What is the Origin of Bile Acid Sequestration?

The term originates from the biological compound 'bile acid' and the Latin word 'sequestrare,' meaning to separate or set aside. The concept arose from the observation that certain non-absorbable resins could interfere with the fat digestion process. Pharmaceutical application developed upon recognizing that forcing the liver to synthesize new bile acids would consume cholesterol, offering a therapeutic target for hypercholesterolemia.

What is the Mechanism of Bile Acid Sequestration?

Sequestrant agents, which are non-absorbable polymers, form a complex with negatively charged bile acids in the small intestine. Because the liver must constantly replenish the pool of excreted bile acids, it upregulates the conversion of cholesterol into new bile acids. This increased utilization of hepatic cholesterol leads to an upregulation of LDL receptors on the liver cell surface, consequently drawing more LDL cholesterol from the bloodstream. This process is an effective way to indirectly manage cholesterol levels.

Bile Acid Sequestration

Meaning

Bile acid sequestration is a therapeutic mechanism that involves binding bile acids in the intestinal lumen to prevent their reabsorption into the enterohepatic circulation. This process effectively interrupts the natural recycling of bile acids, thereby increasing their fecal excretion. Clinically, this mechanism is primarily employed to lower circulating low-density lipoprotein (LDL) cholesterol levels, a key factor in cardiovascular risk and metabolic health. This action forces the liver to synthesize new bile acids from its cholesterol stores.