The Journal of Pediatrics
Volume 154, Issue 6 , Pages 783-784, June 2009

Sour Notes on Sweet Drinks

  • Daniel I. Feig, MD, PhD, MS

      Affiliations

    • Corresponding Author InformationReprint requests: Daniel I. Feig, MD, PhD, MS, Department of Pediatrics, Renal Section, Texas Children's Hospital, Baylor College of Medicine, 6621 Fannin St, MC3-2482, Houston, TX 77030

Department of Pediatrics, Renal Section, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas

Article Outline

Abbreviation: HFCS, High fructose corn syrup

 

The perspective on uric acid has ranged from innocent bystander to cause of many ills. As far back as the 1870s, Frederick Mohamed1 noted patients with gout had higher blood pressures than those without. In 1897, Alexander Haig2 hypothesized that uric acid was the cause of diseases including gout, hypertension, cardiovascular disease, stroke, dementia, and a variety of abdominal and joint complaints. Throughout most of the twentieth century, however, elevated serum uric acid was believed to be a marker of decreased renal function and of no direct clinical significance. Over the past decade, numerous studies have found that an elevated serum uric acid level predicts the development of hypertension.3 An elevated serum uric acid is also common in untreated hypertension and especially common in adolescents with essential hypertension, with rates as high as 88%.4 A recent placebo-controlled cross-over trial of children with newly diagnosed essential hypertension and mildly elevated serum uric acid revealed that blood pressure could be normalized by administration of allopurinol in 67% of children compared with 3% of those treated with placebo.5

See related article, p 807

The prevalence of elevated serum uric acid levels correlates with the rise in the rate of obesity and hypertension.6 Although there is some variability in renal urate clearance because of polymorphisms in renal urate and organic anion channels, a common source of uric acid may be dietary fructose. Sweetener consumption has dramatically increased since the introduction of high fructose corn syrup (HFCS) in the early 1970s.7 Fructose is the only sugar that leads to a rise in serum uric acid levels, and it does so rapidly via activation of the fructokinase pathway in hepatocytes.8 Fructose-fed rats develop features of the metabolic syndrome, hyperuricemia, and hypertension,9 plus the development of preglomerular arteriolopathy. Lowering uric acid prevents these changes.7 Recent human studies also suggest that fructose or hyperuricemia may have a role in other cardiovascular and kidney diseases, including the progression of kidney disease, the risk for acute kidney failure,10 and the development of nonalcoholic fatty liver disease.11 This suggests that uric acid (and fructose) may have a role in the epidemic of hypertension, obesity/metabolic syndrome, and kidney disease.

In this issue of The Journal, Nguyen et al12 present a novel analysis of the National Health and Nutrition Examination Survey 1999–2004 data. They assessed the data collected on 4867 adolescents who had completed 24-hour dietary recall questionnaires. The population sample is particularly strong in its diverse representation of the U.S. population of adolescents. Report of sweetened beverage (soda, fruit drinks, sports drinks, and sweetened coffee or tea) consumption was used as a surrogate for sugar and HFCS intake. The children were separated into 5 groups by level daily consumption (0 oz, 1-12 oz, 13-24 oz, 25-36 oz, >36 oz). Compared with lower intake groups, the highest intake group was more likely to be slightly older (15.4 vs 16.4 years), more likely to be male (43% vs 53%), and had higher caloric intake, sodium intake, caffeine intake (all statistically significant), and greater tendency toward tobacco and alcohol use. These trends suggest that sweetened beverage intake trends are at some level a surrogate for less healthy lifestyle choices in adolescents. In both unadjusted and adjusted analyses (for age, race/ethnicity, sex, total caloric intake, body mass index z-score, alcohol consumption, smoking, dietary fiber intake, milk, caffeine intake, and diet beverage consumption), the trend from lower to higher sweetened beverage consumption was associated with statistically significant increase in serum uric acid and in systolic blood pressure z-score. Even though the absolute values of the differences are relatively small, the trend is important and concerning. Because the dietary recall did not specifically include intake of other sweets, particularly candies, baked goods, and other sweet snacks that may be consumed across the groups, the observations could be an underestimate of the impact of total sugar and HFCS intake. Although sweetened beverage intake has previously been associated with obesity in children,13 these data indicate a health impact in addition to weight gain.

The mechanism by which serum uric acid mediates hypertension and metabolic syndrome is under study. Uric acid has multiple effects on endothelial cells, vascular smooth muscle cells, and adipocytes. Some of the effects include the inhibition of endothelial Nitric Oxide levels, the stimulation of inflammatory pathways including C-reactive protein, the stimulation of local angiotensin II production, the stimulation of nicotinamide adenine dinucleotide phosphate oxidase, and the inhibition of adipokines.14, 15 These studies provide numerous prospective targets for pharmaceutical intervention to study the primary or secondary prevention of uric acid–mediated morbidity. The results of Nguyen et al12 suggest a simpler possibility. By demonstrating the impact of sweetened beverage on serum uric acid and blood pressure in a young population, they emphasize that the public health importance of reducing the intake of sugar-sweetened beverages and other sweets is even greater than its impact on obesity. Obesity-related comorbidities may, in part, be mediated by the biochemical results of fructose intake, as well as the weight gain. This is particularly important for the pediatric community to realize as we advise our patients and their families. Members of the American Academy of Pediatrics recently received mailings from the Corn Refiner's Association, an industry group that is launching a public relations campaign to preserve the image of HFCS against “unwarranted attacks.” Families will likely come to their pediatricians having heard that HFCS is wholesome. It remains the responsibility of pediatricians to teach families that reducing sweetener consumption in all children, especially those who are overweight and obese, may have a positive health impact that extends beyond weight alone.

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References 

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  5. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924–932
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PII: S0022-3476(09)00213-3

doi:10.1016/j.jpeds.2009.02.054

Refers to article:

  • Sugar-Sweetened Beverages, Serum Uric Acid, and Blood Pressure in Adolescents , 20 April 2009

    Stephanie Nguyen, Hyon K. Choi, Robert H. Lustig, Chi-yuan Hsu
    The Journal of Pediatrics June 2009 (Vol. 154, Issue 6, Pages 807-813)

The Journal of Pediatrics
Volume 154, Issue 6 , Pages 783-784, June 2009

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