Are Seed Oils Behind Your Oxalate Problem?

Probably.

Oxalate is a mitochondrial toxin that suppresses the citric acid cycle by 48% at the upper end of the normal range found in human blood, so if you feel like crap all the time you might have a problem with high oxalate levels.

If your oxalate levels disappear on a low-oxalate diet, you are probably absorbing too many from food.

But if they go nowhere on a low-oxalate diet, you are making them yourself.

One major source of high oxalates is glyoxylate.

Figure credit.

We know this pathway is relevant because primary hyperoxaluria type I is due to a genetic defect in the conversion of glyoxylate to glycine, and primary hyperoxaluria type II is due to a genetic defect in the conversion of glyoxylate to glycolic acid.

One of the major sources of glyoxylate is glyoxal.

Where does glyoxal come from?

In vitro experiments show it mostly comes from the spoilage of seed oils within the body, or, more technically, from the peroxidation of polyunsaturated fatty acids (PUFAs).

Glyoxal is the precursor to the advanced “glycation” endproduct, carboxymethyllysine (CML), and this 1996 paper showed that glucose is horrible at generating CML compared to PUFAs.

First they compared several fatty acids:

Arachidonate generated the most, and oleate generated practically none, while linoleate was in the middle. This is consistent with the number of double bonds being the main factor, and it is the carbon between two double bonds that is vulnerable to peroxidation,

Then they compared arachidonate to glucose:

Then they looked at glyoxal itself instead of CML and showed that arachidonate generated far more glyoxal than it generated CML:

The last finding implies that arachidonic acid was generating CML by generating glyoxal, and together with the previous findings this suggests that lipid peroxidation generates far more glyoxal than glucose does.

That this is due to lipid peroxidation is also supported by their finding that when copper ions are use to peroxidize the PUFAs in LDL particles, it makes CML accumulate:

Returning to the first figure…

…this implies that lipid peroxidation is a major source of oxalate.

The ratio of saturated to polyunsaturated fatty acids in red blood cells are mildly negatively correlated with CML in healthy humans.

Short-term interventions have suggested fish oil may decrease urinary oxalate excretion, despite fish oil increasing the likelihood of lipid peroxidation. However, the mechanisms suggested for this relate to the competing effects of arachidonic acid and EPA on oxalate transporter activity in kidney, so even these short-term findings do not contradict the hypothesis that PUFAs are increasing the production of oxalate.

In rats, soybean oil increases oxalate excretion.

The in vitro finding that arachidonate is worse than linoleate should not be taken as a vindication of linoleate-rich seed oils over arachidonate-rich egg yolk and liver. Arachidonic acid intakes are tiny compared to linoleate intakes. While arachidonic acid is more vulnerable than linoleic acid, you will get far more total burden from large amounts of linoleate in seed oils than from small amounts of arachidonate in egg yolk and liver.

As I covered in How Essential Are the Essential Fatty Acids? we need a small amount of arachidonic acid and are best served by minimizing linoleic acid.

Seed oils do not automatically cause lipid peroxidation. We need to protect them with our antioxidant system. You can learn about the antioxidant system with my antioxidant course.

Important updates on the role of coenzyme Q10 in the antioxidant system can be found in Does CoQ10 Deserve a Spot on Your Longevity Plan?

If you ditch seed oils, your antioxidant requirements stay elevated for years after consuming them, approximately four years on average.

The simplest thing to do is favor tropical oils, olive oil, and grass-fed animal fats over seed oils like soybean, corn, safflower, sunflower, and canola oils, and, if you have been eating these for a long time, get an extra 0.6 milligrams of alpha-tocopherol for each gram of PUFA that you used to consume. Jarrow Toco-Sorb is good as a full-spectrum E and Now E-Oil (one drop per serving, not eight) is good as an isolated alpha-tocopherol .

However, your antioxidant system is only as good as its weakest link. If you are deficient in glutathione, for example, supplementing vitamin E is not the correct strategy. Energy metabolism fuels the antioxidant defense system, so it is often the weakest link in antioxidant defense.

Further, nutrients like biotin, B12, and folate may play roles in detoxifying oxalate to carbon dioxide after it is formed, and vitamin B6 is needed for the conversion of glyoxylate to glycine.

Thus, the middle-of-the-road strategy would be to use the comprehensive nutritional screening to fix the weakest nutritional links, and the best strategy would be to use the comprehensive screening for energy metabolism to identify any energetic bottlenecks. This includes whole genome sequencing, which can identify any mutations in genes related to oxalate metabolism.