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Fructose: Metabolic, Hedonic, and Societal Parallels with Ethanol

      Abstract

      Rates of fructose consumption continue to rise nationwide and have been linked to rising rates of obesity, type 2 diabetes, and metabolic syndrome. Because obesity has been equated with addiction, and because of their evolutionary commonalities, we chose to examine the metabolic, hedonic, and societal similarities between fructose and its fermentation byproduct ethanol. Elucidation of fructose metabolism in liver and fructose action in brain demonstrate three parallelisms with ethanol. First, hepatic fructose metabolism is similar to ethanol, as they both serve as substrates for de novo lipogenesis, and in the process both promote hepatic insulin resistance, dyslipidemia, and hepatic steatosis. Second, fructosylation of proteins with resultant superoxide formation can result in hepatic inflammation similar to acetaldehyde, an intermediary metabolite of ethanol. Lastly, by stimulating the “hedonic pathway” of the brain both directly and indirectly, fructose creates habituation, and possibly dependence; also paralleling ethanol. Thus, fructose induces alterations in both hepatic metabolism and central nervous system energy signaling, leading to a “vicious cycle” of excessive consumption and disease consistent with metabolic syndrome. On a societal level, the treatment of fructose as a commodity exhibits market similarities to ethanol. Analogous to ethanol, societal efforts to reduce fructose consumption will likely be necessary to combat the obesity epidemic.
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      Biography

      R. H. Lustig is professor of pediatrics, Division of Endocrinology, University of California, San Francisco.

      Linked Article

      • Is Fructose a Story of Mice but Not Men?
        Journal of the American Dietetic AssociationVol. 111Issue 2
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          We read with interest the hypothesis by Lustig (1) paralleling the metabolic effects of fructose with those of ethanol. We were concerned, however, that the conclusions drew heavily on animal data and that confounding from excess energy was not addressed.
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      • More on Mice and Men: Fructose Could put Brakes on a Vicious Cycle Leading to Obesity in Humans
        Journal of the American Dietetic AssociationVol. 111Issue 7
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          The role played by dietary fructose in the ‘epidemic’ of obesity has recently been debated in the Journal of the American Dietetic Association (1,2) following the earlier review by Lustig (3) in which fructose is argued to have a prominent role in the causation and perpetuation of obesity. These warrant comment because the arguments do not represent the literature in humans on this topic and literature is cited inaccurately, particularly in regard to my own work.
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