Does Zetia (Ezetimibe) Interfere with Nutrient Absorption?
No, ezetimibe does not interfere with the absorption of fat-soluble vitamins, triglycerides, or bile acids—it selectively inhibits only cholesterol absorption. 1, 2
Mechanism of Action and Selectivity
Ezetimibe works by targeting the Niemann-Pick C1-Like 1 (NPC1L1) protein at the brush border of the small intestine, which specifically blocks cholesterol uptake into enterocytes. 3, 1 This highly selective mechanism means:
Fat-soluble vitamins (A, D, E) are NOT affected: Clinical trials in 113 patients demonstrated no clinically meaningful effect on plasma concentrations of vitamins A, D, and E. 1
Triglyceride absorption remains intact: The drug does not interfere with triglyceride absorption from the intestine. 2, 4, 5
Bile acid absorption is preserved: Unlike bile acid sequestrants, ezetimibe does not affect bile acid absorption. 2, 4
Clinical Evidence Supporting Nutrient Safety
The FDA label explicitly states that ezetimibe inhibits cholesterol absorption "without affecting the absorption of fat-soluble nutrients." 1 Multiple research studies confirm this selectivity:
A 2005 pharmacokinetics review documented that ezetimibe inhibits intestinal cholesterol uptake without affecting fat-soluble nutrient absorption. 2
Studies showed 54-58% inhibition of cholesterol absorption while maintaining normal absorption of other nutrients. 4
The drug localizes specifically at the intestinal brush border to block cholesterol uptake into enterocytes, leaving other absorption pathways unaffected. 5, 6
Important Clinical Considerations
Adrenocortical function is not impaired: In a trial of 118 patients, ezetimibe did not affect adrenocortical steroid hormone production. 1
No dosage adjustment needed for nutrient concerns: The standard 10 mg daily dose can be taken with or without food, as food does not affect the extent of absorption (though high-fat meals increase peak concentration by 38%, this is not clinically significant). 1
Key Distinction from Other Lipid-Lowering Agents
Unlike bile acid sequestrants (which can interfere with absorption of fat-soluble vitamins and other medications), ezetimibe's selective mechanism makes it unique among intestinally-acting lipid-lowering agents. 3, 5 Bile acid sequestrants may cause significant gastrointestinal distress and can interfere with absorption of other medications, whereas ezetimibe does not share these limitations. 3