Oxalic acid is the metabolic end-product of the glyoxylase pathway and is derived from the oxidation of glyoxylate. In the cell, the majority of glyoxylate is converted into glycine or glycolic acid. However, in some instances there may be greater oxidation of glyoxylate to oxalic acid. This leads to increased urinary excretion of oxalic acid. As 80% of kidney stones are calcium-oxalate stones, an increase in oxalic acid is strongly correlated to frequency of urolithiasis. As mentioned previously, there are inborn errors of metabolism that cause elevated oxalic acid such as primary hyperoxaluria. The dramatically elevated levels of oxalic acid in these conditions lead to renal calculi formation and systemic oxalosis. However, there are other clinical circumstances that can predispose an individual to have higher urinary oxalic acid levels, including recent dietary intake of oxalate-rich roods. The relationship between diet and urinary oxalic acid levels is complex and dependent on many variables. While the majority of oxalic acid originates from endogenous production, it is estimated that 40% of urinary oxalic acid is derived from the diet, however these levels are largely dependent on the microbiome and intake of dietary calcium.

Specifically, the gut bacteria Oxalobacter formigenes degrades dietary oxalates and there is a direct correlation between concentrations of this bacteria and lower oxalate levels. The absence of Oxalobacter formigenes is also correlated to increased oxalate stone formation. Food sources that lead to higher oxalic acid excretion include spinach, rhubarb, beets, nuts, chocolate, tea, wheat bran, and strawberries. However, it is welldocumented cooking oxalate-rich foods dramatically reduces the oxalate concentration. Furthermore, often these foods are also high in calcium which inhibits oxalate absorption at the intestinal lining. Aside from dietary intake, oxalic acid concentrations will vary based on a number of factors.

Oxidative stress may play a large role in the formation of oxalic acid. This is because glutathione is responsible for the neutralization of glyoxal created by free radical damage. With lower glutathione levels, glyoxal is more likely to shunt toward glyoxylate and ultimately could become oxalic acid.

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