Caffeine from Coffee consumption associated with less severe liver fibrosis

Contact: Dawn Peters medicalnews@wiley.com 781-388-8408 Wiley-Blackwell

Study finds caffeine in sources other than coffee does not have similar effect

Researchers from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) determined that patients with chronic hepatitis C virus (HCV) who consumed more than 308 mg of caffeine daily had milder liver fibrosis. The daily amount of caffeine intake found to be beneficial is equivalent to 2.25 cups of regular coffee. Other sources of caffeine beyond coffee did not have the same therapeutic effect. Details of this study are available in the January 2010 issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.

Liver fibrosis or scaring of the liver is the second stage of liver disease and characterized by a degradation of liver function due to accumulated connective tissue. Past studies have looked at modifiable behaviors, such as coffee consumption, that mitigate the progression of liver disease. A number of studies have looked at the benefits of higher coffee intake with results that include: lower prevalence of chronic liver disease, reduced risk of hepatocellular carcinoma (liver cancer), and lower risk of death from cirrhosis complications. “From data collected to date it remains unclear whether coffee itself, or caffeine provides the beneficial effect,” said Apurva Modi, M.D. and lead author of the current study that focuses on caffeine intake and its impact on liver fibrosis.

From January 2006 to November 2008 all patients evaluated in the Liver Disease Branch of the National Institutes of Health were asked to complete a questionnaire to determine caffeine consumption. Questions were asked pertaining to all sources of caffeine including regular and diet soft drinks; regular and decaffeinated coffee; black, green, Chinese and herbal teas; cocoa and hot chocolate; caffeine-fortified drinks; chocolate candy; caffeine pills; and medications with caffeine. Participants were asked about their frequency of caffeine consumption, which was quantified as never; 1-3 times per month; 1, 2-4, or 5-6 times per week; 1, 2-3, 4-5, and 6 or more times per day.

The analysis included 177 participants who were undergoing liver biopsy with a mean age of 51 years and mean body mass index (BMI) of 27.5. Of those in the cohort 56% were male, 59% Caucasian, 19% Black, 19% Asian, 3% Hispanic, and 68% had chronic HCV. Daily consumption of caffeine from food and beverages raged from none to 1028 mg/day with an average of 195 mg/day, which is equivalent to 1.4 cups of coffee daily. Most caffeine consumed came from regular coffee (71%) followed by caffeinated soda (13%), and black tea (4%). Repeated administration of the questionnaire within a 6-month period displayed consistent responses suggesting caffeine intake does not significantly change over time.

Patients with an Ishak fibrosis score of less than 3 had a mean caffeine intake of 212 mg/day compared with 154 mg/day for those with more advanced fibrosis. The Ishak fibrosis score is the preferred system that measures degree of liver scarring with 0 representing no fibrosis through 6 indicating cirrhosis. For each 67 mg increase in caffeine consumption (about one half cup of coffee) there was a 14% decrease in the odds of advanced fibrosis for patients with HCV. “Our data suggest that a beneficial effect requires caffeine consumption above a threshold of approximately 2 coffee-cup equivalents daily,” noted Dr. Modi. The protective effects of consuming more than 308 mg of caffeine daily persisted after controlling for age, sex, race, liver disease, BMI and alcohol intake for all study participants.

Researchers further evaluated caffeine and coffee separately to determine the individual effect of each on fibrosis. Results showed that consumption of caffeinated soda, green or black tea was not associated with reduced liver fibrosis. However, a significant protective effect could have been missed due to small numbers, as 71% of total caffeine consumed came from coffee. Caffeinated coffee had the most pronounced effect on reduced liver fibrosis. The authors suggest that further research is needed to determine if the protective benefits of coffee/caffeine intake plateau at amounts beyond the daily consumption threshold.

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Article: “Increased caffeine consumption is associated with reduced hepatic fibrosis.” Apurva A Modi, Jordan J Feld, Yoon Park, David E Kleiner, James E. Everhart, T. Jake Liang, and Jay H. Hoofnagle. Hepatology; Published Online: September 9, 2009 (DOI:10.1002/hep.23279); Print Issue Date: January 2010 http://www3.interscience.wiley.com/journal/122593077/abstract

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://www3.interscience.wiley.com/journal/106570044/home.

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world’s leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.

Increased dietary fructose (high fructose corn syrup) linked to elevated uric acid levels and lower liver energy stores

Contact: Dawn Peters sciencenewsroom@wiley.com 781-388-8408 Wiley

Obese patients with type 2 diabetes who consume higher amounts of fructose display reduced levels of liver adenosine triphosphate (ATP)—a compound involved in the energy transfer between cells. The findings, published in the September issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, indicate that elevated uric acid levels (hyperuricemia) are associated with more severe hepatic ATP depletion in response to fructose intake.

This exploratory study, funded in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), also suggests that uric acid levels may serve as a marker for increased fructose consumption and hepatic ATP depletion. Uric acid is produced by the breakdown of purines, natural substances commonly found in foods. According to the authors, increased dietary fructose can alter the body’s metabolism and energy balance. Energy depletion in the liver may be associated with liver injury in patients with non-alcoholic fatty liver disease (NAFLD) and in those at risk for developing this metabolic condition.

Fructose is a simple sugar that fuels the body, and is found in fruits and vegetables. High fructose corn syrup—a mixture of glucose and fructose—is used as a sweetener in consumer food products such as bread, cereal, and soda. Prior research reports that fructose consumption in the U.S. has more than doubled in the past 30 years. In fact, studies have shown that Americans’ fructose intake climbed from 15 grams per day in the early 1900s to 55 grams per day in 1994, which experts believe stems from an increase in soft drink consumption.

