Q & A: Calcitriol versus Vitamin D3: What's the Difference?

What is the difference between calcitriol and vitamin D3? They both appear to be 1,25-hydroxycholecalciferol.

How about vitamin D2? It that form active at all in dogs and cats with renal failure?

My Response:

Vitamin D is a fat-soluble vitamin that exists in various forms (1). The chemical structure of vitamin D was established in the early 1930's. The main forms are vitamin D2 (ergocalciferol), found in plants, yeasts and fungi and vitamin D3 (cholecalciferol) of animal origin. Vitamin D2 and D3 are not biologically active; rather, they must be modified in the body to have any effect.

Vitamin D2 or D3 must then be first hydroxylated in the liver and then in the kidneys to become active. At this point, as biologically active 1,25-OH-cholecalciferol (also called calcitriol), this form of vitamin D can exert its endocrine effects (1).

By the early 1970's, it had become clear that calcitriol was the active form of vitamin D. It is over 1,000 times as potent as Vitamin D2 and D3 in binding to the vitamin D receptor.

The sun
Vitamin D has long been considered an essential dietary ingredient, but in several species, including humans, sheep, cattle, horses, and pigs, vitamin D3 can be formed in the skin from a cholesterol metabolite (7-dehydrocholesterol) after exposure to natural sun light.

In dogs and cats, however, this skin production of vitamin D3 does not occur (2), so they are dependent entirely on a dietary source of vitamin D.

Food
Large amounts of vitamin D are not found in adequate amounts in most foods. It’s found in fish, cod liver oil, mushrooms, liver and eggs – but usually not in substantial amounts (except in cod liver oil). Thus, getting enough vitamin D naturally from whole foods is difficult.

Both vitamin D2 and D3 have been commercially synthesized and both forms seem to be effective at maintaining blood levels of vitamin D in the body.

Use of vitamin D in renal disease
In severe renal failure, the kidneys cannot produce adequate amounts of the biologically active vitamin D, and this commonly leads to abnormalities of calcium and phosphorus metabolism (3). Oral administration of active calcitriol to animals with chronic kidney disease helps compensate for the reduced production of the active hormone (4).

It is critical to understand that administration of vitamin D2 and D3 will not work to raise active vitamin D concentrations in these animals with renal disease. Active calcitriol must be used as the form of vitamin D to treat these animals (4).

References

1. Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006;92:4-8.
2. How KL, Hazewinkel HA, Mol JA. Dietary vitamin D dependence of cat and dog due to inadequate cutaneous synthesis of vitamin D. Gen Comp Endocrinol. 1994;96:12-18.
3. Gerber B, Hässig M, Reusch CE. Serum concentrations of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in clinically normal dogs and dogs with acute and chronic renal failure. Am J Vet Res. 2003;64:1161-1166.
4. Hostutler RA, DiBartola SP, Chew DJ, et al. Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure. J Vet Intern Med. 2006;20:1307-1313.