Vitamin C Toxicity

The potential toxicity of excessive doses of supplemental vitamin C relates to intra-intestinal events and to the effects of metabolites in the urinary system. Intakes of 2–3 g/day of vitamin C produce unpleasant diarrhoea from the osmotic effects of the unabsorbed vitamin in the intestinal lumen in most people. Gastrointestinal disturbances can occur after ingestion of as little as 1 g because approximately half of the amount would not be absorbed at this dose.

Oxalate is an end product of ascorbate catabolism and plays an important role in kidney stone formation. Excessive daily amounts of vitamin C produce hyperoxaluria. In four volunteers who received vitamin C in the range of 5–10 g/day, this amounted to approximately a doubling of urinary oxalate excretion, from 50 to 87 mg/day (range 60–126 mg/day). However, the risk of oxalate stones formation may become significant at high intakes of vitamin C (>1 g), particularly in subjects with high amounts of urinary calcium.

Vitamin C may precipitate haemolysis in some people, including those with glucose- 6-phosphate dehydrogenase deficiency, paroxysmal nocturnal haemaglobinuria, or other conditions where increased risk of red cell haemolysis may occur or where protection against the removal of the products of iron metabolism may be impaired, as in people with the haptoglobin Hp2-2 phenotype. Of these conditions, only the haptoglobin Hp 2-2 condition was associated with abnormal vitamin C metabolism (lower plasma ascorbate than expected) under conditions where intake of vitamin C was provided mainly from dietary sources. Therefore, 1 g vitamin C appears to be the advisable upper limit of dietary intake.

References:

Kubler, W. & Gehler, J. 1970. On the kinetics of the intestinal absorption of ascorbic
acid: a contribution to the calculation of an absorption process that is not proportional to
the dose. Int. J. Vit. Nutr. Res., 40: 442-453

Schmidt K.-H., Hagmaier, V., Hornig, D.H., Vuilleumier, J. & Rutishauser, G. 1981. Urinary oxalate excretion after large intakes of ascorbic acid in man. Am. J. Clin. Nutr., 34: 305-311

Urivetzky, M., Kessaris D. & Smith, A.D. 1992. Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis. J. Urol., 147: 1215-1218.

Mehta J.B., Singhal S.B. & Mehta B.C. 1990. Ascorbic acid induced haemolysis in G-6-
PD deficiency. Lancet, 336: 944.

Iwamoto, N., Kawaguchi, T., Horikawa, K., Nagakura, S., Hidaka M., Kagimoto T., Takatsuki, K. & Nakakuma H. 1994. Haemolysis induced by ascorbic acid in paroxysmal nocturnal haemoglobinuria. Lancet, 343: 357.

Langlois, M.R., Delanghe, J.R., De Buyzere, M.L., Bernard, D.R. & Ouyang, J. 1997. Effect of haptoglobin on the metabolism of vitamin C. Am. J. Clin. Nutr., 66: 606-610.