20. Garattini, Caffeine, Coffee, and Health, p. 25.
21. Ibid., p. 184.
22. Ibid.
23. In fact, an important study, conducted in the United States in 1990 and published in The New England Journal of Medicine, found an increase in heart attacks correlated with the consumption of decaffeinated coffee, while observing no such effect for regular coffee. Some scientists explain this difference by adducing the possible role of caffeine in counteracting some of the harmful physiological effects of the coffee in which it is found.
24. Alfred Gilman, Goodman and Gilman’s The Pharmacological Basis of Therapeutics, p. 618.
25. D.R.Lima, “Cigarettes and Caffeine,” Chest 95 (1989): 255–56.
26. James, Caffeine and Health, p. 339.
27. Ibid., p. 22.
28. Garattini, Caffeine, Coffee, and Health, p. 402.
29. Ibid., p. 382.
30. Bonnie Edwards, America‘s Favorite Drug, p. 24.
31. Garattini, Caffeine, Coffee, and Health, p. 34.
32. Ibid., p. 25.
33. A.D.McDonald et al., “Cigarette, alcohol, and coffee consumption and congenital defects,”American Journal of Public Health 82 (1986): 91–93.
34. Marilyn Elias, “Low-Cost Help For Breast-Cyst Pain,” USA Today, April 28, 1992, p. 1D, reporting on a paper presented by Dr. Bruce Drukker, Michigan State University Medical School, East Lansing, addressing the American College of Obstetricians and Gynecologists meeting in Las Vegas in April 1992.
35. Garattini, Caffeine, Coffee, and Health, p. 348.
36. J.L.Brazier and B.Salle, “Conversion of Theophylline to Caffeine by the Human Fetus,” Seminars in Perinatology 5 (1981): 315–20.
37. H.Roberts, “Caffeine Consumption,” paper presented at American Academy of Pediatrics Clinical Pharmacology Session, New Orleans, October 1991.
38. See P.B.Dews, ed., Caffeine, chapter by J.J.Barone and H.Roberts, “Human Consumption of Caffeine.”
39. Committee on GRAS List Survey, Phase III: Estimating Distribution of Daily Intakes of Caffeine, National Academy of Sciences, Washington, D.C.
40. P.B.Dews, “Caffeine Research: An International Overview,” presented at ISLA meeting, Sydney, 1986. See also J.Hathcock, ed., Nutritional Toxicology, chapter by J.Bergman and P. B.Dews, “Dietary Caffeine and Its Toxicity.”
41. Rappoport et al., “Behavioral Effects of Caffeine in Children,” Archives of General Psychology 41 (1984): 1073–79.
42. “Iced Tea and Crazy Kids,” Lidia Wasowicz, UPI Science Writer.
43. Kelly L.Hale and John R.Hughes et al., “Caffeine Self-Administration and Subjective Effects in Adolescents,” Experimental and Clinical Psychopharmacology 3, no. 4 (1995): 364–70.
44. “Vivarin Ad Is Attacked in Philadelphia Inquirer,” United Press International Edition, August 27, 1984, E6.
45. Henry Goldman, “Caffeine Pills Put Man On 3 Years’ Probation,” Philadelphia Inquirer, December 14, 1984.
46. Because cacao contains eight times more theobromine than it does caffeine, theobromine is nearly as important a contributor to its stimulating effects as the smaller amount of caffeine.
47. Theobromine is also highly toxic to dogs, and accidental chocolate poisoning kills quite a few each year. See Clarence M.Fraser, ed., The Merck Veterinary Manual, pp. 1643–44.
48. Garattini, Caffeine, Coffee, and Health, p. 214.
49. “Of all women giving birth in Yale-New Haven Hospital in a four-month period in 1990–1991, only 26% reported no caffeine intake in the first month of pregnancy.” L.Dlugosz and M.B.Bracken, “Reproductive Effects of Caffeine: A Review and Theoretical Analysis,” Epidemological Reviews 14 (1992): 83–98.
50. J.L.Brazier and B.Salle, “Conversion of Theophylline to Caffeine by the Human Fetus,” Seminars in Perinatology 5 (1981): 315–20. See also M.Dumas et al., “Systematic Determination of Caffeine Plasma Concentrations at Birth in Preterm and Fullterm Infants,” Developmental Pharmacology and Therapeutics 4 (1982): 182–86.
51. A.Aldridge et al., “The Disposition of Caffeine during and after Pregnancy,” Seminars in Perinatology 5 (1981): 310–314.
52. “In pregnancy there is a considerable increase in the half-life of caffeine and therefore an increase in exposure,” Garattini, p. 400.
