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DOI: 10.1055/s-0038-1666869
Potential Mechanisms Underlying the Role of Coffee in Liver Health
Publication History
Publication Date:
24 July 2018 (online)
Abstract
Coffee, the most consumed hot beverage worldwide, is composed of many substances, of which polyphenols, caffeine, and diterpenoids are well studied. Evidence on potential effects of coffee on human health has been accumulating over the past decades. Specifically, coffee has been postulated to be hepatoprotective in several epidemiological and clinical studies. Several underlying molecular mechanisms as to why coffee influences liver health have been proposed. In this review, the authors summarized the evidence on potential mechanisms by which coffee affects liver steatosis, fibrosis, and hepatic carcinogenesis. The experimental models reviewed almost unanimously supported the theorem that coffee indeed may benefit the liver. Either whole coffee or its specific compounds appeared to decrease fatty acid synthesis (involved in steatogenesis), hepatic stellate activation (involved in fibrogenesis), and hepatic inflammation. Moreover, coffee was found to induce apoptosis and increased hepatic antioxidant capacity, which are involved in carcinogenesis.
Keywords
coffee - polyphenols - diterpenoids - caffeine - liver steatosis - fibrosis - hepatocellular carcinoma-
References
- 1 Rustan AC, Halvorsen B, Ranheim T. , et al. Cafestol (a coffee lipid) decreases uptake of low-density lipoprotein (LDL) in human skin fibroblasts and liver cells. In, Ann N Y Acad Sci; 1997;827: 158-162
- 2 Treur JL, Taylor AE, Ware JJ. , et al. Associations between smoking and caffeine consumption in two European cohorts. Addiction 2016; 111 (06) 1059-1068
- 3 Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. BMJ 2017; 359: j5024
- 4 Arnesen E, Huseby NE, Brenn T, Try K. The Tromsø Heart Study: distribution of, and determinants for, gamma-glutamyltransferase in a free-living population. Scand J Clin Lab Invest 1986; 46 (01) 63-70
- 5 Ruhl CE, Everhart JE. Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2005; 128 (01) 24-32
- 6 Nakanishi N, Nakamura K, Nakajima K, Suzuki K, Tatara K. Coffee consumption and decreased serum γ-glutamyltransferase: a study of middle-aged Japanese men. Eur J Epidemiol 2000; 16 (05) 419-423
- 7 Xiao Q, Sinha R, Graubard BI, Freedman ND. Inverse associations of total and decaffeinated coffee with liver enzyme levels in National Health and Nutrition Examination Survey 1999-2010. Hepatology 2014; 60 (06) 2091-2098
- 8 Klatsky AL, Armstrong MA. Alcohol, smoking, coffee, and cirrhosis. Am J Epidemiol 1992; 136 (10) 1248-1257
- 9 Corrao G, Lepore AR, Torchio P. , et al; Provincial Group for the Study of Chronic Liver Disease. The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption: a case-control study. Eur J Epidemiol 1994; 10 (06) 657-664
- 10 Alferink LJM, Fittipaldi J, Kiefte-de Jong JC. , et al. Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: the Rotterdam study. J Hepatol 2017; 67 (02) 339-348
- 11 Liu F, Wang X, Wu G. , et al. Coffee consumption decreases risks for hepatic fibrosis and cirrhosis: a meta-analysis. PLoS One 2015; 10 (11) e0142457
- 12 Kennedy OJ, Roderick P, Buchanan R, Fallowfield JA, Hayes PC, Parkes J. Systematic review with meta-analysis: coffee consumption and the risk of cirrhosis. Aliment Pharmacol Ther 2016; 43 (05) 562-574
- 13 Freedman ND, Curto TM, Lindsay KL, Wright EC, Sinha R, Everhart JE. ; HALT-C TRIAL GROUP. Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C. Gastroenterology 2011; 140 (07) 1961-1969
