Abstract
Fructose is a component of natural (sucrose) or industrial (high-fructose corn syrup) sugars. It has a caloric content similar to glucose and a higher sweetening power. All cells of the human body can use glucose as an energy substrate, and most can also use fatty acids. In contrast, most cells cannot use directly fructose, and this substrate needs first to be converted into lactate, glucose, or fatty acids in the gut, liver, and kidneys. Cells of these three organ express a set of fructolytic enzymes: fructokinase, aldolase B, and triokinase which convert fructose into two triose phosphate. Since there is no negative feedback on the activity of these fructolytic enzymes, the ingested fructose is almost completely and immediately metabolized in the gut and the liver. When a large amount of fructose is ingested, splanchnic organs are faced with an overproduction of triose phosphate, which they first release into the systemic circulation as lactate and glucose. When these pathways become saturated, fructose is converted into fatty acids through de novo lipogenesis, and newly synthetized fatty acids are either secreted into the blood as very low density lipoproteins – triglycerides – or temporarily stored as intrahepatic triglycerides. The metabolic fate of ingested fructose is dependent on whole body energy output. In resting conditions, glucose and lactate oxidation are limited by the low whole body energy expenditure, and excess fructose intake leads to a moderate increase in splanchnic glucose output to increased fasting and postprandial blood triglyceride concentration and to increased intrahepatic fat concentrations. During exercise, whole body energy output is high; fructose and glucose and lactate synthetized from glucose are essentially oxidized in skeletal muscle.
References
Liu S, Manson JE, Lee IM, Cole SR, Hennekens CH, Willett WC, Buring JE (2000) Fruit and vegetable intake and risk of cardiovascular disease: the Women’s Health Study. Am J Clin Nutr 72:922–928
Freedman DA, Choi SK, Hurley T, Anadu E, Hebert JR (2013) A farmers’ market at a federally qualified health center improves fruit and vegetable intake among low-income diabetics. Prev Med 56:288–292
Lustig RH, Schmidt LA, Brindis CD (2012) Public health: the toxic truth about sugar. Nature 482:27–29
Bray G, Nielsen S, Popkin B (2004) Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 79:737–743
Macdonald I (1986) Dietary carbohydrate and energy balance. Prog Biochem Pharmacol 21:181–191
Johnson R, Moorthy SN, Padmaja G (2010) Production of high fructose syrup from cassava and sweet potato flours and their blends with cereal flours. Food Sci Technol Int 16:251–258
Hanover LM, White JS (1993) Manufacturing, composition, and applications of fructose. Am J Clin Nutr 58:724S–732S
Rosensweig NS (1972) Dietary sugars and intestinal enzymes. J Am Diet Assoc 60:483–486
Lu Y, Levin GV, Donner TW (2008) Tagatose, a new antidiabetic and obesity control drug. Diabetes Obes Metab 10:109–134
Cook GC (1979) The D-xylose absorption test in different ethnic groups. Trop Geogr Med 31:93–97
Wang YM, van Eys J (1981) Nutritional significance of fructose and sugar alcohols. Annu Rev Nutr 1:437–475
Robayo-Torres CC, Quezada-Calvillo R, Nichols BL (2006) Disaccharide digestion: clinical and molecular aspects. Clin Gastroenterol Hepatol 4:276–287
Clausen MR, Mortensen PB (1997) Lactulose, disaccharides and colonic flora. Clinical consequences. Drugs 53:930–942
Gray GM (1992) Starch digestion and absorption in nonruminants. J Nutr 122:172–177
Laffitte A, Neiers F, Briand L (2014) Functional roles of the sweet taste receptor in oral and extraoral tissues. Curr Opin Clin Nutr Metab Care 17:379–385
Drewnowski A (1999) Sweetness, appetite, and energy intake: physiological aspects. World Rev Nutr Diet 85:64–76
Beauchamp GK (1999) Factors affecting sweetness. World Rev Nutr Diet 85:10–17
Treesukosol Y, Smith KR, Spector AC (2011) The functional role of the T1R family of receptors in sweet taste and feeding. Physiol Behav 105:14–26
Newbrun E, Hoover C, Mettraux G, Graf H (1980) Comparison of dietary habits and dental health of subjects with hereditary fructose intolerance and control subjects. J Am Dent Assoc 101:619–626
