Obesity and related diseases are an important and growing health concern in the United States and around the world. Soft drinks and other sugar-sweetened beverages are now the primary sources of added sugars in Americans’ diets. The metabolic syndrome is a cluster of common pathologies, including abdominal obesity linked to an excess of visceral fat, fatty liver, insulin resistance, hyperinsulinemia, dyslipidemia, and hypertension. Trends in all of these alterations are related to the consumption of dietary fructose and the introduction of high-fructose corn syrup (HFCS) as a sweetener in soft drinks and other foods. Experimental and clinical evidence suggests a progressive association between HFCS consumption, obesity, and the other injury processes. However, experimental HFCS consumption seems to produce some of the changes associated with metabolic syndrome even without increasing the body weight. Metabolic damage associated with HFCS probably is not limited to obesity-pathway mechanisms.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance
Ogden CL, Carroll MD, McDowell MA, Flegal KM: Obesity among adults in the United States—no change since 2003–2004. NCHS data brief no 1. Hyattsville, MD: National Center for Health Statistics. 2007.
Popkin BM, Armstrong LE, Bray GM, et al.: A new proposed guidance system for beverage consumption in the United States. Am J Clin Nutr 2006, 83(3):529–542.
Guzman-Maldonado H, Paredes-Lopez O: Amylolytic enzymes and products derived from starch: a review. Crit Rev Food Sci Nutr 1995, 35(5):373–403.
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(6):1228 S–1235 S.
Forshee RA, Anderson PA, Storey ML: Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. Am J Clin Nutr 2008, 87(6):1662–1671.
•• Johnson RJ, Segal MS, Sautin Y, et al.: Potential role of sugar (fructose) in the epidemic of disease. Am J Clin Nutr 2007, 86(4):899–906. This very important review suggests that fructose intake may be a risk factor for hypertension, insulin resistance, hypertriglyceridemia, obesity, type 2 diabetes, preeclampsia, chronic kidney disease, stroke, cardiovascular disease, and mortality. It also shows that the appearance of these disorders is epidemiologically linked to increased fructose consumption.
Nakagawa T, Tuttle KR, Short RA, Johnson RJ: Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 2005, 1(2):80–86.
Hwang IS, Ho H, Hoffman BB, Reaven GM: Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987, 10(5):512–516.
Hallfrisch J: Metabolic effects of dietary fructose. FASEB J 1990, 4(9):2652–2660.
Havel PJ: Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 2005, 63(5):133–157.
Bray GA, Nielsen SJ, Popkin BM: Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004, 79(4):537–543.
Vuilleumier S: Worldwide production of high-fructose syrup and crystalline fructose. Am J Clin Nutr 1993, 58(5 Suppl):733 S–736 S.
• Stanhope KL, Schwarz JM, Keim NL, 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(5):1322–1334. In this paper, Stanhope et al. demonstrate that consumption of fructose-sweetened (but not glucose-sweetened) beverages for 10 weeks increases de novo lipid synthesis, promotes dyslipidemia, impairs insulin sensitivity, and increases visceral adiposity in overweight or obese adults.
Hellerstein MK, Schwarz JM, Neese RA: Regulation of hepatic de novo lipogenesis in humans. Annu Rev Nutr 1996, 16:523–557.
Mayes PA: Intermediary metabolism of fructose. Am J Clin Nutr 1993, 58(5 Suppl):754 S–765 S.
Abraha A, Humphreys SM, Clark ML, et al.: Acute effect of fructose on postprandial lipaemia in diabetic and non-diabetic subjects. Br J Nutr 1998, 80(2):169–175.
Chen JH, Chuang SY, Chen HJ, et al.: Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum 2009, 61(2):225–232.
Lee MK, Miles PD, Khoursheed M, et al.: Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes 1994, 43(12):1435–1439.
Martinez FJ, Rizza RA, Romero JC: High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs. Hypertension 1994, 23(4):456–463.
Curry DL: Effects of mannose and fructose on the synthesis and secretion of insulin. Pancreas 1989, 4(1):2–9.
