Brief Critical Review
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1 Brief Critical Review January 2006: Coffee: Good, Bad, or Just Fun? A Critical Review of Coffee s Effects on Liver Enzymes David J. Homan and Sohrab Mobarhan, MD Coffee consumption is a regular part of daily life throughout the world. Research into the effects of coffee on human health is ongoing, but a recent study suggests that coffee and caffeine consumption can reduce the risk of elevated alanine aminotransferase activity in individuals at high risk for liver disease. This review will analyze the results of that study in light of the current literature. Key words: coffee, caffeine, alanine aminotransferase, liver disease 2006 International Life Sciences Institute doi: /nr.2006.jan Coffee has had an important place in human society for at least 1200 years. Legend credits an Ethiopian goat herder with discovering coffee s stimulating effects when he noticed his goats frolicking about after munching on coffee cherries. 1 The first commercial cultivation of coffee occurred in the 14th century in Arabia. Constantinople (now Istanbul) so loved the new drink that Turkish law allowed a wife to divorce her husband for failing to keep the family ibrik, or pot, filled with coffee. 1 Despite close guarding of fertile seeds by Arab cultivators, coffee quickly spread to Europe as the Dutch founded the first European-owned coffee farm on colonial Java, now part of Indonesia. From there, coffee spread to South America and then North America. 1 Brazil is now the world s largest producer of coffee, with just over 33.6 million bags (1 bag weighs 132 pounds) produced in , followed by Colombia (11.8 million bags) and Vietnam (10.75 million bags). 2 Coffee shops dot almost every block in any modern city in the world and we are no more than a few dollars Mr. Homan and Dr. Mobarhan are with the Division of Gastroenterology, Hepatology, and Nutrition, Loyola University Medical Center, Maywood, Illinois, USA. Please address all correspondence to: Dr. Sohrab Mobarhan, Division of Gastroenterology, Hepatology, and Nutrition, Loyola University Medical Center, Maywood, IL 60153; Phone: ; Fax: ; smobarh@lumc.edu. away from any of hundreds of preparations such as Americano, cappuccino, espresso, macchiato, decaf, mocha, Italian roast, medium roast, breakfast, latte, etc. According to the Specialty Coffee Association of America, there are over 100 million Americans who consume an average of 3.1 cups of coffee per day. 3 As a largely nutritionless beverage, coffee is consumed exclusively for its taste and, of course, for its caffeine. Beyond that primary component, nutrition guidelines and research are minimal regarding coffee s effects on the digestive system, particularly the liver. This review focuses on the possible beneficial effect of coffee and caffeine on liver enzymes. A high-power (N 61,107), pooled analysis of two prospective Japanese studies found a statistically significant inverse association between coffee consumption and the incidence risk of primary liver cancer. 4 These results have one major drawback in that they did not consider hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, which are prevalent in Japan. 5 However, in an Italian study, the inverse relationship between coffee consumption and the development of liver cirrhosis was determined to be independent of HBV and HCV infection. 6 Dealing more specifically with the effect of coffee and caffeine on liver enzymes, studies demonstrating an inverse relationship between coffee consumption and levels of serum gamma-glutamyltransferase (GGT) have been conducted in Europe, Asia, and North America. 7,8,9,10 GGT is considered to be a poor but widely used...marker of alcohol intake and, subsequently, liver damage. 7 The inverse relationship is more prominent in heavy consumers of alcohol. 7,8 Aminotransferase (ALT) activity is considered to be a more reliable marker for alcohol-induced hepatic cell injury than is GGT, and a recent study in Europe found an inverse relationship between ALT and coffee consumption. 9 Ruhl and Everhart 11 conducted a large (N 5944) study in the United States to look at the effect of coffee consumption on ALT levels in subjects at high risk for liver damage. 11 To include persons at high risk for the most common causes of chronic liver disease, Nutrition Reviews, Vol. 64, No. 1 43
