Hypercalcaemia from non-prescription vitamin A

Sir,

Use of over-the-counter ‘natural’ supplements may have unnatural effects. We report this case as a cautionary example.

A 67-year-old white man was admitted to hospital in late January 2004, with malaise and hypercalcaemia. He had undergone kidney transplantation 6 years earlier for kidney failure of unknown cause. Chronic allograft nephropathy occurred and the plasma creatinine rose to 400 µmol/l. He began to feel unwell in December 2003, and had a 5 kg weight loss. There was constipation, melena and haematochezia. His medications included prednisone, mycophenolate mofetil, atorvastatin, labetalol, bumetanide and potassium chloride. Blood tests showed a total plasma calcium of 4.2 mmol/l and he was admitted to hospital. On examination, there was a tremor and unsteadiness of gait. The plasma creatinine was 450 µmol/l. The ionized calcium level was 1.7 mmol/l (normal 1.2–1.3). Intravenous normal saline was given. Chest X-ray was normal. Upper and lower gastrointestinal endoscopy showed antral gastritis and two benign colonic polyps. Serum and urine protein electrophoresis did not show a paraprotein. The parathormone (PTH) level was 17 pg/ml, (normal 10–65) and that of PTH-related peptide was undetectable. The total plasma calcium reached 2.5 mmol/l by hospital day 4. On that day, further enquiry showed that he had been taking a dietary supplement containing vitamin A, on the advice of an eye doctor, for the possible diagnosis of macular degeneration. This over-the-counter supplement contains 7000 U of ß-carotene per tablet and he had been taking four tablets daily since the autumn of 2003. Because of the possibility of vitamin A-induced hypercalcaemia, this supplement was stopped immediately. A retinol plasma level was 2550 µg/l (expected values 350–1200). A month later, he was feeling his usual self, the total plasma calcium had fallen to 2.4 mmol/l, and the plasma creatinine had fallen to 400 µmol/l.

The increasing use of dietary supplements and over-the-counter medicines, ‘natural’ or otherwise, may pose significant risks. In this case, the total daily dose of vitamin A that this patient was using was 28 000 U, whereas the recommended daily intake is only 5000 U. The association of vitamin A toxicity and hypercalcaemia is rare but well recognized. We found only eight case reports of this association in the past 30 years, the most recent being in 1988 [1].

The hypercalcaemia of vitamin A toxicity may occur because of activation of bone resorption by vitamin A [2]. This man's reduced baseline kidney function may have predisposed him to vitamin A toxicity. Given the modern prevalence of use of alternative medicines and supplements, more such cases may occur, which emphasizes the ongoing importance of vigilance and a careful medication history.

Conflict of interest statement. None declared.

Eric P. Cohen and Chinmaya Trivedi

Department of Medicine Medical College of Wisconsin Milwaukee WI USA Email: ecohen{at}mcw.edu

References

  1. Bergman SM, O’Malia J, Krane NK et al. Vitamin A induced hypercalcemia: reponse to corticosteroids. Nephron 1988; 50: 362–364[ISI][Medline]
  2. Frame B, Jackson CE, Reynolds WA, Umphrey JE. Hypercalcemia and skeletal effects in chronic hypervitaminosis A. Ann Intern Med 1974; 80: 44–48[ISI][Medline]




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