Coffee: grounds for concern? Allen B. Weisse, MD
C
affeine is the most widely ingested nonregulated substance on earth. A major portion of this drug is consumed as coffee, with an annual production of over 7.8 million metric tons. Over 2.5 billion cups of coffee are consumed worldwide each day. Given its popularity, it is hard to conceive of how Western civilization might begin each workday without this critical liquid allotment. Despite the prominent role it has assumed in our daily lives, comparatively little about it has been published in the strictly academic press over the past 300 years or more. The most comprehensive compilation of this literature is, undoubtedly, contained in the two-volume collection of von Hünersdorff and Hasenkamp (1). Included within these 1661 pages are over 16,000 references. However, there is no index, making it difficult to use for research. Furthermore, almost all references predate the late 20th century and thereafter. The references themselves are principally works concerning the distribution, planting, preparation, and other aspects of coffee, with few representing physiological studies or what we would now consider adequate population studies. Often referred to as “the bible” of pharmacology, Goodman and Gilman does not even list coffee among its references and only includes a few remarks about symptoms related to caffeine withdrawal (2). Fortunately, a number of excellent monographs concerning coffee and caffeine have appeared in recent years, and two of these were consulted for this article (3, 4). As well entrenched as coffee is in our daily lives, it might be difficult for some to imagine the trials and tribulations coffee has endured over the centuries. Significant consumption of coffee spread from the Middle East and Africa to Europe in the latter half of the 17th century. The first coffeehouse in England opened in Oxford in 1637. The first in France opened in 1639. Before this, in large cities such as London, the available drinking water was so vile that those who could would fortify themselves with various kinds of beer or wine each morning. On switching to coffee, such consumers were immediately struck by the improvement in their mental alertness and clarity, as the haze of alcohol was removed from the start of each day, and coffeehouses soon became centers of lively debate and enlightened conjecture. This dichotomy of response between alcohol and coffee is well recognized by all today. While coffeehouses became centers of lively debate and conjecture for the concerned public, they were soon seen by
122
some monarchs and other autocrats as breeding places of sedition and unrest. One memorable attempt to abolish them was that of Charles the Second of England. In 1675 he issued a decree banning coffeehouses. This attempt to prohibit the consumption of coffee was no more successful than a similar decree by the ruler of Mecca in 1511. The uproar this caused was so intense that the decree was revoked 11 days following the initial pronouncement. Other attempts to restrict or abolish coffee drinking have also been unsuccessful. A notable response in Germany to such sentiments was Johann Sebastian Bach’s Coffee Cantata (1732), in which, under the glaring disapproval of her father, the young heroine’s right to ingest her favorite beverage is championed. In the United States, another source of opposition was probably related to a puritanical streak that remains with us to this day. It implies that anything that is pleasurable must, ipso facto, be evil. The critic and journalist Alexander Woollcott expressed this in his own inimitable way: All the things I really like to do are illegal, immoral, or fattening. While no one could ever condemn coffee as fattening, some opposed it either on ethical or religious grounds. To this day, coffee—as well as other caffeineladen drinks—is prohibited by the Church of Jesus Christ of Latter-Day Saints, for example. The specific questions regarding the health effects of coffee have only been addressed relatively recently in historical terms, perhaps only during the last five or six decades. One gathers in reading such reports that concerns arose based on suspicions that, more likely than not, bad things could happen to you if you indulged in coffee drinking. What bad things might there be? Many of the complaints about coffee relate to the direct effects of caffeine, to which there is a wide variability in sensitivity. For the highly sensitive imbiber, problems such as insomnia, nervousness, restlessness, anxiety, and palpitations related to extrasystoles are common but easily reversed by reducing intake or abstaining. A withdrawal syndrome including such symptoms as headache and irritability has been described (5). Of greater importance is the possibility of an increased risk of spontaneous abortion among pregnant women consuming large amounts of coffee (6). From the Department of Medicine (retired), Rutgers–New Jersey Medical School. Corresponding author: Allen B. Weisse, MD, 164 Hillside Avenue, Springfield, NJ 07081 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2015;28(1):122–123
Recently a coffee genome has been generated (18). Perhaps secrets about this incredible plant will be disclosed through this investigatory portal. In the meantime, we can all take comfort in continuing to discuss this and other promising breakthroughs in medical science—perhaps over some cups of steaming hot delicious coffee.