53. S.A.Pearlman et al., “Caffeine Pharmokinetics in Pre-Term Infants Older than Two Weeks,” Developmental Pharmacology and Therapeutics 12 (1989): 65–69.
54. A.Wakamatsu et al., “Change of Plasma Half-Life of Caffeine during Caffeine Therapy for Apnea in Premature Infants,” Acta Paediatrica Japonica 29 (1987): 595–99.
55. Ibid.
56. O.Carrier et al., “Maturation of Caffeine Metabolic Pathways in Infancy,” Clinical Pharmacology and Therapeutics 44 (1988): 145– 51.
57. Ghazi M.Al-Hachim, “The Teratogenicity of Caffeine: A Review,” European Journal of Obstetrics and Gynecology and Reproductive Biology 31 (1988): 237.
58. L.Dlugosz and M.B.Bracken, “Reproductive Effects of Caffeine: A Review and Theoretical Analysis,” Epidemiological Reviews 14 (1992): 83–98.
59. Dlugosz states, “In animal studies, caffeine is teratogenic at doses that are almost impossible to reach in humans, the peak level being more important than the total exposure over time.” Garattini, Caffeine, Coffee, and Health, p. 95.
60. Ibid., p. 353.
61. Victor Cohn, “Caffeine Warning Is Reassessed,” Philadelphia Inquirer, March 2, 1984, p. A3.
62. Jack James, Caffeine and Health, p. 223.
63. J.Olsen et al., “Coffee Consumption, Birthweight, and Reproductive Failures,” Epidemiology 2 (1991): 370–74. See also S.Linn et al., “No Association between Coffee Consumption and Adverse Outcomes of Pregnancy,” NEJM 306 (1982): 141–45.
64. Brenda Eskenazi, “Caffeine During Pregnancy: Grounds for Concern?” JAMA 270, no. 24 (1993): 2973–74. Perhaps surprisingly, the evidence against a positive correlation with prematurity is regarded as evidence in favor of a positive correlation with low birthweight, because it means that increasing rates of prematurity can be ruled out as a contributing factor where low birthweights seem to occur. One researcher cites more than fifteen studies that have examined the relationship between caffeine consumption and low birthweight, claiming that all of the larger and better constructed studies demonstrate no correlation. (See Olsen et al., and Linn et al., note 63). In contrast, citing a 1989 study of caffeine and low birthweight by B.J.Caan and M.K.Goldhaber (“Caffeinated Beverages and Low Birthweight: A Case Controlled Study,” American Journal of Public Health 79 [1989]: 1299–1300), in which caffeine users had three times the likelihood of non-users of delivering a low birthweight baby, Jack James asserts that, although no correlation has been proved, there are serious reasons for concern. A commentary on the literature appearing in JAMA in 1993 agrees with James, asserting that most studies find consumption of more than 300 mg a day increases the risk for low birthweight, while stating that the results for lower consumption levels are ambiguous or conflicting.
65. Linn et al. (see note 63).
66. B.Watkinson and P.A.Fried, “Maternal Caffeine Use before, during, and after Pregnancy and Effects upon Offspring,” Neurobehavioral Toxicology and Teratology 7 (1985): 9–17.
67. B.G.Armstrong et al., “Cigarette, Alcohol, and Coffee Consumption and Congenital Defects,” American Journal of Public Health 82 (1993): 91–93.
68. Until recently, no study had been undertaken to exclude the possible confounding effects of nausea on the relationship between spontaneous abortion and caffeine consumption, the Epiphenomena of Pregnancy: Specifying the Analytic Model,” Epidemiology 2 [1991]: known as the Stein-Susser hypothesis (Z.Stein and M.Susser, “Miscarriage, Caffeine, and 163–67). Because nausea is more common in pregnancies that come to term, aversion for alcohol, food, and caffeine is possible, and such aversion would skew the results of epidemiological studies to falsely suggest that the use of caffeine was correlated with miscarriage. However, one study
, by Kline in 1991, found that an adjustment for nausea and vomiting did not affect the results.
69. A.Goldstein and R.Warren, “Passage of Caffeine into Human Gonadal and Fetal Tissue” Biochemical Pharmacology 11 (1962): 168.
70. Dlugosz and Bracken, p. 90 (see note 58).
71. S.W.Jacobson et al., “Neonatal Correlates of Prenatal Exposure to Smoking, Caffeine, and Alcohol,” Infantile Behavioral Development 7 (1984): 253–65.
72. Eskenazi (see note 64).
73. D.B.Thomas, “Neonatal Abstinence Syndrome,” Medical Journal of Australia 148 (1988): 598.
74. J.D.McGowan et al., “Neonatal Withdrawal Symptoms after Chronic Ingestion of Caffeine,” Southern Medical Journal 81 (1988): 1092–94.
