Further Implications of Lowered Gluconeogenesis: Vitamin C Synthesis

This is a follow up post to "Evolutionary Trade-Offs: Fast Versus Famine" and "Detox, Antioxidants, and Scurvy: Protein Beats Plants".

We already looked at how we manage without the ability to synthesise ascorbic acid aka vitamin C, by using uric acid derived from protein instead, but why do we do this? Why not just make vitamin C like other carnivores do? Indeed all carnivores make ascorbic acid, so why are we different?

I believe that our lower level of gluconeogenesis (GNG) is to blame. Ascorbic acid is synthesised from glucose, and with a diminished capacity to make glucose then we don't really have any spare, the muscles need all they can get. So to converse the precious small glucose pool we switched from using ascorbic acid (derived from glucose) to uric acid (derived from protein), and one big difference is the amount of the substance needed for the same anti-oxidant potential.

Most animals synthesise tens to hundreds of grams (not milligrams  of ascorbic acid daily, where-as in humans if we supplement 10 or more grams we can experience diarrhoea from too much vitamin C (less on a ketogenic diet). It's almost as if the body doesn't want extra vitamin C, and high levels can only be achieved through IVs. Amounts over 1.5mg/dL (or 1.3mgdL in females) is rapidly excreted through the urine (this is about 75mg (or 65mg in females)  in the whole blood) with a half life of about 15 minutes, this is less than the USDA RDA at 90mg (75mg for females)! The body is actually very good at maintaining tight levels of ascorbic acid in the blood, and the daily turn-over on a vitamin C free diet (but grain-rich) can be as little as 2.5mg, so perhaps even less on a ketogenic diet.

Where-as the amount of uric acid in the blood ranges from 3mg/dL to 7mg/dL in males and 3mg/dL to 6mg/dL in females (150-350mg or 150-300mg in the whole blood). Also although 'hyperuricaemia' (high uric acid levels) is set at 6 or 7 mg/dL, some people can have as high as 9.6mg/dL and not develop gout. Vegetarians can have as little as 2.7mg/dL uric acid.

So a normal uric acid level is two to ~4.5 times as much as the saturation level of ascorbic acid!

Not only do we not make ascorbic acid (because of lowered GNG) but the blood has very low saturation levels compared to uric acid and excess is rapidly excreted, excess uric acid is less easily excreted suggesting a preference for higher levels. This further supports by theory that uric acid replaced ascorbic acid in humans.