The Gardener said:
Excessive Vitamin C can cause diarrhea in the short term, and kidney stones in the long term.
For many years, experts have speculated that the intake of large amounts of vitamin C may contribute to the formation of oxalate-type kidney stones because of the metabolic conversion of vitamin C to oxalic acid. If the amount of oxalic acid in the urine increases as the dose of vitamin C increases, they reasoned, then a prolonged intake of large amounts of vitamin C may cause kidney stones. Some experimental evidence supports this concern. For instance, Dr. Constance Tsao, formerly with the Linus Pauling Institute of Science and Medicine, published two studies in the 1980s that investigated the relationship between vitamin C and oxalic acid. In one study, Dr. Tsao demonstrated that doses of 3-10 grams/day of vitamin C taken by ten subjects for 2-10 years did not result in abnormal levels of oxalic acid in the blood. In the other study, however, she showed that the ingestion of 10 grams/day of vitamin C by six subjects resulted in slightly elevated levels of oxalic acid in the urine, although the amount was within the range obtained by the consumption of normal diets. In contrast, a study with six subjects published in 1996 by Dr. Mark Levine and colleagues at the National Institutes of Health found that increasing the daily intake of vitamin C from 200 mg to 1,000 mg resulted in an increase in urinary oxalic acid of about 30%. Consequently, Dr. Levine suggested that the "upper safe doses of vitamin C are less than 1,000 mg daily in healthy people", although he noted that several earlier studies had not found any association between the incidence of kidney stones and the regular daily intake of 1,000 mg or more of vitamin C.
Dr. Carol Johnston of Arizona State University published an article in Nutrition Reviews in March in which she reviewed the scientific and medical evidence that might allow the establishment of an "upper intake level" for vitamin C. She examined the evidence on "rebound scurvy", kidney stones, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency, enhanced iron absorption, pro-oxidant effects, and the destruction of vitamin B12. She noted that the experimental, clinical, and epidemiological evidence does not support a detrimental role for vitamin C in any of these conditions, although we still do not know the effect of large amounts of vitamin C in people with hemochromatosis, or iron-overload disease. Her analysis is in agreement with the many other reviews of the safety of supplemental vitamin C. Dr. Johnston concludes that "the available data indicate that very high intakes of vitamin C (2-4 g/day) are well tolerated biologically in healthy mammalian systems. Currently, strong scientific evidence to define and defend a UL [Tolerable Upper Intake Level] for vitamin C is not available." In other words, we cannot establish a threshold of toxicity for vitamin C.
To this evidence, we can add another recently published study by Dr. Gary Curhan and colleagues at Harvard, Brigham and Women’s Hospital, and Massachusetts General Hospital. For 14 years, Dr. Curhan et al. followed a group of 85,557 women with no prior history of kidney stones. Their intake of vitamin B6 and vitamin C was assessed and correlated with the development of stones. Daily intakes of 40 mg or more of vitamin B6 provided significant protection against the formation of stones, but there was no significant difference in stone formation between the groups with the lowest (less than 250 mg/day) and highest (1,500 mg/day or more) intake of vitamin C. In a previous study of a group of over 45,000 men followed for 6 years, the authors found a protective role for vitamin C but not for vitamin B6. They conclude, "...our findings for vitamin C, which have been consistent for women and men, do not support the practice of routine restriction of vitamin C to prevent kidney stones." Addressing previous experimental studies that associated vitamin C with increased urinary oxalate (the salt of oxalic acid), the authors point to another study from 1994, which showed that vitamin C is easily converted to oxalate during analytical procedures. Therefore, the increased amounts of oxalate observed in urine may have been artifactually produced and have no relation to what happens in the body.
The accumulated evidence demonstrates that vitamin C, even in large amounts, is a remarkably safe substance. This evidence strongly supports the role of vitamin C as an important antioxidant, not a pro-oxidant. While we know that the relatively small amount of 100-200 mg/day provides substantial protection against age-related diseases, including heart disease, cancer, and cataract, and that a still smaller amount prevents scurvy, we do not yet know the optimal amount of vitamin C (see "The Optimal Intake of Vitamin C" by Stephen Lawson, LPI Newsletter Spring/Summer 1997). Large doses of vitamin C have been shown to be of therapeutic benefit in promoting relaxation of the arteries (vasodilation), which benefits patients with heart disease and "coronary risk factors", such as diabetes, high serum cholesterol levels, and high serum homocysteine levels. Large doses of vitamin C are also useful in combating viral infections, preventing toxemia in pregnant women (possibly through vasodilation), and as an adjunct to the appropriate conventional treatment of cancer. There is also a tremendous amount of anecdotal evidence and some clinical evidence that vitamin C may be of benefit in treating other illnesses and conditions. The difficulty of determining the optimal intake of vitamin C is due to its many different functions in the body, biochemical individuality, and the impracticability of measuring the vitamin C content of various tissues and organs in healthy people in order to correlate those amounts with blood levels and optimal function.
Over twenty years ago, Linus Pauling proposed that the RDA for vitamin C should be increased to 200 mg/day. At about the same time, he mustered theoretical and experimental arguments to support his belief at that time that the optimal intake for humans is about 2 grams/day. While the merits of ingesting that much vitamin C or more each day are debatable, at least we can be confident that large doses are not harmful for healthy people and may be of therapeutic benefit in many cases.
In particular, the concern about the role of vitamin C in kidney stone formation, a source of speculation for several decades, appears to be no longer justified.
