Vitamin D2 supplements lower vitamin D3 in trial review

University of Surrey researchers said in an Oct. 8 ScienceDaily research summary that vitamin D2 supplementation reduced 25-hydroxyvitamin D3 by about 9 to 18 nmol/L in a 2025 randomized-trial review.

Evidence grade: Strong (large randomized trials or meta-analysis). The finding matters because vitamin D3, compared with vitamin D2, is generally better at raising and sustaining the main vitamin D blood marker, according to current U.S. National Institutes of Health information cited in the source.

The review, published in Nutrition Reviews, assessed 20 randomized controlled trials, with 11 included in the main meta-analysis. Compared with people who did not receive vitamin D2, those taking D2 had significantly lower concentrations of 25-hydroxyvitamin D3, the D3-derived form of 25-hydroxyvitamin D measured in blood tests.

Emily Brown, PhD Research Fellow and lead researcher from the University of Surrey's Nutrition, Exercise, Chronobiology & Sleep Discipline, said: "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."

Vitamin D2, or ergocalciferol, is commonly made from fungi or yeast exposed to ultraviolet light. Vitamin D3, or cholecalciferol, is the form produced in human skin after ultraviolet B exposure from sunlight; supplements have often used lanolin from sheep's wool, though animal-free D3 from lichen is also available.

The source said both forms can raise overall vitamin D status. D2 raises 25-hydroxyvitamin D2, while D3 raises 25-hydroxyvitamin D3. The new question is whether increasing the D2-derived form prompts the body to reduce the D3-derived form through vitamin D regulation and clearance mechanisms.

The supplied report did not provide total participant numbers, ages, trial durations, doses, funding or declared conflicts. The study cannot show that the reduction in circulating D3 causes worse bone, muscle, nerve or immune outcomes, or that one supplement form prevents specific infections better than the other.

The immune evidence is also indirect. A separate Frontiers in Immunology study led by Professor Colin Smith from the University of Surrey found different blood gene-activity responses to D2 and D3, including D3-linked type I interferon signaling, an early immune alert system. Smith said: "We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signaling system in the body -- a key part of the immune system that provides a first line of defense against bacteria and viruses.

Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body."

Newer evidence complicates the picture. A 2026 systematic review and meta-analysis of 26 randomized trials found vitamin D2 reduced parathyroid hormone levels and slightly increased blood calcium, meaning D2 can still have biological effects even if it lowers circulating D3.

For readers, the research applies most directly to people comparing vitamin D supplement forms, not to people making treatment decisions for deficiency or illness. The next scientific issue is whether the biochemical difference between D2 and D3 changes long-term health outcomes, rather than only blood markers.

Source: ScienceDaily research summary based on University of Surrey materials, Oct. 8, 2026.

Atlas360 reports health research and does not provide medical advice.