Arner P: Free fatty acids—Do they play a central role in type 2 diabetes? Diabetes Obes Metab 2001, 3(Suppl 1):S11–S19.
Schwartz MW, Baskin DG, Kaiyala KJ, Woods SC: Model for the regulation of energy balance and adiposity by the central nervous system. Am J Clin Nutr 1999, 69(4):584–596.
Tordoff MG, Alleva AM: Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. Am J Clin Nutr 1990, 51(6):963–969.
Anderson JW, Story LJ, Zettwoch NC, et al.: Metabolic effects of fructose supplementation in diabetic individuals. Diabetes Care 1989, 12(5):337–344.
Faeh D, Minehira K, Schwarz JM, et al.: Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. Diabetes 2005, 54(7):1907–1913.
Hallfrisch J, Reiser S, Prather ES: Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Am J Clin Nutr 1983, 37(5):740–748.
Dai S, McNeill JH: Fructose-induced hypertension in rats is concentration- and duration-dependent. J Pharmacol Toxicol Methods 1995, 33(2):101–107.
Daly ME, Vale C, Walker M, et al.: Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications. Am J Clin Nutr 1997, 66(5):1072–1085.
Vasdev S, Ford CA, Longerich L, et al.: Role of aldehydes in fructose induced hypertension. Mol Cell Biochem 1998, 181(1-2):1–9.
Verma S, Bhanot S, McNeill JH: Decreased vascular reactivity in metformin-treated fructose-hypertensive rats. Metabolism 1996, 45(9):1053–1055.
Rajasekar P, Palanisamy N, Anuradha CV: Increase in nitric oxide and reductions in blood pressure, protein kinase C beta II and oxidative stress by L-carnitine: a study in the fructose-fed hypertensive rat. Clin Exp Hypertens 2007, 29(8):517–530.
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(2):H1083–H1089.
Sechi LA: Mechanisms of insulin resistance in rat models of hypertension and their relationships with salt sensitivity. J Hypertens 1999, 17(9):1229–1237.
Reaven GM: Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988, 37(12):1595–1607.
Giacchetti G, Sechi LA, Griffin CA, et al.: The tissue renin-angiotensin system in rats with fructose-induced hypertension: overexpression of type 1 angiotensin II receptor in adipose tissue. J Hypertens 2000, 18(6):695–702.
Jalal DI, Smits G, Johnson R: Increased fructose intake is independently associated with elevated blood pressure. Findings from the National Health and Nutrition Examination Survey (2003-2006) [abstract TH-FC037]. Presented at American Society of Nephrology Renal Week. San Diego, CA; October 27–November 1, 2009.
Ran J, Hirano T, Fukui T, et al.: Angiotensin II infusion decreases plasma adiponectin level via its type 1 receptor in rats: an implication for hypertension-related insulin resistance. Metabolism 2006, 55(4):478–488.
Shinozaki K, Ayajiki K, Nishio Y, et al.: Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance. Hypertension 2004, 43(2):255–262.
Miatello R, Risler N, Castro C, et al.: Aortic smooth muscle cell proliferation and endothelial nitric oxide synthase activity in fructose-fed rats. Am J Hypertens 2001, 14(11 Pt 1):1135–1141.
Hsieh PS: Reversal of fructose-induced hypertension and insulin resistance by chronic losartan treatment is independent of AT2 receptor activation in rats. J Hypertens 2005, 23(12):2209–2217.
Nakagawa T, Mazzali M, Kang DH, et al.: Hyperuricemia causes glomerular hypertrophy in the rat. Am J Nephrol 2003, 23(1):2–7.
Fernandez JM, Da Silva-Grigoletto ME, Gomez-Puerto JR, et al.: A dose of fructose induces oxidative stress during endurance and strength exercise. J Sports Sci 2009, 27(12):1323–1334.
Delbosc S, Paizanis E, Magous R, et al.: Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 2005, 179(1):43–49.
