2018, Number 5
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Rev Med Inst Mex Seguro Soc 2018; 56 (5)
Molecular alterations induced by fructose and its impact on metabolic diseases
Loza-Medrano SS, Baiza-Gutman LA, Ibáñez-Hernández MÁ, Cruz-López M, Díaz-Flores M
Language: Spanish
References: 91
Page: 491-504
PDF size: 1989.09 Kb.
ABSTRACT
Scientific evidence has identified that the excessive
consumption of products made from high-fructose corn
syrup is a trigger for obesity, whose prevalence
increased in recent years. Due to the metabolic
characteristics of fructose, a rapid gastric emptying is
produced, altering signals of hunger-satiety and
decreasing the appetite. In addition to the hepatic level
during catabolism, triose phosphate is generated and
adenosine triphosphate (ATP) is reduced, producing
uric acid. Triose phosphate triggers the synthesis of
fatty acids that increase the production and
accumulation of triglycerides, diacylglycerols and
ceramides that induce insulin resistance.
Hyperlipidemia, insulin resistance and hyperuricemia
contribute to the development of hypertension,
cardiovascular disease, kidney failure, non-alcoholic
fatty liver disease and some kinds of cancer.
Understanding the molecular mechanisms and
signaling pathways altered by the consumption of
fructose is relevant to understand the development of
metabolic diseases, as well as to seek therapeutic
strategies to improve quality of life.
REFERENCES
Brown CM, Dulloo AG, Montani JP. Sugary drinks in the pathogenesis of obesity and cardiovascular diseases. Int J Obes (Lond). 2008;32 Suppl 6:S28-34. doi: 10.1038/ijo.2008.204.
O'Connor L, Imamura F, Lentjes MA, Khaw KT, Wareham NJ, Forouhi NG.. Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia. 2015;58(7):1474-83.
Tappy L, Rosser R, Surowska A. Pathogenesis of cardiovascular and metabolic diseases: are fructosecontaining sugars more involved than other calories? Curr Hypertens Rep. 2016;18(6):44.
Feinman RD, Fine EJ. Fructose in perspective. Nutr Metab (Lond). 2013;10(45):1-11.
Marshall RO, Kooi ER. Enzymatic convertion of Dglucose to D-fructose. Science. 1957;125(3249):648-9. Figura 4 Impacto de la fructosa en el desarrollo de enfermedades metabólicas. La ingesta de fructosa se asocia con enfermedades metabólicas, afecta corazón, riñón e hígado. La hipertensión y la enfermedad cardiovascular son provocadas por hiperuricemia que genera disfunción endotelial y, además, sobreproducción de VLDL o LDL, inductoras de ateromas. A nivel renal, la hipertensión y la acumulación de cristales de urato reducen la tasa de filtración glomerular y la consecuente enfermedad renal crónica. En el hígado, la producción descontrolada de ácidos grasos, la formación de triacilglicéridos y su acumulación en hepatocitos produce esteatosis con progresión a esteatohepatitis no alcohólica (con o sin presencia de fibrosis) y potencial evolución a cirrosis hepática. El consumo excesivo y prolongado de fructosa se ha asociado con ciertos tipos de cáncer por el incremento de insulina y la activación de IGF-1, por la vía de las pentosas fosfato, inductoras de proliferación celular VLDL = lipoproteína de muy baja densidad; LDL = lipoproteína de baja densidad; IGF-1 = factor de crecimiento insulínico-1 Estrógeno Cáncer Insulina IGF-1 Activación de vía de las pentosas fosfato Endometrial tipo I Proliferación celular Hipertensión Ácido úrico Disfunción endotelial Óxido nítrico Reabsorción de sodio Enfermedad cardiovascular VLDL LDL ox-LDL Célula Ateroma espumosa Enfermedad hepàtica Ácidos grasos de novo VLDL Esteatosis Lipoperoxidación Transaminasas FIbrosis Esteatohepatitis Enfermedad renal crónica Presión arterial Tasa de filtración glomerular Fibrosis intersticial Cristales de urato Inflamación 2
Hanover LM, White JS. Manufacturing, composition, and applications of fructose. Am J Clin Nutr. 1993;58 (5):724S-32.
