Recent research is shedding new light on vitamin D supplementation, challenging long-held beliefs and suggesting a rethink on choices between forms of this essential vitamin.
Research conducted by teams from the University of Surrey, John Innes Centre, and Quadram Institute Bioscience raises intriguing questions about two common forms of vitamin D: D2 and D3. Their findings indicate that these forms may perform differently within the body, and in some situations, one could potentially hinder the effectiveness of the other.
Vitamin D is widely recognized for its role in promoting bone health and enhancing immune function, particularly during seasons when sunlight exposure is limited. In the U.S., adults are generally recommended to consume 15 micrograms (µg) or 600 IU per day, although individual needs may vary based on age and overall health. However, the different behaviors of various supplements can lead to unexpected outcomes.
Understanding Vitamin D2 and D3
Vitamin D comes in two primary forms: D3, which the body produces naturally when exposed to sunlight, and D2, primarily sourced from plants like UV-exposed mushrooms. Historically, D2 has been considered a viable alternative for those unable to receive adequate D3.
However, the recent meta-analysis published in Nutrition Reviews revealed that supplementation with D2 could actually lower levels of D3 in the body. The researchers analyzed data from randomized controlled trials and found that individuals taking D2 often exhibited diminished D3 levels—sometimes even lower than those not taking any supplements at all.
Unexpected Interactions Between Forms
This surprising interaction may explain why some people experience varying benefits from different forms of vitamin D supplements.
“Vitamin D supplements are crucial, particularly from October to March when sunlight exposure in the UK is limited,” says Emily Brown, PhD Research Fellow and lead author from the University of Surrey. “However, we found that D2 supplements can lower D3 levels, a previously unknown effect. This suggests that, depending on individual circumstances, D3 may be a more beneficial option for the majority.”
The research aligns with growing evidence that D3 plays a significant role in the immune system. Previous studies published in Frontiers in Immunology indicated that D3 activates type I interferon signaling, a critical early defense mechanism against viral and bacterial infections.
Professor Colin Smith elaborated, “Our findings indicate that D3, unlike D2, stimulates the type I interferon signaling system, which is vital for an effective immune response. Consequently, maintaining adequate D3 levels may help block infections from establishing in the body.”
Real-World Health Considerations
Low vitamin D levels have been associated with compromised immune responses, increased infection rates, and weakened bone health. If D2 results in lower overall vitamin D levels and suppresses D3, it may not provide sufficient protective effects.
Accessibility and dietary preferences must also be taken into account. While D3 is traditionally obtained from animal sources, lichen-derived plant-based versions are increasingly available.
Highlighting the significance of accessibility, Professor Cathie Martin of the John Innes Centre stated, “This meta-analysis underscores the urgent need for plant-based vitamin D3 to be more widely available in the UK.”
Future investigations will focus on the performance of these two forms across diverse populations and whether existing recommendations should favor D3 as the preferred supplementation option.
Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, noted, “Vitamin D deficiency is a pressing public health issue, particularly during winter months, with notable deficiency levels across the UK population. This collaborative research aligns with the Quadram Institute’s mission of enhancing public health through innovative food solutions.”
References include: “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 et al. (September 18, 2025) in 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 et al. (February 9, 2022) in Frontiers in Immunology, DOI: 10.3389/fimmu.2022.790444.
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