Hypervitaminosis D

A colleague once told me, “There cannot be vitamin D toxicity without excess calcium.” In most situations of acute overdose and without other comorbidities, I agree.

I am aware of more than a few cases where 50,000 units of ergocalciferol was mistakenly dispensed by the pharmacy to be taken three-times daily instead of twice-weekly for a month as prescribed. In each case, the patients did fine. Despite serum 25-OH vitamin D levels >200 ng/mL, there was no hypercalcemia or other adverse effects.

Chronic overdose of vitamin D, however, is another question. I once saw a woman sent to me for hypothyroidism and thyroid nodules. She also happened to have a slightly high total calcium of 10.3 mg/dL (8.9 mg/dL to 10.1 mg/dL) on the labs I ordered. She did not have a history of kidney stones. All of her other serum calcium levels were normal. She mentioned that she had been seeing a rheumatologist for chondrocalcinosis.

I ordered additional laboratory studies and was surprised to discover that her 25-OH vitamin D was 287 ng/mL (25 ng/mL to 80 ng/mL). Parathyroid hormone was below normal. She denied taking any medications or supplements other than an angiotensin converting inhibitor (without thiazide diuretic), thyroid hormone replacement therapy, 81 mg aspirin daily and calcium with vitamin D.

When I asked her more directly how much vitamin D she was ingesting, she had been taking ergocalciferol 50,000 units three-times weekly for about 7 years. After going through menopause, a general internist prescribed it instead of hormone replacement therapy to protect her bones. After he retired, the patient’s new family physician continued to refill her prescription every year.

After reviewing her records, in addition to chondrocalcinosis, I found that nephrocalcinosis and calcification of other internal organs including the spleen had been mentioned on a CT report a few years earlier. Unfortunately, no one had put her picture together before me. Even more unfortunate, she had chronic renal insufficiency with an estimated glomerular filtration rate of 22 mL/min. This was probably not reversible, even with cessation of intake.

There has been a great deal of excitement in the medical community as well as lay media regarding vitamin D deficiency, which is common and I test for frequently. I replace deficiency aggressively and advocate for appropriate intake to maintain levels. Many now suggest that our current safe tolerable upper intake level of vitamin D of 2,000 units/day is too low and should be revised.

I share in the enthusiasm about vitamin D. Emerging research on the non-bone effects of vitamin D is exciting, even though it must be proven by additional research. However, we must not forget that with vitamins, just as with hormones, if too little is not good and more is better, a whole lot more could potentially be harmful.

How much vitamin D intake is too much?

The answer is probably different individual to individual. It very likely depends on factors such as the baseline vitamin D level, how high a dose and for how long, concomitant calcium intake, the presence of comorbidities, etc.