In Does CoQ10 Deserve a Spot on Your Longevity Plan?, I pointed out that phenylalanine hydroxylase is strongly inhibited by the concentrations of vitamin C achieved by intravenous use, and probably mildly inhibited by high oral doses on the order of 3 grams.
Phenylalanine hydroxylase is needed to convert phenylalanine to tyrosine, and tyrosine is the precursor to the “head” of coenzyme Q10.
Thus, it is very likely that such use of vitamin C inhibits CoQ10 synthesis.
In Vitamin C, Whole Food Vs. Synthetic: Does It Matter?, I covered a study suggesting 500 milligrams of vitamin C taken three times a day with meals for two months lowers serum copper by 5% and lowers ceruloplasmin by 25%. This raises the possibility that taking 1500 milligrams of vitamin C per day with meals decreases copper status, which would be expected to decrease the availability of copper to form complex IV of the mitochondrial respiratory chain. Every oxygen molecule that you use to generate energy is tightly held between a heme iron and a copper ion until it receives the protons and electrons needed to become water. Oxygen is what powers nearly all of metabolism in this way, and that cannot be done without sufficient copper.
As I pointed out in Cancer, IV Drips, and the Glutathione-Vitamin C Connection, vitamin C in excess of the many factors needed for its recycling will generate oxalate, which itself is a mitochondrial toxin that inhibits citric acid cycle activity by 48% at concentrations found on the high end of the “normal” range.
As also pointed out in Cancer, IV Drips, and the Glutathione-Vitamin C Connection, high-dose intravenous vitamin C acts as a pro-oxidant outside the context of sepsis, and this is probably true of repeated oral megadosing. This has the potential to cause oxidative damage to mitochondria. Moreover, oxidation of the glutathione pool has the potential to interfere with the synthesis of mitochondrial proteins.
On the other hand, several case reports (here and here) show that one gram of vitamin C taken every six hours (alongside 10 milligrams of menadione, which I would replace with MK-4 can help mitigate impairments in complex III of the respiratory chain by delivering electrons to a site after complex III, most likely to cytochrome C, so that some ATP can still be made through the activity of complex IV (which of course might stop working if you induce a copper deficiency).
The negative effect on copper absorption can probably be avoided simply by taking high-dose vitamin C away from meals. However, that does not stop it from acting as a pro-oxidant, generating oxalate, or interfering with CoQ10 synthesis.
This is not to say that vitamin C at high doses will necessarily wreck your mitochondria. It is, rather, to say that doses above 400 milligrams should be used with greater caution.
When vitamin C is used at high doses to rewire the respiratory chain it can help if you need it. This is partially analogous to methylene blue, which has a broader number of ways it can rewire the respiratory chain than vitamin C, but also fulfills the principle that it helps you if you need it and hurts you if you don’t.
The best way to test the safety and utility would be to use the Comprehensive Screening for Energy Metabolism to ensure that oxalate levels are not elevated, to look for evidence of a complex III impairment, and to determine its cause, if found, to see if there are other more effective ways to fix it. It would would also be helpful to verify that high-dose vitamin C does not increase resting fasted lactate. Lactate would likely rise in response to a CoQ10 or copper deficit, but could conceivably decrease in response to oxalate inhibiting the citric acid cycle.
If you don’t have a specific reason to megadose vitamin C, it is best to stick to the doses you could get from a very vitamin C-rich whole-foods diet.
this is interesting & worrisome at the same time, i’ve been mega’in vitamin C for years since i grew up with pauling & cathcart; but i’m always open to new ideas & data, i do not wish to create problems in my body; i take the vit C in the hopes of heart disease prevention…
thank you for all you do (and share)
Vitamin C is also a cofactor for Dopamine beta hydroxylase with copper. intriguing.