http://www.vitamindcouncil.org/vitaminDToxicity.shtmlIn 1999, Vieth indirectly asked the medical community to produce any evidence 10,000 units of vitamin D a day was toxic, saying "Throughout my preparation of this review, I was amazed at the lack of evidence supporting statements about the toxicity of moderate doses of vitamin D." He added: "If there is published evidence of toxicity in adults from an intake of 250 ug (10,000 IU) per day, and that is verified by the 25(OH)D concentration, I have yet to find it." Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842–56.
Like most medication, cholecalciferol is certainly toxic in excess, and, like Coumadin, is used as a rodent poison for this purpose. Animal data indicates signs of toxicity can occur with ingestion of 0.5 mg/kg (20,000 IU/kg ), while the oral LD50 (the dose it takes to kill half the animals) for cholecalciferol in dogs is about 88 mg/kg, or 3,520,000 IU/kg. An Overview of Cholecalciferol Toxicosis. The American Board of Veterinary Toxicology (ABVT). This would be equivalent to a 110-pound adult taking 176,000,000 IU or 440,000 of the 400 unit cholecalciferol capsules. Vieth reports human toxicity probably begins to occur after chronic daily consumption of approximately 40,000 IU/day (100 of the 400 IU capsules). Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety.Am J Clin Nutr. 1999;69:842–56. Heavy sun exposure when combined with excessive supplement use is a theoretical risk for vitamin D toxicity, but if such a case has been reported, I am not aware of it. Physician ignorance about vitamin D toxicity is widespread. A case report of four patients appeared in the 1997 Annals of Internal Medicine, accompanied by an editorial warning about vitamin D toxicity. Adams JS, Lee G. Gains in bone mineral density with resolution of vitamin D intoxication. Ann Intern Med. 1997 Aug 1;127(3):203–6. Marriott BM. Vitamin D supplementation: a word of caution. Ann Intern Med. 1997 Aug 1;127(3):231–3. However, careful examination of the patients reveals that both papers are a testimony to the fact that incompetence about vitamin D toxicity can reach the highest levels of academia. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842–56. Heaney R, Davies K, Chen T, Holick M, Barger-Lux MJ. Human serum 25 hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10. See worst science for a full critique.
Cholecalciferol, Not Ergocalciferol, Is Safe
Although there are documented cases of pharmacological overdoses from ergocalciferol, the only documented case of pharmacological—not industrial—toxicity from cholecalciferol we could find in the literature was intoxication from an over-the-counter supplement called Prolongevity. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med. 2001 Jul 5;345(1):66–7. On closer inspection, it seemed more like an industrial accident but it was interesting because it gave us some idea of the safety of cholecalciferol. The capsules consumed contained up to 430 times the amount of cholecalciferol contained on the label (2,000 IU). The man had been taking between 156,000–2,604,000 IU of cholecalciferol a day (equivalent to between 390–6,500 of the 400 unit capsules) for two years. He recovered uneventfully after proper diagnosis, treatment with steroids, and sunscreen.
It is true that a few people may have problems with high calcium due to undiagnosed vitamin D hypersensitivity syndromes such as primary hyperparathyroidism, granulomatous disease, or occult cancers, but a blood calcium level, PTH, 25(OH)D, and calcitriol level should help clarify the cause of the hypersensitivity. Although D can be toxic in excess, the same can be said for water.
Therapeutic Index
As a physician, I know that psychotic patients should drink about 8 glasses of water a day. However, many would hurt themselves by regularly drinking 40 glasses a day (called compulsive water intoxication). So you could say that water has a therapeutic index of 5 (40/8).
Heaney's recent research indicates that healthy humans utilize about 4,000 units of vitamin D a day (from all sources). Heaney R, Davies K, Chen T, Holick M, Barger-Lux MJ. Human serum 25 hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10. However, 40,000 units a day, over several years, will hurt them. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842–56. Therefore, vitamin D has a therapeutic index of 10 (40,000/4,000)—twice as safe as water. We are not saying vitamin D is as safe as water, we are saying vitamin D is safe when used in the doses nature uses.
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety.The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D <25(OH)D> response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.
I used to think D was more dangerous that the studies and articles I am reading seem to indicate. In other words it takes aLOT more D that I feared to reach a toxic level unless a person has one of the diseases that would require them to avoid d in any case.
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