HOUSTON— Calcium and vitamin D supplements appear to be associated with high calcium levels in the blood and urine, and this could increase the risk of kidney stones, according to a new study presented at The Endocrine Society's 94th Annual Meeting.

“The use of calcium and vitamin D supplementation may not be as benign as previously thought,” said principal investigator J. Christopher Gallagher, MD, Professor of Medicine and director of the Bone Metabolism Unit at Creighton University Medical Center, Omaha, Neb. “Pending further information, people should not exceed the guidelines suggested by the Institute of Medicine, which are 800 international units of vitamin D, and 800-1,200 mg per day of calcium.”

Dr. Gallagher and his colleagues studied 163 healthy, postmenopausal women aged 52-85 years.  The women were randomly assigned to receive either a vitamin D supplement of 400, 800, 1,600, 2,400, 3,200, 4,000, or 4,800 IU a day or placebo. In this study, calcium intake was increased from an initial intake of 691 mg to 1,200-1,400 mg (average 1,280 mg) per day. The investigators measured urine and blood calcium levels at the beginning of the study, and then every three months for one year.

Inclusion criteria for this study were vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D (25OHD) level below 20 ng/mL. Exclusion criteria were illness or medications known to affect vitamin D metabolism. The researchers defined hypercalcemia as a value greater than the normal range (8.9-10.3 mg/dL) and they defined hypercalciuria using a 24-hour urine calcium test that showed levels greater than normal (300 mg). Any abnormal event was verified after seven days; if the high values continued then the dose of the calcium supplements was reduced or the vitamin D supplementation was stopped.

The mean baseline serum 25OHD level was 15.6 ng/mL. The level increased on the highest dose of vitamin D to 45 ng/mL. Mean baseline serum calcium level was 9.47 mg/dL. This increased to 9.52 mg/dL. The mean 24-hour urine calcium level was 142 mg. This increased to 186 mg, according to the researchers.

The investigators found that 33% of subjects had an episode of hypercalciuria and approximately 10% had an episode of hypercalcemia on vitamin D and calcium. Altogether, the researchers observed 88 episodes of hypercalciuria and 25 episodes of hypercalcemia. The final 24-hour urine calcium increased slightly with vitamin D dose.  However, no significant associations were found between episodes of hypercalcemia or hypercalciuria and vitamin D dose or serum 25 OHD. Prolonged hypercalciuria led to discontinuation of calcium in two subjects and discontinuation of vitamin D in one. No incidents of kidney stones were reported during this 12-month study.

“Because of the unpredictable response, it is not clear whether it is the extra calcium, the vitamin D or both together that cause these problems,” Dr. Gallagher said.  “However, it is possible that long-term use of supplements causes hypercalciuria and hypercalcemia, and this can contribute to kidney stones. For these reasons, it is important to monitor blood and urine calcium levels in people who take these supplements on a long-term basis. This is rarely done in clinical practice.”

Taking vitamin supplements has become a widespread practice throughout many parts of the world. In the United States alone, it is estimated that nearly two-thirds of women take vitamin supplements, with calcium and vitamin D among the most commonly used. Despite their popularity, the precise health effects of long-term calcium and vitamin D supplementation remain unclear. Previous research has indicated that hypercalciuria may increase the risk of kidney stones. Hypercalcemia has been associated with many complications, including bone and kidney problems.  However, there currently are no long-term data on hypercalcemia and hypercalciuria with regard to supplement use, according to Dr. Gallagher. In the Women's Health Initiative study, researchers observed significant increases in renal stone incidents in women on a 400 IU a day dose of vitamin D3 and 1,000 mg extra calcium (total calcium intake 2,000 mg) after seven years.

“We think these hypercalciuric and hypercalcemic events occur in those women in the population that is hyper-absorbers, such as we see in idiopathic stone formers,” Dr. Gallagher told Renal & Urology News. “We expect that about 8% of the population has idiopathic hypercalciuria. So if 40 million women take calcium and vitamin D, then four million are at risk for hypercalciuria.”

With respect to screening those at risk who should not take calcium supplements, he said their analyses suggest that baseline 24-hour urine calcium should not exceed 180 mg.

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