- 14 Carrieri MP, Protopopescu C, Marcellin F. , et al; ANRS CO13 HEPAVIH Study Group. Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients. J Hepatol 2017; 67 (06) 1157-1167
- 15 Cardin R, Piciocchi M, Martines D, Scribano L, Petracco M, Farinati F. Effects of coffee consumption in chronic hepatitis C: a randomized controlled trial. Dig Liver Dis 2013; 45 (06) 499-504
- 16 Shen H, Rodriguez AC, Shiani A. , et al. Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis. Therap Adv Gastroenterol 2016; 9 (01) 113-120
- 17 Zelber-Sagi S, Salomone F, Webb M. , et al. Coffee consumption and nonalcoholic fatty liver onset: a prospective study in the general population. Transl Res 2015; 165 (03) 428-436
- 18 Wijarnpreecha K, Thongprayoon C, Ungprasert P. Coffee consumption and risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2017; 29 (02) e8-e12
- 19 Veronese N, Notarnicola M, Cisternino AM. , et al. Coffee intake and liver steatosis: a population study in a Mediterranean area. Nutrients 2018; 10 (01) 89
- 20 Bravi F, Tavani A, Bosetti C, Boffetta P, La Vecchia C. Coffee and the risk of hepatocellular carcinoma and chronic liver disease: a systematic review and meta-analysis of prospective studies. Eur J Cancer Prev 2017; 26 (05) 368-377
- 21 Kennedy OJ, Roderick P, Buchanan R, Fallowfield JA, Hayes PC, Parkes J. Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: a systematic review and dose-response meta-analysis. BMJ Open 2017; 7 (05) e013739
- 22 Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr 2011; 51 (04) 363-373
- 23 Sacchetti G, Di Mattia C, Pittia P. , et al. Effect of roasting degree, equivalent thermal effect and coffee type on the radical scavenging activity of coffee brews and their phenolic fraction. J Food Eng 2009; 90: 74-80
- 24 Lang R, Yagar EF, Wahl A. , et al. Quantitative studies on roast kinetics for bioactives in coffee. J Agric Food Chem 2013; 61 (49) 12123-12128
- 25 Moroney KM, Lee WT, O'Brien SB, Suijver F, Marra J. Coffee extraction kinetics in a well mixed system. J Math Ind 2016; 7: 3
- 26 Mojska H, Gielecińska I. Studies of acrylamide level in coffee and coffee substitutes: influence of raw material and manufacturing conditions. Rocz Panstw Zakl Hig 2013; 64 (03) 173-181
- 27 Duarte GS, Farah A. Effect of simultaneous consumption of milk and coffee on chlorogenic acids' bioavailability in humans. J Agric Food Chem 2011; 59 (14) 7925-7931
- 28 Renouf M, Marmet C, Guy P. , et al. Nondairy creamer, but not milk, delays the appearance of coffee phenolic acid equivalents in human plasma. J Nutr 2010; 140 (02) 259-263
- 29 Williamson G. The role of polyphenols in modern nutrition. Nutr Bull 2017; 42 (03) 226-235
- 30 Yagasaki K, Miura Y, Okauchi R, Furuse T. Inhibitory effects of chlorogenic acid and its related compounds on the invasion of hepatoma cells in culture. Cytotechnology 2000; 33 (1-3): 229-235
- 31 Gross G, Jaccaud E, Huggett AC. Analysis of the content of the diterpenes cafestol and kahweol in coffee brews. Food Chem Toxicol 1997; 35 (06) 547-554
- 32 Urgert R, Katan MB. The cholesterol-raising factor from coffee beans. J R Soc Med 1996; 89 (11) 618-623
- 33 Cavin C, Holzhaeuser D, Scharf G, Constable A, Huber WW, Schilter B. Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity. Food Chem Toxicol 2002; 40 (08) 1155-1163
- 34 Moreira AS, Nunes FM, Domingues MR, Coimbra MA. Coffee melanoidins: structures, mechanisms of formation and potential health impacts. Food Funct 2012; 3 (09) 903-915
- 35 Cronstein BN. Caffeine, a drug for all seasons. J Hepatol 2010; 53 (01) 207-208
- 36 Dranoff JA. Coffee consumption and prevention of cirrhosis: in support of the caffeine hypothesis. Gene Expr 2018; 18 (01) 1-3
