Vitamin D supplementation and risk of vitamin D excess (toxicity)

• Excess vitamin D supplementation can cause hypercalcemia.
  • However, vitamin D toxicity is extremely rare and generally occurs only after ingestion of large doses of vitamin D (>10,000 IU/d) for prolonged periods in patients with normal gut absorption or in patients who may be concurrently ingesting generous if not excessive amounts of calcium (1).
  • A 25(OH)D level of 80 ng/mL is the lowest reported level associated with toxicity in patients without primary hyperparathyroidism with normal renal function
  • Most patients with vitamin D toxicity have levels greater than 150 ng/mL.
  • It has been reported that vitamin D supplementation with 1600 IU/d or 50,000 IU monthly was not associated with any laboratory parameters of toxicity [eg, 25(OH)D, PTH, bone alkaline phosphatase, and 24-hour urine calcium] and even failed to increase total 25(OH)D levels above 30 ng/mL in 19% of participants.
  • One year of D2 or D3 dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals (2).

Notes:

• Vitamin D toxicity should not be diagnosed solely on the basis of an elevated 25(OH)D level; instead, it should be recognized as a clinical syndrome of both hypervitaminosis D and hypercalcemia, in which hyperphosphatemia and hypercalciuria also commonly (although not always) occur (1)
  • patients with vitamin D toxicity could present with clinical symptoms and signs of hypercalcemia (eg, nausea, dehydration, and constipation) and hypercalciuria (eg, polyuria and kidney stones)
  • hypervitaminosis D in the absence of hypercalcemia may prompt further investigation to evaluate the aetiology of increased vitamin D levels
    • but unlike hypercalcemia, it is not a medical emergency (1)

Reference

• (1) Kennel KA, Drake MT, Hurley DL. Vitamin D Deficiency in Adults: When to Test and How to Treat. Mayo Clinic Proceedings. 2010;85(8):752-758.
• (2) Binkley N, Gemar D, Engelke J, Gangnon R, Ramamurthy R, Krueger D, Drezner MK. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. 2011 Apr;96(4):981-8. doi: 10.1210/jc.2010.