Vitamin C (ascorbic acid) Safety

Toxicity

A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports, including: genetic mutations, birth defects, cancer, atherosclerosis, kidney stones, "rebound scurvy", increased oxidative stress, excess iron absorption, vitamin B-12 deficiency, and erosion of dental enamel. However, none of these adverse health effects have been confirmed, and there is no reliable scientific evidence that large amounts of vitamin C (up to 10 grams/day in adults) are toxic or detrimental to health. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time. A UL of 2 grams (2,000 milligrams) daily was recommended in order to prevent most adults from experiencing diarrhea and gastrointestinal disturbances. Such symptoms are not generally serious, especially if they resolve with temporary discontinuation or reduction of high-dose vitamin C supplementation.

Tolerable Upper Intake Level (UL) for Vitamin C
Age Group	UL (mg/day)
Infants 0-12 months	Not possible to establish*
Children 1-3 years	400
Children 4-8 years	650
Children 9-13 years	1,200
Adolescents 14-18 years	1,800
Adults 19 years and older	2,000

*Source of intake should be from foods or formula only.

Does vitamin C promote oxidative damage under physiological conditions? Vitamin C is known to function as a highly effective antioxidant in living organisms. However, in test tube experiments, vitamin C can interact with some free metal ions to produce potentially damaging free radicals. Although free metal ions are not generally found under physiological conditions, the idea that high doses of vitamin C might be able to promote oxidative damage in vivo has received a great deal of attention. Widespread publicity has been given to a few studies suggesting a pro-oxidant effect of vitamin C, but these studies turned out to be either flawed or of no physiological relevance. A recent comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans. Studies that report a pro-oxidant effect for vitamin C should be evaluated carefully to determine whether the study system was physiologically relevant, and to rule out the possibility of methodological and design flaws.

For example, a study in the June 15, 2001, issue of the journal Science shows that lipid hydroperoxides (rancid fat molecules) can react with vitamin C to form products that could potentially harm DNA, although the reaction of these products with DNA was not demonstrated in the study.

Drug interactions

A number of drugs are known to lower vitamin C levels, requiring an increase in its intake. Estrogen-containing contraceptives (birth control pills) are known to lower vitamin C levels in plasma and white blood cells. Aspirin can lower vitamin C levels if taken frequently. For example, two aspirin tablets taken every six hours for a week has been reported to lower white blood cell vitamin C by 50%, primarily by increasing urinary excretion of vitamin C.

There is some evidence, though controversial, that vitamin C interacts with anticoagulant medications (blood thinners) such as warfarin (Coumadin). Large doses of vitamin C may block the action of warfarin, requiring an increase in dose to maintain its effectiveness. Individuals on anticoagulants should limit their vitamin C intake to 1 gram/day and have their prothrombin time monitored by the clinician following their anticoagulant therapy. Because high doses of vitamin C have also been found to interfere with the interpretation of certain laboratory tests (e.g., serum bilirubin, serum creatinine, and the guaiac assay for occult blood) it is important to inform one's health care provider of any recent supplement use.