Gastrointestinal Health

Liver Health:

Epidemiology and Prevention Division (MI, ST) and Statistics and Cancer Control Division (IY, TS), Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan

An association between coffee drinking and reduced risk of liver cancer has been suggested by animal studies, but epidemiologic evidence of such an association in a high-risk population is lacking. We conducted a large-scale population-based cohort study of the association between coffee drinking and hepatocellular carcinoma (HCC) in a Japanese population. Methods: Newly diagnosed case patients (250 men and 84 women) with HCC were identified from a 10-year follow-up of the Japan Public Health Center-based Prospective Study, which consists of 90 452 middle-aged and elderly Japanese subjects (43 109 men and 47 343 women). Case patients were grouped according to coffee intake and were stratified by hepatitis virus infection, sex, age, diet, lifestyle factors, and previous history of liver disease. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for HCC were calculated with Cox proportional-hazards modeling. All statistical tests were two-sided. Results: Subjects (men and women combined) who consumed coffee on a daily or almost daily basis had a lower HCC risk than those who almost never drank coffee (HR = 0.49 [95% CI = 0.36 to 0.66]); risk decreased with the amount of coffee consumed (compared with nondrinkers, the HR for 1–2 cups per day = 0.52 [95% CI = 0.38 to 0.73]; for 3–4 cups per day = 0.48 [95% CI = 0.28 to 0.83]; for ≥5 cups per day = 0.24 [95% CI = 0.08 to 0.77], Ptrend < .001). The risk of liver cancer in almost never drinkers in this population was 547.2 cases per 100 000 people over 10 years, but it was 214.6 cases per 100 000 people with drinking coffee on a daily basis. The inverse association persisted when the participants were stratified by lifestyle factors. Similar associations were observed when the analysis was restricted to hepatitis C virus-positive patients (all daily drinkers compared with nondrinkers: HR =0.57 [95% CI = 0.37 to 0.86]), to hepatitis B virus-positive patients (HR = 0.60 [95% CI = 0.31 to 1.18]) and to subjects with no past history of chronic liver disease (HR = 0.45 [95% CI = 0.30 to 0.67]). Conclusions: In the Japanese population, habitual coffee drinking may be associated with reduced risk of HCC.

Coffee intake and mortality from liver cirrhosis. Tverdal A, Skurtveit S. Ann Epidemiol.  2003 Jul;13(6):419-23.

Norwegian Institute of Public Health, Oslo, Norway.

PURPOSE: The aim of the study was to evaluate the association between coffee consumption and mortality from liver cirrhosis. METHODS: We conducted a mortality follow-up of 51,306 adults who underwent screening for cardiovascular disease from 1977 to 1983. During the subsequent 17 years, the total number of deaths from all causes in the studied cohort was 4207. Fifty-three had the diagnosis of cirrhosis mentioned on the death certificate; of these, 36 had alcoholic cirrhosis. RESULTS: The relative risk of liver cirrhosis mentioned on the death certificate associated with an increase of two cups of coffee, adjusted for sex, age, alcohol use and other major cardiovascular risk factors was 0.6 (95% confidence interval, 0.5-0.8). For alcoholic cirrhosis the results were identical. When studying cirrhosis as the underlying cause of death, the inverse relationship becomes somewhat stronger. CONCLUSIONS: The present study confirms the existence of an inverse association between coffee consumption and liver cirrhosis.

Alcohol, smoking, coffee, and cirrhosis. Klatsky AL, Armstrong MA. Am J Epidemiol.  1992 Nov 15;136(10):1248-57.

Department of Medicine, Kaiser Permanente Medical Care Program (Northern California Region), Oakland, CA.

Since most heavy drinkers do not develop alcoholic cirrhosis, other causes or predisposing factors are probable. The authors studied traits of 128,934 adults who underwent health examinations at the Oakland and San Francisco, California, facilities of the Kaiser Permanente Medical Care Program from January 1978 to December 1985 in relation to subsequent hospitalization or death from cirrhosis of the liver. In analyses adjusted for nine covariates, past and current alcohol drinking were strongly related to cirrhosis risk, but usual choice of alcoholic beverage had no independent relation. Cigarette smoking was independently related to risk of alcoholic cirrhosis, with cigarette smokers of a pack or more per day at trebled risk compared with lifelong nonsmokers. Coffee drinking, but not tea drinking, was inversely related to alcoholic cirrhosis risk, with persons who drank four or more cups per day at one-fifth the risk of noncoffee drinkers. This inverse relation between coffee consumption and risk of alcoholic cirrhosis was consistent in many subsets, including persons free of gastrointestinal disease and those with 5 or more years before hospitalization or death. Cigarette smoking and coffee consumption were not consistently related to risk of hospitalization or death for nonalcoholic cirrhosis. These data could mean that cigarette smoking promotes alcoholic cirrhosis and that coffee drinking might be protective.

