Fructose has always been present in our diet, but its consumption has increased markedly over the past 200 years. This is mainly due to consumption of sucrose or high-fructose corn syrup in industrial foods and beverages. Unlike glucose, fructose cannot be directly used as an energy source by all cells of the human body and needs first to be converted into glucose, lactate or fatty acids in the liver, intestine and kidney. Because of this specific two-step metabolism, some energy is consumed in splanchnic organs to convert fructose into other substrates, resulting in a lower net energy efficiency of fructose compared with glucose. A high intake of fructose-containing sugars is associated with body weight gain in large cohort studies, and fructose can certainly contribute to energy imbalance leading to obesity. Whether fructose-containing foods promote obesity more than other energy-dense foods remains controversial, however. A short-term (days–weeks) high-fructose intake is not associated with an increased fasting glycemia nor to an impaired insulin-mediated glucose transport in healthy subjects. It, however, increases hepatic glucose production, basal and postprandial blood triglyceride concentrations and intrahepatic fat content. Whether these metabolic alterations are early markers of metabolic dysfunction or merely adaptations to the specific two-step fructose metabolism remain unknown.
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Lustig RH, Schmidt LA, Brindis CD . Public health: the toxic truth about sugar. Nature 2012; 482: 27–29.
Taubes G . Treat obesity as physiology, not physics. Nature 2012; 492: 155.
Stanhope KL . Sugar consumption, metabolic disease and obesity: the state of the controversy. Crit Rev Clin Lab Sci 2016; 53: 52–57.
Hargrove JL . Adipose energy stores, physical work, and the metabolic syndrome: lessons from hummingbirds. Nutr J 2005; 4: 36.
Suarez RK, Gass CL . Hummingbird foraging and the relation between bioenergetics and behaviour. Comp Biochem Physiol A Mol Integr Physiol 2002; 133: 335–343.
Shimozuru M, Kamine A, Tsubota T . Changes in expression of hepatic genes involved in energy metabolism during hibernation in captive, adult, female Japanese black bears (Ursus thibetanus japonicus. Comp Biochem Physiol B Biochem Mol Biol 2012; 163: 254–261.
Verkhovtseva NV, Filina N, Pukhov DE . [Evolutionary role of iron in metabolism of prokaryotes and biogeochemical processes]. Zh Evol Biokhim Fiziol 2001; 37: 338–343.
Hansen TA . Metabolism of sulfate-reducing prokaryotes. Antonie Van Leeuwenhoek 1994; 66: 165–185.
Hochachka PW . Cross-species studies of glycolytic function. Adv Exp Med Biol 1999; 474: 219–229.
Hochachka PW, Rupert JL, Monge C . Adaptation and conservation of physiological systems in the evolution of human hypoxia tolerance. Comp Biochem Physiol A Mol Integr Physiol 1999; 124: 1–17.
Jungas RL, Halperin ML, Brosnan JT . Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev 1992; 72: 419–448.
Mayes PA . Intermediary metabolism of fructose. Am J Clin Nutr 1993; 58: 754S–765S.
Williams CA, Macdonald I . Metabolic effects of dietary galactose. World Rev Nutr Diet 1982; 39: 23–52.
Mascord D, Smith J, Starmer GA, Whitfield JB . Effects of increasing the rate of alcohol metabolism on plasma acetate concentration. Alcohol Alcohol 1992; 27: 25–28.
Heinz F, Weiner F . Enzymes of fructose metabolism in the liver of some vertebrates. Comp Biochem Physiol 1969; 31: 283–296.
Springer N, Lindbloom-Hawley S, Schermerhorn T . Tissue expression of ketohexokinase in cats. Res Vet Sci 2009; 87: 115–117.
Schermerhorn T . Normal glucose metabolism in carnivores overlaps with diabetes pathology in non-carnivores. Front Endocrinol (Lausanne) 2013; 4: 188.
Tanaka A, Inoue A, Takeguchi A, Washizu T, Bonkobara M, Arai T . Comparison of expression of glucokinase gene and activities of enzymes related to glucose metabolism in livers between dog and cat. Vet Res Commun 2005; 29: 477–485.
Gilbertson TA, Khan NA . Cell signaling mechanisms of oro-gustatory detection of dietary fat: advances and challenges. Prog Lipid Res 2014; 53: 82–92.
