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Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response



Excessive fructose intake causes metabolic syndrome in animals and can be partially prevented by lowering the uric acid level. We tested the hypothesis that fructose might induce features of metabolic syndrome in adult men and whether this is protected by allopurinol.


A randomized, controlled trial of 74 adult men who were administered 200 g fructose daily for 2 weeks with or without allopurinol. Primary measures included changes in ambulatory blood pressure (BP), fasting lipids, glucose and insulin, homeostatic model assessment (HOMA) index, body mass index and criteria for metabolic syndrome.


The ingestion of fructose resulted in an increase in ambulatory BP (7±2 and 5±2 mm Hg for systolic (SBP) and diastolic BP (DBP), P<0.004 and P<0.007, respectively). Mean fasting triglycerides increased by 0.62±0.23 mmol l−1 (55±20 mg per 100 ml), whereas high-density lipoprotein cholesterol decreased by 0.06±0.02 mmol l−1 (2.5±0.7 mg per 100 ml), P<0.002 and P<0.001, respectively. Fasting insulin and HOMA indices increased significantly, whereas plasma glucose level did not change. All liver function tests showed an increase in values. The metabolic syndrome increased by 25–33% depending on the criteria. Allopurinol lowered the serum uric acid level (P<0.0001) and prevented the increase in 24-h ambulatory DBP and daytime SBP and DBP. Allopurinol treatment did not reduce HOMA or fasting plasma triglyceride levels, but lowered low-density lipoprotein cholesterol relative to control (P<0.02) and also prevented the increase in newly diagnosed metabolic syndrome (0–2%, P=0.009).


High doses of fructose raise the BP and cause the features of metabolic syndrome. Lowering the uric acid level prevents the increase in mean arterial blood pressure. Excessive intake of fructose may have a role in the current epidemics of obesity and diabetes.

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  1. Reaven GM . Banting Lecture 1988. Role of insulin resistance in human disease 1988. Nutrition 1997; 13: 65.

    CAS  PubMed  Google Scholar 

  2. Havel PJ . Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 2005; 63: 133–157.

    Article  Google Scholar 

  3. Johnson RJ, Perez-Pozo SE, Sautin YY, Manitius J, Sanchez-Lozada LG, Feig DI et al. Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Endocr Rev 2009; 30: 96–116.

    Article  CAS  Google Scholar 

  4. Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol 2006; 290: F625–F631.

    CAS  Google Scholar 

  5. Stanhope KL, Havel PJ . Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. Am J Clin Nutr 2008; 88: 1733S–1737S.

    Article  CAS  Google Scholar 

  6. Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL 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: 1322–1334.

    Article  CAS  Google Scholar 

  7. Teff KL, Grudziak J, Townsend RR, Dunn TN, Grant RW, Adams SH et al. 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 2009; 94: 1562–1569.

    Article  CAS  Google Scholar 

  8. Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ . Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol 2008; 295: R1370–R1375.

    Article  CAS  Google Scholar 

  9. Maenpaa PH, Raivio KO, Kekomaki MP . Liver adenine nucleotides: fructose-induced depletion and its effect on protein synthesis. Science (New York, NY) 1968; 161: 1253–1254.

    Article  CAS  Google Scholar 

  10. Cirillo P, Gersch MS, Mu W, Scherer PM, Kim KM, Gesualdo L et al. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol 2009; 20: 545–553.

    Article  CAS  Google Scholar 

  11. Glushakova O, Kosugi T, Roncal C, Mu W, Heinig M, Cirillo P et al. Fructose induces the inflammatory molecule ICAM-1 in endothelial cells. J Am Soc Nephrol 2008; 19: 1712–1720.

    Article  CAS  Google Scholar 

  12. Stirpe F, Della Corte E, Bonetti E, Abbondanza A, Abbati A, De Stefano F . Fructose-induced hyperuricaemia. Lancet 1970; 2: 1310–1311.

    Article  CAS  Google Scholar 

  13. Sautin YY, Nakagawa T, Zharikov S, Johnson RJ . Adverse effects of the classical antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 2007; 293: C584–C596.

    Article  CAS  Google Scholar 

  14. Reungjui S, Roncal CA, Mu W, Srinivas TR, Sirivongs D, Johnson RJ et al. Thiazide diuretics exacerbate fructose-induced metabolic syndrome. J Am Soc Nephrol 2007; 18: 2724–2731.

    Article  CAS  Google Scholar 

  15. Feig DI, Soletsky B, Johnson RJ . Effect of allopurinol on the blood pressure of adolescents with newly diagnosed essential hypertension. JAMA 2008; 300: 922–930.

    Article  Google Scholar 

  16. Martin-Moreno JM, Boyle P, Gorgojo L, Maisonneuve P, Fernandez-Rodriguez JC, Salvini S et al. Development and validation of a food frequency questionnaire in Spain. Int J Epidemiol 1993; 22: 512–519.

