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Vitamin D pharmacology


Pharmacology is the branch of medicine that is focused on the use and study of drugs and their actions. This page discusses vitamin D in pharmacology, its different forms and the use of vitamin D analogues.

This is an advanced topic, primarily focused to educate health professionals, or to answer any questions a person might have on some form of vitamin D their doctor prescribed

What do we mean when we say vitamin D?

When we say vitamin D, we are talking about vitamin D nutritionally, in the form of cholecalciferol (vitamin D₃) or ergocalciferol (vitamin D₂). Cholecalciferol is made in the skin in response to UVB radiation. Ergocalciferol is produced in plants and fungus, also in response to UVB radiation.

Cholecalciferol and ergocalciferol can both be found in the form of a supplement. In the United States, “over the counter” vitamin D is usually cholecalciferol, but this is not always the case. Cholecalciferol is produced by irradiating sheep wool. Cholecalciferol is also in cod liver oil products. Ergocalciferol supplements are produced much more complicatedly, often involving irradiating sugars and yeasts.

Vitamin D is scarcely found in food. Fatty fish have small quantities of cholecalciferol, while irradiated mushrooms have small quantities of ergocalciferol.

What are the RDAs for vitamin D?

In the United States and Canada, the Institute of Medicine currently recommends the following daily intakes:

Infants, 0-12 months 400 IU
Children, pregnant women and adults, 1-70 years 600 IU
Seniors, >70 years 800 IU

The European Union recommends the following daily intake:

All ages/groups 200 IU (5μg)
What is a ‘physiologic dose’ of vitamin D?

Sometimes you’ll hear scientists refer to “physiologic doses of vitamin D.” A physiologic dose of vitamin D is the dose required to maintain vitamin D blood levels [25(OH)D] in the range that ancestral humans maintained. Since ancestral humans received much more sun exposure than modern day humans get, researchers and doctors will study or prescribe physiologic doses of vitamin D, to make up for the absence of sunlight.

So what is a physiologic dose? This is a dose between 3,000-5,000 IU/day, which will help you achieve the same vitamin D levels of someone who gets lots of year-round full-body sun exposure around the equator.

Some researchers, as well as the Vitamin D Council, believe that physiologic doses of vitamin D should be the public recommendation until research guides us otherwise. This is why the Vitamin D Council recommends 5,000 IU/day, to make up for the sunshine most modern day humans don’t get.

What is a ‘pharmacologic dose’ of vitamin D?

A “pharmacologic dose of vitamin D” is a term referring to any dose greater than a daily physiologic dose. These are also sometimes called ‘mega doses,’ ‘loading doses’ or ‘Stoss doses.’ Doctors will sometimes use pharmacologic doses to quickly raise vitamin D blood levels. A common practice is to prescribe a pharmacologic dose of vitamin D (50,000 IU once per week) when a patient tests low in vitamin D. Researchers will also sometimes use pharmacologic doses in their studies, also to quickly raise vitamin D blood levels.

In general, the Vitamin D Council believes that daily physiologic doses are preferable to pharmacologic doses, though every individual has different needs. If a patient is low in vitamin D, sometimes it is prudent to prescribe both a pharmacologic and physiologic dose. Or in simpler terms, a mega dose for the short term, and a daily maintenance dose for the long term.

Does it matter what kind of vitamin D to take?

A few studies have shown that cholecalciferol (vitamin D₃) is better than ergocalciferol (vitamin D₂) at increasing vitamin D levels and better for various health outcomes and mortality risk. Also, since the body produces cholecalciferol rather than ergocalciferol, it is commonly thought that cholecalciferol is better for people than ergocalciferol.

There are no studies that show whether vitamin D in tablet, gel, capsule, drop or sublingual form is preferable. There are a few vitamin D cream products on the market. At this time, there are no studies that examine how well, if at all, vitamin D is absorbed through applying creams to the skin.

Where and how are vitamin D supplements available?

Vitamin D supplements are widely available “over the counter” in the United States. These supplements are usually vitamin D₃, but it’s important to check the label to make sure. Vitamin D supplements come in a variety of IUs per pill, some of the most common sizes being 400 IU, 1,000 IU, 2,000 IU and 5,000 IU, though products vary.

Vitamin D is also usually found in multi-vitamins, found in amounts of 400 to 1,000 IU, though sometimes more. Vitamin D is also sometimes coupled with calcium and promoted for bone health.

What do doctors prescribe?

Unless a doctor takes extra care in prescribing their patient vitamin D, patients are prescribed a product called Drisdol. Drisdol is ergocalciferol (vitamin D₂) in 50,000 IU pills, usually prescribed to take once or twice weekly, fortnightly or monthly.

The Vitamin D Council generally recommends against this because vitamin D₃ is preferable to vitamin D₂. It should also be considered, that rather than just take a weekly dose of vitamin D in the short run, a long term strategy should be setup to get daily vitamin D in the long run.

Are there any contraindications with vitamin D?

