Metabolic effects of excessive consumption of fructose

Zakład Medycyny Społecznej i Zdrowia Publicznego, Warszawski Uniwersytet Medyczny
Zakład Opieki Zdrowotnej, Instytut Medycyny Wsi w Lublinie
MONZ 2017;23(3):165–170
At the end of 2011, the United Nations announced that for the first time in human history, non-communicable diseases have become a greater threat to human health than infectious diseases. Non-communicable diseases, primarily cardiovascular diseases which are directly associated with metabolic disorders such as obesity, type 2 diabetes and metabolic syndrome, are a global crisis and the leading cause of death worldwide. Food choice and eating habits have changed dramatically in developed countries over the last few decades. The average diet has become richer in energy, saturated fatty acids and sugars. The World Health Organization recommends limiting intake of free sugars to less than 10% of total daily energy intake. Other recommendations suggest limiting the consumption of simple sugars to 5% of the overall caloric value of the diet. Although, the American Heart Association recommends reduction in the intake of added sugars. A prudent upper limit of intake for most women is no more than 100 calories per day and for most men is no more than 150 calories per day from added sugars. The top source of fructose are sugar-sweetened beverages, desserts, breakfast cereals and candy, containing usually glucose-fructose syrup, which requires an assessment of the effect of this sugar on the metabolic processes. This paper presents available data on the metabolic effects of over-consumption of fructose, which may be useful for practitioners.
Piotr Zbigniew Tyszko   
Zakład Opieki Zdrowotnej, Instytut Medycyny Wsi w Lublinie, ul. Oczki 3, 02-007 Warszawa, Polska
1. Tappy L, Lê K. Metabolic Effects of Fructose and the Worldwide Increase in Obesity. Physiol Rev. 2010; 23–46.
2. White J. Straight talk about high-fructose corn syrup: what it is and what it ain’t. Am J Clin Nutr. 2008; 88: 1716–1721.
3. Hanover L, White J. Manufacturing, composition, and applications of fructose. Am J Clin Nutr. 1993; 58: 724–732.
4. Park Y, Yetley E. Intakes and food sources of fructose in the United States. Am J Clin Nutr. 1993; 58: 737–747.
5. Marriott B, Cole N, Lee E. National estimates of dietary fructose intake increased from 1977 to 2004 in the United States. J Nutr. 2009; 139: 1228–1235.
6. Macdonald I. Influence of fructose and glucose on serum lipid levels in men and pre- and postmenopausal women. Am J Clin Nutr. 1966; 18: 369–372.
7. Bantle J, Laine D, Thomas J. Metabolic effects of dietary fructose and sucrose in types I and II diabetic subjects. JAMA. 1986; 256: 3241–3246.
8. Crapo P, Kolterman O. The metabolic effects of 2-week fructose feeding in normal subjects. Am J Clin Nutr. 1984; 39: 525–534.
9. Chong M, Fielding B, Frayn K. Mechanisms for the acute effect of fructose on postprandial lipemia. Am J Clin Nutr. 2007; 85: 1511–1520.
10. Parks E, Skokan L, Timlin M, Dingfelder C. Dietary sugars stimulate fatty acid synthesis in adults. J Nutr. 2008; 138: 1039–1046.
11. Khitan Z, Kim D. Fructose: a key factor in the development of metabolic syndrome and hypertension. J Nutr Metab. 2013; 2013.
12. Pagliassotti M, Prach P, Koppenhafer T, Pan D. Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol. 1996; 271: R1319–26.
13. Leˆ K, Faeh D, Stettler R, 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.
14. Le K, Ith M, Kreis R, et al. Fructose overconsumption causes dyslipide¬mia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Am J Clin Nutr. 2009; 89: 1760–5.
15. Rizkalla S, Boillot J, Tricottet V, et al. Effects of chronic dietary fru¬ctose on glomerular basement membrane thickness and on glycemic and lipid control in normal rats. Effect of copper supplementation. Br J Nutr. 1993; 70: 199–209.
16. Rizkall S. Health implications of fructose consumption: A review of recent data. Nutrition and Metabolism 2010; 7: 82.
17. Mamikutty N, Thent Z, Sapri S, et al. The establishment of metabolic syndrome model by induction of fructose drinking water in male Wistar rats. BioMed Research International, 2014; 263897.
18. Havel P. Dietary Fructose: Implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005; 63: 133–157.
19. Livesey G, Taylor R. Fructose consumption and consequences for gly¬cation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr. 2008; 88: 1419–1437.
20. Huttunen J. Serum lipids, uric acid and glucose during chronic con¬sumption of fructose and xylitol in healthy human subjects. Int Z Vitam Ernahrungsforsch Beih. 1976; 15: 105–15.
21. Sievenpiper J, Carleton A, Chatha S, 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: 1930–7.
22. Koivisto V, Yki-Järvinen H. Fructose and insulin sensitivity in patients with type 2 diabetes. J Intern Med. 1993; 233: 145–53.
23. Malerbi D, Paiva E, Duarte A, Wajchenberg B. Metabolic effects of dietary sucrose and fructose in type II diabetic subjects. Diabetes Care 1996; 19: 1249–56.
24. Wang D, Sievenpiper J, de Souza R, et al. Effect of fructose on postpran¬dial triglycerides: a systematic review and meta-analysis of controlled feeding trials. Atherosclerosis. 2014, 232.1: 125–133.
25. Zhang Y, An T, Zhang R, et al. Very high fructose intake increases serum LDL-cholesterol and total cholesterol: a meta-analysis of controlled feeding trials. J Nutr, 2013; 143(9), 1391–1398.
