A single-blind, parallel trial of l-hydroxyproline in healthy adult subjects

As calcium oxalate is the most common constituent of urinary stones animal model of the urolithiasis has been established by feeding l-hydroxyproline, an endogenous precursor of oxalate. However, the influence of oral l-hydroxyproline on human urinary oxalate excretion has not been clearly demonstrated. We herein report a clinical study examining the influence of daily ingestion of l-hydroxyproline on urinary oxalate levels with a focus on measuring oxalic acid excreted in the urine.

On the 24-h urine test, almost no markers changed, but there was a significant change in total l-hydroxyproline excretions in the 2000 mg l-hydroxyproline group compared to control group at the point of 8 weeks after first intake. Moreover, oxalic acid levels also increased significantly in the 2000 mg group at the point of 8 and 12 weeks after first intake. However, all values returned to basal values after 4 weeks from the last l-hydroxyproline intake (Table 1). Various dietary factors can change urine oxalate excretion; one is a high-protein diet. Many studies have addressed urinary oxalate excretion after high-protein intake, but conclusions are still uncertain. For example, Knight et al. [1] not only showed significant changes in urinary oxalate with 5 and 10 g of gelatine administered to healthy subjects, but also indicated that the high-protein diet did not influence total daily urinary oxalate excretion [2]. Collagen contains approximately 10 % of l-hydroxyproline, and the daily turnover of collagen in humans is estimated to be 2–3 g/day so the metabolism of l-hydroxyproline will be 240–420 mg [1]. In this study, the urinary oxalate level following 500 or 1000 mg/day l-hydroxyproline ingestion did not change compared with control but 2000 mg/day l-hydroxyproline ingestion increased the urinary oxalate excretion, but the values did not exceed the level of stone forming individuals with a mean oxalate excretion 40 mg/day [2]. As noted, there are various opinions on the association of dietary and urinary oxalate. Recently, it was reported that the Dietary-Approaches to Stop Hypertension (DASH)-style diet is more effective in reducing calcium oxalate supersaturation than a low-oxalate diet, although it includes a lot of fruits and vegetables which contain much oxalate [3]. Thus, the influence of the diet in conjunction with oxalate is still unclear in human metabolism. Moreover, we found no accumulation of l-hydroxyproline and oxalate in the withdrawal period same as the animal model. The metabolic significance of l-hydroxyproline is still unclear and further investigation is warranted.