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J Intern Med. 2019 Oct 17. doi: 10.1111/joim.12993. [Epub ahead of print]

Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts.

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From the, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Division of Renal Diseases, Karolinska Institute, Stockholm, Sweden.
Museum of Natural History, London, UK.
Department of Nephrology, INC Ignacio Chávez, Mexico City, Mexico.
Department of Nephrology, Rakuwakai Otowa Hospital, Kyoto, Japan.
Department of Biology, Georgia State University, Atlanta, GA, USA.
Division of Renal Diseases, Ewha University, Seoul, Korea.
Department of Biology, Boston University, Boson, MA, USA.


Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.


fructose; metabolic syndrome; metabolic water; uric acid; vasopressin


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