NutriStack
What is happening. Ezetimibe blocks intestinal absorption of cholesterol via the Niemann-Pick C1-Like 1 (NPC1L1) transporter. Because fat-soluble vitamin D shares a dependence on intact micellar lipid uptake in the small intestine, ezetimibe has the potential to modestly reduce vitamin D absorption. Clinical studies have generally found only small or non-significant effects on serum 25-hydroxyvitamin D, but individuals who are already vitamin D insufficient or who take low doses may see a measurable difference over time.
Mechanism. Ezetimibe inhibits the NPC1L1 enterocyte sterol transporter and reduces intestinal uptake of cholesterol and, to a lesser degree, co-absorbed fat-soluble micronutrients including vitamin D, which depends on micellar lipid solubilization for absorption.
Recommendation. Routine vitamin D3 supplementation does not need to be stopped. For patients on long-term ezetimibe, especially those with baseline insufficiency, periodically check serum 25-hydroxyvitamin D and supplement to maintain adequate status. No strict dose-separation is required, though taking vitamin D3 with a fat-containing meal supports absorption.