Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 121, 295-305; discussion 305-8

Theodore E. Woodward Award. The Evolution of Obesity: Insights From the mid-Miocene


Theodore E. Woodward Award. The Evolution of Obesity: Insights From the mid-Miocene

Richard J Johnson et al. Trans Am Clin Climatol Assoc.

Erratum in

  • Trans Am Clin Climatol Assoc. 2013;124:294


All humans are double knockouts. Humans lack the ability to synthesize vitamin C due to a mutation in L-gulono-lactone oxidase that occurred during the late Eocene, and humans have higher serum uric acid levels due to a mutation in uricase that occurred in the mid Miocene. In this paper we review the hypothesis that these mutations have in common the induction of oxidative stress that may have had prosurvival effects to enhance the effects of fructose to increase fat stores. Fructose was the primary nutrient in fruit which was the main staple of early primates, but this food likely became less available during the global cooling that occurred at the time of these mutations. However, in today's society, the intake of fructose, primarily in the form of added sugars, has skyrocketed, while the intake of natural fruits high in vitamin C has fallen. We suggest that it is the interaction of these genetic changes with diet that is responsible for the obesity epidemic today. Hence, we propose that Neel's thrifty gene hypothesis is supported by these new insights into the mechanisms regulating fructose metabolism.

Keywords: ascorbate; metabolic syndrome; obesity; uricase; vitamin C.

Conflict of interest statement

Potential Conflicts of Interest: Dr. Johnson has one patent and several pending patents related to uric acid management in patients with hypertension and cardiovascular disease.


Fig. 1
Fig. 1
James V. Neel drawing a blood sample from a young Yanomamö Indian (42). Dr Oliver (author) and Dr Neel performed several studies of the Yanomamö Indians that live in the jungles of southern Venezuela. In particular, this is an indigenous people with normal blood pressure and a diet high in potassium and low in sodium (42).
Fig. 2
Fig. 2
William J. Oliver with Yanomamö children.
Fig. 3
Fig. 3
Major pathways for generating uric acid.

Similar articles

See all similar articles

Cited by 16 articles

See all "Cited by" articles

Publication types

MeSH terms