26. Cefalu W. Insulin resistance: cellular and clinical concepts. J. Exp. Biol. 2001; 226: 13–26.
27. Dekker M, Su Q, Baker C, et al. Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis, and the metabolic syndrome. Am J Physiol Endocrinol Metab. 2010; 299(5), E685–E694.
28. Shulman G. Cellular mechanisms of insulin resistance. J Clin Invest. 2000; 106: 171–176.
29. Virkamäki A, Korsheninnikova E, Seppälä-Lindroos A, et al. Intramy¬ocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes. 2001; 50: 2337–43.
30. Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA: Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J. Hypertens. 2003; 16: 973–8.
31. Beck-Nielsen H, Pederson O, Lindskov H. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Am J Clin Nutr. 1980; 33: 273–278.
32. Hallfrisch J, Ellwood K, Michaelis O, Reiser S, O’Dorisio T, Prather E. Effects of dietary fructose on plasma glucose and hormone responses in normal and hyperinsulinemic men. J Nutr. 1983; 113: 1819–26.
33. Bossetti B, Kocher L, Moranz J, Falko J. The effects of physiologic amounts of simple sugars on lipoprotein, glucose, and insulin levels in normal subjects. Diabetes Care. 1984; 7(4): 309–12.
34. Couchepin C, Lê K, Bortolotti M, et al. Markedly blunted metabolic effects of fructose in healthy young female subjects compared with male subjects. Diabetes Care. 2008; 31: 1254–6.
35. Stanhope K, Schwarz J, Keim N, 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.
36. Wu T, Giovannucci E, Pischon T, et al. Fructose, glycemic load, and quantity and quality of carbohydrate in relation to plasma C-peptide concentrations in US women. Am J Clin Nutr. 2004; 80: 1043–9.
37. Reiser S, Powell A, Scholfield D, et al. Day-long glucose, insulin, and fructose responses of hyperinsulinemic and nonhyperinsulinemic men adapted to diets containing either fructose or high-amylose cornstarch. Am J Clin Nutr. 1989; 50: 1008–1014.
38. Moore M, Davis S, Mann S, Cherrington A. Acute fructose admini¬stration improves oral glucose tolerance in adults with type 2 diabetes. Diabetes Care. 2001; 24: 1882–7.
39. Clement K, Pueyo M, Vaxillaire M, et al. Assessment of insulin sens¬itivity in glucokinase-deficient subjects. Diabetologia. 1996; 39: 82–90.
40. Ter Horst K, Schene M, Holman R, et al. Effect of fructose consumption on insulin sensitivity in nondiabetic subjects: a systematic review and meta-analysis of diet-intervention trials. Am J Clin Nutr. 2016; 104(6): 1562–1576.
41. Galipeau D, Arikawa E, Sekirov I, McNeill J. Chronic thromboxane synthase inhibition prevents fructose-induced hypertension. Hyper¬tension. 2001; 38: 872–876.
42. Hsieh P, Tai Y, Loh C, et al. Functional interaction of AT1 and AT2 receptors in fructose-induced insulin resistance and hypertension in rats. Metabolism. 2005; 54: 157–164.
43. Busserolles J, Gueux E, Rock E, et al. High fructose feeding of magne¬sium deficient rats is associated with increased plasma triglyceride con-centration and increased oxidative stress. Magnes Res. 2003; 16: 7–12.
44. Fields M, Lewis C. Dietary fructose but not starch is responsible for hyperlipidemia associated with copper deficiency in rats: effect of high¬-fat diet. J Am Coll. Nutr. 1999; 18: 83–87.
45. Stanhope K, Havel P. Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr Opin Lipidol. 2008; 19: 16–24.
46. Forman J, Choi H, Curhan G. Fructose and vitamin C intake do not influence risk for developing hypertension. J Am Soc Nephrol. 2009, 20: 863–71.
47. Brown C, Dulloo A, Yepuri G, Montani J-P. Fructose ingestion acutely elevates blood pressure in healthy young humans. Am J Physiol Regul Integr Comp Physiol. 2008, 294: R730–737.
48. Kanarek R, Orthen-Gambill N. Differential effects of sucrose, fructose and glucose on carbohydrate-induced obesity in rats. J Nutr. 1982; 112: 1546–54.
49. Kasim-Karakas S, Vriend H, Almario R, et al. Effects of dietary carbo¬hydrates on glucose and lipid metabolism in golden Syrian hamsters. J Lab Clin. Med. 1996; 128: 208–13.
50. Suga A, Hirano T, Kageyama H, et al. Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-le-sionedobese rats. Am J Physiol Endocrinol Metab. 2000; 278: E677–83.
51. Berkey C, Rockett H, Field A et al. Sugar-added beverages and adolescent weight change. Obes Res. 2004; 12: 778–788.
52. Giammattei J, Blix G, Marshak H, et al. Television watching and soft drink consumption: associations with obesity in 11- to 13-year-old school children. Arch Pediatr Adolesc Med. 2003; 157: 882–886.
53. Blum J, Jacobsen D, Donnelly J. Beverage consumption patterns in elementary school aged children across a two-year period. J Am Coll Nutr. 2005; 24: 93–98.
54. Forshee R, Storey M. Total beverage consumption and beverage choices among children and adolescents. Int J Food Sci Nutr. 2003; 54: 297–307.
55. Bantle J, Raatz S, Thomas W, Georgopoulos A. Effects of dietary fructose on plasma lipids in healthy subjects. Am J Clin Nutr. 2000; 72: 1128–34.
56. Osei K, Bossetti B. Dietary fructose as a natural sweetener in poorly controlled type 2 diabetes: a 12-month crossover study of effects on glucose, lipoprotein and apolipoprotein metabolism. Diabet Med. 1989; 6: 506–11.