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12.1: Vitamin D

Vitamin D is unique among the vitamins in that it is part vitamin, part hormone. It is considered part hormone for two reasons: (1) we have the ability to synthesize it, and (2) it has hormone-like functions. The amount synthesized, however, is often not enough to meet our needs. Thus, we need to consume this vitamin under certain circumstances, meaning that vitamin D is a conditionally essential micronutrient.

Figure \(\PageIndex{1}\): Structure of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol)1,2

There are two major dietary forms of vitamin D: the form produced by plants and yeast is vitamin D2 (ergocalciferol), and the form made by animals is vitamin D3 (cholecalciferol) (Figure \(\PageIndex{1}\)). Notice that the only difference is the presence of a double bond in D2 that is not in D3.

Figure \(\PageIndex{2}\): Vitamin D synthesis and activation4

We synthesize vitamin D3 from cholesterol, as shown below. In the skin, cholesterol is converted to 7-dehydrocholesterol. In the presence of UV-B light, 7-dehydrocholesterol is converted to vitamin D3. Synthesized vitamin D will combine with vitamin D-binding protein (DBP) to be transported to the liver (Figure \(\PageIndex{2}\)). Dietary vitamin D2 and D3 is transported to the liver via chylomicrons and then taken up in chylomicron remnants.


Figure \(\PageIndex{3}\): Synthesis of 25(OH)D (calcidiol) from vitamin D3 by 25-hydroxylase5,6

Once in the liver, the enzyme 25-hydroxylase (25-OHase) adds a hydroxyl (-OH) group at the 25th carbon, forming 25-hydroxy vitamin D (25(OH)D, calcidiol) (Figure \(\PageIndex{3}\)). This is the circulating form of vitamin D, thus 25(OH)D blood levels are measured to assess a person's vitamin D status. The active form of vitamin D is formed with the addition of another hydroxyl group by the enzyme 1alpha-hydroxylase (1alpha-OHase) in the kidney, forming 1,25 hydroxy vitamin D (1,25(OH)2D) (Figure \(\PageIndex{4}\)).

Figure \(\PageIndex{4}\): Synthesis of 1,25(OH)2D (calcitriol) from 25(OH)D by 1alpha-hydroxylase6

However, there are a number of other tissues that have been found to have 1alpha-hydroxylase activity. Therefore, these tissues can activate circulating 25(OH)D to 1,25(OH)2D for their own use.

Vitamin D2 and D3 were once thought to be equivalent forms of vitamin D, but more recent research found that D2 supplementation increases 25(OH)D2 levels, but decreases 25(OH)D3 levels. On the other hand, vitamin D3 supplementation increases 25(OH)D3 levels such that total 25(OH)D levels are significantly higher than with D2 supplementation. As a result, D3 is generally viewed as being a superior source of vitamin D, although there is still debate ongoing about this7.

References & Links

  3. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
  7. Lehmann U, Hirch F, Stangl GI, Hinz K, Westphal S, Dierkes J. (2013) Bioavailability of vitamin D2 and D3 in Healthy Volunteers, a randomized placebo-controlled trial. J Clin Endocrinol Metab.