Correspondence

Dietary Supplement–Induced Vitamin D Intoxication

N Engl J Med 2007; 357:308-309July 19, 2007

Article

To the Editor:

Vitamin D intoxication that is associated with the consumption of dietary supplements is reported rarely.1 In 2004, the Food and Drug Administration (FDA) learned of the following case.

A 58-year-old woman with diabetes mellitus and rheumatoid arthritis began taking a dietary supplement called Solutions IE Ageless Formula II on January 12, 2004. Fatigue, constipation, back pain, forgetfulness, nausea, and vomiting soon developed. On March 15, 2004, she was hospitalized because her speech was slurred, and a blood glucose reading taken at home was 30 mg per deciliter. On admission, her serum levels were as follows: calcium, more than 3.75 mmol per liter; 25-hydroxyvitamin D, 1171 nmol per liter (normal range, 22 to 135); 1,25-dihydroxyvitamin D, 305 pmol per liter (normal range, 36 to 144); parathyroid hormone, 12 ng per liter (normal range, 10 to 65); calcitonin, 4.5 ng per liter (normal range, 0 to 4.6); albumin, 31 g per liter; phosphorus, 0.81 mmol per liter; blood urea nitrogen, 18.6 mmol per liter; and creatinine, 265 μmol per liter.

The patient was treated with intravenous normal saline, furosemide, and pamidronate disodium. On March 19, 2004, while still hospitalized, she was informed by the product distributor of an error in product formulation such that 188,640 IU of vitamin D₃ had been added to the daily serving size of six capsules instead of the intended 400 IU. At discharge on March 24, the patient's serum levels were as follows: calcium, 2.60 mmol per liter; blood urea nitrogen, 10.0 mmol per liter; and creatinine, 221 μmol per liter. The patient died from a cause unknown to us on January 8, 2005.

Laboratory analysis of the product by the FDA, obtained from one of two lots reportedly overfortified with vitamin D₃, revealed 186,906 IU of vitamin D₃ in each serving size of six capsules, indicating that the patient had consumed roughly 90 times the recommended safe upper limit of 2000 IU per day. Long-term daily vitamin D consumption of more than 40,000 IU (1000 μg) is needed to cause hypercalcemia in healthy persons.2 In March 2004, the product distributor announced that during the previous month it had received three complaints from customers who had been hospitalized for hypercalcemia and vitamin D toxicity. The same month, the product manufacturer recalled 1600 bottles of the product. The case described here underscores the need for the manufacturers of dietary supplements to rigorously monitor levels of ingredients in products and for physicians to be aware of supplements their patients may be taking.

Karl C. Klontz, M.D.
David W. Acheson, M.D.
Food and Drug Administration, College Park, MD 20740

2 References

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   Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-67
   Full Text | Web of Science | Medline

2. 2

   Veith R. Do we really need ≥100 μg vitamin D/d, and is it safe for all of us? Am J Clin Nutr 2001;74:862-864
   Web of Science | Medline

Citing Articles (8)

Citing Articles

1. 1

   Francisco J.A. de Paula, Clifford J. Rosen. (2011) Vitamin D safety and requirements. Archives of Biochemistry and Biophysics
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2. 2

   Fernando López Azorín, Natalia Sancho Rodríguez, Francisco Ruiz Espejo, Francisco Cañizares Hernández, Isabel Tovar Zapata. (2011) Intoxicación por sobredosificación de vitamina D en un lactante. Revista del Laboratorio Clínico
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3. 3

   L. Alonso Canal, J. Ruiz Herrero, J. Villalobos Reales, J. Gaitero Tristán, T. Pérez Rodríguez, E. Cañedo Villaroya. (2011) Intoxicación por vitamina D en hijos de inmigrantes latinoamericanos. Serie de 3 casos. Anales de Pediatría 74:6, 409-412
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4. 4

   Scott Powers, W. Bradley Nelson, Enette Larson-Meyer. (2011) Antioxidant and Vitamin D supplements for athletes: Sense or nonsense?. Journal of Sports Sciences 29:sup1, S47-S55
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5. 5

   H. A. Bischoff-Ferrari, A. Shao, B. Dawson-Hughes, J. Hathcock, E. Giovannucci, W. C. Willett. (2010) Benefit–risk assessment of vitamin D supplementation. Osteoporosis International 21:7, 1121-1132
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6. 6

   G.K. Schwalfenberg, S.J. Genuis, M.N. Hiltz. (2010) Addressing vitamin D deficiency in Canada: A public health innovation whose time has come. Public Health 124:6, 350-359
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7. 7

   Merav Baz-Hecht, Allison B Goldfine. (2010) The impact of vitamin D deficiency on diabetes and cardiovascular risk. Current Opinion in Endocrinology, Diabetes and Obesity 17:2, 113-119
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8. 8

   Diane L. Kamen, Cynthia Aranow. (2008) The link between vitamin D deficiency and systemic lupus erythematosus. Current Rheumatology Reports 10:4, 273-280
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