Excess Iron Absorption. Another possible adverse effect of high vitamin C intake is enhanced iron absorption leading to iron overload. Bendich and Cohen (1990) evaluated 24 studies to determine whether daily ascorbic acid intakes (ranging from 1 to 1,000 mg, with most in the 10- to 100-mg range) could increase iron stores above recommended levels in apparently healthy individuals. They found that vitamin C intakes did not increase the number of high iron absorbers, and limited data involving ascorbic acid intakes above 100 mg/day showed no change in iron absorption values. Another study by Cook et al. (1984) showed no increase in iron stores following vitamin C intakes up to 2 g/day (taken with meals for 20 months) in iron-replete subjects who consumed foods that contain iron. This suggests that vitamin C does not induce excess iron absorption in apparently healthy individuals. However, it is unknown if individuals with hereditary hemochromatosis, which affects between 1 in 200 and 1 in 400 persons of northern European descent (Bacon et al., 1999), could be adversely affected by long-term ingestion of large doses of vitamin C (McLaran et al., 1982).

Lowered Vitamin B12Levels. An in vitro study showed that increasing destruction of vitamin B12 was associated with increasing vitamin C levels (Herbert and Jacob, 1974). However, when this study was performed using different analytical procedures, no loss of vitamin B12 was observed (Newmark et al., 1976). In a review of the stability of cobalamins under varying conditions, Hogenkamp (1980) found that only aquocobalamin was decreased and destroyed by ascorbic acid. Aquocobalamin is not a major cobalamin in biological tissues. Furthermore, results of in vivo studies in human subjects have shown that vitamin C intakes up to 4 g/day did not induce vitamin B12 deficiency (Afroz et al., 1975; Ekvall et al., 1981).

Systemic Conditioning. Evidence of systemic conditioning (the accelerated metabolism or excretion of ascorbic acid) exists from uncontrolled observations in humans following abrupt discontinuation of prolonged, high-dose vitamin C supplementation (Rhead and Schrauzer, 1971; Siegel et al., 1982). Omaye et al. (1986) showed increased turnover of plasma ascorbic acid in apparently healthy human adults who abruptly decreased their vitamin C intake from 605 to 5 mg/day. Two other studies showed that high intakes resulted in increased clearance but did not result in blood levels lower than normal (Schrauzer and Rhead, 1973; Tsao and Leung, 1988). Other studies have reported no rebound scurvy or excessive lowering of ascorbate blood levels after cessation of high



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