Table. Some benefits of coffee Lowers risk of Parkinson’s disease Reduces risk of prostate cancer Reduces risk of liver cancer Decreases risk of type 2 diabetes Protects against cirrhosis Decreases risk of depression in women Reduces mortality
1. 2.
The possibility of an increased risk of developing cancer by coffee drinking has been entertained for some years. A high point in this literature was reached in 1981 with an article in the New England Journal of Medicine claiming that “a strong association between coffee consumption and pancreatic cancer was evident in both sexes” (7). However, other groups of investigators performing similar studies were unable to confirm these results, and the study is now considered to have been flawed (8). Let us now consider some of the notable benefits of coffee drinking reported relatively recently (Table). Coffee has been found to lower the risk of developing Parkinson’s disease (9). Rather than increase susceptibility to cancer, coffee has been found to prevent both prostate cancer (10) and liver cancer (11). The risk of developing type 2 diabetes is reduced (12, 13). Coffee has also been found to protect against cirrhosis of the liver (14); decrease the risk of depression among women (15); and decrease total and cause-specific mortality (16). We continue to discover new things about caffeine itself. In 1989, a report from Boston appeared demonstrating extreme daytime sleepiness rather than acuity in five heavy coffee drinkers who finally wound up for evaluation in a sleep laboratory (17). The effects of the sleepiness upon their daily routines were often considerable. Although the incidence of extreme daytime sleepiness is not known, the condition seems to be somewhat rare but not insignificant. All individuals returned to a normal sleeping/awake pattern of behavior upon eliminating caffeine from their diet. How can this occur? Normally adenosine has a sedating effect, but caffeine eliminates this effect by blocking the adenosine receptors in the central nervous system. However, in a few patients, coffee triggers an overly robust response with an increase in adenosine and the number of receptors to counteract the caffeine. This accounts for somnolence rather than the usual increase in awareness among these individuals. While this response might prove disabling in some patients, as reported by Regestein, in others this effect might prove tolerable or even desirable when ingesting coffee shortly before retiring. In reviewing the multitude of effects that coffee has demonstrably elicited, one must conclude that all of these are not due to the effects of caffeine alone. There are many other chemically active substances in coffee, and we are just beginning to recognize what they are and what they do. Within each coffee bean are carbohydrates, proteins, phosphates, volatile and nonvolatile acids, and, of great interest, polyphenols with their antioxidant properties. How do they relate to reducing the risk of such diverse conditions as cancer, cirrhosis, and Parkinson’s disease? January 2015
3. 4. 5.
6.
7. 8. 9.
10.
11.
12. 13.
14. 15.
16.
17. 18.
