Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: A systematic review and meta-analysis

American Journal of Clinical Nutrition

Volumn 100, Issue 3, 2014, Pages 833-849

  Chung, Mei ^a,b   Ma, Jiantao ^c   Patel, Kamal ^a   Berger, Samantha ^a   Lau, Joseph ^a,d   Lichtenstein, Alice H ^c  

^a TUFTS MEDICAL CENTER   (United States)

^b TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c TUFTS UNIVERSITY   (United States)

^d BROWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; FAT; FRUCTOSE; GAMMA GLUTAMYLTRANSFERASE; HIGH FRUCTOSE CORN SYRUP; LIVER ENZYME; LIVER FAT; SUCROSE; SWEETENING AGENT; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; CORN SYRUP; NUTRITIVE SWEETENER; SUGAR INTAKE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CALORIC INTAKE; CARBOHYDRATE INTAKE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; GLUCOSE INTAKE; HUMAN; LIPOGENESIS; NONALCOHOLIC FATTY LIVER; SUGAR INTAKE; SYSTEMATIC REVIEW; COMPARATIVE STUDY; EVIDENCE BASED MEDICINE; HYPERPHAGIA; LIVER; META ANALYSIS; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; PATHOPHYSIOLOGY;

BIOLOGICAL MARKERS; DIETARY SUCROSE; ENERGY INTAKE; EVIDENCE-BASED MEDICINE; FRUCTOSE; HIGH FRUCTOSE CORN SYRUP; HUMANS; HYPERPHAGIA; LIVER; NON-ALCOHOLIC FATTY LIVER DISEASE; NUTRITIVE SWEETENERS;

EID: 84907334403     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.114.086314     Document Type: Article

References (86)

1. Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008;28:27-38.
2. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005-23.
3. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31.
4. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011;332:1519-23.
5. Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr 2007;86:285-300. (Pubitemid 47256910)
6. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116:1793-801. (Pubitemid 44033299)
7. Narasimhan S, Gokulakrishnan K, Sampathkumar R, Farooq S, Ravikumar R, Mohan V, Balasubramanyam M. Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes. Clin Biochem 2010;43:815-21.
8. McCullough AJ. The clinical features, diagnosis and natural history of non-alcoholic fatty liver disease. Clinics in Liver Disease 2004;8:521-33, viii. (Pubitemid 39141140)
9. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006;6:33.
10. Bedogni G, Kahn HS, Bellentani S, Tiribelli C. A simple index of lipid overaccumulation is a good marker of liver steatosis. BMC Gastroenterol 2010;10:988.
11. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011;34:274-85.
12. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010. J Pediatr 2013;162:496-500.e1.
13. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, Srishord M. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524-30e1; quiz e60.
14. White JS. Challenging the fructose hypothesis: new perspectives on fructose consumption and metabolism. Adv Nutr 2013;4:246-56.
15. Lustig RH. Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc 2010;110:1307-21.
16. Montonen J, Jarvinen R, Knekt P, Heliovaara M, Reunanen A. Consumption of sweetened beverages and intakes of fructose and glucose predict type 2 diabetes occurrence. J Nutr 2007;137:1447-54. (Pubitemid 46855484)
17. Ackerman Z, Oron-Herman M, Grozovski M, Rosenthal T, Pappo O, Link G, Sela BA. Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension 2005;45:1012-8. (Pubitemid 40628952)
18. Armutcu F, Coskun O, Gurel A, Kanter M, Can M, Ucar F, Unalacak M. Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats. Clin Biochem 2005;38:540-7. (Pubitemid 40693468)
19. Davail S, Rideau N, Bernadet MD, Andre JM, Guy G, Hoo-Paris R. Effects of dietary fructose on liver steatosis in overfed mule ducks. Horm Metab Res 2005;37:32-5. (Pubitemid 40269449)
20. Kawasaki T, Igarashi K, Koeda T, Sugimoto K, Nakagawa K, Hayashi S, Yamaji R, Inui H, Fukusato T, Yamanouchi T. Rats fed fructose-enriched diets have characteristics of nonalcoholic hepatic steatosis. J Nutr 2009;139:2067-71.
21. Takahashi Y, Soejima Y, Fukusato T. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World journal of gastroenterology. World J Gastroenterol 2012;18:2300-8.
22. Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004;79:537-43.
23. Welsh JA, Sharma AJ, Grellinger L, Vos MB. Consumption of added sugars is decreasing in the United States. Am J Clin Nutr 2011;94:726-34.
24. Russell R, Chung M, Balk EM, Atkinson S, Giovannucci EL, Ip S, Lichtenstein AH, Mayne ST, Raman G, Ross AC, et al. Opportunities and challenges in conducting systematic reviews to support the development of nutrient reference values: vitamin A as an example. Am J Clin Nutr 2009;89:728-33.
25. IOM. Finding what works in health care: standards for systematic reviews. Washington, DC: National Academy of Sciences, 2011.
26. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.
27. Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Beyene J, Chiavaroli L, Di Buono M, Jenkins AL, Leiter LA, et al. Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis. Ann Intern Med 2012;156:291-304.
28. Wang DD, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, Di Buono M, et al. The effects of fructose intake on serum uric acid vary among controlled dietary trials. J Nutr 2012;142:916-23.
29. Sievenpiper JL, Chiavaroli L, de Souza RJ, Mirrahimi A, Cozma AI, Ha V, Wang DD, Yu ME, Carleton AJ, Beyene J, et al. 'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials. Br J Nutr 2012;108:418-23.
30. Ha V, Sievenpiper JL, de Souza RJ, Chiavaroli L, Wang DD, Cozma AI, Mirrahimi A, Yu ME, Carleton AJ, Dibuono M, et al. Effect of fructose on blood pressure: a systematic review and meta-analysis of controlled feeding trials. Hypertension 2012;59:787-95.
31. Sievenpiper JL, Carleton AJ, Chatha S, Jiang HY, de Souza RJ, Beyene J, Kendall CW, Jenkins DJ. Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans. Diabetes Care 2009;32:1930-7.