Tappy L, Mittendorfer B. Fructose toxicity: is the science ready for public health actions? Curr Opin Clin Nutr Metab Care. 2012;15(4):357-61.
Tappy L, Lê KA. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010;90 (1):23-46.
Corpe CP, Basaleh MM, Affleck J, Gould G, Jess TJ, Kellett GL. The regulation of GLUT5 and GLUT2 activity in the adaptation of intestinal brush-border fructose transport in diabetes. Pflugers Arch. 1996;432(2):192- 201.
Sanders FW, Griffin JL. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biol Rev Camb Philos Soc. 2016;91(2):452-68.
Moore JB, Gunn PJ, Fielding BA. The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease. Nutrients. 2014;6(12):5679-703.
Lustig RH. Fructose: metabolic, hedonic, and societal parallels with etanol. J Am Diet Assoc. 2010;110(9):1307-21.
Bellisle F, Drewnowski A, Anderson GH, Westerterp- Plantenga M, Martin CK. Sweetness, satiation, and satiety. J Nutr. 2012;142(6):1149S-54S.
Page KA, Chan O, Arora J, Belfort-Deaguiar R, Dzuira J, Roehmholdt B, et al. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA. 2013;309(1):63-70. doi: 10.1001/jama.2012.116975.
Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest. 2005;115 (5):1298-305.
Ochoa M, Lallès JP, Malbert CH, Val-Laillet D. Dietary sugars: their detection by the gut-brain axis and their peripheral and central effects in health and diseases. Eur J Nutr. 2015;54(1):1-24. doi: 10.1007/s00394-014-0776-y.
Lindqvist A, Baelemans A, Erlanson-Albertsson C. Effects of sucrose, glucose and fructose on peripheral and central appetite signals. Regul Pept. 2008 Oct 9;150(1-3): 26-32. doi: 10.1016/j.regpep.2008.06.008.
Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, et al. Ghrelin, a novel growth hormonereleasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000;141(11):4255-61.
Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407(6806):908-13.
Yau AM, McLaughlin J, Maughan RJ, Gilmore W, Evans GH. The Effect of Short-Term Dietary Fructose Supplementation on Gastric Emptying Rate and Gastrointestinal Hormone Responses in Healthy Men. Nutrients. 2017 Mar 10;9(3). pii: E258. doi: 10.3390/ nu9030258.
Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell. 2008 Feb 8; 132(3):387-96. doi: 10.1016/j.cell.2008.01.017.
Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409(6817):194-8.
Van Name M, Giannini C, Santoro N, Jastreboff AM, Kubat J, Li F, Kursawe R, et al. Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance. Obesity (Silver Spring). 2015;23 (3):653-61. doi: 10.1002/oby.21019.
Flier JS. Leptin expression and action: new experimental paradigms. Proc Natl Acad Sci U S A. 1997;94(9):4242-5.
Carlo AS, Pyrski M, Loudes C, Faivre-Baumann A, Epelbaum J, Williams LM, et al. Leptin sensitivity in the developing rat hypothalamus. Endocrinology. 2007 Dec;148 (12):6073-82.
Ozias MK, Li S, Hull HR, Brooks WM, Carlson SE. Relationship of circulating adipokines to body composition in pregnant women. Adipocyte. 2014;4(1): 44-9. doi: 10.4161/adip.29805.
Rodríguez L, Panadero MI, Roglans N, Otero P, Alvarez- Millán JJ, Laguna JC, et al. Fructose during pregnancy affects maternal and fetal leptin signaling. J Nutr Biochem. 2013 Oct;24(10):1709-16. doi: 10.1016/j.jnutbio.2013.02. 011.
Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent highfat feeding. Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1370-5. doi: 10.1152/ajpregu.00195.2008.
Banks WA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, et al. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes. 2004 May; 53(5):1253-60.
