A widely used vitamin D supplement might have an unexpected consequence within the body. Research published in 2025 revealed that taking vitamin D2 may actually lower levels of vitamin D3, the form that our bodies naturally produce when exposed to sunlight.
This distinction is crucial because vitamin D2 and vitamin D3 are often viewed as synonymous sources of the same nutrient. While both can help increase overall vitamin D levels, evidence is mounting that vitamin D3 is generally more effective at raising and sustaining the primary type of vitamin D found in the bloodstream. Current recommendations from the U.S. National Institutes of Health reflect this, indicating that D3 is better at boosting vitamin D levels and keeping them elevated for more extended periods than D2.
Vitamin D is vital for aiding the body in absorbing calcium and maintaining healthy bones. It also influences muscle, nerve, and immune system functions. In the UK, there are suggestions for individuals to take 10 micrograms (µg) of vitamin D daily during the darker months when sunlight isn’t strong enough for the body to produce sufficient amounts of the vitamin.
Differences Between Vitamin D2 and D3
Vitamin D supplements typically come in two forms. Vitamin D2, or ergocalciferol, is usually derived from fungi or yeast that have been exposed to ultraviolet light. In contrast, vitamin D3, or cholecalciferol, is the form our bodies synthesize after skin exposure to UVB rays from sunlight.
Traditionally, vitamin D3 supplements have been sourced from lanolin, which is extracted from sheep’s wool. However, there are now animal-free D3 supplements available, including those derived from lichen, making them suitable for people adhering to vegan or plant-based diets.
Once vitamin D enters the body, it undergoes several processing steps. The liver converts it into 25-hydroxyvitamin D— the form commonly measured in blood tests to assess an individual’s vitamin D status. Vitamin D2 yields 25-hydroxyvitamin D2, while vitamin D3 produces 25-hydroxyvitamin D3.
It’s this D3-derived form that researchers found could decrease after individuals ingest vitamin D2.
Vitamin D2 Associated with Decreased Vitamin D3 Levels
The 2025 study from the University of Surrey, John Innes Centre, and Quadram Institute Bioscience, published in Nutrition Reviews, consolidated findings from randomized controlled trials to explore this issue in more detail. Researchers analyzed 20 studies, with 11 providing data suitable for the primary meta-analysis. Those receiving vitamin D2 showed significantly lower concentrations of 25-hydroxyvitamin D3 compared to those who did not take D2. Depending on the method of analysis, the average decrease was about 9 to 18 nanomoles per liter.
However, this doesn’t mean that vitamin D2 merely erases vitamin D from the body or that taking it is harmful. Vitamin D2 does raise levels of 25-hydroxyvitamin D2 and can play a role in overall vitamin D status. The surprising revelation here is that an increase in one form seems to coincide with a decrease in the other.
Emily Brown, a PhD Research Fellow and the study’s lead researcher from the University of Surrey, commented:
“Vitamin D supplements are crucial, especially between October and March when our bodies can’t synthesize vitamin D from sunlight in the UK. Yet, we’ve found that vitamin D2 supplements may actually lower vitamin D3 levels, a finding that was not previously known. This suggests that, depending on individual circumstances, vitamin D3 supplements could be more beneficial for most people than vitamin D2.”
Why Would Vitamin D2 Lower Vitamin D3 Levels?
Scientists are still trying to understand why this happens.
One theory might involve the body’s regulatory systems for vitamin D. As levels of vitamin D metabolites rise, the body may ramp up the breakdown and elimination of these compounds to maintain balance. Thus, an increase in vitamin D2 could prompt the body to dispose of some existing 25-hydroxyvitamin D3.
Previous experiments have suggested that this interaction could work both ways, with D3 supplementation sometimes resulting in reduced metabolites from D2 as well. However, how significant this balancing effect is for health is still unclear.
Professor Cathie Martin, a Group Leader at the John Innes Centre, stated:
“This meta-analysis emphasizes the need for accessible plant-based vitamin D3 in the UK.”
This goal is becoming increasingly feasible as both plant-based and animal-free forms of vitamin D3 are now available, including sources derived from lichen.
D3 May Influence the Immune System Differently
The results from the study also align with earlier research suggesting that D2 and D3 may not have the same effects beyond just boosting vitamin D levels.
A separate study published in Frontiers in Immunology, led by Professor Colin Smith from the University of Surrey, investigated how supplementation impacted gene activity in the blood. They found significant differences in the responses between D2 and D3, especially concerning immune system activity. Notably, vitamin D3 appeared to trigger responses related to type I interferon signaling, unlike D2.
Type I interferons are signaling proteins that alert cells to the onset of infections and are vital for the body’s early defense against various pathogens.
Professor Colin Smith remarked:
“Our findings indicate that vitamin D3, unlike vitamin D2, activates the type I interferon signaling system, which is crucial for combating bacteria and viruses. Therefore, maintaining healthy levels of vitamin D3 could help ward off infections.”
While these immune response findings are intriguing, they shouldn’t be taken as definitive proof that D3 supplementation will prevent specific illnesses. Changes in gene activity and immune signaling don’t automatically equate to fewer health issues, and larger clinical studies will be needed to better understand the implications for everyday health.
Emerging Research Adds a Layer of Complexity
Subsequent research since the 2025 analysis has added more complexity to the narrative.
A 2026 systematic review and meta-analysis of 26 randomized trials involving vitamin D2 found that D2 supplementation indeed reduced parathyroid hormone levels and led to a modest increase in blood calcium levels. This suggests that D2 continues to exert biological effects, even if it might lower circulating D3 levels.
This finding is significant because the drop in D3 shouldn’t be mistaken for a lack of efficacy of D2. Current NIH information maintains that both D2 and D3 can enhance overall vitamin D levels in the blood. The distinction lies in the accumulating evidence favoring D3 for achieving a more substantial increase and ensuring that boost lasts longer.
This aligns with prior meta-analyses comparing the two forms directly. One analysis encompassing 24 studies found D3 to be more effective than D2 in improving vitamin D status, while another concentrated on frequent dosing supported similar conclusions.
Unresolved Questions About the Differences
The central question that remains is not whether D2 can lower circulating D3, as the evidence from randomized trials indicates that it indeed does. The uncertainty revolves around whether this reduction has significant implications for health outcomes.
Further studies are required to explore how D2 and D3 are metabolized, whether their impacts on immune functions differ meaningfully, and whether D3 should be the preferred option for standard supplementation unless specific reasons exist to use D2.
Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, commented:
“Vitamin D deficiency is a significant public health issue, particularly in winter months when many in the UK experience inadequate levels. This collaborative research aligns well with the Quadram Institute’s mission to promote healthier lifestyles through food innovation aimed at enhancing the nutrient density of our diets. Addressing this concern with the most effective vitamin D supplementation or fortification is vital for national health.”
In conclusion, the evidence increasingly suggests that the specific type of vitamin D supplement you choose is important. While D2 and D3 can both help boost vitamin D levels, they are not necessarily metabolically equivalent, and D3 seems to provide an edge when the aim is to elevate and maintain vitamin D levels effectively. What researchers still need to determine is whether these biochemical differences translate into meaningful differences in long-term health.
