Current recommendations are that doses above 2 g per day should be avoided to prevent side effects, particularly bloating and osmotic diarrhea (82).
Although a number of possible problems (e.g., birth defects, cancer, atherosclerosis, increased oxidative stress, kidney stones) with very large doses of vitamin C have been suggested in case reports, 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.
Gastrointestinal adverse effects are not generally serious, especially if they are resolved with temporary discontinuation or reduction of high-dose vitamin C supplementation.
Vitamin C is known to function as a highly effective antioxidant in living organisms. However, in in vitroexperiments, 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 such an effect for vitamin C (46, 47), but these studies turned out to be either flawed or of no physiological relevance.
A comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans (48). Studies that report such an 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.
Because ‘oxalate’ is a compound derived from the metabolism of vitamin C, there is some concern that high vitamin C intake could increase the risk of oxalate kidney stones.
Some (49, 50, 51) but not all (52, 53, 54) studies have reported that supplemental vitamin C increases urinary oxalate levels. Two large prospective studies, one following 45,251 men for six years and the other following 85,557 women for 14 years, reported that consumption of equal to or greater 1,500 mg of vitamin C daily did not increase the risk of kidney stone formation compared to those consuming less than 250 mg daily.
However, a more recent prospective study that followed 45,619 men for 14 years found that those who consumed equal to or greater 1,000 mg/day of vitamin C had a 41% higher risk of kidney stones compared to men consuming less than 90 mg of vitamin C daily (54). In this study, low intakes (90-249 mg/day) of vitamin C (primarily from the diet), which are thought to generally benefit health (See Disease Risk Reduction), were also associated with a significantly elevated risk. Supplemental vitamin C intake was only weakly associated with increased risk of kidney stones in this study (55).
Despite conflicting results, it may be prudent for individuals predisposed to oxalate kidney stone formation to avoid high-dose vitamin C supplementation.
Supplemental vitamin C can cause hemolysis in those with glucose 6-phosphate dehydrogenase deﬁciency (86) and in patients with Paroxysmal Nocturnal Hemoglobinuria (87, 88). Vitamin C consumption may also predispose to oxalate accumulation in those with impaired renal function (89).
In those without contraindications, supplemental vitamin C appears to be safe (17, 90).
Vitamin C plus other antioxidants
Results of a clinical trial in 40 healthy young men gave rise to speculate that antioxidant supplements, i.e. vitamins C and vitamin E in particular, may increase the risk of diabetes in athletes (56). Athletic strain leads to oxidative stress through potentially damaging free radicals, which, on the other hand, seem to stimulate the uptake of glucose in the cell. As lower glucose uptake is to be understood as an insulin resistance, promoting type 2 diabetes, physical exercise is thought to be preventive in developing diabetes. The authors concluded that antioxidative substances, such as vitamins C and E, might block the glucose uptake-stimulating effects of free radicals, thereby increasing the risk of developing diabetes.
However, experts commented that the results are of very limited validity as the study was performed only in healthy individuals and not in people with existing insulin resistance. In addition, antioxidants have shown well-documented effects in preventing the long-term damaging effects of free radicals (e.g. atherosclerosis), while the diabetes-preventing effects of free radicals is highly speculative (see also Expert Opinion).
The European Food Safety Authority has decided that there are insufficient data to establish a tolerable upper intake level for vitamin C (57).
A tolerable upper intake level (UL) for vitamin C has been set by the U.S. Food and Nutrition Board in order to prevent most adults from experiencing diarrhea and disturbances in the digestive tract (17):
|Infants 0-12 months
|Not possible to establish*
|Children 1-3 years
|Children 4-8 years
|Children 9–13 years
|Adolescents 14–18 years
|Adults 19 years and older
* Source of intake should be from foods or formula only.
Because of the potential for interactions, dietary supplements should not be taken with medication without first talking to an experienced healthcare provider.
A number of drugs are known to lower vitamin C levels, necessitating an increase in its intake: birth control pills (estrogen-containing contraceptives), and aspirin taken frequently (e.g., two tablets every six hours for a week) (58) are known to lower blood vitamin C levels.
There is some controversial evidence that vitamin C interacts with blood thinners (‘anticoagulant’ medications) like warfarin: 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 g/day and have their therapy monitored by the treating physician (59).
In a randomized controlled trial in patients with coronary heart disease (CHD), the cardio-protective effects of a cholesterol-lowering medication (simvastatin-vitamin B3 combination) were diminished when an antioxidant combination (1,000 mg vitamin C, 800 IU vitamin E, 100 mcg selenium, and 25 mg beta-carotene daily) was taken simultaneously (60). Since the antioxidants were taken together in this trial, the individual contribution of vitamin C cannot be determined.
In contrast, a much larger randomized controlled trial of simvastatin and an antioxidant combination (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) in more than 20,000 men and women with coronary artery disease or diabetes found that the antioxidant combination did not diminish the cardio-protective effects of simvastatin therapy over a 5-year period (61).
These contradictory findings indicate that further research is needed on potential interactions.
Authored by Dr Peter Engel in 2010, reviewed and revised by Dr. Volker Elste on 22.05.2017