Vitamin D3 Cholecalciferol Pharmacology
Vitamin D Pharmacology
Different Forms of Vitamin D
To understand vitamin D pharmocology one needs to be familiar with the different forms of vitamin D, namely cholecalciferol, calcidiol, and calcitriol.
Cholecalciferol (vitamin D3)
Cholecalciferol is the naturally occurring form of vitamin D. It is the substance made in large quantities in your skin when sunlight strikes your bare skin. It can also be taken as a supplement. Cholecalciferol is vitamin D; all other compounds are either metabolic products or chemical modifications.
Calcidiol (25(OH)D3 or 25D3)
Calcidiol (25-hydroxyvitamin D) is a prehormone in your blood that is directly made from cholecalciferol. When being tested for vitamin D deficiency, calcidiol is the only blood test that should be drawn. When someone refers to vitamin D blood levels, they are usually referring to calcidiol levels. Your doctor can order calcidiol levels but both your doctor and the lab will know the calcidiol blood test as 25-hydroxyvitamin D.
Calcitriol (1,25(OH)2D3 or 1,25D3)
Calcitriol (1,25-dihydroxyvitamin D) is made from calcidiol in the kidneys and in tissues and is the most potent steroid hormone derived from cholecalciferol. In fact, it is the most potent steroid hormone in the human body. Calcitriol has signifigant anti-cancer activity. It is sometimes referred to as the active form of vitamin D. Calcitriol levels should never be used to determine if you are deficient in vitamin D.
What Forms of Vitamin D are Available?
Non-prescription vitamin D supplements are available in the United States as either Vitamin D2 Ergocalciferol or Vitamin D3 Cholecalciferol. Both are referred to as "vitamin D" although they are different in their origins, metabolism, and potential toxicity.
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Furthermore, the body turns vitamin D into two very important hormones, calcidiol and calcitriol. These two hormones are also called vitamin D! This borders on the ridiculous as it would be like calling both testosterone and estrogen "cholesterol," as both are made from cholesterol. However, cholesterol, estrogen, and testosterone are very different molecules with very different functions. Likewise, cholecalciferol, calcidiol, and calcitriol are different molecules with different functions.
Potency and Dose
Cholecalciferol is manufactured from the fat of lambs wool by purifying the fat and extracting the cholecalciferol. It is quite potent as vitamin D is active in tiny quantities. One capsule at 1,000 IU is equivalent to 0.025 mg—only 0.000025 of a gram!
Potency just means the dose necessary for a response. The lower the dose, the greater the potency. For example, you might take two Tylenol tablets (1,000 mg) to relieve a headache. Current studies indicate one needs about 4,000 units of cholecalciferol a day to meet the body's need for vitamin D. 4,000 units of cholecalciferol is equal to 100 micrograms, or 0.1 milligrams. So the 1,000 milligrams of Tylenol needed to help your headache is 10,000 times the 0.1 milligrams of cholecalciferol needed to help your body. Therefore, cholecalciferol is 10,000 times more potent than Tylenol.
This potency is one of the reason vitamin D has a reputation as being toxic. Very few other vitamins and supplements, or even medications, are effective in microgram quantities.
You will read that cholecalciferol is a hormone; it is not. It is a prehormone. In fact, it is no more of a hormone than cholesterol. In a way it is similar to cholesterol. For example, some of the cholesterol you eat is turned into hormones: estrogen, testosterone, progesterone, etc. Some of the cholecalciferol from your skin, or from supplements you take, will be turned into hormones by the body. So cholecalciferol is no more of a hormone than is cholesterol.
However, some of your cholecalciferol will be turned into calcitriol, a very potent steroid with anti-cancer properties. Remember when I showed you how cholecalciferol is 10,000 times more potent than Tylenol? Well calcitriol is 10,000,000,000 (10 billion) times more potent than Tylenol! It is active in picogram quantities (1/1,000,000,000,000 of a gram)!
Another substance that is often called vitamin D is ergocalciferol (also referred to as vitamin D2 or Calciferol). It is derived by radiating fungus. It is not the naturally occurring vitamin D for humans. Fungus contains fat-like substances called sterols which are commercially irradiated to form ergocalciferol. As it is derived from plants, and not animals, ergocalciferol is considered Kosher.
Ergocalciferol is available to U.S. doctors in prescription strength and is sometimes used in multivitamin preparations—usually at 400 IU per pill. Your doctor can write a prescription for 50,000 units of ergocalciferol (brand names Drisdol and Calciferol).
Ergocalciferol does not exist in detectable quantities in the human body, only in tiny quantities in plants and as such is "unnatural" when in the human body. You can not get any appreciable ergocalciferol by eating vegetables. Ergocalciferol is metabolized to various substances in the body, some of which are not normally present in humans, although these metabolites have never been shown to be dangerous. There is also some evidence that ergocalciferol is more toxic in overdose, which is curious as it is only about half as potent as the naturally occurring vitamin D, cholecalciferol. Your body also metabolizes ergocalciferol more quickly than cholecalciferol.
Vitamin D as a Prescription Medication
A number of the naturally occurring products of cholecalciferol metabolism are extremely potent and are only available as prescription medications. They are also sometimes called vitamin D. These include calcidiol (also sometimes called calcifediol with the brand names of Calderol and Dedrogyl), dihydrotachysterol (brand name DHT Intensol), and calcitriol (brand names are Rocaltrol and Calcijex when injected).
Vitamin D Analogues
Finally, a number of compunds are based on variations of one of the naturally occurring vitamin D metabolites, usually calcitriol, and these are called vitamin D analogues. They are frequently used in chronic renal disease when the kidney has lost the ability to make calcitriol. The best known are doxercalciferol (taken orally with a brand name of Hectorol) and paricalcitol (intravenous with the brand name Zemplar).
Supplement With Cholecalciferol
The important thing to know: cholecalciferol is the vitamin D to take. Do not let your doctor give you any prescription medication for vitamin D. The only exception to this is ergocalciferol. Although with ergocalciferol you must remember you are taking a drug—not a vitamin—that does not normally occur in the human body.
John Jacob Cannell MD Executive Director 2006.01.03