diarrhea and other gastrointestinal disturbances, increased oxalate excretion and kidney stone formation, increased uric acid excretion, pro-oxidant effects, systemic conditioning (“rebound scurvy”), increased iron absorption leading to iron overload, reduced vitamin B12 and copper status, increased oxygen demand, and erosion of dental enamel (Hornig and Moser, 1981; Rivers, 1987). The data on these adverse effects are reviewed below. The UL for vitamin C applies to intake from both food and supplements.
Gastrointestinal Effects. Gastrointestinal disturbances such as nausea, abdominal cramps, and diarrhea are the most common adverse effects of high vitamin C intake (Hoffer, 1971). These effects are attributed to the osmotic effect of unabsorbed vitamin C passing through the intestine. Intestinal absorption of ascorbic acid occurs by a saturable process (Rumsey and Levine, 1998; Tsao, 1997). The remainder is not absorbed and is eliminated in the stool. The evidence of gastrointestinal disturbances following high vitamin C intakes is primarily from uncontrolled case reports (Hoffer, 1971; Hoyt, 1980). However, some studies have been conducted to evaluate gastrointestinal effects. Cameron and Campbell (1974) reported diarrhea, transient colic, and flatulent distension in normal healthy volunteers at doses of 3 to 4 g/day. Another study, which evaluated the adverse effects of 1-, 5-, and 10-g/day supplemental ascorbate for 5 days in apparently healthy adults, reported diarrhea in 2 of 15 subjects at 10 g/day (Wandzilak et al., 1994). Stein et al. (1976) reported mild diarrhea in one of three subjects following ingestion of 4 g of ascorbic acid.
Increased Oxalate Excretion and Kidney Stone Formation. Controversy exists as to whether increased intake of vitamin C can significantly increase urinary excretion of oxalate and, therefore, lead to an increase in the potential for renal calcium oxalate stone formation. The findings from studies evaluating the effect of vitamin C intake (0.03 to 10 g/day) on urinary oxalate excretion in apparently healthy individuals are conflicting (Hughes et al., 1981; Lamden and Chrystowski, 1954; Levine et al., 1996a; Mitch et al., 1981; Schmidt et al., 1981; Tiselius and Almgard, 1977; Tsao and Salimi, 1984; Wandzilak et al., 1994). An intervention study by Hughes et al. (1981) reported significant increases in mean urinary oxalate excretion in 39 apparently healthy adults consuming 1, 3, 6, and 9 g/day of ascorbic acid. However, Tsao and Salimi (1984) reported normal plasma oxalate concentrations in healthy subjects ingesting 3–10 g/day of ascorbic acid for at least two years, and no significant