While both supplement forms increase overall vitamin D status, researchers caution that D3 is more effective at raising and maintaining blood concentrations.
Taking vitamin D2 can reduce levels of vitamin D3, the form humans naturally make when skin is exposed to sunlight, according to a study published in 2025 by researchers from the University of Surrey, John Innes Centre, and Quadram Institute Bioscience. Vitamin D supplements are frequently purchased as interchangeable sources of the same essential nutrient, which helps the human body absorb calcium and maintain healthy bones. Out of 20 studies reviewed in the meta-analysis, 11 provided data suitable for the main evaluation.
University of Surrey Researchers Track Metabolic Trade-off
Once vitamin D enters the human body, the liver converts it into 25-hydroxyvitamin D, which is the specific form doctors commonly measure in blood tests to estimate a person’s vitamin D status. Vitamin D2 produces 25-hydroxyvitamin D2, whereas vitamin D3 produces 25-hydroxyvitamin D3. It is this D3-derived form that investigators found drops after individuals consume vitamin D2.
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 and Lead Researcher of the study from the University of Surrey’s Nutrition, Exercise, Chronobiology & Sleep Discipline
Scientists do not yet have a definitive explanation for why vitamin D2 lowers vitamin D3. One possibility centers on how the body regulates vitamin D. When concentrations of these metabolites rise, the body may accelerate the breakdown and removal of the compounds to keep levels under control. Researchers propose that increasing vitamin D2 could therefore accelerate the disposal of existing 25-hydroxyvitamin D3. Earlier experiments also suggest the relationship might work in reverse, with D3 supplementation occasionally reducing D2-derived metabolites, though the exact health significance remains unresolved.
Vitamin D3 Stimulates Immune System Signaling
Professor Colin Smith pointed out that vitamin D3, but not vitamin D2, appears to stimulate the body’s type I interferon signaling system, which forms a key part of the immune system’s first line of defense against bacteria and viruses, moving beyond standard bone health benefits. Investigators emphasize that these immune findings do not prove that taking D3 will prevent any specific infection, as changes in gene activity do not automatically translate directly into fewer illnesses without larger clinical trials.
Professor Cathie Martin, Group Leader at the John Innes Centre, said the meta-analysis shows that plant-based vitamin D3 must be accessible in the UK, noting that D3 derived from lichen is now available to help consumers get the preferred nutrient form.
Recent 2026 Evidence and U.S. National Institutes of Health Guidance
A separate 2026 systematic review and meta-analysis examining 26 randomized trials found that D2 supplementation significantly reduced parathyroid hormone levels and produced a small increase in blood calcium, introducing an important caveat regarding vitamin D2 from research published since the 2025 analysis. This demonstrates that D2 retains meaningful biological effects even while lowering circulating D3 levels.
National Institutes of Health states that both D2 and D3 can increase overall blood levels of vitamin D, but accumulated evidence favors D3 for producing a larger increase and keeping those levels elevated for longer. Previous analyses, including one examining 24 studies and another focusing on frequent dosing, reached similar conclusions regarding D3’s effectiveness in improving overall status.
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