- 37 Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berl) 2010; 211 (03) 245-257
- 38 Farag NH, Vincent AS, McKey BS, Whitsett TL, Lovallo WR. Hemodynamic mechanisms underlying the incomplete tolerance to caffeine's pressor effects. Am J Cardiol 2005; 95 (11) 1389-1392
- 39 Cadden IS, Partovi N, Yoshida EM. Review article: possible beneficial effects of coffee on liver disease and function. Aliment Pharmacol Ther 2007; 26 (01) 1-8
- 40 Hemmerle H, Burger HJ, Below P. , et al. Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase. J Med Chem 1997; 40 (02) 137-145
- 41 Rodriguez de Sotillo DV, Hadley M. Chlorogenic acid modifies plasma and liver concentrations of: cholesterol, triacylglycerol, and minerals in (fa/fa) Zucker rats. J Nutr Biochem 2002; 13 (12) 717-726
- 42 Ong KW, Hsu A, Tan BKH. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem Pharmacol 2013; 85 (09) 1341-1351
- 43 Ma Y, Gao M, Liu D. Chlorogenic acid improves high fat diet-induced hepatic steatosis and insulin resistance in mice. Pharm Res 2015; 32 (04) 1200-1209
- 44 Shokouh P, Jeppesen PB, Hermansen K. , et al. A combination of coffee compounds shows insulin-sensitizing and hepatoprotective effects in a rat model of diet-induced metabolic syndrome. Nutrients 2017; 10 (01) 10
- 45 Murase T, Misawa K, Minegishi Y. , et al. Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice. Am J Physiol Endocrinol Metab 2011; 300 (01) E122-E133
- 46 Vitaglione P, Morisco F, Mazzone G. , et al. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology 2010; 52 (05) 1652-1661
- 47 Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 1996; 239 (01) 70-76
- 48 Panchal SK, Poudyal H, Waanders J, Brown L. Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J Nutr 2012; 142 (04) 690-697
- 49 Salomone F, Li Volti G, Vitaglione P. , et al. Coffee enhances the expression of chaperones and antioxidant proteins in rats with nonalcoholic fatty liver disease. Transl Res 2014; 163 (06) 593-602
- 50 Watanabe S, Takahashi T, Ogawa H. , et al. Daily coffee intake inhibits pancreatic beta cell damage and nonalcoholic steatohepatitis in a mouse model of spontaneous metabolic syndrome, Tsumura-Suzuki obese diabetic mice. Metab Syndr Relat Disord 2017; 15 (04) 170-177
- 51 Takahashi S, Egashira K, Saito K. , et al. Coffee intake down-regulates the hepatic gene expression of peroxisome proliferator-activated receptor gamma in C57BL/6J mice fed a high-fat diet. J Funct Foods 2014; 6: 157-167
- 52 Yun JW, Shin ES, Cho SY. , et al. The effects of BADGE and caffeine on the time-course response of adiponectin and lipid oxidative enzymes in high fat diet-fed C57BL/6J mice: correlation with reduced adiposity and steatosis. Exp Anim 2008; 57 (05) 461-469
- 53 Sinha RA, Farah BL, Singh BK. , et al. Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice. Hepatology 2014; 59 (04) 1366-1380
- 54 Helal MG, Ayoub SE, Elkashefand WF, Ibrahim TM. Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention. Hum Exp Toxicol 2017; 960327117747026 . doi:10.1177/0960327117747026
- 55 Sugiura C, Nishimatsu S, Moriyama T, Ozasa S, Kawada T, Sayama K. Catechins and caffeine inhibit fat accumulation in mice through the improvement of hepatic lipid metabolism. J Obes 2012; 2012: 520510
- 56 Zheng X, Dai W, Chen X. , et al. Caffeine reduces hepatic lipid accumulation through regulation of lipogenesis and ER stress in zebrafish larvae. J Biomed Sci 2015; 22: 105
- 57 Reyes MT, Mourelle M, Hong E. , et al. Caffeic acid prevents liver damage and ameliorates liver fibrosis induced by CCl4 in the rat. Drug Dev Res 1995; 36: 125-128
- 58 Janbaz KH, Saeed SA, Gilani AH. Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine 2004; 11 (05) 424-430
