Skip to main content

Dietary Fructose and Hypertension


The association between fructose and increased blood pressure is still incompletely defined, because experimental studies have produced dissimilar conclusions. Amplified vasopressor responses to minimal stimuli and differing responses to fructose in peripheral versus central sites may explain the controversy. Fructose induces systemic hypertension through several mechanisms mainly associated with deleterious effects on target organs (kidney, endothelium, heart) exerted by the byproducts of its metabolism, such as uric acid. The kidney is particularly sensitive to the effects of fructose because high loads of this sugar reach renal tissue. In addition, fructose increases reabsorption of salt and water in the small intestine and kidney; thus the combination of salt and fructose has a synergistic effect in the development of hypertension. Clinical and epidemiologic studies have also linked fructose consumption with hypertension. Further studies are warranted in order to understand the role of fructose in the development of hypertension.

This is a preview of subscription content, access via your institution.

Fig. 1


Papers of particular interest, published recently, have been highlighted as: •Of importance; •• Of major importance

  1. 1.

    Johnson RJ, Segal MS, Sautin Y, et al.: Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 2007, 86:899–906.

    CAS  PubMed  Google Scholar 

  2. 2.

    Ferder L, Ferder MD, Inserra F: the role of high-fructose corn syrup in metabolic syndrome and hypertension. Curr Hypertens Rep 2010, 12:105–112.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    •• Tappy L, Le KA: Metabolic Effects of fructose and the worldwide increase in obesity. Physiol Rev 2010, 90:23–46. This is an excellent review on the deleterious effects attributed to fructose. Both human and experimental studies are discussed.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    D’Angelo G, Elmarakby AA, Pollock DM, Stepp DW: Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats. Hypertension 2005, 46:806–811.

    Article  PubMed  Google Scholar 

  5. 5.

    Hwang IS, Ho H, Hoffman BB, Reaven GM: Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987, 10:512–516.

    CAS  PubMed  Google Scholar 

  6. 6.

    •• 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. This is a comprehensive review on the operative mechanisms related to the effects of fructose ingestion in rats.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    • Robbez Masson V, Lucas A, Gueugneau AM, et al.: Long-chain (n-3) polyunsaturated fatty acids prevent metabolic and vascular disorders in fructose-fed rats. J Nutr 2008, 138:1915–1922. The authors showed a mild but significant increment in systolic and pulse blood pressure, (measured by telemetry) induced by fructose consumption.

    PubMed  Google Scholar 

  8. 8.

    Sanchez-Lozada LG, Tapia E, Jimenez A, et al.: Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am J Physiol Renal Physiol 2007, 292:F423–F429.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Kurtz TW, Griffin KA, Bidani AK, et al.: Recommendations for blood pressure measurement in humans and experimental animals: Part 2: blood pressure measurement in experimental animals: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Arterioscler Thromb Vasc Biol 2005, 25:e22–e33.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    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:H1083–H1089.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Farah V, Elased KM, Chen Y, et al.: Nocturnal hypertension in mice consuming a high fructose diet. Auton Neurosci 2006, 130:41–50.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Pelaez LI, Manriquez MC, Nath KA, et al.: Low-dose angiotensin II enhances pressor responses without causing sustained hypertension. Hypertension 2003, 42:798–801.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Swali A, McMullen S, Langley-Evans SC: Prenatal protein restriction leads to a disparity between aortic and peripheral blood pressure in Wistar male offspring. J Physiol 2010 Aug 6 (Epub ahead of print).

  14. 14.

    Peredo HA, Mayer MA, Rodríguez Fermepín M, et al.: Oral treatment and in vitro incubation with fructose modify vascular prostanoid production in the rat. Auton Autacoid Pharmacol 2006, 26:15–20.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Bouhanick B, Chamontin B: Should pulse pressure and day/night variations in blood pressure be seen as independent risk factors requiring correction or simply as markers to be taken into account when evaluating overall vascular risk? Diabetes Metab 2007, 33:321–330.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Johnson RJ, Rodriguez-Iturbe B, Nakagawa T, et al.: Subtle renal injury is likely a common mechanism for salt-sensitive essential hypertension. Hypertension 2005, 45:326–330.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Vasdev S, Gill V, Parai S, Gadag V: Fructose-induced hypertension in Wistar-Kyoto rats: interaction with moderately high dietary salt. Can J Physiol Pharmacol 2007, 85:413–421.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Petersen A, Kappler F, Szwergold BS, Brown TR: Fructose metabolism in the human erythrocyte. phosphorylation to fructose 3-phosphate. Biochem J 1992, 284(Pt 2):363–366.

    CAS  PubMed  Google Scholar 

  19. 19.

    Kizhner T, Werman MJ: Long-term fructose intake: biochemical consequences and altered renal histology in the male rat. Metabolism 2002, 51:1538–1547.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Tasevska N, Runswick SA, Welch AA, et al.: Urinary sugars biomarker relates better to extrinsic than to intrinsic sugars intake in a metabolic study with volunteers consuming their normal diet. Eur J Clin Nutr 2009, 63: 653–659.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Mate A, de la Hermosa MA, Barfull A, et al.: Characterization of D-fructose transport by rat kidney brush-border membrane vesicles: changes in hypertensive rats. Cell Mol Life Sci 2001, 58:1961–1967.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Concha II, Velasquez FV, Martinez JM, et al.: Human erythrocytes express GLUT5 and transport fructose. Blood 1997, 89:4190–4195.

