How to Stop Vitamin C from Forming Oxalate
In a recent email I discussed potential issues that can arise when taking high doses of synthetic vitamin C (ascorbic acid or ascorbate), including the formation of oxalate, which can cause pain, mitochondrial function, oxidative stress, inflammation, and kidney stones.
Oxalate can be formed from vitamin C
after it gets oxidized to the ascrobyl radical and is further metabolized ultimately to oxalate.
This does not happen if oxidized vitamin C gets recycled back to ascorbic acid.
NADH and
NADPH (the body's main reducing agent / electron donor) and
glutathione recycle vitamin C.
NADPH is produced from glucose via the pentose phosphate pathway, and the efficiency of this process depends on various factors, including ...
- Metabolic issues that affect the availability of glucose
- Genetics affecting various enzymatic steps in the pentose phosphate pathway that produces NADPH
- Nutrients that act as cofactors in this pathway, including riboflavin, niacin, selenium, calcium, magnesium
Metabolic issues that affect glucose availability for the pentose phosphate pathway and its formation of NADPH include things like ...
- Diabetes, thyroid disorders, and adrenal disorders
- Oxidative stress
- Deficiencies in nutrients involved in energy metabolism (e.g. B vitamins, electrolytes, iron, copper, sulfur, and magnesium)
- Genetic variants affecting energy metabolism (too many to name here)
Then, recycling of vitamin C using NADPH probably requires a well-functioning enzyme called thioredoxin reductase to transfer electrons from NADPH to ascobyl radicals to regenerate ascorbic acid.
How well thioredoxin reductase uses NADPH to recycle vitamin C can be affected by the genes that code for this enzyme (TXNRD1 and TXNRD2 genes).
If vitamin C does not get recycled by NADPH, then it falls to glutathione to do it via glutathione-utilizing enzymes like glutathione S-transferases, which means that
variants in certain GST genes can affect how well glutathione can recycle vitamin C.
If glutathione does not recycle vitamin C, then oxidized vitamin C can be irreversibly converted via several steps to oxalate.
However, oxidized vitamin C can also be excreted in the urine as a metabolite that has not yet converted all the way to oxalate.
So in general, oxalate formation from vitamin C occurs when NADPH / thioredoxin reductase and glutathione / glutathione S-transferase both fail to recycle it, but not all oxidized vitamin C necessarily converts to oxalate before getting excreted.
Oxalate can accumulate in the body if the body's pathways for converting oxalate to other substances (e.g. the amino acid glycine) are not working well.
The conversion of oxalate to other substances involves genes like LDHA, LDHB, LDHC, LDHD, AGXT, GRHPR and cofactors like vitamin B6.
In general, maintaining good NADPH and glutathione status seems important when engaging in high-dose vitamin C therapy, except when a prooxidant effect is desired (e.g. in cancer therapy) or when treating a dangerous condition like snake venom poisoning or polio infection that requires rapid treatment that is best accomplished immediately and without delay, using high-dose vitamin C.
In such cases, the risk of high-dose vitamin C therapy increasing oxidative stress or causing oxalate formation pale in comparison to the risk of death or permanent dysfigurement.
In general, oxalate formation from high-dose vitamin C therapy can most likely be prevented by ....
- Maintaining good levels of NADPH and glutathione
- Ensuring the availability of glucose (e.g. supporting insulin sensitivity, ensuring thryoid and adrenal function, and possibly not relying on a ketogenic diet if the body is struggling to produce enough glucose)
- Supplying he nutrients that are required in the relevant metabolic pathways
- Potentially also emplying extra measures to compensate for any genetic vulnerabilities in relevant metabolic pathways
There is still much that we do not know about what happens under various conditions in response to high-dose vitamin C therapy.
There are reasons to employ caution, reasons to not worry excessively about it, and also steps that can be taken to minimize problems with high-dose vitamin C therapy.
Keep in mind that
infection, stress, and toxins (including bacterial endotoxin), appear to cause vitamin C to leave the adrenal glands (the richest reservoir of vitamin C in the body) to go to the liver (to deal with toxins) and other parts of the body (e.g. the thymus gland to support immune function).
Depletion of vitamin C from the adrenal glands due to chronic infection or toxicity may be a contributor to fatigue caused by reduced adrenal function.
Ultimately, vitamin C is a powerful neutralizer of many types of infection and toxicity and also needs to be replenished in the adrenal glands.
Whether vitamin C is taken only in food-based forms or also in high-dose synthetic forms, vitamin C is very important in both the prevention of and recovery from infection and toxicity.
When it comes to assessing your risk for potential side effects from vitamin C supplementation, it can be
helpful to look at variants in genes like G6PD, TXNRD1, TXNRD2, GST, LDHA, LDHB, LDHC, LDHD, AGXT, GRHPR, etc and
markers for glutathione status, and
markers of enzyme cofactors like B vitamins, minerals, and electrolytes.