Wei Y, Pagliassotti MJ: Hepatospecific effects of fructose on c-jun NH2-terminal kinase: implications for hepatic insulin resistance. Am J Physiol 2004, 287(5):E926–E933.
Rudin E, Barzilai N: Inflammatory peptides derived from adipose tissue [editorial]. Immun Ageing 2005, 2(1):1.
Sjoholm A, Nystrom T: Inflammation and the etiology of type 2 diabetes. Diabetes Metab Res Rev 2006, 22(1):4–10.
Armutcu F, Coskun O, Gurel A, et al.: Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats. Clin Biochem 2005, 38(6):540–547.
Nakagawa T, Hu H, Zharikov S, et al.: A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 2006, 290(3):F625–F631.
Assy N, Nasser G, Kamayse I, et al.: Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol 2008, 22(10):811–816.
• Collison KS, Saleh SM, Bakheet RH, et al.: Diabetes of the liver: the link between nonalcoholic fatty liver disease and HFCS-55. Obesity (Silver Spring) 2009, 17(11):2003–2013. The aim of this study was to establish whether HFCS could contribute to the pathogenesis of NAFLD, by examining the effects of HFCS-55 on hepatocyte lipogenesis, insulin signaling, and cellular function in vitro and in vivo. Taken together, the findings indicate a potential mechanism by which HFCS may contribute to the pathogenesis of NAFLD.
Chen J, Muntner P, Hamm LL, et al.: The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004, 140(3):167–174.
• Sánchez-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(1):F423–F429. A good experimental design showing that fructose administration in diet or drinking water induced hypertension, hyperuricemia, and hypertriglyceridemia. In addition, rats given higher fructose doses developed kidney hypertrophy, glomerular hypertension, cortical vasoconstriction, and arteriolopathy of preglomerular vessels. In summary, fructose-induced metabolic syndrome is associated with renal disturbances characterized by renal hypertrophy, arteriolopathy, glomerular hypertension, and cortical vasoconstriction.
Schwieger J, Fine LG: Renal hypertrophy, growth factors, and nephropathy in diabetes mellitus. Semin Nephrol 1990, 10(3):242–253.
Coresh J, Byrd-Holt D, Astor BC, et al.: Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol 2005, 16(1):180–188.
Wang Z, Hoy WE: Albuminuria as a marker of the risk of developing type 2 diabetes in non-diabetic Aboriginal Australians. Int J Epidemiol 2006, 35(5):1331–1335.
Shoham DA, Durazo-Arvizu R, Kramer H, et al.: Sugary soda consumption and albuminuria: results from the National Health and Nutrition Examination Survey, 1999-2004. PloS One 2008, 3(10):e3431.
•• Neilson EG: The fructose nation. J Am Soc Nephrol 2007, 18(10):2619–2621. This very good editorial summarizes the problem of high fructose intake and its emergence as a cheaper, widely used alternative to sucrose. This author also points out that obesity may not be the only driver of metabolic syndrome.
Gersch MS, Mu W, Cirillo P, et al.: Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am J Physiol Renal Physiol 2007, 293(4):F1256–F1261.
Taylor EN, Curhan GC: Fructose consumption and the risk of kidney stones. Kidney Int 2008, 73(2):207–212.
Choi HK, Curhan G: Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 2008, 336(7639):309–312.
• Johnson RK, Appel LJ, Brands M, et al.: Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation 2009, 120(11):1011–1020. In this review, Johnson et al. analyze national survey data and show that excessive consumption of added sugars is contributing to overconsumption of discretionary calories by Americans. The American Heart Association recommends reductions in the intake of added sugars to no more than 100 calories per day for most American women and no more than 150 calories per day for most American men.
No potential conflicts of interest relevant to this article were reported.
About this article
Cite this article
Ferder, L., Ferder, M.D. & Inserra, F. The Role of High-Fructose Corn Syrup in Metabolic Syndrome and Hypertension. Curr Hypertens Rep 12, 105–112 (2010). https://doi.org/10.1007/s11906-010-0097-3
- High fructose corn syrup
- Cardiovascular disease
- Metabolic syndrome