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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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