Vitamin D intoxication with severe hypercalcemia due to manufacturing and labeling errors of two dietary supplements made in the United States
Journal Title (Medline/Pubmed accepted abbreviation):  J. Clin. Endocrinol. Metab.
Year: 2012
Volume: 96
Issue: 12
Page numbers: 3603-3608
doi (if applicable): 10.1210/jc.2011-1443

Summary of background and research design:
Background: Because of the more publicized commonality of vitamin D deficiency, many people are taking vitamin D supplements, yet most do not report their use of these supplements to their physician.

Vitamin D is present mainly in 2 chemical forms in the body: 25-hydroxyvitamin D3 [25(OH)D] or 1,25-dihydroxyvitamin D3 [1,25(OH)2D]. 1,25(OH)2D is the hormonally active form of vitamin D and its blood levels are tightly regulated. Vitamin D plays a key role in calcium uptake and metabolism.

Objective: To describe 2 cases of vitamin D overdose and its effects on vitamin D and calcium equilibrium.

Subjects: Two healthy men, one 58 and one 40 yrs old.

Experimental design: case studies

Protocol: History, including that of supplement use, was acquired via questionnaire. Blood levels of vitamin D were measured throughout the hospital stay and then until vitamin D levels were normal.

Summary of research findings:
Case 1
For 3 wks, a 58 yr old man was abnormally tired, hungry, was urinating excessively, and could not concentrate. He went to the doctor with obtundation (reduced level of consciousness) and was admitted into the hospital. His creatinine levels were high, he was mildly anemic, his blood calcium level was 15.0 mg/dl (normal levels are 9-10.5 mg/dl and tightly regulated), and his 25(OH)D3 levels were 1220 mg/mL (normally 30-80 ng/mL). 1,25(OH)2D was also elevated at 106 pg/mL (normally 15-75 pg/mL). After several inquiries, he reported supplement use. One supplement (a vitamin supplement) claimed 1600 IU of vitamin D per dose. However, further analysis showed it to have 186,400 IU. Also, a typo on the label recommended 10 capsules/day instead of 1, so the individual was taking 1,864,000 IU of vitamin D per day daily for 2 mos (3000 times the government's recommended intake!) Blood calcium levels normalized with hospital treatment. Despite a low vitamin D, low calcium diet and lots of hydration, the person required regular hospital visits for 3 wks. Calcium levels eventually stabilized, but it took 13 mos for the vitamin D levels to stabilize. The company who sold the supplement (in the UK) soon discontinued the supplement.

Case 2
A 40 yr old male had had excessive thirst, muscle aches, and frequent urination for 2 wks. He went to the doctor with nausea and vomiting. He was admitted to the hospital with blood concentrations of 25(OH)D at 645 ng/mL, 1,25(OH)2D at 99 pg/mL, and calcium at 13.2 mg/dl (all extremely elevated). Only after being asked several times, the man disclosed that he was taking a supplement he bought online (from the US). The product claimed to have 1000 IU of vitamin D per serving. Analysis yielded 970,000 IU/dose (about 1500 times the government's recommended daily dose). IV hydration was successful at normalizing calcium levels, but it took 1 month for the man to be asymptomatic, 10 mos for blood 25(OH)D to normalize, and 1 yr for 1,25(OH)2D to normalize.

Key practice applications:

These case studies highlight the poor quality control associated with some brands of vitamin D supplements and the potentially serious health consequences that can arise from taking such supplements. Vitamin D can be toxic at 100,000 IU/day for at least 1 mo. Calcium and vitamin D are strongly linked, and blood levels of both can be drastically affected by dietary stress to either system. In these studies, serum calcium levels were linked with 25(OH)D but not 1,25(OH)2D. It would seem advisable for those taking vitamin D supplements to alert their physician and periodically monitor vitamin D levels in the blood.
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