People turning to supplements during the darker winter months may want to examine the fine print on their bottles, as a growing body of evidence indicates that one common form of vitamin D might inadvertently deplete another.
A meta-analysis conducted by scientists at the University of Surrey, the John Innes Centre and Quadram Institute Bioscience in the United Kingdom found that taking vitamin D2 supplements led to a noticeable drop in circulating vitamin D3, ScienceDaily reported. Vitamin D3 is the primary form that human skin creates when exposed to sunlight.
The analysis, published in the journal Nutrition Reviews, reviewed 20 clinical studies and evaluated data from 11 randomized controlled trials. Participants receiving vitamin D2 experienced an average reduction in their blood concentrations of 25-hydroxyvitamin D3 ranging from roughly 9 to 18 nanomoles per liter compared to individuals who did not take D2.
How the Two Forms Differ
Vitamin D plays an essential role in bone health, calcium absorption and immune function. In areas where winter sunlight is too weak for the skin to synthesize adequate amounts, health guidelines frequently recommend daily supplementation of 10 micrograms.
However, commercially available supplements generally come in two distinct varieties. Vitamin D2, known chemically as ergocalciferol, is typically produced by exposing yeast or fungi to ultraviolet rays. Vitamin D3, or cholecalciferol, mirrors the compound made by human skin and is traditionally harvested from sheep’s wool lanolin, though plant-based alternatives made from lichen are also available.
Once ingested, the liver processes these nutrients into 25-hydroxyvitamin D, which clinicians test to evaluate a patient’s overall vitamin status. Emily Brown, a doctoral research fellow at the University of Surrey and lead author of the study, noted in a university statement that while supplements remain critical when sunlight is scarce, D2 can decrease D3 levels in the body. Brown suggested that “vitamin D3 supplements may be more beneficial for most individuals over vitamin D2.”
Immunity and Metabolism
Researchers do not yet have a definitive explanation for why introducing D2 prompts a decrease in D3. One prevailing theory suggests that when concentrations of vitamin D compounds rise, the body accelerates its natural breakdown and disposal mechanisms, potentially clearing existing D3 at a faster pace.
The two forms also appear to trigger different biological responses. A study published in Frontiers in Immunology showed that vitamin D3 stimulated pathways linked to type I interferon signaling, which helps defend against viruses and bacteria, whereas vitamin D2 did not show that effect.
At the same time, health experts emphasize that taking vitamin D2 is neither dangerous nor ineffective. Current guidance from the U.S. National Institutes of Health confirms that both forms elevate overall vitamin D numbers in the bloodstream. Furthermore, a separate 2026 meta-analysis of 26 trials demonstrated that D2 successfully lowered parathyroid hormone and slightly increased blood calcium, confirming its ongoing biological activity. Still, the NIH notes that D3 tends to produce larger increases that remain elevated for longer periods.
Unanswered Questions
What scientists still do not know is whether the drop in circulating D3 leads to any meaningful changes in real-world health outcomes. While researchers have documented the biochemical decline, larger clinical studies are required to establish whether choosing D3 over D2 yields tangible medical advantages over time.
