**2.2 Effect of ascorbic acid on kidney stone formation**

In adults, the recommended daily dose of vitamin C is 75 mg/day based on average requirements. This value varies according to age, gender, and some genetic diseases. Furthermore, the upper limit of tolerability in humans has been reported to be 2000 mg/ day [11]. Consumed vitamin C is partly converted into oxalate crystals and excreted in the urine. This increases the risk of the formation of calcium oxalate crystals [23].

Despite the fact that studies on the relationship between ascorbic acid and the formation of calcium oxalate stones have been ongoing for more than half a century, the nature of this relationship is still unknown. The foundations that are defended theoretically have not corresponded in practice exactly. The studies conducted in this context have led to differences of opinion. Studies on ascorbic acid causing stone formation can be summarized as follows.

Ascorbic acid's potential to cause kidney stone formation has been discussed since the discovery of oxalate formation as a result of its metabolism. Hellman and Burns conducted the first studies demonstrating that ascorbic acid can be converted to oxalate as a result of metabolism in 1958. In their study, they suggested that ascorbic acid is metabolized to oxalate and excreted in the urine. As a result, it has been proposed that ascorbic acid is the most important oxalate precursor in the structure of calcium oxalate stones [13, 24]. In studies conducted to prove this hypothesis, evidence was presented by Atkins et al. in 1964 and Baker et al. in 1966 that endogenous oxalate synthesis from ascorbic acid contributes approximately 40% to urinary oxalate excretion [13, 25, 26]. However, due to the difficulty in applying the methods used for oxalate determination at the time, these results are now contradicted. Since ascorbic acid can be metabolized non-enzymatically to oxalate *in vitro*, these inconsistencies in urinary oxalate measurement persist to this day [15, 23].

Taylor et al. were the first to investigate the effect of ascorbic acid consumption on kidney stone formation in the most comprehensive way. They studied the relationship between stone formation and dietary diversity in men for 14 years, as well as how this relationship changes with age. A total of 1473 cases of kidney stones were reported in this study of nearly 50,000 people, with a higher proportion in men aged 45–59 years. In the face of this ratio, vitamin C was thought to affect kidney stone formation. The role of calcium, magnesium, and potassium in the diet, as well as their potential impact on stone formation, were also investigated. The study also presented opinions that calcium consumption reduces oxalate excretion in the urine by forming a complex with oxalate in the intestine and prevents stone formation [27]. Although high-dose vitamin C supplements are restricted to prevent stone formation in men,