2 Table 1. Inclusion Criteria for Ruhl and Everhart Study 11 Criterion N More than two alcoholic drinks per day 863 Positive serum hepatitis B surface antigen and core antibody 69 Positive serum hepatitis C antibody 379 Transferrin saturation 50% 473 Hemoglobin A 1C 6.5% (95th percentile) 1185 Diagnosed diabetes 1163 Body-mass index (BMI) 26.9 kg/m 2 (60th percentile) and waist-to-hip ratio at least 0.94 (60th percentile) ,258 persons were screened for participation. Participants were included if they met one or more of the criteria listed in Table 1. Twenty-two percent of the participants had more than one risk factor. Weekly serum ALT samples were drawn on each participant. Each participant also reported their daily coffee consumption in cups per day as one of four categories: none, 1, 1 2, and 2. The consumption of caffeinated tea and sodas was also included to determine each participant s estimated total caffeine intake (mg/d). Among participants, coffee consumption ranged from 0 to 20 cups/d, and the total consumption of caffeine from beverages ranged from 0 to 2954 mg/d. According to the Specialty Coffee Association of America, 75% of Americans list coffee as their only source of caffeine, 3 while in this study 51% of caffeine intake was exclusively from coffee. 11 In the group who estimated their coffee consumption as 0 cups/d, the average serum ALT activity was U/L (Table 1). In the group who estimated their coffee consumption as 1 cups/d (average 0.3 cups/d), the average serum ALT activity was U/L. In the group who estimated their coffee consumption as 1 2 cups/d (average 1.0 cups/d), the average serum ALT activity was U/L. In the group who estimated their coffee consumption as 2 cups/d (average 3.0 cups/d), the average serum ALT activity was U/L. 11 The total daily caffeine consumption increased across each group, from an average of 79 4 mg/d in the group reporting 0 cups/d to an average of mg/d in the group reporting 2 cups/d. When the data were distributed into analytical groups based on average daily caffeine consumption instead of average cups of coffee per day, the results were essentially the same. As caffeine consumption went up from an average of 23 1 mg/d to an average of mg/d, the serum ALT activity decreased from U/L to U/L, respectively (Table 2). 11 With these interesting results, Ruhl and Everhart concluded that among persons at high risk for liver injury, consumption of coffee and caffeine was associated with lower risk of abnormal ALT activity. 11 They reported that persons drinking 2 or more cups of coffee per day had approximately one half the risk of elevated ALT activity, and persons in the highest quintile ( 2 cups daily) were only one third as likely to have elevated ALT activity as those in the lower quintile. They further concluded that these findings suggest that the protective relationships of coffee and caffeine occurred regardless of whether participants were at risk for liver injury. 11 A limitation to the Ruhl and Everhart study is that they did not account for differences in the types of coffee consumed by the participants. For their calculations, they assumed an average amount of caffeine from regular coffee was 136 mg per cup. However, a Canadian study using high-performance liquid chromatography found significant differences in caffeine concentration in coffee prepared from 17 different brands of instant coffee. They also found a considerable range of caffeine concentrations when they analyzed 12 samples of coffee prepared in an office setting by different individuals using the same jar of instant coffee. Additionally, the Canadian study demonstrated a significant day-to-day variability in caffeine concentration in coffee samples from commercial coffee shops. The researchers also found a mean intake of approximately 80 mg of caffeine per cup of coffee prepared both at home and at work. When that amount was used to estimate the daily intake of caffeine Figure 1. Relationship of serum aminotransferase (ALT) activity to coffee consumption Nutrition Reviews, Vol. 64, No. 1