Burmeister LA, Valdivia T, Nuttall FQ (1991) Adult hereditary fructose intolerance. Arch Intern Med 151:773–776
Flatt JP (1978) The biochemistry of energy expenditure. In: Bray GA (ed) Recent advances in obesity research. Newman Publishing, London, pp 211–228
Raninen KJ, Lappi JE, Mukkala ML, Tuomainen TP, Mykkanen HM, Poutanen KS, Raatikainen OJ (2016) Fiber content of diet affects exhaled breath volatiles in fasting and postprandial state in a pilot crossover study. Nutr Res 36:612–619
Trichopoulou A, Lagiou P (1997) Healthy traditional Mediterranean diet: an expression of culture, history, and lifestyle. Nutr Rev 55:383–389
Sheehy T, Kolahdooz F, Roache C, Sharma S (2015) Traditional food consumption is associated with better diet quality and adequacy among Inuit adults in Nunavut, Canada. Int J Food Sci Nutr 66:445–451
Boyce VL, Swinburn BA (1993) The traditional Pima Indian diet. Composition and adaptation for use in a dietary intervention study. Diabetes Care 16:369–371
Cordain L, Eaton SB, Miller JB, Mann N, Hill K (2002) The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr 56(Suppl 1):S42–S52
Sluik D, van Lee L, Engelen AI, Feskens EJ (2016) Total, free, and added sugar consumption and adherence to guidelines: the Dutch National Food Consumption Survey 2007–2010. Nutrients 8:70
Marriott BP, Olsho L, Hadden L, Connor P (2010) Intake of added sugars and selected nutrients in the United States, National Health and Nutrition Examination Survey (NHANES) 2003–2006. Crit Rev Food Sci Nutr 50:228–258
Lei L, Rangan A, Flood VM, Louie JC (2016) Dietary intake and food sources of added sugar in the Australian population. Br J Nutr 115:868–877
Campos VC, Tappy L (2016) Physiological handling of dietary fructose-containing sugars: implications for health. Int J Obes (Lond) 40(Suppl 1):S6–S11
Mayes PA (1993) Intermediary metabolism of fructose. Am J Clin Nutr 58:754S–765S
Mueckler M, Thorens B (2013) The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med 34:121–138
Kinne RK, Castaneda F (2011) SGLT inhibitors as new therapeutic tools in the treatment of diabetes. Handb Exp Pharmacol:105–126
Douard V, Ferraris RP (2008) Regulation of the fructose transporter GLUT5 in health and disease. Am J Physiol Endocrinol Metab 295:E227–E237
Barone S, Fussell SL, Singh AK, Lucas F, Xu J, Kim C, Wu X, Yu Y, Amlal H, Seidler U et al (2009) Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J Biol Chem 284:5056–5066
Sugawara-Yokoo M, Suzuki T, Matsuzaki T, Naruse T, Takata K (1999) Presence of fructose transporter GLUT5 in the S3 proximal tubules in the rat kidney. Kidney Int 56:1022–1028
Sun SZ, Empie MW (2012) Fructose metabolism in humans – what isotopic tracer studies tell us. Nutr Metab 9:89
Theytaz F, de Giorgi S, Hodson L, Stefanoni N, Rey V, Schneiter P, Giusti V, Tappy L (2014) Metabolic fate of fructose ingested with and without glucose in a mixed meal. Nutrients 6:2632–2649
Paquot N, Schneiter P, Jequier E, Gaillard R, Lefebvre PJ, Scheen A, Tappy L (1996) Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects. Diabetologia 39:580–586
Bizeau ME, Pagliassotti MJ (2005) Hepatic adaptations to sucrose and fructose. Metabolism 54:1189–1201
Tappy L, Le KA (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90:23–46
Samuel VT (2011) Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab: TEM 22:60–65
Faeh D, Minehira K, Schwarz J, Periasami R, Seongus P, Tappy L (2005) Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy males. Diabetes 54:1907–1913
Le KA, Faeh D, Stettler R, Ith M, Kreis R, Vermathen P, Boesch C, Ravussin E, Tappy L (2006) A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. Am J Clin Nutr 84:1374–1379
Haidari M, Leung N, Mahbub F, Uffelman KD, Kohen-Avramoglu R, Lewis GF, Adeli K (2002) Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. Evidence that chronic fructose feeding in the hamster is accompanied by enhanced intestinal de novo lipogenesis and ApoB48-containing lipoprotein overproduction. J Biol Chem 277:31646–31655
Teff KL, Grudziak J, Townsend RR, Dunn TN, Grant RW, Adams SH, Keim NL, Cummings BP, Stanhope KL, Havel PJ (2009) Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab 94:1562–1569
