Popular Vitamin D Supplement Has “Previously Unknown” Negative Effect, Study Finds

A new meta-analysis is challenging long-standing assumptions about vitamin D supplements.

New research from researchers at the University of Surrey, the John Innes Centre, and Quadram Institute Bioscience is raising questions about a common choice in supplements: vitamin D2 versus vitamin D3. Their findings suggest the two forms may not be interchangeable and, in some cases, one could even work against the other.

Vitamin D is widely used to support bone health and immune function, especially during times of year when sunlight is limited. In the United States, adults are generally advised to get 15 micrograms (µg) (600 IU) per day, though needs can vary by age and health status. But not all supplements work the same way.

Understanding Vitamin D2 and D3

There are two main types of vitamin D. Vitamin D3 is produced naturally in the skin after sun exposure and is also found in foods like oily fish and egg yolks. Vitamin D2 typically comes from plant sources such as mushrooms exposed to ultraviolet light and has long been considered a suitable alternative.

However, the new study, published in Nutrition Reviews, found that taking vitamin D2 may actually lower the body’s levels of vitamin D3. Researchers reviewed data from randomized controlled trials and observed that people taking D2 supplements often had reduced D3 levels, in some cases dropping below those seen in people taking no supplement at all.

Unexpected Interactions Between Forms

This unexpected interaction could help explain why some individuals do not see the same benefits from different types of vitamin D supplements.

Emily Brown, PhD Research Fellow and lead author from the University of Surrey, 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.”

The findings add to growing evidence that D3 may play a more active role in the immune system. Earlier research in Frontiers in Immunology showed that vitamin D3, but not D2, helps activate type I interferon signaling, a key early defense against viruses and bacteria.

Professor Colin Smith explained: “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 defence against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body.”

Real-World Health Considerations

Low vitamin D levels have been linked to weaker immune responses, higher infection risk, and poor bone health. If D2 both raises total vitamin D less effectively and reduces D3, it may not provide the same level of protection.

At the same time, access and dietary preferences remain important. Vitamin D3 is traditionally derived from animal sources, but plant-based versions made from lichen are now becoming more available.

Professor Cathie Martin of the John Innes Centre emphasized this point: “This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK.”

Future research will focus on how these two forms behave in different populations and whether guidelines should shift toward recommending vitamin D3 as the default option.

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.”

References: “Effect of Vitamin D2 Supplementation on 25-Hydroxyvitamin D3 Status: A Systematic Review and Meta-Analysis of Randomized Controlled Trials” by Emily I G Brown, Andrea L Darling, Tracey M Robertson, Kathryn H Hart, Jie Li, Cathie Martin, Martin J Warren, Colin P Smith, Susan A Lanham-New and Ruan M Elliott, 18 September 2025, Nutrition Reviews.
DOI: 10.1093/nutrit/nuaf166

“Vitamins D2 and D3 Have Overlapping But Different Effects on the Human Immune System Revealed Through Analysis of the Blood Transcriptome” by Louise R. Durrant, Giselda Bucca, Andrew Hesketh, Carla Möller-Levet, Laura Tripkovic, Huihai Wu, Kathryn H. Hart, John C. Mathers, Ruan M. Elliott, Susan A. Lanham-New and Colin P. Smith, 9 February 2022, Frontiers in Immunology.
DOI: 10.3389/fimmu.2022.790444

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