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.

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). The structures of these two forms are shown below. Notice that the only difference is the presence of a double bond in D2 that is not in D3.

Figure 12.11 Structure of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol)^1,2

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. Dietary vitamin D2 and D3 is transported to the liver via chylomicrons and then taken up in chylomicron remnants. 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). 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). The synthesis and activation of vitamin D is shown in the figures below.

Figure 12.12 Vitamin D synthesis and activation⁴

Figure 12.13 Synthesis of 25(OH)D (calcidiol) from vitamin D3 by 25-hydroxylase^5,6 

Figure 12.14 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 research has found that D3 supplementation increases 25(OH)D levels more than D2 supplementation^7,8.

Subsections:

12.11 Environmental Factors That Impact Vitamin D3 Synthesis

12.12 Dietary or Supplemental Vitamin D

12.13 Response to Low Blood Calcium

12.14 Response to High Blood Calcium

12.15 Vitamin D Receptor

12.16 Vitamin D Deficiency, Toxicity, & Insufficiency

References & Links

1. http://en.wikipedia.org/wiki/File:Ergocalciferol.svg

2. http://en.wikipedia.org/wiki/File:Cholecalciferol.svg

3. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

4. http://commons.wikimedia.org/wiki/File:Liver.svg

5. https://en.wikipedia.org/wiki/Vitamin_D#/media/File:Reaction_-_cholecalciferol_to_calcidiol.png

6. https://en.wikipedia.org/wiki/Vitamin_D#/media/File:Reaction_-_calcidiol_to_calcitriol.png

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. 98(11): 4339-4345.

8. Tripkovic L, Wilson LR, Hart K, Johnsen S, de Lusignan S, Smith CP, Bucca G, Penson S, Chope G, Elliott R, Hypponen E, Berry JL Lanham-New SA. (2017) Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. Am J Clin Nutr 106 (2): 481-490.