with glucose-6-phosphate dehydrogenase deficiency (Campbell et al., 1975; Rees et al., 1993). However, a clinical study does not support the association (Beutler, 1991).

Summary

Based on considerations of causality, relevance, and the quality and completeness of the database, osmotic diarrhea and related gastrointestinal disturbances were selected as the critical endpoints on which to base a UL. The in vivo data do not clearly show a causal relationship between excess vitamin C intake by apparently healthy individuals and other adverse effects (i.e., kidney stone formation, excess iron absorption, reduced vitamin B12 and copper levels, increased oxygen demand, systemic conditioning, pro-oxidant effects, dental enamel erosion, or allergic response) in adults and children.

The data regarding possible vitamin C deficiency in two newborns resulting from abrupt withdrawal from mothers consuming high levels of vitamin C during pregnancy were considered too anecdotal and uncertain to warrant derivation of a separate UL for pregnant women.

Dose-Response Assessment
Adults

Data Selection. The data on osmotic diarrhea and gastrointestinal disturbances were selected as most relevant on which to base a UL for apparently healthy adults. The effects are generally not serious and are self-limiting; individuals experiencing them may easily eliminate them by reducing supplemental vitamin C intakes.

Identification of a No-Observed-Adverse-Effect Level (NOAEL) and Lowest-Observed-Adverse-Effect Level (LOAEL). A LOAEL of 3 g/day can be identified based on the data of Cameron and Campbell (1974). These investigators reported symptoms of flatulent distension, transient colic, and diarrhea at doses of 3 to 4 g/day in normal healthy volunteers (number of volunteers not stated). The volunteers increased oral ascorbic acid intake by increments of 1g/day in successive weeks. Supporting evidence is provided by case reports (Hoffer, 1971; Hoyt, 1980), a graded dose study by Stein et al. (1976), and a multiple crossover study by Wandzilak et al. (1994). Stein et al. (1976) gave three patients 8 g/day in four divided doses of 2 g for 3 to 7 days. This study reported mild diarrhea in one of three subjects following ingestion of 4 g/day of ascorbic acid. Wandzilak et al. (1994) investigated the effect of high-dose ascorbic acid in-



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