Correspondence

Vitamin D Intoxication Associated with an Over-the-Counter Supplement

N Engl J Med 2001; 345:66-67July 5, 2001

Article

To the Editor:

As a group, fat-soluble vitamins are lifesaving at physiologic levels and dangerous at megavitamin levels.1 For many people the word “vitamin” implies something that is beneficial and essential, not potentially poisonous.2 More than one third of people in the United States regularly use dietary supplements.3 We describe a patient with hypercalcemia associated with the ingestion of an over-the-counter vitamin D supplement.

A 42-year-old man was hospitalized with symptoms of hypercalcemia of a few weeks' duration. For the past two years, he had been taking a supplement that contained vitamin D₃. On admission his serum levels were as follows: 25-hydroxyvitamin D, 487.3 ng per milliliter (normal range, 8.9 to 46.7); calcium, 15.0 mg per deciliter (normal range, 8.8 to 10.1); creatinine, 2.4 mg per deciliter; and hemoglobin, 10.5 mg per deciliter (all measurements were performed at the Nichols Institute, San Juan Capistrano, Calif.). The patient had normal levels of 1,25-dihydroxyvitamin D, parathyroid hormone, angiotensin-converting enzyme, and thyroid hormone and had normal findings on radiography, computed tomography of the chest, neck, and abdomen, and bone marrow–aspiration biopsy. He received intravenous hydration. The vitamin D₃ was discontinued, and he was advised to wear sunscreen at all times when he was outdoors. He was not treated with glucocorticoids. At discharge his serum calcium level was 9.8 mg per deciliter, his hemoglobin level was 11.2 mg per deciliter, and his creatinine level was 1.7 mg per deciliter. His creatinine level remained elevated for one year. Thirty months later, the results of all blood tests were normal, including serum levels of calcium and 25-hydroxyvitamin D (Figure 1Figure 1Serum Levels of Calcium and 25-Hydroxyvitamin D in a Patient Who Had Vitamin D Intoxication after the Ingestion of an Over-the-Counter Vitamin D Supplement.).

The patient sent us two bottles of his vitamin D₃ supplement (Prolongevity, Markham, Ont., Canada), and we purchased one from the manufacturer. All supplements were from different lots. The vitamin D₃ supplement was extracted with methanol and analyzed by high-performance liquid chromatography.4 The supplements from each of the three lots that we analyzed contained a mean of 1.3±0.1 mg, 12.8±0.1 mg, and 21.7±0.2 mg of vitamin D₃ per gram of powder, respectively, or about 26 to 430 times the amount listed by the manufacturer (2000 IU or 50 μg of vitamin D per gram of powder). The patient consumed one teaspoon (or 3 g) of powder daily, or 156,000 to 2,604,000 IU of vitamin D₃ per day. This amount was 78 to 1302 times the recommended safe upper limit of 2000 IU per day.

To diagnose vitamin D intoxication, one must consider it in the differential diagnosis and obtain a history of vitamin D intake in patients with hypercalcemia, azotemia, and anemia of obscure origin.1 The renal disease is reversible if the use of vitamin D is stopped. Hypervitaminosis D is characterized by high serum levels of 25-hydroxyvitamin D, hypercalcemia, hypercalciuria, and hyperphosphatemia.5 In severe cases of vitamin D intoxication, glucocorticoids are used for short-term management. Renal and hematologic abnormalities may persist despite striking symptomatic improvement.1

Polyxeni Koutkia, M.D.
Tai C. Chen, Ph.D.
Michael F. Holick, M.D., Ph.D.
Boston University Medical Center, Boston, MA 02118
mfholick@bu.edu

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