    CAS  PubMed  Google Scholar 

  23. 23.

    •• Singh AK, Amlal H, Haas PJ, et al.: Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5. Kidney Int 2008, 74:438–447. This study clearly demonstrated the fundamental role of increased sodium reabsorption in hypertension induced by fructose ingestion.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Barone S, Fussell SL, Singh AK, et al.: Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J Biol Chem 2009, 284:5056–5066.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    He FJ, Marrero NM, MacGregor GA: Salt intake is related to soft drink consumption in children and adolescents: a link to obesity? Hypertension 2008, 51:629–634.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Catena C, Cavarape A, Novello M, et al.: Insulin receptors and renal sodium handling in hypertensive fructose-fed rats. Kidney Int 2003, 64:2163–2171.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Diggle CP, Shires M, Leitch D, et al.: Ketohexokinase: expression and localization of the principal fructose-metabolizing enzyme. J Histochem Cytochem 2009, 57:763–774.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Nakayama T, Kosugi T, Gersch M, et al.: Dietary fructose causes tubulointerstitial injury in the normal rat kidney. Am J Physiol Renal Physiol 2010, 298:F712–F720.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B: Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med 2002, 346:913–923.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Sanchez-Lozada LG, Tapia E, Bautista-Garcia P, et al.: Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 2008, 294:F710–F718.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

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

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Hu QH, Wang C, Li JM, et al.: Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement. Am J Physiol Renal Physiol 2009, 297:F1080–F1091.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Vitart V, Rudan I, Hayward C, et al.: SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet 2008, 40:437–442.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Wallace C, Newhouse SJ, Braund P, et al.: Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet 2008, 82:139–149.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Schalkwijk CG, Stehouwer CD, van Hinsbergh VW: Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification. Diabetes Metab Res Rev 2004, 20:369–382.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    D’Agati V, Schmidt AM: RAGE and the pathogenesis of chronic kidney disease. Nat Rev Nephrol 2010, 6:352–360.

    Article  PubMed  Google Scholar 

  37. 37.

    Glushakova O, Kosugi T, Roncal C, et al.: fructose induces the inflammatory molecule ICAM-1 in endothelial cells. J Am Soc Nephrol 2008, 19:1712–1720.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Zhao CX, Xu X, Cui Y, et al.: Increased endothelial nitric-oxide synthase expression reduces hypertension and hyperinsulinemia in fructose-treated rats. J Pharmacol Exp Ther 2009, 328:610–620.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

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

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Chao HH, Liu JC, Lin JW, et al.: Uric acid stimulates endothelin-1 gene expression associated with NADPH oxidase in human aortic smooth muscle cells. Acta Pharmacol Sin 2008, 29:1301–1312.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Sanchez-Lozada LG, Soto V, Tapia E, et al.: Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia. Am J Physiol Renal Physiol 2008, 295:F1134–F1141.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Wang X, Jia X, Chang T, et al.: Attenuation of Hypertension Development by Scavenging Methylglyoxal in Fructose-Treated Rats. J Hypertens 2008, 26:765–772.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH: Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. J Hypertens 2010, 28:1234–1242.

    PubMed  Google Scholar 

  44. 44.

    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.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Chen L, Caballero B, Mitchell DC, et al.: Reducing consumption of sugar-sweetened beverages is associated with reduced blood pressure: a prospective study among United States adults. Circulation 2010, 121:2398–2406.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Dhingra R, Sullivan L, Jacques PF, et al.: Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation 2007, 116:480–488.

    Article  PubMed  Google Scholar 

  47. 47.

    Jalal DI, Smits G, Johnson RJ, Chonchol M: Increased fructose associates with elevated blood pressure. J Am Soc Nephrol 2010, 21:1543–1549.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Perez-Pozo SE, 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 (Lond) 2010, 34:454–461.

    CAS  Article  Google Scholar 

  49. 49.

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

    CAS  PubMed  Google Scholar 

Download references


Conflicts of Interest: M Madero: none; SE Perez-Pozo: none; D Jalal: none; RJ Johnson has a book, The Sugar Fix:The High-Fructose Fallout That Is Making You Fat and Sick (Rodale, 2008; Simon and Schuster, 2009), which discusses the potential role of fructose in the obesity epidemic, and he is listed as an inventor on several patent applications related to blocking fructose metabolism and/or lowering uric acid as a means for treating hypertension and metabolic syndrome; LG Sánchez-Lozada: none.

Author information



Corresponding author

Correspondence to Laura G. Sánchez-Lozada.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Madero, M., Perez-Pozo, S.E., Jalal, D. et al. Dietary Fructose and Hypertension. Curr Hypertens Rep 13, 29–35 (2011).

Download citation


  • Fructose
  • Hypertension
  • Metabolic syndrome
  • Uric acid
  • Renal disease
  • Sodium reabsorption