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Forms of Vitamin D

There are two key forms of vitamin D: ergocalciferol (D2) and cholecalciferol (D3).

These are the relevant forms for most discussions on dietary vitamin D, vitamin D supplements, getting vitamin D “from the sun,” and so on. Though there are also synthetic forms of vitamin D given for certain health conditions, as well as countless other forms catalogued by the scientific community, you are unlikely to ever hear mention of those forms again (unless you are a doctor or researcher).

Below, we attempt to help you understand the differences between these forms so that you can make an informed decision on which is best for you. Of course, there is a lot more research and history than can be fully captured here. We’ll try to make everything as interesting and comprehensible as possible.


Cholecalciferol (vitamin D3)

In 1922, a scientist proposed the existence of a new vitamin. Found in cod liver oil, Salmon covered in thyme - a delicious meal with the potential of providing lots of vitamin D, as well as other nutrients!this necessary nutrient had the important ability to “regulate the metabolism of the bones.”1 This vitamin was vitamin D.

Specifically, the nutrient of interest in cod liver oil was cholecalciferol (D3), though it was not known as such till years later. At the same time, research on the effects of exposure to UV light found benefits similar to those of The skeletal structure of the chemical Cholecalciferol.Cholecalciferol the vitamin discovered in cod liver oil. Those initial observed benefits of UV irradiation were also thanks to cholecalciferol.2

It would take a decade for scientists to isolate cholecalciferol and begin to realize that this “vitamin” they had been observing was not a vitamin. Vitamin D is not present in many food sources, and though it took some time for this to be definitively shown, we humans (and many animals) produce our own vitamin D — in the form of cholecalciferol.

Ergocalciferol (vitamin D2)

However, cholecalciferol was not the first form of vitamin D to be chemically isolated. Ergocalciferol, the “plant” form of vitamin D, was isolated before cholecalciferol.The skeletal structure of the chemical Ergocalciferol. Notably similar to that of Cholecalciferol.Ergocalciferol

Ergocalciferol is similar in structure to cholecalciferol. Ergocalciferol is most easily synthesized via irradiation of a particular molecule common to some fungi and yeasts, while cholecalciferol is synthesized via irradiation of a particular molecule found in animal skins or oils. As far as we know, these molecules follow the same general metabolic path in our bodies — A mushroom. Some mushrooms - such as the portobello - may contain a notable amount of vitamin D following UV irradiation.though research has suggested that they are treated differently by our bodies, depending on their metabolic stage.


Vitamin D2 vs Vitamin D3

What are the real differences between vitamin D2 and vitamin D3, though? Do our bodies distinguish between vitamin D2 and vitamin D3?

Research shows that they do. But how — and is it in a way that matters?

Vitamin D plays a complex role within our bodies. The forms of vitamin D we’ve been discussing get metabolized more than once before they reach their most active state. This means there are multiple points at which researchers can disagree over the effectiveness of one form of vitamin D over another. Additionally, there are vitamin D receptors throughout our bodies and vitamin D metabolites we’re only just beginning to learn about — leaving yet more room for disagreement regarding the differences between vitamin D forms.

Add to this complex landscape the problems that often plague research — small sample sizes, poor controls, etc. — and it becomes very difficult to answer our original questions.

In Other Animals

Research has found that different species prefer different forms of vitamin D. Studies dating all the way back to the early days of vitamin D research have found that rats respond more strongly to vitamin D2 than vitamin D3 — whether we’re looking at the effects of vitamin D, or measuring vitamin D blood serum levels. 3,4 On the other hand, many other species react more strongly to vitamin D3 than to vitamin D2 — including pigs, chickens, and a number of species of monkey.4,5,6

In Humans

It’s much more difficult to prove the effectiveness of one form of vitamin D over another in humans. However, studies have suggested that vitamin D3 is, in fact, more effective than D2. A meta-analysis conducted in 2012 found that vitamin D3 does raise vitamin D blood serum levels to a greater extent than vitamin D2.7 This seems to be especially true when we’re talking about less frequent, larger doses of vitamin D. Vitamin D blood serum levels seems to return to baseline much more quickly following supplementation with vitamin D2 than with D3.8

Additionally, numerous studies have suggested that the preference for vitamin D3 over vitamin D2 in humans extends beyond blood serum levels. A review published in 2006 discusses the differences in metabolites for vitamin D forms, how these forms may follow significantly different metabolic pathways, and how these pathways may result in vitamin D3 metabolites that are more biologically active.9

On the Shelf

There is another consideration regarding the difference between vitamin D2 and vitamin D3, and it isn’t discussed enough. Vitamin D3 tends to have a longer shelf-life than vitamin D2 — which means a vitamin D2 supplement is more likely to have less vitamin D than advertised as time goes on.9

At the end of the day, though, it must be acknowledged that we simply do not know everything about vitamin D. As more research is published on the effects of vitamin D, the potential for the effects of vitamin D2 and vitamin D3 to differ only increases. We need much more research regarding these differences — after all, many people in the industrialized world are no longer receiving the vitamin D3 of their ancestors, but rather the relatively new vitamin D2 of fortified foods and some supplements.


References

1: McCollum EV, Simmonds N, Becker JE, Shipley PG. An experimental demonstration of the existence of a vitamin which promotes calcium deposition. J Biol Chem 1922;53:293–298.

2: DeLuca HF. History of the discovery of vitamin D and its active metabolites. BoneKEy Reports. 2014;3: 479.

3: Harris, R. S., Ross, B. D., & Bunker, J. W. (1939). Histological study of hypervitaminosis D. The American Journal of Digestive Diseases, 6(2), 81-83. Chicago

4: Horst RL, Napoli JL, Littledike ET. Discrimination in the metabolism of orally dosed ergocalciferol and cholecalciferol by the pig, rat and chick. Biochem J 1982;204:185–9

5: MARX, S. J., JONES, G., WEINSTEIN, R. S., CHROUSOS, G. P., & RENQUIST, D. M. (1989). Differences in Mineral Metabolism among Nonhuman Primates Receiving Diets with Only Vitamin D3 or Only Vitamin D2*. The Journal of Clinical Endocrinology & Metabolism, 69(6), 1282-1290.

6: Hunt, R. D., Garcia, F. G., & Walsh, R. J. (1972). A comparison of the toxicity of ergocalciferol and cholecalciferol in rhesus monkeys (Macaca mulatta). The Journal of nutrition, 102(8), 975-986.

7: Tripkovic, L., Lambert, H., Hart, K., Smith, C. P., Bucca, G., Penson, S., … & Lanham-New, S. (2012). Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. The American journal of clinical nutrition, 95(6), 1357-1364.

8: Armas, L. A., Hollis, B. W., & Heaney, R. P. (2004). Vitamin D2 is much less effective than vitamin D3 in humans. The Journal of Clinical Endocrinology & Metabolism, 89(11), 5387-5391.

9: Houghton, L. A., & Vieth, R. (2006). The case against ergocalciferol (vitamin D2) as a vitamin supplement. The American journal of clinical nutrition, 84(4), 694-697.