von Hünersdorff R, Hasenkamp HG. Coffee: A Bibliography (2 Vols). London: Hünersdorff, 2002. Brunton LL, Chabner BA, Knollman BC, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw Hill, 2011:663. Pendergrast M. Uncommon Grounds: The History of Coffee and How It Transformed Our World, rev. ed. New York: Basic Books, 2010. Weinberg BA, Bealer BK. The World of Caffeine. The Science and Culture of the World’s Most Popular Drug. New York: Routledge, 2001. Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 1992;327(16):1109–1114. Klebanoff MA, Levine RJ, DerSimonian R, Clemens JD, Wilkins DG. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341(22):1639–1644. MacMahon B, Yen S, Trichopoulos D, Warren K, Nardi G. Coffee and cancer of the pancreas. N Engl J Med 1981;304(11):630–633. Gordis L. Consumption of methylxanthine-containing beverages and risk of pancreatic cancer. Cancer Lett 1990;52(1):1–12. Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000;283(20):2674–2679. Wilson KM, Kasperzyk JL, Rider JR, Kenfield S, van Dam RM, Stampfer MJ, Giovannucci E, Mucci LA. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst 2011;103(11):876–884. Inoue M, Yoshimi I, Sobue T, Tsugane S; JPHC Study Group. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J Natl Cancer Inst 2005;97(4):293–300. van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005;294(1):97–104. Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Arch Intern Med 2006;166(12):1311–1316. Klatsky AL, Morton C, Udaltsova N, Friedman GD. Coffee, cirrhosis, and transaminase enzymes. Arch Intern Med 2006;166(11):1190–1195. Lucas M, Mirzaei F, Pan A, Okereke OI, Willett WC, O’Reilly ÉJ, Koenen K, Ascherio A. Coffee, caffeine, and risk of depression among women. Arch Intern Med 2011;171(17):1571–1578. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012;366(20):1891–1904. Regestein QR. Pathologic sleepiness induced by caffeine. Am J Med 1989;87(5):586–588. Denoeud F, Carretero-Paulet L, Dereeper A, Droc G, Guyot R, Pietrella M, Zheng C, Alberti A, Anthony F, Aprea G, Aury JM, Bento P, Bernard M, Bocs S, Campa C, Cenci A, Combes MC, Crouzillat D, Da Silva C, Daddiego L, De Bellis F, Dussert S, Garsmeur O, Gayraud T, Guignon V, Jahn K, Jamilloux V, Joët T, Labadie K, Lan T, Leclercq J, Lepelley M, Leroy T, Li LT, Librado P, Lopez L, Muñoz A, Noel B, Pallavicini A, Perrotta G, Poncet V, Pot D, Priyono, Rigoreau M, Rouard M, Rozas J, Tranchant-Dubreuil C, VanBuren R, Zhang Q, Andrade AC, Argout X, Bertrand B, de Kochko A, Graziosi G, Henry RJ, Jayarama, Ming R, Nagai C, Rounsley S, Sankoff D, Giuliano G, Albert VA, Wincker P, Lashermes P. The coffee genome provides insight into the convergent evolution of caffeine biosynthesis. Science 2014;345(6201):1181–1184.
Coffee: grounds for concern?
123
C
affeine is the most widely ingested nonregulated substance on earth. A major portion of this drug is consumed as coffee, with an annual production of over 7.8 million metric tons. Over 2.5 billion cups of coffee are consumed worldwide each day. Given its popularity, it is hard to conceive of how Western civilization might begin each workday without this critical liquid allotment. Despite the prominent role it has assumed in our daily lives, comparatively little about it has been published in the strictly academic press over the past 300 years or more. The most comprehensive compilation of this literature is, undoubtedly, contained in the two-volume collection of von Hünersdorff and Hasenkamp (1). Included within these 1661 pages are over 16,000 references. However, there is no index, making it difficult to use for research. Furthermore, almost all references predate the late 20th century and thereafter. The references themselves are principally works concerning the distribution, planting, preparation, and other aspects of coffee, with few representing physiological studies or what we would now consider adequate population studies. Often referred to as “the bible” of pharmacology, Goodman and Gilman does not even list coffee among its references and only includes a few remarks about symptoms related to caffeine withdrawal (2). Fortunately, a number of excellent monographs concerning coffee and caffeine have appeared in recent years, and two of these were consulted for this article (3, 4). As well entrenched as coffee is in our daily lives, it might be difficult for some to imagine the trials and tribulations coffee has endured over the centuries. Significant consumption of coffee spread from the Middle East and Africa to Europe in the latter half of the 17th century. The first coffeehouse in England opened in Oxford in 1637. The first in France opened in 1639. Before this, in large cities such as London, the available drinking water was so vile that those who could would fortify themselves with various kinds of beer or wine each morning. On switching to coffee, such consumers were immediately struck by the improvement in their mental alertness and clarity, as the haze of alcohol was removed from the start of each day, and coffeehouses soon became centers of lively debate and enlightened conjecture. This dichotomy of response between alcohol and coffee is well recognized by all today. While coffeehouses became centers of lively debate and conjecture for the concerned public, they were soon seen by
122
