Ursodeoxycholic Acid for Trans Intestinal Cholesterol Excretion Stimulation: A Randomized Placebo Controlled...

Area of Science:

• Biochemistry and Metabolism
• Cardiovascular Research
• Gastroenterology

Background:

• Trans intestinal cholesterol excretion (TICE) is a pathway for reducing plasma LDL cholesterol.
• TICE involves direct cholesterol excretion by enterocytes into feces.
• In mice, TICE is stimulated by hydrophilic bile acids, increasing fecal sterol loss and lowering plasma cholesterol.

Purpose of the Study:

• To investigate if ursodeoxycholic acid (UDCA), a hydrophilic bile acid, increases fecal neutral sterols in humans.
• To evaluate UDCA's effect on the trans intestinal cholesterol excretion (TICE) pathway as a proxy.
• To assess UDCA's impact on plasma LDL cholesterol levels in conjunction with ezetimibe.

Main Methods:

• A randomized, double-blind, placebo-controlled, cross-over trial involving 20 male participants with LDL cholesterol ≥2.6 mmol/L.
• Participants received ezetimibe 20 mg daily for 3 weeks, followed by randomization to UDCA 600 mg or placebo daily for 2 weeks.
• A 3-week washout period preceded the alternate treatment; fecal neutral sterols and plasma LDL cholesterol were measured.

Main Results:

• UDCA treatment significantly reduced plasma bile acid hydrophobicity compared to placebo (P<0.001).
• Fecal neutral sterol excretion showed no significant change between UDCA and placebo groups (P=0.51).
• UDCA treatment resulted in a significant increase in LDL cholesterol compared to placebo (+8.1% vs -3.64%, P=0.002).

Conclusions:

• UDCA, when combined with ezetimibe, increases bile acid hydrophilicity in humans but does not enhance fecal neutral sterol excretion.
• The findings suggest that TICE is not stimulated by increased bile acid pool hydrophilicity in humans.
• This combination therapy did not decrease LDL cholesterol and unexpectedly increased it, challenging UDCA's role in TICE stimulation.