75. J.Tuomilehto et al., “Coffee Consumption as a Trigger for Insulin Dependent Diabetes Milletus in Childhood,” BMJ 300 (1990): 623–42.
76. Eskenazi (see note 64).
77. “Caffeine and Women’s Health,” pamphlet published by the Association of Women’s Health, Obstetric & Neonatal Nurses in conjunction with IFIC, May 1994.
78. M.R.Joesoef et al., “Are Caffeinated Beverages Risk Factors for Delayed Conception?” Lancet (January 20, 1990): 136–37.
79. The credibility of these studies is undermined by confounders. For example, a Danish study of more than ten thousand pregnant women conducted by Olsen in 1991 found a drop in fertility in women who had regularly consumed more than eight cups of coffee or tea a day, but as these women were also smokers, no conclusions about caffeine can be drawn.
A controversial study from Johns Hopkins University of more than fifteen hundred women, conducted by Cynthia Stanton and published in 1995 in the American Journal of Epidemiology found that, of women who neither smoked nor consumed large amounts of caffeine, less than 10 percent took a year or more to conceive, while of women who consumed more than 300 milligrams of caffeine a day, 20 percent took a year or more to conceive. One finding that may at first seem peculiar was that though smokers were about 15 to 20 percent less likely than non-smokers to become pregnant in any given month, their rate of conception was not affected by caffeine intake. A possible explanation is that, because smoking greatly increases the rate of caffeine metabolism, the exposure of smokers is much lower than it otherwise appears.
The merits of the study’s conclusions have been challenged by some fertility specialists. Dr. Mona Shangold, professor of obstetrics and gynecology at the Medical College of Pennsylvania and Hahnemann University, said the study’s protocol was seriously flawed because the investigators made no attempt to control for co-variables such as the frequency of intercourse, or the health and habits of the men involved in the pregnancy attempts. Dr. Shangold concludes women who are trying to become pregnant should not be advised to avoid caffeine on the basis of this article. The National Coffee Association, not surprisingly, agrees that the study should not cause concern.
80. J.V.Ruzich et al., “Objective Assessment of the Effect of Caffeine on Sperm Motility and Velocity,” Fertility and Sterility 48 (1987): 891–93.
81. Jack James, Caffeine and Health, p. 250.
82. Dlugosz and Bracken, p. 90 (see note 58).
83. Garattini, Caffeine, Coffee, and Health, pp. 97–150.
84. Jack James, Caffeine and Health, p. 30.
85. For comparison, consider that Wilcox has determined that two to three hours after consumption, two cups of coffee or a Vivarin would produce urinary levels of only about 3 mg/litre.
86. International Intrigue and Virtue Rewarded as Innocent Britisher Triumphs Over German Attempts to Frame Him as Caffeine Hound:
In 1994 Simon Wigg, a former captain of the England speedway team, before a crowd of 22,000 and on his Czech-made Jawa bike won a record fifth world long-track cycling title in a competition staged in Mariensky-Lasne, in the Czech Republic. According to Speedway Times, a London magazine:
Just a year ago, the British rider won the world title only to be accused of testing positive for excessive caffeine, disqualified and then reinstated when the tests, carried out by the respected Koln Institute in Germany, were discredited,
Wigg’s caffeine level, initially below the minimum limit, was arbitrarily multiplied by a factor of three by the institute, and it was not until the Auto Cycle Union, the governing body in Britain, supported by drug-testing centres in Canada and Australia, strongly objected to the decision, that Wigg’s test was nullified. To add to the suspicions, Karl Maier, a German, would have become the world champion had Wigg’s ban been upheld….
[Despite vindication,] Wigg, twice the British speedway champion and six times the grass-track champion, still lost an estimated £30,000 in sponsorship because of the accusations.
According to the newspaper story, the villain of the tale was the head of the Koln Institute and a member of the medical commission of the International Olympic Committee. Wigg said that if he ever met the man face to face, he would, “punch him on the nose.”
87. Barry Steven Cohen, “Does Caffeine Have An Ergogenic Benefit On Low Intensity Exercise Performance in a Warm Environment?” unpublished manuscript, p. 56, note 110.
88. Ibid., p. 58.
CHAPTER 16
thinking over caffeine
1. H.O.G.Holck, “Effect of Caffeine on Chess Problem Solving,” Journal of Comparative Psychology (1933): 301–11.
2. J.E.Barmack, “The Time of Administration and Some Effects of 2 grams of Alkaloid Caffeine,” Joumal of Experimental Psychology 27 (1940): 690–98.