3 Figure 2. Relationship of serum aminotransferase (ALT) activity to caffeine consumption. 11 among self-reporting participants (number of cups/day), the researchers found obvious potential for misrepresentation of individual consumption. Compared with actual consumption, it was found that 39% of selfreporting participants overestimated their caffeine consumption and 36% underestimated their caffeine consumption, while only 25% of participants correctly estimated their caffeine consumption. 12 Additionally, Ruhl and Everhart did not gather data on the study participants consumption of decaffeinated coffee (all of them were assumed to be drinking caffeinated coffee). In order to qualify as decaffeinated coffee in the United States, a coffee must have 97% of its caffeine removed. This results in an average of only 5 mg of caffeine per 5-ounce cup of decaffeinated coffee. A study done by the Coca-Cola Company suggests that standard values for 5 ounces of coffee in the United States are 85 mg of caffeine for ground roast coffee, 60 mg of caffeine for instant coffee, and 3 mg of caffeine for decaffeinated coffee. 13 Caffeine content varies greatly, not only between coffee brands/ types, but among all beverages, as demonstrated by the Mayo Clinic (Table 2). 14 Further, the differences in brewing methods and in the volume of one cup were not considered in the analysis performed by Ruhl and Everhart. There is a great degree of variability in what constitutes a cup of coffee or any other caffeinated beverage. To conduct a study to determine the effect of coffee consumption on any measurable variable, it is important to standardize the volume, type, caffeine content, and brewing method, because a cup of coffee can be defined in an infinite number of ways. Despite these issues, overall, the Ruhl and Everhart study of the relationship between coffee consumption and liver function is highly significant. Whether coffee affects other parts of the alimentary tract is not yet known. An extensive search of the literature showed no studies finding direct action of either coffee or caffeine in human hepatic cells, although one study did explore the effects of the coffee-specific diterpenes, cafestol and kahweol, in human- Table 2. Caffeine Content of Common Beverages 14 Caffeine Content Per Beverage Serving (mg) Coffee (8 ounces unless noted) Brewed 85 Instant (1 rounded teaspoon, dry) 75 Espresso (1 fluid ounce) 40 Flavored Decaffeinated, brewed 3 Decaffeinated, instant 3 Tea (8 ounces) Black tea 40 Green tea 40 Decaffeinated black tea 4 Iced tea, ready to drink 30 Iced tea mix, unsweetened 13 Carbonated beverages (12 fluid ounces) Coca-Cola Classic, Cherry Coca-Cola 34 Diet Coke 45 Barq s Root Beer 22 Mello Yello (regular and diet) 51 Pepsi-Cola, Wild Cherry Pepsi 38 Diet Pepsi-Cola 36 Sunkist Orange Soda 41 Surge 51 Red Flash 40 Mountain Dew (regular and diet) 55 Code Red Mountain Dew 55 Royal Crown Edge 70 Other beverages Cocoa (5 ounces) 5 Planet Java Caramocha (9.5 ounces) 65 Planet Java Javadelic (9.5 ounces) 65 Planet Java Tremble (9.5 ounces) 129 KMX Orange, KMX Blue (8.4 ounces) 38 SoBe Adrenaline Rush (8.3 ounces) 79 SoBe No Fear (8 ounces) 79 Red Bull (8.5 ounces) 80 Nutrition Reviews, Vol. 64, No. 1 45
4 derived hepatoma cells. The investigators found a protective effect of cafestol and kahweol against N-nitrosodimethylamine and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine, two carcinogens contained in the human diet. 15 A few animal studies, particularly in rats, have also explored the effects of these coffee-specific diterpines. Cafestol and kahweol are thought to modulate host activationdetoxification processes preventing reactive chemical intermediates to reach and/or interact with target sites such as DNA. 16 Significant protection against genotoxicity caused by aflatoxin B1 has been demonstrated to be due to cafestol and kahweol-mediated modulation of metabolism in the rat in vivo, in rat hepatocyte cultures, and in recombinant cell lines of human origin. 17,18 Cafestol and kahweol have also been shown to be protective against the genotoxic effect of benzo[a]pyrene in rats. This substance is found in cigarette smoke, barbecued and smoked foods, and industrial waste. 