According to researchers, previous studies of the association between vitamin C and kidney stones were limited because they were conducted mostly in men. In addition, the studies either demonstrated disparate results for supplemental and dietary vitamin C, or did not examine dietary vitamin C at all.
In a study reported in the American Journal of Kidney Diseases [2016;67(3):400-407], Pietro Manuel Ferraro, MD, MSc, and colleagues analyzed data from the Nurses’ Health Study II (NHS II) cohort to identify the independent association of total, supplemental, and dietary vitamin C intake with the risk for kidney stones in women. To provide greater statistical power, the researchers also updated their previous analysis of the NHS I and Health Professionals Follow-up Study (HPFS) cohorts to include 12 years of additional follow-up for each cohort.
Kidney stones have an approximately 10% prevalence in the United States. Intakes of calcium, sodium, fructose, water, and other beverages are all thought to play a role in the development of kidney stones. Ascorbic acid, or Vitamin C, acts as a cofactor in several enzymatic pathways. Vitamin C is partly converted to oxalate and excreted in urine, which may increase the risk of calcium oxalate stone formation.
Prior to the current analysis, NHS I cohort provided the only data on the association between vitamin C intake and the risk of kidney stones in women. There was no association found between vitamin C and the risk for kidney stones in that cohort. However, according to Dr. Ferraro et al., the relationship between vitamin C and kidney stone risk is unclear and warrants further investigation.
This prospective cohort analysis included 156,735 women in the NHS I and II and 40,536 men in the HPFS, with 2,494,789 person-years of follow-up. Median follow-up for NHS I was 11.7 years, for NHS II, 11.5 years, and for HPFS, 11.3 years. During follow-up, there were 6245 incident kidney stone events.
Vitamin C intake was stratified into five categories: <90 mg per day, 90-249 mg per day, 250-499 mg per day, 500-999 mg per day, and ≥1000 mg per day. In all three cohorts, calcium supplement use and potassium magnesium, oxalate, and phytate intakes tended to be higher across vitamin C categories. NHS I participants tended to be older and dietary calcium intake greater across total vitamin C categories, and in NHS II participants, body mass index tended to be lower across total vitamin C categories.
For the NHS cohorts, the age-adjusted hazard ratio (HR) of incident kidney stones for total vitamin C intake of ≥1000 mg per day compared with <90 mg per day was 0.76 (95% confidence interval [CI], 0.69-0.82; P for trend =.001). Following multivariable adjustment, the HR for the same comparison was 0.99 (95% CI, 0.90-1.09; P for trend =.1).
Analysis of quintiles of total vitamin C intake yielded similar results. The adjusted HR for the highest quintile compared with the lowest was 1.05 (95% CI, 0.92-1.20; P for trend = .6). In multivariable analysis, the HR of incident kidney stones for total vitamin C intake of ≥1000 mg per day compared with taking less than the recommended daily allowance of 75 mg per day was 1.04 (95% CI, 0.93-1.17).
For the HPFS cohort, the age-adjusted HR of incident kidney stones for total vitamin C intake of ≥1000 mg per day compared with <90 mg per day was 0.98 (95% CI, 0.80-1.20; P for trend =.6). Following multivariable adjustment, the HR was 1.43 (95% CI, 1.15-1.79; P for trend = .005).
In only the highest two categories of vitamin C intake was the association between intake and higher risk of kidney stones statistically significant. Median total vitamin C intake for the 500 to 999 mg per day category averaged approximately 700 mg per day over the course of the study.
There was no significant association between supplemental vitamin C intake and the risk of kidney stones in women, but there was a significant association among men (HR, 1.19; 95% CI, 1.01-1.40) for ≥1000 mg per day, P for trend=.001. There was no association between dietary vitamin C intake and the risk of kidney stones among women or men, although few participants had dietary intakes of more than 700 mg per day.
Study limitations included being unable to exclude unmeasured or residual confounding factors; deriving nutrient intakes from food-frequency questionnaires; lack of stone composition reports or 24-hour urine data for most of the study participants; the possibility that much higher levels than seen in this study might increase the risk for kidney stones in women; and the cohorts were predominately white, limiting the generalizability of the findings to other races.
“In conclusion, higher total and supplemental vitamin C intakes were not associated with risk for incident kidney stones in two large cohorts of women, whereas they were associated with higher risk in a large cohort of men. Dietary vitamin C was not associated with risk in any cohort. We advise that male calcium oxalate stone formers abstain from supplemental but not dietary vitamin C intake. Future studies are needed to examine associations between vitamin C, oxalate metabolism, and kidney stone formation and explore the possible effects of sex on the relationship between vitamin C intake and kidney stone risk,” the researchers said.
- This study was designed to examine the association of vitamin C intake with the risk of incident kidney stones in a large cohort of women as well as a large cohort of men.
- Among the women study participants, there was no association between supplemental vitamin C intake and the risk of kidney stones; there was an association among the men.
- There was no association between dietary vitamin C intake and the risk of kidney stones in either women or men.