3. Garattini, Caffeine, Coffee, and Health, p. 296.
4. The information-processing approach consists of studying the flow of information through the system, monitoring the sequence of processing and transformations between input and output. In its various forms, the information-processing metaphor has guided research on quite complex behavior and has allowed the generation of extensive theories concerning the nature of such phenomena as perception, memory, attention, problem solving, language, and decision making. Garattini, Caffeine, Coffee, and Health, p. 301.
5. A.F.Sanders, “Towards a Model of Stress and Human Performance,” Act Psychology 1, no. 53 (1983): 61–97.
6. In a visual-search task, caffeine hurt performance when the target was six letters but helped when it was only two. In a recent study, the ability to solve a maze was unaffected by caffeine, while caffeine promoted the regularity and fluency of letter cancellation task performance.
7. A.C.Bittner et al., “Performance Evaluation Tests for Environmental Research (PETER): Evaluation of 114 measures,” Precept. Mot. Skills 63 (1986): 683–708.
8. This analysis is apparently is in accord with the Yerkes-Dodson principle. See Jack James, Caffeine and Health, p. 250.
9. M.S.Humphreys and W.Revelle, “Personality, Motivation, and Performance: A Theory of the Relationship between Individual Differences and Information Processing,” Psychological Review 91 (1984): 153–84.
10. V.E.Mitchell et al., “Drugs and Placebos: Effects of Caffeine on Cognitive Performance,” Psychological Reports, 35 (1974): 875–83.
11. Segal’s findings were presented in a proceeding of the National Academy of Sciences, October 1999.
12. “In the context of learning and memory, it is interesting to note that xanthines, such as theophylline, enhanced long-term potentiation, an elector-physiological model of memory” in guinea pigs. Y.Tank et al., “Effect of Xanthine Derivatives on Hippocampal Long-term Potentiation,” Brain Research 522 (1990): 63–68.
13. Jack James, Caffeine and Health, p. 305.
14. Ibid., p. 248.
15. J.D.Roache and R.R.Griffiths, “Interactions of Diazepam and Caffeine: Behavioral and Subjective Dose Effects in Humans,” Pharmacology, Biochemistry and Behavior 26 (1987): 801–12.
16. B.H.Jacobson and B.M.Edgley, “Effects of Caffeine on Simple Reaction Time and Movement Time,” Aviation, Space, and Environmental Medicine 58 (1987): 1153–56.
17. W.J.Baker and G.C.Theologus, “Effects of Caffeine on Visual
Monitoring,” Journal of Applied Psychology 56 (1972): 422–27. E.G.Regina et al., “Effects of Caffeine on Alertness in Simulated Automobile Driving” Journal of Applied Psychology 59 (1974): 483–89.
A 1993 study of ten coffee drinkers at Wake Forest University, Winston-Salem, North Carolina, found that caffeine does improve certain reflex brain functions. Subjects drank one or two cups of coffee twenty minutes before beginning “eyeblink startle reflex” tests, consisting of short bursts of “white noise” images. Schiacato, lead researcher, said that the blink reflexes, the sort of involuntary responses that occur too fast for voluntary control, of the coffee drinkers sustained a performance better than the non-drinkers. When exposed to redundant or repeated stimuli, involuntary responses taper off as a result of fatigue. In effect, the brain learns to ignore the stimulus. If caffeine can slow this “ignoring” response, as these experiments suggest, it may increase performance of repetitive tasks, such as driving late at night and seeing the same highway lights, white lines, and road surface, over and over. (“Cup Of Coffee Really Does Perk Up Brain,” USA Today)
18. Michael H.Bonnet et al., “The Use of Caffeine Versus Prophylactic Naps in Sustained Performance,” Sleep 18 (2): 97–104. (The American Sleep Disorders Association and Sleep Research Society)
19. Jack James, “Does Caffeine Enhance or Merely Restore Degraded Psychomotor Performance?” Neuropsychobiology 30 (1994): 124– 25.
20. James, Caffeine and Health, p. 290.
21. W.H.Loke et al., “Caffeine and Diazepam: Separate and Combined Effects on Mood, Memory, and Psychomotor Performance,” Psychopharmacology 87 (1985): 344–50. See also Loke, “Effects of Caffeine on Mood and Memory,” Physiology and Behavior 44 (1988): 367–72.
22. James, Caffeine and Health, p. 294.
23. M.A.Lee, “Anxiety and Caffeine Consumption in People with Anxiety Disorders,” Psychiatry Research 15 (1985): 211–17.
The World of Caffeine Page 55