Converting Micrograms (mcg) Of Calcitriol To International Units

Charles asked

What is the equivalent of calcitriol 0.25 mcg in international units for vitamin D3? Thank you

Answer

We wrote a recent article on the subject of converting units of vitamin D to both micrograms and milligrams. We didn't however, touch on a calcitriol conversion to international units, but for good reason... you can't!

There are are a variety of strengths available for over the counter vitamin D products (vitamin D₂ and vitamin D₃), and their strength can be labeled variously as micrograms, milligrams, or international units.

Calcitriol, on the other hand, is technically considered a vitamin D 'analog'. It is not measured in international units, ever. I discuss this more in the next sections.

What Are International Units?

The topic of international units and its use on labels, instead of the more commonly recognized metric unit of measure (e.g milligrams), often leads to confusion.

In a nutshell, international units are used as a method of standardizing different forms of the same substance, thus, making them easier to compare in terms of their biological activity. For one example, take vitamin A, which is available in multiple forms, including:

• Retinol
• Beta-carotene

Tests have shown that different strengths of these 'vitamin A' forms are needed to have the same biological activity (i.e. effect in the body).

It was determined that 0.3 mcg of retinol or 0.6 mcg of beta-carotene are equivalent in terms of their biologic activity and each respective strength is assigned one international unit. So, overall:

• Vitamin A: One international unit (IU) equals 0.3 mcg of retinol or 0.6 mcg of beta-carotene.
  

Going back to Vitamin D, both vitamin D₂ (ergocalciferol) and Vitamin D₃ (cholecalciferol) are considered equivalent in terms of their biological activity.

Thus, one international unit IU of vitamin D₂ is equal to one international unit of vitamin D₃.

There is considerable controversy as to whether one form of vitamin D is more effective than the other at raising blood levels, but that is a topic for another article.

Having said all of the above about international units, you may see their use on labels decrease, or at the very least, be accompanied by their strength in metric terms.

By January 2021, products that use international units as a measure (such as vitamin D), will, by law, list the strength as a metric measure (e.g., milligrams or micrograms). This is according to new labeling requirements from the FDA (Food Labeling: Revision of the Nutrition and Supplement Facts Labels).

In the next section, I focus on calcitriol, and why international units are not used as a measurement.

What Is Calcitriol?

Calcitriol is a prescription only product (in the United States) and is similar to vitamin D₃. Specifically, it is the active form of vitamin D₃ and goes by the chemical name of 1,25-dihydroxycholecalciferol, which is can be shortened to (1,25-(OH)₂D₃)

Calcitriol is often referred to as a 'vitamin D analog' since it is a derivation of vitamin D (even though our body would naturally convert vitamin D₃ to calcitriol).

It plays an important role in many bodily functions, including maintaining calcium and phosphorus balance as well as the regulation of parathyroid hormone.

Based on its actions, it is used for a variety of indications, including:

• Secondary hyperparathyroidism
• Bone disease in chronic renal failure patients wh
• Hypoparathyroidism
• Hypophosphatemia
• Rickets
• Plaque psoriasis (a topical form of calcitriol)

Where Does Calcitriol Come From?

As mentioned earlier, calcitriol is the active form of vitamin D and all activity associated with vitamin D is due to it.

Vitamin D, whether we get it from our own production (from sunlight) or through dietary means, is considered a prohormone that must be metabolized to calcitriol via multiple reactions and transformations:

• The first stop is the liver, where vitamin D is converted to 25-hydroxyvitamin D (25(OH)D, calcifediol), the predominant form of vitamin D found in the blood.
• The next stop is the kidney, where calcifediol is synthesized to calcitriol, the active form of vitamin D.

Is Calcitriol Measured In International Units Like Other Vitamin D Products?

Calcitriol is not measured in 'international units', unlike over the counter vitamin D supplements like vitamin D₂ and vitamin D₃.

Remember that international units are used to standardize the biological activity of different forms of the same substance (like Vitamin D). Our body reacts quite differently to the intake of calcitriol versus the intake of vitamin D and you shouldn't consider the two synonymous.

A letter to the editor in the journal Multiple Sclerosis International describes the difference well:

"In order to produce the active metabolite, calcitriol (or 1,25-dihydroxyvitamin D; 1,25(OH)₂D), vitamin D must be hydroxylated in two subsequent reactions by two separate hydroxylases. The second hydroxylation step—conversion of 25-hydroxyvitamin D [25(OH)D] to 1,25(OH)₂D via 1α-hydroxylase—is under tight regulatory control [in the body]. By providing adequate substrate (i.e., vitamin D), circulating 25(OH)D concentrations increase and cells are able to locally produce and use 1,25(OH)2D in a self-regulated manner without affecting circulating levels of calcitriol. In contrast, supplying calcitriol directly produces a systemic increase in calcitriol, thus bypassing the key regulatory steps..."

The excerpt above also explains why calcitriol is a prescription only item, and not over the counter like vitamin D products. To put it simply, there is a much higher risk of adverse effects with calcitriol.

While our bodies have complex regulatory mechanisms to control how much calcitriol is produced from vitamin D intake, taking calcitriol itself directly increases blood levels.

Taking too much calcitriol can significantly increase the risk of adverse effects like hypercalcemia (too much calcium), which in turn can have deleterious effects on your bones, kidneys, heart, and brain. Vitamin D supplements, on the other hand, are much more forgiving, although it is still possible to take too much.

Converting Calcitriol To International Units Example

To illustrate the difference in effect calcitriol has on the body when compared to vitamin D, let's just convert it to international units based on how vitamin D is converted.

Below is an image of a vitamin D product, as well as a chart of conversions between micrograms (mcg) and international units (IU) for the most popular strengths of vitamin D.

Calcitriol is available in the following strengths:

• 0.25 mcg capsule
• 0.5 mcg capsule
• 1 mcg/mL solution
• 1 mcg/mL injection
• 2 mcg/mL injection
• 3 mcg/g topical ointment

For Vitamin D, since 1 international unit (IU) is equal to 0.025 mcg, using the same conversion for calcitriol, 0.25 mcg would equate to only 10 international units. Clearly, something is off. Taking only 10 units of vitamin D would have negligible effects. As described above, calcitriol is not considered vitamin D and therefore, it doesn't have a standardized international unit value associated with it.

The overall point is that you can't measure calcitriol in international units.

Vitamin D3 And Calcitriol Conversion

There is no conversion between calcitriol and supplemental vitamin D. It's near impossible to say that a specific amount of vitamin D will have the same effect as a certain amount of calcitriol.

The most important reason for this is that vitamin D is converted in the kidneys to calcitriol. Calcitriol is often prescribed to those with kidney diseases since its production from vitamin D will be significantly impaired.

There certainly are individuals who may calcitriol that don't have kidney disease, but again, there is no accurate way of knowing what dose would correlate to a specified amount of vitamin D.