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Safety of vitamin C

Department of Human Nutrition and Dietetics
Washington State University
PO Box 1495
Spokane WA 99210-1495
E-mail: massey{at}wsu.edu

Dear Sir:

Hathcock et al (1) cite the 2000 Food and Nutrition Board statement on the lack of evidence that vitamin C increases oxalate formation (2) as confirmation that vitamin C intakes of 2000 mg/d do not increase the risk of kidney stone formation. However, research published since that panel concluded their literature review suggests otherwise. Chai et al (3) reported in 2004 that 2000 mg ascorbic acid (AA)/d increased both oxalate synthesis and absorption. Additional analysis of the responses of 29 calcium stone formers (SFs) and 19 non-stone formers (NSFs) found that consumption of 1000 mg AA twice daily resulted in 2 distinctly different oxaluric responses. Forty percent of the subjects, including both SFs and NSFs, experienced increases of 10% in 24-h urinary oxalate (4). The other 60% of the subjects had essentially no oxaluric response. Examination of individual responses from 3 published studies in which supplements of 1000–2000 mg AA/d were given (5-7) showed that 7 of the 19 total subjects (38%) had similar increases in urinary oxalate of >10%. Genetic susceptibility in the study participants probably accounted for most of the discordance in response to AA that was previously reported; small sample sizes and the lack of a dietary control probably contributed as well.

Three other studies with less rigorous designs also came to similar conclusions about the risk of kidney stone formation related to AA supplements. Baxmann et al (8) reported an increase in urinary oxalate of 61% in SFs after 1000 mg AA/d, 41% in SFs after 2000 mg AA/d, and 56% in NSFs after 2000 mg AA/d. Chalmers et al (9) studied 17 SFs and 11 NSFs who consumed 2000 mg AA/d. They found that, compared with the NSFs, the SFs excreted 12% more oxalate with no AA supplementation and 22% more with AA supplementation. Traxer et al (10) conducted a similar study with 12 SFs and 12 NSFs who ingested 1000 mg AA with each morning and evening meal. Urinary oxalate excretion increased 33% (10 mg oxalate/d) in the SFs and 20% (6 mg oxalate/d) in the NSFs. As did we, Traxer et al (10) identified responders in both the SFs and the NSFs. Baxmann et al (8) identified increases in the Tiselius Risk Index and in urinary oxalate in 47 SFs and 20 NSFs who were randomly assigned to either 1000 mg AA/d (500 mg ingested twice/d) or 2000 mg AA/d (1000 mg ingested twice/d) for 3 d. Before day 1 and on day 3, a 24-h urine sample was obtained. The increase in the Tiselius Risk Index with 1000 mg AA/d (0.51) was similar to that with 2000 mg AA/d (0.56), which suggests that lower doses of AA may also be lithogenic in genetically susceptible individuals. Because hyperoxaluric responses have been shown at doses of both 1000 and 2000 mg AA/d, current evidence suggests that 500 mg AA/d is the maximum dose that can be considered safe, at least until additional testing at lower doses is done.

ACKNOWLEDGMENTS

The author had no conflicts of interest.

REFERENCES

1. Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr 2005;81:736–45.[Abstract/Free Full Text]
2. Food and Nutrition Board, Institute of Medicine. Vitamin C. In: Reference dietary intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press, 2000:95–185.
3. Chai W, Liebman M, Kynast-Gales S, Massey L. Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers. Am J Kidney Dis 2004;44:1060–9.[Medline]
4. Massey L, Liebman M, Kynast-Gales S. Ascorbic acid, oxalate and risk of kidney stones. J Nutr 2005 (in press).
5. Schwille PO, Schmiedl A, Herrmann U, et al. Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans—does it have an abettor role in oxalate, and calcium oxalate crystallization? Urol Res 2000;28:167–77.[Medline]
6. Tiselius HG, Almgard L-E. The diurnal urinary excretion of oxalate and the effect of pyridoxine and ascorbate on oxalate excretion. Eur Urol 1977;3:41–6.[Medline]
7. Liebman M, Chai W, Harvey E, Boenisch L. Effect of supplemental ascorbate and orange juice on urinary oxalate. Nutr Res 1997;7:415–25.
8. Baxmann A, Mendonca C, Heilberg I. Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients. Kidney Int 2003;63:1066–71.[Medline]
9. Chalmers AH, Cowley DM, Brown JM. A possible etiological role for ascorbate in calculi formation. Clin Chem 1986;32:333–6.[Abstract/Free Full Text]
10. Traxer O, Huet B, Poindexter J, Pak C, Pearle M. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;70:397–401.

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