issued jointly by Organon Inc., makers the most popular oral contraceptive, Desogen, and Medical Economics, an excerpt from The PDR Family Guide to Women’s Health and Prescription Drugs, pp. 6–7.
9. R.P.Heaney and R.R.Recker, “Effects of Nitrogen, Phosphorus, and Caffeine on Calcium Balance in Women,” Journal of Laboratory Clinical Medicine 99 (1982): 46–55. M.J. Burger-Lux, R.P.Heaney, and M.R.Stegman, “Effect of Moderate Caffeine Intake on the Calcium Economy of Premenopausal Women,” American Journal of Clinical Nutrition 52 (1990): 722–25.
10. D.P.Kiel et al., “Caffeine and the Risk of Hip Fracture: Framingham Study,” American Journal of Epidemiology 132 (1990): 675–84.
11. E.Barett-Connor et al., “Coffee-Associated Osteoporosis Offset by Daily Milk Consumption,” JAMA 271, no. 4 (1994): 280-83.
12. Ibid.
13. Ibid.
14. C.G.Swift and B.Tiplady, “The Effects of Age on the Response to Caffeine,” Psychopharmacology 94 (1988): 24-31.
15. Edwards, America’s Favorite Drug, p. 71.
16. J.Onrot et al., “Hemodynamic and Humoral Effects of Caffeine in Autonomic Failure, Therapeutic Implications for Post-Prandial Hypotension,” NEJM 313 (1985): 549-54.
17. C.Sue Sewester, ed., Drug Facts and Comparisons, p. 929.
18. Alfred Gilman, ed., Goodman and Gilman’s The Pharmacological Basis of Therapeutics, p. 619.
19. Adapted from D.M.Graham, Nutrition Reviews 36, April 4, 1976, p. 101.
20. Jack James, Caffeine and Health, p. 336.
21. Her talk at the Sleep Research Society meeting in Boston, reported in Marilyn Elias et al., “Coffee and a Wake-Up Call May Help Ground Jet Lag,” USA Today, June 9, 1994, p. 5D.
22. David Robertson et al., “Hemodynamic and Humoral Effects of Caffeine in Autonomic Failure,” NEJM 313 (1985): 549–55.
23. Sewester, Drug Facts, p. 928.
APPENDIX D
methodological pitfalls
1. Garattini, Caffeine, Coffee, and Health, p. 344. Our discussion relies on the work of Alan Leviton, who in his 1992 article “Coffee, Caffeine, and Reproductive Hazards in Humans” provides a clear, well-reasoned expose of a range of protocol defects and the ways in which they can undermine the putative value of a study's conclusions.
2. Ibid., p. 343.
3. Ibid., p. 347.
4. C.M.Friedenreich et al., “An Investigation of Recall Bias in the Reporting of Past Food Intake Among Breast Cancer Cases and Controls,” Annals of Epidemiology 1 (1991): 439-53.
5. L.Fenster et al., “Assessment of Reporting Consistency in a Case Control Study of Spontaneous Abortions” American Journal of Epidemiology 133 (1991): 477-88.
6. A.Aldridge et al., “The Disposition of Caffeine during and after Pregnancy,” Seminars in Prenatal Care 5 (1981): 310–14. See also R.Knutti et al., “The Effect of Pregnancy on the Pharmacokinetics of Caffeine,” Archives of Toxicology (supplement) 5 (1982): 187-92.
7. Garattini, Caffeine, Coffee, and Health, p. 348.
8. J.Istvan and J.D.Matarazzo, “Tobacco, Alcohol, and Caffeine Use: A Review of their Interrelationships,” Psychological Bulletins 95 (1984): 301-26.
9. An example of possible confounding within the area of reproductive hazards is an apparent relationship between coffee consumption and spontaneous abortions. Because nausea is more common in pregnancies that come to term, and nausea decreases the use of coffee, the supposed correlation between coffee and abortions is probably an artifact, because both relatively higher coffee consumption and spontaneous abortions are each co-variables of an unseen underlying factor, in this case, probably suboptimal implantation of the egg in the uterine wall, rather than coffee being a cause of fetal loss. To complicate the question still further, a new supposition has recently arisen that caffeine or coffee interferes with optimal implantation, and may thus be a cause of spontaneous abortions after all.
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