Most people can take vitamin D supplements with no problems. However, care is needed in a few situations. These situations include:

  • If you’re taking certain other medicines: digoxin for an irregular heartbeat (atrial fibrillation) or thiazide diuretics such as hydrochlorothiazide or bendroflumethiazide (commonly used to treat high blood pressure). In this situation, don’t take high doses of vitamin D. You should also have your digoxin level monitored more closely if you’re taking vitamin D.
  • If you have one of these medical conditions: primary hyperparathyroidism, Hodgkin’s or non-Hodgkin’s lymphoma, a granulomatous disease, kidney stones, some types of kidney disease, liver disease or hormonal disease, you should get advice from a specialist. See our Hypersensitivity page for more information.
  • Don’t take vitamin D if you have high blood calcium levels, unless under the care of your physician.
  • You may need more than the usual dose of vitamin D if you’re taking certain medicines which interfere with vitamin D. These include: carbamazepine, phenytoin, primidone, barbiturates and some medicines used for the treatment of HIV infection.
Are vitamin D metabolites ever prescribed?

A vitamin D metabolite is a chemical in the body that the body produces when you take vitamin D. When vitamin D is taken, the liver turns vitamin D into 25(OH)D. Then the kidney and many other tissues in the body take this 25(OH)D and turn it into 1,25(OH)₂D. Since these are the forms the body wants and uses, sometimes doctors prescribe these forms if you can’t produce them yourself when you take vitamin D.

However, in the United States, 25(OH)D is not available over the counter or by prescription. It has been available in the past. It is not known if it will be available in the future.

1,25(OH)₂D (activated vitamin D) is available by prescription, sold under the trade names Rocaltrol, Calcijex and Decostriol. The use of 1,25(OH)₂D is not to treat vitamin D deficiency, but rather treat hypocalcemia and bone disease in people with abnormal conditions like hypoparathyroidism, kidney disease, osteomalacia, rickets and others. 1,25(OH)₂D is prescribed in these instances because the person has difficulty producing 1,25(OH)₂D in their kidney, or maybe they need extra 1,25(OH)₂D to compensate for lack of parathyroid hormone and more. Sometimes doctors recommend those with kidney diseases to take both plain vitamin D and 1,25(OH)₂D.

What are vitamin D analogs?

Vitamin D analogs are drugs chemically and physiologically similar to vitamin D or its metabolites. They are developed by researchers for specific purposes.

Most analogs on the market are used to treat people with kidney disease, those at risk of low blood calcium, and those at risk of bone diseases and other rare medical conditions. There are also analog creams that have also been developed to treat skin disorders like psoriasis.

Here are some analogs currently available on the market:

  • Alfacalcidiol. Alfacalcidiol is an analog with a hydroxyl group at the 1α-position of the A-ring. This means that alfacalcidiol can hydroxylate into activated vitamin D in the liver rather than kidney. This is useful to people with kidney disease who have difficulty producing activated vitamin D with the use of vitamin D alone.
  • Paricalcitol. Paricalcitol is an analog of calcitriol with modifications to the side chain and the A-ring. It is used primarily to treat secondary hyperparathyroidism in patients associated with kidney disease. Paricalcitol is sold under the name Zemplar.
  • Doxercalciferol. Doxercalciferol is similar to paricalcitol for clinical purposes. It is used to treat secondary hyperparathyroidism associated with kidney disease. Doxercalciferol is sold under the trade name Hectoral.
  • Tacalcitol. Tacalcitol is an analog of activated vitamin D manufactured into a topical cream. It is used to apply topically for the treatment of psoriasis. Tacalcitol reduces excessive skin cell turnover, which is why it is used for chronic chapped lips sometimes as well. It is marketed under the trade names Curatoderm and Bonalfa.
  • Maxacalcitol. Maxacalcitol is also a topical cream analog of activated vitamin D. It is also used for the treatment of psoriasis. It is marketed under the name Oxarol.
  • Calcipotriol. Calcipotriol is also a topical cream analog of activated vitamin D. It is also used for the treatment of psoriasis. It is marketed under the names Dovonex or Daivonex.
  • Falecalcitriol. Falecalcitriol is an analog of calcitriol. It is also used primarily to treat secondary hyperparathyroidism in patients associated with kidney disease.
  • Eldecalcitol. Eldecalcitol is a relatively new analog of calcitriol. It has a high affinity for vitamin D binding protein and has been proposed for the treatment of osteoporosis.
  1. Barker JN, Ashton RE, Marks R, Harris RI, Berth-Jones J. Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-finding study with active comparator. Br J Dermatol. 1999.
  2. Fukuoka M, Sakurai K, Ohta T, Kiyoki M, Katayama I. Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes. Skin Pharmacol Appl Skin Physiol. 2001
  3. Kragbelle, K. Treatment of psoriasis with calcipotriol and other Vitamin D analogues. J. Am. Acad. Dermatol., 1992.
  4. Kubodera, N and Takahashi F. “Analogs for the Treatment of Osteoporosis.” In Vitamin D, Third Edition, by Feldman D, Pike JW and Adams JS, 995-1018. Elsevier Academic Press, 2011.
  5. Morii H. Falecalcitriol as a new therapeutic agent for secondary hyperparathyroidism. Clin Calcium. 2005.
  6. Vieth, R. “The Pharmacology of Vitamin D, Including Fortification Strategies.” In Vitamin D, Second Edition, by Feldman D, Pike JW and Gloreieux FH, 995-1018. Elsevier Academic Press, 2005.
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