Taking vitamin D2 supplements can unexpectedly reduce natural levels of vitamin D3 inside the human
- Taking vitamin D2 supplements can unexpectedly reduce natural levels of vitamin D3 inside the human body, according to research published in Nutrition Reviews.
- A meta-analysis published in 2025 combined data from 20 randomized controlled trials to examine how different supplement forms affect the body.
- Vitamin D2, or ergocalciferol, is typically derived from UV-exposed fungi or yeast, whereas vitamin D3, or cholecalciferol, matches the form produced naturally by human skin during sunlight exposure.
Taking vitamin D2 supplements can unexpectedly reduce natural levels of vitamin D3 inside the human body, according to research published in Nutrition Reviews. While both vitamin D2 and vitamin D3 are commonly used to boost overall nutrient status, a growing body of scientific evidence shows that the two forms are not metabolically interchangeable. Researchers found that increasing vitamin D2 intake corresponds with a noticeable drop in the specific blood metabolites generated by vitamin D3, suggesting that routine supplementation choices for the public may be ineffective.
How Vitamin D2 Lowers Vitamin D3 Levels
A meta-analysis published in 2025 combined data from 20 randomized controlled trials to examine how different supplement forms affect the body. Researchers from the University of Surrey, the John Innes Centre, and the Quadram Institute Bioscience found that individuals taking vitamin D2 experienced significantly lower concentrations of 25-hydroxyvitamin D3 compared to those who did not take D2. Depending on the specific analytical method used, the average reduction ranged roughly from 9 to 18 nanomoles per liter.
Vitamin D2, or ergocalciferol, is typically derived from UV-exposed fungi or yeast, whereas vitamin D3, or cholecalciferol, matches the form produced naturally by human skin during sunlight exposure. The liver converts both forms into 25-hydroxyvitamin D variants to regulate overall status. However, introducing D2 appears to trigger a balancing or disposal mechanism that accelerates the breakdown of existing D3 metabolites.
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.
Emily Brown, PhD Research Fellow, University of Surrey
Immune System Differences Between Supplement Types
Beyond overall blood concentration numbers, separate research indicates that vitamin D2 and D3 influence bodily systems differently. A study published in Frontiers in Immunology, led by Professor Colin Smith at the University of Surrey, investigated how the two supplement types alter gene activity in the blood. The findings revealed that vitamin D3 stimulates activity linked to type I interferon signaling, while vitamin D2 does not.
Type I interferons act as critical signaling proteins that alert cells to developing infections, serving as an early line of defense against viruses and bacteria. Researchers noted that while these genetic shifts are notable, they do not automatically prove that taking D3 prevents specific illnesses, and larger clinical trials remain necessary to understand the everyday health implications.
Continued Biological Effects of Vitamin D2
Despite lowering circulating D3 levels, vitamin D2 retains clear biological activity. A subsequent 2026 systematic review and meta-analysis of 26 randomized trials demonstrated that D2 supplementation significantly reduces parathyroid hormone levels while producing a modest increase in blood calcium. Current guidance from the U.S. National Institutes of Health continues to acknowledge that both supplement forms raise overall blood levels of the vitamin, even though accumulated evidence favors D3 for achieving larger and longer-lasting increases.
Unresolved Questions in Vitamin D Research
Scientists still need to establish whether the observed reduction in circulating D3 translates into meaningful differences in long-term clinical outcomes. Researchers have not yet mapped out the exact metabolic pathways driving the interaction between the two nutrient forms.