- 59 Shi H, Dong L, Jiang J. , et al. Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology 2013; 303: 107-114
- 60 Pang C, Shi L, Sheng Y. , et al. Caffeic acid attenuated acetaminophen-induced hepatotoxicity by inhibiting ERK1/2-mediated early growth response-1 transcriptional activation. Chem Biol Interact 2016; 260: 186-195
- 61 Pang C, Zheng Z, Shi L. , et al. Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system. Free Radic Biol Med 2016; 91: 236-246
- 62 Ghahhari J, Vaezi G, Riazi G. , et al. The protective effect of chlorogenic acid on arsenic trioxide induced hepatotoxicity in mice. Biosci Biotechnol Res Communicat 2017; 10: 165-172
- 63 Cavin C, Marin-Kuan M, Langouët S. , et al. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver. Food Chem Toxicol 2008; 46 (04) 1239-1248
- 64 Ali N, Rashid S, Nafees S. , et al. Protective effect of chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: an experimental approach. Chem Biol Interact 2017; 272: 80-91
- 65 Lee KJ, Choi JH, Jeong HG. Hepatoprotective and antioxidant effects of the coffee diterpenes kahweol and cafestol on carbon tetrachloride-induced liver damage in mice. Food Chem Toxicol 2007; 45 (11) 2118-2125
- 66 Poyrazoglu OK, Bahcecioglu IH, Ataseven H. , et al. Effect of unfiltered coffee on carbon tetrachloride-induced liver injury in rats. Inflammation 2008; 31 (06) 408-413
- 67 Seo HY, Jung YA, Lee SH. , et al. Kahweol decreases hepatic fibrosis by inhibiting the expression of connective tissue growth factor via the transforming growth factor-beta signaling pathway. Oncotarget 2017; 8 (50) 87086-87094
- 68 He P, Noda Y, Sugiyama K. Suppression of lipopolysaccharide-induced liver injury by various types of tea and coffee in D-galactosamine-sensitized rats. Biosci Biotechnol Biochem 2001; 65 (03) 670-673
- 69 Ozercan IH, Dagli AF, Ustundag B. , et al. Does instant coffee prevent acute liver injury induced by carbon tetrachloride (CCl4)?. Hepatol Res 2006; 35 (03) 163-168
- 70 Shi H, Dong L, Zhang Y, Bai Y, Zhao J, Zhang L. Protective effect of a coffee preparation (Nescafe pure) against carbon tetrachloride-induced liver fibrosis in rats. Clin Nutr 2010; 29 (03) 399-405
- 71 Shin JW, Wang JH, Kang JK, Son CG. Experimental evidence for the protective effects of coffee against liver fibrosis in SD rats. J Sci Food Agric 2010; 90 (03) 450-455
- 72 Abreu RV, Moraes-Santos T. The protective effect of coffee against paracetamol-induced hepatic injury in rats. J Food Biochem 2011; 35: 1653-1659
- 73 Moreno MG, Chávez E, Aldaba-Muruato LR. , et al. Coffee prevents CCl4-induced liver cirrhosis in the rat. Hepatol Int 2011; 5 (03) 857-863
- 74 Furtado KS, Prado MG, Aguiar E Silva MA. , et al. Coffee and caffeine protect against liver injury induced by thioacetamide in male Wistar rats. Basic Clin Pharmacol Toxicol 2012; 111 (05) 339-347
- 75 Arauz J, Moreno MG, Cortés-Reynosa P, Salazar EP, Muriel P. Coffee attenuates fibrosis by decreasing the expression of TGF-β and CTGF in a murine model of liver damage. J Appl Toxicol 2013; 33 (09) 970-979
- 76 Arauz J, Zarco N, Hernández-Aquino E. , et al. Coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans. Nutr Res 2017; 40: 65-74
- 77 Sugiyama K, Noda Y, He P. Suppressive effect of caffeine on hepatitis and apoptosis induced by tumor necrosis factor-alpha, but not by the anti-Fas antibody, in mice. Biosci Biotechnol Biochem 2001; 65 (03) 674-677
- 78 Chan ESL, Montesinos MC, Fernandez P. , et al. Adenosine A2A receptors play a role in the pathogenesis of hepatic cirrhosis. Br J Pharmacol 2006; 148 (08) 1144-1155
