Vitamin D2 Supplements May Secretly Deplete Your Body's Own Vitamin D3

Vitamin D supplementation is one of the most common health practices worldwide, yet a growing body of evidence suggests that the two main supplement forms — D2 and D3 — are not interchangeable. A 2025 meta-analysis published in Nutrition Reviews by researchers from the University of Surrey, John Innes Centre, and Quadram Institute Bioscience has highlighted an unexpected and clinically meaningful difference between them.

The study reviewed 20 randomized controlled trials, with 11 contributing data to the primary meta-analysis. The key finding: people taking vitamin D2 had significantly lower circulating levels of 25-hydroxyvitamin D3 compared to those who did not take D2. The reduction ranged from approximately 9 to 18 nanomoles per liter depending on the analytical approach used. This suggests that increasing D2 in the body somehow suppresses the metabolism or retention of D3 — the form produced naturally in human skin upon sunlight exposure.

This matters because 25-hydroxyvitamin D3 is the dominant and more bioavailable metabolite. D3 has been shown to raise and sustain overall vitamin D blood levels more effectively than D2. Prior research also links D3 to stronger immune defenses against viral and bacterial infections — a distinction with real relevance to aging, since immune competence declines with age.

Practically, the findings suggest that people choosing vitamin D supplements — particularly during winter months when sunlight is insufficient — would likely benefit more from D3 than D2. Vegan consumers concerned about animal-derived D3 (traditionally sourced from lanolin) can now access lichen-based D3 as a cruelty-free alternative.

Important caveats apply. D2 is not harmful and does raise total vitamin D status through its own metabolite. The mechanism behind D3 suppression is not yet fully established. These findings are based on a meta-analysis, and individual responses may vary based on baseline levels, diet, and genetics.