Erlanson-Albertsson C, Lindqvist A. Fructose affects enzymes involved in the synthesis and degradation of 4 hypothalamic endocannabinoids. Regul Pept. 2010;161 (1-3):87-91. doi: 10.1016/j.regpep.2010.01.003.
London E, Castonguay TW. High fructose diets increase 11β-hydroxysteroid dehydrogenase type 1 in liver and visceral adipose in rats within 24-h exposure. Obesity (Silver Spring). 2011;19(5):925-32.
Legeza B, Balázs Z, Nashev LG, Odermatt A. The microsomal enzyme 17β-hydroxysteroid dehydrogenase 3 faces the cytoplasm and uses NADPH generated by glucose-6-phosphate dehydrogenase. Endocrinology. 2013 Jan;154(1):205-13. doi: 10.1210/en.2012-1778.
Newman E, O'Connor DB, Conner M. Daily hassles and eating behaviour: the role of cortisol reactivity status. Psychoneuroendocrinology. 2007;32(2):125-32.
Chong MF, Fielding BA, Frayn KN. Mechanisms for the acute effect of fructose on postprandial lipemia. Am J Clin Nutr. 2007;85(6):1511-20.
Park OJ, Cesar D, Faix D, Wu K, Shackleton CH, Hellerstein MK. Mechanisms of fructose-induced hypertriglyceridaemia in the rat. Activation of hepatic pyruvate dehydrogenase through inhibition of pyruvate dehydrogenase kinase. Biochem J. 1992 Mar 15;282 (Pt 3):753-7.
Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH. Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics. 1995;25(3):667-73.
Koo HY, Miyashita M, Cho BH, Nakamura MT. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus. Biochem Biophys Res Commun. 2009 Dec 11;390(2):285-9. doi: 10.1016/j.bbrc.2009.09.109.
Samuel VT. Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab. 2011 Feb;22(2):60-5. doi: 10.1016/j.tem.2010.10.003.
Uyeda K, Repa JJ. Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis. Cell Metab. 2006 Aug;4(2):107-10.
Softic S, Cohen DE, Kahn CR. Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease. Dig Dis Sci. 2016 May;61(5):1282-93. doi: 10.1007/s10620-016-4054-0.
Tobey TA, Mondon CE, Zavaroni I, Reaven GM. Mechanism of insulin resistance in fructose-fed rats. Metabolism. 1982;31(6):608-612.
Galipeau D, Verma S, McNeill JH. Female rats are protected against fructose-induced changes in metabolism and blood pressure. Am J Physiol Heart Circ Physiol. 2002;283(6):H2478-84.
Aburasayn H, Batran R, Ussher JR. Targeting ceramide metabolism in obesity. Am J Physiol Endocrinol Metab. 2016;311(2):E423-35.
Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005;63(5):133-57.
Szendroedi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, et al. Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans. Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9597-602. doi: 10.1073/pnas.1409229111.
Krssak M, Brehm A, Bernroider E, Anderwald C, Nowotny P, Dalla Man C, et al. Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes. Diabetes. 2004; 53(12):3048-56.
Maiztegui B, Borelli MI, Raschia MA, Del Zotto H, Gagliardino JJ. Islet adaptive changes to fructoseinduced insulin resistance: beta-cell mass, glucokinase, glucose metabolism, and insulin secretion. J Endocrinol. 2009 Feb;200(2):139-49. doi: 10.1677/JOE-08-0386.
Asghar ZA, Cusumano A, Yan Z, Remedi MS, Moley KH. Reduced islet function contributes to impaired glucose homeostasis in fructose-fed mice. Am J Physiol Endocrinol Metab. 2017;312(2):E109-16. doi: 10.1152/ajpendo.00279.2016.
Balakumar M, Raji L, Prabhu D, Sathishkumar C, Prabu P, Mohan V, et al. High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress. Mol Cell Biochem. 2016 Dec;423 (1-2):93-104.
Tilg H, Hotamisligil GS. Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology. 2006;131(3):934-45.
Stack AG, Hanley A, Casserly LF, Cronin CJ, Abdalla AA, Kiernan TJ, et al. Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality. QJM. 2013;106(7):647-58. doi: 10.1093/qjmed/hct083.