Cancer of the colon:

Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003. Tavani A, Vecchia CL. Cancer Causes Control. 2004 Oct;15(8):743-57.

Biol Sci D, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

The literature from 1990 to 2003 on the relation between coffee, decaffeinated coffee, tea and colorectal cancer risk has been reviewed. For the relation with coffee, three cohort (517 total cases) and nine case-control studies (7555 cases) analysed colon cancer; three cohort (307 cases) and four case-control studies (2704 cases) rectal cancer; six case-control studies (854 cases) colorectal cancer. For colon cancer most case-control studies found risk estimates below unity; the results are less clear for cohort studies. No relation emerged for rectal cancer. A meta-analysis, including five cohort and twelve case-control studies, reported a pooled relative risk of 0.76 (significant). Any methodological artefact is unlikely to account for the consistent inverse association in different countries and settings. Plausible biological explanations include coffee-related reductions of cholesterol, bile acids and neutral sterol secretion in the colon; antimutagenic properties of selected coffee components; increased colonic motility. Decaffeinated coffee was not related to either colon or rectal cancer in three case-control studies. No overall association between tea and either colon or rectal cancer risk emerged in seven cohort (1756 total cases of colon, 759 of rectal and 60 of colorectal cancer) and 12 case-control studies (8058 cases of colon, 4865 of rectal, 604 of colorectal cancer).

 Coffee and its chemopreventive components Kahweol and Cafestol increase the activity of O6-methylguanine-DNA methyltransferase in rat liver--comparison with phase II xenobiotic metabolism. Huber WW, Scharf G, Nagel G, Prustomersky S, Schulte-Hermann R, Kaina B. Mutat Res. 2003 Jan 28;522(1-2):57-68.

Institut fur Krebsforschung, University of Vienna, Vienna, Austria.

A lower rate of colon cancer was observed in consumers of coffee with a high content of the diterpenes Kahweol and Cafestol (K/C). In animal models, K/C have been found to protect against the mutagenic/carcinogenic effects of compounds such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), aflatoxin B1, and 7,12-dimethylbenz[a]anthracene. Thus far, such chemoprotection by K/C has been attributed to modifications of xenobiotic metabolism, e.g. enhanced detoxification by UDP-glucuronosyltransferase (UDPGT) and/or glutathione transferase (GST). In the present study, we investigated the potential of several coffee-related treatments (K/C [1:1], Cafestol-alone, Turkish coffee) to modify the expression level of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) which is involved in the reversal of the precarcinogenic DNA damage O(6)-alkylguanine induced by alkylating agents. The results show that, in the male F344 rat, K/C and Cafestol increase hepatic MGMT in a dose-dependent manner up to a maximum of 2.6-fold at 0.122% K/C in the feed. Turkish coffee led to enhancements of up to 16%, the more moderate increase being associated with the lower estimated K/C intake through the beverage. In the livers of the rats receiving Turkish coffee, we also found 10-30% increases in several GST-related parameters (overall GST, GST-pi, glutathione, gamma-glutamylcysteine-synthetase) and a two-fold increase in UDPGT activity. Dose-response studies with K/C revealed that MGMT increased in parallel with three of the four GST-related parameters whereas the dose-response curves of UDPGT and of GST-pi activity displayed a steeper slope. Increased expression level of MGMT may extend the antimutagenic/anticarcinogenic potential of coffee components to protection against DNA alkylating agents.

Coffee and tea consumption and cancers of the bladder, colon and rectum. Woolcott CG,King WD, Marrett LD. Eur J Cancer Prev. 2002 Apr;11(2):137-45.

Department of Community Health Sciences, University of Calgary, Canada.

