what is the purpose of vitamin d3

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Vitamin D3 Cholecalciferol Toxicity

The Truth About Vitamin D Toxicity
==================================

Vitamin D Toxicity Fears Unwarranted
------------------------------------

Is vitamin D toxic? Not if we take the same amount nature intended
when we go out in the sun. Vieth R. Vitamin D supplementation,
25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr.
1999;69:842–56. Vieth attempted to dispel unwarranted fears in medical
community of physiological doses of vitamin D in 1999 with his
exhaustive and well-written review.

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Is toxicity a concern for you? If so, then increase your levels the
way nature intended, with ultraviolet B light! His conclusions: fear
of vitamin D toxicity is unwarranted, and such unwarranted fear,
bordering on hysteria, is rampant in the medical profession. Vieth R,
Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake
exceeding the lowest observed adverse effect level. Am J Clin Nutr.
2001 Feb;73(2):288–94. Even Ian Monroe, the chair of the relevant IOM
committee, wrote to the Journal to compliment Vieth's work and to
promise his findings will be considered at the time of a future
Institute of Medicine review. Munro I. Derivation of tolerable upper
intake levels of nutrients. Letter, Am J Clin Nutr. 2001;74:865. That
was more than two years ago.

In 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.

Sun Supplies 10,000 Units Of Vitamin D
--------------------------------------

The single most important fact anyone needs to know about vitamin D is
how much nature supplies if we behave naturally, e.g., go into the
sun. Humans make at least 10,000 units of vitamin D within 30 minutes
of full body exposure to the sun, what is called a minimal erythemal
dose. Holick MF. Environmental factors that influence the cutaneous
production of vitamin D. Am J Clin Nutr. 1995 Mar;61(3
Suppl):638S–645S. Vitamin D production in the skin occurs within
minutes and is already maximized before your skin turns pink.

Fear of the fatal form of skin cancer, malignant melanoma, keeps many
people out of the sun. The problem with the theory is that the
incidence of melanoma continues to increase dramatically although many
people have been completely avoiding the sun for years. Hemminki K,
Zhang H, Czene K. Incidence trends and familial risks in invasive and
in situ cutaneous melanoma by sun-exposed body sites. Int J Cancer.
2003 May 10;104(6):764–71. We are not saying sunburns are safe, they
are not. We are saying that brief, full-body sun exposure (minimal
erythemal doses) may slightly increase your risk of skin cancer but it
is a much smarter thing to do than dying of vitamin D deficiency.

Hypersensitivity, Not Toxicity
------------------------------

Vitamin D hypersensitivity syndromes are often mistaken for vitamin D
toxicity, as they cause hypercalcemia. The most common is primary
hyperparathyroidism although some cases of "primary"
hyperparathyroidism are actually secondary to Vitamin D deficiency.
Patients with hyperparathyroidism should only take vitamin D under the
care of a knowledgeable endocrinologist. Granulomatous diseases such
as sarcoidosis, granulomatous TB, and some cancers can also cause
Vitamin D hypersensitivity, as the granuloma or the tumor may make
excessive amounts of activated Vitamin D, thus raising serum calcium.
These patients should not take vitamin D except when under the care of
a knowledgeable physician.

Other syndromes occur when abnormal tissue subverts the kidney's
normal regulation of endocrine calcitriol production. Aberrant
tissues, usually granulomatous, convert 25(OH)D into calcitriol
causing high blood calcium. The most common such conditions are
sarcoidosis, oat cell carcinoma of the lung, and non-Hodgkin's
lymphoma but other illnesses can cause the syndrome and they can occur
while the patient's 25(OH)D levels are normal, or even low. For that
reason, while rare, it is advisable to seek a knowledgeable
physician's care when repleting your vitamin D system, especially if
you are older, have sarcoidosis, cancer, or other granulomatous
diseases. In such high-risk patients, periodic monitoring of 25(OH)D
levels and serum calcium will alert the physician to the need to do
more tests—such as calcitriol or PTH—and take further action.

It seems clear that restoring physiological serum levels of 25(OH)D
will help many more patients that it will hurt. In fact, living in
America today while worrying about vitamin D toxicity is like dying of
thirst in the desert while worrying about drowning.

John Jacob Cannell MD Executive Director 2003.09.05 updated 2009.06.20

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