Alterations in organic acid testing results can be interpreted in many ways. Here is a sulfite focused interpretation of changes in organic acid testing.
*****THIS IS NOT MEDICAL ADVICE – PLEASE CONSULT WITH YOUR PROVIDER BEFORE MAKING ANY CHANGES*****
Marker#59 2-hydroxybutyric acid is typically thought to be from increased CBS activity to produce more glutathione. However, this could be the product of a block at BKCDH as the alpha-ketobutyrate is metabolized to propionyl CoA via the enzyme branched chain keto acid dehydrogenase (needs B1, CoA, lipoate, FAD, NAD – of which sulfite toxicity destroys all of these). Alpha ketobutyrate will then be forced to produce 2-hydroxybutyric acid. In sulfite toxicity due to SUOX deficiency, it has been shown that CBS activity is negligible. Most of the H2S is coming from 3-MST. https://pmc.ncbi.nlm.nih.gov/articles/PMC7711302/pdf/main.pdf Another possibility is a competition between BCKA and alpha ketobutyrurate for BCKDH due to the catabolism of BCAA to restore TCA cycle metabolism through succinyl CoA repletion. This has been shown to occur in this study. In theory, this would lead to increased propionyl CoA levels, competition for PCC, and possibly a build-up of butyryl CoA (see Marker #45 below).
Marker#24 Succinate could be FAD deficiency, itaconate (but will have high #30 3-methylglutaric acid as well if itaconate), but could also be inhibition of succinate dehydrogenase by free sulfite. Normal succinate doesn’t mean you are not having a sulfite issue. It could be that you are deficient in B12 (mopping up sulfite), preventing the flux of methylmalonyl CoA to succinyl CoA.
Marker #50 Methymalonic Acid. This marker is associated with vitamin B12 deficiency. However, if you have a deficiency in a cofactor at BCKDH (B1, CoA, lipoate, FAD, NAD), then you won’t have enough methylmalonyl CoA to show up B12 deficient. In addition, you could have competition for MUT by ethylmalonyl CoA if ACADS is inhibited by CoASSH (from glutathione deficiency, which causes CoASH to be used for the cofactor for SQR)
Marker #45 Ethylmalonic Acid. This could be high due to excess H2S, a known inhibitor of ACAD (SCAD), but we should not have excess butyrate in our general circulation. This may indicate a leaky gut. It can also mean that ACADS is being inhibited by CoASSH because of SEVERE GLUTATHIONE deficiency. In addition, this marker could be elevated due to increased BCAA catabolism, causing a tying up of propionyl-CoA carboxylase and making it less available for butyryl-CoA metabolism.
Marker #47, 48, 49 Adipic, Sebacic, Suberic acid. These are signs of MCAD. This could be because HIF-1alpha is currently active, either due to an immune response or hypoxia. HIF-1alpha inhibits MCAD activity. Sebacic acid is a great antimicrobial. Suberic acid is great at counteracting LPS toxins. So….It’s a good-ish thing? Not sure about adipic acid. Needs more research.