Coffee has been observed to be associated weakly or not at all with bladder cancer risk, inversely with colon cancer risk, and inconsistently with rectal cancer risk. The association between these cancers and consumption of coffee and tea was examined in a single case-control study conducted in Ontario, Canada from 1992 to 1994. A questionnaire was filled out by 927 bladder cancer cases, 991 colon cancer cases, 875 rectal cancer cases, and 2118 population controls. Although bladder cancer risk was not associated with coffee or tea, risk estimates associated with coffee among subjects who had never smoked were non-significantly increased. Colon cancer risk was inversely associated with coffee. Relative to those drinking less than 1 cup of coffee per day, the odds ratios (OR) for those drinking 1-2 cups was 0.9 (95% CI 0.8-1.1), for those drinking 3-4 cups was 0.8 (95% CI 0.7-1.0), and for those drinking 5 or more cups was 0.7 (95% CI 0.5-0.9); these ORs decreased linearly (P = 0.008). The reduced risk estimates were more pronounced with cancer of the proximal colon than the distal colon. Rectal cancer risk was not associated with either coffee or tea. Coffee consumption was observed to have a different relationship for each of the cancer sites and tea consumption was not related to any cancer site.

Coffee and cancer: a review of epidemiological studies, 1990-1999. Tavani A, La Vecchia C. Eur J Cancer Prev. 2000 Aug;9(4):241-56.

Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.

Epidemiological studies on the relation between coffee consumption and cancer risk have been mainly focused on cancers of the urinary bladder, pancreas and colorectum. The relation between coffee and bladder cancer is controversial, despite a large number of studies published over the last three decades. In most studies, the risk tends to be higher in coffee drinkers than in those who do not drink coffee, but the excess risk is generally moderate and is neither dose- nor duration-related. Thus, a strong association between coffee drinking and bladder cancer can be excluded, although it is still unclear whether the weak association is causal or nonspecific and due to some bias or confounding. For pancreatic cancer, a possible association with coffee consumption has been postulated in a large case-control study published in 1981; since then, however, most studies have shown no substantial association, and overall evidence suggests that coffee is not materially related to pancreatic cancer risk. Overall evidence on the coffee-colorectal cancer relation suggests an inverse association, since most case-control studies found odds ratios below unity, particularly for colon cancer. The pattern of risk is less clear for cohort studies. A plausible biological explanation has been given in terms of coffee-related reduction of bile acids and neutral sterol secretion in the colon. For other cancer sites, including oral cavity, oesophagus, stomach, liver, breast, ovary, kidney and lymphoid neoplasms, the relation of coffee drinking with cancer risk has been less extensively investigated, but the evidence is largely reassuring.

Meta-analysis of coffee consumption and risk of colorectal cancer.  Giovannucci E. Am J Epidemiol.  1998 Jun 1;147(11):1043-52

Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA.

Several studies have found that coffee consumption is related to a lower risk of colorectal cancer, but results have not been consistent. Thus, a meta-analysis of the published articles was conducted to examine this relation. Because of the various ways data were collected and analyzed, a "semiquantitative" approach that compared the high versus the low category of intake for each study was used. The combined results from 12 case-control studies showed an inverse association between coffee consumption and risk of colorectal cancer (pooled relative risk (estimated by odds ratio) for high vs. low category of coffee consumption (RR) = 0.72, 95% confidence interval (CI) 0.61-0.84); the findings were similar in population-based and hospital-based case-control studies. Five cohort studies did not support an association (pooled RR = 0.97, 95% CI 0.73-1.29). The combined results of all studies were driven largely by the case-control studies, which comprised 85 percent of the cases (RR = 0.76, 95% CI 0.66-0.89). The lower risk of colorectal cancer among substantial coffee drinkers was observed in studies from Asia, Northern and Southern Europe, and North America. The results of this meta-analysis indicate a lower risk of colorectal cancer associated with substantial consumption of coffee, but they are inconclusive because of inconsistencies between case-control and prospective studies, the lack of control for important covariates in many of the studies, and the possibility that individuals at high risk of colorectal cancer avoid coffee consumption. Several ongoing prospective cohort studies, based on extensive dietary questionnaires, may provide important new data to evaluate this hypothesis.

Gallstones:

Coffee intake is associated with lower risk of symptomatic gallstone disease in women.  Leitzmann MF, Stampfer MJ, Willett WC, Spiegelman D, Colditz GA, Giovannucci EL. Gastroenterology.  2002 Dec;123(6):1823-30.

Department of Nutrition, Harvard School of Public Health, Boston, MA.

