A common vitamin D supplement can have an unexpected effect on the body. Research published in 2025 found that taking vitamin D2 can reduce levels of vitamin D3, the natural form that humans produce when skin is exposed to sunlight.
This distinction is important because vitamin D2 and vitamin D3 are often considered interchangeable sources of the same nutrient. Both can increase overall vitamin D status, but growing evidence indicates that D3 is generally more effective in increasing and maintaining the primary form of vitamin D measured in the blood. Current guidelines from the U.S. National Institutes of Health reflect this evidence, noting that D3 tends to increase vitamin D levels more and keep them elevated longer than D2.
Vitamin D is essential for helping the body absorb calcium and maintain healthy bones. It also plays a role in muscle, nerve and immune function. In the UK, it is advisable to consider taking 10 micrograms (µg) of vitamin D each day during the darker months, when sunlight is usually too little for the skin to produce enough of the vitamin.
Vitamins D2 and D3 are not quite the same
Vitamin D supplements generally contain one of two forms. Vitamin D2, also called ergocalciferol, is usually produced from fungi or yeast exposed to ultraviolet light. Vitamin D3, or cholecalciferol, is the same form produced by human skin after exposure to ultraviolet B rays from the sun.
Traditionally, vitamin D3 in supplements often comes from lanolin obtained from sheep’s wool. However, animal-free D3, made from sources such as lichen, is also available, an important consideration for people following a vegan or plant-based diet.
Once vitamin D enters the body, it goes through several stages of processing. The liver converts it to 25-hydroxyvitamin D, the form that doctors commonly measure in blood tests to estimate a person’s vitamin D status. Vitamin D2 produces 25-hydroxyvitamin D2, while vitamin D3 produces 25-hydroxyvitamin D3.
It is this derived form of D3 that researchers believe may drop after people take vitamin D2.
Vitamin D2 was linked to lower vitamin D3
The 2025 study, published in Nutritional advice by researchers from the University of Surrey, the John Innes Center and the Quadram Institute Bioscience, brought together evidence from randomized controlled trials to examine this effect more closely.
The researchers reviewed 20 studies, 11 of which provided data suitable for the main meta-analysis. Compared to people who did not receive vitamin D2, those who took it had significantly lower concentrations of 25-hydroxyvitamin D3. Depending on how the results were analyzed, the average reduction was about 9 to 18 nanomoles per liter.
Importantly, this does not mean that vitamin D2 simply removes vitamin D from the body or that taking it is necessarily harmful. Vitamin D2 itself increases 25-hydroxyvitamin D2 and may contribute to total vitamin D status. What is surprising is that an increase in one form appears to coincide with a reduction in the other.
Emily Brown, PhD researcher and principal investigator of the study from the Department of Nutrition, Exercise, Chronobiology and Sleep Discipline at the University of Surrey, said:
“Vitamin D supplements are important, particularly between October and March, when our bodies cannot produce vitamin D from sunlight in the UK. However, we have found that vitamin D2 supplements can actually decrease vitamin D3 levels in the body, which is a previously unknown effect of taking these supplements. This study suggests that, subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals than vitamin D2.”
Why would vitamin D2 reduce vitamin D3?
Scientists do not yet have a definitive explanation.
One possibility concerns the mechanisms by which the body regulates vitamin D. When concentrations of vitamin D metabolites increase, the body can speed up the breakdown and elimination of these compounds to keep levels under control. The researchers proposed that increasing vitamin D2 could therefore increase the elimination of existing 25-hydroxyvitamin D3.
Previous experiments have also suggested that the relationship may work both ways, with D3 supplementation sometimes reducing D2-derived metabolites. The exact importance of this balancing effect for health remains to be determined.
Professor Cathie Martin, group leader at the John Innes Centre, said:
“This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK.”
This goal has become increasingly practical as plant-based and animal-free sources of vitamin D3 are now available, including lichen-derived D3.
D3 may affect the immune system differently
The results also agree with previous work suggesting that D2 and D3 may not have identical effects beyond their ability to increase vitamin D levels.
A study published in Frontiers in immunology and led by Professor Colin Smith of the University of Surrey, looked at how supplementation affected gene activity in the blood. Researchers found substantial differences between responses to D2 and D3, including changes involving the immune system. In particular, vitamin D3 appears to stimulate activity associated with type I interferon signaling, while vitamin D2 does not.
Type I interferons are signaling proteins that help alert cells when an infection is developing and are an important part of the body’s first defenses against viruses and other pathogens.
Professor Colin Smith said:
“We showed that vitamin D3, but not vitamin D2, appears to stimulate the body’s type I interferon signaling system, a key part of the immune system that provides a first line of defense against bacteria and viruses. So a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.”
The immune results are intriguing, but they should not be interpreted as proof that taking D3 will prevent a particular infection. Changes in gene activity and immune signaling do not necessarily translate directly into fewer diseases, and larger clinical studies are needed to establish the impact of these differences on everyday health.
More recent evidence adds an important caution
Research published since the 2025 analysis makes the picture more nuanced.
A separate systematic review and meta-analysis from 2026 examined 26 randomized trials of vitamin D2. D2 supplementation was found to significantly reduce parathyroid hormone levels and produce a small increase in blood calcium, demonstrating that D2 continues to have significant biological effects even though it can reduce circulating D3.
This finding is important because reduction of D3 should not be confused with evidence that D2 is ineffective. Current information from the NIH continues to support that both D2 and D3 can increase overall blood levels of vitamin D. The difference is that the accumulated evidence favors D3 to produce a greater increase and maintain that increase longer.
This is also consistent with previous meta-analyses directly comparing the two forms. An analysis of 24 studies found that D3 was more effective than D2 in improving overall vitamin D status, while another focused on frequent doses came to a similar conclusion.
Scientists still need to know what the difference means
The central unanswered question is not whether D2 can reduce D3 in circulation. Evidence from randomized trials strongly suggests that it is possible. What remains unclear is whether this reduction results in meaningful differences in health outcomes.
Researchers say additional studies are needed to determine how D2 and D3 are metabolized, whether their effects on immune function differ significantly, and whether D3 should become the preferred form for routine supplementation when there is no individual reason to use D2.
Professor Martin Warren, Scientific Director of the Quadram Institute, said:
“Vitamin D deficiency represents a significant public health problem, particularly during the winter months, with significant deficiency in the UK population. This collaborative research effort aligns well with the Quadram Institute’s mission to deliver healthier lives through food innovation to improve the nutrient density of the foods we eat. Addressing this problem with the most effective form of vitamin D supplementation or fortification is of utmost importance to the health of the nation.
For now, evidence increasingly suggests that a vitamin D supplement’s label matters. Both D2 and D3 may contribute to vitamin D status, but they are not necessarily interchangeable metabolically, and D3 appears to have an advantage when the goal is to increase and maintain vitamin D levels. What scientists have yet to determine is whether these biochemical differences translate into important differences in long-term health.
Gn Health