32. Lichtenstein AH, Yetley EA, Lau J. Application of systematic review methodology to the field of nutrition. J Nutr 2008;138:2297-306.
33. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343.
34. Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, Lichtenstein A, Patel K, Raman G, Tatsioni A, et al. Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess (Full Rep) 2009;183:1-420.
35. Well G, Shea B, O'Connel D, Peterson J, Welch V, Bosos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analysis. 2011. Available from: http://www.ohri.ca/programs/clinical- epidemiology/oxford.asp (cited 3 July 2014).
36. Agency for Healthcare Research and Quality. Methods guide for effectiveness and comparative effectiveness reviews. AHRQ publication no. 10(14)-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality, 2014.
37. Dahabreh IJ, Hadar N, Chung M. Emerging magnetic resonance imaging technologies for musculoskeletal imaging under loading stress: scope of the literature. Ann Intern Med 2011;155:616-24.
38. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. (Pubitemid 17189972)
39. Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2009. Available from: www.cochrane-handbook.org.
40. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. (Pubitemid 37088507)
41. Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, Johnson RJ, Abdelmalek MF. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 2008;48:993-9.
42. Thuy S, Ladurner R, Volynets V, Wagner S, Strahl S, Konigsrainer A, Maier KP, Bischoff SC, Bergheim I. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J Nutr 2008;138:1452-5.
43. Volynets V, Kuper MA, Strahl S, Maier IB, Spruss A, Wagnerberger S, Konigsrainer A, Bischoff SC, Bergheim I. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci 2012;57:1932-41.
44. Davis JN, Le KA, Walker RW, Vikman S, Spruijt-Metz D, Weigensberg MJ, Allayee H, Goran MI. Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption. Am J Clin Nutr 2010;92:1522-7.
45. Mager DR, Patterson C, So S, Rogenstein CD, Wykes LJ, Roberts EA. Dietary and physical activity patterns in children with fatty liver. Eur J Clin Nutr 2010;64:628-35.
46. Aeberli I, Gerber PA, Hochuli M, Kohler S, Haile SR, Gouni-Berthold I, Berthold HK, Spinas GA, Berneis K. Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial. Am J Clin Nutr 2011;94:479-85.
47. Koh ET, Ard NF, Mendoza F. Effects of fructose feeding on blood parameters and blood pressure in impaired glucose-tolerant subjects. J Am Diet Assoc 1988;88:932-8.
48. Ngo Sock ET, Le KA, Ith M, Kreis R, Boesch C, Tappy L. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Br J Nutr 2010;103:939-43.
49. Silbernagel G, Lutjohann D, Machann J, Meichsner S, Kantartzis K, Schick F, Haring HU, Stefan N, Fritsche A. Cholesterol synthesis is associated with hepatic lipid content and dependent on fructose/glucose intake in healthy humans. Exp Diabetes Res 2012;2012:361863.
50. Silbernagel G, Machann J, Unmuth S, Schick F, Stefan N, Haring HU, Fritsche A. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Br J Nutr 2011;106:79-86.
51. Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009;119:1322-34.
52. Al-Waili NS. Effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individuals. J Med Food 2003;6:135-4049.
53. Couchepin C, Le KA, Bortolotti M, da Encarnacao JA, Oboni JB, Tran C, Schneiter P, Tappy L. Markedly blunted metabolic effects of fructose in healthy young female subjects compared with male subjects. Diabetes Care 2008;31:1254-6.
54. Lê KA, Ith M, Kreis R, Faeh D, Bortolotti M, Tran C, Boesch C, Tappy L. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J Clin Nutr 2009;89:1760-56.
55. Faeh D, Minehira K, Schwarz JM, Periasamy R, Park S, Tappy L. Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. Diabetes 2005;54:1907-13. (Published erratum appears in Diabetes 2006;55:563.)
56. Lê KA, Faeh D, Stettler R, Ith M, Kreis R, Vermathen P, Boesch C, Ravussin E, Tappy L. A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. Am J Clin Nutr 2006;84:1374-9. (Pubitemid 44912820)
57. Perez-Pozo SE, Schold J, Nakagawa T, Sanchez-Lozada LG, Johnson RJ, Lillo JL. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond) 2010;34:454-61.
58. Sobrecases H, Le KA, Bortolotti M, Schneiter P, Ith M, Kreis R, Boesch C, Tappy L. Effects of short-term overfeeding with fructose, fat and fructose plus fat on plasma and hepatic lipids in healthy men. Diabetes Metab 2010;36:244-6.
59. Bravo S, Lowndes J, Sinnett S, Yu Z, Rippe J. Consumption of sucrose and high-fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles. Appl Physiol Nutr Metab 2013;38:681-8.
