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Reply to L Massey

Council for Responsible Nutrition
1828 L Street NW
Suite 900
Washington, DC 20036
E-mail: jhathcock{at}crnusa.org

Dear Sir:

Massey cites 5 studies (one in press) on the relation between urinary oxalate and vitamin C published since the Food and Nutrition Board (FNB) revised the dietary reference intakes for vitamin C in 2000 (1). These studies reported that supplemental vitamin C (1000–2000 mg/d) was associated with increases in urinary oxalate ranging from 10% to 61%. Several studies identified 2 subpopulations in oxaluric response to vitamin C among stone formers and non-stone formers in the small groups examined. About 40% of the subjects showed an increase in urinary oxalate of 10%. The FNB reviewed earlier studies, which also found increases in urinary oxalate associated with supplemental vitamin C.

Although the increase in oxalate observed in some studies may be attributable to the ex vivo conversion of urinary vitamin C to its metabolic product oxalic acid (2), supplemental vitamin C may indeed increase the urinary excretion of oxalic acid, especially in genetically susceptible individuals. Several large-scale, long-term prospective studies have investigated the clinical significance of these findings. In the Health Professionals Follow-Up Study (HPFS), Curhan et al (3) followed 45 251 men with no history of kidney stones for 6 y and found a lower age-adjusted relative risk (RR) of kidney stone formation of 0.78 (P for trend = 0.11) in the cohort that consumed 1500 mg vitamin C/d than in the cohort whose intake was <250 mg vitamin C/d. In the Nurses' Health Study, a prospective study of 85 557 women followed for 14 y, Curhan et al (4) found no statistically significant difference in the age-adjusted RR for stone formation between subjects with vitamin C intakes of 1500 and subjects with vitamin C intakes of <250 mg/d. However, in a 14-y follow-up of 45 619 men from the HPFS, in which the referent intake of vitamin C was lowered, Taylor et al (5) found that the multivariate RR for stone formation was 1.41 (P for trend = 0.01) in men whose total intake (dietary and supplemental) of vitamin C was 1000 mg/d compared with men whose total intake was <90 mg/d (the recommended dietary allowance). The difference in age-adjusted RR between these quintiles was not statistically significant. The multivariate RR for stone formation between men with a total intake <90 mg vitamin C/d and men with a total intake <250 mg vitamin C/d was 1.22. The increased risk associated with vitamin C emerged only after dietary potassium, which was inversely associated with stone formation, was included in the multivariate analysis. The multivariate RR for stone formation in men who consumed 1000 mg supplemental vitamin C/d was 1.16 (P for trend = 0.01).

Routine restriction of vitamin C in the general population to prevent renal calculi is unwarranted based on the results of the few prospective studies that have been conducted (3–5). According to the recent follow-up to the HPFS (5), which is the only prospective study that has shown a positive association between total vitamin C intake and nephrolithiasis, prophylaxis in men would require restriction of vitamin C to intakes that are less than the recommended dietary allowance and may adversely affect health. As indicated above, the HPFS follow-up found a modestly increased risk at an intake of 90–249 mg vitamin C/d, which would easily be provided by following the recommendation of the US Department of Agriculture to consume 9 daily servings of fruit and vegetables to reduce the risk of cardiovascular disease, certain cancers, type 2 diabetes, and obesity. The observed risk associated with vitamin C in the HPFS follow-up largely occurred at dietary intakes, and high supplemental doses only slightly increased the risk. The Tolerable Upper Intake Level (2000 mg/d) is the highest intake of vitamin C that poses no risk of serious adverse effects for almost all individuals in the general population. The FNB concluded that restriction of vitamin C is warranted in certain subpopulations, such as those who have a glucose-6-phosphate dehydrogenase deficiency or renal disease. The limited data support the restriction of supplemental vitamin C to prevent stone formation only in men who have a propensity for oxalate nephrolithiasis.

ACKNOWLEDGMENTS

JNH is employed by a dietary supplement trade association. None of the other responding authors had any conflicts of interest.

REFERENCES

1. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. A report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Washington, DC: National Academy Press, 2000.
2. Wandzilak TR, D'Andre SD, Davis PA, et al. Effect of high dose vitamin C on urinary oxalate levels. J Urol 1994;151:834–7.[Medline]
3. Curhan GC, Willett WC, Rimm EB, et al. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. J Urol 1996;155:1847–51.[Medline]
4. Curhan GC, Willett WC, Speizer FE, et al. Intake of vitamins B6 and C and the risk of kidney stones in women. J Am Soc Nephrol 1999;10:840–5.[Abstract/Free Full Text]
5. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225–32.[Abstract/Free Full Text]

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