Regardless of whether or not high intakes of ascorbate have any beneficial effects, large numbers of people habitually take between 1 and 5 g/day of vitamin C supplements (compared with reference intakes of 40–90 mg/day) and some take considerably more.
There is little evidence of significant toxicity from these high intakes. Once the plasma concentration of ascorbate reaches the renal threshold, it is excreted more or less quantitatively with increasing intake, and there is no evidence that higher intakes increase the body pool above about 110 μmol/kg body weight. Unabsorbed ascorbate in the intestinal lumen is a substrate for bacterial fermentation, and may cause diarrhea and intestinal discomfort.
Ascorbate can react non-enzymically with amino groups in proteins to glycate the proteins, in the same way as occurs in poorly controlled diabetes mellitus, and there is some evidence of increased cardiovascu-lar mortality associated with vitamin C supplements in diabetics.
Up to 5% of the population are at risk from the development of renal oxalate stones. The risk is from both ingested oxalate and that formed endogenously, mainly from the metabolism of glycine. Some reports have suggested that people consuming high intakes of vitamin C excrete more oxalate in the urine. However, no pathway for the formation of oxalate from ascor-bate is known, and it seems that the oxalate is formed non-enzymically under alkaline conditions either in the bladder or after collection, and hence high vitamin C intake is not a risk factor for renal stone formation.
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