Why is LDL so dangerous?

Cholesterol Down: Ten Simple Steps to Lower Your Cholesterol in Four Weeks - Without Prescription Drugs
by Janet Bond Brill, Ph.D., R.D., LDN

(Page 3 of 3)

LDL is commonly referred to as the "bad" cholesterol because high levels of circulating LDL have been linked to an increased risk for atherosclerosis and cardiovascular disease. LDL is the most dangerous lipoprotein, not only because each particle is made up of mostly cholesterol (roughly 45 percent) but also because of its destination. LDL carries cholesterol to the arteries, infiltrates their walls, and goes through a series of transformations that trigger plaque buildup.

What does this "bad" cholesterol look like?

LDL cholesterol is a round lipoprotein that shuttles the bulk of the cholesterol in the blood. The inner core contains oily cholesterol molecules, each with a fatty acid chain dangling from it. Also found within the core is a lesser amount of triglyceride molecules intermingling with the cholesterol esters. Seventy-five percent of the cholesterol within the LDL is in this bound-up (esterified) form, concentrated within the inner core. The greater the concentration of these "chained" cholesterol molecules in the LDL, the more susceptible the LDL molecule is to oxidation (which instigates the catastrophic events that make up the atherosclerotic process), and the higher your risk for developing heart disease.

Surrounding the fatty core of LDL is an outer shell consisting of many fat-like molecules called phospholipids, plus some "unchained" cholesterol. The entire LDL ball is encircled by one big spaghetti- like strand of protein called Apo B (apolipoprotein B-100) (Figure 1.2). This protein molecule plays a crucial role in mooring the LDL molecule onto LDL receptors (more on these later).

Eating Your Way to a Heart Attack

What most people don't realize is that cholesterol comes from two sources: from food and from our own cells. In fact, we actually make three times more cholesterol (about 1,000-1,200 milligrams per day) than we typically eat. So we don't need to eat cholesterol because the body is perfectly capable of manufacturing enough of this waxy substance on its own. Still, Americans continue to consume an appreciable amount of cholesterol from dietary sources, which can raise "bad" cholesterol levels and increase our risk of heart disease. The average American ingests approximately 300-400 milligrams of cholesterol every day from animal sources. This amount exceeds the government's cholesterol-lowering dietary recommendation of no more than 200 milligrams a day. It is simple to eat this much cholesterol: seven ounces of liver (providing 762 milligrams of cholesterol) or two egg yolks (424 milligrams) will easily put you over the top.

In the intestine is a reservoir of cholesterol called the cholesterol pool. The amount of cholesterol that enters the pool from bile is up to five times greater than the amount of cholesterol derived from our diet. Where does all that cholesterol floating around in the intestine go? About half of the approximately 2,000 milligrams in the pool is excreted and half is reabsorbed into the intestinal cells, ultimately going back to the liver. If you could block reabsorption of some of the cholesterol in the intestinal pool so that it gets excreted and not returned to the liver, then you would decrease your circulating LDL level. One class of cholesterol-lowering drugs in particular capitalizes on this concept.

How is cholesterol absorbed from the intestinal pool into the body?

For cholesterol, the gateway into the body is a layer of cells lining the upper intestine known as enterocytes. The only way for cholesterol to get to this layer is to attach itself to a transporter called a micelle. Micelles are small, round transport packages formed by bile salts and phospholipids that carry cholesterol and fat (triglycerides) to the intestinal cell wall. The cholesterol must then take a second transport vehicle-a protein carrier called Niemann- Pick C1 Like 1, or NPC1L1 for short. The NPC1L1 travels through the wall and into the intestinal cell where the cholesterol is packaged into chylomicrons for travel in the lymph system and ultimately the bloodstream. Zetia, the new cholesterol-lowering drug, blocks cholesterol absorption from the intestine by targeting the NPC1L1 protein.

Once in the bloodstream, chylomicrons off-load lots of triglycerides to needy cells, eventually arriving at the liver as small, cholesterol-rich particles known as chylomicron remnants. These remnants signal to the liver cells that they don't have to make more cholesterol, as a new cholesterol shipment has arrived-cholesterol that may have come from your breakfast omelet. The liver extracts the cholesterol from the remnants to make whatever is required for the day. Typically, the cholesterol is converted into bile acids for its launch into the body's cholesterol recycling system. But the liver could instead package the cholesterol up as a lipoprotein (primarily VLDL) and send it back into the bloodstream, ultimately increasing the amount of "bad" LDL cholesterol. Eat a huge amount of cholesterol and you increase the delivery of cholesterol to the liver by chylomicron remnants. Therefore, you should avoid foods with high cholesterol in order to lower the amount of cholesterol in your intestinal pool. Less cholesterol overloading the liver means less VLDL exported and less LDL produced.

Copyright © 2006 by Dr. Janet Brill.

About the Author

Dr. Janet Brill is a registered and licensed dietitian/nutritionist, exercise physiologist, and certified wellness coach. She has been published in the International Journal of Obesity and the International Journal of Sport Nutrition, as well as in the popular press.