Vitamin C disease". Reviews state that "data from epidemiological studies do not support an association between excess ascorbic acid intake and kidney stone formation in apparently healthy individuals", although one large, multi-year trial did report a nearly two-fold increase in kidney stones in men who regularly consumed a vitamin C supplement. Recommendations for vitamin C intake by adults have been set by various national agencies: In 2000 the North American Dietary Reference Intake chapter on vitamin C updated the Recommended Dietary Allowance (RDA) to 90 milligrams per day for adult men and 75 mg/day for adult women, and set a Tolerable upper
L-gulonolactone oxidase deficiency living in a malarial infested environment". He based his observation on evidence which indicates that G6PD deficient individuals display enhanced sensitivity to ascorbic acid induced hemolysis. Studies of human diseases have benefited from the availability of small laboratory animal models. However, the tissues of animal models with a GULO gene generally have high levels of ascorbic acid and so are often only slightly influenced by exogenous vitamin C. Guinea pigs, for instance, are a popular human model but lost the ability to synthesize L-gulono-gamma-lactone oxidase 20 million years ago. This is a major handicap for studies involving the endogenous