Vitamin D is one of the most widely taken supplements in the world — but a new systematic review finds its two main forms are not interchangeable. Taking vitamin D2 may lower blood levels of vitamin D3, the very form the human body uses most effectively.
The research was a collaboration between the University of Surrey, the John Innes Centre and the Quadram Institute Bioscience, published in the journal Nutrition Reviews. The team searched the literature from 1975 to early 2023, including 20 studies, with 11 randomized controlled trials (655 participants total) providing data suitable for combined analysis. The pattern was consistent: people who received D2 supplements had lower blood concentrations of 25-hydroxyvitamin D3 than control groups — and in many trials, lower than people taking no supplement at all.
25-hydroxyvitamin D is the main marker doctors measure when checking vitamin D status. "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," said lead researcher Emily Brown, a PhD research fellow at Surrey. "This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2."
The two common forms differ in origin: D2 (ergocalciferol) comes mostly from plant or fungal sources and dominates vegetarian supplements; D3 (cholecalciferol) is the form human skin makes after UVB exposure, also extracted from lanolin. The long-standing assumption — that it doesn't matter which one you take — is what this study challenges.
An earlier immunology study (Frontiers in Immunology, led by Surrey's Professor Colin Smith) found the two forms also play different immune roles: only D3 appeared to stimulate the type I interferon signaling system, a first line of defense against bacteria and viruses. D2 did not.
The researchers urge caution against overreading the result: lower D3 does not mean D2 is useless. A newer 2026 systematic review and meta-analysis of 26 randomized trials found D2 supplementation significantly reduced parathyroid hormone levels and produced a small increase in blood calcium — meaningful biological effects. Current NIH guidance continues to state that both D2 and D3 raise overall blood vitamin D; the difference is that the evidence favors D3 for a larger increase that lasts longer.
Professor Cathie Martin of the John Innes Centre said the meta-analysis "highlights the importance of ensuring plant-based vitamin D3 is accessible" — so vegetarians don't have to choose between their diet and the more effective form. Plant-derived D3 is increasingly available, offering a third option.
The practical takeaway: if you take vitamin D, check the label for D2 (ergocalciferol) versus D3 (cholecalciferol). Without specific dietary restrictions, the accumulated evidence favors D3; vegetarians can look for plant-based D3.
But don't dose up on your own. Vitamin D is fat-soluble and accumulates in the body; excess intake can cause hypercalcemia — dangerously high blood calcium — damaging kidneys and disrupting heart rhythm. Anyone needing high doses to correct a deficiency should get blood work first and follow a clinician's guidance. The logic of supplementation was never "more is better" — it's "replace what's missing, in the right form."