Vitamin C large dose include nausea, abdominal cramps and diarrhea. These effects are attributed to the osmotic effect of unabsorbed vitamin C passing through the intestine. In theory, high vitamin C intake may cause excessive absorption of iron. A summary of reviews of supplementation in healthy subjects did not report this problem but left as untested the possibility that individuals with hereditary hemochromatosis might be adversely affected. There is a longstanding belief among the mainstream medical community that vitamin C increases risk of kidney stones. "Reports of kidney stone formation associated with excess ascorbic acid intake are limited to individuals with renal
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