Vitamin D2 supplements can reduce levels of vitamin D3 in the body, according to a 2025 study published in Nutrition Reviews by researchers at the University of Surrey, the John Innes Centre, and Quadram Institute Bioscience. The research reveals that while both forms raise overall vitamin D metrics, introducing ergocalciferol actively lowers circulating concentrations of cholecalciferol, altering how the body maintains the nutrient essential for bone density and immune function.
University of Surrey Trial Results
Researchers reviewed 20 randomized controlled trials to evaluate the metabolic impact of different supplement forms, with 11 studies providing data for the primary meta-analysis. Participants taking vitamin D2 experienced an average reduction of 25-hydroxyvitamin D3 ranging from 9 to 18 nanomoles per liter compared to control groups not receiving D2. Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey’s Nutrition, Exercise, Chronobiology & Sleep Discipline, noted that while supplements remain vital during darker months when sunlight is insufficient, the drop in D3 is a previously unknown biological reaction.
The findings indicate that vitamin D3 supplements may offer superior benefits for most individuals seeking to raise and maintain blood levels. U.S. National Institutes of Health guidance supports this distinction, noting that D3 consistently raises vitamin D concentrations higher and keeps them elevated longer than D2. Supplements typically derive D2 from UV-exposed fungi or yeast, whereas D3 traditionally comes from sheep lanolin, though newer animal-free lichen sources provide plant-based alternatives.
Vitamin D3 Stimulates Interferon Signaling for Infection Alerts
Beyond simple nutrient levels, the two forms trigger distinct genetic responses inside the body. A study published in Frontiers in Immunology, led by University of Surrey professor Colin Smith, investigated gene activity following supplementation. Researchers discovered that vitamin D3 stimulates activity linked to type I interferon signaling, while vitamin D2 does not. Type I interferons act as signaling proteins that alert cells to developing viral and bacterial infections.
Despite these differences in gene activity, newer research highlights that vitamin D2 retains distinct biological utility. A 2026 systematic review and meta-analysis of 26 randomized trials found that D2 supplementation significantly reduced parathyroid hormone levels while producing a slight increase in blood calcium. This evidence confirms that D2 continues to function effectively within the body, even as it coincides with lower circulating D3 levels.
Unresolved Questions in Vitamin D Metabolism
Scientists have not yet established a definitive physiological mechanism explaining why increasing vitamin D2 accelerates the removal or breakdown of 25-hydroxyvitamin D3. Researchers suggest that the body’s regulatory systems may clear out existing metabolites when total concentrations rise, or that the relationship may work in both directions, with D3 supplementation sometimes reducing D2-derived metabolites. Professor Cathie Martin of the John Innes Centre emphasized that these findings make accessible plant-based D3 options a priority for public health initiatives in the UK.
Future clinical trials must determine whether these biochemical differences translate into tangible health outcomes for everyday populations. Professor Martin Warren of the Quadram Institute stated that addressing seasonal vitamin D deficiency with the most effective supplementation form remains paramount for public health. Until larger studies clarify the long-term clinical impacts, the scientific community continues to evaluate whether D3 should become the preferred clinical standard for routine supplementation.
Common Questions About Vitamin D Forms
Do vitamin D2 and vitamin D3 come from the same sources?
No. Vitamin D2, or ergocalciferol, is produced commercially from UV-exposed fungi or yeast, whereas vitamin D3, or cholecalciferol, is the form naturally created in human skin via ultraviolet B sunlight. Plant-based D3 sourced from lichen is also available for vegans.
Does taking vitamin D2 remove vitamin D entirely from the body?
No, vitamin D2 successfully raises overall blood status by increasing 25-hydroxyvitamin D2 levels. The 2025 study found specifically that higher D2 intake coincides with a measurable decrease in the separate 25-hydroxyvitamin D3 metabolite.
Which vitamin D form is recommended during winter months?
Public health guidelines in the UK advise considering a 10-microgram daily supplement during darker months when sunlight is too weak for natural skin synthesis. Recent research suggests D3 is more effective at raising and sustaining those blood levels over time.