Glycolate

Glycolic acid is another byproduct of the oxalate pathway and comes from the conversion of glyoxylic acid. Urinary levels of glycolic acid have most commonly been studied in the rare inborn error of metabolism primary hyperoxaluria type 1 (PH1). PH1 is caused by a deficiency of alanine:glyoxylate aminotransferase (AGT) which converts glyoxylic acid into glycine.

When this pathway is blocked, due to inborn error, glyoxylic acid ultimately leads to higher production of glycolic acid and oxalic acid.

Clinically, PH1 results in a similar clinical presentation as PH2 with increased oxalic acid excretion and calcium oxalate deposition (oxalosis). This can ultimately progress to renal calcinosis and kidney failure.

Aside from inborn error, a large portion of glycolic acid is derived from metabolism of glycine and hydroxyproline. It has been projected that between 20% and 50% of urinary glycolate comes from hydroxyproline in the form of collagen turnover in the body.

Supplementation or recent intake of collagen or collagen-rich foods may influence levels of glycolic acid in the urine. Another important source of glycolic acid is the molecule glyoxal.

Glyoxal is derived, in part, from oxidative stress in the forms of lipid peroxidation and protein glycation.

The majority of this glyoxal is converted into glycolic acid utilizing glutathione as a cofactor.

Extremely high levels of urinary glycolic acid are suspicious of a metabolic defect in the glyoxylate pathway such as in PH1. However, this rare inborn error is commonly diagnosed early in life. To note, Genova’s urinary organic acid testing is not designed for the diagnosis of metabolic inborn errors. However, the enzyme defect responsible for PH1 (AGT) is dependent on vitamin B6 as a cofactor.

The extent to which urinary glycolic acid could be a functional indicator of vitamin B6 insufficiency has not been studied, however patients with PH1 have shown improvement with B6 intervention.

Aside from inborn error, higher levels of glycolic acid may be indicative of increased oxidative stress.

This is because oxidative stress causes higher levels of glyoxal which is ultimately converted into glycolic acid for excretion utilizing glutathione as a cofactor.

Lower levels of glutathione may promote more conversion of glyoxal to oxalic acid.

HOW CAN HIGH OXALATES BE TREATED?

Implement a low-oxalate diet. This may be especially important if the individual has had Candida for long periods of time and there is high tissue oxalate buildup. 

- Use antifungal drugs to reduce yeast and fungi that may be causing high oxalates. Children with Autism Spectrum Disorders frequently require years of antifungal treatment. Arabinose, a marker used for years for yeast/fungal overgrowth in the Organic Acids Test is correlated with high amounts of oxalates. 

- Supplements of calcium and magnesium citrate can reduce oxalate absorption from the intestine. Citrate is the preferred calcium form to reduce oxalate because citrate also inhibits oxalate absorption from the intestinal tract. 

- N-Acetyl glucosamine supplements can stimulate the production of the intercellular cement, hyaluronic acid, to reduce pain caused by oxalates. 

- Chondroitin sulfate can prevent the formation of calcium oxalate crystals. 

- Vitamin B6 is a cofactor for one of the enzymes that degrades oxalate in the body and has been shown to reduce oxalate production. 

- Excessive fats in the diet may cause elevated oxalates if the fatty acids are poorly absorbed because of bile salt deficiency. If taurine is low, supplementation with taurine may help stimulate bile salt production (taurocholic acid), leading to better fatty acid absorption and diminished oxalate absorption. 

- Probiotics may be very helpful in degrading oxalates in the intestine. Individuals with low amounts of oxalate-degrading bacteria are much more susceptible to kidney stones. Both Lactobacillus acidophilus and Bifidobacterium lactis have enzymes that degrade oxalates. 

- Increase intake of essential omega-3 fatty acids, commonly found in fish oil and cod liver oil, which reduces oxalate problems. High amounts of the omega-6 fatty acid, arachidonic acid, are associated with increased oxalate problems. Meat from grain fed animals is high in arachidonic acid. 

- Supplements of vitamin E, selenium, and arginine have been shown to reduce oxalate damage. 

- Increase water intake to help eliminate oxalates.