Approximately 50% of women in the United States take calcium and vitamin D supplements [Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/data/databriefs/db61.pdf. Accessed March 12, 2015]. From 1988 to 2002, vitamin D use increased from 50% to 56%, and from 1988 to 2006, calcium use increased from 28% to 61% in women aged > 60 years. Around this same time, the prevalence of kidney stones in the United States has increased from about 1 in 20 persons to 1 in 11 persons [Scales CD et al. Eur Urol. 2012]. Additionally, the Women’s Health Initiative study found an increased risk of kidney stones with the use of vitamin D 400 IU/d plus calcium 2100 mg/d [Jackson RD et al. N Engl J Med. 2006].

Until now there have been no studies on the effect of different doses of vitamin D and calcium supplementation on hypercalcemia and hypercalciuria. Two double-blinded randomized trials by Vinod Yalamanchili, MD, Creighton University School of Medicine, Omaha, Nebraska, USA, and his group assessed the effect of vitamin D and calcium supplementation on serum 25-hydroxyvitamin D and serum and urine calcium levels in older (age range, 57–90 years) and young (age range, 25–45 years) women with vitamin D insufficiency. A total of 163 white and 110 black older women were randomized to vitamin D₃ 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/d or placebo. The young women (113 white, 79 black) were randomized to vitamin D₃ 400, 800, 1600, or 2400 IU/d or placebo. All groups received calcium supplementation. Calcium intake was estimated from 7-day diaries. The average daily calcium supplementation was 580 mg in the elderly women and 450 mg in the young women.

Hypercalcemia occurred in 11% of the elderly white women, 2.5% of the elderly black women, and 1% of the young white and black women. Hypercalciuria was present in 36% of the elderly white women, 25% of elderly black women, 27% of young white women, and 21% of young black women. There was no dose-response relationship between hypercalcemia or hypercalciuria and the vitamin D dose.

Receiver operating characteristic curves (specificity 90%) showed that women with a baseline 24-hour urine calcium > 132 mg were more likely to develop hypercalciuria > 300 mg. Women with a baseline 24-hour urine calcium > 180 mg had a 20-fold increased risk of developing hypercalciuria > 300 mg. Baseline urine calcium was < 300 mg in 66%, 300 to 400 mg in 20%, and > 400 mg in 13% of the women.

Women with hypercalciuria > 400 mg (n = 19) or 300 to 400 mg (n = 28) had a significantly higher mean 24-hour calcium (P < .0001), baseline 1,25-dihydroxyvitamin D (P = .008), and higher baseline calcium absorption (P = .032) compared with women with hypercalciuria < 300 mg or 300 to 400 mg. Further, women with hypercalciuria > 400 mg were also significantly younger (P = .0005) than those with hypercalciuria < 300 mg or 300 to 400 mg.

This study showed that hypercalcemia and hypercalciuria are not associated with the vitamin D dose, but more likely related to calcium supplementation and calcium hyperabsorption. Based on the study results and the number of women taking calcium and vitamin D supplements, the investigators estimated that approximately 15 million women on supplements have periodic hypercalcemia and may be at increased risk for kidney stones. Women with hyperabsorption (24-hour urine calcium > 132 mg) do not need calcium or vitamin D supplementation.Summary