16 It has also been suggested that the anti-carcinogenic effects of cafestol and kahweol may be due to their ability to induce glutathione S-transferases, particularly placental glutathione S-transferase. Cafestol and kahweol have demonstrated a dose-dependent induction of glutathione S-transferase-P in the liver of both male and female Sprague-Dawley rats, which suggests a role for glutathione S-transferase-P in the detoxification of carcinogenic compounds. 19 However, a recent study of 18 volunteers in the Netherlands raises doubts about the effects of kahweol on the elevation of certain liver enzymes, namely alanine aminotransferase and aspartate aminotransferase. 20 These studies are a good beginning toward understanding the mechanism of coffee on the various enzymes of the liver, but need to be expanded further in animal models and human hepatic cells. REFERENCES 1. Starbird, E. The Bonanza Bean: Coffee. National Geographic. 1981;159: United States Department of Agriculture. Trade Products: World Markets and Trade. Available at: June%202003%20Cover2.pdf. Accessed: December 12, Specialty Coffee Association of America. The Press Resources Page. Available at: press_resources.asp. Accessed: December 12, Shimazu T, Tsubono Y, Kuriyama S, et al. Coffee consumption and the risk of primary liver cancer: Pooled analysis of two prospective studies in Japan. Int J Cancer. 2005;116: Orito E, Mizokami M. Hepatitis B virus genotypes and hepatocellular carcinoma in Japan. Intervirology. 2003;46: Corrao G, Zambon A, Bagnardi V, D Amicis A, Klatsky A; Collaborative SIDECIR Group. Coffee, caffeine, and the risk of liver cirrhosis. Ann Epidemiol. 2001;11: Poikolainen K, Vartiainen E. Determinants of -glutamyltransferase: positive interaction with alcohol and body mass index, negative association with coffee. Am J Epidemiol. 1997;146: Casiglia E, Spolaore P, Ginocchio G, Ambrosio G. Unexpected effects of coffee consumption on liver enzymes. Eur J Epidemiol. 1993;9: Aubin H, Laureaux C, Zerah F, et al. Joint influence of alcohol, tobacco, and coffee on biological markers of heavy drinking in alcoholics. Biol Psychiatry. 1998;44: Nakanishi N, Nakamura K, Nakajima K, Suzuki K, Tatara K. Coffee consumption and decreased serum gamma-glutamyltransferase: a study of middle-aged Japanese men. Eur J Epidemiol. 2000;16: Ruhl C, Everhart J. Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2005;128: Stavric B, Klassen R, Watkinson B, Karpinski K, Stapley R, Fried P. Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies. Food Chem Toxicol. 1988; 26: Barone J, Roberts H. Caffeine consumption. Food Chem Toxicol. 1996;34: Mayo Clinic. Caffeine Content of Common Beverages. Available at: Accessed December 12, Majer BJ, Hofer E, Cavin C, et al. Coffee diterpenes prevent the genotoxic effects of 2-amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine (PhIP) and N-nitrosodimethylamine in a human derived liver cell line (HepG2). Food Chem Toxicol. 2005;43: Cavin C, Bezencon C, Guignard G, Schilter B. Coffee diterpenes prevent benzo[a]pyrene genotoxicity in rat and human culture systems. Biochem Biophys Res Commun. 2003;306: Cavin C, Holzhauser D, Constable A, Huggett A, Schilter B. The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism. Carcinogenesis. 1998;19: Cavin C, Mace K, Offord E, Schilter B. Protective effects of coffee diterpenes against aflatoxin B1- induced genotoxicity: mechanisms in rat and human cells. Food Chem Toxicol. 2001;39; Schilter B, Perrin I, Cavin C, Huggett A. Placental glutathione S-transferase (GST-P) induction as a potential mechanism for the anti-carcinogenic effect of the coffee-specific components cafestol and kahweol. Carcinogenesis. 1996;17: Boekschoten MV, Schouten EG, Katan MB. Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers. Nutr J. 2004;3:7. 46 Nutrition Reviews, Vol. 64, No. 1
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Author's response to reviews
Author's response to reviews Title: Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers Authors: Mr Mark V Boekschoten (Mark.Boekschoten@wur.nl)
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