60. Kelsay JL, Behall KM, Holden JM, Prather ES. Diets high in glucose or sucrose and young women. Am J Clin Nutr 1974;27:926-36.
61. Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 2012;95:283-9.
62. Porikos KP, Van Itallie TB. Diet-induced changes in serum transaminase and triglyceride levels in healthy adult men. Role of sucrose and excess calories. Am J Med 1983;75:624-30. (Pubitemid 13012156)
63. Purkins L, Love ER, Eve MD, Wooldridge CL, Cowan C, Smart TS, Johnson PJ, Rapeport WG. The influence of diet upon liver function tests and serum lipids in healthy male volunteers resident in a phase I unit. Br J Clin Pharmacol 2004;57:199-208. (Pubitemid 38223532)
64. Theytaz F, Noguchi Y, Egli L, Campos V, Buehler T, Hodson L, Patterson BW, Nishikata N, Kreis R, Mittendorfer B, et al. Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans. Am J Clin Nutr 2012;96:1008-16.
65. Vos MB, Weber MB, Welsh J, Khatoon F, Jones DP, Whitington PF, McClain CJ. Fructose and oxidized low-density lipoprotein in pediatric nonalcoholic fatty liver disease: a pilot study. Arch Pediatr Adolesc Med 2009;163:674-5.
66. Goletzke J, Buyken AE, Gopinath B, Rochtchina E, Barclay AW, Cheng G, Brand-Miller JC, Mitchell P. Carbohydrate quality is not associated with liver enzyme activity and plasma TAG and HDL concentrations over 5 years in an older population. Br J Nutr 2013;110:918-25.
67. Johnston RD, Stephenson MC, Crossland H, Cordon SM, Palcidi E, Cox EF, Taylor MA, Aithal GP, Macdonald IA. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 2013;145:1016-25.e2.
68. Cox CL, Stanhope KL, Schwarz JM, Graham JL, Hatcher B, Griffen SC, Bremer AA, Berglund L, McGahan JP, Keim NL, et al. Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans. Nutr Metab (Lond) 2012;9:68.
69. Volynets V, Machann J, Kuper MA, Maier IB, Spruss A, Konigsrainer A, Bischoff SC, Bergheim I. A moderate weight reduction through dietary intervention decreases hepatic fat content in patients with non-alcoholic fatty liver disease (NAFLD): a pilot study. Eur J Nutr 2013;52:527-35.
70. Cuthbertson DJ, Irwin A, Pugh CJ, Jones H, Sprung VS, Daousi C, Adams VL, Bimson WE, Shojaee-Moradie F, Umpleby AM, et al. Ectopic lipid storage in Non-Alcoholic Fatty Liver Disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle. Clin Sci (Epub ahead of print 16 April 2014).
71. Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician 1999;59:2223-30. (Pubitemid 29197947)
72. Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr 2007;74:663-71. (Pubitemid 350030794)
73. Chiu S, Sievenpiper JL, de Souza RJ, Cozma AI, Mirrahimi A, Carleton AJ, Ha V, Di Buono M, Jenkins AL, Leiter LA, et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr 2014;68:416-23.
74. Sanyal AJ. NASH: a global health problem. Hepatol Res 2011;41:670-4.
75. Torres DM, Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology 2008;134:1682-98. (Pubitemid 351615413)
76. Lazo M, Hernaez R, Bonekamp S, Kamel IR, Brancati FL, Guallar E, Clark JM. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011;343:d6891.
77. Schindhelm RK, Heine RJ, Diamant M. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30:e94; author reply e95.
78. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005;288:E462-8. (Pubitemid 40110657)
79. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011;140:124-31.
80. Mensink RP, Plat J, Schrauwen P. Diet and nonalcoholic fatty liver disease. Curr Opin Lipidol 2008;19:25-9.
81. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005;100:1082-90. (Pubitemid 40769045)
82. Bugianesi E, Marzocchi R, Villanova N, Marchesini G. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): treatment. Best Pract Res Clin Gastroenterol 2004;18:1105-16. (Pubitemid 39517695)
83. Clark JM. Weight loss as a treatment for nonalcoholic fatty liver disease. J Clin Gastroenterol 2006;40(suppl 1):S39-43a.
84. Wagenknecht LE, Palmer ND, Bowden DW, Rotter JI, Norris JM, Ziegler J, Chen YD, Haffner S, Scherzinger A, Langefeld CD. Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study. Liver Int 2011;31:412-6.
85. Chung M, Balk EM, Ip S, Lee J, Terasawa T, Raman G, Trikalinos T, Lichtenstein AH, Lau J. Systematic review to support the development of nutrient reference intake values: challenges and solutions. Am J Clin Nutr 2010;92:273-6.
86. Kirkham JJ, Dwan KM, Altman DG, Gamble C, Dodd S, Smyth R, Williamson PR. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. BMJ 2010;340:c365.