Scientists warn popular vitamin D supplement may have a “previously unknown” downside

The finding comes from research published in 2025 by scientists at the University of Surrey, John Innes Centre, and Quadram Institute Bioscience. It could matter for the many people who rely on supplements to maintain adequate vitamin D, particularly during the darker winter months.

Vitamin D plays an important role in bone health because it helps the body absorb calcium. It also contributes to normal muscle and immune function. In the UK, the government recommends that people consider taking 10 micrograms (µg) of vitamin D each day during autumn and winter, when sunlight is often too weak for the skin to produce enough on its own.

Vitamin D2 and D3 May Behave Differently

Vitamin D supplements are commonly available in two forms: vitamin D2 and vitamin D3.

Vitamin D2, also known as ergocalciferol, typically comes from plant or fungal sources. Vitamin D3, or cholecalciferol, is the form the human body naturally produces after exposure to sunlight.

Although both can contribute to vitamin D status, they are not identical. Previous research has shown that vitamin D3 is generally more effective at increasing and maintaining vitamin D concentrations in the blood.

The study, published in Nutrition Reviews, examined data from randomized controlled trials comparing vitamin D2 supplementation with groups that did not take vitamin D2. Researchers found that people receiving vitamin D2 tended to experience a reduction in their vitamin D3 levels.

In many of the trials, vitamin D3 concentrations fell below those recorded in the control groups.

That does not necessarily mean vitamin D2 provides no benefit. Rather, the results suggest that increasing vitamin D2 may alter the balance of different vitamin D forms circulating in the body.

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. 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."

Greater Access to Plant-Based Vitamin D3

The results could also have implications for people who prefer supplements that do not contain animal-derived ingredients.

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."

Plant-based sources of vitamin D3 have become increasingly available, potentially giving people another option when choosing between the two forms.

Vitamin D3 May Affect the Immune System Differently

The findings build on earlier evidence that vitamin D2 and D3 may not perform exactly the same roles in the body.

Previous research published in Frontiers in Immunology, led by Professor Colin Smith from the University of Surrey, found differences in how the two forms affected immune activity.

Vitamin D3 appeared to influence the immune system in ways that vitamin D2 did not. In particular, researchers observed an effect on the type I interferon signaling system.

Interferons are signaling proteins used by the immune system to help coordinate the body's early response to infections. They help cells recognize and respond to threats from 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 findings do not establish that taking vitamin D3 supplements will prevent infections. However, they add to evidence that D2 and D3 may have biological differences beyond simply contributing to a person's overall vitamin D levels.

Is Vitamin D3 the Better Choice?

Researchers say more work is needed to understand exactly how vitamin D2 and D3 function differently and what those differences ultimately mean for health.

One important question is whether vitamin D3 should become the preferred first choice for supplementation when there is no specific reason for someone to take vitamin D2. Individual needs can vary, so the researchers emphasize that supplementation decisions should still take personal circumstances into account.

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."

Together, the findings add to evidence that the type of vitamin D in a supplement may matter. Both D2 and D3 can contribute to vitamin D intake, but they may not be interchangeable inside the body. For most people choosing between the two, the researchers suggest that vitamin D3 could have an advantage, although further research is needed to determine how much the differences matter for long-term health.