A 2025 meta-analysis of 20 studies found vitamin D2 supplementation significantly lowered circulating 25-hydroxyvitamin D3 versus no D2, with average reductions of about 9 to 18 nmol/L.
That matters because D3 generally raises and sustains overall vitamin D levels better than D2, and earlier University of Surrey research linked D3 — but not D2 — to type I interferon signaling involved in early antiviral and antibacterial defense.
Researchers said the drop in D3 does not mean D2 is ineffective: D2 still boosts D2-derived vitamin D, and a 2026 review of 26 trials found it also lowered parathyroid hormone and slightly increased blood calcium.
Scientists still do not know whether D2-driven reductions in D3 translate into worse health outcomes, but the findings strengthen the case for D3 as the preferred routine supplement when no individual reason favors D2.