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The primary purpose of our study was to determine the role of uric acid in fructose-mediated metabolic effects, and as such our study compared the effects of fructose supplementation with or without allopurinol (a xanthine oxidase inhibitor). The reason we used high doses of fructose was to ensure the robust metabolic effects that would better allow distinction of the role of uric acid. Although the study was single blinded, the laboratory tests were performed by technicians blinded to the two groups and the blood pressure readings were made by an automated 24 h ambulatory blood pressure equipment. Hence, all results consisted of ‘hard’ data. An important finding in our study was the observation that fructose can raise blood pressure and that this was uric acid dependent. These studies are consistent with epidemiological studies1, 2 and a recent clinical trial.3

We agree that inclusion of a glucose control group would have been beneficial. However, a carefully performed clinical trial by Stanhope et al.4 has already documented that fructose, but not glucose, induces features of metabolic syndrome in humans. Experimental studies have also documented that fructose is distinct from glucose in its ability to induce metabolic syndrome and that this is independent of energy intake.5, 6 These data are consistent with a recent meta-analysis that found that high-fructose corn syrup-containing beverages increase the risk for metabolic syndrome and diabetes.7

Our finding that we induced metabolic syndrome in 25% of adults within 2 weeks is of great concern. Although we agree that the rapidity of this induction is likely because of the large doses of fructose used in this study, it raises the specter that lower doses of fructose may cause similar effects over a longer period of time and would be consistent with the observation that obesity and metabolic syndrome develop over years in humans. For example, although it takes only 2 months to induce insulin resistance with 60% fructose in rats, studies show that a 15% fructose diet can induce insulin resistance in 15 months.8

In conclusion, we believe our study makes an important contribution on the role of excessive fructose in inducing metabolic syndrome and on the role of fructose-induced hyperuricemia in the blood pressure response. Although the doses of fructose used in the study were large, we must remember that some groups, such as young adults and children, are ingesting as much as 20–30% of their diet as added sugars. Other groups, such as African Americans and Hispanic Americans, are ingesting disproportionately higher amounts of fructose-containing sugars. When one further notes that the coexistent glucose can enhance fructose absorption in the intestine, our study gains additional clinical relevance. Hence, we strongly recommend public health measures to reduce the intake of fructose-containing sugars in the population; we believe this will have a major benefit to prevent obesity, diabetes and hypertension, with overall benefits to cardiovascular health.


  1. 1

    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.

  2. 2

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

  3. 3

    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.

  4. 4

    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.

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    Gersch MS, Mu W, Cirillo P, Reungjui S, Zhang L, Roncal C et al. Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am J Physiol 2007; 293: F1256–F1261.

  6. 6

    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.

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    Hu FB, Malik V, Popkin BM, Bray GA, Despres JP, Willett W . Sugar sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care 2010, e-pub ahead of print 6 August 2010.

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    Blakely SR, Hallfrisch J, Reiser S, Prather ES . Long-term effects of moderate fructose feeding on glucose tolerance parameters in rats. J Nutr 1981; 111: 307–314.

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Correspondence to R J Johnson.

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Competing interests

Dr Johnson has a lay book, The Sugar Fix (Rodale, Simon and Schuster) and is also listed as an inventor on several patent applications related to blocking the effects of fructose to induce obesity and metabolic syndrome. All other authors declare no conflict of interest.

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