Total and supplemental vitamin C intake is associated with a significantly elevated risk of kidney stones in men, according to a new study published online ahead of print in the American Journal of Kidney Diseases.

In a prospective cohort analysis, Pietro Manuel Ferraro, MD, of Columbus-Gemelli University Hospital, Catholic University of the Sacred Heart in Rome, Italy, and colleagues found that total vitamin C intake of 90–249, 250–499, 500–999, and 1,000 mg/day or higher was associated with a 19%, 15%, 29%, and 43% increased risk of kidney stones among men compared with an intake below 90 mg/day (reference). The researchers found no association between total vitamin C intake and stones among women.

Additionally, Dr. Ferraro’s group found that high supplemental vitamin C intake was associated with an increased risk of kidney stones in men, but not women. Supplemental vitamin C intake of 1,000 mg/day or more by men was associated with a significant 19% increased risk of kidney stones compared with no intake. Dietary vitamin C intake was not associated with kidney stone risk in either men or women.

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“We advise that male calcium oxalate stone formers abstain from supplemental but not dietary vitamin C intake,” the researchers concluded.

Dr. Ferraro and his colleagues explained that vitamin C is partly converted to oxalate and excreted in urine, thereby potentially increasing the risk for calcium oxalate stone formation. They cited a study published in The Journal of Urology (2003;170:397-401) showing that 2 g/day of vitamin C increased urinary oxalate excretion by about 22%.

The study included 156,735 women in the Nurses’ Health Study I and II and 40,536 men in the Health Professionals Follow-up Study.

The reason for the disparate findings between men and women is unclear, the researchers noted. “It is possible that the effect of vitamin C on kidney stone formation is different in men and women, and some data suggest the potential for sex differences in vitamin C metabolism,” they wrote.

The researchers acknowledged that their study was limited by the possibility of unmeasured or residual confounding factors. “It is possible that the disparate results between dietary and supplemental vitamin C in men indicate unknown differences between supplement and nonsupplement users that affected our results,” the authors wrote. In addition, food-frequency questionnaires were used to ascertain nutrient intake and the investigators did not have stone composition reports or 24-hour urine data for most participants in the study cohorts. “Although the majority of kidney stones in these cohorts were likely the calcium oxalate type, we would not expect to see associations between vitamin C intake and other types of kidney stones.”

David S. Goldfarb, MD, professor of medicine and physiology at New York University and chief of the nephrology section at the New York Harbor VA Healthcare System, said the investigators’ findings are highly credible because they used data from large prospective cohorts.

“Even though they didn’t show the same effect in women, I caution anybody with kidney stones not to take vitamin C,” Dr. Goldfarb told Renal & Urology News. “In fact, I would tell anybody, whether they have stones or not, that there isn’t any purpose in taking vitamin C.”

Dr. Goldfarb noted that an association between vitamin C and kidney stones is plausible because previous studies have shown that vitamin C is metabolized to oxalate. For example, a Brazilian study published in Kidney International (2003;63:1066-1071) found that both calcium stone-forming patients and healthy controls experienced significant increases in mean urinary oxalate after taking vitamin C supplements (500 or 1,000 mg twice daily) for 3 days.

With respect to the difference between dietary and supplemental vitamin C, Dr. Goldfarb explained that increases in dietary vitamin C are associated with concomitant increases in dietary potential alkali. This results in an increase in urinary citrate excretion, which protects against stone formation.

He pointed out that there is no evidence to show vitamin C has therapeutic effects apart from preventing scurvy. “I don’t think there’s any reason why anyone should be taking a vitamin C supplement if they are eating any kind of diet that contains some amounts of fruits and vegetables,” he said.