Instalab ResearchVitamin D is actually a group of fat-soluble compounds crucial for calcium regulation, bone metabolism, immune health, and more. The two major forms found in supplements and fortified foods are D2, which comes from plants and fungi, and D3, which is produced in human skin through sunlight and found in animal-based foods.
Both forms are biologically inactive until they are converted in the liver to 25-hydroxyvitamin D, or 25(OH)D. This is the form measured in blood tests and is later activated in the kidneys into 1,25-dihydroxyvitamin D, which the body uses to regulate calcium absorption and support other functions.
In theory, either form should work. But that’s where the similarities end.
In study after study, D3 has been shown to raise and maintain blood levels of 25(OH)D more effectively than D2.
For example, one year-long study comparing daily doses of D3 to weekly doses of D2 found that D3 resulted in significantly greater increases in serum vitamin D. D2 was helpful for individuals who were already deficient, but for people with normal levels, it had little effect. D3, in contrast, consistently improved vitamin D status for everyone.
Even when used at high doses, D2 did not perform as well. In long-term treatments lasting several years, high-dose D2 was able to prevent vitamin D deficiency, but only with close monitoring and consistent dosing. D3, by contrast, maintained sufficient levels with fewer fluctuations.
One surprising finding is that D2 supplementation can actually reduce the amount of D3 circulating in the blood. This suggests that the two forms may compete within the body, making D3 not only more potent but also more stable.
The difference in potency becomes even clearer when you look at how each form affects calcium regulation. Both D2 and D3 help the body absorb calcium, but D3 appears to do it more efficiently.
In trials involving elderly adults, those who received D3 showed a significantly greater reduction in parathyroid hormone (PTH). PTH levels typically rise when the body senses a shortage of vitamin D or calcium. Suppressing PTH can help preserve bone density and lower the risk of fractures.
Among children, injectable forms of D3 worked particularly well. After a single dose, most children reached sufficient vitamin D levels within a month, and those levels remained stable for several months. Oral D2, on the other hand, showed limited impact even with regular dosing.
If you are taking vitamin D to support bone health, manage osteoporosis risk, or ensure proper development in children, D3 clearly has the advantage.
Despite its shortcomings, D2 is not useless. It is still effective at treating deficiency, especially in people with low baseline levels. In fact, some long-term clinical protocols use high doses of D2 to prevent recurring deficiency, and these regimens have shown good safety outcomes.
For individuals following vegan or plant-based diets, D2 is often the default option since it is derived from fungi rather than animal sources. Newer formulations of D3 sourced from lichen or algae are becoming more available, but D2 remains the most widely prescribed form in some countries, especially in pharmaceutical preparations.
The issue is not that D2 does nothing. Rather, it requires higher doses, more careful monitoring, and does not maintain levels as consistently as D3.
A handful of studies have found little difference between D2 and D3, particularly when both were consumed in small doses through fortified foods. However, these studies often had limitations, such as short durations or minimal changes in clinical health markers.
For most people, the answer is simple. If you are looking to maintain adequate vitamin D levels over the long term and support your bone and overall health, vitamin D3 is the better choice. It is more potent, more reliable, and better supported by decades of clinical research.
That said, D2 still has its place. It is a viable treatment option, particularly in cases of deficiency or when plant-based sources are necessary. If your doctor prescribes D2, there is no need to worry, as long as you follow the recommended dosage and have your levels monitored.
The most important step is making sure you are not deficient. A blood test can help you determine where you stand and what kind of supplementation, if any, you need. And once you start a regimen, consistency is key, no matter which form you use.