BACKGROUND & AIMS: Metabolic studies have shown that coffee affects several hepatobiliary processes that are involved in cholesterol lithogenesis. We previously showed that coffee drinking was associated with a lower risk of symptomatic gallstone disease in men. METHODS: We prospectively examined the association between coffee drinking and cholecystectomy, a surrogate of symptomatic gallstone disease, in a cohort of 80,898 women age 34-59 years in 1980 who had no history of gallstone disease. Coffee consumption and cholecystectomy were reported by participants on biennial mailed questionnaires. RESULTS: During 20 years of follow-up to the year 2000, 7,811 women reported a cholecystectomy. Compared with women who consistently reported consuming no caffeinated coffee, the multivariate relative risks (adjusting for risk factors for gallstone disease) of cholecystectomy comparing increasing categories of consistent intake of caffeinated coffee (0, 1, 2-3, and > or =4 cups/day) were 1.0, 0.91, 0.78, and 0.72 (95% confidence interval comparing extreme categories, 0.62-0.84; P value of test for trend < 0.0001). Caffeine intake from beverages and dietary sources was also inversely associated with risk of cholecystectomy. The multivariate relative risks comparing increasing categories of caffeine intake (< or =25, 26-100, 101-200, 201-400, 401-800, and >800 mg/day) were 1.0, 1.03, 1.01, 0.94, 0.85, and 0.85 (95% confidence interval comparing extreme categories, 0.74-0.96; P value of test for trend < 0.0001). In contrast, decaffeinated coffee was not associated with risk. CONCLUSIONS: These data suggest that consumption of caffeinated coffee may play a role in the prevention of symptomatic gallstone disease in women.

 [Evidence-based prevention of cholecystolithiasis][Article in German] Lammert F, Matern S. Dtsch Med Wochenschr. 2004 Jul 9;129(28-29):1548-50

Universitatsklinikum Aachen, RWTH Aachen, Aachen.

Evidence based prevention of cholecystolithiasis. Cholesterol cholelithiasis is one of the most common and expensive gastroenterological diseases. Beside common exogenous risk factors, recent molecular genetic studies have identified genetic risk factors for both cholesterol and pigment stone formation. Examples are low phospholipid-associated cholelithiasis due to mutations of the gene encoding the hepatocanalicular phosphatidylcholine transporter, and pigment stones in association with mutations of the ileal bile salt transporter gene. Evidence-based options for primary prevention of cholecystolithiasis include physical activity, slow weight reduction, regular vitamin C supplementation, and moderate coffee consumption. The ongoing genome projects provide the basis for future epidemiological studies of human gallstone (LITH) genes, which might offer new prospects for individual risk assessment and prevention of gallstones.

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men. Leitzmann MF, Willett WC, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E.  JAMA. 1999 Jun 9;281(22):2106-12.

Department of Nutrition, Harvard School of Public Health, Boston, MA.

CONTEXT: Coffee has several metabolic effects that could reduce the risk of gallstone formation. OBJECTIVE: To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. DESIGN AND SETTING: The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996. PARTICIPANTS: A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease. MAIN OUTCOME MEASURES: Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy. RESULTS: During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk. CONCLUSIONS: In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.

 Kidney stones:

Beverage use and risk for kidney stones in women. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Ann Intern Med. 1998 Apr 1;128(7):534-40.

Brigham and Womens' Hospital, Boston, MA.

BACKGROUND: An increase in fluid intake is routinely recommended for patients who have had kidney stones to decrease the likelihood of recurrence. However, data on the effect of particular beverages on stone formation in women are limited. OBJECTIVE: To examine the association between the intake of 17 beverages and risk for kidney stones in women. DESIGN: Prospective cohort study with 8 years of follow-up. SETTING: United States. PARTICIPANTS: 81093 women in the Nurses' Health Study who were 40 to 65 years of age in 1986 and had no history of kidney stones. MEASUREMENTS: Beverage use and diet were assessed in 1986 and 1990 with a validated, self-administered food-frequency questionnaire. The main outcome measure was incident symptomatic kidney stones. RESULTS: During 553 081 person-years of follow-up over an 8-year period, 719 cases of kidney stones were documented. After risk factors other than fluid intake were controlled for, the relative risk for stone formation for women in the highest quintile of total fluid intake compared with women in the lowest quintile was 0.62 (95% CI, 0.48 to 0.80). Inclusion of consumption of specific beverages in the multivariate model significantly added to prediction of risk for kidney stones (P < 0.001). In a multivariate model that adjusted simultaneously for the 17 beverages and other possible risk factors, risk for stone formation decreased by the following amount for each 240-mL (8-oz) serving consumed daily: 10% (CI, 5% to 15%) for caffeinated coffee, 9% (CI, 2% to 15%) for decaffeinated coffee, 8% (CI, 1% to 15%) for tea, and 59% (CI, 32% to 75%) for wine. In contrast, a 44% (CI, 9% to 92%) increase in risk was seen for each 240-mL serving of grapefruit juice consumed daily. CONCLUSIONS: An increase in total fluid intake can reduce risk for kidney stones, and the choice of beverage may be meaningful.