Cholesterol absorption inhibitors are a class of compounds that prevent the uptake of

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

from the small intestine into the circulatory system. Most of these molecules are monobactams but show no

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

activity. An example is

ezetimibe Ezetimibe, sold under the brand name Zetia among others, is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred ...

(SCH 58235) Another example is Sch-48461. The "Sch" is for

Schering-Plough Schering-Plough Corporation was an American pharmaceutical company. It was originally the U.S. subsidiary of the German company Schering AG, which was founded in 1851 by Ernst Christian Friedrich Schering. As a result of nationalization, it becam ...

, where these compounds were developed.

Phytosterols Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phyto ...

are also cholesterol absorption inhibitors. Viscous soluble fiber is available in foods or fiber supplements and can reduce LDL-C. It is hypothesized that this effect is by binding to

bile acids Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

and preventing their resorption.

Psyllium Psyllium (), or ispaghula (), is the common name used for several members of the plant genus ''Plantago'' whose seeds are used commercially for the production of mucilage. Psyllium is mainly used as a dietary fiber to relieve symptoms of both ...

reduces LDL-C by 0.33 mmol/l (12.5 mg/dl) and also reduces

apolipoprotein B Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Its measurement is commonly used to detect the risk of Atherosclerosis, atherosclerotic Coronary artery disease, cardiovascular disease. Isoforms The protein occur ...

, leading one systematic review to conclude that it "effectively improves conventional and alternative lipids markers, potentially delaying the process of atherosclerosis-associated CVD risk in those with or without hypercholesterolemia". Another soluble fiber, konjac

glucomannan Glucomannan is a water-soluble polysaccharide that is considered a dietary fiber. It is a hemicellulose component in the Cell wall#Plant cell walls, cell walls of some plant species. Glucomannan is a food additive used as an emulsifier and thick ...

, reduces LDL by 10 percent.

Physiology

There are two sources of cholesterol in the upper intestine: dietary (from food) and

biliary A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior). Bile is requ ...

(from bile). Dietary cholesterol, in the form of

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

emulsions, combines with

bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

, to form bile salt micelles from which cholesterol can then be absorbed by the intestinal

enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase ...

. Once absorbed by the enterocyte, cholesterol is reassembled into intestinal

lipoproteins A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

called

chylomicrons Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...

. These

chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...

s are then secreted into the lymphatics and circulated to the liver. These cholesterol particles are then secreted by the liver into the blood as

VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, LDL, low-density ...

particles, precursors to

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

. As a class, cholesterol absorption inhibitors block the uptake of micellar cholesterol, thereby reducing the incorporation of cholesterol esters into chylomicron particles. By reducing the cholesterol content in chylomicrons and chylomicron remnants, cholesterol absorption inhibitors effectively reduce the amount of cholesterol that is delivered back to the liver. The reduced delivery of cholesterol to the liver increases hepatic LDL receptor activity and thereby increases clearance of circulating LDL. The net result is a reduction in circulating LDL particles.

Importance

Managing cholesterol at the site of absorption is an increasingly popular strategy in the treatment of

hypercholesterolemia Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...

. Cholesterol absorption inhibitors are known to have a synergistic effect when combined a class of antihyperlipidemics called

statins Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

, to achieve an overall serum cholesterol target. For statin-resistant or statin-sensitive populations that are characterized by low one-year compliance rates, such a combination therapy is proving to be especially effective .

References

{{Lipid modifying agents Hypolipidemic agents

Physiology

Importance

See also

References