some monarchs and other autocrats as breeding places of sedition and unrest. One memorable attempt to abolish them was that of Charles the Second of England. In 1675 he issued a decree banning coffeehouses. This attempt to prohibit the consumption of coffee was no more successful than a similar decree by the ruler of Mecca in 1511. The uproar this caused was so intense that the decree was revoked 11 days following the initial pronouncement. Other attempts to restrict or abolish coffee drinking have also been unsuccessful. A notable response in Germany to such sentiments was Johann Sebastian Bach’s Coffee Cantata (1732), in which, under the glaring disapproval of her father, the young heroine’s right to ingest her favorite beverage is championed. In the United States, another source of opposition was probably related to a puritanical streak that remains with us to this day. It implies that anything that is pleasurable must, ipso facto, be evil. The critic and journalist Alexander Woollcott expressed this in his own inimitable way: All the things I really like to do are illegal, immoral, or fattening. While no one could ever condemn coffee as fattening, some opposed it either on ethical or religious grounds. To this day, coffee—as well as other caffeineladen drinks—is prohibited by the Church of Jesus Christ of Latter-Day Saints, for example. The specific questions regarding the health effects of coffee have only been addressed relatively recently in historical terms, perhaps only during the last five or six decades. One gathers in reading such reports that concerns arose based on suspicions that, more likely than not, bad things could happen to you if you indulged in coffee drinking. What bad things might there be? Many of the complaints about coffee relate to the direct effects of caffeine, to which there is a wide variability in sensitivity. For the highly sensitive imbiber, problems such as insomnia, nervousness, restlessness, anxiety, and palpitations related to extrasystoles are common but easily reversed by reducing intake or abstaining. A withdrawal syndrome including such symptoms as headache and irritability has been described (5). Of greater importance is the possibility of an increased risk of spontaneous abortion among pregnant women consuming large amounts of coffee (6). From the Department of Medicine (retired), Rutgers–New Jersey Medical School. Corresponding author: Allen B. Weisse, MD, 164 Hillside Avenue, Springfield, NJ 07081 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2015;28(1):122–123
Recently a coffee genome has been generated (18). Perhaps secrets about this incredible plant will be disclosed through this investigatory portal. In the meantime, we can all take comfort in continuing to discuss this and other promising breakthroughs in medical science—perhaps over some cups of steaming hot delicious coffee.
Table. Some benefits of coffee Lowers risk of Parkinson’s disease Reduces risk of prostate cancer Reduces risk of liver cancer Decreases risk of type 2 diabetes Protects against cirrhosis Decreases risk of depression in women Reduces mortality
1. 2.
The possibility of an increased risk of developing cancer by coffee drinking has been entertained for some years. A high point in this literature was reached in 1981 with an article in the New England Journal of Medicine claiming that “a strong association between coffee consumption and pancreatic cancer was evident in both sexes” (7). However, other groups of investigators performing similar studies were unable to confirm these results, and the study is now considered to have been flawed (8). Let us now consider some of the notable benefits of coffee drinking reported relatively recently (Table). Coffee has been found to lower the risk of developing Parkinson’s disease (9). Rather than increase susceptibility to cancer, coffee has been found to prevent both prostate cancer (10) and liver cancer (11). The risk of developing type 2 diabetes is reduced (12, 13). Coffee has also been found to protect against cirrhosis of the liver (14); decrease the risk of depression among women (15); and decrease total and cause-specific mortality (16). We continue to discover new things about caffeine itself. In 1989, a report from Boston appeared demonstrating extreme daytime sleepiness rather than acuity in five heavy coffee drinkers who finally wound up for evaluation in a sleep laboratory (17). The effects of the sleepiness upon their daily routines were often considerable. Although the incidence of extreme daytime sleepiness is not known, the condition seems to be somewhat rare but not insignificant. All individuals returned to a normal sleeping/awake pattern of behavior upon eliminating caffeine from their diet. How can this occur? Normally adenosine has a sedating effect, but caffeine eliminates this effect by blocking the adenosine receptors in the central nervous system. However, in a few patients, coffee triggers an overly robust response with an increase in adenosine and the number of receptors to counteract the caffeine. This accounts for somnolence rather than the usual increase in awareness among these individuals. While this response might prove disabling in some patients, as reported by Regestein, in others this effect might prove tolerable or even desirable when ingesting coffee shortly before retiring. In reviewing the multitude of effects that coffee has demonstrably elicited, one must conclude that all of these are not due to the effects of caffeine alone. There are many other chemically active substances in coffee, and we are just beginning to recognize what they are and what they do. Within each coffee bean are carbohydrates, proteins, phosphates, volatile and nonvolatile acids, and, of great interest, polyphenols with their antioxidant properties. How do they relate to reducing the risk of such diverse conditions as cancer, cirrhosis, and Parkinson’s disease? January 2015
3. 4. 5.
