A 2025 review of randomized trials found that vitamin D2 supplements were associated with lower blood levels of 25-hydroxyvitamin D3, a form measured as part of vitamin D status. The finding is a change in a biomarker—not proof that D2 is harmful, that total vitamin D status falls by the same amount, or that vitamin D3 prevents illness. Whether it should change clinical advice remains uncertain.
What the review found
Emily I. G. Brown and colleagues’ systematic review and meta-analysis, published in Nutrition Reviews on September 18, 2025, examined randomized controlled trials of vitamin D2 supplementation. The authors reviewed 20 studies and included 11 in their meta-analysis. Their literature search covered publications from January 1, 1975, through February 1, 2023. Read the review.
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Compared with control groups, people taking D2 had lower measured serum 25(OH)D3 in two pooled analyses:
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| Measure | Finding | How to read it |
|---|---|---|
| End-of-trial difference between groups | −17.99 nmol/L (95% CI, −25.86 to −10.12; P < .00001) | Weighted mean difference in 25(OH)D3 at the end of trials |
| Absolute change over the trial | −9.25 nmol/L (95% CI, −14.40 to −4.10; P = .0004) | Weighted mean difference in change in 25(OH)D3 |
Both numbers describe 25(OH)D3, not a drop of the same size in total vitamin D status. They also do not measure symptoms, infections, or other clinical outcomes. The authors suggest that D2 could affect the metabolism or clearance of D3, but say that explanation needs further study.
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What D2 and D3 mean
Vitamin D2 is ergocalciferol; vitamin D3 is cholecalciferol. D3 is the form produced in human skin after exposure to UVB light. Both forms enter vitamin D metabolism, and D2 can contribute to vitamin D status. A lower 25(OH)D3 result therefore does not mean D2 is ineffective.
Blood testing commonly measures 25-hydroxyvitamin D (25(OH)D) to assess vitamin D status. The review’s specific finding concerns the D3-derived form, 25(OH)D3. That distinction matters: a change in one measured form should not be casually restated as an equivalent change in every measure of vitamin D or as evidence of harm.
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Does this mean D2 is harmful or D3 is better for everyone?
No. The review identifies a difference in a blood biomarker, but it does not establish that D2 causes worse health outcomes or that D3 supplementation prevents infections. Its authors say more research is needed to determine whether the forms produce differences in overall vitamin D metabolism that should affect clinical advice.
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Repair common Windows errors and clear accumulated junk for a smoother, more stable PC - no reinstall needed.Free scan · no reinstallLead researcher Emily Brown, a Research Fellow at the University of Surrey, interpreted the results cautiously: “This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2.” That is the researcher’s interpretation of the evidence, not a universal instruction to switch. Personal circumstances and existing clinical advice still matter.
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What the immune-system comments do—and don’t—show
In coverage of the review, University of Surrey professor Colin Smith said D3, but not D2, appeared to stimulate type I interferon signaling, a part of immune activity. Changes in gene activity or immune signaling are not the same as trials showing that people taking D3 have fewer infections. The available evidence here does not establish infection prevention from D3 supplements.
Professor Cathie Martin of the John Innes Centre emphasized access to plant-based D3: “This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK.” The report notes that lichen-derived D3 is available as an animal-free option. That product detail does not change what the meta-analysis proves about health outcomes.
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How to interpret a supplement label
Check the ingredient name if you want to know which form a product contains: ergocalciferol is D2, and cholecalciferol is D3. For people seeking an animal-free D3 product, the report describes lichen-derived D3 as an available option. The review does not establish that everyone should prefer one form, so use personal considerations and advice from a healthcare professional when making a decision about supplementation.
What remains unknown
- Whether the lower 25(OH)D3 levels seen with D2 translate into a meaningful difference in overall vitamin D status.
- Whether the biomarker difference leads to better or worse health outcomes.
- Whether the result warrants a change in routine clinical recommendations.
- Whether the proposed metabolic-clearance explanation accounts for the finding.
The review gives researchers a reason to investigate how D2 and D3 interact in vitamin D metabolism. It does not, by itself, settle which form is right for a particular person.
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