Reed DR, Knaapila A . Genetics of taste and smell: poisons and pleasures. Prog Mol Biol Transl Sci 2010; 94: 213–240.
Bellisle F, Drewnowski A, Anderson GH, Westerterp-Plantenga M, Martin CK . Sweetness, satiation, and satiety. J Nutr 2012; 142: 1149S–1154S.
Laffitte A, Neiers F, Briand L . Functional roles of the sweet taste receptor in oral and extraoral tissues. Curr Opin Clin Nutr Metab Care 2014; 17: 379–385.
Jiang P, Josue J, Li X, Glaser D, Li W, Brand JG et al. Major taste loss in carnivorous mammals. Proc Natl Acad Sci USA 2012; 109: 4956–4961.
Mintz SN Sweetness and Power: The Place of Sugar in Modern History. Penguin Books: London, UK, 1985.
White JS . Straight talk about high-fructose corn syrup: what it is and what it ain't. Am J Clin Nutr 2008; 88: 1716S–1721S.
Marriott BP, Cole N, Lee E . National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J Nutr 2009; 139: 1228S–1235S.
Langlois K, Garriguet D. Sugar Consumption Among Canadians of all Ages. Health Reports/Statistics Canada, Canadian Centre for Health Information=Rapports sur la Sante/Statistique Canada, vol. 22. Centre Canadien d'Information sur la Sante. Health Reports, 2011, pp 23–27.
Sun SZ, Anderson GH, Flickinger BD, Williamson-Hughes PS, Empie MW . Fructose and non-fructose sugar intakes in the US population and their associations with indicators of metabolic syndrome. Food Chem Toxicol 2011; 49: 2875–2882.
Tappy L, Le KA . Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 2010; 90: 23–46.
Van den Berghe G . Metabolic effects of fructose in the liver. Curr Top Cell Regul 1978; 13: 97–135.
Malaisse WJ, Malaisse-Lagae F, Davies DR, Vandercammen A, Van Schaftingen E . Regulation of glucokinase by a fructose-1-phosphate-sensitive protein in pancreatic islets. Eur J Biochem 1990; 190: 539–545.
Watford M . Small amounts of dietary fructose dramatically increase hepatic glucose uptake through a novel mechanism of glucokinase activation. Nutr Rev 2002; 60: 253–257.
Sun SZ, Empie MW . Fructose metabolism in humans - what isotopic tracer studies tell us. Nutr Metab 2012; 9: 89.
Theytaz F, de Giorgi S, Hodson L, Stefanoni N, Rey V, Schneiter P et al. Metabolic fate of fructose ingested with and without glucose in a mixed meal. Nutrients 2014; 6: 2632–2649.
Grand RJ, Schay MI, Jaksina S . Development and control of intestinal and hepatic fructokinase. Pediatr Res 1974; 8: 765–770.
Korieh A, Crouzoulon G . Dietary regulation of fructose metabolism in the intestine and in the liver of the rat. Duration of the effects of a high fructose diet after the return to the standard diet. Arch Int Physiol Biochim Biophys 1991; 99: 455–460.
Bjorkman O, Crump M, Phillips RW . Intestinal metabolism of orally administered glucose and fructose in Yucatan miniature swine. J Nutr 1984; 114: 1413–1420.
Bjorkman O, Gunnarsson R, Hagstrom E, Felig P, Wahren J . Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls. J Clin Invest 1989; 83: 52–59.
Cozma AI, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Wang DD et al. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes Care 2012; 35: 1611–1620.
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: 1907–1913.
Le KA, Faeh D, Stettler R, Ith M, Kreis R, Vermathen P et al. 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: 1374–1379.
Aeberli I, Hochuli M, Gerber PA, Sze L, Murer SB, Tappy L et al. Moderate amounts of fructose consumption impair insulin sensitivity in healthy young men: a randomized controlled trial. Diabetes Care 2013; 36: 150–156.
Tappy L, Le KA . Health effects of fructose and fructose-containing caloric sweeteners: where do we stand 10 years after the initial whistle blowings? Curr Diab Rep 2015; 15: 627.
David Wang D, Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V et al. Effect of fructose on postprandial triglycerides: a systematic review and meta-analysis of controlled feeding trials. Atherosclerosis 2014; 232: 125–133.
Sievenpiper JL, Carleton AJ, Chatha S, Jiang HY, de Souza RJ, Beyene J et al. 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: 1930–1937.
