Emily Brown and her colleagues at the University of Surrey went looking for the difference between two letters. Not whether vitamin D works, the question everyone treats as settled, but what the fungal-derived form of it does to the body on the way through. The answer, pooled from a stack of randomized trials, is the kind of result that never makes it onto a supplement label: people who took vitamin D2 ended up with less circulating vitamin D3 than the people who took none. It is also, as these things go, an answer with a commercial shape.

The two forms are not interchangeable, whatever the bottle implies. Vitamin D3, cholecalciferol, is what your skin manufactures in sunlight and what comes from animal foods. Vitamin D2, ergocalciferol, is made from fungi or yeast exposed to ultraviolet light, and it is the form marketed to vegans and vegetarians precisely because nothing animal goes into it. For decades the working assumption was that the two did the same job at slightly different speeds. This analysis says one of them works against the other.

In the Surrey team’s review, published in Nutrition Reviews, twenty studies were examined and eleven supplied usable data. Pooling those eleven, people taking D2 carried significantly lower levels of circulating D3: about 18 nmol/L lower by the end of a trial, and about 9 nmol/L lower when the measure was the change from where each person started. In many of the trials the D3 level in the D2 group fell below the level in the controls. You take a pill to raise your vitamin D, and one measurable part of it goes down.

D2 still raises your total vitamin D, the single number a standard blood test reports, so on paper the supplement does exactly what the label promises. The suppression hides inside that total, in the D3 fraction. The report comes back normal while the form your body actually prefers is quietly losing ground.

Why it happens is the part no one can prove yet. The researchers’ best guess is that flooding the system with D2 speeds up the breakdown and clearance of vitamin D metabolites, dragging the native D3 down with the rest. That is a hypothesis, and the paper says so.

None of this is new, only sharper. A 2012 meta-analysis in the American Journal of Clinical Nutrition, ten studies and 1,016 participants, led out of the same Surrey faculty, concluded flatly that D3 is more efficacious than D2 at raising serum vitamin D. What changed is the claim. The old finding was that D2 underperforms. The new one is that D2 may actively depress the D3 your own body made. The gap stopped being about speed and became about subtraction.

There is a physiological reason to prefer D3, not just a bookkeeping one. Work from Surrey’s Professor Colin Smith, reported alongside the review, found that D3, but not D2, appeared to stimulate the type I interferon system, which Smith describes as a first line of defense against bacteria and viruses. He was careful to say this is not proof that D3 prevents infection, and the caution is warranted. It is still one more reason not to shrug at which form is winning inside you.

Now read the author list slowly, because the burden of proof runs in both directions. Among the names on the paper recommending D3 over D2 are Professor Cathie Martin and Dr Jie Li of the John Innes Centre. In 2022, Li and Martin published work in Nature Plants describing tomatoes gene-edited to accumulate provitamin D3, with the leftover leaves pitched as raw material for plant-based D3 supplements and fortified food. When Martin told reporters alongside this meta-analysis that the findings “highlight the importance of ensuring plant-based vitamin D3 is accessible in the UK,” she was describing a market her own lab has spent years building toward. None of that makes the data wrong. It has pointed this way since 2012, through groups with no tomato to sell. It does mean the people holding the microscope have something riding on what it shows, and a reader is entitled to know it.

For whom does this matter most? For the vegan and the vegetarian who chose D2 because it was the animal-free option, and who may be the group doing itself the least good. For the patient handed ergocalciferol on a prescription. For anyone who read the total on a lab report as the whole truth. Brown’s own conclusion stays measured almost to understatement: D3 “may be more beneficial for most individuals” than D2, subject to personal circumstances. The sunlight form, in other words, the one you can get for free by standing outside.

Martin, for her part, is already most of the way to the alternative. Her team has tomatoes engineered to make the D3 kind, a human feeding trial recruiting near Norwich, and a public case that Britain needs the product. The data she helped publish is the best argument yet for the thing she is selling.

Sources

  1. Nutrition Reviews – Brown et al. (2025), “Effect of Vitamin D2 Supplementation on 25-Hydroxyvitamin D3 Status: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”
  2. University of Surrey – “Vitamin D3 concentrations are lowered by a common vitamin D supplement”
  3. ScienceDaily – coverage of the Surrey D2-lowers-D3 meta-analysis, with effect sizes and proposed mechanism
  4. American Journal of Clinical Nutrition – Tripkovic et al. (2012), systematic review and meta-analysis finding D3 more efficacious than D2
  5. FoodNavigator – John Innes Centre (Li, Martin et al.) gene-edited provitamin-D3 tomatoes, Nature Plants (2022)