Journal of Comparative Physiology B

, Volume 179, Issue 1, pp 67–76 | Cite as

Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone awry in western society?

  • Richard J. JohnsonEmail author
  • Yuri Y. Sautin
  • William J. Oliver
  • Carlos Roncal
  • Wei Mu
  • L. Gabriela Sanchez-Lozada
  • Bernardo Rodriguez-Iturbe
  • Takahiko Nakagawa
  • Steven A. Benner


Uric acid has historically been viewed as a purine metabolic waste product excreted by the kidney and gut that is relatively unimportant other than its penchant to crystallize in joints to cause the disease gout. In recent years, however, there has been the realization that uric acid is not biologically inert but may have a wide range of actions, including being both a pro- and anti-oxidant, a neurostimulant, and an inducer of inflammation and activator of the innate immune response. In this paper, we present the hypothesis that uric acid has a key role in the foraging response associated with starvation and fasting. We further suggest that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid stimulating the foraging response and vitamin C countering this response. Finally, we suggest that the mutations in ascorbate synthesis and uricase that characterized early primate evolution were likely in response to the need to stimulate the foraging “survival” response and might have inadvertently had a role in accelerating the development of bipedal locomotion and intellectual development. Unfortunately, due to marked changes in the diet, resulting in dramatic increases in fructose- and purine-rich foods, these identical genotypic changes may be largely responsible for the epidemic of obesity, diabetes and cardiovascular disease in today’s society.


Uric acid Fructose Foraging Metabolic syndrome Obesity Fasting Hibernation 



Supported by US Public Health Service grants HL-68607 (RJ), DK-52121 (RJ).


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Richard J. Johnson
    • 1
    Email author
  • Yuri Y. Sautin
    • 1
  • William J. Oliver
    • 2
  • Carlos Roncal
    • 1
  • Wei Mu
    • 1
  • L. Gabriela Sanchez-Lozada
    • 3
  • Bernardo Rodriguez-Iturbe
    • 4
  • Takahiko Nakagawa
    • 1
  • Steven A. Benner
    • 5
  1. 1.Division of Nephrology, Hypertension and TransplantationUniversity of FloridaGainesvilleUSA
  2. 2.Ann ArborUSA
  3. 3.Cardiologia UniversityMexico CityUSA
  4. 4.University of ZuliaMaracaiboVenezuela
  5. 5.Foundation of Applied Molecular EvolutionGainesvilleUSA

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