- 79 Hsu SJ, Lee FY, Wang SS. , et al. Caffeine ameliorates hemodynamic derangements and portosystemic collaterals in cirrhotic rats. Hepatology 2015; 61 (05) 1672-1684
- 80 Klemmer I, Yagi S, Gressner OA. Oral application of 1,7-dimethylxanthine (paraxanthine) attenuates the formation of experimental cholestatic liver fibrosis. Hepatol Res 2011; 41 (11) 1094-1109
- 81 Gordillo-Bastidas D, Oceguera-Contreras E, Salazar-Montes A, González-Cuevas J, Hernández-Ortega LD, Armendáriz-Borunda J. Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine. World J Gastroenterol 2013; 19 (47) 9020-9033
- 82 Shim SG, Jun DW, Kim EK. , et al. Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model. J Gastroenterol Hepatol 2013; 28 (12) 1877-1884
- 83 Arauz J, Zarco N, Segovia J, Shibayama M, Tsutsumi V, Muriel P. Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β. Eur J Gastroenterol Hepatol 2014; 26 (02) 164-173
- 84 Wang Q, Dai X, Yang W. , et al. Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells. Int Immunopharmacol 2015; 25 (02) 340-352
- 85 Amer MG, Mazen NF, Mohamed AM. Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study. Int J Immunopathol Pharmacol 2017; 30 (01) 13-24
- 86 Cachón AU, Quintal-Novelo C, Medina-Escobedo G, Castro-Aguilar G, Moo-Puc RE. Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats. J Diet Suppl 2017; 14 (02) 158-172
- 87 Mohamed MK, Khalaf MM, Abo-Youssef AM. , et al. Caffeineas a promising antifbrotic agent against CCL4-Induced liver fibrosis. Int J Pharm Pharm Sci 2017; 9: 42-47
- 88 Eraky SM, El-Mesery M, El-Karef A, Eissa LA, El-Gayar AM. Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression. Biomed Pharmacother 2018; 101: 49-57
- 89 Gressner OA, Lahme B, Siluschek M, Gressner AM. Identification of paraxanthine as the most potent caffeine-derived inhibitor of connective tissue growth factor expression in liver parenchymal cells. Liver Int 2009; 29 (06) 886-897
- 90 Stich HF, Rosin MP, Bryson L. Inhibition of mutagenicity of a model nitrosation reaction by naturally occurring phenolics, coffee and tea. Mutat Res 1982; 95 (2-3): 119-128
- 91 Mori H, Tanaka T, Shima H, Kuniyasu T, Takahashi M. Inhibitory effect of chlorogenic acid on methylazoxymethanol acetate-induced carcinogenesis in large intestine and liver of hamsters. Cancer Lett 1986; 30 (01) 49-54
- 92 Yan Y, Liu N, Hou N, Dong L, Li J. Chlorogenic acid inhibits hepatocellular carcinoma in vitro and in vivo. J Nutr Biochem 2017; 46: 68-73
- 93 Schilter B, Perrin I, Cavin C, Huggett AC. 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 (11) 2377-2384
- 94 Cavin C, Holzhäuser D, Constable A, Huggett AC, Schilter B. The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism. Carcinogenesis 1998; 19 (08) 1369-1375
- 95 Huber WW, Prustomersky S, Delbanco E. , et al. Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol. Arch Toxicol 2002; 76 (04) 209-217
- 96 Huber WW, Teitel CH, Coles BF. , et al. Potential chemoprotective effects of the coffee components kahweol and cafestol palmitates via modification of hepatic N-acetyltransferase and glutathione S-transferase activities. Environ Mol Mutagen 2004; 44 (04) 265-276
- 97 Huber WW, Rossmanith W, Grusch M. , et al. Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver. Food Chem Toxicol 2008; 46 (04) 1230-1238
- 98 Sparnins VL, Venegas PL, Wattenberg LW. Glutathione S-transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents. J Natl Cancer Inst 1982; 68 (03) 493-496
- 99 Higgins LG, Cavin C, Itoh K, Yamamoto M, Hayes JD. Induction of cancer chemopreventive enzymes by coffee is mediated by transcription factor Nrf2. Evidence that the coffee-specific diterpenes cafestol and kahweol confer protection against acrolein. Toxicol Appl Pharmacol 2008; 226 (03) 328-337
