Monday, July 16, 2018

Vitamin D Toxicity: A 16-Year Retrospective Study

Interest in vitamin D has increased during the past 2 decades, with a corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D]. The vast majority of specimens tested display normal or deficient levels of 25(OH)D; concentrations rarely fall in the potentially toxic range.

We performed a retrospective investigation of elevated 25(OH)D levels during a 16-year period at the University of Iowa Hospitals and Clinics, a 734-bed medical center. Detailed medical-record review was performed for patients with serum/plasma 25(OH)D concentrations higher than 120 ng per mL.

A total of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent misdosing of liquid formulations.

Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical symptoms or total serum/plasma calcium levels. Our study highlights the potential risks of the liquid formulation of vitamin D.

My Take:
Vitamin D is one of the most common supplements I recommend in my practice. I do use the liquid formulation in which one drop contains 2,000 IU of vitamin D3. I typically recommend two drops daily (4,000 IU) but have recommended higher doses up to 5 drops daily (10,000 IU). Honestly, I have never had an issue with inadvertent overdosing of the supplement.

I am much more concerned with the prescription vitamin D tablet that contains 50,000 IU per pill. This is typically prescribed in doses of 1-2 per week. This is a massive overdose of vitamin D and is likely to have negative effects on the body. Unfortunately, this is dosage used in the landmark study on vitamin D many years ago that stimulated interest in vitamin D supplementation.

Hypercalcemia is responsible for producing most of the symptoms of vitamin D toxicity. Early symptoms of vitamin D toxicity include gastrointestinal disorders like anorexia, diarrhea, constipation, nausea, and vomiting. Bone pain, drowsiness, continuous headaches, irregular heartbeat, loss of appetite, muscle and joint pain are other symptoms that are likely to appear within a few days or weeks; frequent urination, especially at night, excessive thirst, weakness, nervousness and itching; kidney stones.

Vitamin D hypersensitivity syndromes are often mistaken for vitamin D toxicity. The most common is primary hyperparathyroidism. Granulomatous diseases, such as sarcoidosis, granulomatous TB and some cancers also cause vitamin D hypersensitivity, as the granuloma or the tumor may make excessive amounts of calcitriol, thus raising serum calcium levels.

The Bottom Line:
Vitamin D deficiency is very common with some estimates as high at 70% of the population. Daily supplementation is safe and effective. Doses up to 4,000 IU per day require no laboratory monitoring. However, anyone taking more than 4,000 IU of vitamin D daily should have their blood values checked every three months.

Although the medical norm is 30-100 ng per mL, the optimum minimum level is 42 ng per mL. Toxicity symptoms can begin at 80 ng per mL.

Source: Lab Med. 2018:49(2):123-129

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