Megadosages of vitamin C would reduce O2 levels in gastrointestinal tracts by increasing activities of PHD2 resulting in systematic proxidant effects

Hypoxia-inducible factor prolyl hydroxylase (PHD2) is the key sensor of O2 in cells. PHD2 catalyzes the reaction hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 .

PHD2 is highly expressed in gastrointestinal tracts. PHD2 requires ascorbate.

Megadosages of vitamin C would increase activities of PHD2 is gastrointestinal tracts decreasing levels of O2 in gastrointestinal tracts. Reactive oxygen species particularly O2 in gastrointestinal tracts are required to trigger systematic oxidant defenses. See this post. Megadosages of vitamin C have systematic prooxidant effects even where vitamin C is not oxidized.

Megadosages of vitamin C can have immediate unfavorable effects through prooxidant effects of vitamin C where taken in more than around RDA dosages. Megadosages of vitamin C are also a slow poison through decreases in RNA synthesis and DNA synthesis which can lead to peripheral neuropathy and decreases in hyaluronic acid synthesis which can lead to decreases in formations of cartilage. Stopping taking megadosages of vitamin C is not sufficient to counter effects of vitamin C as a slow poison. See this post.