6.
7. 8. 9.
10.
11.
12. 13.
14. 15.
16.
17. 18.
von Hünersdorff R, Hasenkamp HG. Coffee: A Bibliography (2 Vols). London: Hünersdorff, 2002. Brunton LL, Chabner BA, Knollman BC, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw Hill, 2011:663. Pendergrast M. Uncommon Grounds: The History of Coffee and How It Transformed Our World, rev. ed. New York: Basic Books, 2010. Weinberg BA, Bealer BK. The World of Caffeine. The Science and Culture of the World’s Most Popular Drug. New York: Routledge, 2001. Silverman K, Evans SM, Strain EC, Griffiths RR. Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 1992;327(16):1109–1114. Klebanoff MA, Levine RJ, DerSimonian R, Clemens JD, Wilkins DG. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341(22):1639–1644. MacMahon B, Yen S, Trichopoulos D, Warren K, Nardi G. Coffee and cancer of the pancreas. N Engl J Med 1981;304(11):630–633. Gordis L. Consumption of methylxanthine-containing beverages and risk of pancreatic cancer. Cancer Lett 1990;52(1):1–12. Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000;283(20):2674–2679. Wilson KM, Kasperzyk JL, Rider JR, Kenfield S, van Dam RM, Stampfer MJ, Giovannucci E, Mucci LA. Coffee consumption and prostate cancer risk and progression in the Health Professionals Follow-up Study. J Natl Cancer Inst 2011;103(11):876–884. Inoue M, Yoshimi I, Sobue T, Tsugane S; JPHC Study Group. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J Natl Cancer Inst 2005;97(4):293–300. van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005;294(1):97–104. Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Arch Intern Med 2006;166(12):1311–1316. Klatsky AL, Morton C, Udaltsova N, Friedman GD. Coffee, cirrhosis, and transaminase enzymes. Arch Intern Med 2006;166(11):1190–1195. Lucas M, Mirzaei F, Pan A, Okereke OI, Willett WC, O’Reilly ÉJ, Koenen K, Ascherio A. Coffee, caffeine, and risk of depression among women. Arch Intern Med 2011;171(17):1571–1578. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. N Engl J Med 2012;366(20):1891–1904. Regestein QR. Pathologic sleepiness induced by caffeine. Am J Med 1989;87(5):586–588. Denoeud F, Carretero-Paulet L, Dereeper A, Droc G, Guyot R, Pietrella M, Zheng C, Alberti A, Anthony F, Aprea G, Aury JM, Bento P, Bernard M, Bocs S, Campa C, Cenci A, Combes MC, Crouzillat D, Da Silva C, Daddiego L, De Bellis F, Dussert S, Garsmeur O, Gayraud T, Guignon V, Jahn K, Jamilloux V, Joët T, Labadie K, Lan T, Leclercq J, Lepelley M, Leroy T, Li LT, Librado P, Lopez L, Muñoz A, Noel B, Pallavicini A, Perrotta G, Poncet V, Pot D, Priyono, Rigoreau M, Rouard M, Rozas J, Tranchant-Dubreuil C, VanBuren R, Zhang Q, Andrade AC, Argout X, Bertrand B, de Kochko A, Graziosi G, Henry RJ, Jayarama, Ming R, Nagai C, Rounsley S, Sankoff D, Giuliano G, Albert VA, Wincker P, Lashermes P. The coffee genome provides insight into the convergent evolution of caffeine biosynthesis. Science 2014;345(6201):1181–1184.
Coffee: grounds for concern?
123
