For those of you who aren't as fully up to speed on cholecalciferol as I clearly am, I've taken the time to jot down a basic explanation of what it's all about. I hope you find it of some use.
Cholecalciferol is a form of
vitamin D, also called
vitamin D3 or
calciol.
It is structurally similar to
steroids such as
testosterone,
cholesterol, and
cortisol (though vitamin D3 itself is a
secosteroid).
Forms
Vitamin D3 has several forms:
- Cholecalciferol, (sometimes called calciol) which is an inactive, unhydroxylated form of vitamin D3)
- Calcifediol (also called 25-hydroxyvitamin D3), which is the form measured in the blood to assess vitamin D status[3]
- Calcitriol (also called 1,25-dihydroxyvitamin D3), which is the active form of D3.
Metabolism
7-Dehydrocholesterol is the precursor of vitamin D3 and forms cholecalciferol only after being exposed to solar
UV radiation.
Cholecalciferol is then
hydroxylated in the
liver to become
calcifediol (25-hydroxyvitamin D3).
Next, calcifediol is again hydroxylated, this time in the
kidney, and becomes
calcitriol (1,25-dihydroxyvitamin D3). Calcitriol is the most active hormone form of vitamin D3.
Regulation of metabolism
- Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol under the action of ultraviolet B light. It reaches an equilibrium after several minutes depending on several factors including conditions of sunlight (latitude, season, cloud cover, altitude), age of skin, and color of skin.
- Hydroxylation in the endoplasmic reticulum of liver hepatocytes of cholecalciferol to calcifediol (25-hydroxycholecalciferol) by 25-hydroxylase is loosely regulated, if at all, and blood levels of this molecule largely reflect the amount of vitamin D3 produced in the skin or the vitamin D2 or D3 ingested.
or
As food fortification
Although cholecalciferol can be synthesized in the skin (see Metabolism), it is also a form of vitamin D added to fortify foods. Cholecalciferol is produced industrially by the irradiation of
7-dehydrocholesterol extracted from
lanolin found in sheep's wool. In foods where animal products are not desired, an alternative compound is
ergocalciferol (also known as vitamin D2) derived from the fungal sterol
ergosterol.
Dose
One gram of pure vitamin D3 is 40 000 000 (40x106)
IU, where one IU is equivalent to 0.025 μg. "Recommendations are: 5 micrograms (200 IU or International Units) daily for all individuals (males, female, pregnant/lactating women) under the age of 50 years-old. For all individuals from 50-70 years-old, 10 micrograms daily (400 IU) is recommended. For those who are over 70 years-old, 15 micrograms daily (600 IU) is suggested. Some authors have questioned whether the current recommended adequate levels are sufficient to meet physiological needs, particularly for individuals deprived of regular sun exposure. The upper limit (UL) for vitamin D has been recommended as 2,000 IU daily due to toxicities that can occur when taken in higher doses." Patients with severe vitamin D deficiency will require treatment with a loading dose, its magnitude can be calculated based on the actual serum 25-hydroxy-vitamin D level and body weight (European Journal of Endocrinology 2010;162:805-811).
The 25-hydroxy vitamin D (
calcifediol) blood test is used to determine how much vitamin D is in the body. The normal range of calcifediol is 30.0 to 74.0 ng/mL.
"Vitamin D toxicity can result from regular excess intake of this vitamin, and may lead to hypercalcemia and excess bone loss. Individuals at particular risk include those with
hyperparathyroidism, kidney disease,
sarcoidosis,
tuberculosis, or
histoplasmosis. Chronic
hypercalcemia may lead to serious or even life-threatening complications, and should be managed by a physician. Early symptoms of hypercalcemia may include nausea, vomiting, and
anorexia (appetite/weight loss), followed by
polyuria (excess urination),
polydipsia (excess thirst), weakness, fatigue, somnolence, headache, dry mouth, metallic taste, vertigo,
tinnitus (ear ringing), and
ataxia (unsteadiness). Kidney function may become impaired, and metastatic calcifications (calcium deposition in organs throughout the body) may occur, particularly affecting the kidneys. Treatment involves stopping the intake of vitamin D or calcium, and lowering the calcium levels under strict medical supervision, with frequent monitoring of calcium levels. Acidification of urine and
corticosteroids may be necessary."
There are conflicting reports concerning the absorption of cholecalciferol (D3) versus
ergocalciferol (D2), with some studies suggesting less efficacy of D2, and others showing no difference. At present, D2 and D3 doses are frequently considered interchangeable, but more research is needed to clarify this.
Alternative views
There is a minority view, often associated with
Trevor Marshall, which asserts that low levels of calcifediol (25-hydroxyvitamin D3) are often due to overconversion into calcitriol (1,25-dihydroxyvitamin D3, the active form of D3) because of chronic infection rather than calcifediol deficiency.
Stability
Cholecalciferol is very sensitive to
UV radiation and will rapidly, but reversibly, break down to form supra-sterols, which can further irreversibly convert to
ergosterol.
Therapeutic application
A 2008 study published in Cancer Research has shown the addition of vitamin D3 (along with calcium) to the diet of some mice fed a regimen similar in nutritional content to a new Western diet prevented colon cancer development.
Poison
At high doses cholecalciferol is poisonous. Rodents are somewhat more susceptible to high doses than other species, and cholecalciferol has been used in poison bait for the control of these pests. It has been claimed that the compound is less toxic to non-target species. However, in practice it has been found that use of cholecalciferol in
rodenticides represents a significant hazard to other animals, such as dogs and cats. "Cholecalciferol produces hypercalcemia, which results in systemic calcification of soft tissue, leading to renal failure, cardiac abnormalities, hypertension, CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, anorexia, polyuria, and polydipsia."
In
New Zealand,
possums have become a significant pest animal, and cholecalciferol has been used as the active ingredient in lethal gel baits for possum control. The LD50 is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate it added to the bait. Kidneys and heart are target organs. Thanks Mr Pedia.
