Benecol - Healthcare Professionals

Metabolism of Cholesterol

Ingestion of Cholesterol

Typically, the daily cholesterol intake is 200-500 mg/day, whereas total dietary fat intake is 80-100 g/day in Western societies. However, cholesterol absorption from the gut is incomplete, with only 30-60% actually entering the body. All cells in the body can synthesise cholesterol, and taken together, the body synthesises at least as much cholesterol as it absorbs. The ability to synthesise cholesterol is vital, as it is an essential component of cell membranes and the precursor of steroid hormones. Most of this synthesis takes place in the liver, the gut and the central nervous system.

De Novo Synthesis of Cholesterol

Cholesterol biosynthesis is extremely complex. However, a key regulatory step occurs early in the pathway, at the point where 2-hydroxy-3-methylglutaryl CoA is converted to mevalonic acid. The enzyme responsible, HMG-CoA reductase, can be inhibited by a variety of factors, the most important of which, for clinical purposes, is the class of statin drugs. Although almost all body cells can synthesise cholesterol, only hepatocytes can break it down into bile acids or secrete cholesterol dissolved in bile acids into the small intestine. This is the major route through which cholesterol can leave the body. Of the total reaching the small intestine, however, a variable but important quantity is reabsorbed, resulting in enterohepatic cholesterol cycling. Interruption of this cycle by cholesterol absorption inhibitors, such as plant sterol or stanol esters added to food products, or the drug ezetimibe, lowers serum cholesterol.

Transport of Lipids in Lipoproteins

Lipoproteins transport cholesterol and triglycerides from one point in the body to another. Chylomicrons and VLDL are the two triglyceride-rich lipoproteins, whereas LDL and HDL are the two cholesterol-rich lipoproteins. Chylomicrons are produced by the gut after digestion of fat. They are the richest in triglycerides. Triglycerides are removed from chylomicrons either to supply energy to muscles or for storage in adipose tissue. The remnants continue to circulate in the bloodstream until they are taken up by the liver. VLDL particles are produced by the liver and contain more triglycerides than cholesterol. As triglycerides are removed for energy or storage, VLDL remnants continue to circulate as LDL particles. LDL particles are composed primarily of cholesterol - as cholesteryl ester or free cholesterol - and some triglycerides. About 70% of serum cholesterol is carried by these lipoproteins, so the concentration of LDL-cholesterol provides a good estimate of the total concentration of serum cholesterol.

Reverse Cholesterol Transport and Excretion

About one quarter of serum cholesterol is contained in HDL particles. These particles transport excess cholesterol from the tissues to the liver and to other lipoproteins such as VLDL. This process is known as reverse cholesterol transport. Individuals with very high LDL levels are at a substantially increased risk of atherosclerosis and coronary disease, and those with very low levels are at a low risk. Most patients with coronary disease have LDL levels which are average for the society they live in.