Where does endogenous oxalate come from? - a systematic review of endogenous sources of urinary oxalate

Oxalate is a toxic waste product in humans, capable of complexing with calcium to form kidney stones. While some oxalate is consumed in the diet, there are endogenous sources in humans. This review compiles known endogenous sources of urinary oxalate. PubMed and Embase databases were searched, as well as backward citations, for relevant articles published in English. The search strategy relied on terms related to endogenous synthesis and metabolic tracing. Title/abstract review was performed, and articles were excluded from full review if they did not report data on human sources of endogenous oxalate. Risk of bias was assessed using a modified JBI checklist. Weighted averaging was used to combine results and predict endogenous oxalate production. Of 228 unique articles identified, 23 were eligible and included in this study. Total endogenous oxalate production was reported by 7 of the papers, representing 305 healthy subjects. Weighted mean of endogenous oxalate production was 23.8 mg/day (95% CI 23-24.6 mg/day) with a range of 17-34 mg/day. Daily turnover from the metabolic pool of ascorbic acid may account for up to 40% - 60% of total endogenous oxalate production. Other contributors include hydroxyproline (~ 15%), glycine (< 10%), and glycolate (~ 4%). Phenylalanine (< 0.7%), and fructose (negligible) contribute minimally. This review highlights that daily turnover from the metabolic pool of ascorbic acid is the primary source of endogenous oxalate. However, current estimates rely on highly variable data dating back nearly 70 years. Future research using modern metabolomics is required to re-characterize this pathway.