Global sugar consumption is at an all-time high. In previous studies, we and others have demonstrated that, compared with glucose (Gluc), consumption of fructose (Fruc) increases risk factors for cardiovascular disease (CVD), diabetes and metabolic syndrome. However, humans almost exclusively consume Fruc in combination with Gluc. Our aim was to study effects of Gluc, Fruc and their combination - high fructose corn syrup (HFCS) - and identify effects on metabolic risk factors.

We performed a parallel-armed, double blinded intervention study wherein the subjects consumed beverages sweetened with 25% of their energy requirement (Ereq) as Gluc, Fruc or HFCS, or 17.5% Ereq as Fruc or HFCS, or Aspartame (ASP) for two weeks with their usual diet. Procedures, which included fasting and postprandial blood draws, were conducted over a 48-h period at baseline and at the end of intervention while subjects consumed standardized meals containing 30% Ereq as fat, 15% protein, 55% carbohydrate (mainly complex during baseline; complex + sweetened beverage during intervention). As expected, the increases for 24h triglyceride area under the curve (AUC), 24h uric acid AUC, and postprandial apoCIII were highest in both Fruc groups (all P<0.01 versus ASP), next highest in both HFCS groups (all P<0.05 25% Ereq HFCS versus ASP), and lowest in the Gluc group (all P>0.05 versus ASP). Unexpectedly, the increases of LDL- and non-HDL-cholesterol (C) and ApoB were highest in the HFCS groups (all P<0.001 25% HFCS versus ASP, P<0.01 versus Gluc). Re-analyzing the outcomes based on the amounts of Fruc and Gluc contained in the beverages revealed significant interactions between Fruc and Gluc on fasting and postprandial concentrations of LDL-C, non-HDL-C and ApoB (all P<0.01).

While sole consumption of Fruc leads to increases of metabolic risk factors, those increases are exacerbated for several risk factors when Fruc is co-ingested with Gluc as HFCS.


B. Hieronimus: None. V. Medici: None. V. Lee: None. M. Nunez: None. P.J. Havel: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. K.L. Stanhope: None.


National Heart, Lung, and Blood Institute (1R01HL09133, 1R01HL107256); National Center for Research Resources (UL1RR024146); Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD051958); Office of Research on Women’s Health; Office of Dietary Supplements; National Institute on Aging (to K.L.S.)

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