Millions of years of hunting and gathering has shaped our genome and unique metabolism so that we can survive cycles of feast and famine. We are not however, adapted to continual overeating of processed foods.

The inability to synthesise vitamin C helped our ancestors survive cold winters:

Two important genetic deletions that characterise modern humans occurred several million years ago. The loss of ability to synthesise Vitamin C in our prehominid ancestors occurred in the late Eocene (30-40Ma) and was followed by a further mutation loosing uricase activity in the mid Miocene (15Ma).ref These mutations offered resilience to starvation and cold by optimising the formation and storage of body fat during the subsequent periods of climate change over the next half a million years with irregular cooling periods lasting approximately 100,000 years interspersed with periods of rapid warming of approximately 10°C in the Antarctic and 3-4°C in the tropical oceans (source).

During this period there were at least 2 migrations of prehominids from Africa to Eurasia and back again, with this genome adapted to starvation and cold.

Of the many complex factors driving human evolution one can be selected as a crucial selector- the fruit sugar fructose.

Our early primate ancestors, living in the pre-miocene tropical rainforests which extended from Africa to Europe and Asia, would have had fructose-rich fruit as their major staple.

Global cooling in the mid-Miocene reduced the rainforest area and caused seasonal food shortages driving hominid evolution, specifically fructose uptake and fat accumulation.

Recent experiments with laboratory animals suggest that prior to the uricase mutation the disabling of Vit C synthesis may have reduced the antioxidant inhibition of fat synthesis at the mitochondrial level and reduced urate excretion.

Elevated urate is thought to stimulate fructose based fat synthesis (mediated by NADPH oxidase which generates oxygen radicals). Mitochondrial respiratory function is reduced and fat synthesis stimulated.

Dietary factors support this thesis. Fruit consumed in the summer is rich in Vitamin C and this supports the synthesis of tissues, in particular the connective tissue collagen. In Autumn Vitamin C levels fall whilst the fructose content of fruit rises simulating fat accumulation in animals prior to food scarcity in the winter months.   Perhaps even more extreme cooling in the mid-Miocene ice age selected for the uricase mutation to further enhance urate accumulation and the fructose stimulation of fat accretion.

Brain size…a driving force for evolution of energy metabolism?


Compared with all other mammals the human brain is ‘overdeveloped’ or hypertrophied. It contributes 2% of our body weight but consumes 20% of our daily calories. This has led to the evolution of a unique human energy metabolism, which is driven by the energy requirements of the brain. Beta-hydroxybutyrate (BHB) can replace glucose as the brains major energy source during starvation.

We predict that ongoing and future research will confirm the central role of BHB in energy metabolism in active, healthy humans, and will support the need to limit sugar and refined carbohydrates in the human diet.


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Site authors: Professor Rodney Bilton, Dr Larry Booth, and Joseph Bilton M.Sc B.Sc