Jeppesen J, Chen YI, Zhou MY, Schaaf P, Coulston A, Reaven GM (1995) Postprandial triglyceride and retinyl ester responses to oral fat: effects of fructose. Am J Clin Nutr 61:787–791
Livesey G, Taylor R (2008) Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr 88:1419–1437
Sievenpiper JL, Carleton AJ, Chatha S, Jiang HY, de Souza RJ, Beyene J, Kendall CW, Jenkins DJ (2009) 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 32:1930–1937
David Wang D, Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V, Mirrahimi A, Carleton AJ, Di Buono M, Jenkins AL et al (2014) Effect of fructose on postprandial triglycerides: a systematic review and meta-analysis of controlled feeding trials. Atherosclerosis 232:125–133
Sobrecases H, Le KA, Bortolotti M, Schneiter P, Ith M, Kreis R, Boesch C, Tappy L (2010) Effects of short-term overfeeding with fructose, fat and fructose plus fat on plasma and hepatic lipids in healthy men. Diabetes Metab 36:244–246
Egli L, Lecoultre V, Theytaz F, Campos V, Hodson L, Schneiter P, Mittendorfer B, Patterson BW, Fielding BA, Gerber PA et al (2013) Exercise prevents fructose-induced hypertriglyceridemia in healthy young subjects. Diabetes 62:2259–2265
Le KA, Ith M, Kreis R, Faeh D, Bortolotti M, Tran C, Boesch C, Tappy L (2009) 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 89:1760–1765
Bortolotti M, Kreis R, Debard C, Cariou B, Faeh D, Chetiveaux M, Ith M, Vermathen P, Stefanoni N, Le KA et al (2009) High protein intake reduces intrahepatocellular lipid deposition in humans. Am J Clin Nutr 90:1002–1010
Roglans N, Vila L, Farre M, Alegret M, Sanchez RM, Vazquez-Carrera M, Laguna JC (2007) Impairment of hepatic Stat-3 activation and reduction of PPARalpha activity in fructose-fed rats. Hepatology 45:778–788
Lecoultre V, Egli L, Carrel G, Theytaz F, Kreis R, Schneiter P, Boss A, Zwygart K, Le KA, Bortolotti M et al (2013) Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans. Obesity (Silver Spring) 21:782–785
Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W et al (2009) Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 119:1322–1334
Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B (2012) Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 95:283–289
Elwyn DH, Bursztein S (1993) Carbohydrate metabolism and requirements for nutritional support: part I. Nutrition 9:50–66
Bursztein S, Elwyn DH, Askanazi J, Kinney JM (1989) Energy metabolism, indirect calorimetry, and nutrition. Williams & Wilkins, Baltimore, 266 pp
Johnston RD, Stephenson MC, Crossland H, Cordon SM, Palcidi E, Cox EF, Taylor MA, Aithal GP, Macdonald IA (2013) No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 145(1016–1025):e1012
Ngo Sock ET, Le KA, Ith M, Kreis R, Boesch C, Tappy L (2010) Effects of a short-term overfeeding with fructose or glucose in healthy young males. Br J Nutr 103:939–943
Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, Tai VW, Bergeron N, Bersot TP et al (2015) Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab 100:2434–2442
Tappy L, Le KA (2012) Does fructose consumption contribute to non-alcoholic fatty liver disease? Clin Res Hepatol Gastroenterol 36:554–560
Tounian P, Schneiter P, Henry S, Jéquier E, Tappy L (1994) Effects of infused fructose on endogenous glucose production, gluconeogenesis and glycogen metabolism in healthy humans. Am J Physiol 267:E710–E717
Schwarz JM, Acheson KJ, Tappy L, Piolino V, Muller MJ, Felber JP, Jequier E (1992) Thermogenesis and fructose metabolism in humans. Am J Physiol 262:E591–E598
Dirlewanger M, di Vetta V, Guenat E, Battilana P, Seematter G, Schneiter P, Jequier E, Tappy L (2000) Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects. Int J Obes Relat Metab Dis: J Int Assoc Study Obes 24:1413–1418
Mevorach M, Giacca A, Aharon Y, Hawkins M, Shamoon H, Rossetti L (1998) Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus. J Clin Invest 102:744–753
Delarue J, Normand S, Pachiaudi C, Beylot M, Lamisse F, Riou JP (1993) The contribution of naturally labelled 13C fructose to glucose appearance in humans. Diabetologia 36:338–345
