Scientists warn popular vitamin D supplement may have a previously unknown downside
A new academic study suggests that vitamin D supplements in the D2 (ergocalciferol) form, used by millions of people worldwide, may carry a previously unknown side effect on immune function. The study, accessible through ScienceDaily, draws on experiments conducted in mice.
The research was led by the University of Surrey in the United Kingdom. Co-author Professor Colin Smith, of nutritional sciences, summarised the result: 'In mice given high-dose D2 supplementation, we observed a small but statistically significant reduction in the function of regulatory T cells that orchestrate immune responses. In mice given the same dose of D3, no such effect was seen.'
Vitamin D supplementation comes in two main forms: plant-derived D2 (ergocalciferol) and animal-derived or lichen-derived D3 (cholecalciferol). Clinical research has long shown that D3 raises serum vitamin D levels more efficiently than D2, but differential effects on immune function between the two forms are a newer research topic.
In methodological terms, the study followed 60 mice over eight weeks across three groups: control, high-dose D2 and high-dose D3. The findings were published in Frontiers in Immunology on 22 May 2026. The authors emphasise that the work is an animal model; conclusive inferences for human supplementation cannot be drawn without clinical trials.
Yale School of Medicine endocrinologist Dr Karl Insogna, in an independent comment, said: 'This is a very small animal study; one cannot assume the same effect will occur in the human immune system. But a reconsideration of whether to prefer D2 is a useful debate to have.'
Current guidelines from the US National Institutes of Health (NIH) state that the health effects of D2 and D3 supplements are largely similar. NIH notes that D2 is also used at prescription-strength doses to treat osteomalacia and osteoporosis; it does not recommend dosage changes without clinical oversight.
In the UK, D2 supplements are typically preferred by vegan consumers. The Vegan Society's position paper states: 'D2 can be considered an adequate option for immune and bone health in adult vegans.' The Society said the new findings should be confirmed by clinical research.
On cost, D2 supplements are cheaper in bulk than D3. The NHS preferred D2 for hospital budgets in earlier years before transitioning to D3 in line with recent clinical efficacy evidence. The annual additional cost of that decision had been estimated at approximately £14 million.
An independent commentary from the University of Surrey was provided by Professor Susan Lanham-New. Lanham-New's own 2024 clinical study had found that 'D2 and D3 show meaningful differences in their effects on serum 25-hydroxy vitamin D levels.' The new animal model may provide a mechanistic explanation for that clinical finding.
What is being recommended to consumers? The NIH and the UK National Health Service (NHS) advise: 'Consult your healthcare professional before changing your current vitamin D regimen.' The headline message is not to cause alarm but to encourage that dose and form be reviewed as an individualised decision. This article is general information; individual vitamin supplementation decisions should be discussed with your physician or dietitian.