    Article  CAS  Google Scholar 

  17. Hallfrisch J, Reiser S, Prather ES . Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Am J Clin Nutr 1983; 37: 740–748.

    Article  CAS  Google Scholar 

  18. Yudkin J, Eisa O, Kang SS, Meraji S, Bruckdorfer KR . Dietary sucrose affects plasma HDL cholesterol concentration in young men. Ann Nutr Metab 1986; 30: 261–266.

    Article  CAS  Google Scholar 

  19. Duffey KJ, Popkin BM . High-fructose corn syrup: is this what's for dinner? Am J Clin Nutr 2008; 88: 1722S–1732S.

    Article  CAS  Google Scholar 

  20. Dwyer JT, Evans M, Stone EJ, Feldman HA, Lytle L, Hoelscher D et al. Adolescents' eating patterns influence their nutrient intakes. J Am Diet Assoc 2001; 101: 798–802.

    Article  CAS  Google Scholar 

  21. Kranz S, Smiciklas-Wright H, Siega-Riz AM, Mitchell D . Adverse effect of high added sugar consumption on dietary intake in American preschoolers. J Pediatr 2005; 146: 105–111.

    Article  CAS  Google Scholar 

  22. Tran LT, Yuen VG, McNeill JH . The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 2009; 332: 145–159.

    Article  CAS  Google Scholar 

  23. Farah V, Elased KM, Chen Y, Key MP, Cunha TS, Irigoyen MC et al. Nocturnal hypertension in mice consuming a high fructose diet. Auton Neurosci 2006; 130: 41–50.

    Article  CAS  Google Scholar 

  24. Brown CM, Dulloo AG, Yepuri G, Montani JP . Fructose ingestion acutely elevates blood pressure in healthy young humans. Am J Physiol 2008; 294: R730–R737.

    CAS  Google Scholar 

  25. Nguyen S, Choi HK, Lustig RH, Hsu CY . Sugar-sweetened beverages, serum uric acid, and blood pressure in adolescents. J Pediatr 2009; 154: 807–813.

    Article  CAS  Google Scholar 

  26. Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM . Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension 2003; 42: 878–884.

    Article  CAS  Google Scholar 

  27. Bantle JP, Raatz SK, Thomas W, Georgopoulos A . Effects of dietary fructose on plasma lipids in healthy subjects. Am J Clin Nutr 2000; 72: 1128–1134.

    Article  CAS  Google Scholar 

  28. Roncal CA, Reungjui S, Sanchez-Lozada LG, Mu W, Sautin YY, Nakagawa T et al. Combination of captopril and allopurinol retards fructose-induced metabolic syndrome. Am J Nephrol 2009; 30: 399–404.

    Article  CAS  Google Scholar 

  29. Hallfrisch J, Ellwood KC, Michaelis OEt, Reiser S, O'Dorisio TM, Prather ES . Effects of dietary fructose on plasma glucose and hormone responses in normal and hyperinsulinemic men. J Nutr 1983; 113: 1819–1826.

    Article  CAS  Google Scholar 

  30. 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: H2478–H2484.

    Article  CAS  Google Scholar 

  31. Song D, Arikawa E, Galipeau D, Battell M, McNeill JH . Androgens are necessary for the development of fructose-induced hypertension. Hypertension 2004; 43: 667–672.

    Article  CAS  Google Scholar 

  32. Kylin E . Studien uber das Hypertonie-Hyperglykamie-hyperurikamiesyndrome [Studies of the hypertension-hyperglycemia-hyperuricemia syndrome]. Zentralblatt innere Med 1923; 44: 105–127.

    Google Scholar 

  33. Grundy SM . Does the metabolic syndrome exist? Diabetes care 2006; 29: 1689–1692.

    Article  Google Scholar 

  34. Meigs JB . Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 2000; 152: 908–911.

    Article  CAS  Google Scholar 

  35. Pladevall M, Singal B, Williams LK, Brotons C, Guyer H, Sadurni J et al. A single factor underlies the metabolic syndrome: a confirmatory factor analysis. Diab Care 2006; 29: 113–122.

    Article  Google Scholar 

  36. Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143–3421.

  37. Alberti KG, Zimmet P, Shaw J . The metabolic syndrome—a new worldwide definition. Lancet 2005; 366: 1059–1062.

    Article  Google Scholar 

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We thank the volunteers and staff who participated in the study. Dr Enrique Perez-Pozo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Trial registration: identifier number: NCT00639756. Support for this publication was provided by generous funds from the Mateo Orfila Foundation.

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Perez-Pozo, S., Schold, J., Nakagawa, T. et al. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes 34, 454–461 (2010).

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  • fructose
  • high-fructose corn syrup
  • sucrose
  • metabolic syndrome
  • uric acid
  • allopurinol

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