Carran EL, White SJ, Reynolds AN, Haszard JJ, Venn BJ. Acute effect of fructose intake from sugarsweetened beverages on plasma uric acid: a randomised controlled trial. Eur J Clin Nutr. 2016;70 (9):1034-8. doi: 10.1038/ejcn.2016.112.
Nakagawa T, Tuttle KR, Short RA, Johnson RJ. Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol. 2005;1(2):80-6.
Sarnesto A, Linder N, Raivio KO. Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein. Lab Invest. 1996;74(1):48-56.
Bellentani S, Scaglioni F, Marino M, Bedogni G.Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):155-61. doi: 10.1159/000282080.
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387-95.
Sheludiakova A, Rooney K, Boakes RA. Metabolic and behavioural effects of sucrose and fructose/glucose drinks in the rat. Eur J Nutr. 2012;51(4):445-54. doi: 10.1007/s00394-011-0228-x.
Hecker PA, Mapanga RF, Kimar CP, Ribeiro RF Jr, Brown BH, O'Connell KA, et al. Effects of glucose-6- phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets. Am J Physiol Endocrinol Metab. 2012;303(8): E959-72. doi: 10.1152/ajpendo.00202.2012.
Yilmaz Y. Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions? Aliment Pharmacol Ther. 2012;36(9):815-23.
Yki-Järvinen H. Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance. Nutrients. 2015;7(11):9127-38. doi: 10.3390/nu7115454.
Jarukamjorn K, Jearapong N, Pimson C, Chatuphonprasert W. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice. Scientifica (Cairo). 2016;2016:5029414. doi: 10.1155/2016/5029414.
James PE, Lang D, Tufnell-Barret T, Milsom AB, Frenneaux MP. Vasorelaxation by red blood cells and impairment in diabetes: reduced nitric oxide and oxygen delivery by glycated hemoglobin. Circ Res. 2004 Apr 16;94(7):976-83.
Zemančíková A, Török J. Cardiovascular effects of highfructose intake in rats with nitric oxide deficiency. Interdiscip Toxicol. 2014;7(3):159-64. doi: 10.2478/intox-2014-0022.
Gray C, Gardiner SM, Elmes M, Gardner DS. Excess maternal salt or fructose intake programmes sex- 6 specific, stress- and fructose-sensitive hypertension in the offspring. Br J Nutr. 2016;115(4):594-604. doi: 10.1017/S0007114515004936.
Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructoseinduced insulin resistance and hypertension in rats. Hypertension. 1987;10(5):512-6.
Farah V, Elased KM, Morris M. Genetic and dietary interactions: role of angiotensin AT1a receptors in response to a high-fructose diet. Am J Physiol Heart Circ Physiol. 2007;293(2):H1083-9.
Gugliucci A. Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases. Adv Nutr. 2017;8(1):54-62. doi: 10.3945/an.116.013912.
Stanhope KL, Havel PJ. Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr Opin Lipidol. 2008;19(1):16-24. doi: 10.1097/MOL.0b013e3282f2b24a.
Meshkani R, Adeli K. Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin Biochem. 2009; 42(13-14):1331-46.doi:10.1016/j.clinbiochem. 2009.05.018.
Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61(10): 1041-51. doi: 10.1016/j.jacc.2012.10.054.
Estronca LM, Silva JC, Sampaio JL, Shevchenko A, Verkade P, Vaz AD, et al. Molecular etiology of atherogenesis--in vitro induction of lipidosis in macrophages with a new LDL model. PLoS One. 2012;7(4):e34822. doi: 10.1371/journal.pone.0034822.
Kolderup A, Svihus B. Fructose Metabolism and Relation to Atherosclerosis, Type 2 Diabetes, and Obesity. J Nutr Metab. 2015;2015:823081. doi: 10.1155/2015/823081.
Dornas WC, de Lima WG, Dos Santos RC, de Souza MO, Silva M, Diniz MF, et al. Salt overload in fructose-fed insulin-resistant rats decreases paraoxonase-1 activity. Nutr Metab (Lond). 2012;9(1):63. doi: 10.1186/1743- 7075-9-63.
Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, et al. Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension. 2003 Jun;41(6):1287-93.
Xu C, Lu A, Lu X, Zhang L, Fang H, Zhou L, et al. Activation of Renal (Pro)Renin Receptor Contributes to High Fructose-Induced Salt Sensitivity. Hypertension. 2017;69(2):339-48.doi:10.1161/HYPERTENSIONAHA. 116.08240.
Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Shafiu M, Sundaram S, Le M, et al. Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes. 2013;62(10): 3307-15. doi: 10.2337/db12-1814.
Sánchez-Lozada LG, Tapia E, Santamaría J, Avila- Casado C, Soto V, Nepomuceno T, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int. 2005;67(1):237-47.
Gersch MS, Mu W, Cirillo P, Reungjui S, Zhang L, Roncal C, et al. Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am J Physiol Renal Physiol. 2007;293(4):F1256-61.
Bjornstad P, Lanaspa MA, Ishimoto T, Kosugi T, Kume S, Jalal D, et al. Fructose and uric acid in diabetic nephropathy. Diabetologia. 2015;58(9):1993-2002. doi: 10.1007/s00125-015-3650-4.
Yu G, Bai Z, Chen Z, Chen H, Wang G, Wang G, et al. The NLRP3 inflammasome is a potential target of ozone therapy aiming to ease chronic renal inflammation in chronic kidney disease. Int Immunopharmacol. 2017;43:203-209. doi: 10.1016/j.intimp.2016.12.022.
Parekh N, Chandran U, Bandera EV. Obesity in cancer survival. Annu Rev Nutr. 2012;32:311-42. doi: 10.1146/annurev-nutr-071811-150713.
Sieri S, Pala V, Brighenti F, Pellegrini N, Muti P, Micheli A, et al. Dietary glycemic index, glycemic load, and the risk of breast cancer in an Italian prospective cohort study. Am J Clin Nutr. 2007 Oct;86(4):1160-6.
Zhang X, Albanes D, Beeson WL, van den Brandt PA, Buring JE, Flood A, et al. Risk of colon cancer and coffee, tea, and sugar-sweetened soft drink intake: pooled analysis of prospective cohort studies. J Natl Cancer Inst. 2010;102(11):771-83. doi: 10.1093/jnci/djq107.
Drake I, Sonestedt E, Gullberg B, Ahlgren G, Bjartell A, Wallström P, et al. Dietary intakes of carbohydrates in relation to prostate cancer risk: a prospective study in the Malmö Diet and Cancer cohort. Am J Clin Nutr. 2012;96 (6):1409-18. doi: 10.3945/ajcn.112.039438.
Larsson SC, Bergkvist L, Wolk A. Consumption of sugar and sugar-sweetened foods and the risk of pancreatic cancer in a prospective study. Am J Clin Nutr. 2006 Nov; 84(5):1171-6.
Laguna JC, Alegret M, Roglans N. Simple sugar intake and hepatocellular carcinoma: epidemiological and mechanistic insight. Nutrients. 2014;6(12):5933-54. doi: 10.3390/nu6125933. 8
Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet. 2005;366(9484):491-505.
Stamp D, Zhang XM, Medline A, Bruce WR, Archer MC. Sucrose enhancement of the early steps of colon carcinogenesis in mice. Carcinogenesis. 1993;14(4):777-9.
Michaud DS, Fuchs CS, Liu S, Willett WC, Colditz GA, Giovannucci E. Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. 2005;14(1):138-47.
Liu H, Huang D, McArthur DL, Boros LG, Nissen N, Heaney AP. Fructose induces transketolase flux to promote pancreatic cancer growth. Cancer Res. 2010 Aug 1;70(15): 6368-76. doi: 10.1158/0008-5472.CAN-09-4615.
Port AM, Ruth MR, Istfan NW. Fructose consumption and cancer: is there a connection? Curr Opin Endocrinol Diabetes Obes. 2012 Oct;19(5):367-74. doi: 10.1097/MED.0b013e328357f0cb.