Scientists warn a popular vitamin D supplement may have a hidden downside
Not all vitamin D supplements are created equal, and new research suggests that one popular form may have an unexpected downside. Scientists found that taking vitamin D2 can actually lower the body's levels of vitamin D3, the form naturally produced by sunlight and more effective at boosting overall vitamin D. Previous studies also suggest that vitamin D3 may provide stronger immune protection against viruses and bacteria.
A common vitamin D supplement may have an unexpected effect inside the body. Research published in 2025 found that taking vitamin D2 can reduce levels of vitamin D3, the form humans naturally make when skin is exposed to sunlight. That distinction matters because vitamin D2 and vitamin D3 are often treated as interchangeable sources of the same nutrient.
Both can increase overall vitamin D status, but a growing body of evidence indicates that D3 is generally more effective at raising and maintaining the main form of vitamin D measured in the blood. Current guidance from the U.S. National Institutes of Health reflects that evidence, noting that D3 tends to raise vitamin D levels more and keep them elevated for longer than D2.
Vitamin D is essential for helping the body absorb calcium and maintain healthy bones. It also plays roles in muscle, nerve, and immune function. In the UK, people are advised to consider taking 10 micrograms (μg) of vitamin D each day during the darker months, when sunlight is generally too weak for the skin to make enough of the vitamin.
Vitamin D2 and D3 Are Not Quite the Same Vitamin D supplements generally contain one of two forms. Vitamin D2, also called ergocalciferol, is commonly produced from fungi or yeast exposed to ultraviolet light. Vitamin D3, or cholecalciferol, is the same form produced in human skin after exposure to ultraviolet B radiation from sunlight.
Traditionally, vitamin D3 in supplements has often come 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 vegan or plant-based diets. Once vitamin D enters the body, it goes through several processing steps.
The liver converts it into 25-hydroxyvitamin D, the form 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 D3-derived form that researchers found could fall after people took vitamin D2.
Vitamin D2 Was Linked to a Drop in Vitamin D3 The 2025 study, published in Nutrition Reviews by researchers from the University of Surrey, John Innes Centre and Quadram Institute Bioscience, brought together evidence from randomized controlled trials to examine this effect more closely.
Researchers reviewed 20 studies, with 11 providing data suitable for the main meta-analysis. Compared with people who did not receive vitamin D2, those taking D2 had significantly lower concentrations of 25-hydroxyvitamin D3. Depending on how the results were analyzed, the average reduction was roughly 9 to 18 nanomoles per liter.
Importantly, that does not mean vitamin D2 simply removes vitamin D from the body or that taking it is necessarily harmful. Vitamin D2 itself raises 25-hydroxyvitamin D2 and can contribute to total vitamin D status. Instead, the surprising finding is that increasing one form appears to coincide with a reduction in the other.
Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey's Nutrition, Exercise, Chronobiology & Sleep Discipline, said: "Vitamin D supplements are important, especially between October and March, when our bodies cannot make vitamin D from sunlight in the UK.
Continue reading
Watch a short ad to unlock the full article
The rest stays locked if you skip or close the ad early.
However, we discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 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 over vitamin D2." Why Would Vitamin D2 Lower Vitamin D3?
Scientists do not yet have a definitive explanation. One possibility involves the body's mechanisms for regulating vitamin D. When concentrations of vitamin D metabolites rise, the body may accelerate the breakdown and removal of these compounds to keep levels under control.
Researchers have proposed that increasing vitamin D2 could therefore increase the disposal of existing 25-hydroxyvitamin D3. Earlier experiments have also suggested that the relationship may work in both directions, with D3 supplementation sometimes reducing D2-derived metabolites.
Exactly how important this balancing effect is for health remains unresolved. 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." That goal has become increasingly practical because plant-based and animal-free sources of vitamin D3 are now available, including D3 derived from lichen.
D3 May Affect the Immune System Differently The findings also fit with earlier work suggesting that D2 and D3 may not have identical effects beyond their ability to raise vitamin D levels. A study published in Frontiers in Immunology and led by Professor Colin Smith from the University of Surrey examined how supplementation affected gene activity in the blood.
The researchers found substantial differences between the responses to D2 and D3, including changes involving the immune system. In particular, vitamin D3 appeared to stimulate activity associated with type I interferon signaling, while vitamin D2 did not. Type I interferons are signaling proteins that help alert cells when an infection is developing and form an important part of the body's early defenses against viruses and other pathogens.
Professor Colin Smith said: "We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signaling system in the body -- a key part of the immune system that provides a first line of defense against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body." The immune findings 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 illnesses, and larger clinical studies are needed to establish what the differences mean for everyday health. Newer Evidence Adds an Important Caveat Research published since the 2025 analysis makes the picture more nuanced.
A separate 2026 systematic review and meta-analysis examined 26 randomized trials involving vitamin D2. It found that D2 supplementation significantly reduced parathyroid hormone levels and produced a small increase in blood calcium, demonstrating that D2 continues to have meaningful biological effects even though it may reduce circulating D3.
That finding is important because the reduction in D3 should not be confused with evidence that D2 is ineffective. Current NIH information continues to state that both D2 and D3 can increase overall blood levels of vitamin D. The difference is that the accumulated evidence favors D3 for producing a larger increase and maintaining that increase for longer.
This is also consistent with previous meta-analyses comparing the two forms directly. One analysis of 24 studies found D3 was more effective than D2 at improving overall vitamin D status, while another focused on frequent dosing reached a similar conclusion. Scientists Still Need to Know What the Difference Means The central unanswered question is not whether D2 can reduce circulating D3.
The randomized trial evidence strongly suggests that it can. What remains uncertain is whether that reduction produces 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 meaningfully differ, and whether D3 should become the preferred form for routine supplementation when there is no individual reason to use D2.
Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, said: "Vitamin D deficiency represents a significant public health concern, especially during the winter months with significant deficiency across the UK population. This collaborative research effort aligns well with the Quadram Institute's mission to deliver healthier lives through food innovation to enhance the nutrient density of the food we eat.
Tackling this with the most effective form of vitamin D supplementation or fortification is of the utmost importance to the health of the nation." For now, the evidence increasingly suggests that the label on a vitamin D supplement matters. D2 and D3 can both contribute to vitamin D status, but they are not necessarily metabolically interchangeable, and D3 appears to have an advantage when the goal is raising and sustaining vitamin D levels.
What scientists still need to establish is whether those biochemical differences translate into important differences in long-term health.
Article text via FreeNewsAPI. Rights remain with ScienceDaily.
Read on publisher site → Opens ScienceDaily in a new tab
