Research published in Nutrition Reviews suggests that vitamin D2 supplement effects include an unexpected reduction in circulating vitamin D3, the form the body produces naturally when skin is exposed to sunlight. The finding, from a systematic review and meta-analysis led by the University of Surrey, challenges the long-standing assumption that D2 and D3 are interchangeable sources of the same nutrient.
What the meta-analysis found on vitamin D2 supplement effects
The researchers reviewed 20 studies, with 11 providing data suitable for their main meta-analysis. According to Qredible, those 11 trials included a combined 655 adults. Compared with participants who did not receive vitamin D2, those who did had significantly lower concentrations of 25-hydroxyvitamin D3, the blood marker doctors use to estimate vitamin D status. Depending on how the results were analysed, the average reduction was roughly 9 to 18 nanomoles per litre.
The study was conducted in collaboration with the John Innes Centre and the Quadram Institute Bioscience in Norwich, and the University of Surrey published its news item on 23 September 2025. Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey’s Nutrition, Exercise, Chronobiology and 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.’
A point worth keeping precise: this does not mean vitamin D2 strips vitamin D from the body or that taking it is necessarily harmful. Vitamin D2 raises its own metabolite, 25-hydroxyvitamin D2, and can contribute to total vitamin D status. The surprise is that increasing one form appears to coincide with a reduction in the other.
Why D2 may suppress D3, and what it means for immune function
Scientists do not yet have a definitive explanation for the suppression. One hypothesis involves the body’s regulatory machinery: when concentrations of vitamin D metabolites rise, the body may accelerate the breakdown and clearance of these compounds to keep levels in check. Researchers have proposed that increasing vitamin D2 could therefore speed the disposal of existing 25-hydroxyvitamin D3. Earlier experiments have also suggested the relationship may work in both directions, with D3 supplementation sometimes reducing D2-derived metabolites. How important this balancing effect is for health remains unresolved.
Separate work, 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 and found substantial differences between the responses to D2 and D3. Vitamin D3 appeared to stimulate activity associated with type I interferon signalling, while D2 did not. Professor Colin Smith said: ‘We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signalling 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.’
That caveat deserves emphasis. Changes in gene activity and immune signalling do not necessarily translate directly into fewer illnesses. Larger clinical studies are needed before anyone can claim that taking D3 rather than D2 will prevent a specific infection.
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 and animal-free sources of vitamin D3, including D3 derived from lichen, are already available, which matters for people following vegan or plant-based diets who would otherwise default to D2, which is typically produced from fungi or yeast.
A 2026 review adds nuance
Research published after the 2025 analysis complicates any simple verdict on D2. A separate 2026 systematic review and meta-analysis, also published in Nutrition Reviews, examined 26 randomised 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 as it may reduce circulating D3. The reduction in D3, therefore, should not be read as evidence that D2 is simply inert.
Current information from the US National Institutes of Health continues to state that both D2 and D3 can increase overall blood levels of vitamin D. The accumulated evidence favours D3 for producing a larger increase and maintaining it for longer, a pattern consistent with earlier meta-analyses comparing the two forms directly.
Professor Martin Warren, Chief Scientific Officer at the Quadram Institute Bioscience, framed the stakes plainly: ‘Vitamin D deficiency represents a significant public health concern, especially during the winter months with significant deficiency across the UK population. Tackling this with the most effective form of vitamin D supplementation or fortification is of the utmost importance to the health of the nation.’ In the UK, current guidance advises considering 10 micrograms of vitamin D daily during the darker months. Whether that guidance should specify the form is precisely what further research aims to determine.