“There is an alarming trend of increased rates of obesity, type 2 diabetes and NAFLD in the U.S.,” said lead author Dr. Manal Abdelmalek from Duke University Medical Center. “Given the concurrent rise in fructose consumption and metabolic diseases, we need to fully understand the impact of a high-fructose diet on liver function and liver disease.”

For the present study, 244 obese and diabetic adults from the Look AHEAD Study were evaluated, with dietary fructose consumption estimated by the food frequency questionnaire. Liver ATP and uric acid levels were measured in 105 patients who participated in the Look AHEAD Fatty Liver Ancillary Study. Researchers assessed the change in liver ATP content using an IV fructose challenge in 25 subjects, comparing patients with low fructose consumption (less than 15 grams per day) to those with high fructose consumption (greater than 15 grams per day).

The team found that participants with a high intake of dietary fructose had lower liver ATP levels at baseline and a greater change in ATP content following the fructose challenge than those who consumed a lower amount of fructose. Patients with high uric acid levels (5.5 mg/dL or more) displayed lower ATP stores in response to fructose.

Dr. Abdelmalek concludes, “High fructose consumption and elevated levels of uric acid are associated with more severe depletion of liver ATP. Our findings suggest that increased dietary fructose intake may impair liver “energy balance.” Further research to define the clinical implications of these findings on metabolism and NAFLD is necessary.” The authors highlight the importance of public awareness of the risks associated with a diet high in fructose.

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This study is published in Hepatology. Media wishing to receive a PDF of this articles may contact sciencenewsroom@wiley.com.

Full Citation: “Higher Dietary Fructose Is Associated with Impaired Hepatic ATP Homeostasis in Obese Individuals with Type 2 Diabetes.” Manal F. Abdelmalek, Mariana Lazo, Alena Horska, Susanne Bonekamp, Edward W. Lipkin, Ashok Balasubramanyam, John P. Bantle, Richard J. Johnson, Anna Mae Diehl, Jeanne M. Clark, and the Fatty Liver Subgroup of the Look AHEAD Research Group. Hepatology; (DOI: 10.1002/hep.25741); Print Issue Date: September, 2012. URL: http://onlinelibrary.wiley.com/doi/10.1002/hep.25741/abstract

Author Contact:

To arrange an interview with Dr. Abdelmalek, please contact Rachel Bloch with Duke University at rachel.bloch@duke.edu or at +1 919-419-5069.

About the Journal:

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on is published by Wiley on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://wileyonlinelibrary.com/journal/hep.

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Grapefruit compound may help combat hepatitis C infection ” may be able to block the secretion of hepatitis C virus “

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital

MGH study reveals mechanism key to maintaining chronic infection, potential therapy target

A compound that naturally occurs in grapefruit and other citrus fruits may be able to block the secretion of hepatitis C virus (HCV) from infected cells, a process required to maintain chronic infection.  A team of researchers from the Massachusetts General Hospital Center for Engineering in Medicine (MGH-CEM) report that HCV is bound to very low-density lipoprotein (vLDL, a so-called “bad” cholesterol) when it is secreted from liver cells and that the viral secretion required to pass infection to other cells may be blocked by the common flavonoid naringenin.

If the results of this study extend to human patients, a combination of naringenin and antiviral medication might allow patient to clear the virus from their livers.  The report will appear in an upcoming issue of the journal Hepatology and has been released online.

“By finding that HCV is secreted from infected cells by latching onto vLDL, we have identified a key pathway in the viral lifecycle,” says Yaakov Nahmias, PhD, of the MGH-CEM, the paper’s lead author. “These results suggest that lipid-lowering drugs, as well as supplements, such as naringenin, may be combined with traditional antiviral therapies to reduce or even eliminate HCV from infected patients”

HCV is the leading cause of chronic viral liver disease in the United States and infects about 3 percent of the world population. Current antiviral medications are effective in only half of infected patients, 70 percent of whom develop chronic infection that can lead to cirrhosis or liver cancer.  Since the virus does not integrate its genetic material into the DNA of infected cells the way HIV does, totally clearing the virus could be possible if new cells were not being infected by secreted virus.

“Identifying the route by which HCV is released from cells introduces a new therapeutic target,” says Martin Yarmush, MD, PhD, director of the MGH-CEM and the paper’s senior author. “That pathway’s dependence on cholesterol metabolism could allow us to interfere with viral  propagation to other cells and tissues, using tools already developed for atherosclerosis treatment.”  Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School (HMS).

Grapefruit’s bitter taste is caused the presence of the flavonoid naringin, which is metabolized into naringenin, an antioxidant previously reported to help lower cholesterol levels. Considerable research has suggested that HCV infects liver cells by, in essence, “hitching a ride” onto the natural lipoprotein-cholesterol metabolic pathway.  Since earlier evidence has shown that naringenin can reduce secretion of vLDL from liver cells, the researchers examined whether the compound might also lower HCV secretion from infected cells. Their experiments confirmed that naringenin does reduce the secretion of HCV from infected cell lines and showed that the compound inhibits the mechanism for secreting a specific lipoprotein that binds HCV.

“This work presents the possibility that non-toxic levels of a dietary supplement, such as naringenin, could effectively block HCV secretion,” says Raymond Chung, MD, MGH director of Hepatology and one of the study authors, “This approach might eventually be used to treat patients who do not respond to or cannot take traditional interferon-based treatment or be used in combination with other agents to boost success rates.”

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Chung is an associate professor of Medicine at HMS, and Nahmias is an instructor in Surgery and Bioengineering. Additional co-authors of the Hepatology paper are Jonathan Goldwasser, Monica Casali, PhD, Daan van Poll, MD, MGH-CEM; and Takaji Wakita, MD, Tokyo Metropolitan Institute. The work was supported by grants from the National Institutes of Health and Shriners Hospitals for Children.

Massachusetts General Hospital (www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.