Cholesterol Lowering Medications, and How They Work

High cholesterol is a battle many Americans face. Nearly 94 million, or 40% of adults, in the US have total cholesterol levels above 200 mg/dL, the recommended threshold. Conditions associated with high cholesterol, also called hyperlipidemia, include heart attacks and stroke. High cholesterol is often a silent killer as it does not show any symptoms before manifesting in deadly diseases.

While an excessive concentration does pose health risks, cholesterol is not all bad. In fact, a certain level is necessary, and even produced in the liver. Cholesterol is a fatty molecule that is incorporated into cell membranes to stabilize the structure and allow cells to hold their shape. 

However, not all cholesterol is stored equally. There are two main types of cholesterol storage molecules: low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL is considered “bad cholesterol” while HDL is considered “good cholesterol”. Let’s take a look at how they differ, and why you’ll want to keep LDL levels down.

Cholesterol is both absorbed from the small intestine from the foods we eat, as well as created in the liver. Because cholesterol cannot be dissolved in water, and thus can’t enter the blood by itself, it must be put into a water-soluble container. Thus, the liver packages cholesterol along with triglycerides (another form of free fatty acids, otherwise just known as fat) into a water-soluble container known as a very low density lipoprotein (VLDL) which eventually converts into LDL as it drops off triglycerides at the muscles to be used as an energy source. The liver can recycle LDL to be used to traffic more cholesterol, however if it’s levels are too high, the LDL particles will be stuck in the bloodstream and end up being deposited in the artery walls where they can cause artery wall hardening, called atherosclerosis that can lead to heart disease. It’s not so hard to see how this is a bad thing. 

On the other hand, HDL is also secreted by the liver and the intestine. It is made up of mostly protein and a small amount of triglyceride, which is what makes it “high density”. Instead of packing up the cholesterol from the liver like LDL does, HDL’s job is to go out into the blood and extract extra cholesterol from the body to package it up, leaving less cholesterol to be stuck in the arteries. Because HDL ultimately pulls free floating cholesterol out of the blood, it is helpful in preventing atherosclerosis. 

As it turns out, lowering “bad cholesterol”, or LDL,  is more cardio-protective than increasing “good cholesterol”, HDL. So how does someone lower their LDL if it’s too high? The most important LDL lowering drugs are statins.  

If you or someone you know is taking medication to lower their cholesterol, chances are they are taking a statin. Statin drugs are so called because many of the generic drugs end with “statin”, but the real drug class name is HMG-CoA reductase inhibitors. Remember when I said the liver created its own cholesterol? It does so by using an enzyme called HMG-CoA reductase, and statins work by blocking this enzyme. As you can imagine, if you stop producing your own cholesterol, the body will utilize the cholesterol already in circulation, thus lowering the total amount in your body. Statins are the number one most effective drug that lowers LDL and increases survival in patients with cardiovascular disease. It sounds like a wonder drug, but the major drawback is that it may cause muscle weakness or soreness, otherwise known as myopathy. Although the side effects may prove too uncomfortable for some patients, these drugs remain the mainstay of hyperlipidemia fighting medications.

While statins are the clear winner when it comes to lowering bad cholesterol levels, there are six other drug classes worth mentioning. 

• Bile acid resins
• Ezetimibe
• Fibrates
• Niacin
• PCSK9 inhibitors
• Fish oil / Omega-3 fatty acids

Bile is a substance that is used to help digest fats and make them more easily absorbed into our bloodstream, similar to the lipoproteins discussed earlier. And just like those lipoproteins, they can also be reabsorbed and recycled by the liver. Bile acid resins work by causing bile to be excreted and preventing the liver from being able to reuse it. Since the body does need bile to be able to absorb the fats we eat, it makes fresh stores from cholesterol that is already in the body, lowering the amount of free cholesterol floating around in the blood waiting to clog your arteries. While they are effective in lowering LDL and even slightly increasing HDL, they do disrupt the absorption of fat soluble vitamins and other drugs that might rely on bile to be absorbed into the body. 

Another way we might think to decrease the amount of cholesterol in the body is by simply blocking the absorption of dietary cholesterol from the intestine in the first place. Ezetimibe is a drug that does exactly that, however it may cause diarrhea.  

Fibrates are a class of drugs that work a little more mysteriously, but to put it simply, they work by increasing a receptor that lowers LDL cholesterol and increases HDL synthesis. Major side effects include myopathy (especially when combined with statins) and cholesterol gallstones.

PSCK9 inhibitors work on the same receptor that fibrates do, but instead of upregulating the receptor, they decrease the breakdown of the receptor, both effects leading to a decrease in the total amount of LDL cholesterol in the blood. Major side effects include muscle pain, dementia, delirium, and other neurological effects

Niacin, another name for vitamin B3, is another cholesterol lowering substance, although its effects are not as pronounced as some of the other drugs. It works by decreasing the release of fats from fat cells (known as adipose tissue) and lower liver synthesis of VLDL. Taken in high quantities, niacin may cause facial flushing.

Fish oil and omega-3 fatty acids are another supplement to help moderately decrease LDL cholesterol levels. They also lead to a slight increase in HDL cholesterol and a moderate decrease in triglycerides. While the effects of fish oil are not as dramatic as some of the other drugs, they can be a great alternative for someone looking for an over the counter alternative with little side effects. Nausea is occasionally reported, but the most common side effect is a fishy aftertaste.