Vitamin C is essential in humans because they lack the gulonolactone oxidase enzyme necessary for its synthesis. In this respect, humans are different to most other mammals which possess the necessary intact metabolic pathway for producing vitamin C. Complete deficiency of vitamin C results in scurvy which is caused by the absence of the ascorbate co-factor activity within the iron and copper hydroxylases necessary for the synthesis of collagen and for the production hormones such as adrenaline and serotonin. Ascorbate is also required for the hypoxia-inducible factor 1α (HIF-1) which is a transcription factor that up regulates gene expression is response to metabolic stress such as low cellular oxygen concentrations. Hypoxia-inducible factor 1α are iron containing hydroxylases and possess a specific binding site for ascorbate, absence of which impairs their ability to regulate glycolysis, apoptosis and angiogenesis in response to metabolic stress.
The Gulo mouse model has been used by researchers to understand the effects of vitamin C deficiency on tissue concentrations of vitamin C, something that would be unethical in humans. Gulo mice are genetically bred to be missing the gulonolactone enzyme necessary for vitamin C synthesis, and deficiency of vitamin C in their diet results in symptoms similar to scurvy in humans. Comparison with wild type mice possessing the gulonolactone enzyme allows detailed investigation into the plasma and tissue levels of various dietary intakes. Using this model researchers1 found that decreasing the plasma levels of ascorbate caused ascorbate concentrations in the liver, heart, kidney and white blood cells to fall quickly below those seen in wild type mice. When vitamin C was removed from the diet all tissues were rapidly depleted except the brain tissue, highlighting the labile nature of tissue vitamin C concentrations.
Re-introduction of vitamin C into the diet as kiwi fruit was 5 times more effective at raising tissue levels of ascorbate compared to ascorbate in the drinking water. This would suggest that the bioavailability of vitamin C is higher from food than from ascorbic acid supplements. The authors noted that the heart liver and kidney requires much larger concentrations of plasma vitamin C in order to reach optimal ascorbate concentrations, and that on removal of the dietary source of vitamin C, levels in these tissues dropped the most quickly. Mice maintained on a low dose of vitamin C became depleted of all but brain ascorbate within 1 week of withdrawal of the dietary source. Scurvy symptoms coincided with the depletion of brain vitamin C, but most tissues were vitamin C deficient long before the onset of the symptoms of scurvy.
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