Brief Critical Review

January 2006: 43 46

Coffee: Good, Bad, or Just Fun? A Critical Review of Coffees 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: 10.1301/nr.2006.jan.43 46

Coffee has had an important place in human society for at least 1200 years. Legend credits an Ethiopian goat herder with discovering coffees stimulating effects when he noticed his goats frolicking about after munching on coffee cherries.1 The rst 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, lled with coffee.1 Despite close guarding of fertile seeds by Arab cultivators, coffee quickly spread to Europe as the Dutch founded the rst 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 worlds largest producer of coffee, with just over 33.6 million bags (1 bag weighs 132 pounds) produced in 20032004, 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: 708-216-9230; Fax: 708-2164113; E-mail: smobarh@lumc.edu.
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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 coffees effects on the digestive system, particularly the liver. This review focuses on the possible benecial 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 specically 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 Everhart11 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,
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Table 1. Inclusion Criteria for Ruhl and Everhart Study11

Criterion N

More than two alcoholic drinks per day Positive serum hepatitis B surface antigen and core antibody Positive serum hepatitis C antibody Transferrin saturation 50% Hemoglobin A1C 6.5% (95th percentile) Diagnosed diabetes Body-mass index (BMI) 26.9 kg/m2 (60th percentile) and waist-to-hip ratio at least 0.94 (60th percentile)

863 69 379 473 1185 1163

4021

23,258 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, 12, and 2. The consumption of caffeinated tea and sodas was also included to determine each participants 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 23.4 0.9 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 26.1 1.6 U/L. In the group who estimated their coffee consumption as 12 cups/d (average 1.0 cups/d), the average serum ALT activity was 22.1 1.0 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 20.7 0.8 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 585 14 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 694 17 mg/d, the serum ALT activity decreased from 24.7 1.3 U/L to 20.3 0.7 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 ndings 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 signicant 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 ofce setting by different individuals using the same jar of instant coffee. Additionally, the Canadian study demonstrated a signicant 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.11

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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 dened in an innite number of ways. Despite these issues, overall, the Ruhl and Everhart study of the relationship between coffee consumption and liver function is highly signicant. Whether coffee affects other parts of the alimentary tract is not yet known. An extensive search of the literature showed no studies nding direct action of either coffee or caffeine in human hepatic cells, although one study did explore the effects of the coffee-specic diterpenes, cafestol and kahweol, in humanNutrition Reviews , Vol. 64, No. 1

Table 2. Caffeine Content of Common Beverages14

Caffeine Content Per Serving (mg)

Beverage

Coffee (8 ounces unless noted) Brewed Instant (1 rounded teaspoon, dry) Espresso (1 uid ounce) Flavored Decaffeinated, brewed Decaffeinated, instant Tea (8 ounces) Black tea Green tea Decaffeinated black tea Iced tea, ready to drink Iced tea mix, unsweetened Carbonated beverages (12 uid ounces) Coca-Cola Classic, Cherry Coca-Cola Diet Coke Barqs Root Beer Mello Yello (regular and diet) Pepsi-Cola, Wild Cherry Pepsi Diet Pepsi-Cola Sunkist Orange Soda Surge Red Flash Mountain Dew (regular and diet) Code Red Mountain Dew Royal Crown Edge Other beverages Cocoa (5 ounces) Planet Java Caramocha (9.5 ounces) Planet Java Javadelic (9.5 ounces) Planet Java Tremble (9.5 ounces) KMX Orange, KMX Blue (8.4 ounces) SoBe Adrenaline Rush (8.3 ounces) SoBe No Fear (8 ounces) Red Bull (8.5 ounces)

85 75 40 2575 3 3 40 40 4 30 13 34 45 22 51 38 36 41 51 40 55 55 70 5 65 65 129 38 79 79 80

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derived hepatoma cells. The investigators found a protective effect of cafestol and kahweol against N-nitrosodimethylamine and 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine, two carcinogens contained in the human diet.15 A few animal studies, particularly in rats, have also explored the effects of these coffee-specic diterpines. Cafestol and kahweol are thought to modulate host activationdetoxication processes preventing reactive chemical intermediates to reach and/or interact with target sites such as DNA.16 Signicant protection against genotoxicity caused by aatoxin 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 detoxication 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. 2. Starbird, E. The Bonanza Bean: Coffee. National Geographic. 1981;159:388 405. United States Department of Agriculture. Trade Products: World Markets and Trade. Available at: http://www.fas.usda.gov/htp/tropical/2003/06-03/ June%202003%20Cover2.pdf. Accessed: December 12, 2005. Specialty Coffee Association of America. The Press Resources Page. Available at: http://www.scaa.org/ press_resources.asp. Accessed: December 12, 2005. 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;116:150 154. Orito E, Mizokami M. Hepatitis B virus genotypes and hepatocellular carcinoma in Japan. Intervirology. 2003;46:408 412.

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