Zhang YH, An T, Zhang RC, Zhou Q, Huang Y, Zhang J . Very high fructose intake increases serum LDL-cholesterol and total cholesterol: a meta-analysis of controlled feeding trials. J Nutr 2013; 143: 1391–1398.
Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Bergeron N, Bersot TP et al. Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab 2015; 100: 2434–2442.
Egli L, Lecoultre V, Theytaz F, Campos V, Hodson L, Schneiter P et al. Exercise prevents fructose-induced hypertriglyceridemia in healthy young subjects. Diabetes 2013; 62: 2259–2265.
Lowndes J, Sinnett S, Yu Z, Rippe J . The effects of fructose-containing sugars on weight, body composition and cardiometabolic risk factors when consumed at up to the 90th percentile population consumption level for fructose. Nutrients 2014; 6: 3153–3168.
Lecoultre V, Egli L, Carrel G, Theytaz F, Kreis R, Schneiter P et al. Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans. Obesity 2013; 21: 782–785.
Sobrecases H, Le KA, Bortolotti M, Schneiter P, Ith M, Kreis R et al. Effects of short-term overfeeding with fructose, fat and fructose plus fat on plasma and hepatic lipids in healthy men. Diabetes Metab 2010; 36: 244–246.
Johnston RD, Stephenson MC, Crossland H, Cordon SM, Palcidi E, Cox EF et al. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 2013; 145: 1016–1025; e1012.
Te Morenga L, Mallard S, Mann J . Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. Br Med J 2013; 346: e7492.
Yang Q, Zhang Z, Gregg EW, Flanders WD, Merritt R, Hu FB . Added sugar intake and cardiovascular diseases mortality among US adults. JAMA Intern Med 2014; 174: 516–524.
Jayalath VH, Sievenpiper JL, de Souza RJ, Ha V, Mirrahimi A, Santaren ID et al. Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts. J Am Coll Nutr 2014; 33: 328–339.
Hu FB, Malik VS . Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav 2010; 100: 47–54.
Choi HK, Willett W, Curhan G . Fructose-rich beverages and risk of gout in women. JAMA 2010; 304: 2270–2278.
Choi HK, Curhan G . Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. Br Med J 2008; 336: 309–312.
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: 1447–1454.
Blum JW, Jacobsen DJ, Donnelly JE . Beverage consumption patterns in elementary school aged children across a two-year period. J Am Coll Nutr 2005; 24: 93–98.
Rodriguez-Artalejo F, Garcia EL, Gorgojo L, Garces C, Royo MA, Martin Moreno JM et al. Consumption of bakery products, sweetened soft drinks and yogurt among children aged 6-7 years: association with nutrient intake and overall diet quality. Br J Nutr 2003; 89: 419–429.
Kvaavik E, Andersen LF, Klepp KI . The stability of soft drinks intake from adolescence to adult age and the association between long-term consumption of soft drinks and lifestyle factors and body weight. Public Health Nutr 2005; 8: 149–157.
Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK et al. A randomized trial of sugar-sweetened beverages and adolescent body weight. N Engl J Med 2012; 367: 1407–1416.
de Ruyter JC, Olthof MR, Seidell JC, Katan MB . A trial of sugar-free or sugar-sweetened beverages and body weight in children. N Engl J Med 2012; 367: 1397–1406.
Campos VC, Despland C, Brandejsky V, Kreis R, Schneiter Ph, Chioléro A et al. Sugar- and artificially sweetened beverages and intrahepatic fat: a randomized controlled trial. Obesity 2015; 23: 2335–2339.
This article is based on a symposium entitled ‘Sweeteners and Health: Findings from Recent Research and their Impact on Obesity and Related Metabolic Conditions’ presented at the European Congress on Obesity on 7 May 2015 with sponsorship from Rippe Lifestyle Institute. The work reported in this review has been supported by the Swiss National Science Foundation grant to Luc Tappy (Numbers 32003B_156167 and 320030_138428).
LT has received lecture fees from Rippe Lifestyle Institute, Nestlé SA and Soremartec. He has also received grant support from Swiss National Foundation for Science and Federal Office for Sport BASPO, Switzerland and serves as an expert witness for the French food security agency ANSES. The VC declares no conflict of interest.
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Campos, V., Tappy, L. Physiological handling of dietary fructose-containing sugars: implications for health. Int J Obes 40, S6–S11 (2016). https://doi.org/10.1038/ijo.2016.8
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