title: Ezetimibe decreases serum oxidized cholesterol without impairing bile acid synthesis in Japanese hypercholesterolemic patients.
abstract: OBJECTIVE
  Cholesterol and diet-derived oxidized cholesterol are absorbed in the small intestine and eliminated by bile acids. We determined whether ezetimibe, a selective cholesterol absorption inhibitor, changes serum oxidized cholesterol levels.
  
  
  METHODS
  We measured levels of plant sterols, cholesterol precursors, and oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics and 32 controls. Twenty-four hypercholesterolemics received 10 mg ezetimibe/day for 4 weeks.
  
  
  RESULTS
  Plant sterols were 30-42% higher in hypercholesterolemics than in controls and positively correlated with low-density lipoprotein-cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53%, but did not change bile acid synthesis markers. 7β-hydroxycholesterol, a marker for non-enzymatic oxidation of cholesterol, was 66% higher in hypercholesterolemics than controls. Ezetimibe decreased 7β-hydroxycholesterol levels by 15% regardless of LDL-C reduction.
  
  
  CONCLUSIONS
  Ezetimibe decreases serum oxidized cholesterol generated by non-enzymatic reactions without impairing bile acid synthesis. Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet-derived oxidative burden.
authors: Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan. sthiraya@juntendo.ac.jp
authors: Satoshi
authors: S
authors: Hirayama
authors: Saori
authors: S
authors: Nakagawa
authors: Satoshi
authors: S
authors: Soda
authors: Yumiko
authors: Y
authors: Kamimura
authors: Emiko
authors: E
authors: Nishioka
authors: Tsuyoshi
authors: T
authors: Ueno
authors: Yoshifumi
authors: Y
authors: Fukushima
authors: Ken-ichi
authors: K
authors: Higuchi
authors: Masanori
authors: M
authors: Inoue
authors: Utako
authors: U
authors: Seino
authors: Hirotoshi
authors: H
authors: Ohmura
authors: Susumu
authors: S
authors: Yamato
authors: Takashi
authors: T
authors: Miida
mesh_terms: D000042:Absorption; D000368:Aged; D000886:Anthropometry; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism*; D015992:Body Mass Index; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D004032:Diet; D000069438:Ezetimibe; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D007421:Intestine, Small / Q000378:metabolism; D007564:Japan; D008019:Life Style; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D010840:Phytosterols / Q000378:metabolism; D013261:Sterols / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; D010840:Phytosterols; D013261:Sterols; D014280:Triglycerides; C011724:cholest-5-en-3 beta,7 alpha-diol; D002784:Cholesterol; D000069438:Ezetimibe; D010100:Oxygen
keywords: Cholesterol precursors; Ezetimibe; Gas chromatography–mass spectrometry (GC–MS); NPC1L1; Oxysterols; Plant sterols