- 100 Morii H, Kuboyama A, Nakashima T. , et al. Effects of instant coffee consumption on oxidative DNA damage, DNA repair, and redox system in mouse liver. J Food Sci 2009; 74 (06) H155-H161
- 101 Kalthoff S, Ehmer U, Freiberg N, Manns MP, Strassburg CP. Coffee induces expression of glucuronosyltransferases by the aryl hydrocarbon receptor and Nrf2 in liver and stomach. Gastroenterology 2010; 139 (05) 1699-1710 , 1710.e1–1710.e2
- 102 Pietrocola F, Malik SA, Mariño G. , et al. Coffee induces autophagy in vivo. Cell Cycle 2014; 13 (12) 1987-1994
- 103 Hasegawa R, Ogiso T, Imaida K, Shirai T, Ito N. Analysis of the potential carcinogenicity of coffee and its related compounds in a medium-term liver bioassay of rats. Food Chem Toxicol 1995; 33 (01) 15-20
- 104 Miura Y, Ono K, Okauchi R, Yagasaki K. Inhibitory effect of coffee on hepatoma proliferation and invasion in culture and on tumor growth, metastasis and abnormal lipoprotein profiles in hepatoma-bearing rats. J Nutr Sci Vitaminol (Tokyo) 2004; 50 (01) 38-44
- 105 Silva-Oliveira EM, Fernandes PA, Moraes-Santos T. Effect of coffee on chemical hepatocarcinogenesis in rats. Nutr Cancer 2010; 62 (03) 336-342
- 106 Ferk F, Huber WW, Grasl-Kraupp B. , et al. Protective effects of coffee against induction of DNA damage and pre-neoplastic foci by aflatoxin B1 . Mol Nutr Food Res 2014; 58 (02) 229-238
- 107 Furtado KS, Polletini J, Dias MC, Rodrigues MA, Barbisan LF. Prevention of rat liver fibrosis and carcinogenesis by coffee and caffeine. Food Chem Toxicol 2014; 64: 20-26
- 108 Katayama M, Donai K, Sakakibara H. , et al. Coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the Long-Evans Cinnamon rat. Clin Nutr 2014; 33 (02) 302-310
- 109 Fujise Y, Okano J, Nagahara T, Abe R, Imamoto R, Murawaki Y. Preventive effect of caffeine and curcumin on hepato-carcinogenesis in diethylnitrosamine-induced rats. Int J Oncol 2012; 40 (06) 1779-1788
- 110 Hosaka S, Kawa S, Aoki Y. , et al. Hepatocarcinogenesis inhibition by caffeine in ACI rats treated with 2-acetylaminofluorene. Food Chem Toxicol 2001; 39 (06) 557-561
- 111 Boekschoten MV, Hofman MK, Buytenhek R, Schouten EG, Princen HM, Katan MB. Coffee oil consumption increases plasma levels of 7α-hydroxy-4-cholesten-3-one in humans. J Nutr 2005; 135 (04) 785-789
- 112 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
- 113 Bichler J, Cavin C, Simic T. , et al. Coffee consumption protects human lymphocytes against oxidative and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) induced DNA-damage: results of an experimental study with human volunteers. Food Chem Toxicol 2007; 45 (08) 1428-1436
- 114 Shaposhnikov S, Hatzold T, Yamani NE. , et al. Coffee and oxidative stress: a human intervention study. Eur J Nutr 2018; 57 (02) 533-544
- 115 Shahmohammadi HA, Hosseini SA, Hajiani E. , et al. Effects of green coffee bean extract supplementation on patients with non-alcoholic fatty liver disease: a randomized clinical trial. Hepat Mon 2017; 17
- 116 Jaquet M, Rochat I, Moulin J, Cavin C, Bibiloni R. Impact of coffee consumption on the gut microbiota: a human volunteer study. Int J Food Microbiol 2009; 130 (02) 117-121
- 117 Nakayama T, Oishi K. Influence of coffee (Coffea arabica) and galacto-oligosaccharide consumption on intestinal microbiota and the host responses. FEMS Microbiol Lett 2013; 343 (02) 161-168
- 118 Cowan TE, Palmnäs MS, Yang J. , et al. Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics. J Nutr Biochem 2014; 25 (04) 489-495
- 119 Santhekadur PK, Kumar DP, Sanyal AJ. Preclinical models of non-alcoholic fatty liver disease. J Hepatol 2018; 68 (02) 230-237