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Orally, the adverse effects of vitamin C are dose-related and include nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal obstruction, fatigue, flushing, headache, insomnia, sleepiness, and diarrhea.
Doses greater than the tolerable upper intake level can increase the risk of significant adverse effects such as osmotic diarrhea and gastrointestinal upset.
Vitamin C may also cause precipitation of urate, oxalate, or cysteine stones or drugs in the urinary tract.
Hyperoxaluria, hyperuricosuria, hematuria, and crystalluria have occurred in people taking 1 gram or more per day.
In people with a history of oxalate kidney stones (the most common type of nephrolithiasis), supplemental vitamin C 1 gram per day appears to increase stone risk by 40%.
Large amounts of vitamin C are associated with deep vein thrombosis. Prolonged use of large amounts of vitamin C can also result in increased metabolism of vitamin C, and scurvy can occur when vitamin C intake is reduced.
High doses of vitamin C might not be safe for some people. In postmenopausal women with diabetes, supplemental vitamin C in doses greater than 300 mg per day is associated with increased risk of cardiovascular mortality.
Oral supplementation with vitamin C has also been associated with an increased rate of carotid inner wall thickening in men.
There is preliminary evidence that supplemental intake of vitamin C 500 mg daily for 18 months can cause a 2.5-fold increased rate of carotid inner wall thickening in non-smoking men and a 5-fold increased rate in men who smoked.
The men in this study were 40-60 years old. This effect was not associated with vitamin C from dietary sources .
There is also some concern that supplements of vitamin C 200 mg might increase production reactive oxygen molecules capable of damaging DNA.
This is based on very preliminary in vitro evidence that vitamin C can induce decomposition of lipid hydroperoxides to reactive molecules. More evidence is needed to determine if this is clinically relevant in humans taking vitamin C supplements.