Aeberli I, Hochuli M, Gerber PA, Sze L, Murer SB, Tappy L, Spinas GA, Berneis K (2013) Moderate amounts of fructose consumption impair insulin sensitivity in healthy young men: a randomized controlled trial. Diabetes Care 36:150–156
Tappy L, Le KA (2015) Health effects of fructose and fructose-containing caloric sweeteners: where do we stand 10 years after the initial whistle blowings? Curr Diab Rep 15:627
Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Shafiu M, Sundaram S, Le M, Ishimoto T, Sautin YY, Lanaspa MA (2013) Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes 62:3307–3315
Teff KL, Elliott SS, Tschop M, Kieffer TJ, Rader D, Heiman M, Townsend RR, Keim NL, D’Alessio D, Havel PJ (2004) Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 89:2963–2972
Soenen S, Westerterp-Plantenga MS (2007) No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. Am J Clin Nutr 86:1586–1594
Rodin J, Reed D, Jamner L (1988) Metabolic effects of fructose and glucose: implications for food intake. Am J Clin Nutr 47:683–689
Payne AN, Chassard C, Lacroix C (2012) Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host-microbe interactions contributing to obesity. Obes Rev 13:799–809
Jandrain BJ, Pallikarakis N, Normand S, Pirnay F, Lacroix M, Mosora F, Pachiaudi C, Gautier JF, Scheen AJ, Riou JP et al (1993) Fructose utilization during exercise in men: rapid conversion of ingested fructose to circulating glucose. J Appl Physiol 74:2146–2154
Jeukendrup AE (2010) Carbohydrate and exercise performance: the role of multiple transportable carbohydrates. Curr Opin Clin Nutr Metab Care 13:452–457
Lecoultre V, Benoit R, Carrel G, Schutz Y, Millet GP, Tappy L, Schneiter P (2010) Fructose and glucose co-ingestion during prolonged exercise increases lactate and glucose fluxes and oxidation compared with an equimolar intake of glucose. Am J Clin Nutr 92:1071–1079
Egli L, Lecoultre V, Cros J, Rosset R, Marques AS, Schneiter P, Hodson L, Gabert L, Laville M, Tappy L (2016) Exercise performed immediately after fructose ingestion enhances fructose oxidation and suppresses fructose storage. Am J Clin Nutr 103:348–355
Bidwell AJ, Fairchild TJ, Redmond J, Wang L, Keslacy S, Kanaley JA (2014) Physical activity offsets the negative effects of a high-fructose diet. Med Sci Sports Exerc 46:2091–2098
Koutsari C, Karpe F, Humphreys SM, Frayn KN, Hardman AE (2001) Exercise prevents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet. Arterioscler Thromb Vasc Biol 21:1520–1525
Tappy L, Egli L, Lecoultre V, Schneider P (2013) Effects of fructose-containing caloric sweeteners on resting energy expenditure and energy efficiency: a review of human trials. Nutr Metab 10:54
Tran C, Jacot-Descombes D, Lecoultre V, Fielding BA, Carrel G, Le KA, Schneiter P, Bortolotti M, Frayn KN, Tappy L (2010) Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load. Br J Nutr 104:1139–1147
Couchepin C, Le KA, Bortolotti M, da Encarnacao JA, Oboni JB, Tran C, Schneiter P, Tappy L (2008) Markedly blunted metabolic effects of fructose in healthy young female subjects compared with male subjects. Diabetes Care 31:1254–1256
Busserolles J, Mazur A, Gueux E, Rock E, Rayssiguier Y (2002) Metabolic syndrome in the rat: females are protected against the pro-oxidant effect of a high sucrose diet. Exp Biol Med (Maywood) 227:837–842
Wilder-Smith CH, Li X, Ho SS, Leong SM, Wong RK, Koay ES, Ferraris RP (2014) Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance. U Eur Gastroenterol J 2:14–21
Fedewa A, Rao SS (2014) Dietary fructose intolerance, fructan intolerance and FODMAPs. Curr Gastroenterol Rep 16:370
Acknowledgments
The author’s research in this field has been supported by grant from the Swiss National Science Foundation 26074044 and by grants from the Swiss Federal Office for Sport Science. I warmly thank Dr. Kevin Seyssel for having reviewed and commented the manuscript.
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Tappy, L. (2018). Health Implications of Fructose Consumption in Humans. In: Mérillon, JM., Ramawat, K. (eds) Sweeteners. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-27027-2_29
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